TY - JOUR T1 - Direct and Indirect Measures of Frequency Monitoring in Young and Elderly Adults AN - 85603395; 9500177 AB - Memory for frequency of occurrence of novel material (Turkish words) was investigated in English-speaking young & elderly adults in two experiments (N = 15 each, mean ages 24.5 & 76.5, & 24 each, mean ages 21.8 & 72.9, respectively) via direct (absolute & relative frequency judgments) & indirect (reading speed) measures. Both young & elderly adults showed increased reading speed as a function of frequency of occurrence (experiment 1). However, when asked explicitly to identify how often a word occurred (experiment 1) or which word occurred more often (experiment 2), elderly Ss were less accurate than young adults. These results support & extend research on age-related dissociations in memory. 4 Tables, 2 Figures, 52 References. Adapted from the source document JF - Aging and Cognition AU - Wiggs, Cheri L AU - Martin, Alex AU - Howard, Darlene V AD - Laboratory Clinical Science National Instit Mental Health, 9000 Rockville Pike Bethesda MD 20892 cwiggs@helix.nih.gov Y1 - 1994///0, PY - 1994 DA - 0, 1994 SP - 247 EP - 259 VL - 1 IS - 3 SN - 0928-9917, 0928-9917 KW - word frequency memory KW - age KW - experiments KW - English-speaking young /elderly adults mean ages 24.5/76.5/21.8/72.9 KW - Elderly (21350) KW - Word Frequency (97450) KW - Memory (52750) KW - Age Differences (01150) KW - article KW - 4016: psycholinguistics; verbal learning: paired associate, serial learning, memory, recognition UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85603395?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Allba&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Aging+and+Cognition&rft.atitle=Direct+and+Indirect+Measures+of+Frequency+Monitoring+in+Young+and+Elderly+Adults&rft.au=Wiggs%2C+Cheri+L%3BMartin%2C+Alex%3BHoward%2C+Darlene+V&rft.aulast=Wiggs&rft.aufirst=Cheri&rft.date=1994-01-01&rft.volume=1&rft.issue=3&rft.spage=247&rft.isbn=&rft.btitle=&rft.title=Aging+and+Cognition&rft.issn=09289917&rft_id=info:doi/ LA - English DB - Linguistics and Language Behavior Abstracts (LLBA) N1 - Date revised - 2003-10-01 N1 - Last updated - 2016-09-27 N1 - CODEN - AGCOEW N1 - SubjectsTermNotLitGenreText - Age Differences (01150); Word Frequency (97450); Memory (52750); Elderly (21350) ER - TY - JOUR T1 - Regional cerebral blood flow imaging with 99mTc-bicisate SPECT in asymmetric Parkinson's disease: studies with and without chronic drug therapy. AN - 85273686; pmid-8263064 AB - Regional cerebral perfusion was assessed in six patients with asymmetric Parkinson's disease (PD) of mild to moderate severity and in six matched normal subjects using 99mTc-bicisate single photon emission computed tomography (SPECT). Regional activity was normalized to whole-brain activity. Each subject was studied twice, separated by 15.2 +/- 9.2 and 18.0 +/- 4.8 days in normals and PD patients, respectively. There was low intrasubject scan-rescan variability in normals, with all regions showing an average intrasubject difference in repeat studies of < 3%. In PD patients after chronic oral antiparkinsonian drugs had been withdrawn, as compared with normal subjects, there was increased perfusion in the caudate and lenticular nuclei contralateral to the worst affected extremities. This increased basal ganglia perfusion was attenuated by chronic oral therapy. The clinical relevance of these changes is indicated by the high positive correlation between various measures of clinical PD severity and the lenticular perfusion. These differences in basal ganglia perfusion measured with 99mTc-bicisate SPECT in mild to moderate, asymmetric PD may be secondary to increased metabolic demand resulting from alterations of synaptic activity. JF - Journal of Cerebral Blood Flow and Metabolism AU - Miletich, R S AU - Quarantelli, M AU - Di, Chiro G AD - Neuroimaging Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/01// PY - 1994 DA - January 1994 SP - S106 EP - S114 VL - 14 Suppl 1 SN - 0271-678X, 0271-678X KW - Reference Values KW - Parkinson Disease KW - Human KW - Adult KW - Brain KW - Antiparkinson Agents KW - Middle Age KW - Female KW - Male KW - Organotechnetium Compounds KW - Tomography, Emission-Computed, Single-Photon KW - Cerebrovascular Circulation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85273686?accountid=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+Cerebral+Blood+Flow+and+Metabolism&rft.atitle=Regional+cerebral+blood+flow+imaging+with+99mTc-bicisate+SPECT+in+asymmetric+Parkinson%27s+disease%3A+studies+with+and+without+chronic+drug+therapy.&rft.au=Miletich%2C+R+S%3BQuarantelli%2C+M%3BDi%2C+Chiro+G&rft.aulast=Miletich&rft.aufirst=R&rft.date=1994-01-01&rft.volume=14+Suppl+1&rft.issue=&rft.spage=S106&rft.isbn=&rft.btitle=&rft.title=Journal+of+Cerebral+Blood+Flow+and+Metabolism&rft.issn=0271678X&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Abnormal pattern of cerebral glucose metabolic rates involving language areas in young adults with Down syndrome. AN - 85161781; pmid-8131038 AB - Correlational and discriminant analyses were applied to "resting" state (eyes covered, ears plugged) regional cerebral glucose metabolic data, obtained with positron emission tomography (PET) and [18F] fluorodeoxyglucose in 14 retarded adults with Down syndrome (10 men, 4 women; age 26-38 years) and 17 age- and sex-matched controls. Down and control subjects showed no differences in the pattern of correlations. However, a discriminant function, reflecting regional interactions involving primary language areas, successfully classified the Down (100%) and control (88%) subjects. The results are consistent with a disruption of brain regional interactions involving language areas in adults with Down syndrome. JF - Brain and Language AU - Azari, N P AU - Horwitz, B AU - Pettigrew, K D AU - Grady, C L AU - Haxby, J V AU - Giacometti, K R AU - Schapiro, M B AD - Laboratory of Neurosciences, National Institute on Aging, Bethesda, Maryland 20892. PY - 1994 SP - 1 EP - 20 VL - 46 IS - 1 SN - 0093-934X, 0093-934X UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85161781?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain+and+Language&rft.atitle=Abnormal+pattern+of+cerebral+glucose+metabolic+rates+involving+language+areas+in+young+adults+with+Down+syndrome.&rft.au=Azari%2C+N+P%3BHorwitz%2C+B%3BPettigrew%2C+K+D%3BGrady%2C+C+L%3BHaxby%2C+J+V%3BGiacometti%2C+K+R%3BSchapiro%2C+M+B&rft.aulast=Azari&rft.aufirst=N&rft.date=1994-01-01&rft.volume=46&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Brain+and+Language&rft.issn=0093934X&rft_id=info:doi/ LA - English DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Corticosteroid therapy, nonendocrine disease, and corticosteroid withdrawal. AN - 77816130; 7704695 JF - Current therapy in endocrinology and metabolism AU - Magiakou, M A AU - Chrousos, G P AD - Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland. Y1 - 1994 PY - 1994 DA - 1994 SP - 120 EP - 124 VL - 5 SN - 0831-652X, 0831-652X KW - Glucocorticoids KW - 0 KW - Index Medicus KW - Drug Interactions KW - Half-Life KW - Humans KW - Drug Monitoring KW - Adult KW - Child KW - Administration, Inhalation KW - Administration, Topical KW - Substance Withdrawal Syndrome KW - Glucocorticoids -- administration & dosage KW - Glucocorticoids -- adverse effects KW - Glucocorticoids -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77816130?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+therapy+in+endocrinology+and+metabolism&rft.atitle=Corticosteroid+therapy%2C+nonendocrine+disease%2C+and+corticosteroid+withdrawal.&rft.au=Magiakou%2C+M+A%3BChrousos%2C+G+P&rft.aulast=Magiakou&rft.aufirst=M&rft.date=1994-01-01&rft.volume=5&rft.issue=&rft.spage=120&rft.isbn=&rft.btitle=&rft.title=Current+therapy+in+endocrinology+and+metabolism&rft.issn=0831652X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-05-05 N1 - Date created - 1995-05-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transcriptional regulation of multidrug resistance gene expression. AN - 77789848; 7710910 JF - Cancer treatment and research AU - Thorgeirsson, S S AU - Gant, T W AU - Silverman, J A AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, Bethesda, MD 20892-0037. Y1 - 1994 PY - 1994 DA - 1994 SP - 57 EP - 68 VL - 73 SN - 0927-3042, 0927-3042 KW - MDR1 KW - mdr KW - mdr1 KW - mdr1a KW - mdr1b KW - mdr2 KW - Antineoplastic Agents KW - 0 KW - Carcinogens KW - Neoplasm Proteins KW - P-Glycoprotein KW - Transcription Factors KW - Xenobiotics KW - Index Medicus KW - Animals KW - Carcinogens -- pharmacology KW - Transcription Factors -- metabolism KW - Sequence Homology, Nucleic Acid KW - Humans KW - Xenobiotics -- pharmacology KW - Mice KW - Gene Amplification KW - Structure-Activity Relationship KW - Rats KW - Promoter Regions, Genetic KW - Antineoplastic Agents -- pharmacology KW - Species Specificity KW - Cricetinae KW - Neoplasm Proteins -- biosynthesis KW - Transcription, Genetic -- drug effects KW - P-Glycoprotein -- genetics KW - Neoplasm Proteins -- genetics KW - P-Glycoprotein -- biosynthesis KW - Gene Expression Regulation, Neoplastic -- drug effects KW - Drug Resistance, Multiple -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77789848?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+treatment+and+research&rft.atitle=Transcriptional+regulation+of+multidrug+resistance+gene+expression.&rft.au=Thorgeirsson%2C+S+S%3BGant%2C+T+W%3BSilverman%2C+J+A&rft.aulast=Thorgeirsson&rft.aufirst=S&rft.date=1994-01-01&rft.volume=73&rft.issue=&rft.spage=57&rft.isbn=&rft.btitle=&rft.title=Cancer+treatment+and+research&rft.issn=09273042&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-05-18 N1 - Date created - 1995-05-18 N1 - Date revised - 2017-01-13 N1 - Gene symbol - MDR1; mdr; mdr1; mdr1a; mdr1b; mdr2 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A Southwest Oncology Group phase II evaluation of fluderabine monophosphate in sarcoma. AN - 77776251; 7534752 JF - Investigational new drugs AU - Grever, M R AU - Benedetti, J AU - Balcerzak, S P AU - Taylor, S A AU - Miller, T P AU - Dakhil, S R AD - National Cancer Institute, Bethesda, MD. Y1 - 1994 PY - 1994 DA - 1994 SP - 259 EP - 261 VL - 12 IS - 3 SN - 0167-6997, 0167-6997 KW - Antimetabolites, Antineoplastic KW - 0 KW - Vidarabine Phosphate KW - 106XV160TZ KW - fludarabine phosphate KW - 1X9VK9O1SC KW - Index Medicus KW - Nausea -- chemically induced KW - Hematologic Diseases -- chemically induced KW - Sleep Stages KW - Humans KW - Neoplasm Metastasis KW - Middle Aged KW - Vidarabine Phosphate -- therapeutic use KW - Vidarabine Phosphate -- adverse effects KW - Antimetabolites, Antineoplastic -- adverse effects KW - Sarcoma -- drug therapy KW - Antimetabolites, Antineoplastic -- therapeutic use KW - Vidarabine Phosphate -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77776251?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Investigational+new+drugs&rft.atitle=A+Southwest+Oncology+Group+phase+II+evaluation+of+fluderabine+monophosphate+in+sarcoma.&rft.au=Grever%2C+M+R%3BBenedetti%2C+J%3BBalcerzak%2C+S+P%3BTaylor%2C+S+A%3BMiller%2C+T+P%3BDakhil%2C+S+R&rft.aulast=Grever&rft.aufirst=M&rft.date=1994-01-01&rft.volume=12&rft.issue=3&rft.spage=259&rft.isbn=&rft.btitle=&rft.title=Investigational+new+drugs&rft.issn=01676997&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-04-26 N1 - Date created - 1995-04-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetic and phylogenetic analyses of endangered species. AN - 77774229; 7893136 JF - Annual review of genetics AU - O'Brien, S J AD - Laboratory of Viral Carcinogenesis, National Cancer Institute, Frederick, Maryland 21702-1201. Y1 - 1994 PY - 1994 DA - 1994 SP - 467 EP - 489 VL - 28 SN - 0066-4197, 0066-4197 KW - Index Medicus KW - Animals KW - Phylogeny KW - Conservation of Natural Resources KW - Animals, Wild -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77774229?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annual+review+of+genetics&rft.atitle=Genetic+and+phylogenetic+analyses+of+endangered+species.&rft.au=O%27Brien%2C+S+J&rft.aulast=O%27Brien&rft.aufirst=S&rft.date=1994-01-01&rft.volume=28&rft.issue=&rft.spage=467&rft.isbn=&rft.btitle=&rft.title=Annual+review+of+genetics&rft.issn=00664197&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-04-19 N1 - Date created - 1995-04-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - gp120 as an etiologic agent for NeuroAIDS: neurotoxicity and model systems. AN - 77760464; 7874383 AB - The search for an agent that can mediate the symptoms of NeuroAIDS has been directed at gp120, the major envelope protein from HIV. The toxicity associated with gp120 was examined as a model and predictor of the neuropathological and neuropsychiatric manifestations of AIDS. Studies of the neurotoxic effects of purified gp120 on neurons from the rodent CNS cell cultures indicated the following: potent and selective killing of subpopulations of hippocampal neurons; varying potency of gp120s obtained from various HIV isolates; complete and potent protection from gp120 killing action after treatment with peptides related to vasoactive intestinal peptide; and obligatory presence of glia for gp120-related toxicity. Investigations of gp120 treatment of rodents revealed: cortical neurodystrophy with reduced arborizations and swollen processes; delays in developmental behaviors involving motor skills; peptide T prevention or attenuation of the morphological and behavioral deficits/delays produced by administration of gp120; and impairment of learning in the Morris swim maze. In addition, studies of subcutaneously administered, radiolabeled gp120 in neonatal animals demonstrated the presence of toxic fragments of gp120 in the developing brain. With the use of model test systems of non-human derived cell cultures and neonatal rats, we have captured and predicted a number of the morphological and behavioral deficits associated with AIDS. These multi-disciplinary studies of the actions of gp120 and associated fragments in rodents and rodent cells predict that the loss of cognitive and neurological function in patients with AIDS are attributed in part to interference of critical brain functions by the envelope protein, gp120. JF - Advances in neuroimmunology AU - Brenneman, D E AU - McCune, S K AU - Mervis, R F AU - Hill, J M AD - Section on Developmental and Molecular Pharmacology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994 PY - 1994 DA - 1994 SP - 157 EP - 165 VL - 4 IS - 3 SN - 0960-5428, 0960-5428 KW - Cytokines KW - 0 KW - HIV Envelope Protein gp120 KW - Peptide Fragments KW - Peptide T KW - 106362-33-8 KW - Vasoactive Intestinal Peptide KW - 37221-79-7 KW - Index Medicus KW - AIDS/HIV KW - Vasoactive Intestinal Peptide -- pharmacology KW - Peptide T -- pharmacology KW - Animals KW - Peptide Fragments -- toxicity KW - Disease Models, Animal KW - Amino Acid Sequence KW - Mice KW - Behavior, Animal KW - Neurons -- pathology KW - Rats KW - Animals, Newborn KW - Cells, Cultured KW - Cell Death KW - Molecular Sequence Data KW - Cytokines -- physiology KW - Cytopathogenic Effect, Viral KW - Species Specificity KW - HIV Envelope Protein gp120 -- physiology KW - AIDS Dementia Complex -- etiology KW - HIV Envelope Protein gp120 -- toxicity KW - AIDS Dementia Complex -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77760464?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Advances+in+neuroimmunology&rft.atitle=gp120+as+an+etiologic+agent+for+NeuroAIDS%3A+neurotoxicity+and+model+systems.&rft.au=Brenneman%2C+D+E%3BMcCune%2C+S+K%3BMervis%2C+R+F%3BHill%2C+J+M&rft.aulast=Brenneman&rft.aufirst=D&rft.date=1994-01-01&rft.volume=4&rft.issue=3&rft.spage=157&rft.isbn=&rft.btitle=&rft.title=Advances+in+neuroimmunology&rft.issn=09605428&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-04-06 N1 - Date created - 1995-04-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Neurotrophic factor gene expression in astrocytes during development and following injury. AN - 77759992; 7532097 AB - Astrocyte cultures were utilized to examine regulation of the expression of several trophic factor genes. Regulation by the beta-adrenergic receptor was demonstrated by exposure of striatal and cortical astrocytes to isoproterenol, which resulted in increased content of mRNAs for nerve growth factor (NGF), brain-derived neurotrophic factor, and proenkephalin (PE), as well as NGF and Met-enkephalin. Developmental regulation was analyzed by preparing cortical astrocytes from animals of four different ages--embryonic day 20, postnatal days 3 and 8, and adult. Because both the PE and NGF genes showed developmental downregulation, we asked whether we could prepare reactive astrocytes from lesioned adult brain and see expression turned back on. Astrocytes prepared from 6-hydroxydopamine-lesioned rat striatum or MPTP-lesioned mouse striatum contained increased GFAP and NGF mRNA. Comparable changes in GFAP and NGF could be achieved by treatment of control cultures with interferon-gamma or interleukin-1 beta. These results suggest that locus coeruleus neurons could control astrocyte synthesis of neurotrophic factors through release of of norepinephrine, but that in injured brain other factors, such as cytokines, may become equally important. JF - Brain research bulletin AU - Schwartz, J P AU - Nishiyama, N AD - Molecular Genetics Section, NINDS, NIH, Bethesda, MD 20892. Y1 - 1994 PY - 1994 DA - 1994 SP - 403 EP - 407 VL - 35 IS - 5-6 SN - 0361-9230, 0361-9230 KW - Brain-Derived Neurotrophic Factor KW - 0 KW - Enkephalins KW - Glial Fibrillary Acidic Protein KW - Nerve Growth Factors KW - Nerve Tissue Proteins KW - Protein Precursors KW - Receptors, Adrenergic, beta KW - proenkephalin KW - Enkephalin, Methionine KW - 58569-55-4 KW - RNA KW - 63231-63-0 KW - Oxidopamine KW - 8HW4YBZ748 KW - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine KW - 9P21XSP91P KW - Index Medicus KW - Animals KW - Blotting, Northern KW - Sympathectomy, Chemical KW - Substantia Nigra -- growth & development KW - Substantia Nigra -- drug effects KW - Nerve Tissue Proteins -- biosynthesis KW - Glial Fibrillary Acidic Protein -- biosynthesis KW - Nucleic Acid Hybridization KW - RNA -- biosynthesis KW - Rats KW - Rats, Sprague-Dawley KW - Enkephalins -- biosynthesis KW - Receptors, Adrenergic, beta -- biosynthesis KW - Cells, Cultured KW - Protein Precursors -- biosynthesis KW - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine -- pharmacology KW - Receptors, Adrenergic, beta -- drug effects KW - Enkephalin, Methionine -- metabolism KW - Substantia Nigra -- physiology KW - Male KW - Gene Expression Regulation, Developmental -- physiology KW - Nerve Growth Factors -- biosynthesis KW - Nerve Growth Factors -- genetics KW - Astrocytes -- drug effects KW - Astrocytes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77759992?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain+research+bulletin&rft.atitle=Neurotrophic+factor+gene+expression+in+astrocytes+during+development+and+following+injury.&rft.au=Schwartz%2C+J+P%3BNishiyama%2C+N&rft.aulast=Schwartz&rft.aufirst=J&rft.date=1994-01-01&rft.volume=35&rft.issue=5-6&rft.spage=403&rft.isbn=&rft.btitle=&rft.title=Brain+research+bulletin&rft.issn=03619230&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-03-21 N1 - Date created - 1995-03-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CONF T1 - Summary of workshop contributions. Third Workshop on NeuroAIDS. AN - 77759391; 7874382 JF - Advances in neuroimmunology AU - Black, R AU - Sager, P Y1 - 1994 PY - 1994 DA - 1994 SP - 149 EP - 156 VL - 4 IS - 3 KW - Cytokines KW - 0 KW - HIV Envelope Protein gp120 KW - Quinolinic Acid KW - F6F0HK1URN KW - Index Medicus KW - AIDS/HIV KW - Animals KW - Gene Expression Regulation, Viral KW - Humans KW - Simian Acquired Immunodeficiency Syndrome -- virology KW - Quinolinic Acid -- toxicity KW - Child KW - HIV Envelope Protein gp120 -- physiology KW - Microglia -- virology KW - HIV -- physiology KW - Adult KW - Cytokines -- physiology KW - Cytopathogenic Effect, Viral KW - Macaca mulatta KW - Blood-Brain Barrier KW - AIDS Dementia Complex -- virology KW - AIDS Dementia Complex -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77759391?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&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=Advances+in+neuroimmunology&rft.atitle=Summary+of+workshop+contributions.+Third+Workshop+on+NeuroAIDS.&rft.au=Black%2C+R%3BSager%2C+P&rft.aulast=Black&rft.aufirst=R&rft.date=1994-01-01&rft.volume=4&rft.issue=3&rft.spage=149&rft.isbn=&rft.btitle=&rft.title=Advances+in+neuroimmunology&rft.issn=09605428&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-04-06 N1 - Date created - 1995-04-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Comparative metabolism and disposition of acrylonitrile and methacrylonitrile in rats. AN - 77730662; 7857200 AB - Aliphatic nitriles are a class of chemicals used in high volumes in the production of plastics and elastomers, in organic synthesis, and in production of a number of food packaging containers. Toxicity and metabolism of acrylonitrile (AN) are well characterized. On the other hand, minimal information is available on the toxicity or fate of structurally related, methacrylonitrile (MAN). In an attempt to predict the toxicity of MAN, the present studies were designed to compare the disposition of both nitriles in rats. After gavage administration of equimolar doses (0.87 mmol/kg) of 2-14C-MAN or 2-14C-AN to male F344 rats, both chemicals were well absorbed from the GI tract and distributed to all major tissues. However, major differences in the disposition of the two nitriles were observed. While approximately 39% of the administered MAN dose was eliminated as CO2 in 24 h after dosing, only 11% of an equimolar dose of AN was eliminated as such. In addition, 31% of the MAN dose was exhaled as organic volatiles in 24 h compared to less than 2% of an equivalent AN dose. MAN and acetone were identified by HPLC analysis of expired organic volatiles from MAN-treated rats. HPLC analysis showed that AN is the only organic volatile exhaled by AN-treated rats. Urinary excretion of MAN was 22% compared to 67% of an equivalent dose of AN. The major urinary metabolite from AN results from direct conjugation with GSH, whereas the major urinary metabolite from MAN results from conjugation of the epoxide with GSH.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Archives of toxicology AU - Burka, L T AU - Sanchez, I M AU - Ahmed, A E AU - Ghanayem, B I AD - National Institute of Environmental Health Sciences Experimental Toxicology Branch, Research Triangle Park, North Carolina. Y1 - 1994 PY - 1994 DA - 1994 SP - 611 EP - 618 VL - 68 IS - 10 SN - 0340-5761, 0340-5761 KW - Methacrylates KW - 0 KW - Nitriles KW - methacrylonitrile KW - 04S4K38612 KW - Acetone KW - 1364PS73AF KW - Proadifen KW - A510CA4CBT KW - Acrylonitrile KW - MP1U0D42PE KW - Phenobarbital KW - YQE403BP4D KW - Index Medicus KW - Administration, Oral KW - Animals KW - Digestive System -- metabolism KW - Tissue Distribution KW - Lung -- metabolism KW - Intestinal Absorption -- drug effects KW - Chromatography, High Pressure Liquid KW - Structure-Activity Relationship KW - Rats KW - Phenobarbital -- pharmacology KW - Proadifen -- pharmacology KW - Rats, Inbred F344 KW - Acetone -- metabolism KW - Male KW - Nitriles -- pharmacokinetics KW - Methacrylates -- pharmacokinetics KW - Methacrylates -- toxicity KW - Acrylonitrile -- toxicity KW - Nitriles -- administration & dosage KW - Acrylonitrile -- urine KW - Nitriles -- toxicity KW - Methacrylates -- administration & dosage KW - Acrylonitrile -- administration & dosage KW - Acrylonitrile -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77730662?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+toxicology&rft.atitle=Comparative+metabolism+and+disposition+of+acrylonitrile+and+methacrylonitrile+in+rats.&rft.au=Patterson%2C+R+M%3BWitcher%2C+L+L%3BHe%2C+C%3BSelkirk%2C+J+K%3BMerrick%2C+B+A&rft.aulast=Patterson&rft.aufirst=R&rft.date=1993-05-01&rft.volume=14&rft.issue=5&rft.spage=752&rft.isbn=&rft.btitle=&rft.title=BioTechniques&rft.issn=07366205&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-03-16 N1 - Date created - 1995-03-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chromosome fragility and instability in human cancer. AN - 77719596; 7849084 AB - The development of cancer is a multistep process triggered by physical, chemical, or biological carcinogenic factors, with the progression to an invasive phenotype requiring cumulative genetic alterations. Not all cellular genomic sequences are equally susceptible to carcinogenic factors or involved in pathologically relevant genetic alterations. Because of structural chromatin organization and DNA replication, certain genomic regions exhibit an increased fragility and tendency to recombination. At these regions, called fragile sites, there is a convergence of specific deletions, translocations, chemically induced lesions, and virus integrations. Isolation and cloning of sequences at fragile sites are important to a better understanding of the carcinogenesis process and to development of preventive measures. JF - Critical reviews in oncogenesis AU - Popescu, N C AD - Laboratory of Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994 PY - 1994 DA - 1994 SP - 121 EP - 140 VL - 5 IS - 2-3 SN - 0893-9675, 0893-9675 KW - Index Medicus KW - Humans KW - Chromosome Fragile Sites KW - Chromosome Fragility KW - Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77719596?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+oncogenesis&rft.atitle=Chromosome+fragility+and+instability+in+human+cancer.&rft.au=Popescu%2C+N+C&rft.aulast=Popescu&rft.aufirst=N&rft.date=1994-01-01&rft.volume=5&rft.issue=2-3&rft.spage=121&rft.isbn=&rft.btitle=&rft.title=Critical+reviews+in+oncogenesis&rft.issn=08939675&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-03-10 N1 - Date created - 1995-03-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Neurofilament phosphorylation is enhanced in cultured chick spinal cord neurons exposed to cerebrospinal fluid from amyotrophic lateral sclerosis patients. AN - 77717774; 7839827 AB - Amyotrophic lateral sclerosis (ALS), a neurodegenerative disease, is characterized by degeneration of lower and upper motor neurons. Serum and cerebrospinal fluid (CSF) of ALS patients have been found to exert toxic effects on neurons in culture. We report here increased phosphorylation of neurofilaments (NF) in the soma of chick spinal cord neurons in culture when exposed to CSF of ALS patients. Spinal cord neurons were cultured from 10-day embryonic chick and exposed to culture medium supplemented with CSF or serum (10%) from ALS and non-ALS patients for 48 h. There was a significant increase in the number of neuronal soma staining with antibodies against phosphorylated NF, following exposure to CSF from ALS patients. Such an increase, however, was not observed in cultures exposed to serum from ALS patients and also serum and CSF from non-ALS patients. These results suggest that the CSF of ALS patients may contain factor(s) which induces aberrant phosphorylation of NF in the soma, a probable forerunner to the formation of neurofibrillary tangles and eventual degeneration of neurons. JF - Acta neuropathologica AU - Nagaraja, T N AU - Gourie-Devi, M AU - Nalini, A AU - Raju, T R AD - Department of Neurophysiology, National Institute of Mental Health and Neuro Sciences, Bangalore, India. Y1 - 1994 PY - 1994 DA - 1994 SP - 349 EP - 352 VL - 88 IS - 4 SN - 0001-6322, 0001-6322 KW - Culture Media KW - 0 KW - Neurofilament Proteins KW - Index Medicus KW - Microscopy, Fluorescence KW - Animals KW - Phosphorylation KW - Cells, Cultured KW - Humans KW - Chick Embryo KW - Spinal Cord -- pathology KW - Male KW - Female KW - Amyotrophic Lateral Sclerosis -- pathology KW - Neurons -- metabolism KW - Amyotrophic Lateral Sclerosis -- cerebrospinal fluid KW - Neurofilament Proteins -- metabolism KW - Amyotrophic Lateral Sclerosis -- blood KW - Neurons -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77717774?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Journal+of+Medical+Genetics&rft.atitle=Cognitive+and+behavioral+profile+of+the+oculocerebrorenal+syndrome+of+Lowe.&rft.au=Kenworthy%2C+L%3BPark%2C+T%3BCharnas%2C+L+R&rft.aulast=Kenworthy&rft.aufirst=L&rft.date=1993-05-01&rft.volume=46&rft.issue=3&rft.spage=297&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Medical+Genetics&rft.issn=01487299&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-02-27 N1 - Date created - 1995-02-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Intrapleural photodynamic therapy: results of a phase I trial. AN - 77715117; 7834425 AB - The management of pleural neoplasms, specifically mesothelioma, remains difficult. We performed a phase I trial in 54 patients with isolated hemithorax pleural malignancy to determine (a) the feasibility of intraoperative, intrapleural photodynamic therapy after debulking surgery; (b) the influence of light dose/sensitizer interval on postoperative morbidity in order to define the photodynamic therapy (PDT) maximal tolerated dose (MTD); and (c) whether first order dosimetry could be applied to this complex geometry. Cohorts of three patients were given escalating intraoperative light doses of 15-35 J/cm2 48 h after i.v. delivery of 2.0 mg/kg Photofrin II (Quadra Logic Technologies, Vancouver, British Columbia, Canada), and then escalating light doses of 30-32.5 J/cm2 after a 24-h sensitizer/operation interval. Twelve patients could not be debulked to the prerequisite 5 mm residual tumor thickness. The remaining 42 patients underwent 19 modified pleuropneumonectomies, five lobectomy-pleurectomies, and 18 pleurectomies. Intrapleural PDT was delivered using 630 nm light from two argon pump-dye lasers, and real-time and cumulative light doses were monitored using seven uniquely designed, computer-interfaced photodiodes. There was one 30-day mortality from intraoperative hemorrhage. In the 48-h sensitizer/operation group (n = 33), possible PDT-related complications included an empyema with late hemorrhage in one of three patients at 17.5 J/cm2 and a bronchopleural fistula at 35 J/cm2. At each of these light doses, three additional patients were treated without complication. Two patients subjected to 24-h sensitizer dosing and 32.5 J/cm2 developed esophageal perforations after pleuropneumonectomy at identical sites. The MTD was declared as 30 J/cm2 light with a 24-h dosing interval when none of the six patients (three original, three repeat) at that level developed toxicity. These data demonstrate that resection and intrapleural PDT can be performed safely with currently available sensitizers and lasers. Phase II and III trials are now warranted at this MTD in a homogeneous population of patients with pleural malignancies. JF - Annals of surgical oncology AU - Pass, H I AU - DeLaney, T F AU - Tochner, Z AU - Smith, P E AU - Temeck, B K AU - Pogrebniak, H W AU - Kranda, K C AU - Russo, A AU - Friauf, W S AU - Cole, J W AD - Thoracic Oncology Section, National Cancer Institute, National Institutes of Health, Besthesda, Maryland 20892. Y1 - 1994/01// PY - 1994 DA - January 1994 SP - 28 EP - 37 VL - 1 IS - 1 SN - 1068-9265, 1068-9265 KW - Index Medicus KW - Mesothelioma -- drug therapy KW - Survival Rate KW - Combined Modality Therapy KW - Mesothelioma -- surgery KW - Humans KW - Adult KW - Mesothelioma -- mortality KW - Aged KW - Middle Aged KW - Male KW - Female KW - Photochemotherapy -- adverse effects KW - Pleural Neoplasms -- mortality KW - Pleural Neoplasms -- drug therapy KW - Photochemotherapy -- methods KW - Pleural Neoplasms -- surgery UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77715117?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+surgical+oncology&rft.atitle=Intrapleural+photodynamic+therapy%3A+results+of+a+phase+I+trial.&rft.au=Pass%2C+H+I%3BDeLaney%2C+T+F%3BTochner%2C+Z%3BSmith%2C+P+E%3BTemeck%2C+B+K%3BPogrebniak%2C+H+W%3BKranda%2C+K+C%3BRusso%2C+A%3BFriauf%2C+W+S%3BCole%2C+J+W&rft.aulast=Pass&rft.aufirst=H&rft.date=1994-01-01&rft.volume=1&rft.issue=1&rft.spage=28&rft.isbn=&rft.btitle=&rft.title=Annals+of+surgical+oncology&rft.issn=10689265&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-03-02 N1 - Date created - 1995-03-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Perinatal morbidity and mortality in substance using families: effects and intervention strategies. AN - 77696686; 7833901 AB - The epidemic of drug abuse has overwhelmed men, women and children and caused incalculable damage to an honoured structure in human civilization--the family. Moreover, during the past decade, increasing numbers of pregnant drug-dependent women have been presenting themselves to medical facilities, some to receive ongoing prenatal care, but others only to deliver their babies without the benefit of any medical services. The present chapter reviews the current literature, as well as the experiences of the author, with regard to the sociomedical characteristics of pregnant, drug-dependent women. The effects of substances of abuse on pregnancy, the foetus and the newborn with respect to morbidity and mortality are presented. Recommendations for management of both the pregnant drug-dependent women and her child, on the basis of clinical research, are also outlined. Although overall medical advances have escalated during the past three decades, there is still much to learn with regard to the effects of drugs of abuse upon families. Moreover, methods of prevention and treatment still need considerable study. By re-evaluating the areas of strength and weakness in the body of available knowledge, future research will be able to enhance the ability to help those unfortunate families that are effected by substance abuse. JF - Bulletin on narcotics AU - Finnegan, L P AD - National Institute on Drug Abuse, National Institutes of Health, Bethesda, Maryland. Y1 - 1994 PY - 1994 DA - 1994 SP - 19 EP - 43 VL - 46 IS - 1 SN - 0007-523X, 0007-523X KW - Index Medicus KW - Risk Factors KW - Humans KW - Forecasting KW - Research KW - Female KW - Pregnancy KW - Pregnancy Outcome -- epidemiology KW - Pregnancy Complications -- psychology KW - Pregnancy Complications -- prevention & control KW - Substance-Related Disorders -- complications KW - Primary Prevention -- methods KW - Substance-Related Disorders -- psychology KW - Family -- psychology KW - Substance-Related Disorders -- prevention & control KW - Substance-Related Disorders -- epidemiology KW - Pregnancy Complications -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77696686?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Bulletin+on+narcotics&rft.atitle=Perinatal+morbidity+and+mortality+in+substance+using+families%3A+effects+and+intervention+strategies.&rft.au=Finnegan%2C+L+P&rft.aulast=Finnegan&rft.aufirst=L&rft.date=1994-01-01&rft.volume=46&rft.issue=1&rft.spage=19&rft.isbn=&rft.btitle=&rft.title=Bulletin+on+narcotics&rft.issn=0007523X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-03-02 N1 - Date created - 1995-03-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Impairments in reflective cognitive functions in alcoholics: a neuropharmacological model. AN - 77134680; 8974349 AB - The ability to make use of reflective cognitive operations in monitoring and evaluating remembered events is impaired in subgroups of nominally cognitively unimpaired, detoxified alcoholics. Alcoholics, relative to controls, make more errors in identifying the source of remembered information (i.e. whether a remembered word was self-generated or was a stimulus word presented by the experimenter), and are impaired in their ability to inhibit confabulatory errors (intrusions). The cognitive-memory impairment expressed in benzodiazepine-treated normal volunteers mimics this impairment in alcoholics. Disturbances in prefrontal and frontal lobe functions may be involved in this selective impairment in cognition in many alcoholics and may also contribute to what accounts for the failures in reflective cognitive operations observed in amnestic patients. JF - Alcohol and alcoholism (Oxford, Oxfordshire). Supplement AU - Weingartner, H J AU - Eckardt, M J AU - Hommer, D AU - Johnson, D N AD - Cognitive Neurosciences Section, LCS, NIAAA, Bethesda, MD 20892, USA. Y1 - 1994 PY - 1994 DA - 1994 SP - 291 EP - 298 VL - 2 SN - 1358-6173, 1358-6173 KW - Anti-Anxiety Agents KW - 0 KW - Lorazepam KW - O26FZP769L KW - Index Medicus KW - Anti-Anxiety Agents -- pharmacology KW - Double-Blind Method KW - Memory -- drug effects KW - Neuropharmacology KW - Humans KW - Case-Control Studies KW - Middle Aged KW - Mental Recall KW - Models, Neurological KW - Lorazepam -- pharmacology KW - Cognition Disorders -- etiology KW - Cognition Disorders -- drug therapy KW - Alcoholism -- physiopathology KW - Cognition Disorders -- physiopathology KW - Alcoholism -- psychology KW - Alcoholism -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77134680?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Alcohol+and+alcoholism+%28Oxford%2C+Oxfordshire%29.+Supplement&rft.atitle=Impairments+in+reflective+cognitive+functions+in+alcoholics%3A+a+neuropharmacological+model.&rft.au=Weingartner%2C+H+J%3BEckardt%2C+M+J%3BHommer%2C+D%3BJohnson%2C+D+N&rft.aulast=Weingartner&rft.aufirst=H&rft.date=1994-01-01&rft.volume=2&rft.issue=&rft.spage=291&rft.isbn=&rft.btitle=&rft.title=Alcohol+and+alcoholism+%28Oxford%2C+Oxfordshire%29.+Supplement&rft.issn=13586173&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-04-07 N1 - Date created - 1997-04-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A quantitative comparison of DNA sequence assembly programs. AN - 77130374; 8790470 AB - We have compared 11 sequence assembly programs for the accuracy and reproducibility with which they assemble DNA fragments into a completed sequence. To test the assemblers under controlled conditions, the rat multidrug resistance (RATMDRM) gene sequence was randomly divided into overlapping 200- to 400-base fragments. Various degrees of error, in the form of miss-identified bases, missed bases, and duplicated bases, were randomly added to these fragments. The probability of an error, and the type of error, was modified using an error distribution template that was developed by comparing the original fragments used to sequence RATMDRM with the final, edited sequence stored in GenBank. From 0 to 15% error was then added to independent sets of fragments, and assemblage was attempted. The quality of the assemblages was evaluated by comparing the number of differences between the assembled sequence and the original sequence. Tests were also done to determine if the order in which fragments were added to a project affected the final sequence and if the quality of assemblage was sequence dependent. Similar results were also obtained using other, unrelated sequences. The programs could be roughly divided into three groups based on the accuracy and reproducibility of assembly. Three (GCG, FAB, and AutoAssembler) consistently produced consensus sequences of low error and high reproducibility. Intermediate results were obtained with five other programs (Sequencher, AssemblyLIGN, XBAP, SeqMan, and AutoAssembler in a mode that made use of an external special processor). Less satisfactory results were obtained with the remaining three programs (GeneWorks, GENeration, and PC/Gene). The ability of the programs to edit the assembled sequence was also compared. Five of the programs were able to display and edit automatic sequencer trace files. The Sequencher program had a particularly well-designed sequence editor that allowed rapid examination and correction of assembly errors. JF - Journal of computational biology : a journal of computational molecular cell biology AU - Miller, M J AU - Powell, J I AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, Bethesda, MD 20892, USA. mark@helix.nih.gov Y1 - 1994 PY - 1994 DA - 1994 SP - 257 EP - 269 VL - 1 IS - 4 SN - 1066-5277, 1066-5277 KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Rats KW - Animals KW - Base Sequence KW - Sequence Alignment KW - Reproducibility of Results KW - Drug Resistance, Multiple -- genetics KW - Software KW - DNA -- chemistry KW - Models, Chemical UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77130374?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+computational+biology+%3A+a+journal+of+computational+molecular+cell+biology&rft.atitle=A+quantitative+comparison+of+DNA+sequence+assembly+programs.&rft.au=Miller%2C+M+J%3BPowell%2C+J+I&rft.aulast=Miller&rft.aufirst=M&rft.date=1994-01-01&rft.volume=1&rft.issue=4&rft.spage=257&rft.isbn=&rft.btitle=&rft.title=Journal+of+computational+biology+%3A+a+journal+of+computational+molecular+cell+biology&rft.issn=10665277&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-11-22 N1 - Date created - 1996-11-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - p16INK4 mutations and altered expression in human tumors and cell lines. AN - 77119965; 7587103 JF - Cold Spring Harbor symposia on quantitative biology AU - Okamoto, A AU - Demetrick, D J AU - Spillare, E A AU - Hagiwara, K AU - Hussain, S P AU - Bennett, W P AU - Forrester, K AU - Gerwin, B AU - Greenblatt, M S AU - Serrano, M AD - Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1994 PY - 1994 DA - 1994 SP - 49 EP - 57 VL - 59 SN - 0091-7451, 0091-7451 KW - Carrier Proteins KW - 0 KW - Cyclin-Dependent Kinase Inhibitor p16 KW - Cyclins KW - DNA Primers KW - Enzyme Inhibitors KW - Oncogene Proteins KW - Cyclin D1 KW - 136601-57-5 KW - Cyclin-Dependent Kinases KW - EC 2.7.11.22 KW - Index Medicus KW - Homozygote KW - DNA Primers -- genetics KW - Humans KW - Oncogene Proteins -- genetics KW - Gene Deletion KW - Gene Expression Regulation, Neoplastic KW - Base Sequence KW - Genes, Retinoblastoma KW - Molecular Sequence Data KW - Cyclin-Dependent Kinases -- antagonists & inhibitors KW - Enzyme Inhibitors -- metabolism KW - Cell Line KW - Cyclins -- genetics KW - Female KW - Neoplasms -- enzymology KW - Genes, Tumor Suppressor KW - Carrier Proteins -- genetics KW - Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77119965?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cold+Spring+Harbor+symposia+on+quantitative+biology&rft.atitle=p16INK4+mutations+and+altered+expression+in+human+tumors+and+cell+lines.&rft.au=Okamoto%2C+A%3BDemetrick%2C+D+J%3BSpillare%2C+E+A%3BHagiwara%2C+K%3BHussain%2C+S+P%3BBennett%2C+W+P%3BForrester%2C+K%3BGerwin%2C+B%3BGreenblatt%2C+M+S%3BSerrano%2C+M&rft.aulast=Okamoto&rft.aufirst=A&rft.date=1994-01-01&rft.volume=59&rft.issue=&rft.spage=49&rft.isbn=&rft.btitle=&rft.title=Cold+Spring+Harbor+symposia+on+quantitative+biology&rft.issn=00917451&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-11-29 N1 - Date created - 1995-11-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Defining the steps in a multistep mouse model for mammary carcinogenesis. AN - 77119598; 7587104 JF - Cold Spring Harbor symposia on quantitative biology AU - Varmus, H E AU - Godley, L A AU - Roy, S AU - Taylor, I C AU - Yuschenkoff, L AU - Shi, Y P AU - Pinkel, D AU - Gray, J AU - Pyle, R AU - Aldaz, C M AD - Office of the Director, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1994 PY - 1994 DA - 1994 SP - 491 EP - 499 VL - 59 SN - 0091-7451, 0091-7451 KW - Proto-Oncogene Proteins KW - 0 KW - Wnt Proteins KW - Zebrafish Proteins KW - Fibroblast Growth Factors KW - 62031-54-3 KW - Receptor Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - TYRO3 protein, human KW - Index Medicus KW - Breast Neoplasms -- genetics KW - Animals KW - Receptor Protein-Tyrosine Kinases -- genetics KW - Genes, Tumor Suppressor KW - Humans KW - Disease Models, Animal KW - Mice KW - Proto-Oncogenes KW - Genes, p53 KW - Breast Neoplasms -- etiology KW - Fibroblast Growth Factors -- genetics KW - Proto-Oncogene Proteins -- genetics KW - Mutation KW - Female KW - Cocarcinogenesis KW - Mammary Neoplasms, Experimental -- genetics KW - Mammary Neoplasms, Experimental -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77119598?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cold+Spring+Harbor+symposia+on+quantitative+biology&rft.atitle=Defining+the+steps+in+a+multistep+mouse+model+for+mammary+carcinogenesis.&rft.au=Varmus%2C+H+E%3BGodley%2C+L+A%3BRoy%2C+S%3BTaylor%2C+I+C%3BYuschenkoff%2C+L%3BShi%2C+Y+P%3BPinkel%2C+D%3BGray%2C+J%3BPyle%2C+R%3BAldaz%2C+C+M&rft.aulast=Varmus&rft.aufirst=H&rft.date=1994-01-01&rft.volume=59&rft.issue=&rft.spage=491&rft.isbn=&rft.btitle=&rft.title=Cold+Spring+Harbor+symposia+on+quantitative+biology&rft.issn=00917451&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-11-29 N1 - Date created - 1995-11-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cellular senescence and cancer. AN - 77117920; 7587095 JF - Cold Spring Harbor symposia on quantitative biology AU - Barrett, J C AU - Annab, L A AU - Alcorta, D AU - Preston, G AU - Vojta, P AU - Yin, Y AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 1994 PY - 1994 DA - 1994 SP - 411 EP - 418 VL - 59 SN - 0091-7451, 0091-7451 KW - CDKN1A protein, human KW - 0 KW - Carrier Proteins KW - Cyclin-Dependent Kinase Inhibitor p16 KW - Cyclin-Dependent Kinase Inhibitor p21 KW - Cyclins KW - Retinoblastoma Protein KW - Index Medicus KW - Animals KW - Genes, Tumor Suppressor KW - Apoptosis -- physiology KW - Carrier Proteins -- genetics KW - Humans KW - Retinoblastoma Protein -- physiology KW - Models, Biological KW - Cyclins -- physiology KW - Apoptosis -- genetics KW - Carrier Proteins -- physiology KW - Retinoblastoma Protein -- genetics KW - Cyclins -- genetics KW - Cell Division KW - Cell Aging -- physiology KW - Cell Aging -- genetics KW - Neoplasms -- genetics KW - Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77117920?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cold+Spring+Harbor+symposia+on+quantitative+biology&rft.atitle=Cellular+senescence+and+cancer.&rft.au=Barrett%2C+J+C%3BAnnab%2C+L+A%3BAlcorta%2C+D%3BPreston%2C+G%3BVojta%2C+P%3BYin%2C+Y&rft.aulast=Barrett&rft.aufirst=J&rft.date=1994-01-01&rft.volume=59&rft.issue=&rft.spage=411&rft.isbn=&rft.btitle=&rft.title=Cold+Spring+Harbor+symposia+on+quantitative+biology&rft.issn=00917451&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-11-29 N1 - Date created - 1995-11-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Strategy and planning for chemopreventive drug development: clinical development plans. Chemoprevention Branch and Agent Development Committee. National Cancer Institute. AN - 77114423; 7616753 AB - At the National Cancer Institute, Division of Cancer Prevention and Control, the Chemoprevention Branch and Agent Development Committee develop strategies for efficiently identifying, procuring, and advancing the most promising drugs into clinical trials. Scientific expertise is applied at each phase of development to critically review the testing methods and results, and to establish and apply criteria for evaluating the agents for further development. The Clinical Development Plan, prepared by the Chemoprevention Branch and the Agent Development Committee, is a summary of the status of the agent regarding evidence for safety and chemopreventive efficacy in preclinical and clinical studies. It also contains the strategy for further development of the drug that addresses pharmacodynamics, drug effect measurements, intermediate biomarkers for monitoring efficacy, toxicity, supply and formulation, regulatory approval, and proposed clinical trials. Sixteen Clinical Development Plans are presented here: N-acetyl-l-cysteine (NAC), aspirin, calcium, beta-carotene, 2-difluoromethylornithine (DFMO), DHEA analog 8354, 18 beta-glycyrrhetinic acid, N-(4-hydroxyphenyl)retinamide (4-HPR), ibuprofen, oltipraz, piroxicam, Proscar, sulindac, tamoxifen, vitamin D3 and analogs, and vitamin E. The objective of publishing these plans is to stimulate interest and thinking among the scientific community on the prospects for developing chemopreventive drugs. JF - Journal of cellular biochemistry. Supplement AU - Kelloff, G J AU - Crowell, J A AU - Boone, C W AU - Steele, V E AU - Lubet, R A AU - Greenwald, P AU - Alberts, D S AU - Covey, J M AU - Doody, L A AU - Knapp, G G AD - Chemoprevention Branch, National Cancer Institute (NCI), Bethesda, MD 20892, USA. Y1 - 1994 PY - 1994 DA - 1994 SP - 55 EP - 62 VL - 20 SN - 0733-1959, 0733-1959 KW - Index Medicus KW - Humans KW - Clinical Trials as Topic KW - Drug Approval -- legislation & jurisprudence UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77114423?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Correlations+between+chemically+related+site-specific+carcinogenic+effects+in+long-term+studies+in+rats+and+mice.&rft.au=Haseman%2C+J+K%3BLockhart%2C+A+M&rft.aulast=Haseman&rft.aufirst=J&rft.date=1993-04-22&rft.volume=101&rft.issue=1&rft.spage=50&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 - 1995-08-24 N1 - Date created - 1995-08-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Preclinical efficacy evaluation of potential chemopreventive agents in animal carcinogenesis models: methods and results from the NCI Chemoprevention Drug Development Program. AN - 77111604; 7616752 AB - In the NCI, Chemoprevention Branch drug development program, potential chemopreventive agents are evaluated for efficacy against chemical carcinogen-induced tumors in animal models. This paper summarizes the results of 144 agents in 352 tests using various animal efficacy models. Of these results, 146 were positive, representing 85 different agents. The target organs selected for the animals model are representative of high-incidence human cancers. The assays include inhibition of tumors induced by MNU in hamster trachea, DEN in hamster lung, AOM in rat colon (including inhibition of AOM-induced aberrant crypts), MAM in mouse colon, DMBA and MNU in rat mammary glands, DMBA promoted by TPA in mouse skin, and OH-BBN in mouse bladder. The agents tested may be classified into various pharmacological and chemical structural categories that are relevant to their chemopreventive potential. These categories include antiestrogens, antiinflammatories (e.g., NSAIDs), antioxidants, arachidonic acid metabolism inhibitors, GST and GSH enhancers, ODC inhibitors, protein kinase C inhibitors, retinoids and carotenoids, organosulfur compounds, calcium compounds, vitamin D3 and analogs, and phenolic compounds (e.g., flavonoids). The various categories of compounds have different spectra of efficacy in animal models. In hamster lung, GSH-enhancing agents and antioxidants appear to have high potential for inhibiting carcinogenesis. In the colon, NSAIDs and other antiinflammatory agents appear particularly promising. Likewise, NSAIDs are very active in mouse bladder. In rat mammary glands, retinoids and antiestrogens (as would be expected) are efficacious. Several of the chemicals evaluated also appear to be promising chemopreventive agents based on their activity in several of the animal models. Particularly, the ODC inhibitor DFMO was active in the colon, mammary glands, and bladder models, while the dithiolthione, oltipraz, was efficacious in all the models listed above (i.e., lung, colon, mammary glands, skin, and bladder). JF - Journal of cellular biochemistry. Supplement AU - Steele, V E AU - Moon, R C AU - Lubet, R A AU - Grubbs, C J AU - Reddy, B S AU - Wargovich, M AU - McCormick, D L AU - Pereira, M A AU - Crowell, J A AU - Bagheri, D AD - Chemoprevention Branch, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD 20892, USA. Y1 - 1994 PY - 1994 DA - 1994 SP - 32 EP - 54 VL - 20 SN - 0733-1959, 0733-1959 KW - Anticarcinogenic Agents KW - 0 KW - Index Medicus KW - Animals KW - Mice KW - Colonic Neoplasms -- chemically induced KW - Rats KW - Evaluation Studies as Topic KW - Mammary Neoplasms, Experimental -- chemically induced KW - Mice, Inbred Strains KW - Rats, Sprague-Dawley KW - Rats, Inbred F344 KW - Neoplasms, Experimental -- chemically induced KW - Precancerous Conditions -- chemically induced KW - Mice, Inbred C57BL KW - Mesocricetus KW - Mice, Inbred SENCAR KW - Female KW - Male KW - Cricetinae KW - Anticarcinogenic Agents -- pharmacology KW - Drug Screening Assays, Antitumor -- standards KW - Disease Models, Animal KW - Drug Screening Assays, Antitumor -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77111604?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+cellular+biochemistry.+Supplement&rft.atitle=Preclinical+efficacy+evaluation+of+potential+chemopreventive+agents+in+animal+carcinogenesis+models%3A+methods+and+results+from+the+NCI+Chemoprevention+Drug+Development+Program.&rft.au=Steele%2C+V+E%3BMoon%2C+R+C%3BLubet%2C+R+A%3BGrubbs%2C+C+J%3BReddy%2C+B+S%3BWargovich%2C+M%3BMcCormick%2C+D+L%3BPereira%2C+M+A%3BCrowell%2C+J+A%3BBagheri%2C+D&rft.aulast=Steele&rft.aufirst=V&rft.date=1994-01-01&rft.volume=20&rft.issue=&rft.spage=32&rft.isbn=&rft.btitle=&rft.title=Journal+of+cellular+biochemistry.+Supplement&rft.issn=07331959&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-08-24 N1 - Date created - 1995-08-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mechanistic considerations in chemopreventive drug development. AN - 77109951; 7616736 AB - This overview of the potential mechanisms of chemopreventive activity will provide the conceptual groundwork for chemopreventive drug discovery, leading to structure-activity and mechanistic studies that identify and evaluate new agents. Possible mechanisms of chemopreventive activity with examples of promising agents include carcinogen blocking activities such as inhibition of carcinogen uptake (calcium), inhibition of formation or activation of carcinogen (arylalkyl isothiocyanates, DHEA, NSAIDs, polyphenols), deactivation or detoxification of carcinogen (oltipraz, other GSH-enhancing agents), preventing carcinogen binding to DNA (oltipraz, polyphenols), and enhancing the level or fidelity of DNA repair (NAC, protease inhibitors). Chemopreventive antioxidant activities include scavenging reactive electrophiles (GSH-enhancing agents), scavenging oxygen radicals (polyphenols, vitamin E), and inhibiting arachidonic acid metabolism (glycyrrhetinic acid, NAC, NSAIDs, polyphenols, tamoxifen). Antiproliferation/antiprogression activities include modulation of signal transduction (glycyrrhetinic acid, NSAIDs, polyphenols, retinoids, tamoxifen), modulation of hormonal and growth factor activity (NSAIDs, retinoids, tamoxifen), inhibition of aberrant oncogene activity (genistein, NSAIDs, monoterpenes), inhibition of polyamine metabolism (DFMO, retinoids, tamoxifen), induction of terminal differentiation (calcium, retinoids, vitamin D3), restoration of immune response (NSAIDs, selenium, vitamin E), enhancing intercellular communication (carotenoids, retinoids), restoration of tumor suppressor function, induction of programmed cell death (apoptosis) (butyric acid, genistein, retinoids, tamoxifen), correction of DNA methylation imbalances (folic acid), inhibition of angiogenesis (genistein, retinoids, tamoxifen), inhibition of basement membrane degradation (protease inhibitors), and activation of antimetastasis genes. A systematic drug development program for chemopreventive agents is only possible with continuing research into mechanisms of action and thoughtful application of the mechanisms to new drug design and discovery. One approach is to construct pharmacological activity profiles for promising agents. These profiles are compared among the promising agents and with untested compounds to identify similarities. Classical structure-activity studies are used to find optimal agents (high efficacy with low toxicity) based on good lead agents. Studies evaluating tissue-specific and pharmacokinetic parameters are very important. A final approach is design of mechanism-based assays and identification of mechanism-based intermediate biomarkers for evaluation of chemopreventive efficacy. JF - Journal of cellular biochemistry. Supplement AU - Kelloff, G J AU - Boone, C W AU - Steele, V E AU - Fay, J R AU - Lubet, R A AU - Crowell, J A AU - Sigman, C C AD - Chemoprevention Branch, Division of Cancer Prevention and Control (DCPC), National Cancer Institute (NCI), Bethesda, MD 20892, USA. Y1 - 1994 PY - 1994 DA - 1994 SP - 1 EP - 24 VL - 20 SN - 0733-1959, 0733-1959 KW - Anticarcinogenic Agents KW - 0 KW - Index Medicus KW - Rats KW - Animals KW - Humans KW - Mice KW - Anticarcinogenic Agents -- therapeutic use KW - Anticarcinogenic Agents -- pharmacology KW - Anticarcinogenic Agents -- metabolism KW - Neoplasms, Experimental -- metabolism KW - Neoplasms -- prevention & control KW - Neoplasms, Experimental -- prevention & control KW - Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77109951?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+National+Cancer+Institute&rft.atitle=Effect+of+high-protein+diet+on+pyrimidine+synthesis+and+response+to+PALA+in+mouse+tissues.&rft.au=Zaharevitz%2C+D+W%3BGrubb%2C+M+F%3BHyman%2C+R%3BChisena%2C+C%3BCysyk%2C+R+L&rft.aulast=Zaharevitz&rft.aufirst=D&rft.date=1993-04-21&rft.volume=85&rft.issue=8&rft.spage=662&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+National+Cancer+Institute&rft.issn=00278874&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-08-24 N1 - Date created - 1995-08-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Guidance for development of chemopreventive agents. AN - 77109304; 7616748 JF - Journal of cellular biochemistry. Supplement AU - Kelloff, G J AU - Johnson, J R AU - Crowell, J A AU - Boone, C W AU - DeGeorge, J J AU - Steele, V E AU - Mehta, M U AU - Temeck, J W AU - Schmidt, W J AU - Burke, G AD - Chemoprevention Branch, National Cancer Institute (NCI), National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1994 PY - 1994 DA - 1994 SP - 25 EP - 31 VL - 20 SN - 0733-1959, 0733-1959 KW - Anticarcinogenic Agents KW - 0 KW - Index Medicus KW - Rats KW - Animals KW - Humans KW - Drug Evaluation -- legislation & jurisprudence KW - Clinical Trials as Topic -- standards KW - Rabbits KW - Mice KW - Guidelines as Topic KW - Drug Evaluation -- standards KW - Drug Evaluation, Preclinical KW - Toxicity Tests -- standards KW - Drug Approval -- legislation & jurisprudence KW - Anticarcinogenic Agents -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77109304?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+cellular+biochemistry.+Supplement&rft.atitle=Guidance+for+development+of+chemopreventive+agents.&rft.au=Kelloff%2C+G+J%3BJohnson%2C+J+R%3BCrowell%2C+J+A%3BBoone%2C+C+W%3BDeGeorge%2C+J+J%3BSteele%2C+V+E%3BMehta%2C+M+U%3BTemeck%2C+J+W%3BSchmidt%2C+W+J%3BBurke%2C+G&rft.aulast=Kelloff&rft.aufirst=G&rft.date=1994-01-01&rft.volume=20&rft.issue=&rft.spage=25&rft.isbn=&rft.btitle=&rft.title=Journal+of+cellular+biochemistry.+Supplement&rft.issn=07331959&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-08-24 N1 - Date created - 1995-08-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Immunological monitoring and clinical trials of biological response modifiers. AN - 77103151; 7540029 JF - Cancer chemotherapy and biological response modifiers AU - Kopp, W C AU - Holmlund, J T AU - Urba, W J AD - Program Resources Inc., National Cancer Institute, Frederick Cancer Research and Development Center, MD, USA. Y1 - 1994 PY - 1994 DA - 1994 SP - 226 EP - 286 VL - 15 SN - 0921-4410, 0921-4410 KW - Immunologic Factors KW - 0 KW - Interleukin-2 KW - Interleukin-3 KW - Tumor Necrosis Factor-alpha KW - Macrophage Colony-Stimulating Factor KW - 81627-83-0 KW - Interferons KW - 9008-11-1 KW - Melatonin KW - JL5DK93RCL KW - Index Medicus KW - Interleukin-3 -- therapeutic use KW - Animals KW - Macrophage Colony-Stimulating Factor -- therapeutic use KW - Monitoring, Immunologic KW - Melatonin -- therapeutic use KW - Interleukin-2 -- therapeutic use KW - Humans KW - Clinical Trials as Topic KW - Tumor Necrosis Factor-alpha -- therapeutic use KW - Interleukin-2 -- toxicity KW - Interferons -- therapeutic use KW - Immunologic Factors -- therapeutic use KW - Neoplasms -- therapy KW - Neoplasms -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77103151?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+biological+response+modifiers&rft.atitle=Immunological+monitoring+and+clinical+trials+of+biological+response+modifiers.&rft.au=Kopp%2C+W+C%3BHolmlund%2C+J+T%3BUrba%2C+W+J&rft.aulast=Kopp&rft.aufirst=W&rft.date=1994-01-01&rft.volume=15&rft.issue=&rft.spage=226&rft.isbn=&rft.btitle=&rft.title=Cancer+chemotherapy+and+biological+response+modifiers&rft.issn=09214410&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-07-14 N1 - Date created - 1995-07-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Structural characterization of cytosolic NADP(+)-dependent isocitrate dehydrogenase from rat ovary. AN - 77102305; 7787968 AB - Cytosolic NADP(+)-dependent isocitrate dehydrogenase was purified to homogeneity from superovulated rat ovaries. Amino acid sequence information was obtained by analyzing peptides generated by digestion with either cyanogen bromide or trypsin. Eleven peptides were sequenced and a total of 146 amino acids were identified. Nine of these peptides were found to be 60-100% identical with sequences from mitochondrial NADP(+)-dependent isocitrate dehydrogenase. Conservation of amino acids was observed for residues that were previously identified as potentially binding isocitrate-Mg2+. Circular dichroism measurements showed that the structure is composed of approximately 35% alpha-helix and 21% beta-sheet segments. Temperature denaturation studies indicated that the enzyme is more stable in the presence of isocitrate. JF - Enzyme & protein AU - Sechi, S AU - Parmelee, D AU - Roller, P P AU - Jennings, G T AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, Bethesda, Md., USA. PY - 1994 SP - 27 EP - 36 VL - 48 IS - 1 SN - 1019-6773, 1019-6773 KW - Isocitrates KW - 0 KW - isocitric acid KW - 320-77-4 KW - Isocitrate Dehydrogenase KW - EC 1.1.1.41 KW - isocitrate dehydrogenase (NADP+) KW - EC 1.1.1.42 KW - Index Medicus KW - Animals KW - Protein Structure, Secondary KW - Isocitrates -- pharmacology KW - Cytosol -- enzymology KW - Temperature KW - Protein Denaturation KW - Circular Dichroism KW - Amino Acid Sequence KW - Chromatography, High Pressure Liquid KW - Rats KW - Sequence Analysis KW - Molecular Sequence Data KW - Protein Folding KW - Sequence Homology, Amino Acid KW - Female KW - Protein Conformation KW - Ovary -- enzymology KW - Isocitrate Dehydrogenase -- isolation & purification KW - Isocitrate Dehydrogenase -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77102305?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Enzyme+%26+protein&rft.atitle=Structural+characterization+of+cytosolic+NADP%28%2B%29-dependent+isocitrate+dehydrogenase+from+rat+ovary.&rft.au=Sechi%2C+S%3BParmelee%2C+D%3BRoller%2C+P+P%3BJennings%2C+G+T&rft.aulast=Sechi&rft.aufirst=S&rft.date=1994-01-01&rft.volume=48&rft.issue=1&rft.spage=27&rft.isbn=&rft.btitle=&rft.title=Enzyme+%26+protein&rft.issn=10196773&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-07-24 N1 - Date created - 1995-07-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mitotic inhibitors. AN - 77101871; 7779600 JF - Cancer chemotherapy and biological response modifiers AU - Chabner, B A AU - Chabner, E S AD - Division of Cancer Treatment, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Y1 - 1994 PY - 1994 DA - 1994 SP - 58 EP - 66 VL - 15 SN - 0921-4410, 0921-4410 KW - Taxoids KW - 0 KW - Vinca Alkaloids KW - docetaxel KW - 15H5577CQD KW - Paclitaxel KW - P88XT4IS4D KW - Index Medicus KW - Animals KW - Humans KW - Paclitaxel -- toxicity KW - Vinca Alkaloids -- pharmacology KW - Paclitaxel -- analogs & derivatives KW - Paclitaxel -- pharmacology KW - Mitosis -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77101871?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+biological+response+modifiers&rft.atitle=Mitotic+inhibitors.&rft.au=Chabner%2C+B+A%3BChabner%2C+E+S&rft.aulast=Chabner&rft.aufirst=B&rft.date=1994-01-01&rft.volume=15&rft.issue=&rft.spage=58&rft.isbn=&rft.btitle=&rft.title=Cancer+chemotherapy+and+biological+response+modifiers&rft.issn=09214410&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-07-14 N1 - Date created - 1995-07-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Antimetabolites. AN - 77100567; 7779582 JF - Cancer chemotherapy and biological response modifiers AU - Chu, E AU - Johnston, P G AU - Grem, J L AU - Takimoto, C H AU - Van Groeningen, C AU - Chabner, B A AU - Allegra, C J AD - Navy Medical Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Y1 - 1994 PY - 1994 DA - 1994 SP - 1 EP - 31 VL - 15 SN - 0921-4410, 0921-4410 KW - Antimetabolites, Antineoplastic KW - 0 KW - Cytarabine KW - 04079A1RDZ KW - 6-Mercaptopurine KW - E7WED276I5 KW - Vidarabine KW - FA2DM6879K KW - fludarabine KW - P2K93U8740 KW - Fluorouracil KW - U3P01618RT KW - Methotrexate KW - YL5FZ2Y5U1 KW - Index Medicus KW - Cytarabine -- pharmacology KW - Vidarabine -- analogs & derivatives KW - Animals KW - Methotrexate -- pharmacology KW - Methotrexate -- pharmacokinetics KW - Humans KW - Fluorouracil -- pharmacology KW - Drug Resistance KW - Vidarabine -- pharmacology KW - Fluorouracil -- pharmacokinetics KW - 6-Mercaptopurine -- pharmacology KW - Antimetabolites, Antineoplastic -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77100567?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+biological+response+modifiers&rft.atitle=Antimetabolites.&rft.au=Chu%2C+E%3BJohnston%2C+P+G%3BGrem%2C+J+L%3BTakimoto%2C+C+H%3BVan+Groeningen%2C+C%3BChabner%2C+B+A%3BAllegra%2C+C+J&rft.aulast=Chu&rft.aufirst=E&rft.date=1994-01-01&rft.volume=15&rft.issue=&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Cancer+chemotherapy+and+biological+response+modifiers&rft.issn=09214410&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-07-14 N1 - Date created - 1995-07-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - New directions for free radical cancer research and medical applications. AN - 77099991; 7771256 AB - The nitroxides are stable, low molecular weight free radical compounds which are freely membrane permeable. These properties make the nitroxides valuable for the study of and possible protection against oxidative stresses. It is becoming increasingly clear that oxidative stress is important to the pathogenesis of cancer as well as to the development of treatments for cancer. Several nitroxides have been shown to interrupt the toxicity of oxidative stress with the protection against H2O2 toxicity and possibly ischemia/reperfusion injury being of primary importance. With respect to radiation, the nitroxides have afforded both in vitro and in vivo protection. The redox activity of the nitroxides may allow for the differential activity of these agents in normal versus tumor tissues. Further study of these compounds may yield a nitroxide with clinical applications as well as provide insight into the mechanisms of radiation cytotoxicity. Finally, the nitroxides have allowed us to explore the mechanisms of action of several chemotherapeutic agents. Understanding these processes is important to the process of ameliorating the toxicity of therapies and to the rationale design of future agents. JF - Advances in experimental medicine and biology AU - Hahn, S M AU - Krishna, C M AU - Mitchell, J B AD - Radiation Biology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1994 PY - 1994 DA - 1994 SP - 241 EP - 251 VL - 366 SN - 0065-2598, 0065-2598 KW - Antioxidants KW - 0 KW - Cyclic N-Oxides KW - Free Radical Scavengers KW - Free Radicals KW - Radiation-Protective Agents KW - Spin Labels KW - Index Medicus KW - Animals KW - Cell Survival -- drug effects KW - Humans KW - Free Radical Scavengers -- pharmacology KW - Cell Line KW - Neoplasms -- drug therapy KW - Radiation-Protective Agents -- therapeutic use KW - Antioxidants -- pharmacology KW - Antioxidants -- therapeutic use KW - Cyclic N-Oxides -- pharmacology KW - Neoplasms -- prevention & control KW - Radiation-Protective Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77099991?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Advances+in+experimental+medicine+and+biology&rft.atitle=New+directions+for+free+radical+cancer+research+and+medical+applications.&rft.au=Hahn%2C+S+M%3BKrishna%2C+C+M%3BMitchell%2C+J+B&rft.aulast=Hahn&rft.aufirst=S&rft.date=1994-01-01&rft.volume=366&rft.issue=&rft.spage=241&rft.isbn=&rft.btitle=&rft.title=Advances+in+experimental+medicine+and+biology&rft.issn=00652598&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-07-05 N1 - Date created - 1995-07-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Reversal of multidrug resistance. AN - 76952269; 7827870 JF - Journal of hematotherapy AU - Bates, S E AU - Zhan, Z AU - Dickstein, B AU - Lee, J S AU - Scala, S AU - Fojo, A T AU - Paull, K AU - Wilson, W AD - Medicine Branch, National Cancer Institute, Bethesda, MD 20892. Y1 - 1994 PY - 1994 DA - 1994 SP - 219 EP - 223 VL - 3 IS - 3 SN - 1061-6128, 1061-6128 KW - mdr-1 KW - Antineoplastic Agents KW - 0 KW - P-Glycoprotein KW - Vincristine KW - 5J49Q6B70F KW - Verapamil KW - CJ0O37KU29 KW - Paclitaxel KW - P88XT4IS4D KW - Index Medicus KW - Paclitaxel -- toxicity KW - Tumor Cells, Cultured KW - P-Glycoprotein -- genetics KW - Cell Survival -- drug effects KW - Humans KW - Clinical Trials as Topic KW - Antineoplastic Agents -- toxicity KW - Verapamil -- pharmacology KW - Vincristine -- toxicity KW - P-Glycoprotein -- antagonists & inhibitors KW - Neoplasms -- drug therapy KW - Drug Resistance, Multiple -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76952269?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cross-talk+between+m1+muscarinic+acetylcholine+and+beta+2-adrenergic+receptors.+cAMP+and+the+third+intracellular+loop+of+m1+muscarinic+receptors+confer+heterologous+regulation.&rft.au=Lee%2C+N+H%3BFraser%2C+C+M&rft.aulast=Lee&rft.aufirst=N&rft.date=1993-04-15&rft.volume=268&rft.issue=11&rft.spage=7949&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 - 1995-02-17 N1 - Date created - 1995-02-17 N1 - Date revised - 2017-01-13 N1 - Gene symbol - mdr-1 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tumor necrosis factor involvement in the toxicity of TCDD: the role of endotoxin in the response. AN - 76950725; 7826662 AB - We have previously demonstrated that tumor necrosis factor is involved in the acute toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), since therapies designed to attenuate the effects of tumor necrosis factor resulted in reduced mortality and toxicity in mice exposed to an LD75 dose of TCDD. The current study addresses whether endotoxin may be a contributing factor in the cachexia and mortality resulting from TCDD exposure. Endotoxin-nonresponsive C3H/HeJ mice and endotoxin-responsive C57BL/6 mice were treated with 350 micrograms/kg TCDD and body weight and mortality were recorded. C3H/HeJ mice showed no trend in body weight loss (p = 0.554), while C57BL/6 mice demonstrated a statistically significant (p < 0.01) linear decline in body weight of -0.23 g/day, resulting in a net loss of 3.5 g over 15 days preceding mortality. Mortality was observed in the C57BL/6 mice beginning on day 16 with 100% of the mice dying by the 23rd day while no mortality was observed in C3H/HeJ mice until the 24th day of the study with only 22% mortality observed. These data further demonstrate that endotoxin is a contributing factor to the cachexia and lethality of TCDD. JF - Experimental and clinical immunogenetics AU - Clark, G C AU - Taylor, M J AD - National Institute of Environmental Health Sciences, Research Triangle Park, N.C. 27709. Y1 - 1994 PY - 1994 DA - 1994 SP - 136 EP - 141 VL - 11 IS - 2-3 SN - 0254-9670, 0254-9670 KW - Endotoxins KW - 0 KW - Polychlorinated Dibenzodioxins KW - Tumor Necrosis Factor-alpha KW - Index Medicus KW - Animals KW - Mice, Inbred C57BL KW - Mice, Inbred C3H KW - Mice KW - Species Specificity KW - Male KW - Cachexia -- chemically induced KW - Polychlorinated Dibenzodioxins -- toxicity KW - Tumor Necrosis Factor-alpha -- physiology KW - Cachexia -- immunology KW - Endotoxins -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76950725?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+clinical+immunogenetics&rft.atitle=Tumor+necrosis+factor+involvement+in+the+toxicity+of+TCDD%3A+the+role+of+endotoxin+in+the+response.&rft.au=Clark%2C+G+C%3BTaylor%2C+M+J&rft.aulast=Clark&rft.aufirst=G&rft.date=1994-01-01&rft.volume=11&rft.issue=2-3&rft.spage=136&rft.isbn=&rft.btitle=&rft.title=Experimental+and+clinical+immunogenetics&rft.issn=02549670&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-02-23 N1 - Date created - 1995-02-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Further ultrastructural studies of lesions produced in the optic nerve by tumor necrosis factor alpha (TNF-alpha): a comparison with experimental Creutzfeldt-Jakob disease. AN - 76943047; 7817836 AB - We report here that intraocular injection of recombinant TNF-alpha produces lesions in the optic nerve indistinguishable from those reported for the panencephalopathic type of Creutzfeldt-Jakob disease (CJD). The lesions were patchy and confined to the injected optic nerve. Axons show variable features of degenerations. Numerous vacuoles distended the myelin sheath. Hypertrophic astrocytes were numerous and many active macrophages containing digested myelin debris and lyre-like paracrystalline bodies. At high power, myelinated axons were observed as enveloped by astrocytic processes; formation of labyrinth-like network of such processes around damaged axons were observed. In conclusions, lesions produced by TNF-alpha mimic those of the panencephalopathic type of CJD, in direct support of our previous ultrastructural, immunohistochemical and molecular data on TNF-alpha involvement in CJD pathogenesis. JF - Acta neurobiologiae experimentalis AU - Liberski, P P AU - Yanagihara, R AU - Nerurkar, V AU - Gajdusek, D C AD - Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994 PY - 1994 DA - 1994 SP - 209 EP - 218 VL - 54 IS - 3 SN - 0065-1400, 0065-1400 KW - Recombinant Proteins KW - 0 KW - Tumor Necrosis Factor-alpha KW - Index Medicus KW - Animals KW - Recombinant Proteins -- pharmacology KW - Humans KW - Disease Models, Animal KW - Middle Aged KW - Mice KW - Male KW - Creutzfeldt-Jakob Syndrome -- pathology KW - Tumor Necrosis Factor-alpha -- toxicity KW - Optic Nerve -- pathology KW - Optic Nerve -- ultrastructure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76943047?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+neurobiologiae+experimentalis&rft.atitle=Further+ultrastructural+studies+of+lesions+produced+in+the+optic+nerve+by+tumor+necrosis+factor+alpha+%28TNF-alpha%29%3A+a+comparison+with+experimental+Creutzfeldt-Jakob+disease.&rft.au=Liberski%2C+P+P%3BYanagihara%2C+R%3BNerurkar%2C+V%3BGajdusek%2C+D+C&rft.aulast=Liberski&rft.aufirst=P&rft.date=1994-01-01&rft.volume=54&rft.issue=3&rft.spage=209&rft.isbn=&rft.btitle=&rft.title=Acta+neurobiologiae+experimentalis&rft.issn=00651400&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-02-08 N1 - Date created - 1995-02-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Surrogate endpoint biomarkers for phase II cancer chemoprevention trials. AN - 76942615; 7823579 AB - Three critical aspects govern successful Phase II cancer chemoprevention trials--well-characterized agents, suitable cohorts, and reliable intermediate biomarkers for measuring efficacy. Requirements for the agent are experimental or epidemiological data showing chemopreventive efficacy, safety on chronic administration, and a mechanistic rationale for the chemopreventive activity observed. The cohort should be suitable for measuring the chemopreventive activity of the agent and the intermediate biomarkers chosen. Also, many cohorts proposed for Phase II trials are patients with previous cancers or premalignant lesions. For such patients, the trials should be conducted within the context of standard treatment to avoid unusual risks. The criteria for biomarkers are that they fit expected biological mechanisms (i.e., differential expression in normal and high-risk tissue, on or closely linked to the causal pathway for the cancer, modulated by chemopreventive agents, and short latency compared with cancer), may be assayed reliably and quantitatively, measured easily, and correlate to decreased cancer incidence. They must occur in sufficient incidence to allow their biological and statistical evaluation relevant to cancer. Since carcinogenesis is a multipath process, single biomarkers are difficult to validate as surrogate endpoints, as they may appear on only one or a few of the many possible causal pathways. Panels of biomarkers, particularly those representing the range of carcinogenesis pathways, may prove more useful as surrogate endpoints. It is important to avoid relying solely on biomarkers representing isolated events that may or may not be on the causal pathway or otherwise associated with carcinogenesis. These include markers of normal cellular processes that may be increased or expressed during carcinogenesis, but are nonspecific.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Journal of cellular biochemistry. Supplement AU - Kelloff, G J AU - Boone, C W AU - Crowell, J A AU - Steele, V E AU - Lubet, R AU - Doody, L A AD - Chemoprevention Investigational Studies Branch (CISB), National Cancer Institute (NCI), National Institutes of Health, Bethesda, MD 20892. Y1 - 1994 PY - 1994 DA - 1994 SP - 1 EP - 9 VL - 19 SN - 0733-1959, 0733-1959 KW - Anticarcinogenic Agents KW - 0 KW - Biomarkers, Tumor KW - Index Medicus KW - Humans KW - Anticarcinogenic Agents -- toxicity KW - Neoplasms -- pathology KW - Anticarcinogenic Agents -- therapeutic use KW - Clinical Trials, Phase II as Topic KW - Neoplasms -- epidemiology KW - Biomarkers, Tumor -- analysis KW - Neoplasms -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76942615?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+cellular+biochemistry.+Supplement&rft.atitle=Surrogate+endpoint+biomarkers+for+phase+II+cancer+chemoprevention+trials.&rft.au=Kelloff%2C+G+J%3BBoone%2C+C+W%3BCrowell%2C+J+A%3BSteele%2C+V+E%3BLubet%2C+R%3BDoody%2C+L+A&rft.aulast=Kelloff&rft.aufirst=G&rft.date=1994-01-01&rft.volume=19&rft.issue=&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Journal+of+cellular+biochemistry.+Supplement&rft.issn=07331959&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-02-10 N1 - Date created - 1995-02-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Lipoprotein lipase: structure, function and mechanism of action. AN - 76937777; 7819594 AB - Lipoprotein lipase (LPL) plays a central role in the hydrolysis of circulating triglycerides present in chylomicrons, and very low density lipoproteins. The active form of the enzyme is a non-covalent homodimer which contains multiple functional domains required for normal hydrolytic activity including a catalytic domain, as well as sites involved in co-factor, heparin and lipid binding. Recent studies involving site-directed mutagenesis, the elucidation of the three dimensional crystallographic structure of different lipases, as well as analysis of the molecular defects that result in the expression of the familial chylomicronemia syndrome have provided new insights into the structure-function relationship of LPL. As a result, our understanding of structural domains involved in catalysis, heparin, lipid binding, and enzyme-cofactor interaction as well as the mechanism of action of LPL as an acylglycerol hydrolase has been greatly enhanced. JF - International journal of clinical & laboratory research AU - Santamarina-Fojo, S AU - Brewer, H B AD - Molecular Disease Branch, National Heart, Lung and Blood Institute, National Institute of Health, Bethesda, MD 20892. Y1 - 1994 PY - 1994 DA - 1994 SP - 143 EP - 147 VL - 24 IS - 3 SN - 0940-5437, 0940-5437 KW - Chylomicrons KW - 0 KW - Triglycerides KW - Lipoprotein Lipase KW - EC 3.1.1.34 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Models, Molecular KW - Syndrome KW - Humans KW - Triglycerides -- metabolism KW - Chylomicrons -- blood KW - Hydrolysis KW - Structure-Activity Relationship KW - Lipoprotein Lipase -- genetics KW - Lipoprotein Lipase -- physiology KW - Lipoprotein Lipase -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76937777?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+clinical+%26+laboratory+research&rft.atitle=Lipoprotein+lipase%3A+structure%2C+function+and+mechanism+of+action.&rft.au=Santamarina-Fojo%2C+S%3BBrewer%2C+H+B&rft.aulast=Santamarina-Fojo&rft.aufirst=S&rft.date=1994-01-01&rft.volume=24&rft.issue=3&rft.spage=143&rft.isbn=&rft.btitle=&rft.title=International+journal+of+clinical+%26+laboratory+research&rft.issn=09405437&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-02-14 N1 - Date created - 1995-02-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Protease inhibitors in chemoprevention of cancer. An overview. AN - 76936585; 7818916 AB - In the search for chemopreventive agents for cancer many natural products have been identified. Among them extensive experimental studies have been made on protease inhibitors which not only occur naturally in many plant products, but have also been synthesized in the laboratory. Many of these studies revealed the fact that protease inhibitors are able to prevent carcinogenesis and tumour promotion. A review of the reports available to date suggests that protease inhibitors are potential chemopreventive agents although their biological role and mechanism of action are not very clear. JF - Acta oncologica (Stockholm, Sweden) AU - Das, S AU - Mukhopadhyay, P AD - Department of Experimental Leukemia, Chittaranjan National Cancer Institute, Calcutta, India. Y1 - 1994 PY - 1994 DA - 1994 SP - 859 EP - 865 VL - 33 IS - 8 SN - 0284-186X, 0284-186X KW - Antineoplastic Agents KW - 0 KW - Protease Inhibitors KW - Index Medicus KW - Animals KW - Tumor Cells, Cultured -- drug effects KW - Humans KW - Neoplasms, Experimental -- prevention & control KW - Protease Inhibitors -- therapeutic use KW - Protease Inhibitors -- pharmacology KW - Neoplasms -- prevention & control KW - Antineoplastic Agents -- therapeutic use KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76936585?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Acta+oncologica+%28Stockholm%2C+Sweden%29&rft.atitle=Protease+inhibitors+in+chemoprevention+of+cancer.+An+overview.&rft.au=Das%2C+S%3BMukhopadhyay%2C+P&rft.aulast=Das&rft.aufirst=S&rft.date=1994-01-01&rft.volume=33&rft.issue=8&rft.spage=859&rft.isbn=&rft.btitle=&rft.title=Acta+oncologica+%28Stockholm%2C+Sweden%29&rft.issn=0284186X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-02-14 N1 - Date created - 1995-02-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Multiple p53 protein isoforms and formation of oligomeric complexes with heat shock proteins Hsp70 and Hsp90 in the human mammary tumor, T47D, cell line. AN - 76924997; 7811761 AB - At least eleven isoforms of p53 protein were observed in a human mammary tumor cell line. T47D. Comparative 33P and 35S incorporation analysis showed an equal distribution of P53 isoforms within cytoplasmic and nuclear compartments, although phosphorylation was unequal among isoforms and the most basic p53 species was unphosphorylated. Using a combination of immunoprecipitation with monoclonal antibodies for p53 and heat shock proteins Hsp70 & Hsp90, and two-dimensional gel electrophoretic analysis, T47D p53 protein oligomers were observed with several species of Hsp70 and Hsp90. The p53/Hsp70/Hsp90 aggregate dissociates after nuclear translocation. Immunoprecipitation of Hsp70 and Hsp90 using monoclonal antibodies showed formation of a heteroligomer between Hsp70 and Hsp90 in cytoplasm but not nucleus. This suggests these Hsp proteins can form a complex in the cytoplasm but undergo a conformational change after nuclear translocation such that Hsp/Hsp binding sites are no longer recognized. These data indicate T47D cells have multiple p53 precursor molecules probably at different stages of phosphorylation, and which may be sequestered from proteases by binding to Hsp proteins. Hsp proteins also can heterocomplex in the cytoplasm, also possibly as protection against protease degradation until bound to p53. After translocation, p53 is freed from Hsp proteins for binding to DNA where Hsp70 and Hsp90 are no longer able to form a nuclear complex probably rendering Hsp's labile to proteolysis. JF - Applied and theoretical electrophoresis : the official journal of the International Electrophoresis Society AU - Selkirk, J K AU - Merrick, B A AU - Stackhouse, B L AU - He, C AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1994 PY - 1994 DA - 1994 SP - 11 EP - 18 VL - 4 IS - 1 SN - 0954-6642, 0954-6642 KW - Antibodies, Monoclonal KW - 0 KW - HSP70 Heat-Shock Proteins KW - HSP90 Heat-Shock Proteins KW - Macromolecular Substances KW - Tumor Suppressor Protein p53 KW - Index Medicus KW - Tumor Cells, Cultured KW - Phosphorylation KW - Cytoplasm -- metabolism KW - Cell Nucleus -- metabolism KW - Humans KW - Electrophoresis, Gel, Two-Dimensional KW - Immunosorbent Techniques KW - Protein Conformation KW - HSP70 Heat-Shock Proteins -- metabolism KW - Tumor Suppressor Protein p53 -- analysis KW - HSP70 Heat-Shock Proteins -- chemistry KW - Tumor Suppressor Protein p53 -- chemistry KW - HSP90 Heat-Shock Proteins -- metabolism KW - HSP90 Heat-Shock Proteins -- chemistry KW - Breast Neoplasms -- metabolism KW - Tumor Suppressor Protein p53 -- metabolism KW - Breast Neoplasms -- ultrastructure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76924997?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Applied+and+theoretical+electrophoresis+%3A+the+official+journal+of+the+International+Electrophoresis+Society&rft.atitle=Multiple+p53+protein+isoforms+and+formation+of+oligomeric+complexes+with+heat+shock+proteins+Hsp70+and+Hsp90+in+the+human+mammary+tumor%2C+T47D%2C+cell+line.&rft.au=Selkirk%2C+J+K%3BMerrick%2C+B+A%3BStackhouse%2C+B+L%3BHe%2C+C&rft.aulast=Selkirk&rft.aufirst=J&rft.date=1994-01-01&rft.volume=4&rft.issue=1&rft.spage=11&rft.isbn=&rft.btitle=&rft.title=Applied+and+theoretical+electrophoresis+%3A+the+official+journal+of+the+International+Electrophoresis+Society&rft.issn=09546642&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-02-03 N1 - Date created - 1995-02-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characterization of gene expression in the cerebral cortices of rat brains containing subcortical lesions. AN - 76924695; 7811765 AB - Neurotoxic lesion of the nucleus basalis of Meynert in the rat brain, which results in the loss of subcortical cholinergic innervation to the cerebral cortex, is an animal model for the cortical cholinergic deficits that are characteristic of Alzheimer's disease. Previously, we have shown that amyloid precursor protein is induced in the cortex in response to this disrupted innervation. We have investigated the synthesis and accumulation of proteins in lesioned versus control cortices. Total proteins from cortices were separated by high resolution two-dimensional gel electrophoresis and visualized by silver stain. Of the greater than 1,000 polypeptides examined, only one exhibited a consistent alteration in the lesioned sample. This unidentified protein (Mr 34 kD, pI 5.5) was normally present in scant amounts but was virtually absent in the lesioned cortex (0.056% total integrated density (TID) and 0.008% TID, respectively; p < 0.04). To investigate gene expression more directly, polysomes purified from lesioned and control cortices were assayed in vitro. Examination of [35S] incorporation into translation products by two-dimensional gels and autoradiography revealed three newly synthesized polypeptide differences in the lesioned samples. One protein (M(r) 47 kD, pI 6.1) exhibited elevated levels with the lesion (0.05% to 0.16%; p = 0.02) while two other proteins (M(r) 34 kD, pI 5.5, and M(r) 33 kD, pI 5.7) exhibited reduced levels (0.20% to 0.04%, p < 0.02, and 0.34% to 0.12%, p = 0.04, respectively). JF - Applied and theoretical electrophoresis : the official journal of the International Electrophoresis Society AU - Wallace, W AU - Brane, D AU - Hsu, N AU - Khowong, N AU - Merril, C R AU - Haroutunian, V AD - Laboratory of Biochemical Genetics, NIMH, St. Elizabeths Hospital, Washington, D.C. 20032. Y1 - 1994 PY - 1994 DA - 1994 SP - 33 EP - 38 VL - 4 IS - 1 SN - 0954-6642, 0954-6642 KW - Heat-Shock Proteins KW - 0 KW - Nerve Tissue Proteins KW - N-Methylaspartate KW - 6384-92-5 KW - Index Medicus KW - Heat-Shock Proteins -- metabolism KW - Animals KW - Isoelectric Point KW - Nerve Tissue Proteins -- biosynthesis KW - Polyribosomes -- metabolism KW - Molecular Weight KW - Rats KW - Rats, Sprague-Dawley KW - N-Methylaspartate -- pharmacology KW - Electrophoresis, Gel, Two-Dimensional KW - Nerve Tissue Proteins -- metabolism KW - Substantia Innominata -- drug effects KW - Silver Staining KW - Substantia Innominata -- physiology KW - Cerebral Cortex -- metabolism KW - Gene Expression UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76924695?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Applied+and+theoretical+electrophoresis+%3A+the+official+journal+of+the+International+Electrophoresis+Society&rft.atitle=Characterization+of+gene+expression+in+the+cerebral+cortices+of+rat+brains+containing+subcortical+lesions.&rft.au=Wallace%2C+W%3BBrane%2C+D%3BHsu%2C+N%3BKhowong%2C+N%3BMerril%2C+C+R%3BHaroutunian%2C+V&rft.aulast=Wallace&rft.aufirst=W&rft.date=1994-01-01&rft.volume=4&rft.issue=1&rft.spage=33&rft.isbn=&rft.btitle=&rft.title=Applied+and+theoretical+electrophoresis+%3A+the+official+journal+of+the+International+Electrophoresis+Society&rft.issn=09546642&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-02-03 N1 - Date created - 1995-02-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - OxyR regulon. AN - 76920163; 7528872 JF - Methods in enzymology AU - Storz, G AU - Altuvia, S AD - Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994 PY - 1994 DA - 1994 SP - 217 EP - 223 VL - 234 SN - 0076-6879, 0076-6879 KW - oxyR KW - Bacterial Proteins KW - 0 KW - DNA Primers KW - DNA, Bacterial KW - DNA-Binding Proteins KW - Escherichia coli Proteins KW - RNA, Bacterial KW - Repressor Proteins KW - Transcription Factors KW - oxyR protein, E coli KW - Deoxyribonuclease I KW - EC 3.1.21.1 KW - Oxygen KW - S88TT14065 KW - Index Medicus KW - Space life sciences KW - Repressor Proteins -- biosynthesis KW - RNA, Bacterial -- biosynthesis KW - Oxygen -- toxicity KW - Transcription, Genetic KW - DNA, Bacterial -- metabolism KW - RNA, Bacterial -- isolation & purification KW - Mutagenesis KW - Chromatography, Affinity -- methods KW - Salmonella typhimurium -- metabolism KW - Escherichia coli -- metabolism KW - Bacterial Proteins -- genetics KW - Bacterial Proteins -- biosynthesis KW - Escherichia coli -- genetics KW - Bacterial Proteins -- isolation & purification KW - Regulon KW - Salmonella typhimurium -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76920163?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Methods+in+enzymology&rft.atitle=OxyR+regulon.&rft.au=Storz%2C+G%3BAltuvia%2C+S&rft.aulast=Storz&rft.aufirst=G&rft.date=1994-01-01&rft.volume=234&rft.issue=&rft.spage=217&rft.isbn=&rft.btitle=&rft.title=Methods+in+enzymology&rft.issn=00766879&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-01-30 N1 - Date created - 1995-01-30 N1 - Date revised - 2017-01-13 N1 - Gene symbol - oxyR N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Immunotoxin therapy of leptomeningeal neoplasia. AN - 76916545; 7807185 AB - Malignant tumors of the central nervous system can result from metastatic dissemination of a variety of cancers. Percutaneous intracisternal injection of an anti-idiotype monoclonal antibody (M6) ricin immunotoxin was shown to be moderately effective in prolonging the survival of tumor bearing animals supporting the use of immunotoxins for the treatment of central nervous system neoplasia (Zovickian J and Youle R.J. J. Neurosurg 68: 767, 1988). This report describes a method that significantly improves the survival of immunotoxin treated Strain 2 guinea pigs in a syngeneic animal model of leptomeningeal neoplasia. Strain 2 guinea pigs, implanted with subarachnoid catheters, received three courses of treatment with an (M6)-intract ricin immunotoxin following intracisternal inoculation of L2C leukemia tumor cells. Animals were treated with three to four micrograms of immunotoxin in three divided doses. This was found to be less toxic and more effective than single bolus administration of immunotoxin. These results demonstrate that a permanent indwelling catheter in this animal model facilitates multiple dose delivery of immunotoxin therapy allowing the assessment of various treatment schedules and the achievement of enhanced therapeutic effect. Furthermore, these results support the continued evaluation of immunotoxins for the treatment of central nervous system neoplasia. JF - Journal of neuro-oncology AU - Walbridge, S AU - Rybak, S M AD - Surgical Neurology Branch, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994 PY - 1994 DA - 1994 SP - 59 EP - 65 VL - 20 IS - 1 SN - 0167-594X, 0167-594X KW - Antibodies, Monoclonal KW - 0 KW - Immunoglobulin G KW - Immunotoxins KW - Ricin KW - 9009-86-3 KW - Index Medicus KW - Animals KW - Tumor Cells, Cultured KW - Guinea Pigs KW - Immunoglobulin G -- administration & dosage KW - Leukemic Infiltration -- mortality KW - Leukemia -- therapy KW - Leukemia -- mortality KW - Ricin -- administration & dosage KW - Ricin -- therapeutic use KW - Immunotoxins -- therapeutic use KW - Leukemic Infiltration -- therapy KW - Immunotoxins -- administration & dosage KW - Arachnoid -- pathology KW - Immunoglobulin G -- therapeutic use KW - Antibodies, Monoclonal -- administration & dosage KW - Antibodies, Monoclonal -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76916545?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+neuro-oncology&rft.atitle=Immunotoxin+therapy+of+leptomeningeal+neoplasia.&rft.au=Walbridge%2C+S%3BRybak%2C+S+M&rft.aulast=Walbridge&rft.aufirst=S&rft.date=1994-01-01&rft.volume=20&rft.issue=1&rft.spage=59&rft.isbn=&rft.btitle=&rft.title=Journal+of+neuro-oncology&rft.issn=0167594X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-01-30 N1 - Date created - 1995-01-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Reactions of polycyclic aromatic hydrocarbons with DNA. AN - 76913910; 7806307 JF - IARC scientific publications AU - Dipple, A AD - Chemistry of Carcinogenesis Laboratory, ABL-Basic Research Program, National Cancer Institute-Frederick Cancer Research and Development Center, MD. Y1 - 1994 PY - 1994 DA - 1994 SP - 107 EP - 129 IS - 125 SN - 0300-5038, 0300-5038 KW - Carcinogens KW - 0 KW - DNA Adducts KW - Environmental Pollutants KW - Polycyclic Compounds KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Animals KW - Environmental Pollutants -- metabolism KW - Environmental Pollutants -- toxicity KW - Humans KW - Environmental Pollutants -- pharmacokinetics KW - DNA Adducts -- biosynthesis KW - Carcinogens -- metabolism KW - Polycyclic Compounds -- pharmacokinetics KW - DNA Adducts -- chemistry KW - DNA -- metabolism KW - Carcinogens -- pharmacokinetics KW - Polycyclic Compounds -- toxicity KW - Carcinogens -- toxicity KW - Polycyclic Compounds -- metabolism KW - DNA -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76913910?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=IARC+scientific+publications&rft.atitle=Reactions+of+polycyclic+aromatic+hydrocarbons+with+DNA.&rft.au=Dipple%2C+A&rft.aulast=Dipple&rft.aufirst=A&rft.date=1994-01-01&rft.volume=&rft.issue=125&rft.spage=107&rft.isbn=&rft.btitle=&rft.title=IARC+scientific+publications&rft.issn=03005038&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-01-30 N1 - Date created - 1995-01-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Reaction of aralkyl halides with nucleic acid components and DNA. AN - 76913743; 7806317 JF - IARC scientific publications AU - Moschel, R C AD - Chemistry of Carcinogenesis Laboratory, ABL-Basic Research Program, National Cancer Institute-Frederick Cancer Research and Development Center, MD. Y1 - 1994 PY - 1994 DA - 1994 SP - 25 EP - 36 IS - 125 SN - 0300-5038, 0300-5038 KW - DNA Adducts KW - 0 KW - Hydrocarbons, Halogenated KW - Nucleic Acids KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Animals KW - Hydrocarbons, Halogenated -- toxicity KW - Nucleic Acids -- chemical synthesis KW - DNA Adducts -- chemistry KW - DNA -- chemistry KW - Nucleic Acids -- chemistry KW - Hydrocarbons, Halogenated -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76913743?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=IARC+scientific+publications&rft.atitle=Reaction+of+aralkyl+halides+with+nucleic+acid+components+and+DNA.&rft.au=Moschel%2C+R+C&rft.aulast=Moschel&rft.aufirst=R&rft.date=1994-01-01&rft.volume=&rft.issue=125&rft.spage=25&rft.isbn=&rft.btitle=&rft.title=IARC+scientific+publications&rft.issn=03005038&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-01-30 N1 - Date created - 1995-01-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Gene-specific damage and repair of DNA adducts and cross-links. AN - 76912802; 7806325 JF - IARC scientific publications AU - Bohr, V A AD - Laboratory of Molecular Genetics, National Institutes on Aging, National Institutes of Health, Baltimore, MD. Y1 - 1994 PY - 1994 DA - 1994 SP - 361 EP - 369 IS - 125 SN - 0300-5038, 0300-5038 KW - c-myc KW - dhfr KW - p53 KW - Cross-Linking Reagents KW - 0 KW - DNA Adducts KW - Index Medicus KW - Sensitivity and Specificity KW - Animals KW - Base Sequence KW - Humans KW - Molecular Sequence Data KW - Genome KW - Genes -- physiology KW - DNA Repair KW - DNA Damage KW - Cross-Linking Reagents -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76912802?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=IARC+scientific+publications&rft.atitle=Gene-specific+damage+and+repair+of+DNA+adducts+and+cross-links.&rft.au=Bohr%2C+V+A&rft.aulast=Bohr&rft.aufirst=V&rft.date=1994-01-01&rft.volume=&rft.issue=125&rft.spage=361&rft.isbn=&rft.btitle=&rft.title=IARC+scientific+publications&rft.issn=03005038&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-01-30 N1 - Date created - 1995-01-30 N1 - Date revised - 2017-01-13 N1 - Gene symbol - c-myc; dhfr; p53 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Modulation of progesterone-induced Xenopus oocyte maturation by prostaglandins E1 and E2. AN - 76912363; 7804327 AB - Prostaglandins E1 (PGE1) and E2 (PGE2), the general local modulators or "local" hormones, were able to inhibit the progesterone-induced maturation of Xenopus oocytes in vitro, but could not induce maturation by themselves. This inhibition was observed on the sensitivity of the maturation process of the oocyte responses to progesterone, but not on the maximum response or responsiveness. The decreased sensitivity of oocytes to progesterone by prostaglandin E1 or E2 was evident in both the increased concentration of progesterone and the prolonged time required for the maturation of 50% of the oocyte. PGE1 and PGE2 did not appear to affect either the basal level or the progesterone-reduced cAMP level of oocytes. Microinjection of PGE1 or PGE2 into the oocytes had no effect on progesterone-induced oocyte maturation, suggesting that other cell surface-mediated signaling events might be responsible for this modulatory effect of the progstaglandins. JF - Cellular & molecular biology research AU - Zhao, J AU - Kung, H F AD - Laboratory of Biochemical Physiology, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21701-1201. Y1 - 1994 PY - 1994 DA - 1994 SP - 63 EP - 68 VL - 40 IS - 1 SN - 0968-8773, 0968-8773 KW - Progesterone KW - 4G7DS2Q64Y KW - Cyclic AMP KW - E0399OZS9N KW - Alprostadil KW - F5TD010360 KW - Dinoprostone KW - K7Q1JQR04M KW - Index Medicus KW - Xenopus laevis KW - Animals KW - Oocytes -- growth & development KW - Drug Interactions KW - Oocytes -- metabolism KW - In Vitro Techniques KW - Oocytes -- drug effects KW - Cyclic AMP -- metabolism KW - Microinjections KW - Female KW - Alprostadil -- pharmacology KW - Dinoprostone -- pharmacology KW - Alprostadil -- administration & dosage KW - Oogenesis -- physiology KW - Progesterone -- pharmacology KW - Progesterone -- administration & dosage KW - Oogenesis -- drug effects KW - Dinoprostone -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76912363?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cellular+%26+molecular+biology+research&rft.atitle=Modulation+of+progesterone-induced+Xenopus+oocyte+maturation+by+prostaglandins+E1+and+E2.&rft.au=Zhao%2C+J%3BKung%2C+H+F&rft.aulast=Zhao&rft.aufirst=J&rft.date=1994-01-01&rft.volume=40&rft.issue=1&rft.spage=63&rft.isbn=&rft.btitle=&rft.title=Cellular+%26+molecular+biology+research&rft.issn=09688773&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-01-30 N1 - Date created - 1995-01-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - DNA alkylation by triazenes and related compounds. AN - 76911693; 7806322 JF - IARC scientific publications AU - Michejda, C J AU - Smith, R H AU - Kroeger Koepke, M B AD - Molecular Aspects of Drug Design Section, ABL-Basic Research Program, National Cancer Institute-Frederick Cancer Research and Development Center, MD. Y1 - 1994 PY - 1994 DA - 1994 SP - 323 EP - 337 IS - 125 SN - 0300-5038, 0300-5038 KW - DNA Adducts KW - 0 KW - Triazenes KW - DNA KW - 9007-49-2 KW - Index Medicus KW - DNA Adducts -- biosynthesis KW - Animals KW - Humans KW - Alkylation KW - Triazenes -- metabolism KW - DNA -- metabolism KW - Triazenes -- chemistry KW - Triazenes -- toxicity KW - DNA -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76911693?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=IARC+scientific+publications&rft.atitle=DNA+alkylation+by+triazenes+and+related+compounds.&rft.au=Michejda%2C+C+J%3BSmith%2C+R+H%3BKroeger+Koepke%2C+M+B&rft.aulast=Michejda&rft.aufirst=C&rft.date=1994-01-01&rft.volume=&rft.issue=125&rft.spage=323&rft.isbn=&rft.btitle=&rft.title=IARC+scientific+publications&rft.issn=03005038&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-01-30 N1 - Date created - 1995-01-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutational spectra of protooncogenes and tumour suppressor genes: clues in predicting cancer etiology. AN - 76910478; 7806329 JF - IARC scientific publications AU - Lehman, T A AU - Harris, C C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, MD. Y1 - 1994 PY - 1994 DA - 1994 SP - 399 EP - 412 IS - 125 SN - 0300-5038, 0300-5038 KW - aprt KW - hprt KW - p53 KW - ras KW - Index Medicus KW - Animals KW - Neoplasms, Experimental -- genetics KW - Humans KW - DNA Mutational Analysis KW - Spectrum Analysis -- methods KW - Predictive Value of Tests KW - Genes, Tumor Suppressor KW - Proto-Oncogenes KW - Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76910478?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=IARC+scientific+publications&rft.atitle=Mutational+spectra+of+protooncogenes+and+tumour+suppressor+genes%3A+clues+in+predicting+cancer+etiology.&rft.au=Lehman%2C+T+A%3BHarris%2C+C+C&rft.aulast=Lehman&rft.aufirst=T&rft.date=1994-01-01&rft.volume=&rft.issue=125&rft.spage=399&rft.isbn=&rft.btitle=&rft.title=IARC+scientific+publications&rft.issn=03005038&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-01-30 N1 - Date created - 1995-01-30 N1 - Date revised - 2017-01-13 N1 - Gene symbol - aprt; hprt; p53; ras N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The motivational correlates of drinking, smoking, and illicit drug use during pregnancy. AN - 76907739; 7804015 AB - Despite attempts to eliminate the consumption of alcohol, tobacco, and other substances of abuse by women of childbearing age, especially during gestation, apparently many do not curtail these negative lifestyle behaviors, as evidenced by the number of poor birth outcomes and developmentally disabled children born each year. This study examined the relationship of depression, attitude toward pregnancy, a number of sociodemographic variables, and substance use by women of child-bearing age prior to and after learning of their pregnancies. Results indicated that attitude independently, and depression independently and in interaction with socio-demographic factors are associated with substance use at both time points. From this we conclude that preventive efforts should be designed and targeted at those women who are depressed, especially those who have the sociodemographic characteristics associated with heavier substance use. JF - Journal of substance abuse AU - Hanna, E Z AU - Faden, V B AU - Dufour, M C AD - National Institute on Alcohol Abuse and Alcoholism, Division of Biometry and Epidemiology, Rockville, MD 20892-7003. Y1 - 1994 PY - 1994 DA - 1994 SP - 155 EP - 167 VL - 6 IS - 2 SN - 0899-3289, 0899-3289 KW - Street Drugs KW - 0 KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Fetal Alcohol Spectrum Disorders -- psychology KW - Humans KW - European Continental Ancestry Group -- psychology KW - Infant, Newborn KW - Cocaine -- adverse effects KW - Pregnancy KW - Depression -- prevention & control KW - Marital Status KW - Fetal Alcohol Spectrum Disorders -- prevention & control KW - Marijuana Smoking -- psychology KW - Risk Factors KW - Marijuana Smoking -- adverse effects KW - African Americans -- psychology KW - Depression -- psychology KW - Adult KW - Health Knowledge, Attitudes, Practice KW - Adolescent KW - Marijuana Smoking -- prevention & control KW - Female KW - Motivation KW - Pregnancy Complications -- psychology KW - Pregnancy Complications -- prevention & control KW - Street Drugs -- adverse effects KW - Alcohol Drinking -- psychology KW - Alcohol Drinking -- adverse effects KW - Smoking -- adverse effects KW - Alcohol Drinking -- prevention & control KW - Smoking -- psychology KW - Smoking -- prevention & control KW - Substance-Related Disorders -- psychology KW - Substance-Related Disorders -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76907739?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+substance+abuse&rft.atitle=The+motivational+correlates+of+drinking%2C+smoking%2C+and+illicit+drug+use+during+pregnancy.&rft.au=Hanna%2C+E+Z%3BFaden%2C+V+B%3BDufour%2C+M+C&rft.aulast=Hanna&rft.aufirst=E&rft.date=1994-01-01&rft.volume=6&rft.issue=2&rft.spage=155&rft.isbn=&rft.btitle=&rft.title=Journal+of+substance+abuse&rft.issn=08993289&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-01-30 N1 - Date created - 1995-01-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Rodent models of memory dysfunction in Alzheimer's disease and normal aging: moving beyond the cholinergic hypothesis. AN - 76888726; 7997063 AB - The Stone maze paradigm has been developed for use as a rat model of memory impairment observed in normal aging and in Alzheimer's disease. Results from several studies have demonstrated the involvement of both cholinergic and glutamatergic systems in acquisition performance in this complex maze task. Although results of clinical studies on the cognitive enhancing abilities of cholinomimetics for treatment of memory impairment in Alzheimer's disease have been inconsistent, new classes of cholinesterase inhibitors offer greater potential for therapeutic efficacy. The physostigimine derivative, phenserine, appears to have marked efficacy for improving learning performance of aged rats or of young rats treated with scopolamine in the Stone maze. Declines in markers of glutamatergic neurotransmission in Alzheimer's disease and in normal aging suggest that pharmacological manipulation of this system might also prove beneficial for cognitive enhancement. Treatment with glycine and/or polyamine agonists is suggested as a strategy for activating the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor. In addition, the use of combined pharmacological activation of cholinergic and glutamatergic systems is suggested. Manipulation of signal transduction events should also be considered as a strategy for cognitive enhancement. The influx of Ca2+ through the channel formed by the NMDA receptor stimulates the production of the oxyradical, nitric oxide (NO*), via the action of nitric oxide synthase (NOS). Compounds that inhibit NOS activity impair acquisition in the Stone maze, suggesting an involvement of NO*. Thus, strategies for inducing NO* production to enhance cognitive performance may be beneficial. Because of the potential neurotoxicity for NO*, this strategy is not straightforward. Although many new directions beyond the cholinergic hypothesis can be suggested, each has its potential benefits which must be weighed against its risks. Nonetheless, an important unifying area for neurobiological research examining mechanisms of normal brain aging and of age-related neuropathology, as observed in Alzheimer's disease, might emerge from the identification of NO* as a simple molecule serving vital physiological functions but representing potential for neurotoxicity. JF - Life sciences AU - Ingram, D K AU - Spangler, E L AU - Iijima, S AU - Ikari, H AU - Kuo, H AU - Greig, N H AU - London, E D AD - Nathan W. Shock Laboratories, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224. Y1 - 1994 PY - 1994 DA - 1994 SP - 2037 EP - 2049 VL - 55 IS - 25-26 SN - 0024-3205, 0024-3205 KW - Receptors, Cholinergic KW - 0 KW - Receptors, N-Methyl-D-Aspartate KW - Nitric Oxide KW - 31C4KY9ESH KW - Scopolamine Hydrobromide KW - 451IFR0GXB KW - Index Medicus KW - Rats KW - Maze Learning KW - Animals KW - Receptors, N-Methyl-D-Aspartate -- physiology KW - Scopolamine Hydrobromide -- pharmacology KW - Receptors, Cholinergic -- physiology KW - Disease Models, Animal KW - Nitric Oxide -- physiology KW - Aging -- physiology KW - Memory -- drug effects KW - Alzheimer Disease -- physiopathology KW - Aging -- psychology KW - Aging -- drug effects KW - Alzheimer Disease -- psychology KW - Memory -- physiology KW - Alzheimer Disease -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76888726?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+National+Cancer+Institute&rft.atitle=Report+of+the+Cancer+Therapy+Evaluation+Program+monitoring+plan+for+secondary+acute+myeloid+leukemia+following+treatment+with+epipodophyllotoxins.&rft.au=Smith%2C+M+A%3BRubinstein%2C+L%3BCazenave%2C+L%3BUngerleider%2C+R+S%3BMaurer%2C+H+M%3BHeyn%2C+R%3BKhan%2C+F+M%3BGehan%2C+E&rft.aulast=Smith&rft.aufirst=M&rft.date=1993-04-07&rft.volume=85&rft.issue=7&rft.spage=554&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+National+Cancer+Institute&rft.issn=00278874&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-01-18 N1 - Date created - 1995-01-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - D-cycloserine treatment of Alzheimer disease. AN - 76872628; 7986489 AB - Degeneration of cortical glutamatergic projections may contribute to the cognitive decline in Alzheimer disease (AD). To evaluate whether 1glutamate system stimulation might confer symptomatic benefit, we administered D-cycloserine, a putative partial indirect agonist at certain N-methyl-D-aspartate (NMDA) glutamate receptors, to 12 patients with probable AD. The patients (seven men, five women) had a mean age of 65 +/- 8.4 years; Mini Mental State Examination scores ranged from 15 to 25. A dose escalation phase, in which cycloserine was given in daily oral doses from 25 to 500 mg (total of six dose levels, 1 week per dose), was followed by a "best dose" crossover comparison with placebo under double-blind conditions. The crossover phase consisted of 2 weeks of cycloserine and 2 weeks of placebo, separated by a 1-week washout period. We observed no significant or consistent effect on neuropsychological outcome measures. The results suggest that short-term potentiation of NMDA-mediated glutamatergic transmission may not prove useful in the symptomatic treatment of Alzheimer dementia. JF - Alzheimer disease and associated disorders AU - Randolph, C AU - Roberts, J W AU - Tierney, M C AU - Bravi, D AU - Mouradian, M M AU - Chase, T N AD - Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland. Y1 - 1994 PY - 1994 DA - 1994 SP - 198 EP - 205 VL - 8 IS - 3 SN - 0893-0341, 0893-0341 KW - Receptors, N-Methyl-D-Aspartate KW - 0 KW - Cycloserine KW - 95IK5KI84Z KW - Index Medicus KW - Brain -- physiopathology KW - Double-Blind Method KW - Dose-Response Relationship, Drug KW - Humans KW - Brain -- drug effects KW - Mental Status Schedule KW - Aged KW - Middle Aged KW - Neuropsychological Tests KW - Geriatric Assessment KW - Male KW - Female KW - Receptors, N-Methyl-D-Aspartate -- physiology KW - Receptors, N-Methyl-D-Aspartate -- drug effects KW - Cycloserine -- therapeutic use KW - Alzheimer Disease -- physiopathology KW - Alzheimer Disease -- drug therapy KW - Cycloserine -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76872628?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Alzheimer+disease+and+associated+disorders&rft.atitle=D-cycloserine+treatment+of+Alzheimer+disease.&rft.au=Randolph%2C+C%3BRoberts%2C+J+W%3BTierney%2C+M+C%3BBravi%2C+D%3BMouradian%2C+M+M%3BChase%2C+T+N&rft.aulast=Randolph&rft.aufirst=C&rft.date=1994-01-01&rft.volume=8&rft.issue=3&rft.spage=198&rft.isbn=&rft.btitle=&rft.title=Alzheimer+disease+and+associated+disorders&rft.issn=08930341&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-01-12 N1 - Date created - 1995-01-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regulation of bacterial gene expression in response to oxidative stress. AN - 76842337; 7968610 JF - Methods in enzymology AU - Storz, G AU - Toledano, M B AD - Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994 PY - 1994 DA - 1994 SP - 196 EP - 207 VL - 236 SN - 0076-6879, 0076-6879 KW - katF KW - katG KW - lacZ KW - momR KW - oxyR KW - sodA KW - soxR KW - soxS KW - Bacterial Proteins KW - 0 KW - Oxidants KW - Sulfates KW - Sulfur Radioisotopes KW - Superoxides KW - 11062-77-4 KW - Hydrogen Peroxide KW - BBX060AN9V KW - Oxygen KW - S88TT14065 KW - Index Medicus KW - Sulfates -- metabolism KW - Superoxides -- pharmacology KW - Genes, Bacterial KW - Electrophoresis, Gel, Two-Dimensional -- methods KW - Hydrogen Peroxide -- pharmacology KW - Drug Resistance, Microbial KW - Cloning, Molecular -- methods KW - Autoradiography -- methods KW - Mutagenesis KW - Genes, Regulator KW - Salmonella typhimurium -- metabolism KW - Escherichia coli -- metabolism KW - Bacterial Proteins -- biosynthesis KW - Oxidants -- pharmacology KW - Oxygen -- pharmacology KW - Oxidative Stress KW - Gene Expression Regulation, Bacterial -- drug effects KW - Escherichia coli -- drug effects KW - Escherichia coli -- genetics KW - Bacterial Proteins -- isolation & purification KW - Salmonella typhimurium -- drug effects KW - Salmonella typhimurium -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76842337?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Methods+in+enzymology&rft.atitle=Regulation+of+bacterial+gene+expression+in+response+to+oxidative+stress.&rft.au=Storz%2C+G%3BToledano%2C+M+B&rft.aulast=Storz&rft.aufirst=G&rft.date=1994-01-01&rft.volume=236&rft.issue=&rft.spage=196&rft.isbn=&rft.btitle=&rft.title=Methods+in+enzymology&rft.issn=00766879&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-12-06 N1 - Date created - 1994-12-06 N1 - Date revised - 2017-01-13 N1 - Gene symbol - katF; katG; lacZ; momR; oxyR; sodA; soxR; soxS N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Brain parenchyma apparent diffusion coefficient alterations associated with experimental complex partial status epilepticus. AN - 76825906; 7968286 AB - The objective of this study was to evaluate whether water apparent diffusion coefficient (ADC) measurements provide more specific information than T2-weighted MRI about the evolution of brain parenchyma lesions secondary to prolonged complex partial seizures. We measured the ADC in the brain of rats exhibiting prolonged complex partial seizures induced by intraperitoneal injection of kainic acid (KA). The animals were imaged with diffusion and T2-weighted MRI at 2 T from 3 h up to 9 days after KA injection. In the piriform cortex and amygdala, the T2-weighted MRI signal intensity appeared to be uniformly increased from 24 to 72 h after KA injection, and returned to normal by 9 days. In the same regions between 24 and 72 h, the ADC first decreased and then increased. The ADC changes were consistent with the known histopathologic alterations. In this complex partial seizure model, the ADC measurement provides more specific information than T2-weighted MRI about the histopathologic evolution of the lesions. This supports the proposal that diffusion MRI may be valuable for the evaluation of the neuropathologic sequelae in patients with multiple or prolonged seizures. JF - Magnetic resonance imaging AU - Righini, A AU - Pierpaoli, C AU - Alger, J R AU - Di Chiro, G AD - Neuroimaging Branch, NINDS, National Institutes of Health (NIH), Bethesda, MD 20892. Y1 - 1994 PY - 1994 DA - 1994 SP - 865 EP - 871 VL - 12 IS - 6 SN - 0730-725X, 0730-725X KW - Kainic Acid KW - SIV03811UC KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Male KW - Magnetic Resonance Imaging KW - Epilepsy, Complex Partial -- diagnosis KW - Status Epilepticus -- chemically induced KW - Brain -- pathology KW - Status Epilepticus -- diagnosis KW - Epilepsy, Complex Partial -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76825906?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Magnetic+resonance+imaging&rft.atitle=Brain+parenchyma+apparent+diffusion+coefficient+alterations+associated+with+experimental+complex+partial+status+epilepticus.&rft.au=Righini%2C+A%3BPierpaoli%2C+C%3BAlger%2C+J+R%3BDi+Chiro%2C+G&rft.aulast=Righini&rft.aufirst=A&rft.date=1994-01-01&rft.volume=12&rft.issue=6&rft.spage=865&rft.isbn=&rft.btitle=&rft.title=Magnetic+resonance+imaging&rft.issn=0730725X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-12-01 N1 - Date created - 1994-12-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Vitamin E in the genesis and prevention of cancer. A review. AN - 76788310; 7946437 AB - A review of current literature reveals that the relationships between vitamin E and cancer is not yet fully understood though many experimental and clinical studies have shown that vitamin E can protect against carcinogenesis and tumour growth. This vitamin also appears to reduce toxicity of several anticancer therapies. Such effects are probably due to the antioxidant property and immunomodulatory function of vitamin E. The findings of different groups suggest that this vitamin may be helpful as a cancer chemopreventive agent. JF - Acta oncologica (Stockholm, Sweden) AU - Das, S AD - Department of Experimental Leukaemia, Chittaranjan National Cancer Institute, Calcutta, India. Y1 - 1994 PY - 1994 DA - 1994 SP - 615 EP - 619 VL - 33 IS - 6 SN - 0284-186X, 0284-186X KW - Anticarcinogenic Agents KW - 0 KW - Antioxidants KW - Vitamin E KW - 1406-18-4 KW - Index Medicus KW - Animals KW - Humans KW - Immunity -- drug effects KW - Anticarcinogenic Agents -- pharmacology KW - Vitamin E -- pharmacology KW - Neoplasms -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76788310?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Acta+oncologica+%28Stockholm%2C+Sweden%29&rft.atitle=Vitamin+E+in+the+genesis+and+prevention+of+cancer.+A+review.&rft.au=Das%2C+S&rft.aulast=Das&rft.aufirst=S&rft.date=1994-01-01&rft.volume=33&rft.issue=6&rft.spage=615&rft.isbn=&rft.btitle=&rft.title=Acta+oncologica+%28Stockholm%2C+Sweden%29&rft.issn=0284186X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-12-21 N1 - Date created - 1994-12-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Randomised phase II study of methotrexate (MTX) versus methotrexate plus lonidamine (MTX + LND) in recurrent and/or metastatic carcinoma of the head and neck. AN - 76779033; 7946585 AB - Between March 1990 and March 1992, 89 patients with recurrent and/or metastatic squamous cell cancer of the head and neck were randomised to receive either intravenous methotrexate (MTX) at a weekly dose of 40 mg/m2 plus lonidamine (LND) given orally at a starting dose of 75 mg three times daily for 3 days and then at a dose of 150 mg three times daily (arm MTX + LND) or methotrexate alone (arm MTX) at the same doses as arm MTX + LND. Complete remissions were observed in 10.5% of the patients in arm MTX + LND, and partial remissions in another 15.8%, yielding a 26.3% response rate. In arm MTX, only partial remissions were observed, yielding an overall response rate of 18.2%. Haematological toxicity was mild in both groups. Mild testicular pain (21%) and myalgias (31%) occurred only in patients treated with LND. JF - European journal of cancer (Oxford, England : 1990) AU - Colella, E AU - Merlano, M AU - Blengio, F AU - Angelini, F AU - Ausili Cefaro, G P AU - Scasso, F AU - Lo Russo, V AU - Cirulli, S AU - Giannarelli, D AU - Cognetti, F AD - Regina Elena National Cancer Institute, Rome, Italy. Y1 - 1994 PY - 1994 DA - 1994 SP - 928 EP - 930 VL - 30A IS - 7 SN - 0959-8049, 0959-8049 KW - Indazoles KW - 0 KW - lonidamine KW - U78804BIDR KW - Methotrexate KW - YL5FZ2Y5U1 KW - Index Medicus KW - Indazoles -- adverse effects KW - Indazoles -- administration & dosage KW - Methotrexate -- adverse effects KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Neoplasm Recurrence, Local KW - Methotrexate -- administration & dosage KW - Male KW - Female KW - Head and Neck Neoplasms -- secondary KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Head and Neck Neoplasms -- drug therapy KW - Carcinoma, Squamous Cell -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76779033?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=European+journal+of+cancer+%28Oxford%2C+England+%3A+1990%29&rft.atitle=Randomised+phase+II+study+of+methotrexate+%28MTX%29+versus+methotrexate+plus+lonidamine+%28MTX+%2B+LND%29+in+recurrent+and%2For+metastatic+carcinoma+of+the+head+and+neck.&rft.au=Colella%2C+E%3BMerlano%2C+M%3BBlengio%2C+F%3BAngelini%2C+F%3BAusili+Cefaro%2C+G+P%3BScasso%2C+F%3BLo+Russo%2C+V%3BCirulli%2C+S%3BGiannarelli%2C+D%3BCognetti%2C+F&rft.aulast=Colella&rft.aufirst=E&rft.date=1994-01-01&rft.volume=30A&rft.issue=7&rft.spage=928&rft.isbn=&rft.btitle=&rft.title=European+journal+of+cancer+%28Oxford%2C+England+%3A+1990%29&rft.issn=09598049&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-12-12 N1 - Date created - 1994-12-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Activation of cholera toxin by ADP-ribosylation factors: 20-kDa guanine nucleotide-binding proteins. AN - 76763847; 7935017 JF - Methods in enzymology AU - Moss, J AU - Haun, R S AU - Tsai, S C AU - Welsh, C F AU - Lee, F J AU - Price, S R AU - Vaughan, M AD - Laboratory of Cellular Metabolism, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994 PY - 1994 DA - 1994 SP - 44 EP - 63 VL - 237 SN - 0076-6879, 0076-6879 KW - 'NMT1 KW - Carbon Radioisotopes KW - 0 KW - DNA Primers KW - Recombinant Proteins KW - NAD KW - 0U46U6E8UK KW - Adenosine Diphosphate Ribose KW - 20762-30-5 KW - Cholera Toxin KW - 9012-63-9 KW - Acyltransferases KW - EC 2.3.- KW - glycylpeptide N-tetradecanoyltransferase KW - EC 2.3.1.97 KW - Poly(ADP-ribose) Polymerases KW - EC 2.4.2.30 KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - ADP-Ribosylation Factors KW - EC 3.6.5.2 KW - Index Medicus KW - Animals KW - Cytosol -- metabolism KW - Genes, Fungal KW - Chromatography, Ion Exchange -- methods KW - Humans KW - Protein Processing, Post-Translational KW - Cloning, Molecular -- methods KW - Radioisotope Dilution Technique KW - Saccharomyces cerevisiae -- enzymology KW - Adenosine Diphosphate Ribose -- metabolism KW - Poly(ADP-ribose) Polymerases -- metabolism KW - Molecular Weight KW - Recombinant Proteins -- isolation & purification KW - Acyltransferases -- biosynthesis KW - Base Sequence KW - Cattle KW - Recombinant Proteins -- metabolism KW - Polymerase Chain Reaction -- methods KW - Molecular Sequence Data KW - Acyltransferases -- metabolism KW - Cell Membrane -- metabolism KW - NAD -- metabolism KW - GTP-Binding Proteins -- metabolism KW - GTP-Binding Proteins -- isolation & purification KW - Brain -- metabolism KW - Cholera Toxin -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76763847?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Methods+in+enzymology&rft.atitle=Activation+of+cholera+toxin+by+ADP-ribosylation+factors%3A+20-kDa+guanine+nucleotide-binding+proteins.&rft.au=Moss%2C+J%3BHaun%2C+R+S%3BTsai%2C+S+C%3BWelsh%2C+C+F%3BLee%2C+F+J%3BPrice%2C+S+R%3BVaughan%2C+M&rft.aulast=Moss&rft.aufirst=J&rft.date=1994-01-01&rft.volume=237&rft.issue=&rft.spage=44&rft.isbn=&rft.btitle=&rft.title=Methods+in+enzymology&rft.issn=00766879&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-10-31 N1 - Date created - 1994-10-31 N1 - Date revised - 2017-01-13 N1 - Gene symbol - 'NMT1 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Suppression of hydroxyl radical formation by MAO inhibitors: a novel possible neuroprotective mechanism in dopaminergic neurotoxicity. AN - 76756711; 7931226 AB - Prior studies concluded that 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, a toxin causing parkinsonism) and its analogues are bioactivated by monoamine oxidase (MAO) to toxic pyridinium metabolites. Recently, a dissociation between the neuroprotective effects of deprenyl and its MAO inhibiting effects has been proposed. Furthermore, we have demonstrated that pyridinium metabolites of MPTP stimulate dopamine efflux and the formation of cytotoxic hydroxyl free radicals (.OH) in the striatum. Therefore, we investigated possible neuroprotective mechanisms of propargyl MAO inhibitors by studying their effects on the formation of oxygen free radicals produced by dopamine autoxidation. Our recent in vivo results indicate that deprenyl and clorgyline given systemically suppressed the generation of .OH that followed administration of 2'-methyl-MPTP. Combined deprenyl and clorgyline pretreatment are needed to block dopamine neurotoxicity elicited by 2'-methyl-MPTP. The present in vitro studies reveal that propargyl MAO inhibitors suppress non-enzymatic dopamine autoxidation and associated free radical production. Thus, .OH generation evoked by MPTP analogues may be due mainly to a burst increase in iron-catalyzed autoxidation of released dopamine in the basal ganglia where high levels of iron and oxygen are present. Our present in vitro and prior in vivo results suggest that a novel antioxidant property of propargyl MAO inhibitors may contribute to protection against nigral lesions elicited by dopamine autoxidation following the administration of MPTP analogues. JF - Journal of neural transmission. Supplementum AU - Chiueh, C C AU - Huang, S J AU - Murphy, D L AD - Laboratory of Clinical Science, National Institute of Mental Health, NIH, Bethesda, Maryland. Y1 - 1994 PY - 1994 DA - 1994 SP - 189 EP - 196 VL - 41 SN - 0303-6995, 0303-6995 KW - Dopamine Agents KW - 0 KW - Dopamine Antagonists KW - Melanins KW - Monoamine Oxidase Inhibitors KW - Selegiline KW - 2K1V7GP655 KW - Hydroxyl Radical KW - 3352-57-6 KW - Pargyline KW - 9MV14S8G3E KW - Clorgyline KW - LYJ16FZU9Q KW - Ascorbic Acid KW - PQ6CK8PD0R KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Melanins -- biosynthesis KW - Selegiline -- pharmacology KW - Oxidation-Reduction -- drug effects KW - Pargyline -- pharmacology KW - Dopamine Antagonists -- pharmacology KW - Dopamine -- metabolism KW - Clorgyline -- pharmacology KW - Ascorbic Acid -- pharmacology KW - Hydroxyl Radical -- antagonists & inhibitors KW - Nervous System -- drug effects KW - Dopamine Agents -- pharmacology KW - Monoamine Oxidase Inhibitors -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76756711?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+neural+transmission.+Supplementum&rft.atitle=Suppression+of+hydroxyl+radical+formation+by+MAO+inhibitors%3A+a+novel+possible+neuroprotective+mechanism+in+dopaminergic+neurotoxicity.&rft.au=Chiueh%2C+C+C%3BHuang%2C+S+J%3BMurphy%2C+D+L&rft.aulast=Chiueh&rft.aufirst=C&rft.date=1994-01-01&rft.volume=41&rft.issue=&rft.spage=189&rft.isbn=&rft.btitle=&rft.title=Journal+of+neural+transmission.+Supplementum&rft.issn=03036995&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-11-23 N1 - Date created - 1994-11-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Administration of the antimycotic agents fluconazole and itraconazole to leukaemia patients: a comparative pharmacokinetic study. AN - 76750327; 7924899 AB - This report presents the results of a randomized parallel design comparative study of the serum concentrations of fluconazole and itraconazole after administration of 100 mg orally to patients with leukaemia. Each group consisted of ten patients. The antimycotic drugs were administered with a standard breakfast immediately before the start of chemotherapy (day one) and on days eight and fifteen. No significant differences (p > 0.05; ANOVA) in the pharmacokinetic parameters of fluconazole (AUC, Cmax, Tmax) were found during the three days of the trial. It is concluded that there is no clinically important pharmacokinetic interaction between fluconazole and the chemotherapeutic agents given to this group of patients. A pharmacokinetic interaction between fluconazole and the fever suffered by some of the patients also seems unlikely. No significant differences (p < 0.05; ANOVA) in the pharmacokinetic parameters of itraconazole (AUC, Cmax, Tmax) were found during the three days of the trial, although the statistical power of the data was low. The significantly greater variability of all pharmacokinetic parameters for itraconazole than for fluconazole and the sharp increases and decreases in AUC during the course of the trial found for some patients in the itraconazole group suggest the need for caution in this group of patients. JF - Drugs under experimental and clinical research AU - Lazo de la Vega, S AU - Volkow, P AU - Yeates, R A AU - Pfaff, G AD - Department of Infectious Diseases, National Cancer Institute, Mexico City, Mexico. Y1 - 1994 PY - 1994 DA - 1994 SP - 69 EP - 75 VL - 20 IS - 2 SN - 0378-6501, 0378-6501 KW - Antifungal Agents KW - 0 KW - Itraconazole KW - 304NUG5GF4 KW - Fluconazole KW - 8VZV102JFY KW - Index Medicus KW - Drug Interactions KW - Humans KW - Adult KW - Spectrophotometry, Ultraviolet KW - Middle Aged KW - Adolescent KW - Male KW - Female KW - Chromatography, High Pressure Liquid KW - Itraconazole -- pharmacokinetics KW - Antifungal Agents -- pharmacokinetics KW - Leukemia -- metabolism KW - Fluconazole -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76750327?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Drugs+under+experimental+and+clinical+research&rft.atitle=Administration+of+the+antimycotic+agents+fluconazole+and+itraconazole+to+leukaemia+patients%3A+a+comparative+pharmacokinetic+study.&rft.au=Lazo+de+la+Vega%2C+S%3BVolkow%2C+P%3BYeates%2C+R+A%3BPfaff%2C+G&rft.aulast=Lazo+de+la+Vega&rft.aufirst=S&rft.date=1994-01-01&rft.volume=20&rft.issue=2&rft.spage=69&rft.isbn=&rft.btitle=&rft.title=Drugs+under+experimental+and+clinical+research&rft.issn=03786501&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-11-16 N1 - Date created - 1994-11-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of human cytochromes P450 in the metabolic activation of chemical carcinogens and toxins. AN - 76708035; 8082563 JF - Drug metabolism reviews AU - Gonzalez, F J AU - Gelboin, H V AD - National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994 PY - 1994 DA - 1994 SP - 165 EP - 183 VL - 26 IS - 1-2 SN - 0360-2532, 0360-2532 KW - Carcinogens KW - 0 KW - DNA, Complementary KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Index Medicus KW - Animals KW - DNA, Complementary -- genetics KW - Biotransformation KW - Humans KW - Immunochemistry KW - Cell Line KW - Carcinogens -- metabolism KW - Cytochrome P-450 Enzyme System -- genetics KW - Cytochrome P-450 Enzyme System -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76708035?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Maturational+changes+in+dermal+absorption+of+2%2C3%2C7%2C8-tetrachlorodibenzo-p-dioxin+%28TCDD%29+in+Fischer+344+rats.&rft.au=Anderson%2C+Y+B%3BJackson%2C+J+A%3BBirnbaum%2C+L+S&rft.aulast=Anderson&rft.aufirst=Y&rft.date=1993-04-01&rft.volume=119&rft.issue=2&rft.spage=214&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 - 1994-10-13 N1 - Date created - 1994-10-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - DNA strand breaks induced by configurationally isomeric hydrocarbon diol epoxides. AN - 76707883; 8082571 JF - Drug metabolism reviews AU - Bigger, C A AU - Cheh, A AU - Latif, F AU - Fishel, R AU - Canella, K A AU - Stafford, G A AU - Yagi, H AU - Jerina, D M AU - Dipple, A AD - Chemistry of Carcinogenesis Laboratory, NCI-Frederick Cancer Research and Development Center, Maryland 21702. Y1 - 1994 PY - 1994 DA - 1994 SP - 287 EP - 299 VL - 26 IS - 1-2 SN - 0360-2532, 0360-2532 KW - Benz(a)Anthracenes KW - 0 KW - Carcinogens KW - 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide KW - 55097-80-8 KW - 3,4-dihydroxy-1,2-epoxy-1,2,3,4-tetrahydrobenz(a)anthracene KW - 64551-89-9 KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Stereoisomerism KW - Base Sequence KW - Electrophoresis, Polyacrylamide Gel KW - Molecular Sequence Data KW - 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide -- toxicity KW - 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide -- metabolism KW - Carcinogens -- metabolism KW - DNA Damage KW - DNA -- metabolism KW - Carcinogens -- toxicity KW - Benz(a)Anthracenes -- toxicity KW - Benz(a)Anthracenes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76707883?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Drug+metabolism+reviews&rft.atitle=DNA+strand+breaks+induced+by+configurationally+isomeric+hydrocarbon+diol+epoxides.&rft.au=Bigger%2C+C+A%3BCheh%2C+A%3BLatif%2C+F%3BFishel%2C+R%3BCanella%2C+K+A%3BStafford%2C+G+A%3BYagi%2C+H%3BJerina%2C+D+M%3BDipple%2C+A&rft.aulast=Bigger&rft.aufirst=C&rft.date=1994-01-01&rft.volume=54&rft.issue=4&rft.spage=336&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+surgical+research&rft.issn=00224804&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-10-13 N1 - Date created - 1994-10-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutational spectrum of the p53 tumor suppressor gene: clues to cancer etiology and molecular pathogenesis. AN - 76705211; 8082567 JF - Drug metabolism reviews AU - Lehman, T A AU - Greenblatt, M AU - Bennett, W P AU - Harris, C C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1994 PY - 1994 DA - 1994 SP - 221 EP - 235 VL - 26 IS - 1-2 SN - 0360-2532, 0360-2532 KW - aprt KW - hprt KW - p53 KW - Adenine Phosphoribosyltransferase KW - EC 2.4.2.7 KW - Hypoxanthine Phosphoribosyltransferase KW - EC 2.4.2.8 KW - Index Medicus KW - Animals KW - Base Sequence KW - Hypoxanthine Phosphoribosyltransferase -- genetics KW - Humans KW - Adenine Phosphoribosyltransferase -- genetics KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Genes, p53 KW - Carcinoma, Hepatocellular -- etiology KW - Carcinoma, Hepatocellular -- genetics KW - Liver Neoplasms -- etiology KW - Mutation KW - Neoplasms -- genetics KW - Neoplasms -- etiology KW - Liver Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76705211?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Drug+metabolism+reviews&rft.atitle=Mutational+spectrum+of+the+p53+tumor+suppressor+gene%3A+clues+to+cancer+etiology+and+molecular+pathogenesis.&rft.au=Lehman%2C+T+A%3BGreenblatt%2C+M%3BBennett%2C+W+P%3BHarris%2C+C+C&rft.aulast=Lehman&rft.aufirst=T&rft.date=1994-01-01&rft.volume=26&rft.issue=1-2&rft.spage=221&rft.isbn=&rft.btitle=&rft.title=Drug+metabolism+reviews&rft.issn=03602532&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-10-13 N1 - Date created - 1994-10-13 N1 - Date revised - 2017-01-13 N1 - Gene symbol - aprt; hprt; p53 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Human exposure monitoring, dosimetry, and cancer risk assessment: the use of antisera specific for carcinogen-DNA adducts and carcinogen-modified DNA. AN - 76702832; 8082583 JF - Drug metabolism reviews AU - Poirier, M C AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, NIH, Bethesda, Maryland 20892. Y1 - 1994 PY - 1994 DA - 1994 SP - 87 EP - 109 VL - 26 IS - 1-2 SN - 0360-2532, 0360-2532 KW - Carcinogens KW - 0 KW - Immune Sera KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Environmental Monitoring KW - Chromatography, Affinity KW - Risk Factors KW - Humans KW - Immunohistochemistry KW - Carcinogens -- metabolism KW - DNA Damage KW - DNA -- metabolism KW - Neoplasms -- chemically induced KW - Environmental Exposure KW - DNA -- analysis KW - DNA -- immunology KW - Immunoassay UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76702832?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Drug+metabolism+reviews&rft.atitle=Human+exposure+monitoring%2C+dosimetry%2C+and+cancer+risk+assessment%3A+the+use+of+antisera+specific+for+carcinogen-DNA+adducts+and+carcinogen-modified+DNA.&rft.au=Poirier%2C+M+C&rft.aulast=Poirier&rft.aufirst=M&rft.date=1994-01-01&rft.volume=26&rft.issue=1-2&rft.spage=87&rft.isbn=&rft.btitle=&rft.title=Drug+metabolism+reviews&rft.issn=03602532&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-10-13 N1 - Date created - 1994-10-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Prevalence and population validity of DSM-III-R alcohol abuse and dependence: the 1989 National Longitudinal Survey on Youth. AN - 76690756; 8081108 AB - This report presents national estimates of The Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised (DSM-III-R) alcohol abuse and dependence among 24- to 31-year-olds using the 1989 National Longitudinal Survey on Youth (NLS-Y). Population estimates derived from the 1989 NLS-Y are also compared with corresponding estimates from the 1988 National Health Interview Survey (NHIS). The 1-year prevalence of alcohol abuse and dependence was 13.95% in the 1989 NLS-Y. In general, rates of abuse and dependence were greater for men than for women and slightly declined with age. Although the prevalence of abuse was much greater among whites compared to blacks or Hispanics, the rates for dependence among Hispanics and whites exceeded those for their black counterparts. The rates of abuse and dependence were strikingly similar between the 1989 NLS-Y and 1988 NHIS, providing evidence for the population validity or generalizability of the diagnostic measures. JF - Journal of substance abuse AU - Harford, T C AU - Grant, B F AD - Division of Biometry and Epidemiology, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD 20892. Y1 - 1994 PY - 1994 DA - 1994 SP - 37 EP - 44 VL - 6 IS - 1 SN - 0899-3289, 0899-3289 KW - Index Medicus KW - Sex Factors KW - Humans KW - Adult KW - Longitudinal Studies KW - United States -- epidemiology KW - Male KW - Female KW - Prevalence KW - Alcoholism -- epidemiology KW - Alcohol Drinking -- ethnology KW - Alcoholism -- ethnology KW - Alcohol Drinking -- epidemiology KW - Manuals as Topic UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76690756?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+substance+abuse&rft.atitle=Prevalence+and+population+validity+of+DSM-III-R+alcohol+abuse+and+dependence%3A+the+1989+National+Longitudinal+Survey+on+Youth.&rft.au=Harford%2C+T+C%3BGrant%2C+B+F&rft.aulast=Harford&rft.aufirst=T&rft.date=1994-01-01&rft.volume=6&rft.issue=1&rft.spage=37&rft.isbn=&rft.btitle=&rft.title=Journal+of+substance+abuse&rft.issn=08993289&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-10-13 N1 - Date created - 1994-10-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Recombinant toxins. AN - 76684558; 8080817 JF - Advances in pharmacology (San Diego, Calif.) AU - Kreitman, R J AU - Pastan, I AD - Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994 PY - 1994 DA - 1994 SP - 193 EP - 219 VL - 28 SN - 1054-3589, 1054-3589 KW - Bacterial Toxins KW - 0 KW - DAB(486)-interleukin 2 KW - Diphtheria Toxin KW - Exotoxins KW - IL-6-PE40 protein, chimeric KW - Immunotoxins KW - Interleukin-2 KW - Interleukin-6 KW - Recombinant Fusion Proteins KW - Transforming Growth Factor alpha KW - Virulence Factors KW - transforming growth factor type alpha-Pseudomonas exotoxin A KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - toxA protein, Pseudomonas aeruginosa KW - EC 2.4.2.31 KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - Index Medicus KW - Animals KW - Transforming Growth Factor alpha -- therapeutic use KW - Interleukin-2 -- therapeutic use KW - Humans KW - Transforming Growth Factor alpha -- biosynthesis KW - Interleukin-2 -- biosynthesis KW - Receptor, Epidermal Growth Factor -- analysis KW - Recombinant Fusion Proteins -- biosynthesis KW - Interleukin-6 -- therapeutic use KW - Exotoxins -- biosynthesis KW - Diphtheria Toxin -- biosynthesis KW - Immunotoxins -- therapeutic use KW - Diphtheria Toxin -- therapeutic use KW - Interleukin-6 -- biosynthesis KW - Exotoxins -- therapeutic use KW - Recombinant Fusion Proteins -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76684558?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Oral+gossypol+in+the+treatment+of+metastatic+adrenal+cancer.&rft.au=Flack%2C+M+R%3BPyle%2C+R+G%3BMullen%2C+N+M%3BLorenzo%2C+B%3BWu%2C+Y+W%3BKnazek%2C+R+A%3BNisula%2C+B+C%3BReidenberg%2C+M+M&rft.aulast=Flack&rft.aufirst=M&rft.date=1993-04-01&rft.volume=76&rft.issue=4&rft.spage=1019&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 - 1994-10-13 N1 - Date created - 1994-10-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Carcinogen activation by sulfate conjugate formation. AN - 76679242; 8068558 AB - The foregoing pages presented a substantial body of data that established that sulfotransferase conjugation can transform many xenobiotics into agents that can modify cellular macromolecules. However, activation by sulfation is rarely the only metabolic pathway that is open to these compounds; other pathways can become more important in response to a variety of factors. This metabolic switching can be produced by substrate concentration, cofactor availability, kinetic factors that dictate the velocity of the various possible conjugation reactions, and, in some cases, competition between Phase-I and Phase-II metabolism. Also, it is important to realize that demonstration of activation by sulfate ester formation in vitro does not necessarily mean that a similar activation process will occur in vivo. Experience also teaches that argument by analogy can be very misleading in the case of sulfate activation. Small structural differences can upset the delicate balance between sulfate activation and the various other competing pathways. Nevertheless, sulfation is an important mechanism by which a number of chemicals are transformed to their activated forms. JF - Advances in pharmacology (San Diego, Calif.) AU - Michejda, C J AU - Kroeger Koepke, M B AD - Molecular Aspects of Drug Design Section, NCI-Frederick Cancer Research and Development Center, Maryland 21702. Y1 - 1994 PY - 1994 DA - 1994 SP - 331 EP - 363 VL - 27 SN - 1054-3589, 1054-3589 KW - Carcinogens KW - 0 KW - Sulfates KW - Index Medicus KW - Animals KW - Humans KW - Sulfates -- metabolism KW - Carcinogens -- metabolism KW - Biotransformation -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76679242?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Advances+in+pharmacology+%28San+Diego%2C+Calif.%29&rft.atitle=Carcinogen+activation+by+sulfate+conjugate+formation.&rft.au=Michejda%2C+C+J%3BKroeger+Koepke%2C+M+B&rft.aulast=Michejda&rft.aufirst=C&rft.date=1994-01-01&rft.volume=83&rft.issue=2&rft.spage=153&rft.isbn=&rft.btitle=&rft.title=The+Cornell+veterinarian&rft.issn=00108901&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-09-27 N1 - Date created - 1994-09-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chemical and mutagenic specificities of polycyclic aromatic hydrocarbon carcinogens. AN - 76678116; 8067279 JF - Advances in experimental medicine and biology AU - Dipple, A AU - Peltonen, K AU - Cheng, S C AU - Ross, H AU - Bigger, C A AD - Chemistry of Carcinogenesis Laboratory, ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, MD 21702. Y1 - 1994 PY - 1994 DA - 1994 SP - 101 EP - 112 VL - 354 SN - 0065-2598, 0065-2598 KW - Carcinogens KW - 0 KW - Epoxy Compounds KW - Mutagens KW - Polycyclic Compounds KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Animals KW - Base Sequence KW - DNA Damage KW - Humans KW - DNA -- metabolism KW - Epoxy Compounds -- metabolism KW - Molecular Sequence Data KW - DNA -- drug effects KW - Polycyclic Compounds -- pharmacology KW - Polycyclic Compounds -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76678116?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Advances+in+experimental+medicine+and+biology&rft.atitle=Chemical+and+mutagenic+specificities+of+polycyclic+aromatic+hydrocarbon+carcinogens.&rft.au=Dipple%2C+A%3BPeltonen%2C+K%3BCheng%2C+S+C%3BRoss%2C+H%3BBigger%2C+C+A&rft.aulast=Dipple&rft.aufirst=A&rft.date=1994-01-01&rft.volume=354&rft.issue=&rft.spage=101&rft.isbn=&rft.btitle=&rft.title=Advances+in+experimental+medicine+and+biology&rft.issn=00652598&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-09-22 N1 - Date created - 1994-09-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Old protocols, as do old habits, die hard. AN - 76643783; 8050412 JF - Environmental and molecular mutagenesis AU - Zeiger, E AD - Environmental Toxicology Program, N.I.E.H.S., Research Triangle Park, North Carolina. Y1 - 1994 PY - 1994 DA - 1994 SP - 1 EP - 2 VL - 24 IS - 1 SN - 0893-6692, 0893-6692 KW - Index Medicus KW - Rats KW - Animals KW - Genes, Dominant KW - Mice KW - Genes, Lethal KW - Mutagenicity Tests -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76643783?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+and+molecular+mutagenesis&rft.atitle=Old+protocols%2C+as+do+old+habits%2C+die+hard.&rft.au=Zeiger%2C+E&rft.aulast=Zeiger&rft.aufirst=E&rft.date=1994-01-01&rft.volume=24&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Environmental+and+molecular+mutagenesis&rft.issn=08936692&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-09-06 N1 - Date created - 1994-09-06 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Environ Mol Mutagen. 1994;24(4):332-3 [7851346] Environ Mol Mutagen. 1994;24(4):333 [7851347] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Carcinogenicity of TCDD: experimental, mechanistic, and epidemiologic evidence. AN - 76629233; 8042855 JF - Annual review of pharmacology and toxicology AU - Huff, J AU - Lucier, G AU - Tritscher, A AD - Environmental Carcinogenesis Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1994 PY - 1994 DA - 1994 SP - 343 EP - 372 VL - 34 SN - 0362-1642, 0362-1642 KW - Polychlorinated Dibenzodioxins KW - 0 KW - Index Medicus KW - Animals KW - Humans KW - Carcinogenicity Tests KW - Neoplasms -- chemically induced KW - Polychlorinated Dibenzodioxins -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76629233?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annual+review+of+pharmacology+and+toxicology&rft.atitle=Carcinogenicity+of+TCDD%3A+experimental%2C+mechanistic%2C+and+epidemiologic+evidence.&rft.au=Huff%2C+J%3BLucier%2C+G%3BTritscher%2C+A&rft.aulast=Huff&rft.aufirst=J&rft.date=1994-01-01&rft.volume=34&rft.issue=&rft.spage=343&rft.isbn=&rft.btitle=&rft.title=Annual+review+of+pharmacology+and+toxicology&rft.issn=03621642&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-08-25 N1 - Date created - 1994-08-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular epidemiology: a new perspective for the study of toxic exposures in man. A consideration of the influence of genetic susceptibility factors on risk in different lung cancer histologies. AN - 76603666; 8035747 AB - This data in the aggregate suggests that the 3 best studied genetic susceptibility factors (CYP2D6 extensive metabolizers, GST mu null phenotype, and CYP1A1 "mutant" alleles in Asians only) constitute greater risk factors for the more smoking related histologies of lung cancer, but not for adenocarcinoma. The epidemiologic evidence for a these genetic susceptibility factors in tobacco-related cancer is suggestive but not determinant. A consensus estimate of relative risk for extensive metabolizers of debrisoquine is around 2. Variability in study results depend on a number of factors which include: assay misclassification, non-correspondence of phenotype/genotype in certain subjects, disease heterogeneity, exposure variation, ethnic and racial variation. Future studies should emphasize: a high quality approach to data gathering, careful attention to epidemiologic design, and the use of intermediate markers where feasible. Investigators should consider the use of multiple genetic markers since PCR approaches can make this an efficient approach. A meta-analysis may serve to illuminate points of heterogeneity between studies. New discoveries should provide opportunities to explore for analogous associations in other malignancies. It may be speculated that the "specificity" of the association observed for each of the genetic factors tends to support the general causal nature of the hypothesis. The fact that each shares the histologic preference at least suggests that a common mechanism may be operative. The observation that the tobacco-cancer association, though clearly present, is weaker for adenocarcinoma than for the other lung cancer histologies, suggests that the underlying mechanism involves some interaction of the genetic trait with exposure to tobacco smoking, and suggests further attention to this factor to elucidate differences in risk estimates for genetic susceptibility factors among different studies. JF - La Medicina del lavoro AU - Caporaso, N E AU - Landi, M T AD - Genetic Epidemiology Branch, National Cancer Institute, Rockville, MD 20892. PY - 1994 SP - 68 EP - 77 VL - 85 IS - 1 SN - 0025-7818, 0025-7818 KW - Index Medicus KW - Phenotype KW - Genotype KW - Disease Susceptibility KW - Molecular Epidemiology KW - Risk Factors KW - Humans KW - Pharmacogenetics KW - Lung Neoplasms -- epidemiology KW - Environmental Exposure -- statistics & numerical data KW - Lung Neoplasms -- genetics KW - Lung Neoplasms -- chemically induced KW - Environmental Exposure -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76603666?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=La+Medicina+del+lavoro&rft.atitle=Molecular+epidemiology%3A+a+new+perspective+for+the+study+of+toxic+exposures+in+man.+A+consideration+of+the+influence+of+genetic+susceptibility+factors+on+risk+in+different+lung+cancer+histologies.&rft.au=Caporaso%2C+N+E%3BLandi%2C+M+T&rft.aulast=Caporaso&rft.aufirst=N&rft.date=1994-01-01&rft.volume=85&rft.issue=1&rft.spage=68&rft.isbn=&rft.btitle=&rft.title=La+Medicina+del+lavoro&rft.issn=00257818&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-08-16 N1 - Date created - 1994-08-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Potential gene therapy for alcoholism. AN - 76599323; 8032169 AB - Genes that have an actual or a potential relationship to alcoholism may be useful targets for therapy. Candidate genes are considered in relationship to family studies, differences in alcohol preferences in various rodent strains, biochemical reactions, physiologic response mechanisms, and alterations in brain pharmacology. Suggestions are made concerning the identification of candidate genes, design of gene antisense constructs, and techniques for their organ-specific delivery. The complexities surrounding alcoholism in humans make it likely that several simultaneous approaches may be required for effective therapy for alcoholism. JF - EXS AU - Brady, R O AD - Developmental and Metabolic Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994 PY - 1994 DA - 1994 SP - 383 EP - 393 VL - 71 SN - 1023-294X, 1023-294X KW - DNA, Antisense KW - 0 KW - Endorphins KW - RNA, Antisense KW - Aldehyde Dehydrogenase KW - EC 1.2.1.3 KW - Index Medicus KW - Rats KW - Mutagenesis, Site-Directed KW - Animals KW - Rats, Sprague-Dawley KW - Mammals KW - Endorphins -- physiology KW - Mitochondria -- enzymology KW - Humans KW - Alcohol Drinking -- physiopathology KW - Brain -- metabolism KW - Mutation KW - Aldehyde Dehydrogenase -- genetics KW - Alcoholism -- therapy KW - Genetic Therapy KW - Aldehyde Dehydrogenase -- metabolism KW - Alcoholism -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76599323?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=EXS&rft.atitle=Potential+gene+therapy+for+alcoholism.&rft.au=Brady%2C+R+O&rft.aulast=Brady&rft.aufirst=R&rft.date=1994-01-01&rft.volume=71&rft.issue=&rft.spage=383&rft.isbn=&rft.btitle=&rft.title=EXS&rft.issn=1023294X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-08-12 N1 - Date created - 1994-08-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Takayasu's arteritis. AN - 76598126; 7913334 AB - Takayasu's arteritis has become increasingly recognized as a worldwide entity with a variable spectrum of disease expression. Although evidence for immune mechanisms of disease exist, the precise etiopathogenesis remains elusive. Improvements in the evaluation of disease activity beyond the current parameters of clinical symptoms, erythrocyte sedimentation rate, and angiographic findings are needed. Assessment of disease is handicapped by radiologic techniques that may detect diseased vessels but do not distinguish active from chronic lesions. A large proportion of patients with active disease respond to treatment with glucocorticoids, but a significant proportion will either require additional immunosuppression to prevent steroid toxicity or will remain unresponsive to treatment. At present, methotrexate appears to be an effective steroid-sparing agent in the treatment of active Takayasu's arteritis. Surgery continues to play a critical role in the long-term management of Takayasu's arteritis and is recommended when appropriate during inactive disease. Renal autograft transplantation has been offered as a new technique in the management of hypertension in Takayasu's arteritis. JF - Current opinion in rheumatology AU - Kerr, G AD - Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892. Y1 - 1994/01// PY - 1994 DA - January 1994 SP - 32 EP - 38 VL - 6 IS - 1 SN - 1040-8711, 1040-8711 KW - Glucocorticoids KW - 0 KW - Gonadal Steroid Hormones KW - HLA Antigens KW - Index Medicus KW - HLA Antigens -- genetics KW - Combined Modality Therapy KW - Pregnancy Complications -- therapy KW - Humans KW - Adult KW - Child KW - Glucocorticoids -- therapeutic use KW - Gonadal Steroid Hormones -- physiology KW - Male KW - Female KW - Pregnancy KW - Takayasu Arteritis -- therapy KW - Takayasu Arteritis -- diagnosis KW - Takayasu Arteritis -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76598126?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Molecular+alterations+in+the+neostriatum+of+human+cocaine+addicts.&rft.au=Hurd%2C+Y+L%3BHerkenham%2C+M&rft.aulast=Hurd&rft.aufirst=Y&rft.date=1993-04-01&rft.volume=13&rft.issue=4&rft.spage=357&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 - 1994-08-17 N1 - Date created - 1994-08-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Serotonin, violent behavior and alcohol. AN - 76596628; 7518265 AB - At the NIAAA intramural research program, in collaboration with investigators at the Department of Psychiatry, University of Helsinki, we have mounted an extensive research program on early onset male alcoholism. A central serotonergic deficit is common among these patients. This finding has led to behavioral, biochemical, physiological and molecular genetic studies on the serotonin system in early onset, antisocial and violent male alcoholics and in appropriate control populations. The results of the studies completed by the fall of 1993 are summarized in this communication. JF - EXS AU - Linnoila, M AU - Virkkunen, M AU - George, T AU - Eckardt, M AU - Higley, J D AU - Nielsen, D AU - Goldman, D AD - Laboratory of Clinical Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland. Y1 - 1994 PY - 1994 DA - 1994 SP - 155 EP - 163 VL - 71 SN - 1023-294X, 1023-294X KW - Biomarkers KW - 0 KW - Receptors, Serotonin KW - Serotonin KW - 333DO1RDJY KW - Hydroxyindoleacetic Acid KW - 54-16-0 KW - Homovanillic Acid KW - X77S6GMS36 KW - Index Medicus KW - Biomarkers -- cerebrospinal fluid KW - Animals KW - Homovanillic Acid -- cerebrospinal fluid KW - Age Factors KW - Finland KW - Humans KW - Seasons KW - Hydroxyindoleacetic Acid -- cerebrospinal fluid KW - Male KW - Receptors, Serotonin -- physiology KW - Serotonin -- physiology KW - Alcoholism -- physiopathology KW - Alcoholism -- genetics KW - Violence KW - Alcoholism -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76596628?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=EXS&rft.atitle=Serotonin%2C+violent+behavior+and+alcohol.&rft.au=Linnoila%2C+M%3BVirkkunen%2C+M%3BGeorge%2C+T%3BEckardt%2C+M%3BHigley%2C+J+D%3BNielsen%2C+D%3BGoldman%2C+D&rft.aulast=Linnoila&rft.aufirst=M&rft.date=1994-01-01&rft.volume=71&rft.issue=&rft.spage=155&rft.isbn=&rft.btitle=&rft.title=EXS&rft.issn=1023294X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-08-12 N1 - Date created - 1994-08-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Retroviral RNA packaging: a review. AN - 76595516; 8032280 AB - In retroviruses, the "Gag" or core polyprotein is capable of assembling into virus particles and packaging the genomic RNA of the virus. How this protein recognizes viral RNA is not understood. Gag polyproteins contain a zinc-finger domain; mutants with changes in this domain assemble into virions, but a large fraction of these particles lack viral RNA. Thus, one crucial element in the RNA packaging mechanism is the zinc-finger domain. RNA sequences required for packaging ("packing signals") have been studied both by deletion analysis and by measuring encapsidation of nonviral mRNAs containing limited insertions of viral sequence. These experiments show that all or part of the packaging signal in viral RNA is located near the 5 end of the genome. These signals appear to be quite large, i.e., hundreds of nucleotides. Each virus particle actually contains a dimer of two identical, + strand genomic RNA molecules. The nature of the dimeric linkage is not understood. In some experimental situations (including zinc-finger mutants), only a small fraction of the particles in a virus preparation contain genomic RNA. It is striking that the genomic RNA packaged in these situations is dimeric. Because of this important observation, it is speculated that only dimers are packaged, and that the dimeric structure is an element of the packaging signal. It is also suggested that the dimers undergo a conformational change ("RNA maturation") after the virus is released from the cell, and that this change may depend upon the cleavage of the Gag polyprotein, a post-assembly event catalyzed by the virus-coded protease. JF - Archives of virology. Supplementum AU - Rein, A AD - Laboratory of Molecular Virology and Carcinogenesis, NCI-Frederick Cancer Research and Development Center, Maryland. Y1 - 1994 PY - 1994 DA - 1994 SP - 513 EP - 522 VL - 9 SN - 0939-1983, 0939-1983 KW - RNA, Viral KW - 0 KW - Retroviridae Proteins KW - Index Medicus KW - Regulatory Sequences, Nucleic Acid -- genetics KW - Base Sequence KW - Sequence Homology, Nucleic Acid KW - Molecular Sequence Data KW - Genome, Viral KW - Nucleic Acid Conformation KW - Retroviridae Proteins -- metabolism KW - Retroviridae -- growth & development KW - RNA, Viral -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76595516?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+virology.+Supplementum&rft.atitle=Retroviral+RNA+packaging%3A+a+review.&rft.au=Rein%2C+A&rft.aulast=Rein&rft.aufirst=A&rft.date=1994-01-01&rft.volume=9&rft.issue=&rft.spage=513&rft.isbn=&rft.btitle=&rft.title=Archives+of+virology.+Supplementum&rft.issn=09391983&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-08-15 N1 - Date created - 1994-08-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - [3H]resiniferatoxin binding to pig dorsal horn membranes displays positive cooperativity. AN - 76594884; 8035647 AB - In the present report we have reevaluated specific [3H]resiniferatoxin (RTX) binding, thought to represent the vanilloid (capsaicin) receptor, to whole spinal cord and dorsal horn membranes of the pig using a modified [3H]RTX binding assay. The high nonspecific [3H]RTX binding of the original protocol was reduced by the addition of alpha 1-acid glycoprotein (AGP), a plasma protein that binds RTX, to the assay mixture after the binding reaction had been terminated. Specific [3H]RTX binding to pig whole spinal cord and dorsal horn membranes followed sigmoidal saturation kinetics indicating apparent positive cooperativity. The cooperativity index determined by fitting the data to the Hill equation was 2.31 +/- 0.24 in the spinal cord and 2.27 +/- 0.13 in the dorsal horn. The apparent dissociation constants in spinal cord and dorsal horn membranes were 87.8 +/- 2.7 and 103.9 +/- 1.9 pM; the receptor densities were 23 +/- 3 and 203 +/- 5 fmol/mg protein, respectively. In parallel experiments, rat spinal cord membranes bound [3H]RTX with 2 - 3 fold higher affinity, equal positive cooperativity, and a 49 +/- 6 fmol/mg receptor density. As predicted by the modified Hill equation, at low receptor occupancy nonradioactive RTX produced biphasic competition curves. Capsaicin and the competitive antagonist capsazepine also fully displaced specifically bound [3H]RTX from pig dorsal horn membranes with Ki values of 9.7 +/- 1.7 microM and 6.8 +/- 0.7 microM, respectively; the corresponding Hill coefficients were 1.81 +/- 0.17 and 2.32 +/- 0.11. [3H]RTX binding was not inhibited by resiniferonol 9, 13, 14-orthophenylacetate, the biologically inactive parent diterpene of RTX. These findings suggest that the vanilloid receptor present in the dorsal horn of the pig, like those present in human and in the rat, is a receptor cluster in which the subunits cooperate. JF - Life sciences AU - Acs, G AU - Blumberg, P M AD - Molecular Mechanisms of Tumor Promotion Section, National Cancer Institute, Bethesda, MD 20892. Y1 - 1994 PY - 1994 DA - 1994 SP - 337 EP - 346 VL - 55 IS - 5 SN - 0024-3205, 0024-3205 KW - Diterpenes KW - 0 KW - Neurotoxins KW - resiniferatoxin KW - A5O6P1UL4I KW - Capsaicin KW - S07O44R1ZM KW - Index Medicus KW - Swine KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Female KW - Capsaicin -- pharmacology KW - Binding Sites KW - Neurotoxins -- metabolism KW - Spinal Cord -- metabolism KW - Diterpenes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76594884?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Life+sciences&rft.atitle=%5B3H%5Dresiniferatoxin+binding+to+pig+dorsal+horn+membranes+displays+positive+cooperativity.&rft.au=Acs%2C+G%3BBlumberg%2C+P+M&rft.aulast=Acs&rft.aufirst=G&rft.date=1994-01-01&rft.volume=55&rft.issue=5&rft.spage=337&rft.isbn=&rft.btitle=&rft.title=Life+sciences&rft.issn=00243205&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-08-18 N1 - Date created - 1994-08-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Recruitment of enzymes and stress proteins as lens crystallins. AN - 76591317; 8032155 AB - The major water-soluble proteins--or crystallins--of the eye lens are either identical to or derived from proteins with non-refractive functions in numerous tissues. In general, the recruitment of crystallins has come from metabolic enzymes (usually with detoxification functions) or stress proteins. Some crystallins have been recruited without duplication of the original gene (i.e., lactate dehydrogenase B and alpha-enolase), while others have incurred one (i.e., argininosuccinate lyase and a small heat shock protein) or several (i.e., glutathione S-transferase) gene duplications. Enzyme (or stress protein)-crystallins often maintain their non-refractive function in the lens and/or other tissues as well as their refractive role, a process we call gene sharing. alpha-Crystallin/small heat shock protein/molecular chaperone is of special interest since it is the major crystallin of humans. There are two alpha-crystallin genes (alpha A and alpha B), with alpha B retaining the full functions of a small heat shock protein. Here we describe recent evidence indicating that alpha A and alpha B have kinase activity, which would make them members of the enzyme-crystallins. We also describe various regulatory elements of the mouse alpha-crystallin genes responsible for their expression in the lens and, for alpha B, in skeletal muscle. Delineating the control elements for gene expression of these multifunctional protective proteins provides the foundations for their eventual use in gene therapy. Finally, comparison of the mouse and chicken alpha A-crystallin genes reveals similarities and differences in their functional cis-acting elements, indicative of evolution at the level of gene regulation. JF - EXS AU - Piatigorsky, J AU - Kantorow, M AU - Gopal-Srivastava, R AU - Tomarev, S I AD - Laboratory of Molecular and Developmental Biology, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994 PY - 1994 DA - 1994 SP - 241 EP - 250 VL - 71 SN - 1023-294X, 1023-294X KW - Crystallins KW - 0 KW - Enzymes KW - Heat-Shock Proteins KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Animals KW - Base Sequence KW - Lens, Crystalline -- metabolism KW - Multigene Family KW - Humans KW - DNA -- genetics KW - Molecular Sequence Data KW - Binding Sites KW - Heat-Shock Proteins -- metabolism KW - Inactivation, Metabolic KW - Enzymes -- metabolism KW - Crystallins -- genetics KW - Heat-Shock Proteins -- genetics KW - Enzymes -- genetics KW - Crystallins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76591317?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=EXS&rft.atitle=Recruitment+of+enzymes+and+stress+proteins+as+lens+crystallins.&rft.au=Piatigorsky%2C+J%3BKantorow%2C+M%3BGopal-Srivastava%2C+R%3BTomarev%2C+S+I&rft.aulast=Piatigorsky&rft.aufirst=J&rft.date=1994-01-01&rft.volume=71&rft.issue=&rft.spage=241&rft.isbn=&rft.btitle=&rft.title=EXS&rft.issn=1023294X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-08-12 N1 - Date created - 1994-08-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Screening for CF mutations in adult cystic fibrosis patients with a directed and optimized SSCP strategy. AN - 76590848; 7517265 AB - Twenty adolescent and adult cystic fibrosis (CF) patients have been studied for the presence of mutations in the CFTR gene. Mutations other than deltaF508 have been detected by comparison to the single-stranded conformation polymorphism (SSCP) pattern of known mutations in eight exons, in which 80% of the more common mutations are present. Each mutation was confirmed by direct sequencing. For each of the analyzed exons, optimal SSCP conditions have been determined that allow all available known mutations in that exon to be distinguished from each other. This approach allowed mutations to be defined in 75% of the non deltaF508 alleles and 92% of all CF alleles in this cohort. JF - Human mutation AU - Ravnik-Glavac, M AU - Glavac, D AU - Chernick, M AU - di Sant'Agnese, P AU - Dean, M AD - Biological Carcinogenesis and Development Program, Inc./DynCorp, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland 21702-1201. Y1 - 1994 PY - 1994 DA - 1994 SP - 231 EP - 238 VL - 3 IS - 3 SN - 1059-7794, 1059-7794 KW - CFTR KW - CFTR protein, human KW - 0 KW - Chlorides KW - DNA Primers KW - Membrane Proteins KW - Cystic Fibrosis Transmembrane Conductance Regulator KW - 126880-72-6 KW - Index Medicus KW - Sweat -- chemistry KW - Exons KW - Humans KW - Chlorides -- metabolism KW - Base Sequence KW - Adult KW - Polymerase Chain Reaction -- methods KW - Molecular Sequence Data KW - Adolescent KW - Female KW - Male KW - Cystic Fibrosis -- genetics KW - Polymorphism, Genetic KW - Point Mutation KW - Membrane Proteins -- genetics KW - Mutation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76590848?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+mutation&rft.atitle=Screening+for+CF+mutations+in+adult+cystic+fibrosis+patients+with+a+directed+and+optimized+SSCP+strategy.&rft.au=Ravnik-Glavac%2C+M%3BGlavac%2C+D%3BChernick%2C+M%3Bdi+Sant%27Agnese%2C+P%3BDean%2C+M&rft.aulast=Ravnik-Glavac&rft.aufirst=M&rft.date=1994-01-01&rft.volume=3&rft.issue=3&rft.spage=231&rft.isbn=&rft.btitle=&rft.title=Human+mutation&rft.issn=10597794&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-08-04 N1 - Date created - 1994-08-04 N1 - Date revised - 2017-01-13 N1 - Gene symbol - CFTR N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Outlook: prospects for alcoholism treatment. AN - 76587084; 8032171 AB - Treating alcoholism reduces many alcohol-related social, economic, and medical problems. A historical lack of support for alcoholism treatment and for alcoholism treatment research is disappearing, and significant progress is being made toward developing new and improved treatments. Current research findings are the basis of this "Outlook" which is divided into three levels of confidence: clear extrapolations from present research, extrapolations that are reasonable but uncertain, and predictions that attempt to guess the unguessable. It concludes that the future looks promising for new and improved alcoholism treatments. JF - EXS AU - Gordis, E AD - National Institute on Alcohol Abuse and Alcoholism, Rockville, MD 20857. Y1 - 1994 PY - 1994 DA - 1994 SP - 395 EP - 404 VL - 71 SN - 1023-294X, 1023-294X KW - Ethanol KW - 3K9958V90M KW - Index Medicus KW - Ethanol -- adverse effects KW - Substance Withdrawal Syndrome KW - Humans KW - Research -- trends KW - Alcoholism -- therapy KW - Alcoholism -- physiopathology KW - Alcoholism -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76587084?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=EXS&rft.atitle=Outlook%3A+prospects+for+alcoholism+treatment.&rft.au=Gordis%2C+E&rft.aulast=Gordis&rft.aufirst=E&rft.date=1994-01-01&rft.volume=71&rft.issue=&rft.spage=395&rft.isbn=&rft.btitle=&rft.title=EXS&rft.issn=1023294X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-08-12 N1 - Date created - 1994-08-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Sequence analysis of two novel HLA-DMA alleles. AN - 76585817; 8026867 JF - Immunogenetics AU - Carrington, M AU - Harding, A AD - Biological Carcinogenesis and Development Program, Program Resources Inc./DynCorp, National Cancer Institute, Frederick Cancer Research and Development Center, MD 21702. Y1 - 1994 PY - 1994 DA - 1994 SP - 165 VL - 40 IS - 2 SN - 0093-7711, 0093-7711 KW - H2-M antigens KW - 0 KW - HLA-D Antigens KW - HLA-DM antigens KW - Histocompatibility Antigens Class II KW - Index Medicus KW - Exons -- genetics KW - Base Sequence KW - Sequence Homology, Nucleic Acid KW - Humans KW - Molecular Sequence Data KW - Sequence Analysis, DNA KW - Alleles KW - HLA-D Antigens -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76585817?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Immunogenetics&rft.atitle=Sequence+analysis+of+two+novel+HLA-DMA+alleles.&rft.au=Carrington%2C+M%3BHarding%2C+A&rft.aulast=Carrington&rft.aufirst=M&rft.date=1994-01-01&rft.volume=40&rft.issue=2&rft.spage=165&rft.isbn=&rft.btitle=&rft.title=Immunogenetics&rft.issn=00937711&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-08-05 N1 - Date created - 1994-08-05 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - U04878; GENBANK; U04877 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Activation of peripheral large granular lymphocytes with the serine/threonine phosphatase inhibitor, okadaic acid. AN - 76582451; 8020552 AB - The murine polyether fatty acid, okadaic acid, is a potent inhibitor of serine/threonine phosphatases in eukaryotic cells. This compound inhibits both protein phosphatase 1 (PP1) and phosphatase 2A (PP2A). Here we have examined the potential of okadaic acid as an activator of fresh peripheral CD3- large granular lymphocytes (LGL). We demonstrate that overnight exposure of LGL to as little as 1 nM okadaic acid induced an increase in natural killing against the K562 cell line, but does not induce LAK activity. Optimal cytotoxic activation (2-fold) occurred at 0.01-1.0 nM okadaic acid, with a return to baseline levels at 10-20 nM, and inhibition, likely due to toxicity, at 40 nM. In addition, okadaic acid at doses > or = 20 nM induced LGL but not T cells to produce interferon-gamma. Similar to phorbol esters, overnight incubation with okadaic acid causes a dose-dependent reduction in expression of the low-affinity receptor for the Fc portion of IgG (CD16). However, unlike phorbol ester, short-term (5 min) okadaic acid treatment did not block CD16-mediated Ca2+ mobilization in LGL. To address the underlying biochemical mechanisms of okadaic acid activities, the levels of several as-yet-unidentified serine/threonine kinases were assayed after renaturation. Under these conditions, okadaic acid induced similar increases in kinase levels in both T cells and LGL. Taken together, these data suggest an important role for PP1 and PP2A in LGL physiology, and define okadaic acid as a potentially important biological response modifier for the study of LGL and T cell biochemistry, signal transduction, and transcriptional regulation. JF - European journal of immunology AU - McVicar, D W AU - Mason, A T AU - Bere, E W AU - Ortaldo, J R AD - Laboratory of Experimental Immunology, NCI-FCRDC, Frederick, MD 21702-1201. Y1 - 1994/01// PY - 1994 DA - January 1994 SP - 165 EP - 170 VL - 24 IS - 1 SN - 0014-2980, 0014-2980 KW - Ethers, Cyclic KW - 0 KW - Receptors, IgG KW - Receptors, Interleukin-2 KW - Okadaic Acid KW - 1W21G5Q4N2 KW - Interferon-gamma KW - 82115-62-6 KW - Phosphoprotein Phosphatases KW - EC 3.1.3.16 KW - Protein Phosphatase 1 KW - Protein Phosphatase 2 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Humans KW - Receptors, Interleukin-2 -- biosynthesis KW - Interferon-gamma -- biosynthesis KW - Killer Cells, Natural -- drug effects KW - Phosphorylation -- drug effects KW - Calcium -- metabolism KW - Receptors, IgG -- biosynthesis KW - In Vitro Techniques KW - Cytotoxicity Tests, Immunologic KW - Flow Cytometry KW - T-Lymphocytes -- drug effects KW - Phosphoprotein Phosphatases -- antagonists & inhibitors KW - Lymphocyte Activation -- drug effects KW - Lymphocyte Subsets -- drug effects KW - Ethers, Cyclic -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76582451?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Activation+of+peripheral+large+granular+lymphocytes+with+the+serine%2Fthreonine+phosphatase+inhibitor%2C+okadaic+acid.&rft.au=McVicar%2C+D+W%3BMason%2C+A+T%3BBere%2C+E+W%3BOrtaldo%2C+J+R&rft.aulast=McVicar&rft.aufirst=D&rft.date=1994-01-01&rft.volume=24&rft.issue=1&rft.spage=165&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 - 1994-08-02 N1 - Date created - 1994-08-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Local pharmacological manipulation of extracellular dopamine levels in the dorsolateral prefrontal cortex and caudate nucleus in the rhesus monkey: an in vivo microdialysis study. AN - 76564525; 8013591 AB - The prefrontal cortex, caudate nucleus, and their dopaminergic innervations have been implicated in complex information processing. The present study utilized the in vivo microdialysis technique to characterize the extracellular dopamine levels in the prefrontal cortex and the caudate nucleus in the rhesus monkey. Basal levels of dopamine were consistently found in the caudate nucleus, while levels in the prefrontal cortex were less reliably measured. Manipulation of dopamine levels using tetrodotoxin and high potassium demonstrated that dopamine measured was dependent on neuronal firing. Administration of indirect dopamine agonists d-amphetamine and cocaine into the prefrontal cortex and the caudate nucleus increased extracellular dopamine levels 250% and 5000%, respectively. Amphetamine and cocaine had greater effects on dopamine levels in the caudate than in the prefrontal cortex. Cocaine induced increases appeared to be less than that of amphetamine and the actions of cocaine lasted longer than amphetamine. This study demonstrates the feasibility of using in vivo microdialysis in monitoring neurochemicals in different regions of the rhesus monkey brain. JF - Experimental brain research AU - Saunders, R C AU - Kolachana, B S AU - Weinberger, D R AD - Clinical Brain Disorders Branch, NIMH/NIH, NIMH Neurosciences Center at St. Elizabeths Hospital, Washington, DC 20032. Y1 - 1994 PY - 1994 DA - 1994 SP - 44 EP - 52 VL - 98 IS - 1 SN - 0014-4819, 0014-4819 KW - Tetrodotoxin KW - 4368-28-9 KW - Cocaine KW - I5Y540LHVR KW - Potassium KW - RWP5GA015D KW - Dextroamphetamine KW - TZ47U051FI KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Microdialysis KW - Animals KW - Potassium -- pharmacology KW - Macaca mulatta KW - Tetrodotoxin -- pharmacology KW - Cocaine -- pharmacology KW - Male KW - Chromatography, High Pressure Liquid KW - Dextroamphetamine -- pharmacology KW - Caudate Nucleus -- anatomy & histology KW - Caudate Nucleus -- metabolism KW - Prefrontal Cortex -- metabolism KW - Extracellular Space -- metabolism KW - Prefrontal Cortex -- anatomy & histology KW - Dopamine -- metabolism KW - Caudate Nucleus -- drug effects KW - Prefrontal Cortex -- drug effects KW - Extracellular Space -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76564525?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+brain+research&rft.atitle=Local+pharmacological+manipulation+of+extracellular+dopamine+levels+in+the+dorsolateral+prefrontal+cortex+and+caudate+nucleus+in+the+rhesus+monkey%3A+an+in+vivo+microdialysis+study.&rft.au=Saunders%2C+R+C%3BKolachana%2C+B+S%3BWeinberger%2C+D+R&rft.aulast=Saunders&rft.aufirst=R&rft.date=1994-01-01&rft.volume=98&rft.issue=1&rft.spage=44&rft.isbn=&rft.btitle=&rft.title=Experimental+brain+research&rft.issn=00144819&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-07-27 N1 - Date created - 1994-07-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The membrane localization of the G protein alpha s subunit is not dependent on its TENIR sequence or effector domain. AN - 76554995; 8011426 AB - The GS protein alpha subunit (alpha S) sequences conserved in non-myristoylated alpha subunits (TENIR, residues 369-373) or critical for adenylyl cyclase interaction were investigated as possible sites required for membrane localization. Substitutions were created by site-directed mutagenesis in which the TENIR residues were deleted from alpha S or added to the soluble, non-myristoylated alpha i1. After transfection, COS cells were separated by centrifugation into particulate and soluble fractions. Immunoblots showed that these substitutions did not change the localization: alpha S +/- TENIR in the particulate fraction, non-myristoylated alpha i1 +/- TENIR in the soluble fraction. The constitutively active alpha i/alpha S chimera (CH4A), containing four regions of alpha S sufficient for adenylyl cyclase activation, was mutated to prevent myristoylation (GA-CH4A). Immunoblots of transfected COS cell fractions showed CH4A in the particulate and GA-CH4A in the soluble fraction. While these regions did not lead to membrane localization, the soluble GA-CH4A could activate adenylyl cyclase in the intact cell and after reconstitution with cyc- membranes. JF - Cellular signalling AU - Degtyarev, M Y AU - Spiegel, A M AU - Jones, T L AD - Molecular Pathophysiology Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/01// PY - 1994 DA - January 1994 SP - 25 EP - 33 VL - 6 IS - 1 SN - 0898-6568, 0898-6568 KW - Oligopeptides KW - 0 KW - Recombinant Fusion Proteins KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - Adenylyl Cyclases KW - EC 4.6.1.1 KW - Index Medicus KW - Animals KW - Electrophoresis, Polyacrylamide Gel KW - Macaca KW - Adenylyl Cyclases -- metabolism KW - Gene Expression KW - Amino Acid Sequence KW - Structure-Activity Relationship KW - Recombinant Fusion Proteins -- metabolism KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Transfection KW - Cells, Cultured KW - Molecular Sequence Data KW - Cell Line, Transformed KW - Cell Membrane -- metabolism KW - GTP-Binding Proteins -- metabolism KW - Oligopeptides -- genetics KW - Oligopeptides -- metabolism KW - GTP-Binding Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76554995?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cellular+signalling&rft.atitle=The+membrane+localization+of+the+G+protein+alpha+s+subunit+is+not+dependent+on+its+TENIR+sequence+or+effector+domain.&rft.au=Degtyarev%2C+M+Y%3BSpiegel%2C+A+M%3BJones%2C+T+L&rft.aulast=Degtyarev&rft.aufirst=M&rft.date=1994-01-01&rft.volume=6&rft.issue=1&rft.spage=25&rft.isbn=&rft.btitle=&rft.title=Cellular+signalling&rft.issn=08986568&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-07-28 N1 - Date created - 1994-07-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular organization and gene regulation of type IV collagen. AN - 76537961; 8004973 JF - Contributions to nephrology AU - Takami, H AU - Burbelo, P D AU - Fukuda, K AU - Chang, H S AU - Phillips, S L AU - Yamada, Y AD - Laboratory of Developmental Biology, National Institute of Dental Research, National Institutes of Health, Bethesda, Md. Y1 - 1994 PY - 1994 DA - 1994 SP - 36 EP - 46 VL - 107 SN - 0302-5144, 0302-5144 KW - Neoplasm Proteins KW - 0 KW - Recombinant Proteins KW - Transcription Factors KW - Collagen KW - 9007-34-5 KW - Index Medicus KW - Animals KW - Neoplasm Proteins -- biosynthesis KW - Recombinant Proteins -- biosynthesis KW - Transcription Factors -- metabolism KW - Transcription, Genetic KW - Teratocarcinoma -- metabolism KW - Mice KW - Teratocarcinoma -- pathology KW - Rats KW - Base Sequence KW - Promoter Regions, Genetic KW - Tumor Cells, Cultured KW - Basement Membrane -- metabolism KW - Molecular Sequence Data KW - CHO Cells KW - Methylation KW - Cricetinae KW - Collagen -- genetics KW - Gene Expression Regulation KW - Collagen -- biosynthesis KW - Collagen -- classification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76537961?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Contributions+to+nephrology&rft.atitle=Molecular+organization+and+gene+regulation+of+type+IV+collagen.&rft.au=Takami%2C+H%3BBurbelo%2C+P+D%3BFukuda%2C+K%3BChang%2C+H+S%3BPhillips%2C+S+L%3BYamada%2C+Y&rft.aulast=Takami&rft.aufirst=H&rft.date=1994-01-01&rft.volume=107&rft.issue=&rft.spage=36&rft.isbn=&rft.btitle=&rft.title=Contributions+to+nephrology&rft.issn=03025144&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-07-18 N1 - Date created - 1994-07-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Selenium biochemistry--selected topics. AN - 76529040; 8203287 JF - Advances in inorganic biochemistry AU - Stadtman, T C AD - Laboratory of Biochemistry, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994 PY - 1994 DA - 1994 SP - 157 EP - 175 VL - 10 SN - 0190-0218, 0190-0218 KW - Enzymes KW - 0 KW - Selenocysteine KW - 0CH9049VIS KW - Selenium KW - H6241UJ22B KW - Index Medicus KW - Animals KW - Humans KW - Selenocysteine -- chemistry KW - Enzymes -- metabolism KW - Selenium -- metabolism KW - Selenium -- chemistry KW - Selenium -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76529040?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Advances+in+inorganic+biochemistry&rft.atitle=Selenium+biochemistry--selected+topics.&rft.au=Stadtman%2C+T+C&rft.aulast=Stadtman&rft.aufirst=T&rft.date=1994-01-01&rft.volume=10&rft.issue=&rft.spage=157&rft.isbn=&rft.btitle=&rft.title=Advances+in+inorganic+biochemistry&rft.issn=01900218&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-07-05 N1 - Date created - 1994-07-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Anti-IL-2 receptor monoclonal antibody (anti-Tac) treatment of T-cell lymphoma. AN - 76528473; 8206486 AB - The abnormal and activated T cells in certain neoplasms of mononuclear cells, select autoimmune disorders, and organ allograft rejection express the IL-2R alpha subunit identified by the anti-Tac monoclonal antibody. In contrast, normal resting cells do not express this inducible receptor. Patients with ATL were treated with different forms of IL-2R-directed therapy to exploit the difference in IL-2R expression between normal and malignant cells. Using the unmodified anti-Tac monoclonal antibody, 7 of 19 patients with ATL treated have undergone a remission (2 cases complete), with no toxicity observed. Unmodified murine monoclonal antibodies are limited by their immunogenicity and poor effector functions. Genetic engineering was used to produce humanized anti-Tac that contains the complementarity-determining regions from the mouse with the remainder of the molecule derived from human IgG1-kappa. This antibody is less immunogenic than the murine version, has improved pharmacokinetics, and, in contrast with the parent antibody, manifests ADCC with human mononuclear cells. To enhance its effector function, anti-Tac was armed with toxins or with alpha- and beta-emitting radionuclides. In a clinical trial with 90Y-anti-Tac at the doses used (5, 10, and 15 microCi), 11 of the 17 patients with ATL underwent a partial or sustained a complete remission. Thus, the clinical application of IL-2R-directed therapy represents a new perspective for the treatment of T-cell lymphomas, including HTLV-I-associated ATL. JF - Important advances in oncology AU - Waldmann, T A AD - Metabolism Branch, National Cancer Institute, Bethesda, Maryland. Y1 - 1994 PY - 1994 DA - 1994 SP - 131 EP - 141 SN - 0883-5896, 0883-5896 KW - lck KW - lyn KW - tax KW - Antibodies, Monoclonal KW - 0 KW - Antibodies, Neoplasm KW - Bacterial Toxins KW - Exotoxins KW - Immunotoxins KW - Neoplasm Proteins KW - Radioisotopes KW - Receptors, Interleukin-2 KW - Virulence Factors KW - Yttrium Radioisotopes KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - toxA protein, Pseudomonas aeruginosa KW - EC 2.4.2.31 KW - Bismuth KW - U015TT5I8H KW - Index Medicus KW - AIDS/HIV KW - Yttrium Radioisotopes -- therapeutic use KW - Animals KW - Bismuth -- administration & dosage KW - Antibody-Dependent Cell Cytotoxicity KW - Exotoxins -- administration & dosage KW - Humans KW - Mice KW - Amino Acid Sequence KW - HTLV-I Infections -- genetics KW - Gene Expression Regulation, Neoplastic KW - Antibody Specificity KW - Yttrium Radioisotopes -- administration & dosage KW - Protein Engineering KW - Bismuth -- therapeutic use KW - Molecular Sequence Data KW - Radioisotopes -- therapeutic use KW - Immunotoxins -- therapeutic use KW - Exotoxins -- therapeutic use KW - Immunologic Deficiency Syndromes -- etiology KW - Radioisotopes -- administration & dosage KW - Neoplasm Proteins -- biosynthesis KW - Leukemia-Lymphoma, Adult T-Cell -- therapy KW - Neoplasm Proteins -- immunology KW - Receptors, Interleukin-2 -- biosynthesis KW - Antibodies, Neoplasm -- therapeutic use KW - Leukemia-Lymphoma, Adult T-Cell -- genetics KW - Receptors, Interleukin-2 -- genetics KW - Receptors, Interleukin-2 -- immunology KW - Antibodies, Monoclonal -- therapeutic use KW - Neoplasm Proteins -- genetics KW - Leukemia-Lymphoma, Adult T-Cell -- immunology KW - Leukemia-Lymphoma, Adult T-Cell -- mortality KW - Receptors, Interleukin-2 -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76528473?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Suppression+of+oncogene-induced+transformation+by+a+deletion+mutant+of+c-jun.&rft.au=Brown%2C+P+H%3BAlani%2C+R%3BPreis%2C+L+H%3BSzabo%2C+E%3BBirrer%2C+M+J&rft.aulast=Brown&rft.aufirst=P&rft.date=1993-04-01&rft.volume=8&rft.issue=4&rft.spage=877&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-07-14 N1 - Date created - 1994-07-14 N1 - Date revised - 2017-01-13 N1 - Gene symbol - lck; lyn; tax N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Immunotoxins and recombinant toxins for cancer treatment. AN - 76527131; 8206493 JF - Important advances in oncology AU - Pai, L H AU - Pastan, I AD - Laboratory of Molecular Biology, National Cancer Institute, Bethesda, Maryland. Y1 - 1994 PY - 1994 DA - 1994 SP - 3 EP - 19 SN - 0883-5896, 0883-5896 KW - Bacterial Toxins KW - 0 KW - Cytokines KW - Diphtheria Toxin KW - Exotoxins KW - Immunotoxins KW - Recombinant Proteins KW - Virulence Factors KW - Ricin KW - 9009-86-3 KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - toxA protein, Pseudomonas aeruginosa KW - EC 2.4.2.31 KW - Index Medicus KW - Cytokines -- therapeutic use KW - Ricin -- therapeutic use KW - Humans KW - Diphtheria Toxin -- therapeutic use KW - Exotoxins -- therapeutic use KW - Drug Design KW - Neoplasms -- drug therapy KW - Immunotoxins -- therapeutic use KW - Recombinant Proteins -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76527131?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Important+advances+in+oncology&rft.atitle=Immunotoxins+and+recombinant+toxins+for+cancer+treatment.&rft.au=Pai%2C+L+H%3BPastan%2C+I&rft.aulast=Pai&rft.aufirst=L&rft.date=1994-01-01&rft.volume=&rft.issue=&rft.spage=3&rft.isbn=&rft.btitle=&rft.title=Important+advances+in+oncology&rft.issn=08835896&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-07-14 N1 - Date created - 1994-07-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Therapy-related acute myeloid leukemia following treatment with epipodophyllotoxins: estimating the risks. AN - 76523387; 8202047 AB - In the past decade, therapy-related acute myeloid leukemia (t-AML) following treatment with regimens that include inhibitors of topoisomerase-II (TOPO-II) has been reported with increasing frequency. These cases of t-AML generally have a shorter latency period than t-AML following alkylator therapy, are associated with chromosomal translocations (especially involving chromosome band 11q23), and usually present as M4 or M5 FAB subtype. Although the epipodophyllotoxins (etoposide and teniposide) have been most often implicated, similar cases of t-AML occur following therapy with other classes of Topo-II inhibitors (e.g., anthracyclines). There is wide variation in published studies in the estimates of risk of t-AML following epipodophyllotoxin therapy. These varying estimates may reflect a number of factors, including: small sample size leading to large confidence intervals around risk estimates; varying susceptibility of different patient populations; varying schedules of epipodophyllotoxin administration; different cumulative doses of epipodophyllotoxins; and administration of epopodophyllotoxins with additional agents that may alter the leukemogenic effect of the epipodophyllotoxins. Available data suggest that children with acute lymphocytic leukemia (ALL) treated with high cumulative doses of epipodophyllotoxins using either weekly or twice-weekly schedules of administration have a relatively high risk of developing t-AML (5-12% cumulative risk). On the other hand, germ cell patients treated with relatively low cumulative doses of etoposide (usually 1,500-2,500 mg/m2) appear to have a low risk for developing t-AML. There is inadequate experience at this time with higher cumulative doses of etoposide (e.g., 4,000-5,000 mg/m2 as used for pediatric solid tumors) given on a daily x 5 schedule to allow estimates of risk to be developed for this schedule and cumulative dose. The Cancer Therapy Evaluation Program (CTEP) of the National Cancer Institute (NCI) has developed a monitoring plan designed to obtain reliable estimates of the risk of t-AML following epipodophyllotoxin treatment. Twelve Cooperative Group clinical trials that use epipodophyllotoxins at either low ( 4,000 mg/m2) are being prospectively monitored for cases of t-AML occurring among patients entered onto the trials. JF - Medical and pediatric oncology AU - Smith, M A AU - Rubinstein, L AU - Ungerleider, R S AD - Cancer Therapy Evaluation Program, DCT, NCI, Bethesda, Maryland 20892. Y1 - 1994 PY - 1994 DA - 1994 SP - 86 EP - 98 VL - 23 IS - 2 SN - 0098-1532, 0098-1532 KW - Alkylating Agents KW - 0 KW - Topoisomerase II Inhibitors KW - Podophyllotoxin KW - L36H50F353 KW - Index Medicus KW - Leukemia, Myelomonocytic, Acute -- chemically induced KW - Drug Administration Schedule KW - Humans KW - Clinical Trials as Topic KW - Child KW - Translocation, Genetic KW - Chromosomes, Human, Pair 11 KW - Lymphoma, Non-Hodgkin -- drug therapy KW - Leukemia, Monocytic, Acute -- chemically induced KW - Prospective Studies KW - Risk Factors KW - Alkylating Agents -- adverse effects KW - Cell Cycle -- drug effects KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma -- drug therapy KW - Leukemia, Myeloid, Acute -- chemically induced KW - Podophyllotoxin -- adverse effects KW - Neoplasms, Second Primary -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76523387?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Medical+and+pediatric+oncology&rft.atitle=Therapy-related+acute+myeloid+leukemia+following+treatment+with+epipodophyllotoxins%3A+estimating+the+risks.&rft.au=Smith%2C+M+A%3BRubinstein%2C+L%3BUngerleider%2C+R+S&rft.aulast=Smith&rft.aufirst=M&rft.date=1994-01-01&rft.volume=23&rft.issue=2&rft.spage=86&rft.isbn=&rft.btitle=&rft.title=Medical+and+pediatric+oncology&rft.issn=00981532&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-07-06 N1 - Date created - 1994-07-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Comparison of [3H]resiniferatoxin binding to spinal cord and dorsal root ganglia of newborn and adult rats. AN - 76516304; 8196505 AB - Capsaicin is frequently used in neurobiological investigations to selectively inhibit response by the primary sensory afferent neurons. The effectiveness of treatment depends significantly on the age of the animals; newborns are both quantitatively and qualitatively more sensitive than adults. In the present study, we used the [3H]resiniferatoxin binding assay to determine whether this different susceptibility to capsaicin between newborns and adult animals may reflect differences either in receptor affinity or density. We report here that whole spinal cord membranes of neonates bound [3H]RTX with similar affinity and positive cooperativity as did the spinal cord membranes from adult animals (Kd values were 24.8 +/- 3.7 and 26.8 +/- 4.8 pM, respectively; Hill coefficients were 2.25 +/- 0.03 and 2.17 +/- 0.05, respectively). However, the receptor density was three-fold higher in the spinal cord membranes of neonates than of adult rats (Bmax values were 142 +/- 13 and 43 +/- 3 fmol/mg protein, respectively). We found no significant difference in the [3H]RTX binding properties of dorsal root ganglia membranes of newborn and adult animals. Our results suggest that a higher density of the vanilloid receptor in the spinal cord (but not in the dorsal root ganglia) of newborn animals may contribute to the quantitative differences between the sensitivity of adult animals and neonates. JF - Life sciences AU - Acs, G AU - Blumberg, P M AD - Molecular Mechanisms of Tumor Promotion Section, National Cancer Institute, Bethesda, MD 20892. Y1 - 1994 PY - 1994 DA - 1994 SP - 1875 EP - 1882 VL - 54 IS - 24 SN - 0024-3205, 0024-3205 KW - Diterpenes KW - 0 KW - Neurotoxins KW - resiniferatoxin KW - A5O6P1UL4I KW - Index Medicus KW - Rats KW - Animals, Newborn KW - Animals KW - Rats, Sprague-Dawley KW - Age Factors KW - Male KW - Female KW - Binding Sites KW - Neurotoxins -- metabolism KW - Spinal Cord -- metabolism KW - Ganglia, Spinal -- metabolism KW - Diterpenes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76516304?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Life+sciences&rft.atitle=Comparison+of+%5B3H%5Dresiniferatoxin+binding+to+spinal+cord+and+dorsal+root+ganglia+of+newborn+and+adult+rats.&rft.au=Acs%2C+G%3BBlumberg%2C+P+M&rft.aulast=Acs&rft.aufirst=G&rft.date=1994-01-01&rft.volume=54&rft.issue=24&rft.spage=1875&rft.isbn=&rft.btitle=&rft.title=Life+sciences&rft.issn=00243205&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-06-27 N1 - Date created - 1994-06-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - An immunotoxin with increased activity and homogeneity produced by reducing the number of lysine residues in recombinant Pseudomonas exotoxin. AN - 76512843; 8199233 AB - Pseudomonas exotoxin A (PE) is a protein composed of 613 amino acids arranged into three major, and one minor, domains. Immunotoxins (ITs) containing PE38, a mutant form of PE which lacks the cell binding domain (Ia, amino acids 1-252) and 16 amino acids from domain Ib (amino acids 365-380), are extremely potent cytotoxic agents which can cause a complete regression of various human carcinomas grown in nude mice. However, these ITs are a mixture of several different chemical forms since the coupling between the antibody and the toxin may occur between either the light or heavy chain of the antibody and one of the four primary amino groups present on the truncated toxin. To modify the toxin with heterobifunctional crosslinking reagents only at specific sites, we replaced lysines 590 and 606 with glutamines and lysine 613 with arginine (PE38QQR). We also added two different peptide sequences, each containing a lysine residue, at the N-terminus of PE38. In one of these the sequence is ANLAEEAFK ("Lys" peptide), and in the other, the sequence is LQGTKLMAEE ("NLys" peptide). The mutant toxins were coupled using a thioether linkage to monoclonal antibody B3 which recognizes an antigen present in large amounts on many human cancers. PE38QQR-containing recombinant toxins can only be linked to an antibody through the N-terminal methionine or the lysine within the peptide.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Bioconjugate chemistry AU - Debinski, W AU - Pastan, I AD - Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. PY - 1994 SP - 40 EP - 46 VL - 5 IS - 1 SN - 1043-1802, 1043-1802 KW - Antineoplastic Agents KW - 0 KW - Bacterial Toxins KW - Disulfides KW - Exotoxins KW - Immunotoxins KW - Peptide Fragments KW - Recombinant Proteins KW - Sulfides KW - Virulence Factors KW - Adenosine Diphosphate KW - 61D2G4IYVH KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - toxA protein, Pseudomonas aeruginosa KW - EC 2.4.2.31 KW - Lysine KW - K3Z4F929H6 KW - Index Medicus KW - Animals KW - Drug Screening Assays, Antitumor KW - Escherichia coli -- metabolism KW - Humans KW - Sulfides -- chemistry KW - Escherichia coli -- genetics KW - Mice, Nude KW - Mice KW - Amino Acid Sequence KW - Recombinant Proteins -- genetics KW - Neoplasm Transplantation KW - Disulfides -- chemistry KW - Recombinant Proteins -- metabolism KW - Peptide Fragments -- pharmacology KW - Molecular Sequence Data KW - Lethal Dose 50 KW - Escherichia coli -- growth & development KW - Mutation KW - Antineoplastic Agents -- pharmacology KW - Carcinoma, Squamous Cell -- drug therapy KW - Female KW - Adenosine Diphosphate -- metabolism KW - Immunotoxins -- chemistry KW - Exotoxins -- pharmacology KW - Lysine -- chemistry KW - Immunotoxins -- toxicity KW - Exotoxins -- toxicity KW - Exotoxins -- chemistry KW - Immunotoxins -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76512843?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Bioconjugate+chemistry&rft.atitle=An+immunotoxin+with+increased+activity+and+homogeneity+produced+by+reducing+the+number+of+lysine+residues+in+recombinant+Pseudomonas+exotoxin.&rft.au=Debinski%2C+W%3BPastan%2C+I&rft.aulast=Debinski&rft.aufirst=W&rft.date=1994-01-01&rft.volume=5&rft.issue=1&rft.spage=40&rft.isbn=&rft.btitle=&rft.title=Bioconjugate+chemistry&rft.issn=10431802&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-07-07 N1 - Date created - 1994-07-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transgenic mouse models in chemical carcinogenesis studies. AN - 76497999; 8192589 JF - Archives of toxicology. Supplement. = Archiv fur Toxikologie. Supplement AU - Tennant, R AD - Laboratory of Environmental Carcinogenesis and Mutagenesis, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1994 PY - 1994 DA - 1994 SP - 261 EP - 270 VL - 16 SN - 0171-9750, 0171-9750 KW - Index Medicus KW - Animals KW - Disease Models, Animal KW - Oncogenes -- physiology KW - Mice KW - Male KW - Female KW - Neoplasms, Experimental -- chemically induced KW - Mice, Transgenic -- physiology KW - Neoplasms, Experimental -- genetics KW - Mice, Transgenic -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76497999?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+toxicology.+Supplement.+%3D+Archiv+fur+Toxikologie.+Supplement&rft.atitle=Transgenic+mouse+models+in+chemical+carcinogenesis+studies.&rft.au=Tennant%2C+R&rft.aulast=Tennant&rft.aufirst=R&rft.date=1994-01-01&rft.volume=16&rft.issue=&rft.spage=261&rft.isbn=&rft.btitle=&rft.title=Archives+of+toxicology.+Supplement.+%3D+Archiv+fur+Toxikologie.+Supplement&rft.issn=01719750&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-06-21 N1 - Date created - 1994-06-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nonlinearity of dose-response functions for carcinogenicity. AN - 76492818; 8187698 AB - Carcinogenesis data for 315 chemicals were obtained from the National Cancer Institute-National Toxicology Program (NCI-NTP) bioassay programs and were analyzed to examine the shape of carcinogenesis dose-response curves. Tumor site data were more often consistent with a quadratic response than with a linear response, suggesting that the routine use of linear dose-response models will often overestimate risk. Information from in vivo short-term mutagenicity and genotoxicity assays was also obtained for most of these rodent bioassays. It was found that there were no clear relationships between the shape of the carcinogenesis dose-response curve and the result of the short-term test. These observations argue against the concept that carcinogens that are positive in a short-term assay be regulated using a linear dose-response curve and those that are negative be regulated using a sublinear dose-response curve or a safety factor approach. JF - Environmental health perspectives AU - Hoel, D G AU - Portier, C J AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1994/01// PY - 1994 DA - January 1994 SP - 109 EP - 113 VL - 102 Suppl 1 SN - 0091-6765, 0091-6765 KW - Carcinogens KW - 0 KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Mice KW - Models, Biological KW - Male KW - Dose-Response Relationship, Drug KW - Carcinogens -- toxicity KW - Models, Statistical UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76492818?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Nonlinearity+of+dose-response+functions+for+carcinogenicity.&rft.au=Hoel%2C+D+G%3BPortier%2C+C+J&rft.aulast=Hoel&rft.aufirst=D&rft.date=1994-01-01&rft.volume=102+Suppl+1&rft.issue=&rft.spage=109&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 - 1994-06-23 N1 - Date created - 1994-06-23 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cancer Res. 1975 Jun;35(6):1379-86 [1131812] Arch Toxicol. 1987;60(1-3):224-8 [3304212] Proc Natl Acad Sci U S A. 1980 Jun;77(6):3659-63 [6774342] J Natl Cancer Inst. 1981 Jun;66(6):1037-52 [6941039] Science. 1981 Oct 23;214(4519):401-7 [7291981] Science. 1983 Mar 4;219(4588):1032-7 [6823565] Environ Health Perspect. 1983 Apr;50:309-20 [6873021] Nature. 1983 Aug 18-24;304(5927):648-51 [6877385] Science. 1983 Nov 18;222(4625):771-8 [6356358] Environ Res. 1984 Jun;34(1):175-91 [6373246] Science. 1985 Nov 15;230(4727):770-6 [2997917] Fundam Appl Toxicol. 1986 Feb;6(2):263-9 [3699316] Science. 1987 Jan 16;235(4786):305-11 [3541204] Cancer Res. 1987 Feb 15;47(4):1143-8 [3802095] Toxicol Appl Pharmacol. 1987 Feb;87(2):185-205 [3824380] Environ Health Perspect. 1987 Dec;76:65-70 [3447905] Biometrics. 1988 Jun;44(2):417-31 [3390507] Risk Anal. 1988 Sep;8(3):337-42 [2849149] Science. 1989 Mar 24;243(4898):1553 [2928792] Risk Anal. 1988 Dec;8(4):485-97 [3244857] Fundam Appl Toxicol. 1989 May;12(4):731-7 [2744275] Mol Carcinog. 1990;3(1):3-4 [2322387] Science. 1990 Aug 31;249(4972):1007-11 [2204108] Science. 1990 Aug 31;249(4972):970-1 [2136249] Risk Anal. 1991 Sep;11(3):535-43 [1947359] Science. 1977 Nov 18;198(4318):693-9 [910152] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Altered transcriptional regulation of human interstitial collagenase in cultured skin fibroblasts from older donors. AN - 76489092; 8187840 AB - Primary human dermal fibroblasts isolated from the medial aspect of the proximal forearm of young and old donors were compared for the expression of interstitial collagenase, 72 kDa type IV collagenase, the tissue inhibitor of metalloproteinase type 1, and pro-alpha 2 (I) collagen mRNA at basal levels and after stimulation with the tumor promotor 12-O-tetradecanoyl-phorbol-13-acetate. Higher basal and induced steady-state mRNA levels of interstitial collagenase were found in the cells from older donors. Ratios of basal and induced steady-state mRNA levels of interstitial collagenase to pro-alpha 2 (I) collagen, and interstitial collagenase to the tissue inhibitor of metalloproteinases type 1 were also higher in the cells from older donors. Seventy-two kiloDalton type IV collagenase and pro-alpha 2 (I) collagen mRNA showed similar levels of expression in the cells from young and old donors and were not altered by treatment with 12-O-tetradecanoyl-phorbol-13-acetate. Transient transfection assays with the interstitial collagenase promoter linked to a reporter gene showed increased activity of the reporter in cell strains with high interstitial collagenase mRNA levels. Mobility shift assays demonstrated increased binding activity to the specific 12-O-tetradecanoyl-phorbol-13-acetate response element in nuclear extracts from the cell strains with higher induced collagenase mRNA levels and higher reporter gene activity. These findings are consistent with the observed phenotype of interstitial collagenase and its specific tissue inhibitor in the senescent fibroblast aging model. JF - Experimental gerontology AU - Burke, E M AU - Horton, W E AU - Pearson, J D AU - Crow, M T AU - Martin, G R AD - Gerontology Research Center, National Institute on Aging, Baltimore, Maryland 21224. PY - 1994 SP - 37 EP - 53 VL - 29 IS - 1 SN - 0531-5565, 0531-5565 KW - c-fos KW - DNA, Complementary KW - 0 KW - Glycoproteins KW - RNA, Messenger KW - Recombinant Fusion Proteins KW - Tissue Inhibitor of Metalloproteinases KW - Collagenases KW - EC 3.4.24.- KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Recombinant Fusion Proteins -- biosynthesis KW - DNA, Complementary -- genetics KW - Glycoproteins -- biosynthesis KW - Humans KW - Aged KW - RNA, Messenger -- biosynthesis KW - Promoter Regions, Genetic KW - Enzyme Induction -- drug effects KW - Transfection KW - Aged, 80 and over KW - Cell Aging KW - Cells, Cultured KW - Adult KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Adolescent KW - Female KW - Male KW - Collagenases -- genetics KW - Fibroblasts -- drug effects KW - Aging -- metabolism KW - Fibroblasts -- enzymology KW - Transcription, Genetic -- drug effects KW - Skin -- enzymology KW - Skin -- cytology KW - Collagenases -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76489092?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+gerontology&rft.atitle=Altered+transcriptional+regulation+of+human+interstitial+collagenase+in+cultured+skin+fibroblasts+from+older+donors.&rft.au=Burke%2C+E+M%3BHorton%2C+W+E%3BPearson%2C+J+D%3BCrow%2C+M+T%3BMartin%2C+G+R&rft.aulast=Burke&rft.aufirst=E&rft.date=1994-01-01&rft.volume=29&rft.issue=1&rft.spage=37&rft.isbn=&rft.btitle=&rft.title=Experimental+gerontology&rft.issn=05315565&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-06-23 N1 - Date created - 1994-06-23 N1 - Date revised - 2017-01-13 N1 - Gene symbol - c-fos N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Statistical models for genetic susceptibility in toxicological and epidemiological investigations. AN - 76486369; 8187729 AB - Models are presented for use in assessing genetic susceptibility to cancer (or other diseases) with animal or human data. Observations are assumed to be in the form of proportions, hence a binomial sampling distribution is considered. Generalized linear models are employed to model the response as a function of the genetic component; these include logistic and complementary log forms. Susceptibility is measured via odds ratios of response, relative to a background genetic group. Significance tests and confidence intervals for these odds ratios are based on maximum likelihood estimates of the regression parameters. Additional consideration is given to the problem of gene-environment interactions and to testing whether certain genetic identifiers/categories may be collapsed into a smaller set of categories. The collapsibility hypothesis provides an example of a mechanistic context wherein nonhierarchical models for the linear predictor can sometimes make sense. JF - Environmental health perspectives AU - Piegorsch, W W AD - Statistics and Biomathematics Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1994/01// PY - 1994 DA - January 1994 SP - 77 EP - 82 VL - 102 Suppl 1 SN - 0091-6765, 0091-6765 KW - Index Medicus KW - Animals KW - Prospective Studies KW - Logistic Models KW - Humans KW - Linear Models KW - Retrospective Studies KW - Case-Control Studies KW - Environmental Monitoring KW - Mutagenicity Tests KW - Models, Statistical UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76486369?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Statistical+models+for+genetic+susceptibility+in+toxicological+and+epidemiological+investigations.&rft.au=Piegorsch%2C+W+W&rft.aulast=Piegorsch&rft.aufirst=W&rft.date=1994-01-01&rft.volume=102+Suppl+1&rft.issue=&rft.spage=77&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 - 1994-06-23 N1 - Date created - 1994-06-23 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Behaviour. 1966;27(1):107-49 [4957207] Biometrics. 1950 Jun;6(2):105-16 [15420239] Biometrics. 1981 Dec;37(4):775-94 [7337795] Carcinogenesis. 1984 Sep;5(9):1191-2 [6467507] J Natl Cancer Inst. 1985 Nov;75(5):971-4 [3863994] Nature. 1985 Nov 28-Dec 4;318(6044):377-80 [2999610] Science. 1987 Jan 16;235(4786):305-11 [3541204] J Natl Cancer Inst. 1987 Dec;79(6):1351-7 [2891865] Hum Genet. 1988 Apr;78(4):299-312 [2896152] Am J Epidemiol. 1989 Jan;129(1):183-90 [2910059] Cancer Res. 1989 Apr 15;49(8):2141-6 [2649235] Biometrics. 1989 Mar;45(1):219-30 [2720052] Cancer Res. 1989 Jul 1;49(13):3675-9 [2731181] Arch Toxicol Suppl. 1989;13:66-82 [2673152] Mutat Res. 1989 Oct;224(2):247-52 [2477699] Cancer Res. 1990 Mar 15;50(6):1857-62 [2407346] Biometrics. 1990 Jun;46(2):309-16 [2364123] Genet Epidemiol. 1990;7(3):177-85 [2369997] J Natl Cancer Inst. 1990 Aug 1;82(15):1264-72 [2374176] Int J Cancer. 1990 Sep 15;46(3):411-5 [1975565] Birth Defects Orig Artic Ser. 1990;26(1):113-27 [2224074] Mutat Res. 1991 Apr;247(2):199-202 [2011137] Biometrics. 1990 Dec;46(4):1035-46 [2085624] Cancer Cells. 1991 Mar;3(3):93-6 [2054261] J Obstet Gynaecol Br Commonw. 1969 Sep;76(9):806-8 [5387848] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Biostatistical issues in the design and analysis of animal carcinogenicity experiments. AN - 76479344; 8187725 AB - Two-year animal carcinogenicity experiments are used to evaluate the potential carcinogenicity from exposure to chemicals. The choice of exposure levels, the allocation of animals to doses, the length of exposure, and the choice of interim sacrifice times all affect the power of statistical tests for carcinogenic effects and the variance of interpolated estimates of carcinogenic risk. In this paper, one aspect of this problems is considered: the ability of tumor incidence data to provide information on carcinogenic mechanism and the optimal choice of design parameters with which to achieve this purpose. The direct application of biochemical data to the estimation of carcinogenic risk is also discussed in detail. JF - Environmental health perspectives AU - Portier, C J AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1994/01// PY - 1994 DA - January 1994 SP - 5 EP - 8 VL - 102 Suppl 1 SN - 0091-6765, 0091-6765 KW - Index Medicus KW - Neoplasms, Experimental -- epidemiology KW - Animals KW - Biometry KW - Neoplasms, Experimental -- chemically induced KW - Risk Factors KW - Incidence KW - Rodentia KW - Time Factors KW - Models, Biological KW - Research Design -- statistics & numerical data KW - Carcinogenicity Tests -- statistics & numerical data UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76479344?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Biostatistical+issues+in+the+design+and+analysis+of+animal+carcinogenicity+experiments.&rft.au=Portier%2C+C+J&rft.aulast=Portier&rft.aufirst=C&rft.date=1994-01-01&rft.volume=102+Suppl+1&rft.issue=&rft.spage=5&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 - 1994-06-23 N1 - Date created - 1994-06-23 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Risk Anal. 1991 Sep;11(3):535-43 [1947359] Math Biosci. 1991 Jul;105(2):139-66 [1806098] J Natl Cancer Inst. 1981 Jun;66(6):1037-52 [6941039] Environ Health Perspect. 1983 Apr;50:285-91 [6873019] Carcinogenesis. 1984 Apr;5(4):437-45 [6705147] Risk Anal. 1987 Mar;7(1):109-19 [3615992] Science. 1990 Aug 31;249(4972):1007-11 [2204108] Risk Anal. 1988 Jun;8(2):215-21 [3413309] J Toxicol Environ Health. 1989;27(1):21-45 [2724366] Fundam Appl Toxicol. 1989 Oct;13(3):533-44 [2612786] Fundam Appl Toxicol. 1990 Apr;14(3):444-60 [2340975] Carcinogenesis. 1990 Aug;11(8):1271-8 [2143703] Environ Health Perspect. 1987 Dec;76:65-70 [3447905] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Intrathoracic photodynamic therapy: a canine normal tissue tolerance study and early clinical experience. AN - 76473889; 8183046 AB - Surgery with intraoperative photodynamic therapy (PDT) has the potential to improve the treatment of pleural malignancies. Before embarking on such treatment in humans, however, thoracic tissue tolerance to PDT was studied. For each of three (1 week, 1 month, and 6 month) study end-points, one control (no Photofrin II [PII]) and four treated animals underwent thoracotomy 72 hours after I.V. injection (6 mg/kg) PII. Red light (630 nm) was delivered (5-40 J/cm2) to the pleural surface (1 cm diameter) of selected thoracic organs. No clinical differences were observed between PDT and control dogs. The control showed no histological changes; however, in the treated animals focal areas of coagulation necrosis were found at 1 week which progressed to fibrosis at 1 month. The extent and depth of injury was proportional to light dose. The lung was the most sensitive; the chest wall was the most resistant. Myocardium had superficial damage, whereas coronary arteries appeared normal. The results provide the basis for proceeding to phase I human trials in the evaluation of PDT as an intraoperative adjuvant treatment in the management of pleural malignancies. JF - Lasers in surgery and medicine AU - Tochner, Z A AU - Pass, H I AU - Smith, P D AU - DeLaney, T F AU - Sprague, M AU - DeLuca, A M AU - Harrington, F AU - Thomas, G F AU - Terrill, R AU - Bacher, J D AD - Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994 PY - 1994 DA - 1994 SP - 118 EP - 123 VL - 14 IS - 2 SN - 0196-8092, 0196-8092 KW - Dihematoporphyrin Ether KW - 97067-70-4 KW - Index Medicus KW - Mesothelioma -- drug therapy KW - Animals KW - Combined Modality Therapy KW - Thoracotomy KW - Mesothelioma -- surgery KW - Intraoperative Care KW - Dogs KW - Male KW - Female KW - Dihematoporphyrin Ether -- therapeutic use KW - Hematoporphyrin Photoradiation KW - Dihematoporphyrin Ether -- adverse effects KW - Pleura -- surgery KW - Pleural Neoplasms -- drug therapy KW - Pleura -- pathology KW - Pleural Neoplasms -- surgery UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76473889?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Lasers+in+surgery+and+medicine&rft.atitle=Intrathoracic+photodynamic+therapy%3A+a+canine+normal+tissue+tolerance+study+and+early+clinical+experience.&rft.au=Tochner%2C+Z+A%3BPass%2C+H+I%3BSmith%2C+P+D%3BDeLaney%2C+T+F%3BSprague%2C+M%3BDeLuca%2C+A+M%3BHarrington%2C+F%3BThomas%2C+G+F%3BTerrill%2C+R%3BBacher%2C+J+D&rft.aulast=Tochner&rft.aufirst=Z&rft.date=1994-01-01&rft.volume=14&rft.issue=2&rft.spage=118&rft.isbn=&rft.btitle=&rft.title=Lasers+in+surgery+and+medicine&rft.issn=01968092&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-06-16 N1 - Date created - 1994-06-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Prospects for the therapeutic use of antisense oligonucleotides in malignant lymphomas. AN - 76467094; 8172821 AB - Combinations of cytotoxic drugs, based almost entirely upon the results of empirical clinical trials, are the foundation of the modern management of the non-Hodgkin's lymphomas. While highly effective in the high-grade (particularly pediatric) lymphomas, and able to cure a significant fraction of intermediate-grade lymphomas, it has yet to be proven that patients with low-grade lymphomas can be cured by chemotherapy. Yet even if 100% of patients were potentially curable by chemotherapy, the significant medical cost with respect to both immediate and late toxicity is reason enough to search for radically different approaches to therapy. Of particular appeal is the possibility that therapy might be developed that is targeted to the very genetic lesions that are responsible for the pathogenesis of lymphomas. Such therapy should, by definition, be largely specific for the lymphoma cells, and hence devoid of the major side effects presently encountered. Recent advances in the understanding of the molecular basis of lymphomagenesis have provided sufficient information to begin to develop approaches of this kind. Here, I discuss the prospects for sequence-specific therapy, focusing specifically on antisense oligonucleotides. These short stretches of DNA bind specifically to RNA molecules and prevent their translation. If the targeted RNA molecules are specific to the tumor cells, or derived from pathogenetically relevant viral genomes, such therapy has at least the theoretical possibility of inhibiting tumor cell growth, or even killing tumor cells, without causing significant damage to normal cells. JF - Annals of oncology : official journal of the European Society for Medical Oncology AU - Magrath, I T AD - National Cancer Institute, National Institutes of Health, Bethesda, Maryland. Y1 - 1994 PY - 1994 DA - 1994 SP - 67 EP - 70 VL - 5 Suppl 1 SN - 0923-7534, 0923-7534 KW - Oligonucleotides, Antisense KW - 0 KW - Index Medicus KW - Humans KW - Oligonucleotides, Antisense -- therapeutic use KW - Lymphoma -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76467094?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+oncology+%3A+official+journal+of+the+European+Society+for+Medical+Oncology&rft.atitle=Prospects+for+the+therapeutic+use+of+antisense+oligonucleotides+in+malignant+lymphomas.&rft.au=Magrath%2C+I+T&rft.aulast=Magrath&rft.aufirst=I&rft.date=1994-01-01&rft.volume=5+Suppl+1&rft.issue=&rft.spage=67&rft.isbn=&rft.btitle=&rft.title=Annals+of+oncology+%3A+official+journal+of+the+European+Society+for+Medical+Oncology&rft.issn=09237534&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-06-09 N1 - Date created - 1994-06-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Basal ganglia iron in tardive dyskinesia: an MRI study. AN - 76461629; 8167198 AB - Alterations in brain iron could play an important role in the development of tardive dyskinesia in patients receiving neuroleptic medication. To test this hypothesis, magnetic resonance imaging scans of the brain were performed on 21 chronic schizophrenic patients. Ten patients met research diagnostic criteria for persistent tardive dyskinesia, and 11 were free of tardive dyskinesia. All patients had received long-term neuroleptic treatment and were on a stable neuroleptic dose for at least 3 months before scanning. The signal intensity of basal ganglia structures was obtained as a quantitative estimate of brain iron content. No difference was found in the signal intensity ratios between the two groups. This suggests that iron deposition in the basal ganglia, at least as assessed by this measure, does not play a role in the pathophysiology of tardive dyskinesia. JF - Biological psychiatry AU - Elkashef, A M AU - Egan, M F AU - Frank, J A AU - Hyde, T M AU - Lewis, B K AU - Wyatt, R J AD - Neuropsychiatry Branch, NIMH, St. Elizabeths Hospital, Washington, DC 20032. Y1 - 1994/01/01/ PY - 1994 DA - 1994 Jan 01 SP - 16 EP - 21 VL - 35 IS - 1 SN - 0006-3223, 0006-3223 KW - Iron KW - E1UOL152H7 KW - Haloperidol KW - J6292F8L3D KW - Molindone KW - RT3Y3QMF8N KW - Index Medicus KW - Haloperidol -- adverse effects KW - Haloperidol -- therapeutic use KW - Dominance, Cerebral -- physiology KW - Dominance, Cerebral -- drug effects KW - Humans KW - Adult KW - Schizophrenic Psychology KW - Schizophrenia -- drug therapy KW - Middle Aged KW - Molindone -- therapeutic use KW - Molindone -- adverse effects KW - Male KW - Female KW - Magnetic Resonance Imaging KW - Dyskinesia, Drug-Induced -- metabolism KW - Dyskinesia, Drug-Induced -- diagnosis KW - Dyskinesia, Drug-Induced -- etiology KW - Iron -- metabolism KW - Basal Ganglia -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76461629?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biological+psychiatry&rft.atitle=Basal+ganglia+iron+in+tardive+dyskinesia%3A+an+MRI+study.&rft.au=Elkashef%2C+A+M%3BEgan%2C+M+F%3BFrank%2C+J+A%3BHyde%2C+T+M%3BLewis%2C+B+K%3BWyatt%2C+R+J&rft.aulast=Elkashef&rft.aufirst=A&rft.date=1994-01-01&rft.volume=60&rft.issue=4&rft.spage=1436&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 - 1994-06-02 N1 - Date created - 1994-06-02 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Biol Psychiatry. 1995 Jul 15;38(2):133-5 [7578650] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Human germ cell mutagens. AN - 76448352; 8162905 AB - Human genetic disorders constitute a major public health burden in this country and around the world. The possibility that exposures to mutagenic environmental agents may result in induced genetic damage in human germ cells and thereby increase the incidence of genetic disease has been investigated in research laboratories and in epidemiology studies for decades. The capacity of ionizing radiation and some chemicals to induce transmissible genetic damage in the germ cells of laboratory mammals has been clearly demonstrated and extensively investigated. To date, no clear evidence of such effects in humans has been reported although increased frequencies of chromosomal aberrations have been detected in human sperm following exposures to radiation or chemotherapeutic agents. Evolving methods to detect molecular changes in DNA offer to improve our abilities to detect induced genetic changes. The integration of these methods into mutation epidemiology studies promises to help resolve some of the questions regarding human genetic risk. JF - Environmental and molecular mutagenesis AU - Shelby, M D AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1994 PY - 1994 DA - 1994 SP - 30 EP - 34 VL - 23 Suppl 24 SN - 0893-6692, 0893-6692 KW - Antineoplastic Agents KW - 0 KW - Mutagens KW - Index Medicus KW - Animals KW - Molecular Epidemiology KW - Risk Factors KW - Humans KW - DNA Mutational Analysis KW - Chromosome Aberrations KW - Antineoplastic Agents -- toxicity KW - Mice KW - Male KW - Female KW - Mutagens -- toxicity KW - Germ Cells -- drug effects KW - Germ-Line Mutation KW - Germ Cells -- radiation effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76448352?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+and+molecular+mutagenesis&rft.atitle=Human+germ+cell+mutagens.&rft.au=Shelby%2C+M+D&rft.aulast=Shelby&rft.aufirst=M&rft.date=1994-01-01&rft.volume=23+Suppl+24&rft.issue=&rft.spage=30&rft.isbn=&rft.btitle=&rft.title=Environmental+and+molecular+mutagenesis&rft.issn=08936692&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-05-23 N1 - Date created - 1994-05-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Poultry oncogenic retroviruses and humans. AN - 76447451; 8162609 AB - Viruses of the avian leukosis/sarcoma group (ALSV) and reticuloendotheliosis viruses (REV) are highly prevalent in chickens and turkeys and naturally cause tumors in them. Commercial chickens are positive for antibodies, and a proportion actually carry infectious virus. Virus may be present in chicken products and in eggs, thus human exposure is virtually universal. The viruses show little potential for producing infectious viral particles in mammalian cells; nevertheless, they have the capacity to infect and transform mammalian cells (including human cells) in vitro, and to induce tumors in a variety of mammals, including primates. Most, but not all, of the serological studies in humans have been negative. Given the known behavior of these viruses in mammals, this was not unexpected. Moreover, there were methodological problems with most of the studies. There is some epidemiological evidence associating putative poultry exposure with cancer in humans. However, this has not been rigorously investigated. This paper is a comprehensive review of the extent of the carcinogenic potential these viruses show for humans. It is concluded, virological evidence indicates, that these viruses could conceivably have a carcinogenic potential for humans, but if so, at a level much less than in chickens. Whether this is insignificant, or translates to a real risk, is not known at the moment. Therefore, there is a need for definitive studies to completely rule out this possibility. JF - Cancer detection and prevention AU - Johnson, E S AD - Environmental and Molecular Epidemiology Section, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709. Y1 - 1994 PY - 1994 DA - 1994 SP - 9 EP - 30 VL - 18 IS - 1 SN - 0361-090X, 0361-090X KW - Antibodies, Viral KW - 0 KW - Index Medicus KW - Antibodies, Viral -- blood KW - Animals KW - Oncogenes KW - Humans KW - Cell Transformation, Viral KW - Alpharetrovirus -- pathogenicity KW - Reticuloendotheliosis virus -- pathogenicity KW - Reticuloendotheliosis virus -- isolation & purification KW - Alpharetrovirus -- isolation & purification KW - Alpharetrovirus -- immunology KW - Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76447451?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+detection+and+prevention&rft.atitle=Poultry+oncogenic+retroviruses+and+humans.&rft.au=Johnson%2C+E+S&rft.aulast=Johnson&rft.aufirst=E&rft.date=1994-01-01&rft.volume=18&rft.issue=1&rft.spage=9&rft.isbn=&rft.btitle=&rft.title=Cancer+detection+and+prevention&rft.issn=0361090X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-05-23 N1 - Date created - 1994-05-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Toxicity of diethanolamine. 1. Drinking water and topical application exposures in F344 rats. AN - 76446905; 8157863 AB - Toxicology studies of diethanolamine were conducted in male and female F344 rats for 13 weeks' duration to characterize and compare effects of exposure in the drinking water with those caused by topical application. Doses of diethanolamine ranged from 160 to 5000 ppm in the drinking water study (equivalent to daily doses of 25-440 mg kg-1 in males and 15-240 mg kg-1 in females) and from 32 to 500 mg kg-1 in the topical application study. Dose-dependent toxic effects due to exposure to diethanolamine included hematological changes (a poorly regenerative, microcytic anemia), as well as toxic responses in the kidney (increased weight, tubular necrosis, decreased renal function, and/or tubular mineralization), brain and spinal cord (demyelination), testis (degeneration of the seminiferous tubules) and skin (site of application: ulceration, inflammation, hyperkeratosis and acanthosis). A no-observed-adverse-effect level was not achieved for hematological changes, nephropathy or hyperkeratosis of the skin. Differences in dose-response between the drinking water and topical application exposures were attributed largely to the limited dermal absorption of this chemical. JF - Journal of applied toxicology : JAT AU - Melnick, R L AU - Mahler, J AU - Bucher, J R AU - Thompson, M AU - Hejtmancik, M AU - Ryan, M J AU - Mezza, L E AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. PY - 1994 SP - 1 EP - 9 VL - 14 IS - 1 SN - 0260-437X, 0260-437X KW - Ethanolamines KW - 0 KW - diethanolamine KW - AZE05TDV2V KW - Index Medicus KW - Administration, Oral KW - Weight Gain -- drug effects KW - Animals KW - Water Supply KW - Rats KW - Hematologic Diseases -- chemically induced KW - Rats, Inbred F344 KW - Drinking -- drug effects KW - Hematologic Diseases -- blood KW - Administration, Topical KW - Blood Cell Count -- drug effects KW - Female KW - Male KW - Organ Size -- drug effects KW - Ethanolamines -- administration & dosage KW - Ethanolamines -- toxicity KW - Ethanolamines -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76446905?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+applied+toxicology+%3A+JAT&rft.atitle=Toxicity+of+diethanolamine.+1.+Drinking+water+and+topical+application+exposures+in+F344+rats.&rft.au=Melnick%2C+R+L%3BMahler%2C+J%3BBucher%2C+J+R%3BThompson%2C+M%3BHejtmancik%2C+M%3BRyan%2C+M+J%3BMezza%2C+L+E&rft.aulast=Melnick&rft.aufirst=R&rft.date=1994-01-01&rft.volume=14&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Journal+of+applied+toxicology+%3A+JAT&rft.issn=0260437X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-05-19 N1 - Date created - 1994-05-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Looking backward on a century of mutation research. AN - 76446891; 8162900 AB - Our understanding of the mutation process and how it impacts target populations has deepened steadily during the hundred years since 1919. Recent advances in engineering genetically determined social traits points towards the logical culmination of this knowledge. JF - Environmental and molecular mutagenesis AU - Drake, J W AD - Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709-2233. Y1 - 1994 PY - 1994 DA - 1994 SP - 11 EP - 14 VL - 23 Suppl 24 SN - 0893-6692, 0893-6692 KW - Index Medicus KW - History of medicine KW - Religion and Science KW - Molecular Biology -- history KW - History, 20th Century KW - Genetic Engineering -- history KW - Wit and Humor as Topic KW - Mutagenesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76446891?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+and+molecular+mutagenesis&rft.atitle=Looking+backward+on+a+century+of+mutation+research.&rft.au=Drake%2C+J+W&rft.aulast=Drake&rft.aufirst=J&rft.date=1994-01-01&rft.volume=23+Suppl+24&rft.issue=&rft.spage=11&rft.isbn=&rft.btitle=&rft.title=Environmental+and+molecular+mutagenesis&rft.issn=08936692&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-05-23 N1 - Date created - 1994-05-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Promising new developments in the systemic treatment of ovarian cancer. AN - 76443950; 7513218 AB - Advanced-stage cancer of the ovary is the most lethal of gynecologic malignancies, affecting African-American and white women with approximately equal frequency. In large part, ovarian cancer's lethality is due to the fact that most women are diagnosed with disease that is widespread throughout the abdomen and pelvis. This article reviews recent developments in the identification of new treatment approaches to ovarian cancer. Discussion focuses on current drug development activities of the Medical Ovarian Cancer Section of the National Cancer Institute, with reference to pertinent literature from other institutions. The drugs discussed are in clinical trials as of this writing. They include paclitaxel, an agent with a novel molecular mechanism of action; colony-stimulating factors, which enhance the therapeutic index of cytotoxic agents; and the antiproliferative agents suramin and carboxyamidotriazole. JF - Journal of the Association for Academic Minority Physicians : the official publication of the Association for Academic Minority Physicians AU - Reed, E AD - Medical Ovarian Cancer Section, Medicine Branch, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1994 PY - 1994 DA - 1994 SP - 16 EP - 21 VL - 5 IS - 1 SN - 1048-9886, 1048-9886 KW - Antineoplastic Agents KW - 0 KW - Granulocyte Colony-Stimulating Factor KW - 143011-72-7 KW - Suramin KW - 6032D45BEM KW - Paclitaxel KW - P88XT4IS4D KW - Index Medicus KW - Neoplasm Staging KW - Combined Modality Therapy KW - Humans KW - Clinical Trials as Topic KW - Granulocyte Colony-Stimulating Factor -- adverse effects KW - Paclitaxel -- therapeutic use KW - Suramin -- adverse effects KW - Paclitaxel -- adverse effects KW - Neoplasm Recurrence, Local -- drug therapy KW - Granulocyte Colony-Stimulating Factor -- administration & dosage KW - Female KW - Suramin -- therapeutic use KW - Neoplasm Recurrence, Local -- pathology KW - Ovarian Neoplasms -- pathology KW - Antineoplastic Agents -- therapeutic use KW - Ovarian Neoplasms -- drug therapy KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76443950?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=unknown&rft.jtitle=US+Fed+News+Service%2C+Including+US+State+News&rft.atitle=SENATE+PASSES+SENS.+CORNYN%2C+FEINSTEIN+RESOLUTION+TO+ESTABLISH+NATIONAL+DAY+OF+HUMAN+TRAFFICKING+AWARENESS&rft.au=&rft.aulast=&rft.aufirst=&rft.date=2007-06-22&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=US+Fed+News+Service%2C+Including+US+State+News&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-05-27 N1 - Date created - 1994-05-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Toxicity of diethanolamine. 2. Drinking water and topical application exposures in B6C3F1 mice. AN - 76443794; 8157864 AB - Toxicology studies of diethanolamine were conducted in male and female B6C3F1 mice to characterize and compare effects of exposure in the drinking water with those caused by topical application and to compare responses in mice to those observed in rats. Each study consisted of five dose groups plus controls and the size of each group was 10 animals per sex. Doses of diethanolamine ranged from 630 to 10,000 ppm in the drinking water study (approximately equivalent to daily doses of 100-1700 mg kg-1 in males and 140-1100 mg kg-1 in females) and from 80 to 1250 mg kg-1 in the topical application study. Exposure to diethanolamine caused dose-dependent toxic effects in the liver (hepatocellular cytological alterations and necrosis), kidney (nephropathy and tubular epithelial necrosis in males), heart (cardiac myocyte degeneration) and skin (site of application: ulceration, inflammation, hyperkeratosis, and acanthosis). Cytological alterations in the liver consisted of multiple hepatocyte changes, including enlarged cells that were frequently multinucleated, increased nuclear pleomorphism, increased eosinophilia and disruption of hepatic cords. A no-observed-adverse-effect level (NOAEL) was not achieved for hepatocellular cytological alterations or for acanthosis in the skin. JF - Journal of applied toxicology : JAT AU - Melnick, R L AU - Mahler, J AU - Bucher, J R AU - Hejtmancik, M AU - Singer, A AU - Persing, R L AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. PY - 1994 SP - 11 EP - 19 VL - 14 IS - 1 SN - 0260-437X, 0260-437X KW - Ethanolamines KW - 0 KW - diethanolamine KW - AZE05TDV2V KW - Index Medicus KW - Administration, Oral KW - Weight Gain -- drug effects KW - Animals KW - Liver -- pathology KW - Kidney -- pathology KW - Myocardium -- pathology KW - Water Supply KW - Mice KW - Mice, Inbred Strains KW - Drinking -- drug effects KW - Administration, Topical KW - Female KW - Male KW - Organ Size -- drug effects KW - Ethanolamines -- administration & dosage KW - Ethanolamines -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76443794?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+applied+toxicology+%3A+JAT&rft.atitle=Toxicity+of+diethanolamine.+2.+Drinking+water+and+topical+application+exposures+in+B6C3F1+mice.&rft.au=Melnick%2C+R+L%3BMahler%2C+J%3BBucher%2C+J+R%3BHejtmancik%2C+M%3BSinger%2C+A%3BPersing%2C+R+L&rft.aulast=Melnick&rft.aufirst=R&rft.date=1994-01-01&rft.volume=14&rft.issue=1&rft.spage=11&rft.isbn=&rft.btitle=&rft.title=Journal+of+applied+toxicology+%3A+JAT&rft.issn=0260437X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-05-19 N1 - Date created - 1994-05-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The genetic modification of T cells for cancer therapy: an overview of laboratory and clinical trials. AN - 76442372; 8162605 AB - Immunotherapies using high doses of interleukin-2 and tumor-infiltrating lymphocytes (TIL) have been developed for the treatment of advanced cancer. Current efforts are aimed at enhancing the therapeutic efficacy of TIL through genetic modification. Initially, we demonstrated that retroviral-mediated gene transfer into TIL using a neomycin resistance marker gene was practical and safe for use in patient therapy. Because TIL have been shown to localize at tumor sites, we are now introducing the TNF gene into TIL in an attempt to increase the local concentrations of TNF in the tumor microenvironment without inducing systemic toxicity. Another gene being studied for insertion into TIL is a chimeric antibody/T-cell receptor gene. For many histologic types of cancer, it is relatively difficult to obtain specific TIL, but many monoclonal antibodies (mAb) exist that bind tumor-associated antigens. In order to combine the effector function of T cells with the antitumor specificity of antibodies, we have constructed chimeric receptor genes containing the variable region domains from mAb linked to T-cell signal-transducing chains. Human TIL retrovirally transduced with a chimeric receptor gene constructed from an anti-ovarian cancer antibody were redirected to recognize and lyse ovarian cancer cell lines specifically. This approach may allow adoptive immunotherapy against histologies not previously amenable to this treatment modality. JF - Cancer detection and prevention AU - Hwu, P AU - Rosenberg, S A AD - Surgery Branch, National Cancer Institute, Bethesda, MD 20852. Y1 - 1994 PY - 1994 DA - 1994 SP - 43 EP - 50 VL - 18 IS - 1 SN - 0361-090X, 0361-090X KW - Receptors, Antigen, T-Cell, alpha-beta KW - 0 KW - Tumor Necrosis Factor-alpha KW - Index Medicus KW - Humans KW - Tumor Necrosis Factor-alpha -- pharmacology KW - Transduction, Genetic KW - Clinical Trials as Topic KW - Receptors, Antigen, T-Cell, alpha-beta -- genetics KW - Lymphocytes, Tumor-Infiltrating -- immunology KW - Immunotherapy, Adoptive KW - Genetic Therapy KW - Neoplasms -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76442372?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+detection+and+prevention&rft.atitle=The+genetic+modification+of+T+cells+for+cancer+therapy%3A+an+overview+of+laboratory+and+clinical+trials.&rft.au=Hwu%2C+P%3BRosenberg%2C+S+A&rft.aulast=Hwu&rft.aufirst=P&rft.date=1994-01-01&rft.volume=18&rft.issue=1&rft.spage=43&rft.isbn=&rft.btitle=&rft.title=Cancer+detection+and+prevention&rft.issn=0361090X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-05-23 N1 - Date created - 1994-05-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A polymorphic dinucleotide repeat in the third intron of TAP1. AN - 76432525; 8162046 JF - Human molecular genetics AU - Carrington, M AU - Dean, M AD - Biological Carcinogenesis and Development Program, PRI/DynCorp, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702. Y1 - 1994/01// PY - 1994 DA - January 1994 SP - 218 VL - 3 IS - 1 SN - 0964-6906, 0964-6906 KW - TAP1 KW - Antigen Peptide Transporter-1 KW - 0 KW - Carrier Proteins KW - DNA Primers KW - Oligodeoxyribonucleotides KW - TAP1 protein, human KW - Index Medicus KW - Polymerase Chain Reaction KW - Base Sequence KW - Humans KW - Molecular Sequence Data KW - Biological Transport KW - Chromosome Mapping KW - Polymorphism, Genetic KW - Carrier Proteins -- genetics KW - ATP-Binding Cassette Transporters KW - Repetitive Sequences, Nucleic Acid KW - Chromosomes, Human, Pair 6 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76432525?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+molecular+genetics&rft.atitle=A+polymorphic+dinucleotide+repeat+in+the+third+intron+of+TAP1.&rft.au=Carrington%2C+M%3BDean%2C+M&rft.aulast=Carrington&rft.aufirst=M&rft.date=1994-01-01&rft.volume=3&rft.issue=1&rft.spage=218&rft.isbn=&rft.btitle=&rft.title=Human+molecular+genetics&rft.issn=09646906&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-05-23 N1 - Date created - 1994-05-23 N1 - Date revised - 2017-01-13 N1 - Gene symbol - TAP1 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Removal of biological stains from aqueous solution using a flow-through decontamination procedure. AN - 76424202; 8148434 AB - Chromatography columns filled with Amberlite XAD-16 were used to decontaminate, using a continuous flow-through procedure, aqueous solutions of the following biological stains: acridine orange, alcian blue 8GX, alizarin red S, azure A, azure B, brilliant blue G, brilliant blue R, Congo red, cresyl violet acetate, crystal violet, eosin B, eosin Y, erythrosin B, ethidium bromide, Giemsa stain, Janus green B, methylene blue, neutral red, nigrosin, orcein, propidium iodide, rose Bengal, safranine O, toluidine blue O, and trypan blue. Adsorption was most efficient for stains of lower molecular weight (< 600). Adsorption of stain increased as the flow rate decreased; column diameter had little effect on adsorption. Adsorption of stain was greatest when finely ground resin was used, but if the resin particles were too small, column clogging occurred. Limited grinding of the resin gave increased adsorption while retaining good flow characteristics. Amberlite XAD-16 saturated with methylene blue was regenerated to its initial adsorption capacity by passing methanol through the column. The technique described provides an economical, rapid means of removing stains from aqueous solution. JF - Biotechnic & histochemistry : official publication of the Biological Stain Commission AU - Lunn, G AU - Klausmeyer, P J AU - Sansone, E B AD - Program Resources, Inc./DynCorp, Environmental Control and Research Program, NCI-Frederick Cancer Research and Development Center, Maryland 21702-1201. Y1 - 1994/01// PY - 1994 DA - January 1994 SP - 45 EP - 54 VL - 69 IS - 1 SN - 1052-0295, 1052-0295 KW - Coloring Agents KW - 0 KW - Ion Exchange Resins KW - Polymers KW - Resins, Plant KW - Solutions KW - Amberlite XAD-16 KW - 104219-63-8 KW - Methylene Blue KW - T42P99266K KW - Index Medicus KW - Rats KW - Animals KW - Mutagenicity Tests KW - Spectrometry, Fluorescence KW - Particle Size KW - Methylene Blue -- chemistry KW - In Vitro Techniques KW - Spectrophotometry, Ultraviolet KW - Chromatography, Ion Exchange KW - Coloring Agents -- toxicity KW - Coloring Agents -- chemistry KW - Coloring Agents -- isolation & purification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76424202?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biotechnic+%26+histochemistry+%3A+official+publication+of+the+Biological+Stain+Commission&rft.atitle=Removal+of+biological+stains+from+aqueous+solution+using+a+flow-through+decontamination+procedure.&rft.au=Lunn%2C+G%3BKlausmeyer%2C+P+J%3BSansone%2C+E+B&rft.aulast=Lunn&rft.aufirst=G&rft.date=1994-01-01&rft.volume=69&rft.issue=1&rft.spage=45&rft.isbn=&rft.btitle=&rft.title=Biotechnic+%26+histochemistry+%3A+official+publication+of+the+Biological+Stain+Commission&rft.issn=10520295&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-05-09 N1 - Date created - 1994-05-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Suppression of in vivo clearance of N-nitrosodimethylamine in mice by cotreatment with ethanol. AN - 76423369; 8149888 AB - Oral cotreatment of mice with ethanol results in increased tumors in extrahepatic organs caused by some nitrosamines. This action, attributed in part to inhibition of hepatic first-pass carcinogen metabolism by ethanol, has possible relevance to the enhancing effect of alcoholic beverage consumption on human cancer risk. In this study, the effects of ethanol on clearance of N-nitrosodimethylamine (NDMA) were quantified in Swiss female and strain A male mice. In Swiss mice, a 1.6 g/kg ig ethanol dose preceding 1 or 5 mg/kg iv NDMA resulted in 20- to 30-fold increases in area-under-the-blood-concentration-vs.-time curves, mean residence times, and clearance half-times, and similar decreases in clearance. For a 0.5 mg/kg ig NDMA dose, the pharmacokinetic parameters were altered 30-fold and 450-fold by simultaneous ethanol doses of 0.08 and 0.8 g/kg, respectively. With 5 mg NDMA/kg ig, 0.4, 0.8, and 1.6 g/kg ethanol resulted in 6-, 10-, and 20-fold changes in clearance parameters. Comparison of the data with results obtained previously with patas monkeys indicated comparable effects of ethanol on tissue exposure to NDMA in the two species, confirming potential human applicability. In experiments with strain A mice, NDMA concentrations were also monitored in lung and liver. NDMA amounts in lung paralleled those in blood, and were more than sufficient to account for the previously reported increases in DNA adducts and tumors in lungs of similarly treated strain A mice. JF - Drug metabolism and disposition: the biological fate of chemicals AU - Anderson, L M AU - Koseniauskas, R AU - Burak, E S AU - Logsdon, D L AU - Carter, J P AU - Driver, C L AU - Gombar, C T AU - Magee, P N AU - Harrington, G W AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick, MD 21702. PY - 1994 SP - 43 EP - 49 VL - 22 IS - 1 SN - 0090-9556, 0090-9556 KW - Ethanol KW - 3K9958V90M KW - Dimethylnitrosamine KW - M43H21IO8R KW - Index Medicus KW - Mice, Inbred A KW - Animals KW - Liver -- metabolism KW - Mice KW - Lung -- metabolism KW - Male KW - Female KW - Ethanol -- blood KW - Dimethylnitrosamine -- blood KW - Dimethylnitrosamine -- pharmacokinetics KW - Ethanol -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76423369?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Drug+metabolism+and+disposition%3A+the+biological+fate+of+chemicals&rft.atitle=Suppression+of+in+vivo+clearance+of+N-nitrosodimethylamine+in+mice+by+cotreatment+with+ethanol.&rft.au=Anderson%2C+L+M%3BKoseniauskas%2C+R%3BBurak%2C+E+S%3BLogsdon%2C+D+L%3BCarter%2C+J+P%3BDriver%2C+C+L%3BGombar%2C+C+T%3BMagee%2C+P+N%3BHarrington%2C+G+W&rft.aulast=Anderson&rft.aufirst=L&rft.date=1994-01-01&rft.volume=22&rft.issue=1&rft.spage=43&rft.isbn=&rft.btitle=&rft.title=Drug+metabolism+and+disposition%3A+the+biological+fate+of+chemicals&rft.issn=00909556&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-05-06 N1 - Date created - 1994-05-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetic mechanisms of solid tumor oncogenesis. AN - 76413196; 8140969 AB - The study of the genetic alterations of tumor suppressor genes and protooncogenes in solid tumors has greatly increased our understanding of cancer biology. These findings have extended epidemiologic associations of carcinogens with certain tumors. Further analysis of patterns of genetic changes may implicate carcinogenic substances in cases where epidemiology has not been able to do so. Identification of germline mutations in p53, APC, and NF1 has provided improved diagnosis and presymptomatic screening in cancer kindreds. The identification of additional alterations in tumor suppressor genes may further improve the ability to predict inherent cancer risk. Screening strategies based on detection of genetic abnormalities of preinvasive cancerous lesions, such as mutant ras in colonic polyps, may improve early diagnosis. Finally, strategies to replace lost tumor suppressor function may provide a future therapeutic modality. JF - Advances in internal medicine AU - Kelley, M J AU - Johnson, B E AD - Navy Medical Oncology Branch, National Cancer Institute, National Naval Medical Center, Bethesda, Maryland. Y1 - 1994 PY - 1994 DA - 1994 SP - 93 EP - 122 VL - 39 SN - 0065-2822, 0065-2822 KW - APC KW - DCC KW - MCC KW - NF1 KW - p53 KW - ras KW - Index Medicus KW - Humans KW - Gene Expression Regulation, Neoplastic KW - Genes, Tumor Suppressor KW - Proto-Oncogenes KW - Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76413196?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Advances+in+internal+medicine&rft.atitle=Genetic+mechanisms+of+solid+tumor+oncogenesis.&rft.au=Kelley%2C+M+J%3BJohnson%2C+B+E&rft.aulast=Kelley&rft.aufirst=M&rft.date=1994-01-01&rft.volume=39&rft.issue=&rft.spage=93&rft.isbn=&rft.btitle=&rft.title=Advances+in+internal+medicine&rft.issn=00652822&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-04-22 N1 - Date created - 1994-04-22 N1 - Date revised - 2017-01-13 N1 - Gene symbol - APC; DCC; MCC; NF1; p53; ras N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pharmacogenetic phenotyping and genotyping. Present status and future potential. AN - 76412104; 8137598 AB - Enzymes that metabolise foreign compounds exhibit a large degree of interindividual variability in their levels of expression. In a number of instances this variability can be accounted for by null or variant alleles resulting from mutations in genes encoding these enzymes. Human variability in drug metabolism can be determined by biochemical and pharmacological assays. In cases where a genetic change has been characterised, polymerase chain reaction techniques have been developed to diagnose metabolism deficiencies. Genetic differences in certain foreign compound metabolising enzymes such as glutathione S-transferase M1, N-acetyltransferase 2 and CYP2D6 have been shown to be associated with risk for developing environmentally and occupationally based diseases such as cancer. Drug therapy can also be compromised by the existence of genetic deficiencies in a number of enzymes, including CYP2D6. It is anticipated that determination of an individual's drug metabolism capabilities by use of phenotyping and genotyping tests will allow for more rational and safe drug administration protocols. JF - Clinical pharmacokinetics AU - Gonzalez, F J AU - Idle, J R AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland. Y1 - 1994/01// PY - 1994 DA - January 1994 SP - 59 EP - 70 VL - 26 IS - 1 SN - 0312-5963, 0312-5963 KW - Enzymes KW - 0 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Index Medicus KW - Phenotype KW - Genotype KW - Polymorphism, Genetic KW - Humans KW - Biotransformation -- genetics KW - Cytochrome P-450 Enzyme System -- genetics KW - Cytochrome P-450 Enzyme System -- physiology KW - Enzymes -- physiology KW - Cytochrome P-450 Enzyme System -- classification KW - Enzymes -- genetics KW - Enzymes -- classification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76412104?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+pharmacokinetics&rft.atitle=Pharmacogenetic+phenotyping+and+genotyping.+Present+status+and+future+potential.&rft.au=Gonzalez%2C+F+J%3BIdle%2C+J+R&rft.aulast=Gonzalez&rft.aufirst=F&rft.date=1994-01-01&rft.volume=26&rft.issue=1&rft.spage=59&rft.isbn=&rft.btitle=&rft.title=Clinical+pharmacokinetics&rft.issn=03125963&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-04-26 N1 - Date created - 1994-04-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Translational maintenance of frame: mutants of Saccharomyces cerevisiae with altered -1 ribosomal frameshifting efficiencies. AN - 76409165; 8138178 AB - A special site on the (+) strand of the L-A dsRNA virus induces about 2% of ribosomes translating the gag open reading frame to execute a -1 frameshift and thus produce the viral gag-pol fusion protein. Using constructs in which a -1 ribosomal frameshift at this site was necessary for expression of lacZ we isolated chromosomal mutants in which the efficiency of frameshifting was increased. These mutants comprise eight genes, named mof (maintenance of frame). The mof1-1, mof2-1, mof4-1, mof5-1 and mof6-1 strains cannot maintain M1 dsRNA at 30 degrees, but, paradoxically, do not lose L-A. The mof2-1, mof5-1 and mof6-1 strains are temperature sensitive for growth at 37 degrees, and all three show striking cell cycle phenotypes. The mof2-1 strains arrest with mother and daughter cells almost equal in size, mof5-1 arrests with multiple buds and mof6-1 arrests as single large unbudded cells. mof2-1 and mof5-1 strains are also Pet-. The mof mutations show differential effects on various frameshifting signals. JF - Genetics AU - Dinman, J D AU - Wickner, R B AD - Laboratory of Biochemical Pharmacology, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/01// PY - 1994 DA - January 1994 SP - 75 EP - 86 VL - 136 IS - 1 SN - 0016-6731, 0016-6731 KW - gag KW - lacZ KW - mof KW - mof1-1 KW - mof2-1 KW - mof4-1 KW - mof5-1 KW - mof6-1 KW - RNA, Double-Stranded KW - 0 KW - beta-Galactosidase KW - EC 3.2.1.23 KW - Index Medicus KW - RNA, Double-Stranded -- genetics KW - Open Reading Frames KW - Escherichia coli -- genetics KW - RNA Viruses -- genetics KW - Plasmids KW - RNA, Double-Stranded -- metabolism KW - Mutagenesis KW - Genotype KW - Phenotype KW - Base Sequence KW - RNA Viruses -- metabolism KW - beta-Galactosidase -- metabolism KW - Meiosis KW - Genetic Complementation Test KW - beta-Galactosidase -- biosynthesis KW - Genes, gag KW - Saccharomyces cerevisiae -- genetics KW - Frameshift Mutation KW - Ribosomes -- metabolism KW - Protein Biosynthesis KW - Saccharomyces cerevisiae -- metabolism KW - Genes, Fungal UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76409165?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Translational+maintenance+of+frame%3A+mutants+of+Saccharomyces+cerevisiae+with+altered+-1+ribosomal+frameshifting+efficiencies.&rft.au=Dinman%2C+J+D%3BWickner%2C+R+B&rft.aulast=Dinman&rft.aufirst=J&rft.date=1994-01-01&rft.volume=53&rft.issue=6&rft.spage=968&rft.isbn=&rft.btitle=&rft.title=International+journal+of+cancer&rft.issn=00207136&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-04-25 N1 - Date created - 1994-04-25 N1 - Date revised - 2017-01-13 N1 - Gene symbol - gag; lacZ; mof; mof1-1; mof2-1; mof4-1; mof5-1; mof6-1 N1 - SuppNotes - Cited By: Yeast. 1993 Mar;9(3):251-66 [8488726] J Virol. 1993 May;67(5):2764-71 [8474174] J Biol Chem. 1977 Dec 25;252(24):9010-7 [336627] Proc Natl Acad Sci U S A. 1978 Sep;75(9):4224-8 [360211] Genetics. 1980 Aug;95(4):855-79 [7009319] Genetics. 1981 Aug;98(4):691-711 [7037537] J Bacteriol. 1983 Jan;153(1):163-8 [6336730] Methods Enzymol. 1983;101:181-91 [6310321] Anal Biochem. 1983 Jul 1;132(1):6-13 [6312838] Mol Cell Biol. 1984 Apr;4(4):761-70 [6371496] Proc Natl Acad Sci U S A. 1984 Apr;81(7):1991-5 [6326095] Mol Cell Biol. 1986 May;6(5):1552-61 [3537705] Mol Cell Biol. 1987 Jan;7(1):177-84 [3031456] J Virol. 1988 Apr;62(4):1278-85 [3279233] Mol Cell Biol. 1988 Feb;8(2):938-44 [3280972] Proc Natl Acad Sci U S A. 1988 Jun;85(12):4411-5 [3288994] Cell. 1988 Nov 4;55(3):447-58 [2846182] Cell. 1988 Nov 18;55(4):663-71 [2460245] Yeast. 1988 Sep;4(3):159-78 [3059716] Cell. 1989 May 19;57(4):537-47 [2720781] Genetics. 1989 May;122(1):19-27 [2659436] J Biol Chem. 1989 Aug 15;264(23):13373-6 [2547758] Genetics. 1990 Mar;124(3):515-22 [2179051] Cell. 1990 Jul 27;62(2):339-52 [2164889] Curr Top Microbiol Immunol. 1990;157:93-124 [2168307] Proc Natl Acad Sci U S A. 1990 Nov;87(21):8360-4 [2172984] Proc Natl Acad Sci U S A. 1991 Jan 1;88(1):174-8 [1986362] Methods Enzymol. 1991;194:273-81 [2005792] J Biol Chem. 1992 Feb 5;267(4):2708-13 [1733966] Proc Natl Acad Sci U S A. 1992 Mar 15;89(6):2185-9 [1549580] Adv Virus Res. 1992;41:193-239 [1575083] Annu Rev Genet. 1991;25:201-28 [1812806] J Virol. 1992 Jun;66(6):3669-76 [1583726] Proc Natl Acad Sci U S A. 1992 Sep 15;89(18):8636-40 [1528874] J Mol Biol. 1992 Sep 20;227(2):463-79 [1404364] Nature. 1992 Oct 22;359(6397):746-9 [1436038] Genetics. 1976 Mar 25;82(3):429-42 [773743] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ouabain enhances the mitogenic effect of serum in vascular smooth muscle cells. AN - 76404591; 8136113 AB - Recently ouabain has been shown to induce transcription of proto-oncogenes in different cell types. In the present study, we examined the effect of ouabain on the proliferation of cultured vascular smooth muscle cells (VSMCs). Primary aortic VSMCs of spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats, and the rat VSMC cell line A10, were used. Different concentrations of ouabain (10(-9) to 10(-5) mol/L) were added to either quiescent or proliferating cells, and the cell number, the rate of thymidine incorporation into DNA, and the transcription of c-fos and c-myc were examined. The addition of ouabain to proliferating VSMC increased the rate of thymidine incorporation into DNA in a dose-dependent manner, and induced the transcription of the proto-oncogenes within 1 h. This latter response disappeared after 24 h. The number of cells significantly increased in response to low concentrations of ouabain (10(-8) to 10(-7) mol/L), but gradually decreased in response to higher concentrations of the agent, probably due to a toxic effect. Addition of ouabain to quiescent cells, in medium without serum, did not promote cell growth by any of the parameters examined. According to a current theory, endogenous digitalis-like substances possess natriuretic and hypertensive properties, and provide the link between an excessive intake of salt and high blood pressure. The mitogenic effect of ouabain on VSMCs may be a component of this hypertensive action. JF - American journal of hypertension AU - Golomb, E AU - Hill, M R AU - Brown, R G AU - Keiser, H R AD - Hypertension-Endocrine Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/01// PY - 1994 DA - January 1994 SP - 69 EP - 74 VL - 7 IS - 1 SN - 0895-7061, 0895-7061 KW - Culture Media, Serum-Free KW - 0 KW - Mitogens KW - Ouabain KW - 5ACL011P69 KW - DNA KW - 9007-49-2 KW - Thymidine KW - VC2W18DGKR KW - Index Medicus KW - Animals KW - Transcription, Genetic -- drug effects KW - Rats, Inbred WKY KW - Rats, Inbred SHR KW - Cell Division -- drug effects KW - Cell Death -- drug effects KW - DNA -- biosynthesis KW - Thymidine -- metabolism KW - Rats KW - Polymerase Chain Reaction KW - Base Sequence KW - Molecular Sequence Data KW - Cell Line KW - Male KW - Proto-Oncogenes -- drug effects KW - Mitogens -- pharmacology KW - Muscle, Smooth, Vascular -- drug effects KW - Muscle, Smooth, Vascular -- cytology KW - Muscle, Smooth, Vascular -- metabolism KW - Ouabain -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76404591?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+hypertension&rft.atitle=Ouabain+enhances+the+mitogenic+effect+of+serum+in+vascular+smooth+muscle+cells.&rft.au=Golomb%2C+E%3BHill%2C+M+R%3BBrown%2C+R+G%3BKeiser%2C+H+R&rft.aulast=Golomb&rft.aufirst=E&rft.date=1994-01-01&rft.volume=7&rft.issue=1&rft.spage=69&rft.isbn=&rft.btitle=&rft.title=American+journal+of+hypertension&rft.issn=08957061&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-04-26 N1 - Date created - 1994-04-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A biological method for examining the effect of codon changes in a conserved region of DNA polymerase. AN - 76402824; 8136125 AB - The vaccinia virus genome encodes a DNA polymerase that is similar to other DNA polymerases. A mutation in the polymerase gene at a site that is adjacent to conserved residues allows viral replication in the presence of aphidicolin. Since wild-type virus is converted to aphidicolin-resistance by site-directed mutagenesis, it was feasible that active virus with substituted conserved residues could be detected by linking alterations to the aphidicolin-resistance mutation. Altered DNA, from a PCR, was introduced into virus by a marker transfer procedure. DNA from plaques of drug-resistant virus was amplified, and the product was sequenced to check for the conserved residue alteration. An alteration that introduced a Bg1I site was designed to facilitate the selection of drug-resistant virus containing substituted residues. One positive result was the replacement of two amino acids, tyrosine and alanine, by tryptophan and threonine. The failure to substitute aspartic acid for tyrosine indicates that drastic changes of the conserved sequence are not tolerated. Although the limitations associated with negative results apply, the method provides an in vivo assay for selecting a polymerase with conserved residue changes. JF - BioTechniques AU - DeFilippes, F M AD - Laboratory of Viral Diseases, NIAID, National Institutes of Health, Bethesda, MD. Y1 - 1994/01// PY - 1994 DA - January 1994 SP - 122 EP - 127 VL - 16 IS - 1 SN - 0736-6205, 0736-6205 KW - Codon KW - 0 KW - Aphidicolin KW - 38966-21-1 KW - DNA-Directed DNA Polymerase KW - EC 2.7.7.7 KW - Index Medicus KW - Aphidicolin -- pharmacology KW - Base Sequence KW - Conserved Sequence KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Mutation KW - Structure-Activity Relationship KW - Vaccinia virus -- genetics KW - Vaccinia virus -- enzymology KW - DNA-Directed DNA Polymerase -- physiology KW - DNA-Directed DNA Polymerase -- genetics KW - DNA-Directed DNA Polymerase -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76402824?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+immunology&rft.atitle=Residues+in+pockets+B+and+F+of+HLA-B27+are+critical+in+the+presentation+of+an+influenza+A+virus+nucleoprotein+peptide+and+influence+the+stability+of+peptide+-+MHC+complexes.&rft.au=Carreno%2C+B+M%3BWinter%2C+C+C%3BTaurog%2C+J+D%3BHansen%2C+T+H%3BBiddison%2C+W+E&rft.aulast=Carreno&rft.aufirst=B&rft.date=1993-04-01&rft.volume=5&rft.issue=4&rft.spage=353&rft.isbn=&rft.btitle=&rft.title=International+immunology&rft.issn=09538178&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-04-28 N1 - Date created - 1994-04-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Disposition of heroin and its metabolites in heroin-related deaths. AN - 76397197; 8127080 AB - Although many deaths occur annually from heroin intoxication, the presence of heroin has not been reported in postmortem tissues. Recognizing heroin's susceptibility to rapid chemical and metabolic hydrolysis, extraction procedures were developed for the efficient recovery of heroin, 6-acetylmorphine, and morphine from postmortem tissue utilizing solid-phase extraction coupled with gas chromatography/mass spectrometry. From heroin-related deaths, 21 sets of blood and urine specimens were collected. The mode of death in these cases was categorized as rapid, delayed, or undetermined. Compared with delayed deaths, rapid deaths were characterized by the following trends: higher mean concentrations of 6-acetylmorphine, free morphine, and total opiates in blood; a higher ratio of free morphine concentrations to total opiate concentrations in blood; lower mean concentrations of 6-acetylmorphine and morphine in urine; greater likelihood of 6-acetylmorphine detection in blood; and lesser likelihood of heroin detection in urine. The study also included analysis of multiple tissue specimens from two subjects who died of heroin intoxication. Heroin was identified in urine and injection-site tissue. Concentrations of 6-acetylmorphine in cerebrospinal fluid, spleen, and brain were substantially higher than in blood, liver, lung, and kidney. All specimens were positive for morphine. Heroin metabolites were detected in hair specimens. The identification of heroin and 6-acetylmorphine in biological tissues effectively established the presence of heroin in cases of acute narcotic intoxication. These studies demonstrated that measurement of heroin and its metabolites provides useful information for the differential diagnosis of heroin-related deaths. JF - Journal of analytical toxicology AU - Goldberger, B A AU - Cone, E J AU - Grant, T M AU - Caplan, Y H AU - Levine, B S AU - Smialek, J E AD - Addiction Research Center, National Institute on Drug Abuse, Baltimore, MD 21224. PY - 1994 SP - 22 EP - 28 VL - 18 IS - 1 SN - 0146-4760, 0146-4760 KW - Morphine Derivatives KW - 0 KW - Heroin KW - 70D95007SX KW - Morphine KW - 76I7G6D29C KW - 6-O-monoacetylmorphine KW - M5E47P1ZCH KW - Index Medicus KW - Prospective Studies KW - Humans KW - Hair -- chemistry KW - Retrospective Studies KW - Morphine -- analysis KW - Gas Chromatography-Mass Spectrometry KW - Drug Overdose -- metabolism KW - Morphine Derivatives -- analysis KW - Heroin -- poisoning KW - Heroin -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76397197?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+analytical+toxicology&rft.atitle=Disposition+of+heroin+and+its+metabolites+in+heroin-related+deaths.&rft.au=Goldberger%2C+B+A%3BCone%2C+E+J%3BGrant%2C+T+M%3BCaplan%2C+Y+H%3BLevine%2C+B+S%3BSmialek%2C+J+E&rft.aulast=Goldberger&rft.aufirst=B&rft.date=1994-01-01&rft.volume=18&rft.issue=1&rft.spage=22&rft.isbn=&rft.btitle=&rft.title=Journal+of+analytical+toxicology&rft.issn=01464760&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-04-12 N1 - Date created - 1994-04-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Development of human lymphocyte-engrafted SCID mice as a model for immunotoxicity assessment. AN - 76386358; 8125206 AB - Mice with the severe combined immunodeficient (SCID) and triple-deficient (bg/nu/xid) mutations lack select populations of functional immune cells. Studies by several laboratories have demonstrated the ability to restore certain missing immune components in these mice by reconstituting with various lymphoid tissues including peripheral blood lymphocytes (PBL) from mice and humans. Such a model could provide an opportunity to examine human lymphoid cells in an in vivo environment for immunotoxicity assessment. In the present studies, bg/nu/xid and SCID mice were reconstituted by intraperitoneal or intravenous injection with either tetanus-immunized syngeneic mouse splenocytes (mo-SPL) or tetanus-immunized human PBLs (hu-PBL) under various test conditions. Hu-PBL-SCID mice from the C.B-17 strain produced more successful human engraftments than mice from the bg/nu/xid or C3H-SCID strains. Using optimal conditions, mo-SPL-SCID and hu-PBL-SCID mice were engrafted and administered either 2,3,7,8-tetrachlorodibenzo-p-dioxin or cyclosporin A (Cys A) and periodically bled to measure tetanus-specific antibody and class-specific immunoglobulin concentrations. Comparison of the chemical-related changes in immunoglobulin and tetanus antibody concentrations revealed some similarities between control mice and mo-SPL-SCID or hu-PBL-SCID mice, particularly with Cys A groups. However, under the various conditions examined, hu-PBL-SCID mice demonstrated considerable variability in their ability to provide consistent reconstitution, thus, limiting the ability to determine whether human cells are more or less susceptible than mouse cells to the test agents. Provided that this system can be refined to provide consistent reconstitution, hu-PBL-SCID mice may be a promising in vivo model for assessment of potential immunotoxic agents. JF - Fundamental and applied toxicology : official journal of the Society of Toxicology AU - Pollock, P L AU - Germolec, D R AU - Comment, C E AU - Rosenthal, G J AU - Luster, M I AD - Environmental Immunology and Neurobiology Section, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1994/01// PY - 1994 DA - January 1994 SP - 130 EP - 138 VL - 22 IS - 1 SN - 0272-0590, 0272-0590 KW - Polychlorinated Dibenzodioxins KW - 0 KW - Cyclosporine KW - 83HN0GTJ6D KW - Index Medicus KW - Mice, Inbred Strains KW - Animals KW - Spleen -- cytology KW - Lymphocyte Transfusion KW - Humans KW - Enzyme-Linked Immunosorbent Assay KW - Mice KW - Mice, Inbred BALB C KW - Cell Transplantation KW - Male KW - Female KW - Antibody Formation -- drug effects KW - Lymphocytes -- immunology KW - Mice, SCID -- immunology KW - Polychlorinated Dibenzodioxins -- toxicity KW - Cyclosporine -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76386358?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.atitle=Development+of+human+lymphocyte-engrafted+SCID+mice+as+a+model+for+immunotoxicity+assessment.&rft.au=Pollock%2C+P+L%3BGermolec%2C+D+R%3BComment%2C+C+E%3BRosenthal%2C+G+J%3BLuster%2C+M+I&rft.aulast=Pollock&rft.aufirst=P&rft.date=1994-01-01&rft.volume=22&rft.issue=1&rft.spage=130&rft.isbn=&rft.btitle=&rft.title=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.issn=02720590&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-04-14 N1 - Date created - 1994-04-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chemopreventive drug development: perspectives and progress. AN - 76380823; 8118391 AB - Chemoprevention drug development has the goal of identifying safe and effective chemopreventive agents for clinical use. Several distinctive strategies are pursued in developing chemopreventive agents: (a) identifying and validating predysplastic and early dysplastic lesions that can be used instead of cancers as endpoints for measuring chemopreventive activity; (b) identifying and testing candidate agents based on considerations of mechanisms of action; (c) evaluating combinations of agents with potential for maximizing efficacy and minimizing toxicity; and (d) applying a systematic methodology for identifying and ranking candidate agents at each stage of development to ensure discovery of the best agents and most effective use of available resources. This article discusses 22 drugs and three drug combinations which have reached an advanced stage of development as chemopreventive agents. The first generation of drugs are the most advanced, now being in Phase II and Phase III clinical trials. These drugs include several retinoids [vitamin A, 13-cis-retinoic acid, all-trans-N-(4-hydroxyphenyl)retinamide], calcium, beta-carotene, tamoxifen, and finasteride. The second generation drugs are those in Phase I clinical trials. From most to least advanced, these drugs are 2-difluoromethylornithine, sulindac, piroxicam, oltipraz, N-acetyl-I-cysteine, aspirin, ibuprofen, carbenoxolone, 18 beta-glycyrrhetinic acid, and the combination of 2-difluoromethylornithine with piroxicam. The third generation includes agents with significant evidence of chemopreventive activity in animal models. These agents are now in preclinical toxicity testing. They are S-allyl-I-cysteine, phenhexyl isothiocyanate, curcumin, ellagic acid, fumaric acid, fluasterone, and the combinations of all-trans-N-(4-hydroxyphenyl)retinamide with oltipraz and all-trans-N-(4-hydroxyphenyl) retinamide with tamoxifen. JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology AU - Kelloff, G J AU - Boone, C W AU - Crowell, J A AU - Steele, V E AU - Lubet, R AU - Sigman, C C AD - Chemoprevention Investigational Studies Branch, National Cancer Institute, Bethesda, Maryland 20892. PY - 1994 SP - 85 EP - 98 VL - 3 IS - 1 SN - 1055-9965, 1055-9965 KW - Index Medicus KW - Animals KW - Clinical Trials as Topic KW - Forecasting KW - Research KW - Neoplasms, Experimental -- prevention & control KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76380823?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+epidemiology%2C+biomarkers+%26+prevention+%3A+a+publication+of+the+American+Association+for+Cancer+Research%2C+cosponsored+by+the+American+Society+of+Preventive+Oncology&rft.atitle=Chemopreventive+drug+development%3A+perspectives+and+progress.&rft.au=Kelloff%2C+G+J%3BBoone%2C+C+W%3BCrowell%2C+J+A%3BSteele%2C+V+E%3BLubet%2C+R%3BSigman%2C+C+C&rft.aulast=Kelloff&rft.aufirst=G&rft.date=1994-01-01&rft.volume=3&rft.issue=1&rft.spage=85&rft.isbn=&rft.btitle=&rft.title=Cancer+epidemiology%2C+biomarkers+%26+prevention+%3A+a+publication+of+the+American+Association+for+Cancer+Research%2C+cosponsored+by+the+American+Society+of+Preventive+Oncology&rft.issn=10559965&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-04-04 N1 - Date created - 1994-04-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of three features of a job-exposure matrix on risk estimates. AN - 76377298; 8117771 AB - We tested the impact of three features of a job-exposure matrix on risk estimates in a case-control study that evaluated the association of methylene chloride and astrocytic brain cancer. These features were probability of use of the agent; the consideration of decade of predominant use of methylene chloride within each occupation; and the use of a more specific industrial-occupational coding system. We compared the risk estimates obtained with and without these features. The introduction of each feature had a striking effect on the estimate of relative risk. The odds ratio ranged from 1.47 with none of these features, to 2.47 with high probability of exposure within industry and occupation, to 4.15 with high probability of exposure and specific industrial-occupational coding, to 6.08 with the three features together. These results indicate that the degree of exposure misclassification can be reduced by the introduction of these features into the job-exposure matrix. JF - Epidemiology (Cambridge, Mass.) AU - Dosemeci, M AU - Cocco, P AU - Gómez, M AU - Stewart, P A AU - Heineman, E F AD - Occupational Studies Section, National Cancer Institute, Bethesda, MD 20892. Y1 - 1994/01// PY - 1994 DA - January 1994 SP - 124 EP - 127 VL - 5 IS - 1 SN - 1044-3983, 1044-3983 KW - Methylene Chloride KW - 588X2YUY0A KW - Index Medicus KW - Probability KW - Odds Ratio KW - Epidemiologic Methods KW - Risk Factors KW - Humans KW - Case-Control Studies KW - Astrocytoma -- epidemiology KW - Brain Neoplasms -- epidemiology KW - Methylene Chloride -- adverse effects KW - Occupational Exposure -- adverse effects KW - Occupational Diseases -- epidemiology KW - Occupational Diseases -- chemically induced KW - Astrocytoma -- chemically induced KW - Brain Neoplasms -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76377298?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Effects+of+three+features+of+a+job-exposure+matrix+on+risk+estimates.&rft.au=Dosemeci%2C+M%3BCocco%2C+P%3BG%C3%B3mez%2C+M%3BStewart%2C+P+A%3BHeineman%2C+E+F&rft.aulast=Dosemeci&rft.aufirst=M&rft.date=1994-01-01&rft.volume=5&rft.issue=1&rft.spage=124&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 - 1994-04-07 N1 - Date created - 1994-04-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interictal autonomic nervous system function in patients with epilepsy. AN - 76360200; 8112246 AB - We studied 24 patients with partial seizures receiving carbamazepine (CBZ) monotherapy and 40 normal controls, 17 of whom were tested with and without CBZ therapy. Autonomic nervous system assessment included baseline heart rate (HR) and blood pressure (BP); BP and HR changes during orthostasis and cold pressor test (CPT); and HR changes during sinus arrhythmia, Valsalva maneuver, and cold face test with apnea (CFTA). Our study demonstrated normal interictal autonomic function in patients with epilepsy, but, variations in BP and HR during orthostasis and CPT were significantly (p < 0.05) higher in epilepsy patients than in controls with or without CBZ. Epilepsy patients had higher initial increases in BP and greater subsequent decreases in BP than did nonmedicated controls during CPT. Controls with CBZ had higher HR during orthostasis and CFTA than did those without CBZ. CBZ levels correlated with baseline and orthostatic BP and HR during deep breathing (sinus arrhythmia). Our results showed that patients with epilepsy have greater BP and HR variability and reactivity than controls, attributable in part to CBZ levels. JF - Epilepsia AU - Devinsky, O AU - Perrine, K AU - Theodore, W H AD - Clinical Epilepsy Section, NINDS, NIH, Bethesda, Maryland. PY - 1994 SP - 199 EP - 204 VL - 35 IS - 1 SN - 0013-9580, 0013-9580 KW - Carbamazepine KW - 33CM23913M KW - Index Medicus KW - Arrhythmia, Sinus -- etiology KW - Heart Rate -- drug effects KW - Humans KW - Adult KW - Valsalva Maneuver KW - Middle Aged KW - Cold Temperature KW - Blood Pressure -- drug effects KW - Adolescent KW - Male KW - Female KW - Carbamazepine -- adverse effects KW - Autonomic Nervous System -- drug effects KW - Epilepsies, Partial -- drug therapy KW - Electroencephalography KW - Carbamazepine -- pharmacology KW - Autonomic Nervous System -- physiology KW - Carbamazepine -- therapeutic use KW - Epilepsies, Partial -- diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76360200?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Epilepsia&rft.atitle=Interictal+autonomic+nervous+system+function+in+patients+with+epilepsy.&rft.au=Devinsky%2C+O%3BPerrine%2C+K%3BTheodore%2C+W+H&rft.aulast=Devinsky&rft.aufirst=O&rft.date=1994-01-01&rft.volume=35&rft.issue=1&rft.spage=199&rft.isbn=&rft.btitle=&rft.title=Epilepsia&rft.issn=00139580&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-03-25 N1 - Date created - 1994-03-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Residual EDTA bound by lens crystallins accounts for their reported resistance to copper-catalyzed oxidative damage. AN - 76350032; 8311454 AB - It was recently reported that the structural proteins of the lens, the crystallins, possess unusual resistance to oxidative damage from a copper-catalyzed Fenton system. Data presented here demonstrate that this phenomenon is specific to copper-catalyzed systems and is not observed when iron is the metal catalyst. Further investigation has revealed that the apparent resistance to copper-catalyzed oxidation results from the presence of residual EDTA associated with the proteins. EDTA chelates the copper, inactivating it as a redox catalyst. This binding of EDTA to crystallins (or other proteins) occurs when the proteins present in EDTA-containing buffers are dialyzed directly against deionized water. Partial characterization of the association between EDTA and proteins is presented and its potential significance as a confounding factor in studies of the effects of metal-catalyzed oxidation on proteins is discussed. JF - Archives of biochemistry and biophysics AU - Cui, X L AU - Qin, C AU - Zigler, J S AD - Laboratory of Mechanisms of Ocular Diseases, National Eye Institute, Bethesda, Maryland 20892. Y1 - 1994/01// PY - 1994 DA - January 1994 SP - 207 EP - 213 VL - 308 IS - 1 SN - 0003-9861, 0003-9861 KW - Crystallins KW - 0 KW - Fenton's reagent KW - Serum Albumin, Bovine KW - Tissue Extracts KW - Copper KW - 789U1901C5 KW - Edetic Acid KW - 9G34HU7RV0 KW - Hydrogen Peroxide KW - BBX060AN9V KW - Iron KW - E1UOL152H7 KW - Alcohol Dehydrogenase KW - EC 1.1.1.1 KW - Copper Sulfate KW - LRX7AJ16DT KW - Index Medicus KW - Oxidation-Reduction KW - Alcohol Dehydrogenase -- drug effects KW - Animals KW - Cattle KW - Lens, Crystalline -- drug effects KW - Hydrogen Peroxide -- pharmacology KW - Serum Albumin, Bovine -- drug effects KW - Alcohol Dehydrogenase -- chemistry KW - Crystallins -- drug effects KW - Crystallins -- chemistry KW - Edetic Acid -- metabolism KW - Copper -- pharmacology KW - Copper -- toxicity KW - Crystallins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76350032?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Residual+EDTA+bound+by+lens+crystallins+accounts+for+their+reported+resistance+to+copper-catalyzed+oxidative+damage.&rft.au=Cui%2C+X+L%3BQin%2C+C%3BZigler%2C+J+S&rft.aulast=Cui&rft.aufirst=X&rft.date=1994-01-01&rft.volume=308&rft.issue=1&rft.spage=207&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 - 1994-03-15 N1 - Date created - 1994-03-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Suicidality and 5-hydroxyindoleacetic acid concentration associated with a tryptophan hydroxylase polymorphism. AN - 76333390; 7506517 AB - To examine whether the tryptophan hydroxylase (TPH) gene, which codes for the rate-limiting enzyme in the biosynthesis of serotonin, may be a factor influencing serotonin turnover and behaviors controlled by serotonin. Using a polymerase chain reaction-based method, TPH genotype was determined in DNA samples from 56 impulsive and 14 nonimpulsive, alcoholic, violent offenders and 20 healthy volunteers. In the behaviorally extreme impulsive group, we observed a significant association between TPH genotype and cerebrospinal fluid 5-hydroxyindoleacetic acid (5-HIAA) concentration. No association of TPH genotype with impulsive behavior was detected. The polymorphism was also associated with a history of suicide attempts in all violent offenders, independent of impulsivity status and cerebrospinal fluid 5-HIAA concentration. In some individuals, a genetic variant of the TPH gene may influence 5-HIAA concentration in the cerebrospinal fluid and predisposition to suicidal behavior. JF - Archives of general psychiatry AU - Nielsen, D A AU - Goldman, D AU - Virkkunen, M AU - Tokola, R AU - Rawlings, R AU - Linnoila, M AD - Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Md. Y1 - 1994/01// PY - 1994 DA - January 1994 SP - 34 EP - 38 VL - 51 IS - 1 SN - 0003-990X, 0003-990X KW - Serotonin KW - 333DO1RDJY KW - Hydroxyindoleacetic Acid KW - 54-16-0 KW - Tryptophan Hydroxylase KW - EC 1.14.16.4 KW - Abridged Index Medicus KW - Index Medicus KW - Disruptive, Impulse Control, and Conduct Disorders -- genetics KW - Serotonin -- physiology KW - Serotonin -- biosynthesis KW - Suicide, Attempted -- psychology KW - Polymorphism, Genetic KW - Humans KW - Alcoholism -- metabolism KW - Disruptive, Impulse Control, and Conduct Disorders -- metabolism KW - Alcoholism -- genetics KW - Violence KW - Genotype KW - Polymerase Chain Reaction KW - Disruptive, Impulse Control, and Conduct Disorders -- cerebrospinal fluid KW - Suicide, Attempted -- statistics & numerical data KW - Antisocial Personality Disorder -- cerebrospinal fluid KW - Adult KW - Alcoholism -- cerebrospinal fluid KW - Antisocial Personality Disorder -- genetics KW - Serotonin -- metabolism KW - Antisocial Personality Disorder -- metabolism KW - Male KW - Tryptophan Hydroxylase -- genetics KW - Hydroxyindoleacetic Acid -- cerebrospinal fluid KW - Suicide -- statistics & numerical data KW - Suicide -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76333390?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+general+psychiatry&rft.atitle=Suicidality+and+5-hydroxyindoleacetic+acid+concentration+associated+with+a+tryptophan+hydroxylase+polymorphism.&rft.au=Nielsen%2C+D+A%3BGoldman%2C+D%3BVirkkunen%2C+M%3BTokola%2C+R%3BRawlings%2C+R%3BLinnoila%2C+M&rft.aulast=Nielsen&rft.aufirst=D&rft.date=1994-01-01&rft.volume=51&rft.issue=1&rft.spage=34&rft.isbn=&rft.btitle=&rft.title=Archives+of+general+psychiatry&rft.issn=0003990X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-02-07 N1 - Date created - 1994-02-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - 12-O-tetradecanoylphorbol 13-acetate stimulates human T-lymphocyte adherence to the fibronectin RGD domain and the laminin IKVAV domain. AN - 76333032; 8287495 AB - In order for T cells to exit the circulatory system, these cells must attach to extracellular matrix proteins. We have used 12-O-tetradecanoylphorbol 13-acetate (TPA) to study the ability of human T cells to adhere to fibronectin or laminin or to specific domains on these extracellular matrix proteins. Both primary human T-lymphocytes and a T-cell line (H-9) adhered and spread well on solid-phase fibronectin and laminin in the presence of TPA, with maximum activity at 3 hr of treatment. Furthermore, attachment of both cell populations to fibronectin was inhibited using a soluble RGD-containing synthetic peptide or by pretreating the fibronectin with antibodies that block the RGD domain. A synthetic peptide from the CSI alternatively spliced region of fibronectin did not inhibit attachment to fibronectin. The H-9 cells also attached to the laminin A chain IKVAV-containing synthetic peptide, but not to the laminin-derived YIGSR- or RGD-containing sequences. Immunoprecipitation of 32P-labeled H-9 cells with antibodies to the beta 1 integrin subunit demonstrated phosphorylation of an alpha integrin subunit after treatment with TPA. These data demonstrate that TPA activates T-cell adherence to laminin and to fibronectin via specific sites on each protein and that this adhesion may be associated with integrin phosphorylation. JF - Cellular immunology AU - Weeks, B S AU - Holloway, E AU - Klotman, P E AU - Akiyama, S K AU - Schnaper, H W AU - Kleinman, H K AD - Laboratory of Developmental Biology, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/01// PY - 1994 DA - January 1994 SP - 94 EP - 104 VL - 153 IS - 1 SN - 0008-8749, 0008-8749 KW - Fibronectins KW - 0 KW - Integrins KW - Laminin KW - Oligopeptides KW - Peptides KW - arginyl-glycyl-aspartic acid KW - 78VO7F77PN KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Space life sciences KW - Extracellular Matrix -- metabolism KW - Phosphorylation KW - Humans KW - In Vitro Techniques KW - Molecular Sequence Data KW - Peptides -- metabolism KW - Peptides -- chemistry KW - Amino Acid Sequence KW - Protein Binding KW - Laminin -- chemistry KW - Fibronectins -- chemistry KW - T-Lymphocytes -- cytology KW - Laminin -- metabolism KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Fibronectins -- metabolism KW - Cell Adhesion -- drug effects KW - Integrins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76333032?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cellular+immunology&rft.atitle=12-O-tetradecanoylphorbol+13-acetate+stimulates+human+T-lymphocyte+adherence+to+the+fibronectin+RGD+domain+and+the+laminin+IKVAV+domain.&rft.au=Weeks%2C+B+S%3BHolloway%2C+E%3BKlotman%2C+P+E%3BAkiyama%2C+S+K%3BSchnaper%2C+H+W%3BKleinman%2C+H+K&rft.aulast=Weeks&rft.aufirst=B&rft.date=1994-01-01&rft.volume=100&rft.issue=&rft.spage=269&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 - 1994-02-22 N1 - Date created - 1994-02-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Alterations of tumor suppressor genes and allelic losses in human hepatocellular carcinomas in China. AN - 76326876; 7903205 AB - Aflatoxin B1 has been suggested as a causative agent for a G to T mutation at codon 249 in the p53 gene in human hepatocellular carcinomas (HCC) from southern Africa and Qidong in China. The objective of the present work was to test the hypothesis that exposure to aflatoxin B1 either alone or coincident with other environmental carcinogens might be associated with allelic losses occurring during development of human hepatocarcinogenesis in China. The HCCs were obtained from two different areas in China: Qidong, where exposure to hepatitis B virus (HBV) and aflatoxin B1 is high; and Beijing, where exposure to HBV is high but that of aflatoxin B1 is low. We analyzed the tumors for mutations in the p53 gene and loss of heterozygosity for the p53, Rb, and APC genes and at marker loci on chromosomes 4, 13, and 16. Frequencies of mutation, loss, and aberration (mutation and loss) of the p53 gene in 25 HCCs from Qidong were 60, 58, and 80%, respectively. The frequencies in 9 HCCs from Beijing were 56, 57, and 78%. However, the frequency of a G to T transversion at codon 249 in HCCs from Qidong and Beijing were 52 and 0%, respectively. These data indicate that mutation and/or loss of heterozygosity in the p53 gene, independent of the 249 mutation, play a critical role in the development of hepatitis B virus-associated HCCs in China. Loss of the Rb and APC genes was observed in 44 and 7% of HCCs from Qidong, respectively. Allelic losses on chromosome 4 and especially on chromosome 16 were frequent in HCCs from Qidong but were not observed in HCCs from Beijing, while loss of heterozygosity on chromosome 13 occurred at similar frequency in both Qidong and Beijing. These results show a distinct difference in the pattern of allelic losses between HCCs in Qidong and Beijing and suggest that aflatoxin B1 and/or other environmental carcinogens may contribute to this difference. JF - Cancer research AU - Fujimoto, Y AU - Hampton, L L AU - Wirth, P J AU - Wang, N J AU - Xie, J P AU - Thorgeirsson, S S AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1994/01/01/ PY - 1994 DA - 1994 Jan 01 SP - 281 EP - 285 VL - 54 IS - 1 SN - 0008-5472, 0008-5472 KW - Codon KW - 0 KW - Hepatitis B Antigens KW - Index Medicus KW - Chromosomes, Human, Pair 16 KW - Base Sequence KW - Codon -- genetics KW - Polymorphism, Restriction Fragment Length KW - Humans KW - Molecular Sequence Data KW - Hepatitis B Antigens -- analysis KW - Chromosomes, Human, Pair 13 KW - Chromosomes, Human, Pair 4 KW - China KW - Carcinoma, Hepatocellular -- genetics KW - Genes, p53 -- genetics KW - Genes, Retinoblastoma -- genetics KW - Genes, APC -- genetics KW - Carcinoma, Hepatocellular -- immunology KW - Liver Neoplasms -- immunology KW - Liver Neoplasms -- genetics KW - Gene Deletion UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76326876?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+tumor+suppressor+genes+and+allelic+losses+in+human+hepatocellular+carcinomas+in+China.&rft.au=Fujimoto%2C+Y%3BHampton%2C+L+L%3BWirth%2C+P+J%3BWang%2C+N+J%3BXie%2C+J+P%3BThorgeirsson%2C+S+S&rft.aulast=Fujimoto&rft.aufirst=Y&rft.date=1994-01-01&rft.volume=54&rft.issue=1&rft.spage=281&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 - 1994-01-21 N1 - Date created - 1994-01-21 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Cancer Res. 1994 Sep 15;54(18):5022-3 [8069870] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Low incidence of point mutations detected in the p53 tumor suppressor gene from chemically induced rat renal mesenchymal tumors. AN - 76325338; 8261441 AB - Previous studies have shown renal mesenchymal tumors (RMTs) induced in rats by a single intrarenal injection of nickel subsulfide and iron are more pleomorphic and metastatically aggressive than RMTs induced by a single ip injection of methyl(methoxymethyl)nitrosamine (DMN-OMe). While both RMT types contain high levels of K-ras activation, the specific mutational spectra within codon 12 of K-ras are quite different. Nickel subsulfide and iron-induced tumors exhibited codon 12 GGT-->GTT transversions exclusively, while DMN-OMe RMTs showed a wide array of codon 12 mutations, as well as mutations within codons 61 and 63 [K. G. Higinbotham, J. M. Rice, B. A. Diwan, K. S. Kasprzak, C. D. Reed, and A. O. Perantoni, Cancer Res., 52: 4747-4751, 1992; K. G. Higinbotham, J. M. Rice, and A. O. Perantoni, Mol. Carcinog., 5: 136-139, 1992]. In an effort to further correlate carcinogen-specific molecular events in renal tumors, we investigated the p53 tumor suppressor gene in RMTs induced by these two carcinogens for the presence of point mutations. The evolutionarily conserved portion of the coding region of the gene, including part of exon 4 through exon 10, was surveyed for point mutations utilizing single-strand conformation polymorphism and chemical cleavage of mismatches analyses. None (0 of 10) of the nickel subsulfide and iron-induced RMTs and only 1 of 10 DMN-OMe-induced tumors that were evaluated contained point mutations within this portion of the p53 gene. Direct sequencing of the one single-strand conformation polymorphism and chemical cleavage of mismatches-"positive" DMN-OMe-induced RMT revealed a GCC-->GTC (Ala-->Val) transition in codon 345 within exon 10. These results suggest that the different tumorigenic phenotypes exhibited by these two RMTs are not the result of specific mutations or patterns of mutations within the portion of the p53 gene examined and that the mutated p53 tumorigenic pathway, whereby p53 plays a major role in many human neoplasms, does not function in RMTs induced by either agent. JF - Cancer research AU - Weghorst, C M AU - Dragnev, K H AU - Buzard, G S AU - Thorne, K L AU - Vandeborne, G F AU - Vincent, K A AU - Rice, J M AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland 21702. Y1 - 1994/01/01/ PY - 1994 DA - 1994 Jan 01 SP - 215 EP - 219 VL - 54 IS - 1 SN - 0008-5472, 0008-5472 KW - DNA Primers KW - 0 KW - nickel sulfate KW - 4FLT4T3WUN KW - methyl(acetoxymethyl)nitrosamine KW - 56856-83-8 KW - Nickel KW - 7OV03QG267 KW - Dimethylnitrosamine KW - M43H21IO8R KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Base Sequence KW - Molecular Sequence Data KW - Dimethylnitrosamine -- analogs & derivatives KW - Sequence Analysis, DNA KW - Male KW - Kidney Neoplasms -- genetics KW - Genes, p53 -- drug effects KW - Kidney Neoplasms -- chemically induced KW - Genes, p53 -- genetics KW - Point Mutation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76325338?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Low+incidence+of+point+mutations+detected+in+the+p53+tumor+suppressor+gene+from+chemically+induced+rat+renal+mesenchymal+tumors.&rft.au=Weghorst%2C+C+M%3BDragnev%2C+K+H%3BBuzard%2C+G+S%3BThorne%2C+K+L%3BVandeborne%2C+G+F%3BVincent%2C+K+A%3BRice%2C+J+M&rft.aulast=Weghorst&rft.aufirst=C&rft.date=1994-01-01&rft.volume=54&rft.issue=1&rft.spage=215&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 - 1994-01-21 N1 - Date created - 1994-01-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Site-directed mutagenesis of adeno-associated virus type 2 structural protein initiation codons: effects on regulation of synthesis and biological activity. AN - 76324661; 8254726 AB - It has been shown that two of the three adeno-associated virus type 2 capsid proteins, B and C, are synthesized from a single spliced transcript. Protein C arises from an AUG codon at nucleotide 2810, whereas protein B is initiated by a unique eucaryotic initiation codon (ACG) that lies 65 triplets upstream from the C origin. The third capsid component, protein A, is synthesized from a second spliced transcript which uses an alternative 3' acceptor site. In this study we used oligonucleotide-directed mutagenesis to confirm the positions of the B initiation codon and the 3' acceptor sites for the alternatively spliced B/C and A protein messages. We also located definitively the protein A initiation codon, an AUG triplet mapping to nucleotide 2203. Mutagenesis of the B initiator permitted a direct test of the effect of increased B initiator strength on the translational efficiencies of the B and C proteins. It was found that conversion of the relatively inefficient protein B initiator (ACG) to an AUG enhanced the level of B synthesis while abolishing the synthesis of C from its downstream AUG initiator. Protein C synthesis thus depends on the strength of the B initiator, i.e., the relatively higher levels of C (approximately 20-fold greater than B) must result from frequent readthrough of the weak B initiator. Finally, we examined the abilities of mutants deficient in the synthesis of A, B, or C to produce infectious virions. We found that at least two of the structural proteins, B and C, are required for the production of infectious virions and that sequestration of single-stranded adeno-associated virus genomes from the pool of replicating DNA molecules does not occur in the absence of either of these proteins. JF - Journal of virology AU - Muralidhar, S AU - Becerra, S P AU - Rose, J A AD - Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892. Y1 - 1994/01// PY - 1994 DA - January 1994 SP - 170 EP - 176 VL - 68 IS - 1 SN - 0022-538X, 0022-538X KW - Codon KW - 0 KW - Viral Structural Proteins KW - Index Medicus KW - Virulence KW - Mutagenesis, Site-Directed KW - Blotting, Northern KW - Peptide Chain Initiation, Translational -- genetics KW - Blotting, Southern KW - RNA Splicing KW - Humans KW - Cell Line, Transformed KW - Fluorescent Antibody Technique KW - Dependovirus -- pathogenicity KW - Gene Expression Regulation, Viral KW - Capsid -- genetics KW - Dependovirus -- genetics KW - Transcription, Genetic KW - Viral Structural Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76324661?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Site-directed+mutagenesis+of+adeno-associated+virus+type+2+structural+protein+initiation+codons%3A+effects+on+regulation+of+synthesis+and+biological+activity.&rft.au=Muralidhar%2C+S%3BBecerra%2C+S+P%3BRose%2C+J+A&rft.aulast=Muralidhar&rft.aufirst=S&rft.date=1994-01-01&rft.volume=68&rft.issue=1&rft.spage=170&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 - 1994-01-13 N1 - Date created - 1994-01-13 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Biol Chem. 1987 Aug 25;262(24):11847-51 [3040720] Cell. 1988 Jan 29;52(2):185-95 [3277717] EMBO J. 1988 Jan;7(1):245-51 [2834203] J Virol. 1988 Jul;62(7):2508-11 [3373576] J Virol. 1988 Aug;62(8):2745-54 [2839699] J Virol. 1988 Sep;62(9):3356-63 [2841488] J Cell Biol. 1989 Feb;108(2):229-41 [2645293] Virology. 1989 Nov;173(1):120-8 [2554565] J Virol. 1984 Nov;52(2):591-7 [6092680] Proc Natl Acad Sci U S A. 1985 Jan;82(2):488-92 [3881765] J Virol. 1985 May;54(2):630-3 [3989914] Proc Natl Acad Sci U S A. 1985 Dec;82(23):7919-23 [2999784] J Virol. 1986 Sep;59(3):564-73 [2942705] Mol Cell Biol. 1985 Dec;5(12):3621-4 [3837850] Science. 1987 Feb 13;235(4790):766-71 [3544217] Virology. 1990 Dec;179(2):632-9 [2173256] Virology. 1991 Sep;184(1):310-8 [1651593] J Virol. 1971 Nov;8(5):766-70 [5132697] J Gen Virol. 1977 Jul;36(1):59-74 [886304] Proc Natl Acad Sci U S A. 1979 Mar;76(3):1373-6 [286319] Cell. 1980 Nov;22(1 Pt 1):231-42 [6253077] J Virol. 1980 Oct;36(1):79-92 [6255215] J Virol. 1981 Oct;40(1):241-7 [6270377] Eur J Biochem. 1981 Dec;121(1):147-54 [6173214] J Virol. 1983 May;46(2):523-9 [6302317] Virology. 1983 Apr 30;126(2):505-16 [6305001] Gene. 1983 Jul;23(1):65-73 [6352411] J Virol. 1984 Aug;51(2):329-39 [6086948] J Virol. 1984 Sep;51(3):611-9 [6088786] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The RB gene locates on chromosome 15 at band 15q13 in the Syrian hamster. AN - 76323260; 8404065 AB - The retinoblastoma susceptibility gene, which encodes a nuclear phosphoprotein (Rb), plays an important role in cell-cycle progression in both normal development and tumorigenesis. Using a Syrian hamster cDNA probe homologous to the human retinoblastoma gene (RB), we have localized the gene to chromosome band 15q13 by conventional in situ hybridization. JF - Cytogenetics and cell genetics AU - Satoh, H AU - Ebert, R AU - Wiseman, R W AU - Barrett, J C AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC. Y1 - 1994 PY - 1994 DA - 1994 SP - 127 EP - 129 VL - 65 IS - 1-2 SN - 0301-0171, 0301-0171 KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Animals KW - In Situ Hybridization KW - Base Sequence KW - Sequence Homology, Nucleic Acid KW - Cells, Cultured KW - Humans KW - Molecular Sequence Data KW - Mesocricetus KW - Cricetinae KW - Genes, Retinoblastoma KW - Chromosome Mapping UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76323260?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Carcinogenicity+of+1%2C3-butadiene.&rft.au=Melnick%2C+R+L%3BShackelford%2C+C+C%3BHuff%2C+J&rft.aulast=Melnick&rft.aufirst=R&rft.date=1993-04-01&rft.volume=100&rft.issue=&rft.spage=227&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 - 1993-11-22 N1 - Date created - 1993-11-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CPAPER T1 - Traditional Ideas, Economic Development and Nature: The Case of China T2 - International Sociological Association AN - 61737484; 94S28777 AB - In ancient China, many philosophers discussed the relationship between humans & nature. Today, the natural environment is recognized as the objective material base of human society's development. However, natural conditions are increasingly threatened in the People's Republic China. In recent years, industrial & rural economic development within the socialist market economy has brought serious environmental problems. It is concluded that, in present-day China, focus is on economic development, with nature viewed from an economic angle, & not in terms of quality of life. JF - International Sociological Association AU - Li, Guo Qing Y1 - 1994///0, PY - 1994 DA - 0, 1994 KW - environmental problems, People's Republic of China, economic development context KW - Peoples Republic of China KW - Natural Environment KW - Industrial Development KW - Economic Development KW - Environmental Protection KW - proceeding KW - 0715: social change and economic development; social change & economic development KW - 2656: environmental interactions; environmental interactions UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/61737484?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Asocabs&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=International+Sociological+Association&rft.atitle=Traditional+Ideas%2C+Economic+Development+and+Nature%3A+The+Case+of+China&rft.au=Li%2C+Guo+Qing&rft.aulast=Li&rft.aufirst=Guo&rft.date=1994-01-01&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=International+Sociological+Association&rft.issn=&rft_id=info:doi/ LA - English DB - Sociological Abstracts N1 - Date revised - 2009-03-10 N1 - Publication note - 1994 N1 - Last updated - 2016-09-28 ER - TY - JOUR T1 - Adenoviral vector-mediated gene transfer into sheep arteries using a double-balloon catheter AN - 19835758; 3649710 AB - The potential for catheter-based in vivo delivery of genetic material to the arterial wall is incompletely explored. We evaluated the level of recombinant protein production as well as the anatomic distribution and duration of gene expression following adenoviral vector-mediated gene transfer into sheep arteries via a double balloon catheter. Catheters were positioned in the carotid or femoral arteries of 20 sheep via a combined percutaneous and surgical approach, and virions infused over a 30-min period. Three days later, recombinant gene expression was identified in approximately 30% (range 0-80%) of the luminal endothelial cells within the targeted area of the artery. Persistent recombinant protein expression was identified histochemically for up to 4 weeks, although the number of positive cells decreased steadily. High levels of both beta -galactosidase ( beta -Gal) activity and protein (mean 20 mU and 44 ng per vessel) were measured in vessel extracts 3 days after gene transfer, again decreasing significantly over a 4-week period. Transgene expression was limited almost entirely to the intima and adventitia; adventitial gene transfer occurred virtually exclusively along the vasa vasorum. In comparison to previous studies of catheter-based gene transfer, adenoviral vectors delivered by double balloon catheter resulted in a particularly high efficiency of endothelial cell gene transfer. The efficiency and amount of recombinant gene expression achieved in this study suggest that catheter-based gene delivery may eventually be applicable to the treatment of focal human arterial disease. JF - Human Gene Therapy AU - Rome, J J AU - Shayani, V AU - Newman, K D AU - Farrell, S AU - Lee, Sung W AU - Virmani, R AU - Dichek, DA AD - Mol. Hematol. Branch, NHLBI, Build. 10 Rm. 7D-18, Bethesda, MD 20892, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 1249 EP - 1258 VL - 5 IS - 10 SN - 1043-0342, 1043-0342 KW - double-balloon catheter KW - sheep KW - gene transfer KW - adenovirus KW - arteries KW - expression vectors KW - Human Genome Abstracts; Medical and Pharmaceutical Biotechnology Abstracts 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/19835758?accountid=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=Adenoviral+vector-mediated+gene+transfer+into+sheep+arteries+using+a+double-balloon+catheter&rft.au=Rome%2C+J+J%3BShayani%2C+V%3BNewman%2C+K+D%3BFarrell%2C+S%3BLee%2C+Sung+W%3BVirmani%2C+R%3BDichek%2C+DA&rft.aulast=Rome&rft.aufirst=J&rft.date=1994-01-01&rft.volume=5&rft.issue=10&rft.spage=1249&rft.isbn=&rft.btitle=&rft.title=Human+Gene+Therapy&rft.issn=10430342&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2010-08-19 ER - TY - JOUR T1 - Rapid protection against human immunodeficiency virus type 1 (HIV-1) replication mediated by high efficiency non-retroviral delivery of genes interfering with HIV-1 tat and gag AN - 19818142; 3537115 AB - Efficient transduction of inhibitory genes is a critical requirement in the development of a gene therapy strategy against human immunodeficiency virus type 1 (HIV-1). Commonly used systems based on retrovirus-mediated gene delivery are characterized by low efficiency gene transfer into the target cell. Genes were transduced in the absence of cell selection into 60-90% of human CD4 super(+) cells by using a novel technique that allows high efficiency gene transfer mediated by adenoviruses coupled with DNA-polylysine complexes. Protection of these cells against HIV-1 acute infection was evaluated by transducing them with three different inhibitory genes which interfere with HIV-1 replication at separate levels (polymeric Tat activation response element [TAR] decoy, dominant-negative mutant of the gag gene and antisense sequences of the gag gene) and subsequent challenging with HIV-1. The polymeric TAR decoy inhibited HIV-1 replication over 95%. Both the dominant-negative mutant and the antisense sequence of the gag gene were less potent inhibitors than the polymeric-TAR decoy. Combinations of either polymeric-TAR with dominant-negative mutant or antisense of the gag gene synergistically enhanced the inhibitory effects of the single genes. These data suggest that the combination of a highly efficient transduction technique with effective HIV-1 inhibitory genes confers rapid protection against HIV-1 acute infection in vitro. JF - Gene Therapy AU - Lori, F AU - Lisziewicz, J AU - Smythe, J AU - Cara, A AU - Bunnag, T A AU - Curiel, D AU - Gallo, R C AD - Lab. Tumor Cell Biol., NCI/NIH, Bethesda, MD 20892, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 27 EP - 31 VL - 1 IS - 1 SN - 0969-7128, 0969-7128 KW - human immunodeficiency virus 1 KW - replication KW - protection KW - mediation KW - gene transfer KW - adenovirus KW - gene therapy KW - man KW - lymphocytes T KW - in vitro KW - Medical and Pharmaceutical Biotechnology Abstracts; Human Genome Abstracts; Virology & AIDS Abstracts KW - V 22002:AIDS: Molecular and in vitro aspects KW - W 30965:Miscellaneous, Reviews KW - W3 33055:Genetic engineering (general) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19818142?accountid=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=Gene+Therapy&rft.atitle=Rapid+protection+against+human+immunodeficiency+virus+type+1+%28HIV-1%29+replication+mediated+by+high+efficiency+non-retroviral+delivery+of+genes+interfering+with+HIV-1+tat+and+gag&rft.au=Lori%2C+F%3BLisziewicz%2C+J%3BSmythe%2C+J%3BCara%2C+A%3BBunnag%2C+T+A%3BCuriel%2C+D%3BGallo%2C+R+C&rft.aulast=Lori&rft.aufirst=F&rft.date=1994-01-01&rft.volume=1&rft.issue=1&rft.spage=27&rft.isbn=&rft.btitle=&rft.title=Gene+Therapy&rft.issn=09697128&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2010-08-19 ER - TY - JOUR T1 - Phenotypic correction of Fanconi anemia in human hematopoietic cells in a recombinant adeno-associated virus vector AN - 17013444; 3845727 AB - Fanconi anemia (FA) is a recessive inherited disease characterized by defective DNA repair. FA cells are hypersensitive to DNA cross-linking agents that cause chromosomal instability and cell death. FA is manifested clinically by progressive pancytopenia, variable physical anomalies, and predisposition to malignancy. Four complementation groups have been identified, termed A, B, C, and D. The gene for the FA complementation group C, FACC, has been cloned. Expression of the FACC cDNA corrects the phenotypic defect of FA (C) cells, resulting in normalized cell growth in the presence of DNA cross-linking agents such as mitomycin C (MMC). Gene transfer of the FACC gene should provide a survival advantage to transduced hematopoietic cells, suggesting that FA might be an ideal candidate for gene therapy. We demonstrated efficient transduction, expression, and phenotypic correction in lymphoblastoid cell lines derived from FA (C) patients using a recombinant adeno-associated virus (rAAV) vector containing the FACC gene. Molecular characterization of the transduced FACC gene showed an intact unrearranged proviral genome with expression sufficient to normalize cell growth, cell cycle kinetics and chromosomal breakage in the presence of MMC. These observations were extended by testing rAAV transduction in hematopoietic progenitor cells. Peripheral blood CD34+ cells isolated from a FA (C) patient and transduced with rAAV/FACC virus yielded 5-10-fold more progenitor colonies than mock-infected cells, consistent with genetic "rescue" of corrected cells. This is the first demonstration of rAAV gene correction in primary human hematopoietic progenitor cells and has important implications for gene therapy of hematopoietic disorders, specifically FA. JF - Journal of Clinical Investigation AU - Walsh, CE AU - Nienhuis, A W AU - Samulski, R J AU - Brown, M G AU - Miller, J L AU - Young, N S AU - Liu, J M AD - Hematol. Branch, NHLBI, Natl. Inst. Health, Bethesda, MD 20892, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 1440 EP - 1448 VL - 94 IS - 4 SN - 0021-9738, 0021-9738 KW - hematopoiesis KW - Biotechnology and Bioengineering Abstracts; Biochemistry Abstracts 2: Nucleic Acids; Medical and Pharmaceutical Biotechnology Abstracts KW - gene therapy KW - Fanconi syndrome KW - transduction KW - adeno-associated virus KW - DNA repair KW - N 14671: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/17013444?accountid=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+Clinical+Investigation&rft.atitle=Phenotypic+correction+of+Fanconi+anemia+in+human+hematopoietic+cells+in+a+recombinant+adeno-associated+virus+vector&rft.au=Walsh%2C+CE%3BNienhuis%2C+A+W%3BSamulski%2C+R+J%3BBrown%2C+M+G%3BMiller%2C+J+L%3BYoung%2C+N+S%3BLiu%2C+J+M&rft.aulast=Walsh&rft.aufirst=CE&rft.date=1994-01-01&rft.volume=94&rft.issue=4&rft.spage=1440&rft.isbn=&rft.btitle=&rft.title=Journal+of+Clinical+Investigation&rft.issn=00219738&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 - gene therapy; Fanconi syndrome; transduction; DNA repair; adeno-associated virus ER - TY - JOUR T1 - Conformational mimicry of a chlamydial neutralization epitope on filamentous phage AN - 17000628; 3833758 AB - Conformational constraints were imposed on a peptide epitope from Chlamydia trachomatis to improve its ability to elicit antibodies that cross-react with native antigen. Appropriate constraints were discovered by a strategy that required no prior knowledge of the epitope's native conformation. First, we constructed a library of 3.2 x 10 super(5) peptides in which the epitope's contact residues were subject to random conformational constraints, each constrained peptide being fused genetically to the surface of a filamentous phage vector. Next, we selected phage displaying the most native-like peptides in the library by affinity purification with antibodies that bind the epitope only in its native conformation. Finally, we immunized mice with the selected phage and titered the resulting antisera against both whole cells and unconstrained peptide. The ratio of anti-cell titer to anti-peptide titer, which reflects the channeling of the antibody response to the native epitope, was up to five times higher for affinity-selected phage than for unselected peptide phage. In this case, therefore, "antigenic fitness," the ability of a peptide to bind antibodies specific for native epitope, correlated with "immunogenic fitness," its ability to elicit antibodies that are effective against the native antigen on an invading pathogen. If the correlation is general, surveying thousands or millions of peptides for antigenic fitness with phage display technology may be a simple but effective pre-screen for immunogenic fitness, which is costly to assess directly. JF - Journal of Biological Chemistry AU - Zhong, Guangming AU - Smith, G P AU - Berry, J AU - Brunham, R C AD - Lab. Immunol., NIAID/NIH, Bldg. 10, Rm. 11N311, Bethesda, MD 20892, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 24183 EP - 24188 VL - 269 IS - 39 SN - 0021-9258, 0021-9258 KW - filamentous phages KW - Immunology Abstracts; Microbiology Abstracts B: Bacteriology KW - epitopes KW - Chlamydia trachomatis KW - J 02832:Antigenic properties and virulence KW - F 06008:Bacteria UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17000628?accountid=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=Conformational+mimicry+of+a+chlamydial+neutralization+epitope+on+filamentous+phage&rft.au=Zhong%2C+Guangming%3BSmith%2C+G+P%3BBerry%2C+J%3BBrunham%2C+R+C&rft.aulast=Zhong&rft.aufirst=Guangming&rft.date=1994-01-01&rft.volume=269&rft.issue=39&rft.spage=24183&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 - Chlamydia trachomatis; epitopes ER - TY - JOUR T1 - Enzymatic assay for quantification of deoxynucleoside triphosphates in human cells exposed to antiretroviral 2',3'-dideoxynucleosides AN - 16990383; 3827103 AB - Quantification of intracellular 2'-deoxynucleoside-5'-triphosphates (dNTPs) is of importance in studies of antiretroviral 2',3'-dideoxynucleoside analogs (ddNs) and a highly sensitive enzymatic assay for dNTPs has frequently been used for this purpose. However, the susceptibility of the assay to interference from the corresponding substrate analogs, ddNTPs, is still undefined. Ideally, DNA polymerases used in the assay should meet at least two criteria: (i) high fidelity to the template even in the presence of ddNTPs and (ii) low affinity for ddNTPs. None of the currently used exonuclease-free Klenow and Sequenase enzymes met both criteria. However, Sequenase had higher fidelity to the template than did the Klenow enzyme in the presence of pyrimidine-ddNTPs, and its reaction followed first order kinetics. We have, therefore relying primarily on Sequenase, designed a dNTP proportional reduction assay to correct the ddN-induced deviation in the enzymatic assay. With the use of high-fidelity exonuclease-free DNA polymerase and the application of correction factors, we now can accurately quantify dNTPs with a minimum detection limit as low as 0.1 pmol, using as few as 1 x 10 super(4) peripheral blood mononuclear cells. The method described should be useful in the study and development of antiretroviral ddNs. JF - Analytical Biochemistry AU - Gao, Wen-Yi AU - Johns, D G AU - Mitsuya, H AD - Exp. Retrovirol. Sect., Med. Branch, NCI, Bldg. 10, Rm. 5A24, Bethesda, MD 20892, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 116 EP - 122 VL - 222 IS - 1 SN - 0003-2697, 0003-2697 KW - deoxynucleoside triphosphates KW - Toxicology Abstracts KW - antiviral agents KW - enzymes KW - assays KW - man KW - X 24222:Analytical procedures UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16990383?accountid=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=Analytical+Biochemistry&rft.atitle=Enzymatic+assay+for+quantification+of+deoxynucleoside+triphosphates+in+human+cells+exposed+to+antiretroviral+2%27%2C3%27-dideoxynucleosides&rft.au=Gao%2C+Wen-Yi%3BJohns%2C+D+G%3BMitsuya%2C+H&rft.aulast=Gao&rft.aufirst=Wen-Yi&rft.date=1994-01-01&rft.volume=222&rft.issue=1&rft.spage=116&rft.isbn=&rft.btitle=&rft.title=Analytical+Biochemistry&rft.issn=00032697&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 - assays; antiviral agents; man; enzymes ER - TY - JOUR T1 - Intracellular susceptibility to ribozymes in a tethered substrate-ribozyme provirus model is not predicted by secondary structures of human immunodeficiency virus type 1 RNAs in vitro AN - 16984641; 3830617 AB - We have assessed the sensitivity of different sites in HIV-1 genomic RNA to ribozymes. Ribozymes targeted to sequences in U5, Pol, Env, RRE, or R were positioned into nef of an infectious HIV-1 provirus. When these proviral DNAs were introduced into HeLa CD4 super(+) cells, recombinant viruses that contain ribozymes tethered to genomic RNA or viral mRNAs were produced. The growth kinetics of ribozyme-containing viruses in CD4 super(+) lymphocytes (MT4 cells) were distinctly delayed when compared to control viruses. On the basis of the ability of a particular ribozyme to inhibit virus replication, we inferred intracellular ribozyme-sensitive sites. We found that although ribozyme sensitivity in vitro could be correlated with predicted secondary structures of target RNAs, such in vivo correlations could not be made when using the HIV provirus model. We conclude that both Zuker algorithm computer modeling of substrate RNA secondary structures and in vivo cleavage efficiencies cannot be reliably used to determine HIV-1 ribozyme sensitive sites in vivo. JF - ANTISENSE RES. DEV. AU - Dropulic, B AU - Jeang, Kuan-Teh AD - Mol. Virol. Sect., Lab. Mol. Microbiol., NIAID/NIH, Bethesda, MD 20892, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 217 EP - 221 VL - 4 IS - 3 SN - 1050-5261, 1050-5261 KW - nef gene KW - ribozymes KW - Biotechnology and Bioengineering Abstracts; Biochemistry Abstracts 2: Nucleic Acids; Virology & AIDS Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - proviruses KW - RNA KW - human immunodeficiency virus 1 KW - computer applications KW - man KW - N 14711:RNases KW - V 22002:AIDS: Molecular and in vitro aspects KW - W3 33385:DNA/RNA KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16984641?accountid=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=ANTISENSE+RES.+DEV.&rft.atitle=Intracellular+susceptibility+to+ribozymes+in+a+tethered+substrate-ribozyme+provirus+model+is+not+predicted+by+secondary+structures+of+human+immunodeficiency+virus+type+1+RNAs+in+vitro&rft.au=Dropulic%2C+B%3BJeang%2C+Kuan-Teh&rft.aulast=Dropulic&rft.aufirst=B&rft.date=1994-01-01&rft.volume=4&rft.issue=3&rft.spage=217&rft.isbn=&rft.btitle=&rft.title=ANTISENSE+RES.+DEV.&rft.issn=10505261&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 - proviruses; RNA; computer applications; man; human immunodeficiency virus 1 ER - TY - JOUR T1 - Biological potential of basophilic hepatocellular foci and hepatic adenoma induced by the peroxisome proliferator, Wy-14,643 AN - 16979857; 3814312 AB - The biological potential of hepatic foci and tumors induced by peroxisome proliferators such as Wy-14,643 has been poorly characterized. In this study, male F-344 rats (n = 20/group/time point) were fed Wy-14,643 (0.1%) for 22, 37 or 52 weeks ('W-22, 'W-37' or 'W-52' respectively). At each time point some rats were killed and additional Wy-14,643-fed rats were switched to basal diet (Wy-14,643/'stopped') for up to 104 weeks (referred to as 'W-22/S', 'W-37/S' and 'W-52/S'). Homogeneous basophilic foci, but not clear cell foci, increased in number and size in W-37 and W-52 rats. In W-37/S rats, clear cell foci replaced basophilic foci as the most frequent phenotype. In serial section overlays, adenosine triphosphatase deficient foci accounted for only 16% of basophilic foci in W-52 rats and 16% of clear cell foci in W-37/S rats at 52 weeks. The replication of basophilic foci of W-37 rats was markedly increased (focal labeling index, FLI = 61.8% versus non-focal labeling index, LI = 11.4%; control LI = 0.8%). Clear cell foci from W-37/S rats at 52 weeks had a FLI of 1.6% (non-focal LI = 0.6%). Hepatocellular adenomas were increased in W-37 (11/20 rats and 0.8 tumors/rat) and W-52 groups (19/20 rats and 2.8 tumors/rat). Prevalence of hepatocellular carcinomas was elevated in W-52 rats (6/20 rats) but not in W-22 or W-37 rats. Following removal of Wy-14,643, prevalence of animals with malignant, metastatic hepatocellular carcinomas in W-52/S rats was similar to the prevalence in W-52 rats. However, Wy-14,643-induced adenomas completely regressed in W-37/S and W-52/S groups. In summary, significant morphological continuity between highly proliferative basophilic foci and hepatocellular tumors was identified, emphasizing the superiority of basophilia as a marker for lesions leading to development of hepatocellular neoplasia in rats fed Wy-14,643. An important biological distinction was noted between regressive hepatic adenomas and progressive hepatocellular carcinomas induced by a peroxisome proliferator. JF - Carcinogenesis AU - Marsman, D S AU - Popp, JA AD - Environ. Toxicol. Program, NIEHS, PO Box 12233, MD A0-01, Research Triangle Park, NC 27709, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 111 EP - 117 VL - 15 IS - 1 SN - 0143-3334, 0143-3334 KW - peroxisome proliferators KW - rats KW - Wy 14643 KW - Toxicology Abstracts KW - carcinogenesis KW - adenoma KW - liver KW - X 24240:Miscellaneous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16979857?accountid=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=Biological+potential+of+basophilic+hepatocellular+foci+and+hepatic+adenoma+induced+by+the+peroxisome+proliferator%2C+Wy-14%2C643&rft.au=Marsman%2C+D+S%3BPopp%2C+JA&rft.aulast=Marsman&rft.aufirst=D&rft.date=1994-01-01&rft.volume=15&rft.issue=1&rft.spage=111&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 - liver; adenoma; carcinogenesis ER - TY - JOUR T1 - Rescue of a failed polymerase chain reaction catalyzed by vent or deep vent DNA polymerase with 10% dimethyl sulfoxide AN - 16973218; 3819290 JF - Analytical Biochemistry AU - Berger, S L AD - NCI/NIH, Bethesda, MD 20892, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 290 EP - 293 VL - 222 IS - 1 SN - 0003-2697, 0003-2697 KW - DNA-directed DNA polymerase KW - dimethylsulfoxide KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - nucleotide sequence KW - N 14610:Occurrence, isolation & assay KW - W 30965:Miscellaneous, Reviews KW - W3 33130:Genetic based (PCR, etc.) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16973218?accountid=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=Analytical+Biochemistry&rft.atitle=Rescue+of+a+failed+polymerase+chain+reaction+catalyzed+by+vent+or+deep+vent+DNA+polymerase+with+10%25+dimethyl+sulfoxide&rft.au=Berger%2C+S+L&rft.aulast=Berger&rft.aufirst=S&rft.date=1994-01-01&rft.volume=222&rft.issue=1&rft.spage=290&rft.isbn=&rft.btitle=&rft.title=Analytical+Biochemistry&rft.issn=00032697&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 - nucleotide sequence ER - TY - JOUR T1 - Protein antigens of Chlamydia psittaci present in infected cells but not detected in the infectious elementary body AN - 16970753; 3620208 AB - Ocular infection of guinea pigs with the guinea pig inclusion conjunctivitis (GPIC) strain of Chlamydia psittaci produces a clinical condition representative of acute chlamydia conjunctivitis in humans. Guinea pigs which had recovered from two challenges with GPIC were used as a source of sera for the identification of antigens present in GPIC-infected tissue culture cells but absent in the infectious elementary body (EB). Immunoblots of lysates of infected HeLa cells probed with the convalescent-phase sera identified protein antigens of 22, 34, and 52 kDa (p22, p34, and p52, respectively) that were not detected in lysates of purified EB or in uninfected HeLa cells. Protein p22 was also not detected in lysates of purified reticulate bodies. Immunoblotting of lysates of HeLa cells infected with other chlamydiae demonstrated that the antigenicity of p22 and p34 was subspecies specific. Immunoblotting was also used to detect p22 and p34 in lysates of the conjunctivae of infected guinea pigs. Adsorption of convalescent-phase sera with GPIC EB produced a reagent with dominant reactivity toward p22, p34, and a 28-kDa EB protein. Immunofluorescent staining of GPIC-infected HeLa cells demonstrated that these adsorbed sera labeled the inclusion and inclusion membrane, with no apparent reactivity toward EB or reticulate bodies. Collectively, these data identify non-EB chlamydial components which may be released into the inclusion during intracellular growth. JF - Infection and Immunity AU - Rockey, D D AU - Rosquist, J L AD - Lab. Intracell. Parasites, Rocky Mountain Lab., NIAID, Hamilton, MT 59840, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 106 EP - 112 VL - 62 IS - 1 SN - 0019-9567, 0019-9567 KW - guinea-pigs KW - Microbiology Abstracts B: Bacteriology KW - elementary bodies KW - conjunctivitis KW - Chlamydia psittaci KW - proteins KW - antigens KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16970753?accountid=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=Protein+antigens+of+Chlamydia+psittaci+present+in+infected+cells+but+not+detected+in+the+infectious+elementary+body&rft.au=Rockey%2C+D+D%3BRosquist%2C+J+L&rft.aulast=Rockey&rft.aufirst=D&rft.date=1994-01-01&rft.volume=100&rft.issue=&rft.spage=21&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 - Chlamydia psittaci; proteins; antigens; conjunctivitis; elementary bodies ER - TY - JOUR T1 - Manipulating blood T cells and B cells from squirrel monkeys: Some technical considerations AN - 16963697; 3622972 AB - The squirrel monkey Saimiri sciureus is an experimental host for a range of human pathogens, and for the assessment of vaccine candidate antigens and vaccine strategies. This experimental host is thus particularly suitable for the follow-up of humoral responses. To understand some of the mechanisms that underlie the defense against experimental pathogens, there is a need of basic knowledge on cellular immune effectors also. The authors report here their experience in characterizing squirrel monkey blood T and B lymphocytes, and in studying in vitro induced activation and proliferation of T and B cells. Particular emphasis is given to the in vitro differentiation of squirrel monkey B cells into immunoglobulin secreting cells, with respect to Plasmodium falciparum antigens. JF - Journal of Immunological Methods AU - Garraud, O AU - Perraut, R AU - Gysin, Juerg AU - Behr, C AU - Dubois, Philippe AU - Bonnemains, B AU - Jouin, H AU - Michel, J-C AU - Pereira da Silva, L AD - Clin. Parasitol. Sect., Lab. Parasitic Dis., NIAID-NIH, Build. 4, Rm. 126, Bethesda, MD 20892, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 165 EP - 173 VL - 173 IS - 2 SN - 0022-1759, 0022-1759 KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Microbiology Abstracts C: Algology, Mycology & Protozoology; Immunology Abstracts KW - Saimiri sciureus KW - lymphocytes T KW - malaria KW - immune response (humoral) KW - Plasmodium falciparum KW - lymphocytes B KW - K 03086:Immunology & vaccination KW - W3 33240:Immunology KW - F 06803:Protozoa KW - F 06749:Function KW - F 06756:Function KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16963697?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Immunological+Methods&rft.atitle=Manipulating+blood+T+cells+and+B+cells+from+squirrel+monkeys%3A+Some+technical+considerations&rft.au=Garraud%2C+O%3BPerraut%2C+R%3BGysin%2C+Juerg%3BBehr%2C+C%3BDubois%2C+Philippe%3BBonnemains%2C+B%3BJouin%2C+H%3BMichel%2C+J-C%3BPereira+da+Silva%2C+L&rft.aulast=Garraud&rft.aufirst=O&rft.date=1994-01-01&rft.volume=173&rft.issue=2&rft.spage=165&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immunological+Methods&rft.issn=00221759&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - lymphocytes T; malaria; immune response (humoral); lymphocytes B; Saimiri sciureus; Plasmodium falciparum ER - TY - JOUR T1 - In vitro and in vivo antiviral (RNA) evaluation of orotidine 5'-monophosphate decarboxylase inhibitors and analogues including 6-azauridine-5'-(ethyl methoxyalaninyl)phosphate (a 5'-monophosphate prodrug) AN - 16961071; 3618557 AB - A series of 29 pyrimidines comprising analogues of 6-azauridine (e.g. 2- and 4-thio-6-azauridine), 6-substituted uridines (including several known inhibitors of orotidine 5'-monophosphate decarboxylase, ODCase, e.g. pyrazofurin), and 6-azauridine-5'-(ethyl methoxyalaninyl) phosphate (a potential prodrug of 6-AU-5'-MP) were synthesized and evaluated in vitro and in vivo against five RNA viruses: Japanese encephalitis (JE), yellow fever (YF), sandfly fever (SF), Punta Toro (PT) and Venezuelan equine encephalomyelitis (VEE) viruses. 2-Thio-6-azauridine demonstrated the best in vitro activity against all five viruses. However, in vivo activity was not observed in JE-, PT- and VEE-infected mice. The phosphate prodrug of 6-azauridine was significantly more effective than the parent compound in the PT virus mouse model. Optimum in vivo dose/route/schedule was determined for pyrazofurin in PT-virus-infected mice. JF - Antiviral Chemistry & Chemotherapy AU - Gabrielsen, B AU - Kirsi, J J AU - Kwong, C D AU - Carter, DA AU - Krauth, CA AU - Hanna, L K AU - Huggins, J W AU - Monath, T P AU - Kefauver, D F AD - NCI-FCRDC, P.O. Box B, Build. 427, Frederick, MD 21702-1201, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 209 EP - 220 VL - 5 IS - 4 SN - 0956-3202, 0956-3202 KW - orotidine-5'-phosphate decarboxylase KW - pyrazofurin KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Virology & AIDS Abstracts KW - antiviral agents KW - RNA KW - inhibitors KW - viruses KW - activity KW - A 01068:Antiviral & viricidal KW - V 22100:Antiviral agents UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16961071?accountid=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=Environmental+health+perspectives&rft.atitle=Mechanisms+of+multistep+carcinogenesis+and+carcinogen+risk+assessment.&rft.au=Barrett%2C+J+C&rft.aulast=Barrett&rft.aufirst=J&rft.date=1993-04-01&rft.volume=100&rft.issue=&rft.spage=9&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 - RNA; viruses; antiviral agents; inhibitors; activity ER - TY - JOUR T1 - Protein binding of human immunodeficiency virus protease inhibitor KNI-272 and alteration of its in vitro antiretroviral activity in the presence of high concentrations of proteins AN - 16928213; 3613469 AB - KNI-272 represents a peptide-based protease inhibitor having potent antiretroviral activity against human immunodeficiency virus (HIV) in vitro. The structure contains allophenylnorstatine [(2S,3S)-3-amino-2-hydroxy-4-phenylbutyric acid] with a hydroxymethylcarbonyl isostere. We asked whether this experimental anti-HIV agent could exert its activity in vitro in the presence of relatively high concentrations of fetal calf serum (FCS) and assessed its protein-binding properties by using fresh human plasma preparations. Higher levels of KNI-272 in plasma may be required when this compound undergoes clinical trials relative to those inferred from in vitro data involving the use of 10 to 15% FCS-containing culture media. The current data may have a relevance to other antiretroviral drugs that are under development and that have a high protein-binding capacity. JF - Antimicrobial Agents & Chemotherapy AU - Kageyama, S AU - Anderson, B D AU - Hoesterey, B L AU - Hayashi, H AU - Kiso, Y AU - Flora, K P AU - Mitsuya, H AD - Exp. Retrovirol. Sect., Med. Branch, NCI/NIH, Build. 10, Rm. 5A11, Bethesda, MD 20892, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 1107 EP - 1111 VL - 38 IS - 5 SN - 0066-4804, 0066-4804 KW - proteinase inhibitors KW - KNI-272 KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Virology & AIDS Abstracts KW - antiviral activity KW - human immunodeficiency virus KW - binding KW - proteins KW - V 22002:AIDS: Molecular and in vitro aspects KW - A 01068:Antiviral & viricidal UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16928213?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologya&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antimicrobial+Agents+%26+Chemotherapy&rft.atitle=Protein+binding+of+human+immunodeficiency+virus+protease+inhibitor+KNI-272+and+alteration+of+its+in+vitro+antiretroviral+activity+in+the+presence+of+high+concentrations+of+proteins&rft.au=Kageyama%2C+S%3BAnderson%2C+B+D%3BHoesterey%2C+B+L%3BHayashi%2C+H%3BKiso%2C+Y%3BFlora%2C+K+P%3BMitsuya%2C+H&rft.aulast=Kageyama&rft.aufirst=S&rft.date=1994-01-01&rft.volume=38&rft.issue=5&rft.spage=1107&rft.isbn=&rft.btitle=&rft.title=Antimicrobial+Agents+%26+Chemotherapy&rft.issn=00664804&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - human immunodeficiency virus; antiviral activity; proteins; binding ER - TY - JOUR T1 - Isolation of immature and mature T cell receptor complexes by lectin affinity chromatography AN - 16926451; 3605226 AB - The antigen-specific T cell receptor (TCR) is a multisubunit complex composed of at least six different polypeptide chains ( alpha , beta , gamma , delta , epsilon , zeta ), several of which are glycoproteins. Assembly of the TCR occurs in the endoplasmic reticulum (ER) and involves intermediary complexes of CD3- gamma , delta , epsilon proteins and TCR alpha and - beta molecules. Egress of TCR from the ER and transport through the Golgi apparatus is most often monitored by the sensitivity of TCR glycoproteins to endoglycosidase H (Endo H), an enzyme specific for immature oligosaccharides which have not yet been processed by Golgi glycosidases and glycosyltransferases. When both immature and mature TCR glycoproteins are present within a given sample, this becomes extremely difficult. In this report, we describe a method for the physical separation of immature and mature murine TCR complexes based on processing of N-linked carbohydrate side chains. Specifically, we report the use of wheat germ agglutinin-affinity matrices to separate TCR complexes which have reached the trans Golgi compartment of the cell from those that have not. This technique is rapid, sensitive, and does not affect the integrity of assembled TCR complexes. JF - Journal of Immunological Methods AU - Kearse, K P AU - Singer, A AD - Exp. Immunol. Branch, NCI/NIH, Bethesda, MD 20892, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 75 EP - 81 VL - 167 IS - 1-2 SN - 0022-1759, 0022-1759 KW - CD3 antigen KW - completes KW - lectins KW - mice KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - affinity chromatography KW - T-cell receptor KW - lymphocytes T KW - F 06754:Surface KW - W3 33240:Immunology KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16926451?accountid=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=Electroencephalography+and+Clinical+Neurophysiology&rft.atitle=Safety+of+rapid-rate+transcranial+magnetic+stimulation+in+normal+volunteers.&rft.au=Pascual-Leone%2C+A%3BHouser%2C+C+M%3BReese%2C+K%3BShotland%2C+L+I%3BGrafman%2C+J%3BSato%2C+S%3BValls-Sol%C3%A9+J%3BBrasil-Neto%2C+J+P%3BWassermann%2C+E+M%3BCohen%2C+L+G&rft.aulast=Pascual-Leone&rft.aufirst=A&rft.date=1993-04-01&rft.volume=89&rft.issue=2&rft.spage=120&rft.isbn=&rft.btitle=&rft.title=Electroencephalography+and+Clinical+Neurophysiology&rft.issn=00134694&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 - affinity chromatography; T-cell receptor; lymphocytes T ER - TY - JOUR T1 - Cohort-specific risks of developing breast cancer to age 85 in Connecticut AN - 16924601; 3604492 AB - Previous estimates of the lifetime risk of developing breast cancer have used cross-sectional estimates of incidence. Cross-sectional rates, however, yield a biased picture of cohort risks when rates are unstable, as breast cancer trends have been. We developed cohort life tables for Connecticut women born from 1888-1892 to 1948-1952 to generate more specific estimates of breast cancer risk to age 85. Multiple decrement life tables were produced for each birth cohort. We included as cases only the first reports of breast cancer in women with no earlier malignancy. Our results indicate that widely circulated lifetime risks of 1 in 9 may be inflated slightly owing to changing incidence. We estimate that of those women 40-44 years old in 1992, 1 women in 10 will develop breast cancer by age 85. For women born between 1928 and 1932, 1 in 13 will be diagnosed with breast cancer by age 85. The results are insensitive to mortality trends in the past. JF - Epidemiology AU - Campbell, M K AU - Feuer, E J AU - Wun, L-M AD - NCI/NIH, Executive Plaza North, Rm. 313, Bethesda, MD 20892, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 290 EP - 296 VL - 5 IS - 3 SN - 1044-3983, 1044-3983 KW - Risk Abstracts KW - breast cancer KW - USA, Connecticut KW - epidemiology KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16924601?accountid=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=Epidemiology&rft.atitle=Cohort-specific+risks+of+developing+breast+cancer+to+age+85+in+Connecticut&rft.au=Campbell%2C+M+K%3BFeuer%2C+E+J%3BWun%2C+L-M&rft.aulast=Campbell&rft.aufirst=M&rft.date=1994-01-01&rft.volume=5&rft.issue=3&rft.spage=290&rft.isbn=&rft.btitle=&rft.title=Epidemiology&rft.issn=10443983&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, Connecticut; breast cancer; epidemiology ER - TY - JOUR T1 - Induction of plasmacytomas that secrete monoclonal anti-peptide antibodies by retroviral transformation AN - 16922703; 3608065 AB - ABL-MYC, a retrovirus that coexpresses v-abl and c-myc, was used to infect six BALB/c mice that had been immunized twice with a KLH-conjugated peptide that consisted of the 18 carboxyterminal amino acids of protein kinase C- eta (PKC- eta ). All mice developed transplantable, monoclonal plasmacytomas, and five out of six plasmacytomas secreted antigen-specific antibodies, even after transplantation. All these antibodies recognized PKC- eta on Western blots of crude cell lysates and did not cross react with other isoforms of the PKC family. JF - Journal of Immunological Methods AU - Weissinger, E M AU - Henderson, D W AU - Mischak, H AU - Goodnight, J-A AU - Mushinski, J F AD - Lab. Genet., NCI/NIH, Build. 37 Rm. 2B21, 9000 Rockville Pike, Bethesda, MD 20892, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 123 EP - 130 VL - 168 IS - 1 SN - 0022-1759, 0022-1759 KW - Balb/c KW - mice KW - Biotechnology and Bioengineering Abstracts; Biochemistry Abstracts 2: Nucleic Acids; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - secretion KW - retrovirus KW - specificity KW - peptides KW - plasmacytoma KW - monoclonal antibodies KW - transformation KW - W3 33375:Antibodies KW - F 06711:Monoclonal antibodies, hybridomas, antigens and antisera KW - W 30965:Miscellaneous, Reviews KW - N 14672:Transfection UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16922703?accountid=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=Clinical+chemistry&rft.atitle=Measurement+of+heroin+and+its+metabolites+by+isotope-dilution+electron-impact+mass+spectrometry.&rft.au=Goldberger%2C+B+A%3BDarwin%2C+W+D%3BGrant%2C+T+M%3BAllen%2C+A+C%3BCaplan%2C+Y+H%3BCone%2C+E+J&rft.aulast=Goldberger&rft.aufirst=B&rft.date=1993-04-01&rft.volume=39&rft.issue=4&rft.spage=670&rft.isbn=&rft.btitle=&rft.title=Clinical+chemistry&rft.issn=00099147&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 - secretion; retrovirus; specificity; peptides; monoclonal antibodies; plasmacytoma; transformation ER - TY - JOUR T1 - Chemical mutagenesis testing in Drosophila. X. Results of 70 coded chemicals tested for the National Toxicology Program AN - 16914575; 3594543 AB - Seventy chemicals were tested for the ability to induce sex-linked recessive lethal (SLRL) mutations in postmeiotic and meiotic germ cells of male Drosophila melanogaster. Sixteen of the 70 chemicals tested were mutagenic in the SLRL assay: 3-chloro-2-methylpropene, 3-(chloromethyl)pyridine HCl, dimethylcarbamoyl chloride, HC blue 1,3-iodo-1,2-propanediol, malaoxon, N,N'-methylene-bis-acrylamide, 4,4'-methylenedianiline 2HCl, ziram, cis-dichlorodiaminoplatinum II, 1,2-dibromoethane, dibromomannitol, 1,2-epoxypropane, glycidol, myleran, and toluene diisocyanate. The last seven also induced reciprocal translocations. A comparison of the results from the SLRL assay with other assays for mutagens and carcinogens suggests that the SLRL assay is highly specific, but poorly sensitive, both for mutagens and potential carcinogens. JF - Environmental and Molecular Mutagenesis AU - Foureman, P AU - Mason, J M AU - Valencia, R AU - Zimmering, S AD - Lab. Genet., NIEHS, Research Triangle Park, NC 27709-2233, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 208 EP - 227 VL - 23 IS - 3 SN - 0893-6692, 0893-6692 KW - sex-linked recessive lethal mutations KW - sex-linkage KW - Entomology Abstracts; Genetics Abstracts; Toxicology Abstracts KW - lethal mutant KW - mutagenicity testing KW - xenobiotics KW - Drosophila melanogaster KW - G 07220:General theory/testing systems KW - Z 05215:Mutation KW - X 24221:Toxicity testing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16914575?accountid=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+and+Molecular+Mutagenesis&rft.atitle=Chemical+mutagenesis+testing+in+Drosophila.+X.+Results+of+70+coded+chemicals+tested+for+the+National+Toxicology+Program&rft.au=Foureman%2C+P%3BMason%2C+J+M%3BValencia%2C+R%3BZimmering%2C+S&rft.aulast=Foureman&rft.aufirst=P&rft.date=1994-01-01&rft.volume=23&rft.issue=3&rft.spage=208&rft.isbn=&rft.btitle=&rft.title=Environmental+and+Molecular+Mutagenesis&rft.issn=08936692&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Drosophila melanogaster; xenobiotics; mutagenicity testing; lethal mutant ER - TY - JOUR T1 - Block of HIV-1 infection by a combination of antisense tat RNA and TAR decoys: A strategy for control of HIV-1 AN - 16914000; 3593852 AB - The tat gene product (Tat) of HIV-1 is an early regulatory protein necessary for viral gene expression and replication. Tat may also play a role as an extracellular protein in both HIV-1 replication and AIDS-associated disorders such as Kaposi's sarcoma. Thus, Tat represents a good target for gene therapy against AIDS. We show that when vectors expressing antisense tat RNA are transiently transfected into CD4 super(+) cells, they block about 70% of HIV-1 replication and inhibit the rescue of Tat-defective HIV-1 proviruses by inhibition of Tat protein expression and consequent lack of transcriptional activation of the HIV-promoter. However, antisense tat vectors cannot block the activity of extracellular Tat protein. Another tat inhibitory construct (poly-Tat-activation response; TAR) previously suggested to inhibit HIV-1 transactivation by sequestering the Tat protein, inhibited the activity of extracellular Tat, but like antisense tat RNA did not completely block viral gene expression and replication. The results suggested that one mode of inhibition is not sufficient to block Tat function. However, when the antisense tat and the poly-TAR constructs were combined HIV-1 gene expression was completely blocked (94-98%), suggesting that a combination of inhibitory genes blocking Tat by sequential steps may be a better approach for AIDS gene therapy. JF - Gene Therapy AU - Chang, Hsiao-Kuey AU - Gendelman, R AU - Lisziewicz, J AU - Gallo, R C AU - Ensoli, B AD - Lab. Tumor Cell Biol., Build. 37, Rm. 6A09, NCI/NIH, 9000 Rockville Pike, Bethesda, MD 20892, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 208 EP - 216 VL - 1 IS - 3 SN - 0969-7128, 0969-7128 KW - RNA KW - TAR regions KW - Tat protein KW - antisense KW - gene therapy KW - human immunodeficiency virus 1 KW - infection KW - inhibition KW - Biotechnology and Bioengineering Abstracts; Human Genome Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Virology & AIDS Abstracts KW - V 22002:AIDS: Molecular and in vitro aspects 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/16914000?accountid=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=Gene+Therapy&rft.atitle=Block+of+HIV-1+infection+by+a+combination+of+antisense+tat+RNA+and+TAR+decoys%3A+A+strategy+for+control+of+HIV-1&rft.au=Chang%2C+Hsiao-Kuey%3BGendelman%2C+R%3BLisziewicz%2C+J%3BGallo%2C+R+C%3BEnsoli%2C+B&rft.aulast=Chang&rft.aufirst=Hsiao-Kuey&rft.date=1994-01-01&rft.volume=1&rft.issue=3&rft.spage=208&rft.isbn=&rft.btitle=&rft.title=Gene+Therapy&rft.issn=09697128&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 - gene therapy; antisense; RNA; inhibition; infection; human immunodeficiency virus 1 ER - TY - JOUR T1 - Slippage synthesis at the galP2 promoter of Escherichia coli and its regulation by UTP concentration and cAMP-cAMP receptor protein AN - 16913611; 3593480 AB - An intriguing mechanism in regulating transcription initiation from the gal operon in Escherichia coli is described. Initiation from galP2, one of the two promoters of the E. coli galactose operon, is shown to be subject to promoter clearance control in responding to changes in UTP concentration. In vitro, RNA polymerase (RNAP) makes a large amount of nonproductive "stuttering" initiation products at the galP2 promoter at high concentrations of UTP and less of the stuttered products at low concentrations of UTP. Conversely, RNAP makes more productive initiation products at low UTP concentration than at high UTP concentration. The transcription factor cAMP-CRP complex which normally inhibits transcription from galP2 also represses the stuttering synthesis from galP2. When galactose is used as a sole carbon source and the internal UTP pools are adjusted externally, a cya mutant (in which galP2 is mainly responsible for the expression of the gal operon and galP1 activity is minimal) has a slower growth rate and lower expression of the gal operon at high UTP pools than at low UTP pools. Such an apparent correlation between the in vitro and in vivo results allows one to speculate that changes in UTP concentration can modulate the expression of the gal operon. The implication of a gal promoter being controlled by UTP is discussed. JF - Journal of Biological Chemistry AU - Jin, Ding Jun AD - Lab. Mol. Biol., NCI, NIH, 9000 Rockville Pike, Build. 37, Rm. 2E14, Bethesda, MD 20892, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 17221 EP - 17227 VL - 269 IS - 25 SN - 0021-9258, 0021-9258 KW - slippage KW - galP2 gene KW - UTP KW - CRP protein KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - concentration KW - genes KW - promoters KW - regulation KW - Escherichia coli KW - synthesis KW - J 02740:Genetics and evolution KW - N 14662:Gene regulation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16913611?accountid=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=Cell+growth+%26+differentiation+%3A+the+molecular+biology+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=Epidermal+growth+factor+receptor+ligands+regulate+keratin+8+expression+in+keratinocytes%2C+and+transforming+growth+factor+alpha+mediates+the+induction+of+keratin+8+by+the+v-rasHa+oncogene.&rft.au=Cheng%2C+C%3BTennenbaum%2C+T%3BDempsey%2C+P+J%3BCoffey%2C+R+J%3BYuspa%2C+S+H%3BDlugosz%2C+A+A&rft.aulast=Cheng&rft.aufirst=C&rft.date=1993-04-01&rft.volume=4&rft.issue=4&rft.spage=317&rft.isbn=&rft.btitle=&rft.title=Cell+growth+%26+differentiation+%3A+the+molecular+biology+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10449523&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; genes; promoters; synthesis; regulation; concentration ER - TY - JOUR T1 - Processive degradation of proteins by the ATP-dependent Clp protease from Escherichia coli: Requirement for the multiple array of active sites in ClpP but not ATP hydrolysis AN - 16913557; 3602837 AB - ClpP, the proteolytic component of the ATP-dependent ClpAP protease, is composed of 12 identical subunits and has intrinsic degradative activity against short peptides. Degradation of proteins and some peptides by ClpP requires the regulatory component ClpA and ATP. Peptide and protein substrates have been used to distinguish the roles of nucleotide binding and nucleotide hydrolysis in the activation of ClpAP protease. ATP binding alone promoted interaction between ClpA and ClpP, affected the substrate response curves for very short peptides, and activated degradation of larger peptides that were not degraded by ClpP alone. ATP hydrolysis did not increase in proportion to the increase in peptide bond hydrolysis of short peptides. However, ATP hydrolysis was strictly required for degradation of proteins such as alpha -casein; there was no indication of even limited cleavage of protein substrates when nonhydrolyzable analogs of ATP were used. Most large peptides and proteins were degraded in multiple sites without release of high molecular weight intermediates. Partial inactivation of ClpP with diisopropyl fluorophosphate produced ClpP with one to three active subunits/dodecamer. When only a few active sites were available in the active complex of ClpAP, degradation of large peptides and proteins released significant amounts of high molecular weight intermediates. Thus, processive degradation of protein substrates is a function of the multiple array of proteolytic active sites within the ClpP dodecamer. JF - Journal of Biological Chemistry AU - Thompson, M W AU - Singh, S K AU - Maurizi, M R AD - NCI/NIH, Build. 37, Rm. 1B07, Bethesda, MD 20892, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 18209 EP - 18215 VL - 269 IS - 27 SN - 0021-9258, 0021-9258 KW - ClpAP proteinase KW - ATP KW - Microbiology Abstracts B: Bacteriology KW - degradation KW - active sites KW - Escherichia coli KW - hydrolysis KW - subunits KW - proteins KW - J 02728:Enzymes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16913557?accountid=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=Processive+degradation+of+proteins+by+the+ATP-dependent+Clp+protease+from+Escherichia+coli%3A+Requirement+for+the+multiple+array+of+active+sites+in+ClpP+but+not+ATP+hydrolysis&rft.au=Thompson%2C+M+W%3BSingh%2C+S+K%3BMaurizi%2C+M+R&rft.aulast=Thompson&rft.aufirst=M&rft.date=1994-01-01&rft.volume=269&rft.issue=27&rft.spage=18209&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; subunits; active sites; hydrolysis; proteins; degradation ER - TY - JOUR T1 - Activity and specificity of Escherichia coli ClpAP protease in cleaving model peptide substrates AN - 16908119; 3602820 AB - Escherichia coli ClpAP protease is an ATP-dependent protease composed of the proteolytic component ClpP and a regulatory ATPase, ClpA. ClpAP protease degraded a variety of peptide bonds in protein and peptide substrates at a slow rate (k sub(cat) greater than or equal to 30 min super(-1)/subunit of ClpP), but showed very high activity (k sub(cat) greater than or equal to 800 min super(-1)) for a synthetic peptide composed of the first 19 amino acids of ClpP, MSYSGERDNFAPHMALVPV, referred to as the propeptide. The propeptide was not degraded by ClpP alone, but was degraded in the presence of ClpA and ClpP. Degradation was activated by nonhydrolyzable analogs of ATP, indicating that nucleotide-promoted interaction between ClpA and ClpP is sufficient to activate ClpP for propeptide cleavage. The propeptide, as well as truncated forms lacking either the first 9 or the last 3 amino acids, was cleaved at the same Met-Ala bond at which autoprocessing occurs in vivo. No hydrolysis of FAPHMALVPV derivatives was observed when Met was replaced by Glu, Lys, Ser, Tyr, Ile, and D-Met, but cleavage at the same position did occur with Leu or Trp substitutions. A peptide composed of a tandem repeat of FAPHMALVPV was cleaved between both Met-Ala bonds (k sub(cat) values greater than or equal to 39 min super(-1)). Propeptides inhibited degradation of alpha -casein by competition for a binding site on ClpA, and they stimulated the basal ATPase activity of ClpA in the absence of ClpP. Peptides and protein substrates interact at an allosteric site on ClpA, which appears to be the site at which specific substrates are recognized by the Clp protease. JF - Journal of Biological Chemistry AU - Thompson, M W AU - Maurizi, M R AD - NCI/NIH, Build. 37, Rm. 1B07, Bethesda, MD 20892, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 18201 EP - 18208 VL - 269 IS - 27 SN - 0021-9258, 0021-9258 KW - ClpAP proteinase KW - Microbiology Abstracts B: Bacteriology KW - substrates KW - specificity KW - Escherichia coli KW - peptides KW - enzymatic activity KW - cleavage KW - J 02728:Enzymes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16908119?accountid=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=Activity+and+specificity+of+Escherichia+coli+ClpAP+protease+in+cleaving+model+peptide+substrates&rft.au=Thompson%2C+M+W%3BMaurizi%2C+M+R&rft.aulast=Thompson&rft.aufirst=M&rft.date=1994-01-01&rft.volume=269&rft.issue=27&rft.spage=18201&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; enzymatic activity; specificity; peptides; substrates; cleavage ER - TY - JOUR T1 - Algal and bacterial pigments in non-laminated lacustrine sediment: Studies of their sedimentation, degradation and stratigraphy AN - 16907115; 3591278 AB - Natural phyto- and bacterioplankton populations of Lake Vechten (the Netherlands) were subjected to darkness under oxic and anoxic conditions at in situ temperatures in order to test the stability in time of their photosynthetic pigments. Furthermore, sedimentary fluxes and concentrations of pigments were estimated in (respectively) sediment trap catches and at the sediment-water interphase in order to measure the pigment breakdown upon burial into the sediment. The chlorophylls and most of the xanthophylls showed substantial losses of 20% to 60% in the incubation experiments as well as in the surficial sediment. beta -Carotene, okenone and echinenone were most stable (2-10% losses); fucoxanthin and peridinin were degraded extensively; alloxanthin and zeaxanthin held an intermediate position as did the bacteriochlorophylls. Trends in sediment profiles of pigments were compared with limnological data obtained during the enhanced eutrophication of the lake. Evidence was provided that the beta -carotene profile closely followed the increase of phytoplankton biomass. Although susceptible to substantial degradation, several profiles of pigments and of pigment ratios could be related in a qualitative way to biomass and to shifts in species composition which occurred as a result of the changing ecological conditions in the lake. JF - FEMS Microbiology Ecology AU - Steenbergen, CLM AU - Korthals, HJ AU - Dobrynin, E G AD - NEI-Cent. Limnol., 3631 AC Nieuwersluis, Netherlands Y1 - 1994 PY - 1994 DA - 1994 SP - 335 EP - 352 VL - 13 IS - 4 SN - 0168-6496, 0168-6496 KW - carotenoids KW - chlorophylls KW - lacustrine sedimentation KW - paleoecology KW - paleolimnology KW - ASFA 1: Biological Sciences & Living Resources; Ecology Abstracts; Microbiology Abstracts B: Bacteriology; Microbiology Abstracts C: Algology, Mycology & Protozoology KW - community composition KW - degradation KW - biomass KW - lakes KW - Freshwater KW - algae KW - sediments KW - ecology KW - Netherlands KW - Netherlands, Vechten L. KW - pigments KW - primary production KW - photosynthetic pigments KW - bacteria KW - Q1 08221:General KW - D 04310:Freshwater KW - J 02724:Pigments and vitamins KW - Q1 08201:General KW - K 03044:Algae KW - Q1 08187:Palaeontology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16907115?accountid=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+Ecology&rft.atitle=Algal+and+bacterial+pigments+in+non-laminated+lacustrine+sediment%3A+Studies+of+their+sedimentation%2C+degradation+and+stratigraphy&rft.au=Steenbergen%2C+CLM%3BKorthals%2C+HJ%3BDobrynin%2C+E+G&rft.aulast=Steenbergen&rft.aufirst=CLM&rft.date=1994-01-01&rft.volume=14&rft.issue=4&rft.spage=713&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 - 2014-05-06 N1 - SubjectsTermNotLitGenreText - community composition; degradation; biomass; pigments; lakes; primary production; algae; carotenoids; photosynthetic pigments; bacteria; sediments; ecology; chlorophylls; lacustrine sedimentation; paleoecology; paleolimnology; Netherlands, Vechten L.; Netherlands; Freshwater ER - TY - JOUR T1 - Molecular structures that influence the immunomodulatory properties of the lipid A and inner core region oligosaccharides of bacterial lipopolysaccharides AN - 16904299; 3596614 AB - The relationship between chain length as well as the position of fatty acyl groups to the ability of lipid A to abolish the expression of suppressor T-cell (Ts) activity was examined. Fatty acyl chain lengths of C sub(12) to C sub(14), as in the lipid A of Escherichia coli and Salmonella minnesota, appear to be optimal for this bioactivity, since lipid A preparations with fatty acyl groups of relatively short chain length (C sub(10) to C sub(12) for Pseudomonas aeruginosa and Chromobacterium violaceum) or predominantly long chain length (C sub(18) for Helicobacter pylori) are without effect. The minimal structure required for the expression of the added immunosuppression observed appears to be a hexasaccharide containing one 2-keto-3-deoxyoctonate residue, two glucose residues, and three heptose residues to which are attached two pyrophosphorylethanolamine groups. The relevance of these findings to virulence and to the pathogenesis of gram-negative infections is discussed. JF - Infection and Immunity AU - Baker, P J AU - Hraba, T AU - Taylor, CE AU - Stashak, P W AU - Fauntleroy, M B AU - Zaehringer, U AU - Takayama, K AU - Sievert, T R AU - Hronowski, X AD - Div. Microbiol. and Infect. Dis., NIAID, NIH, Solar Build. Rm. 3A37, Bethesda, MD 20892, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 2257 EP - 2269 VL - 62 IS - 6 SN - 0019-9567, 0019-9567 KW - lipopolysaccharides KW - oligosaccharides KW - lipid A KW - mice KW - Immunology Abstracts; Microbiology Abstracts B: Bacteriology KW - Salmonella minnesota KW - cores KW - Chromobacterium violaceum KW - bacteria KW - immunoregulation KW - Escherichia coli KW - Pseudomonas aeruginosa 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/16904299?accountid=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=Molecular+structures+that+influence+the+immunomodulatory+properties+of+the+lipid+A+and+inner+core+region+oligosaccharides+of+bacterial+lipopolysaccharides&rft.au=Baker%2C+P+J%3BHraba%2C+T%3BTaylor%2C+CE%3BStashak%2C+P+W%3BFauntleroy%2C+M+B%3BZaehringer%2C+U%3BTakayama%2C+K%3BSievert%2C+T+R%3BHronowski%2C+X&rft.aulast=Baker&rft.aufirst=P&rft.date=1994-01-01&rft.volume=62&rft.issue=6&rft.spage=2257&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Salmonella minnesota; Pseudomonas aeruginosa; Chromobacterium violaceum; bacteria; cores; immunoregulation ER - TY - JOUR T1 - Collaborative development of a patient simulator for educating nurses in hemofiltration therapies AN - 16904123; 145942 AB - The use of simulators can provide an economical assist in nurse education and evaluation of complex treatment modalities. The purpose of this article is to describe the patient simulator used for performing hemofiltration and its implication for nursing education. In addition, an overview of the renal replacement therapies used in the clinical management of renal dysfunction are reviewed to provide the reader with a basic understanding of the various modalities available to manage renal dysfunction. JF - Biomedical Instrumentation & Technology AU - Talbot, Thomas L AU - Rosenthal, Cathy H AU - Strider, Victoria Church AD - National Institutes of Health, Bethesda, MD, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 271 EP - 281 VL - 28 IS - 4 SN - 0899-8205, 0899-8205 KW - Computer aided instruction KW - Critical care patients KW - Hospitals KW - Patient simulator KW - Personnel training KW - Renal dysfunction KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - W4 912.4:PERSONNEL KW - W4 462.1:BIOMEDICAL EQUIPMENT (GENERAL) KW - W4 461.1:BIOMEDICAL ENGINEERING KW - W4 723.5:COMPUTER APPLICATIONS KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16904123?accountid=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=Biomedical+Instrumentation+%26+Technology&rft.atitle=Collaborative+development+of+a+patient+simulator+for+educating+nurses+in+hemofiltration+therapies&rft.au=Talbot%2C+Thomas+L%3BRosenthal%2C+Cathy+H%3BStrider%2C+Victoria+Church&rft.aulast=Talbot&rft.aufirst=Thomas&rft.date=1994-01-01&rft.volume=28&rft.issue=4&rft.spage=271&rft.isbn=&rft.btitle=&rft.title=Biomedical+Instrumentation+%26+Technology&rft.issn=08998205&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 - Hospitals ER - TY - JOUR T1 - Aromatic amine dehydrogenase, a second tryptophan tryptophylquinone enzyme AN - 16902606; 3591826 AB - Aromatic amine dehydrogenase (AADH) catalyzes the oxidative deamination of aromatic amines including tyramine and dopamine. AADH is structurally similar to methylamine dehydrogenase (MADH) and possesses the same tryptophan tryptophylquinone (TTQ) prosthetic group. AADH exhibits an alpha sub(2) beta sub(2) structure with subunit molecular weights of 39,000 and 18,000 and with a quinone covalently attached to each beta subunit. Neither subunit cross-reacted immunologically with antibodies to the corresponding subunits of MADH, and the N-terminal amino acid sequence of the beta subunit of AADH exhibited no homology with the highly conserved beta subunits of MADH. The absorption spectra for the oxidized, semiquinone, and reduced forms of AADH have been characterized, and extinction coefficients for the absorption maxima of each redox form have been determined. These spectra are very similar to those for MADH, indicating the likelihood of a TTQ cofactor. This was verified by the near identity of the vibrational frequencies and intensities in the resonance Raman spectra for the oxidized forms of AADH and MADH. A stable semiquinone of AADH could be observed during a reductive titration with dithionite, whereas titration with tyramine proceeded directly from the oxidized to the reduced form. AADH was very stable against denaturation by heat and exposure to guanidine. The individual subunits could be separated by gel filtration after incubation in guanidine hydrochloride, and partial reconstitution of activity was observed on recombination of the subunits. Steady-state kinetic analysis of AADH yielded a V sub(max) of 17 mu mol/min/mg and a K sub(m) for tyramine of 5.4 mu M. Substrate inhibition by tyramine was observed. AADH was irreversibly inhibited by hydrazine, phenylhydrazine, hydroxylamine, semicarbazide, and aminoguanidine. Isonicotinic acid hydrazide (isoniazid) and isonicotinic acid 2-isopropyl hydrazide (iproniazid) were reversible noncompetitive inhibitors of AADH and exhibited K sub(i) values of 8 and 186 mu M, respectively. The similarities and differences between AADH and other amine oxidizing enzymes are also discussed. JF - Journal of Bacteriology AU - Govindaraj, S AU - Eisenstein, E AU - Jones, L H AU - Sanders-Loehr, J AU - Chistoserdov, A Y AU - Davidson, V L AU - Edwards, S L AD - Natl. Inst. Health, NIAMS, Build. 6, Room 425, 9000 Rockville Pike, Bethesda, MD 20892, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 2922 EP - 2929 VL - 176 IS - 10 SN - 0021-9193, 0021-9193 KW - aromatic amine dehydrogenase KW - Microbiology Abstracts B: Bacteriology KW - Raman spectroscopy KW - Alcaligenes faecalis KW - inhibitors KW - amino acid sequence KW - Michaelis-Menten parameters KW - J 02728:Enzymes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16902606?accountid=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=Aromatic+amine+dehydrogenase%2C+a+second+tryptophan+tryptophylquinone+enzyme&rft.au=Govindaraj%2C+S%3BEisenstein%2C+E%3BJones%2C+L+H%3BSanders-Loehr%2C+J%3BChistoserdov%2C+A+Y%3BDavidson%2C+V+L%3BEdwards%2C+S+L&rft.aulast=Govindaraj&rft.aufirst=S&rft.date=1994-01-01&rft.volume=176&rft.issue=10&rft.spage=2922&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=00219193&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Alcaligenes faecalis; amino acid sequence; Raman spectroscopy; Michaelis-Menten parameters; inhibitors ER - TY - JOUR T1 - The challenges posed by emerging infectious diseases AN - 16901650; 3595627 JF - ASM American Society for Microbiology News AU - Hughes, J M AU - Montagne, La, JR AD - Div. Microbiol. and Infect. Dis., NIAID/NIH, Rockville, MD 20892, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 248 EP - 250 VL - 60 IS - 5 SN - 0044-7897, 0044-7897 KW - emerging infection KW - Microbiology Abstracts C: Algology, Mycology & Protozoology; Virology & AIDS Abstracts; Microbiology Abstracts B: Bacteriology KW - epidemiology KW - pathogenesis KW - infectious diseases KW - epidemics KW - public health KW - J 02832:Antigenic properties and virulence KW - V 22122:Symptomatology, pathology & etiology KW - K 03092:Others UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16901650?accountid=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=ASM+American+Society+for+Microbiology+News&rft.atitle=The+challenges+posed+by+emerging+infectious+diseases&rft.au=Hughes%2C+J+M%3BMontagne%2C+La%2C+JR&rft.aulast=Hughes&rft.aufirst=J&rft.date=1994-01-01&rft.volume=60&rft.issue=5&rft.spage=248&rft.isbn=&rft.btitle=&rft.title=ASM+American+Society+for+Microbiology+News&rft.issn=00447897&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 - infectious diseases; public health; epidemics; pathogenesis; epidemiology ER - TY - JOUR T1 - Spatial resource partitioning by sympatric grey fox (Dusicyon griseus) and culpeo fox (Dusicyon culpaeus) in southern Chile AN - 16888541; 3802139 AB - The activity patterns, home-range use, and habitat utilization of sympatric South American grey fox (Dusicyon griseus) and culpeo fox (Dusicyon culpaeus) in eastern Torres del Paine National Park, Chile, were studied to determine how the two species were distributed. Both species were primarily nocturnal. Mean percent daily activity did not differ between species or among seasons, but the grey fox had a greater daily activity rate in summer and fall and the culpeo fox in winter and spring. Seasonal and annual home ranges of culpeo foxes were larger than those of grey foxes, but did not differ between sexes or among seasons. Home ranges of grey and culpeo foxes were interspersed in a mosaic-like arrangement and did not overlap. Grey foxes were located more often in upland shrub transition habitat and in areas of medium cover density. Culpeo foxes were found more often in thickets of trees and in areas of high cover density. Within their home range, matorral shrubland or Nothofagus thicket habitat was selected by all culpeo foxes and by 60% of grey foxes monitored. Interference competition by the culpeo fox may have been important in determining fox distribution. JF - Canadian Journal of Zoology/Revue Canadienne de Zoologie AU - Johnson, W E AU - Franklin, W L AD - Lab. Viral Carcinog., NCI, Frederick, MD 21702, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 1788 EP - 1793 VL - 72 IS - 10 SN - 0008-4301, 0008-4301 KW - Dusicyon griseus KW - Dusicyon culpaeus KW - Animal Behavior Abstracts; Ecology Abstracts KW - spatial distribution KW - home range KW - resource partitioning KW - Chile KW - Y 25387:Mammals (excluding primates) KW - D 04672:Mammals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16888541?accountid=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=Canadian+Journal+of+Zoology%2FRevue+Canadienne+de+Zoologie&rft.atitle=Spatial+resource+partitioning+by+sympatric+grey+fox+%28Dusicyon+griseus%29+and+culpeo+fox+%28Dusicyon+culpaeus%29+in+southern+Chile&rft.au=Johnson%2C+W+E%3BFranklin%2C+W+L&rft.aulast=Johnson&rft.aufirst=W&rft.date=1994-01-01&rft.volume=72&rft.issue=10&rft.spage=1788&rft.isbn=&rft.btitle=&rft.title=Canadian+Journal+of+Zoology%2FRevue+Canadienne+de+Zoologie&rft.issn=00084301&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 - Chile; spatial distribution; resource partitioning; home range ER - TY - JOUR T1 - Pseudomonas exotoxin A mutants: Replacement of surface-exposed residues in domain III with cysteine residues that can be modified with polyethylene glycol in a site-specific manner AN - 16885790; 3577780 AB - Pseudomonas exotoxin A (PE) is composed of three structural and functional domains. Domain Ia is responsible for cell recognition, domain II for translocation of PE across the cell membrane, and domain III for ADP-ribosylation of elongation factor 2. To investigate the role of the amino acids exposed on the surface of domain III, we replaced 15 of these, generating 29 different mutants at positions 412, 416, 418, 490, 513, 516, 522, 551, 576, 590, 599, 604, 606, 607 and 608. All but one mutant retained substantial ADP-ribosylation and cytotoxic activities. Modification of proteins with monomethoxy-polyethylene glycol (mPEG) prolongs their circulation in the blood stream and reduces their immunogenicity. Unlike PEGylated enzymes acting on small molecule substrates, PEGylated toxins may lose those functions that are based on macromolecular interactions. Therefore, we selectively PEGylated mutant PEs at positions 490, 513, 516, 522, 604, and 606. Most PEs modified by a 5-kDa mPEG via a disulfide or a thioether bond retained high cytotoxic activity. However, when a 20-kDa mPEG was used there was a decrease in cytotoxic activity with the disulfide-bonded molecules being more active. Positions 522 and 604 are good sites for PEGylation, but 490 is not. We also found that PEGylation of PE 522C prolonged its in vivo circulation time in mice. JF - Journal of Biological Chemistry AU - Benhar, I AU - Wang, Qing-cheng AU - FitzGerald, D AU - Pastan, I AD - Lab. Mol. Biol., Div. Cancer Biol., Diagn. and Cent., NCI/NIH, Bethesda, MD 20892, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 13398 EP - 13404 VL - 269 IS - 18 SN - 0021-9258, 0021-9258 KW - exotoxin A KW - monomethoxy polyethylene glycol KW - Microbiology Abstracts B: Bacteriology KW - site-directed mutagenesis KW - Pseudomonas KW - mutants KW - J 02822:Biosynthesis and physicochemical properties UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16885790?accountid=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=Pseudomonas+exotoxin+A+mutants%3A+Replacement+of+surface-exposed+residues+in+domain+III+with+cysteine+residues+that+can+be+modified+with+polyethylene+glycol+in+a+site-specific+manner&rft.au=Benhar%2C+I%3BWang%2C+Qing-cheng%3BFitzGerald%2C+D%3BPastan%2C+I&rft.aulast=Benhar&rft.aufirst=I&rft.date=1994-01-01&rft.volume=269&rft.issue=18&rft.spage=13398&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 - Pseudomonas; mutants; site-directed mutagenesis ER - TY - JOUR T1 - Polymerase chain reaction-based diagnosis of Onchocerca volvulus infection: Improved detection of patients with onchocerciasis AN - 16880566; 3804046 AB - Definitive diagnosis of Onchocerca volvulus (Ov) infection requires the identification of the parasite in either the skin or subcutaneous nodules. These parasitologic approaches suffer from poor sensitivity. To assess the efficacy and utility of a polymerase chain reaction (PCR)-based diagnosis for Ov infection, skin snips were examined from 94 persons in an Ov-endemic region of Ecuador, and results were compared in a blinded fashion with those of a PCR assay based on the Onchocerca-specific repetitive DNA sequence, O-150. All 60 patients microfilaria-positive on skin snip examination were positive in the PCR-based assay. In addition, 13 of 34 who were microfilaria-negative by skin snips were positive in the PCR assay. This suggests that the PCR-based assay is significantly more sensitive than current methods and overcomes many deficiencies of parasitologic and serologic methodologies in diagnosing active onchocerciasis. JF - Journal of Infectious Diseases AU - Zimmerman, P A AU - Guderian, R H AU - Aruajo, E AU - Elson, L AU - Phadke, P AU - Kubofcik, J AU - Nutman, T B AD - LPD/NIAID/NIH, Bldg. 4, Room 126, 9000 Rockville Pike, Bethesda, MD 20892, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 686 EP - 689 VL - 169 IS - 3 SN - 0022-1899, 0022-1899 KW - onchocerciasis KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Onchocerca volvulus KW - diagnosis KW - polymerase chain reaction KW - man KW - W 30965:Miscellaneous, Reviews KW - W3 33130:Genetic based (PCR, etc.) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16880566?accountid=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=Pediatrics&rft.atitle=Variability+and+self-regulation+of+energy+intake+in+young+children+in+their+everyday+environment.&rft.au=Shea%2C+S%3BStein%2C+A+D%3BBasch%2C+C+E%3BContento%2C+I+R%3BZybert%2C+P&rft.aulast=Shea&rft.aufirst=S&rft.date=1992-10-01&rft.volume=90&rft.issue=4&rft.spage=542&rft.isbn=&rft.btitle=&rft.title=Pediatrics&rft.issn=00314005&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 - diagnosis; man; polymerase chain reaction; Onchocerca volvulus ER - TY - JOUR T1 - Kinetic determination of cellular LacZ expression AN - 16876371; 3580559 AB - A kinetic assay for the expression of beta -galactosidase in cells transfected with the LacZ gene was developed using a 96-well-plant format. The assay involves solubilization of the cells followed by measuring hydrolytic rates of o-nitrophenyl beta -galactosidase on a standard 96-well-plant reader without other manipulations. The protocol requires only that reagent be added sequentially to the wells at ambient temperatures, thus permitting a semiautomated or fully automated determination of reporter expression. The rates of chromophore development were found to be linear over a 6-log enzyme concentration range, from 0.001 to 100 mU. Additionally, the use of kinetic data avoids the complications of non-enzymatic, background optical density. JF - Genetic Analysis: Biomolecular Engineering AU - Marsh, J AD - NIMH, Build. 336, Rm. 1B08, Bethesda, MD 20892, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 20 EP - 23 VL - 11 IS - 1 SN - 1050-3862, 1050-3862 KW - LacZ gene KW - beta -galactosidase KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - genes KW - Escherichia coli KW - gene expression KW - assays KW - kinetics KW - N 14510:Occurrence, isolation & assay KW - J 02726:RNA and ribosomes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16876371?accountid=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=Genetic+Analysis%3A+Biomolecular+Engineering&rft.atitle=Kinetic+determination+of+cellular+LacZ+expression&rft.au=Marsh%2C+J&rft.aulast=Marsh&rft.aufirst=J&rft.date=1994-01-01&rft.volume=11&rft.issue=1&rft.spage=20&rft.isbn=&rft.btitle=&rft.title=Genetic+Analysis%3A+Biomolecular+Engineering&rft.issn=10503862&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; gene expression; kinetics; assays; genes ER - TY - JOUR T1 - Importance of the region around lysine 196 for catalytic activity of adenylyl cyclase from Escherichia coli AN - 16865582; 3786370 AB - Escherichia coli adenylyl cyclase contains no sequence that corresponds to the previously defined ATP/GTP binding consensus (A,G)XXXXGK(S,T). Using a search for lysine residues located adjacent to glycine residues, three regions that were possible candidates for part of the ATP binding site were identified. These were the residues located at positions 59, 90, and 196. A plasmid vector capable of overexpressing the cya gene under the control of the lambda P sub(L) promoter was mutated at these three loci to convert those lysine residues to methionine. Assays for catalytic activity of the mutated hyperexpressed proteins revealed that only the mutation at position 196 led to loss of activity. Photoaffinity labeling experiments using 8-azido-ATP provided evidence that the loss of activity was associated with a loss of the capability of the enzyme to bind ATP. A further series of replacement mutations in the hyperexpression vector was created at position 196. Assays of the adenylyl cyclase activity of the mutated proteins showed that replacement of lysine 196 by arginine led to minimal change in the activity. Replacements by histidine, glutamine, or glutamic acid resulted in approximately 10-20-fold reductions in the activity; replacements by methionine, isoleucine, or aspartic acid resulted in total loss of activity. When the mutated forms of the cya gene were expressed under the control of the cya promoter, the activity of the wild-type protein was higher than that of all the mutants, including the arginine replacement mutant. All of the mutants that retained activity also retained the capability of adenylyl cyclase to be stimulated by either inorganic orthophosphate or GTP. A helical wheel analysis of the region of adenylyl cyclase around lysine 196 revealed a structure compatible with an amphipathic helix with one face enriched with basic amino acid residues. Assays for adenylyl cyclase activity of a series of replacement mutations of residues on the hydrophilic face of the helix (R188I, R192I, G195I) as well as on the hydrophobic face (R197I) indicated that the R188I, G195I, and K196I replacement mutants were inactive, and R192I was approximately 30% as active as the wild-type, while the R197I mutant was equivalent to the wild-type control. A model is suggested for a unique binding motif in E. coli adenylyl cyclase in which there is a repetition of 3 basic residues on one face of a helix where there is an interaction with the three phosphate groups of ATP. JF - Journal of Biological Chemistry AU - Amin, N AU - Peterkofsky, A AD - Lab. Neurochem., NINDS, Bethesda, MD 20892, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 31094 EP - 31079 VL - 269 IS - 49 SN - 0021-9258, 0021-9258 KW - adenylyl cyclase KW - ATP KW - catalytic activity KW - lysine KW - Microbiology Abstracts B: Bacteriology KW - Escherichia coli KW - J 02728:Enzymes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16865582?accountid=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=Importance+of+the+region+around+lysine+196+for+catalytic+activity+of+adenylyl+cyclase+from+Escherichia+coli&rft.au=Amin%2C+N%3BPeterkofsky%2C+A&rft.aulast=Amin&rft.aufirst=N&rft.date=1994-01-01&rft.volume=269&rft.issue=49&rft.spage=31094&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 ER - TY - JOUR T1 - Organization and expression of the Escherichia coli K-12 dad operon encoding the smaller subunit of D-amino acid dehydrogenase and the catabolic alanine racemase AN - 16855898; 3574150 AB - A fragment of the Escherichia coli K-12 chromosome complementing the D-amino acid dehydrogenase and catabolic alanine racemase deficiency of a dad operon deletion mutant was cloned in a mini-Mu plasmid. The dadA and dadX genes were localized to a 3.5-kb part of the plasmid insert. The nucleotide sequence of this fragment revealed two open reading frames encoding 432- and 356-amino-acid-long proteins. We show here that they correspond to the dadA and dadX genes. The dadA gene can encode only the smaller of the two subunits of D-amino acid dehydrogenase. A computer search revealed the presence of a flavin adenine dinucleotide-binding motif in the N-terminal domain of the deduced DadA protein sequence. This is in agreement with biochemical data showing that the D-amino acid dehydrogenase contains flavin adenine dinucleotide in its active center. The predicted dadX gene product appeared to be 85% identical to a dadB-encoded catabolic alanine racemase of Salmonella typhimurium. The organization of the dadA and dadX genes confirmed our previous conclusion based on the genetic data that these genes form an operon. The main transcription start points of the dad operon were determined by primer extension. They are preceded by a putative sigma super(70) promoter sequence and two cyclic AMP-cyclic AMP receptor protein (cAMP-CRP) binding sites, one of higher and one of lower affinity to CRP. We propose that the high-affinity site, centered 59.5 bp upstream of the main transcription start point, plays a role in cAMP-CRP-mediated activation of dad operon expression in the absence of glucose. JF - Journal of Bacteriology AU - Lobocka, M AU - Hennig, J AU - Wild, J AU - Klopotowski, T AD - Lab. Biochem., NCI, NIH, Bldg. 37, Rm. 4D-15, Bethesda, MD 20892, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 1500 EP - 1510 VL - 176 IS - 5 SN - 0021-9193, 0021-9193 KW - dad operon KW - glucose KW - Microbiology Abstracts B: Bacteriology KW - expression KW - operons KW - organization KW - Escherichia coli KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16855898?accountid=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=Carcinogenesis&rft.atitle=The+role+of+O6-alkylguanine-DNA+alkyltransferase+in+protecting+Rat4+cells+against+the+mutagenic+effects+of+O6-substituted+guanine+residues+incorporated+in+codon+12+of+the+H-ras+gene.&rft.au=Bishop%2C+R+E%3BDunn%2C+L+L%3BPauly%2C+G+T%3BDolan%2C+M+E%3BMoschel%2C+R+C&rft.aulast=Bishop&rft.aufirst=R&rft.date=1993-04-01&rft.volume=14&rft.issue=4&rft.spage=593&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 - Escherichia coli; operons; organization; expression ER - TY - JOUR T1 - Cohort mortality and nested case-control study of lung cancer among structural pest control workers in Florida (United States) AN - 16844570; 3782049 AB - A previous report on the mortality of this cohort of Florida (United States) pest control workers found the risk of lung cancer was positively associated with the number of years licensed. An additional follow-up (1977-82) of this male cohort confirmed the excess (SMR = 1.4) and the rising risk with increasing number of years licensed (SMR = 2.2 among workers employed more than 20 years). A nested case-control study was undertaken to determine the effects of smoking and the type of pesticide exposure on lung cancer risk. Occupational histories and other data were obtained on 65 deceased lung cancer cases, 122 deceased controls, and 172 living controls. Interviews were conducted with next-of-kin regardless of the vital status of the subject. Odds ratios (OR) were adjusted by age and smoking. Adjustments for diet and other occupations had no effect on risk estimates and were not included in the final model. Using information from licensing records, ORs for lung cancer were greater for workers first licensed before age 40 (OR = 2.4, 95 percent confidence interval [CI] = 1.0-5.9 with deceased controls) and increased from 1.4 (CI = 0.7-3.0) for subjects licensed 10-19 years to 2.1 (CI = 0.8-5.5) for subjects licensed 20 or more years. JF - Cancer Causes & Control AU - Pesatori, A C AU - Sontag, J M AU - Lubin, J H AU - Consoni, D AU - Blair, A AD - NCI, Executive Plaza N., Rm. 418, Rockville, MD 20892, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 310 EP - 318 VL - 5 IS - 4 SN - 0957-5243, 0957-5243 KW - lung cancer KW - man KW - Toxicology Abstracts; Risk Abstracts; Health & Safety Science Abstracts KW - USA, Florida KW - chemicals KW - occupational exposure KW - males KW - lung KW - mortality KW - pesticides KW - cancer KW - R2 23080:Industrial and labor KW - X 24132:Chronic exposure KW - H SM10.21:CANCER KW - H SE5.3:HAZARD DETERMINATION UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16844570?accountid=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=Cohort+mortality+and+nested+case-control+study+of+lung+cancer+among+structural+pest+control+workers+in+Florida+%28United+States%29&rft.au=Pesatori%2C+A+C%3BSontag%2C+J+M%3BLubin%2C+J+H%3BConsoni%2C+D%3BBlair%2C+A&rft.aulast=Pesatori&rft.aufirst=A&rft.date=1994-01-01&rft.volume=5&rft.issue=4&rft.spage=310&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 - USA, Florida; pesticides; occupational exposure; lung cancer; mortality; chemicals; lung; males; cancer; man ER - TY - JOUR T1 - Relaxation of replication control in chaperone-independent initiator mutants of plasmid P1 AN - 16843069; 3564763 AB - Escherichia coli chaperones DnaJ, DnaK and GrpE increase P1 plasmid initiator binding to the origin by promoting initiator folding. The binding allows initiation and also promotes pairing of origins which is believed to control initiation frequency. Chaperone-independent DNA binding mutants are often defective in replication control. We show here that these mutants have increased rates of association for DNA binding and defects in origin pairing. The increases in association rates were found to be due either to increased protein folding into active forms or to increases in the association rate constant, k sub(on). Since the dissociation rate constants for DNA release with these mutants are not changed, it is unlikely that the DNA binding domain is affected. The pairing domain may thus control replication and modulate DNA binding. The role of the pairing domain in DNA binding can be significant in vivo as the selection for chaperone-independent binding favors pairing-defective mutants. JF - EMBO Journal AU - Mukhopadhyay, G AU - Sozhamannan, S AU - Chattoraj, D K AD - Lab. Biochem., NCI, 37/4D-18 NIH, Bethesda, MD 20892, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 2089 EP - 2096 VL - 13 IS - 9 SN - 0261-4189, 0261-4189 KW - chaperone KW - DnaJ protein KW - DnaK protein KW - GpE protein KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - protein folding KW - domains KW - mutants KW - replication KW - DNA KW - Escherichia coli KW - binding KW - J 02760:Plasmids KW - J 02727:Amino acids, peptides and proteins KW - N 14940:Nucleic acid-binding proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16843069?accountid=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=Relaxation+of+replication+control+in+chaperone-independent+initiator+mutants+of+plasmid+P1&rft.au=Mukhopadhyay%2C+G%3BSozhamannan%2C+S%3BChattoraj%2C+D+K&rft.aulast=Mukhopadhyay&rft.aufirst=G&rft.date=1994-01-01&rft.volume=13&rft.issue=9&rft.spage=2089&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 - Escherichia coli; mutants; DNA; binding; domains; protein folding; replication ER - TY - JOUR T1 - The long- and short-term effects of marriage on drinking AN - 16833974; 3772332 AB - Descriptive and multiple regression analyses of data from the National Longitudinal Survey of Youth (NLSY), a longitudinal survey conducted annually since 1979, offer support for the many studies that demonstrate a relationship between marital status and alcohol consumption. Race, gender, history of heavy drinking, and alcoholic relatives were additional key variables utilized in the analysis. Data from this ongoing survey indicate that long-term marriage is associated with decreased drinking, except among women with a history of heavy drinking. Separation and divorce are not associated with long-term effects on current drinking. Divorce is associated with decreased drinking, at least in the short term, for men and women with a family history of alcoholism. JF - Journal of Substance Abuse AU - Harford, T C AU - Hanna, E Z AU - Faden, V B AD - Div. Biometry and Epidemiol., NIAAA, 6000 Executive Blvd., Suite 514, Rockville, MD 20892-7003, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 209 EP - 217 VL - 6 IS - 2 SN - 0899-3289, 0899-3289 KW - marital status KW - substance abuse KW - alcoholism KW - Risk Abstracts KW - genetics KW - ethnic groups KW - gender KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16833974?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Substance+Abuse&rft.atitle=The+long-+and+short-term+effects+of+marriage+on+drinking&rft.au=Harford%2C+T+C%3BHanna%2C+E+Z%3BFaden%2C+V+B&rft.aulast=Harford&rft.aufirst=T&rft.date=1994-01-01&rft.volume=6&rft.issue=2&rft.spage=209&rft.isbn=&rft.btitle=&rft.title=Journal+of+Substance+Abuse&rft.issn=08993289&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - gender; ethnic groups; genetics ER - TY - JOUR T1 - Thermal inactivation of tryptophan synthase: Stabilization by protein-protein interaction and protein-ligand interaction AN - 16832846; 3562564 AB - This study investigates effects of ligands on thermal inactivation of the tryptophan synthase alpha and beta sub(2) subunits alone and in the alpha sub(2) beta sub(2) complex. Addition of pyridoxal phosphate to the apo- beta sub(2) subunit increases the temperature of one-half inactivation (T sub(i)) from 52 to 77 degree C. Ligands that promote association of the alpha and holo- beta sub(2) subunits markedly stabilize the more temperature-labile alpha subunit in the alpha sub(2) beta sub(2) complex from irreversible thermal denaturation. The combination of a beta sub(2) subunit ligand (L-serine) with an alpha subunit ligand ( alpha -glycerol 3-phosphate) raises the inactivation temperature (T sub(i)) of the alpha subunit in the holo- alpha sub(2) beta sub(2) complex from 54 to 66 degree C. In contrast, values of T sub(i) for inactivation of the alpha and beta subunits in the holo- alpha sub(2) beta sub(2) complex are more similar to respective values for the isolated alpha subunit (50 degree C) and holo- beta sub(2) subunit (77 degree C). Surprisingly, the addition of L-serine results in a larger decrease in the T sub(i) of the beta sub(2) subunit in the holo- alpha sub(2) beta sub(2) complex (78 degree C arrow right 64 degree C) than in T sub(i) of the holo- beta sub(2) subunit alone (77 degree C arrow right 71 degree C). The observation that ligands have different effects on the isolated and associated subunits provides evidence that the alpha and beta sub(2) subunits do not fully dissociate during thermal inactivation of the alpha sub(2) beta sub(2) complex at pH 7.8 and at similar to 0.1 ionic strength. Our results demonstrate that linkage between protein-ligand interactions and protein-protein interactions affects the conformational stability of the tryptophan synthase alpha sub(2) beta sub(2) complex. JF - Journal of Biological Chemistry AU - Ruvinov, S B AU - Miles, E W AD - Lab. Biochem. Pharmacol., NIDDK/NIH, Build. 8, Rm. 2A-09, Bethesda, MD 20892, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 11703 EP - 11706 VL - 269 IS - 16 SN - 0021-9258, 0021-9258 KW - tryptophan synthase KW - Microbiology Abstracts B: Bacteriology KW - ligands KW - heat inactivation KW - interaction KW - conformation KW - Salmonella typhimurium KW - proteins KW - J 02728:Enzymes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16832846?accountid=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=Thermal+inactivation+of+tryptophan+synthase%3A+Stabilization+by+protein-protein+interaction+and+protein-ligand+interaction&rft.au=Ruvinov%2C+S+B%3BMiles%2C+E+W&rft.aulast=Ruvinov&rft.aufirst=S&rft.date=1994-01-01&rft.volume=269&rft.issue=16&rft.spage=11703&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 - Salmonella typhimurium; heat inactivation; conformation; proteins; ligands; interaction ER - TY - JOUR T1 - The use of interleukin-6 to generate tumor-infiltrating lymphocytes with enhanced in vivo antitumor activity AN - 16819561; 3766848 AB - Tumor-infiltrating lymphocytes (TIL) are cytotoxic T cells isolated from solid tumors and expanded in vitro in recombinant interleukin-2 (rIL-2). TIL have antitumor effects in murine models and in some patients with melanoma. In an effort to generate murine TIL with enhanced in vivo therapeutic efficacy, viable tumor cells were coinjected with a collagen matrix plus recombinant human IL-6 (rIL-6) subcutaneously into syngeneic mice to achieve sustained local concentrations of rIL-6 at the tumor site from which TIL were derived. In five separate experiments, single cell suspensions of tumors were admixed with either (a) Hanks' balanced salt solution (HBSS), (b) 2% (20 mg/ml) collagen matrix only, (c) 250 mu g rIL-6 only, or (d) 250 mu g rIL-6 in a 2% collagen matrix (prolonged release) before subcutaneous inoculation. These tumors were subsequently resected and TIL were isolated and expanded in vitro. TIL generated from tumors admixed with matrix plus rIL-6 were significantly more effective than TIL expanded from tumors admixed with HBSS (four of five experiments), TIL from tumors admixed with matrix only (five of five experiments), and TIL from tumors admixed with rIL-6 only (three of four experiments) in an established tumor treatment model. In no experiment was any other TIL culture superior to TIL grown from tumors augmented with collagen matrix plus rIL-6. These results suggest that strategies designed to increase the local concentrations of cytokines at tumor sites may lead to the generation of more potent TIL for clinical administration. JF - Journal of Immunotherapy AU - Marcus, S G AU - Perry-Lalley, D AU - Mule, J J AU - Rosenberg, SA AU - Yang, J C AD - Surg. Branch, NCI/NIH, 9000 Rockville Pike, Build. 10, Rm. 2B-42, Bethesda, MD 20892, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 105 EP - 112 VL - 15 IS - 2 SN - 1053-8550, 1053-8550 KW - mice KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - adoptive immunotherapy KW - tumor-infiltrating lymphocytes KW - interleukin 6 KW - lymphocytes T KW - killer cells KW - F 06818:Cancer immunotherapy KW - W3 33150:Cytokine based KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16819561?accountid=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=The+use+of+interleukin-6+to+generate+tumor-infiltrating+lymphocytes+with+enhanced+in+vivo+antitumor+activity&rft.au=Marcus%2C+S+G%3BPerry-Lalley%2C+D%3BMule%2C+J+J%3BRosenberg%2C+SA%3BYang%2C+J+C&rft.aulast=Marcus&rft.aufirst=S&rft.date=1994-01-01&rft.volume=15&rft.issue=2&rft.spage=105&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immunotherapy&rft.issn=10538550&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - adoptive immunotherapy; tumor-infiltrating lymphocytes; lymphocytes T; interleukin 6; killer cells ER - TY - JOUR T1 - Is taxol a surrogate for a universal regulator of mitosis? AN - 16819270; 3764073 AB - Taxol is well recognized as an antitumor agent and a biochemical tool for studies of microtubules. A proposal is made that taxol is a surrogate for a key endogenous regulator of microtubules, which has the particular function of stabilizing the mitotic spindle. This proposal is based on evidence from the breadth of taxol activity across organisms, data supporting a highly conserved binding site for taxol, low-dose effects of taxol targeting the mitotic spindle, the restriction of the binding site to a highly conserved segment of B-tubulin, data on the biosynthesis and distribution of taxol, and the recent discovery of an anti-idiotype antibody with taxol-like activity. JF - In Vivo AU - Suffness, M AD - Devel. Ther. Program, Div. Cancer Treat., NCI/NIH, Rm. 832 Executive Plaza N., Bethesda, MD 20892, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 867 EP - 878 VL - 8 IS - 5 SN - 0258-851X, 0258-851X KW - taxol KW - tubulin KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - mitosis KW - microtubules KW - reviews KW - antiidiotypes KW - cell cycle KW - spindles KW - W 30965:Miscellaneous, Reviews KW - W3 33390:Products: Others UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16819270?accountid=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=In+Vivo&rft.atitle=Is+taxol+a+surrogate+for+a+universal+regulator+of+mitosis%3F&rft.au=Suffness%2C+M&rft.aulast=Suffness&rft.aufirst=M&rft.date=1994-01-01&rft.volume=8&rft.issue=5&rft.spage=867&rft.isbn=&rft.btitle=&rft.title=In+Vivo&rft.issn=0258851X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - SuppNotes - Special issue on Behalf of the International Society for the Study of Comparative Oncology. N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - mitosis; reviews; microtubules; antiidiotypes; cell cycle; spindles ER - TY - JOUR T1 - Chemical mutagenesis testing in Drosophila AN - 16816404; 3547169 AB - Fifty chemicals were tested for mutagenic activity in post-meiotic and meiotic germ cells of male Drosophila melanogaster using the sex-linked recessive lethal (SLRL) assay. As in the previous studies in this series, feeding was chosen as the first route of administration. If the compound failed to induce mutations by this route, injection exposure was used. One gaseous chemical (1,3-butadiene) was tested only by inhalation. Those chemicals that were mutagenic in the sex-linked recessive lethal assay were further tested for the ability to induce reciprocal translocations. Eleven of the 50 chemicals tested were mutagenic in the SLRL assay. JF - Environmental and Molecular Mutagenesis AU - Foureman, P AU - Mason, J M AU - Valencia, R AU - Zimmering, S AD - P.O. Box 12233, Cell. and Genet. Toxicol. Branch, NIEHS, Research Triangle Park, NC 27709, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 51 EP - 63 VL - 23 IS - 1 SN - 0893-6692, 0893-6692 KW - Entomology Abstracts; Genetics Abstracts; Toxicology Abstracts KW - mutagenicity KW - xenobiotics KW - Drosophila melanogaster KW - genotoxicity testing KW - G 07220:General theory/testing systems KW - Z 05215:Mutation KW - X 24221:Toxicity testing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16816404?accountid=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+and+Molecular+Mutagenesis&rft.atitle=Chemical+mutagenesis+testing+in+Drosophila&rft.au=Foureman%2C+P%3BMason%2C+J+M%3BValencia%2C+R%3BZimmering%2C+S&rft.aulast=Foureman&rft.aufirst=P&rft.date=1994-01-01&rft.volume=23&rft.issue=1&rft.spage=51&rft.isbn=&rft.btitle=&rft.title=Environmental+and+Molecular+Mutagenesis&rft.issn=08936692&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Drosophila melanogaster; xenobiotics; mutagenicity; genotoxicity testing ER - TY - JOUR T1 - Construction of a series of congenic mice with recombinant chromosome 1 regions surrounding the genetic loci for resistance to intracellular parasites (Ity, Lsh, and Bcg), DNA repair responses (Rep-1), and the cytoskeletal protein villin (Vil) AN - 16812018; 3554257 AB - The interval of mouse chromosome 1 extending from Idh-1 to Pep-3 harbors the natural resistance gene Ity/Lsh/Beg; it controls the outcome of infection with Salmonella typhimurium, Leishmania donovani, and several Mycobacterium species. This region also contains a DNA repair gene, Rep-1, which determines the rapidity with which double-strand breaks in chromatin are repaired. BALB/cAnPt and DBA/2N mice differ in their phenotypic expression of these genes. To generate appropriate strains of mice for the study of these genes, a series of 10 C.D2 congenic strains recombinant across a 28-centimorgan interval of mouse chromosome 1 extending from Idh-1 to Pep-3 were derived from crosses of the C.D2-Idh-1 Pep-3 congenic strain back to BALB/cAn. Analyses of these recombinant strains will allow the correlation of biological-immunological phenotypes with defined genetic regions. JF - Infection and Immunity AU - Mock, BA AU - Holiday, D L AU - Cerretti, D P AU - Darnell, S C AU - O'Brien, AD AU - Potter, M AD - Lab. Genet., Build. 37, Rm. 2B-08, NCI, NIH, Bethesda, MD 20892, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 325 EP - 328 VL - 62 IS - 1 SN - 0019-9567, 0019-9567 KW - Beg gene KW - Ity gene KW - Lsh gene KW - mice KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Genetics Abstracts KW - Leishmania donovani KW - Mycobacterium KW - genes KW - Salmonella typhimurium KW - DNA repair KW - W 30965:Miscellaneous, Reviews KW - W3 33055:Genetic engineering (general) KW - G 07124:REPAIR UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16812018?accountid=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=Infection+and+Immunity&rft.atitle=Construction+of+a+series+of+congenic+mice+with+recombinant+chromosome+1+regions+surrounding+the+genetic+loci+for+resistance+to+intracellular+parasites+%28Ity%2C+Lsh%2C+and+Bcg%29%2C+DNA+repair+responses+%28Rep-1%29%2C+and+the+cytoskeletal+protein+villin+%28Vil%29&rft.au=Mock%2C+BA%3BHoliday%2C+D+L%3BCerretti%2C+D+P%3BDarnell%2C+S+C%3BO%27Brien%2C+AD%3BPotter%2C+M&rft.aulast=Mock&rft.aufirst=BA&rft.date=1994-01-01&rft.volume=62&rft.issue=1&rft.spage=325&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - genes; DNA repair; Leishmania donovani; Mycobacterium; Salmonella typhimurium ER - TY - JOUR T1 - Isolation and characterization of a regulatory gene affecting rhamnolipid biosurfactant synthesis in Pseudomonas aeruginosa AN - 16810325; 3555499 AB - A mutant strain (65E12) of Pseudomonas aeruginosa that is unable to produce rhamnolipid biosurfactants and lacks rhamnosyltransferase activity was genetically complemented by using a P. aeruginosa PG201 wild-type gene library. A single complementing cosmid was isolated on the basis of surface tension measurements of subcultures of the transconjugants by using a sib selection strategy. The subcloning of the complementing cosmid clone yielded a 2-kb fragment capable of restoring rhamnolipid biosynthesis, rhamnosyltransferase activity, and utilization of hexadecane as a C source in mutant 65E12. The nucleotide sequence of the complementing 2-kb fragment was determined, and a single open reading frame (rhlR) of 723 bp specifying a putative 28-kDa protein (RhlR) was identified. Sequence homologies between the RhlR protein and some regulatory proteins such as LasR of P. aeruginosa, LuxR of Vibrio fischeri, RhiR of Rhizobium leguminosarum, and the putative activator 28-kDa UvrC of Escherichia coli suggest that the RhlR protein is a transcriptional activator. A putative target promoter which is regulated by the RhlR protein has been identified 2.5 kb upstream of the rhlR gene. Multiple plasmid-based rhlR gene copies had a stimulating effect on the growth of the P. aeruginosa wild-type strain in hexadecane-containing minimal medium, on rhamnolipid production, and on the production of pyocyanin chromophores. Disruption of the P. aeruginosa wild-type rhlR locus led to rhamnolipid-deficient mutant strains, thus confirming directly that this gene is necessary for rhamnolipid biosynthesis. Additionally, such PG201::'rhlR' mutant strains lacked elastase activity, indicating that the RhlR protein is a pleiotropic regulator. JF - Journal of Bacteriology AU - Ochsner, U A AU - Koch, A K AU - Fiechter, A AU - Reiser, J AD - NINDS/NIH, Build. 10, Rm. 4N309, Bethesda, MD 20892, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 2044 EP - 2054 VL - 176 IS - 7 SN - 0021-9193, 0021-9193 KW - RhlR protein KW - rhamnolipids KW - rhamnosyltransferase KW - rhlR gene KW - Biotechnology and Bioengineering Abstracts; Genetics Abstracts; Agricultural and Environmental Biotechnology Abstracts; Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - nucleotide sequence KW - genes KW - amino acid sequence KW - mutation KW - prediction KW - Pseudomonas aeruginosa KW - synthesis KW - activity KW - N 14640:Structure & sequence KW - W2 32060:Microorganisms KW - G 07321:GENERAL KW - W 30965:Miscellaneous, Reviews KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16810325?accountid=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=Isolation+and+characterization+of+a+regulatory+gene+affecting+rhamnolipid+biosurfactant+synthesis+in+Pseudomonas+aeruginosa&rft.au=Ochsner%2C+U+A%3BKoch%2C+A+K%3BFiechter%2C+A%3BReiser%2C+J&rft.aulast=Ochsner&rft.aufirst=U&rft.date=1994-01-01&rft.volume=176&rft.issue=7&rft.spage=2044&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=00219193&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - nucleotide sequence; amino acid sequence; genes; mutation; prediction; synthesis; activity; Pseudomonas aeruginosa ER - TY - JOUR T1 - Selenophosphate synthetase: Enzyme properties and catalytic reaction AN - 16806580; 3555589 AB - Selenophosphate synthetase, the product of the selD gene, produces the biologically active selenium donor compound, monoselenophosphate, from ATP and selenide. Isolation of the enzyme and characterization of some of its physical and catalytic properties are described. Magnesium ion and a monovalent cation, K super(+), NH sub(4) super(+), or Rb super(+), are required for catalytic activity. Polyphosphates and other common nucleotide triphosphates do not replace ATP as substrate. The stoichiometry of the catalytic reaction (Reaction 1) was established using super(31)P NMR, anaerobic molecular sieve chromatography, and radiochemical labeling procedures. In the absence of selenide, ATP is converted completely to AMP and orthophosphate upon prolonged incubation with elevated levels of enzyme. AMP is a competitive inhibitor of ATP, K sub(i) = 170 mu M, whereas selenophosphate and orthophosphate are weak inhibitors indicating a multistep reaction. Attempts to obtain direct evidence for a postulated enzyme-pyrophosphate intermediate using several experimental approaches are described. No exchange of [ super(14)C]AMP with ATP could be detected after the enzyme was freed of traces of contaminating adenylate kinase by chromatography on phenyl-Sepharose. JF - Journal of Biological Chemistry AU - Veres, Z AU - Kim, Ick Young AU - Scholz, T D AU - Stadtman, T C AD - Lab. Biochem., NHLBI, NIH, Build. 3, Rm. 108, Bethesda, MD 20892, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 10597 EP - 10603 VL - 269 IS - 14 SN - 0021-9258, 0021-9258 KW - selenophosphate synthase KW - Microbiology Abstracts B: Bacteriology KW - Escherichia coli KW - enzymatic activity KW - stoichiometry KW - kinetics KW - J 02728:Enzymes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16806580?accountid=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=Selenophosphate+synthetase%3A+Enzyme+properties+and+catalytic+reaction&rft.au=Veres%2C+Z%3BKim%2C+Ick+Young%3BScholz%2C+T+D%3BStadtman%2C+T+C&rft.aulast=Veres&rft.aufirst=Z&rft.date=1994-01-01&rft.volume=269&rft.issue=14&rft.spage=10597&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; enzymatic activity; kinetics; stoichiometry ER - TY - JOUR T1 - Risk of other cancers following Kaposi's sarcoma: Relation to acquired immunodeficiency syndrome AN - 16786534; 3541105 AB - To evaluate the risk of another cancer among persons who initially developed Kaposi's sarcoma, the authors used data from the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute for the years 1973-1990. In persons under 70 years of age, 4,946 cases of Kaposi's sarcoma were observed during the period 1980-1990 (6,217 person-years of follow-up). On the basis of rates seen during the period prior to the epidemic of acquired immunodeficiency syndrome (AIDS), 169 cases were expected. Therefore, cases of Kaposi's sarcoma in this group were assumed to be AIDS-related, while cases occurring in older persons or during the 1970s were assumed to be non-AIDS-related. Rates were compared with the numbers of cases expected overall and by site on the basis of age-, sex-, and calendar year-specific rates from the SEER data. Among the 4,946 persons with AIDS-related Kaposi's sarcoma, the risk of developing non-Hodgkin's lymphoma through 1990 was increased 198-fold (95% confidence interval 169-232). However, the risk of all other cancers was only marginally increased (1.5-fold; 95% confidence interval 0.95-2.3), a risk that was probably biased upward because of ascertainment and misclassification. Among 491 persons with non-AIDS-related Kaposi's sarcoma, the relative risk of all cancers, including non-Hodgkin's lymphoma, was 0.9 (upper 95% confidence limit 1.2), and the risk of non-Hodgkin's lymphoma alone was 0.6 (upper 95% confidence limit 3.3). As of 1990, the risk of having another cancer following Kaposi's sarcoma was increased only in persons infected with human immunodeficiency virus, who were at high risk of non-Hodgkin's lymphoma but probably not of other cancers as a whole. JF - American Journal of Epidemiology AU - Biggar, R J AU - Curtis, R E AU - Cote, T R AU - Rabkin, C S AU - Melbye, M AD - NCI/NIH, Executive Plaza N., Rm. 434, 6130 Executive Blvd., Rockville, MD 20852, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 362 EP - 368 VL - 139 IS - 4 SN - 0002-9262, 0002-9262 KW - risks KW - Kaposi's sarcoma KW - neoplasm KW - colorectal KW - Risk Abstracts; Virology & AIDS Abstracts KW - epidemiology KW - risk assessment KW - acquired immune deficiency syndrome KW - V 22005:AIDS: Epidemiological aspects KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16786534?accountid=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+Epidemiology&rft.atitle=Risk+of+other+cancers+following+Kaposi%27s+sarcoma%3A+Relation+to+acquired+immunodeficiency+syndrome&rft.au=Biggar%2C+R+J%3BCurtis%2C+R+E%3BCote%2C+T+R%3BRabkin%2C+C+S%3BMelbye%2C+M&rft.aulast=Biggar&rft.aufirst=R&rft.date=1994-01-01&rft.volume=139&rft.issue=4&rft.spage=362&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 N1 - SubjectsTermNotLitGenreText - acquired immune deficiency syndrome; epidemiology; risk assessment; risks; Kaposi's sarcoma; colorectal ER - TY - JOUR T1 - Cigarette smoking and pancreas cancer: a case - control study based on direct interviews AN - 16781682; 3740198 AB - Cigarette smoking is the most consistently reported risk factor for pancreas cancer, yet the dose-response relationship in many pancreas cancer studies is weak. Because of the poor prognosis for pancreas cancer, many case-control studies have been based largely on interviews with proxy respondents, who are known to report less reliable information on detailed smoking habits than original subjects. Our purpose was to evaluate cigarette smoking as a risk factor for pancreas cancer based on data obtained only from direct interviews and to estimate the effects of quitting smoking and of switching from nonfiltered to filtered cigarettes on risk. Our objective also was to estimate the contribution of cigarette smoking toward explaining the higher pancreas cancer incidence experienced by black Americans compared with white Americans. JF - Journal of the National Cancer Institute AU - Silverman, D T AU - Dunn, JA AU - Hoover, R N AU - Schiffman, M AU - Lillemoe, K D AU - Schoenberg, J B AU - Brown, L M AU - Greenberg, R S AU - Hayes, R B AU - Swanson, G M AU - Wacholder, S AU - Schwartz, A G AU - Liff, J M AU - Pottern, L M AD - Epidemiol. and Biostatistics Program, Div. Cancer Etiol., NCI, Bethesda, MD, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 1510 EP - 1516 VL - 86 IS - 20 SN - 0027-8874, 0027-8874 KW - pancreas KW - Risk Abstracts; Health & Safety Science Abstracts KW - cigarette smoking KW - cancer KW - R2 23060:Medical and environmental health KW - H SM10.21:CANCER UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16781682?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+National+Cancer+Institute&rft.atitle=Cigarette+smoking+and+pancreas+cancer%3A+a+case+-+control+study+based+on+direct+interviews&rft.au=Silverman%2C+D+T%3BDunn%2C+JA%3BHoover%2C+R+N%3BSchiffman%2C+M%3BLillemoe%2C+K+D%3BSchoenberg%2C+J+B%3BBrown%2C+L+M%3BGreenberg%2C+R+S%3BHayes%2C+R+B%3BSwanson%2C+G+M%3BWacholder%2C+S%3BSchwartz%2C+A+G%3BLiff%2C+J+M%3BPottern%2C+L+M&rft.aulast=Silverman&rft.aufirst=D&rft.date=1994-01-01&rft.volume=86&rft.issue=20&rft.spage=1510&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 - cigarette smoking; cancer ER - TY - JOUR T1 - Absence of changes in metallothionein RNA in the rat testes made refractory to cadmium toxicity by zinc pretreatment AN - 16780871; 3541593 AB - Testicular toxicity and interstitial cell tumours induced by cadmium are prevented by zinc or by low dose cadmium pretreatments. The mechanism of this tolerance is unknown, though metallothionein (MT) is thought to play a role in tissue resistance to cadmium toxicity. Thus, the possible involvement of the testicular MT gene in metal-induced tolerance to cadmium toxicity was studied. Rats were pretreated with zinc (1.0 mmol kg super(-1), s.c.). Histological examination of the testes indicated such pretreatments prevented the necrotizing effects of subsequent doses of cadmium (20 mu mol kg super(-1), s.c.) administered 24 h later. RNA was extracted from testes or liver 24 h after zinc pretreatment, and analysed by the slot blot technique using the p2A10 cDNA probe to the MT gene. Zinc pretreatment had little effect on MT RNA in the testes, and such pretreatments did not alter testicular cadmium-binding protein capacity. In contrast, RNAs derived from livers of zinc pretreated rats showed marked increases in MT RNA and MT protein. JF - Human & Experimental Toxicology AU - Wahba, Z Z AU - Miller AU - Waalkes, M P AD - Lab. Comp. Carcinog.,NCI, Frederick Cancer Res. and Dev. Cent., Build. 538, Room 205E, Frederick, MD 21702-1201, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 65 EP - 67 VL - 13 IS - 1 SN - 0144-5952, 0144-5952 KW - cadmium KW - zinc KW - metallothionein KW - rats KW - heavy metals KW - Toxicology Abstracts KW - RNA KW - testes KW - X 24165:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16780871?accountid=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=Human+%26+Experimental+Toxicology&rft.atitle=Absence+of+changes+in+metallothionein+RNA+in+the+rat+testes+made+refractory+to+cadmium+toxicity+by+zinc+pretreatment&rft.au=Wahba%2C+Z+Z%3BMiller%3BWaalkes%2C+M+P&rft.aulast=Wahba&rft.aufirst=Z&rft.date=1994-01-01&rft.volume=13&rft.issue=1&rft.spage=65&rft.isbn=&rft.btitle=&rft.title=Human+%26+Experimental+Toxicology&rft.issn=01445952&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 - RNA; testes ER - TY - JOUR T1 - A study of the gender differences in morbidity among individuals diagnosed with alcohol abuse and/or dependence AN - 16779371; 3740118 AB - The majority of studies on medical consequences of excessive alcohol consumption have been carried out with male subjects, mostly from clinical or hospitalized samples. The purpose of this report was to study differences in morbidity outcomes of men and women among respondents diagnosed with alcohol abuse and/or dependence. Utilizing data from the 1988 National Health Interview Survey, this study compared several indicators of physical morbidity among male and female respondents meeting the criteria for Diagnostic and Statistical Manual of Mental Disorders (DSM-III-R; American Psychiatric Association, 1987) alcohol abuse and/or dependence. The results revealed complete gender differences, not all of which can be explained by differences in sociodemographic characteristics or drinking practices. Moreover, the results indicated that it is inadequate to generalize results based on morbidity data of men with alcohol abuse and/or dependence to their female counterparts or female drinkers. Implications of these findings are discussed. JF - Journal of Substance Abuse Treatment AU - Chou, S P AU - Dawson, DA AD - Div. Biometry and Epidemiol., NIAAA, Suite 514, 6000 Executive Blvd., Bethesda, MD 20892-7003, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 381 EP - 392 VL - 6 IS - 4 SN - 0899-3289, 0899-3289 KW - alcoholism KW - man KW - sex differences KW - substance abuse KW - ethanol KW - Risk Abstracts; Health & Safety Science Abstracts; Toxicology Abstracts KW - gender KW - morbidity KW - H SE4.26:DRUGS AND ALCOHOL KW - R2 23060:Medical and environmental health KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16779371?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Substance+Abuse+Treatment&rft.atitle=A+study+of+the+gender+differences+in+morbidity+among+individuals+diagnosed+with+alcohol+abuse+and%2For+dependence&rft.au=Chou%2C+S+P%3BDawson%2C+DA&rft.aulast=Chou&rft.aufirst=S&rft.date=1994-01-01&rft.volume=6&rft.issue=4&rft.spage=381&rft.isbn=&rft.btitle=&rft.title=Journal+of+Substance+Abuse+Treatment&rft.issn=08993289&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 - morbidity; ethanol; gender; alcoholism; man; sex differences ER - TY - JOUR T1 - FptA, the Fe(III)-pyochelin receptor of Pseudomonas aeruginosa: A phenolate siderophore receptor homologous to hydroxamate siderophore receptors AN - 16779327; 3536301 AB - The Pseudomonas aeruginosa siderophore pyochelin is structurally unique among siderophores and possesses neither hydroxamate- nor catecholate-chelating groups. The structural gene encoding the 75-kDa outer membrane Fe(III)-pyochelin receptor FptA has been isolated by plasmid rescue techniques and sequenced. The N-terminal amino acid sequence of the isolated FptA protein corresponded to that deduced from the nucleotide sequence of the fptA structural gene. The mature FptA protein has 682 amino acids and a molecular mass of 75,993 Da and has considerable overall homology with the hydroxamate siderophore receptors FpvA of P. aeruginosa, PupA and PupB of Pseudomonas putida, and FhuE of Escherichia coli. This observation indicates that homologies between siderophore receptors are an unreliable predictor of siderophore ligand class recognition by a given receptor. The fptA gene was strongly regulated by iron; fptA transcription was totally repressed by 30 mu M FeCl sub(3), as determined by Northern (RNA) blotting. The promoter of the fptA gene contained the sequence 5'-ATAATGATAAGCATTATC-3', which matches the consensus E. coli Fur-binding site at 17 of 18 positions. The -10 promoter region and transcriptional start site of the fptA gene reside within this Fur-binding site. JF - Journal of Bacteriology AU - Ankenbauer, R G AU - Quan, H N AD - Lab. Microb. Struct. Funct., Rocky Mountain Lab., NIAID, Hamilton, MT 59840, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 307 EP - 319 VL - 176 IS - 2 SN - 0021-9193, 0021-9193 KW - fptA gene KW - FptA protein KW - Genetics Abstracts; Microbiology Abstracts B: Bacteriology KW - genes KW - receptors KW - siderophores KW - nucleotide sequence KW - gene regulation KW - Pseudomonas aeruginosa KW - J 02732:Other cell constituents and metabolites KW - G 07321:GENERAL UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16779327?accountid=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=FptA%2C+the+Fe%28III%29-pyochelin+receptor+of+Pseudomonas+aeruginosa%3A+A+phenolate+siderophore+receptor+homologous+to+hydroxamate+siderophore+receptors&rft.au=Potter%2C+W+Z%3BKetter%2C+T+A&rft.aulast=Potter&rft.aufirst=W&rft.date=1993-04-01&rft.volume=38&rft.issue=3+Suppl+2&rft.spage=S51&rft.isbn=&rft.btitle=&rft.title=Canadian+journal+of+psychiatry.+Revue+canadienne+de+psychiatrie&rft.issn=07067437&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 - Pseudomonas aeruginosa; genes; nucleotide sequence; gene regulation; siderophores; receptors ER - TY - JOUR T1 - Promoter switch in the Escherichia coli pts operon AN - 16776761; 3536473 AB - The ptsH operon of Escherichia coli is controlled by two promoters P0 and P1, each of which is regulated by cyclic AMP receptor protein (CRP) complexed with cAMP (CRP-cAMP). We have studied the in vitro as well as in vivo transcriptional regulation of these two promoters. Each promoter exhibits a switching mechanism in vitro, where, depending upon the presence or absence of CRP-cAMP, transcription is initiated from different start sites termed a and b. PO (POa) is affected by supercoiling: when the template is linear, transcription initiation is switched to a site 3 base pairs upstream (POb) and becomes more CRP-cAMP dependent. Transcription from the P1 promoter (P1a) switches initiation sites to 7 base pairs downstream (P1b) in the presence of CRP-cAMP. Most transcription in vivo was from P1a, and POb could not be detected in vivo. Glucose has independent positive effects on pts expression in vivo. The results indicate that the two different regulatory mechanisms (one through CRP-cAMP, the other through glucose) are working together for fine control of pts expression. JF - Journal of Biological Chemistry AU - Ryu, S AU - Garges, S AD - Lab. Mol. Biol., Build. 37, Rm. 2E06, NCI/NIH, Bethesda, MD 20892, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 4767 EP - 4772 VL - 269 IS - 7 SN - 0021-9258, 0021-9258 KW - ptsH operon KW - phosphoenolpyruvate-glucose phosphotransferase KW - switch KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - operons KW - Escherichia coli KW - promoters KW - N 14555:Miscellaneous KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16776761?accountid=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=Promoter+switch+in+the+Escherichia+coli+pts+operon&rft.au=Ryu%2C+S%3BGarges%2C+S&rft.aulast=Ryu&rft.aufirst=S&rft.date=1994-01-01&rft.volume=269&rft.issue=7&rft.spage=4767&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; operons; promoters ER - TY - JOUR T1 - Treatment with intralesional granulocyte instillations and interferon- gamma for a patient with chronic granulomatous disease and multiple hepatic abscesses AN - 16760248; 3730376 AB - We present the case of a 16-year-old girl with p22 super(phox)-deficient chronic granulomatous disease in whom multiple hepatic abscesses secondary to Staphylococcus aureus infection developed. Infection persisted despite extensive surgery and aggressive antibiotic therapy. Conventional intravenous granulocyte transfusions were not tolerated because of the development of alloantibodies to HLA. Treatment with interferon- gamma and intralesional granulocyte infusions was associated with dramatic clinical and radiographic improvement. No morbidity was associated with this therapy. To our knowledge, this is the first report of treatment with intralesional granulocyte instillations. Intralesional granulocyte instillation in association with interferon- gamma administration may result in clinical improvement in the conditions of patients with chronic granulomatous disease and hepatic abscesses for whom conventional therapy has failed. JF - Clinical Infectious Diseases AU - Lekstrom-Himes, JA AU - Holland, S M AU - DeCarlo, E S AU - Miller, J AU - Leitman, S F AU - Chang, R AU - Baker, A R AU - Gallin, JI AD - NIAID/NIH, Build. 10, Rm. 11N228, 9000 Rockville Pike, Bethesda, MD 20892, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 770 EP - 773 VL - 19 IS - 4 SN - 1058-4838, 1058-4838 KW - Biotechnology and Bioengineering Abstracts; Immunology Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - chronic granulomatous disease KW - infusion KW - case reports KW - gamma -interferon KW - leukocytes (granulocytic) KW - liver KW - Staphylococcus aureus KW - abscesses KW - man KW - F 06773:Interferons KW - W3 33150:Cytokine based KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16760248?accountid=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=Clinical+Infectious+Diseases&rft.atitle=Treatment+with+intralesional+granulocyte+instillations+and+interferon-+gamma+for+a+patient+with+chronic+granulomatous+disease+and+multiple+hepatic+abscesses&rft.au=Lekstrom-Himes%2C+JA%3BHolland%2C+S+M%3BDeCarlo%2C+E+S%3BMiller%2C+J%3BLeitman%2C+S+F%3BChang%2C+R%3BBaker%2C+A+R%3BGallin%2C+JI&rft.aulast=Lekstrom-Himes&rft.aufirst=JA&rft.date=1994-01-01&rft.volume=19&rft.issue=4&rft.spage=770&rft.isbn=&rft.btitle=&rft.title=Clinical+Infectious+Diseases&rft.issn=10584838&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 - chronic granulomatous disease; case reports; infusion; leukocytes (granulocytic); gamma -interferon; liver; man; abscesses; Staphylococcus aureus ER - TY - JOUR T1 - Human monoclonal antibodies heterogeneously express a human cross-reactive idiotype associated with immune function in Schistosoma japonicum infection AN - 16751203; 3725329 AB - Hybridomas secreting human monoclonal antibodies (hMAb) were derived from Epstein Barr Virus (EBV) transformed lymphocytes of a patient with acute Schistosoma japonicum infection. Three IgG1 hMAb SJ-D, SJ-E, and SJ-F bind soluble egg antigens (SEA) as determined by ELISA. These hMAb exhibit identical western blot profiles, recognizing an epitope(s) of multiple antigens with apparent molecular weights between 42 and 75 kDa. Serological analysis of these hMAb revealed a heterogeneity in their expression of a specific human S. japonicum anti-SEA associated cross reactive idiotype designated Hu SJ-CRI sub(M). The differential expression of idiotypy by these hMAb correlates with immunosuppression of blastogenesis of lymphocytes from schistosomiasis patients. The level of suppression mediated by hMAb expressing high levels of Hu SJ-CRI sub(M) ranged from 41% to 52% for antigen and 36% to 43% for mitogen. In contrast, hMAb SJ-D which expressed over two fold lower levels Hu SR-CRI sub(M), on a per weight basis showed no suppressive immune function. The data show the heterogeneous expression of human idiotype associated with S. japonicum infection and the correlation of idiotype expression with immune function. JF - Human Antibodies AU - Wisnewski, A V AU - Olds, G R AU - Kresina, T F AD - NIDDK/NIH, Rm. 6AN 12A, 45. Cent. Dr. MSC6600, Bethesda, MD 20892-6600, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 178 EP - 182 VL - 5 IS - 3-4 SN - 0956-860X, 0956-860X KW - soluble egg antigens KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - infectious diseases KW - immunoglobulin G KW - ova KW - idiotypes KW - monoclonal antibodies KW - man KW - Schistosoma japonicum KW - enzyme-linked immunosorbent assay KW - W3 33375:Antibodies KW - F 06711:Monoclonal antibodies, hybridomas, antigens and antisera KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16751203?accountid=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+Antibodies&rft.atitle=Human+monoclonal+antibodies+heterogeneously+express+a+human+cross-reactive+idiotype+associated+with+immune+function+in+Schistosoma+japonicum+infection&rft.au=Wisnewski%2C+A+V%3BOlds%2C+G+R%3BKresina%2C+T+F&rft.aulast=Wisnewski&rft.aufirst=A&rft.date=1994-01-01&rft.volume=5&rft.issue=3-4&rft.spage=178&rft.isbn=&rft.btitle=&rft.title=Human+Antibodies&rft.issn=0956860X&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 - infectious diseases; immunoglobulin G; ova; idiotypes; monoclonal antibodies; man; enzyme-linked immunosorbent assay; Schistosoma japonicum ER - TY - JOUR T1 - Application of branched DNA signal amplification to monitor human immunodeficiency virus type 1 burden in human plasma AN - 16739038; 3719588 AB - A branched DNA (bDNA)-based quantitation of plasma human immunodeficiency virus type 1 (HIV-1) RNA was used to monitor the virologic status of 102 patients (29-906 CD4 cells/mm super(3)) enrolled in clinical trials of antiretroviral and immune-based therapies. Virion-associated RNA was measurable in plasma of 74% of patients tested (10,000-10,000,000 RNA equivalents/mL). Virus levels measured by the bDNA assay exceeded titers obtained by quantitative plasma culture and were inversely correlated with total CD4 cell counts. The assay was used to demonstrate a significant decline (mean, 5-fold; range, 0- to 30-fold), relative to pretreatment, in virus load after beginning antiviral therapy and a transient increase (mean, 15-fold; range, 2- to 50-fold) after treatment with interleukin-2. The decrease in RNA was more dramatic than changes in serum p24 antigen. The bDNA assay yields reproducible results, is relatively easy, and should be useful in measuring HIV-1 RNA in patients in clinical trials. JF - Journal of Infectious Diseases AU - Dewar, R L AU - Highbarger, H C AU - Sarmiento, MD AU - Todd, JA AU - Vasudevachari, M B AU - Davey, RT Jr AU - Kovacs, JA AU - Salzman, N P AU - Lane, H C AU - Urdea AD - NCI, Frederick Cancer Res. and Dev. Cent., Build. 550, Fort Detrick, Frederick, MD 21701, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 1172 EP - 1179 VL - 170 IS - 6 SN - 0022-1899, 0022-1899 KW - signal amplification KW - Biotechnology and Bioengineering Abstracts; Biochemistry Abstracts 2: Nucleic Acids; Medical and Pharmaceutical Biotechnology Abstracts; Virology & AIDS Abstracts KW - RNA KW - human immunodeficiency virus 1 KW - virions KW - DNA KW - man KW - acquired immune deficiency syndrome KW - V 22002:AIDS: Molecular and in vitro aspects KW - N 14610:Occurrence, isolation & assay 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/16739038?accountid=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+Infectious+Diseases&rft.atitle=Application+of+branched+DNA+signal+amplification+to+monitor+human+immunodeficiency+virus+type+1+burden+in+human+plasma&rft.au=Dewar%2C+R+L%3BHighbarger%2C+H+C%3BSarmiento%2C+MD%3BTodd%2C+JA%3BVasudevachari%2C+M+B%3BDavey%2C+RT+Jr%3BKovacs%2C+JA%3BSalzman%2C+N+P%3BLane%2C+H+C%3BUrdea&rft.aulast=Dewar&rft.aufirst=R&rft.date=1994-01-01&rft.volume=170&rft.issue=6&rft.spage=1172&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 - 2011-12-14 N1 - SubjectsTermNotLitGenreText - RNA; virions; DNA; man; acquired immune deficiency syndrome; human immunodeficiency virus 1 ER - TY - JOUR T1 - Agreement between death certificate and autopsy diagnoses among atomic bomb survivors AN - 16736405; 3521387 AB - Based on the Atomic Bomb Casualty Commission/Radiation Effects Research Foundation series of over 5,000 autopsies, we examined death certificate accuracy for 12 disease categories and assessed the effect of potential modifying factors on agreement and accuracy. The overall percentage agreement between death certificate and autopsy diagnoses was only 52.5%. Although neoplasms had the highest detection rate, almost 25% of cancers diagnosed at autopsy were nevertheless missed on death certificates. Confirmation and detection rates were above 70% for neoplasms and external causes of death only. Confirmation rates were between 50 and 70% for infectious diseases and heart and other vascular diseases. Detection rates reached a similar level for infectious, cerebrovascular, and digestive diseases. Specificity rates were above 90% for all except the cerebrovascular disease category. Overall agreement decreased with increasing age at death and was worse for deaths occurring outside of hospital. There was some suggestion that agreement improved over time, but no indication that radiation dose, sex, city of residence, or inclusion in a biennial clinical examination program influenced agreement. JF - Epidemiology AU - Ron, E AU - Carter, R AU - Jablon, S AU - Mabuchi, K AD - Radiat. Epidemiol. Branch, NCI/NIH, EPN-408, Bethesda, MD 20892, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 48 EP - 56 VL - 5 IS - 1 SN - 1044-3983, 1044-3983 KW - survivors KW - death certificates KW - Toxicology Abstracts KW - diagnosis KW - atomic bombs KW - autopsy KW - man KW - X 24210:Radiation & radioactive materials UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16736405?accountid=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=Epidemiology&rft.atitle=Agreement+between+death+certificate+and+autopsy+diagnoses+among+atomic+bomb+survivors&rft.au=Ron%2C+E%3BCarter%2C+R%3BJablon%2C+S%3BMabuchi%2C+K&rft.aulast=Ron&rft.aufirst=E&rft.date=1994-01-01&rft.volume=5&rft.issue=1&rft.spage=48&rft.isbn=&rft.btitle=&rft.title=Epidemiology&rft.issn=10443983&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 - atomic bombs; autopsy; diagnosis; man ER - TY - JOUR T1 - T-cell receptor repertoire in tumor-infiltrating lymphocytes. Analysis of melanoma-specific long-term lines AN - 16733811; 3718633 AB - Cytotoxic T-lymphocytes (CTLs) can be isolated from human melanoma biopsies that specifically lyse autologous melanoma in vitro and can be effective therapeutic agents for patients with advanced disease. Recent evidence indicates that HLA-A2-restricted, melanoma-specific tumor-infiltrating lymphocytes (TILs) recognize melanomas obtained from different HLA-A2 super(+) patients, suggesting the presence of one or more common melanoma antigens. Furthermore, T-cell receptor (TCR) repertoire analysis by other groups of TILs from fresh melanoma biopsies suggests that there is limited TCR V gene usage in TILs. One serious limitation in analyzing the TCR repertoire in fresh tumors has been the inability to correlate TCR usage with immune function. Therefore, the TCR repertoire was determined in long-term TIL cultures that specifically lysed autologous melanoma in vitro and in many cases mediated in vivo regression of metastatic cancer in patients with advanced disease. The TCR repertoire in cultured melanoma-specific TILs was diverse, with each TIL containing an average of 9.5 plus or minus 5.7 of the 23 V alpha and 11.2 plus or minus 5.9 of the 23 V beta subfamilies. Despite the large diversity observed, several V alpha and V beta genes (V alpha 1, V alpha 2, V alpha 22, V beta 13, V beta 14, and V beta 18) are very commonly found in melanoma-specific TILs. No statistically significant associations were observed between the presence of a TCR V gene subfamily in TILs and clinical response, HLA haplotype, or age of the culture. Even though the results in this study suggest that certain TCR V gene segments may be involved in immune responses to human melanoma, we were unable to demonstrate functionally that a particular T-cell clonotype recognizes melanoma tumor-associated antigens. Only the analysis of melanoma-specific CTL clones can determine which clonotypes are important in lysis of human melanoma. JF - Journal of Immunotherapy AU - Nishimura, MI AU - Kawakami, Y AU - Charmley, P AU - O'Neil, B AU - Shilyansky, J AU - Yannelli, J R AU - Rosenberg, SA AU - Hood, L AD - Surg. Branch, NCI, Build. 10, Rm. 2B04, Bethesda, MD 20892, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 85 EP - 94 VL - 16 IS - 2 SN - 1053-8550, 1053-8550 KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - T-cell receptor KW - lymphocytes T KW - infiltration KW - tumors KW - melanoma KW - man KW - F 06818:Cancer immunotherapy KW - W3 33170:Cellular based KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16733811?accountid=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=T-cell+receptor+repertoire+in+tumor-infiltrating+lymphocytes.+Analysis+of+melanoma-specific+long-term+lines&rft.au=Nishimura%2C+MI%3BKawakami%2C+Y%3BCharmley%2C+P%3BO%27Neil%2C+B%3BShilyansky%2C+J%3BYannelli%2C+J+R%3BRosenberg%2C+SA%3BHood%2C+L&rft.aulast=Nishimura&rft.aufirst=MI&rft.date=1994-01-01&rft.volume=16&rft.issue=2&rft.spage=85&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immunotherapy&rft.issn=10538550&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - T-cell receptor; lymphocytes T; infiltration; tumors; melanoma; man ER - TY - JOUR T1 - Prevention of HIV/AIDS with vaccines AN - 16732400; 3714952 AB - HIV vaccines are urgently needed to help control the relentlessly expanding epidemic. However, the development of a safe and effective vaccine for this rapidly mutating virus which produces life-long infection is elusive. Feasibility of HIV vaccination has been demonstrated by challenge studies in primates and by the presence of neutralizing antibodies which confer passive protection and can be detected in vitro. Given safety considerations, the first vaccines developed have been recombinant subunit vaccines consisting of viral envelope antigens formulated with adjuvants or incorporated into live vectors, such as vaccinia and avipox. Subunit envelope vaccines have proven to be safe and immunogenic in human phase I trials. Two gp120 subunit products are being considered for phase III trials based on ongoing evaluation of data from a phase II trial, primate-challenge studies, and laboratory studies evaluating the breadth, magnitude, and duration of immunogenic responses, including neutralization against recent isolates. Efficacy trials will be large and complex, involving people at high behavioral risk for infection. Baseline studies with recruitment goals of over 10 000 people are being sponsored in the USA, with many additional vaccine preparedness studies being sponsored in developing nations by international and national authorities. Because high-risk populations will be recruited for trials of many year's duration, new approaches to trial design and community participation will be needed in order for these trials to succeed. Systems must be in place to ensure that trial participants receive preventive counseling and services to minimize discrimination from vaccine-related seroconversions. Here we document the urgent need for HIV vaccines, provide a brief preclinical and clinical update, and present the plans and considerations for testing HIV vaccine efficacy. JF - Current Opinion in Infectious Diseases AU - Vermund, SH AU - Schultz, A M AU - Hoff, R AD - Div. AIDS, NIAID/NIH, 6003 Exec. Blvd.-Rm 2A42, Bethesda, MD 20892, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 82 EP - 94 VL - 7 IS - 1 SN - 0951-7375, 0951-7375 KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Virology & AIDS Abstracts KW - vaccines KW - safety KW - human immunodeficiency virus KW - infection KW - efficacy KW - disease control KW - W3 33365:Vaccines (other) KW - V 22003:AIDS: Immunological aspects KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16732400?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+Opinion+in+Infectious+Diseases&rft.atitle=Prevention+of+HIV%2FAIDS+with+vaccines&rft.au=Vermund%2C+SH%3BSchultz%2C+A+M%3BHoff%2C+R&rft.aulast=Vermund&rft.aufirst=SH&rft.date=1994-01-01&rft.volume=7&rft.issue=1&rft.spage=82&rft.isbn=&rft.btitle=&rft.title=Current+Opinion+in+Infectious+Diseases&rft.issn=09517375&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 - vaccines; safety; infection; efficacy; disease control; human immunodeficiency virus ER - TY - JOUR T1 - Enhanced interleukin-2 production in human tumor-infiltrating lymphocytes engineered by 3'-truncated interleukin-2 gene AN - 16732006; 3718727 AB - Tumor-infiltrating lymphocytes (TILs), T lymphocytes associated with solid tumors that can be grown with interleukin (IL)-2 in vitro, preferentially accumulate at tumor sites after adoptive transfer. Therefore, TILs can be considered for use as cellular vehicles in gene therapy. We transduced melanoma TILs with the IL-2 gene and clarified functional characteristics of the TIL transductants. TILs transduced with 3'-end-truncated IL-2 gene (480 bp) produced high amounts of IL-2 detected in supernatants when compared to TILs transduced with the native IL-2 gene containing 3'-end adenine-thymidine (AT)-rich sequences (650 bp). The level of IL-2 in supernatants was higher with the addition of anti-Tac antibody (Ab) to block the consumption of IL-2 by the TILs. These TILs could proliferate autonomously in the absence of exogenous IL-2, and the proliferation of TILs could be completely blocked by anti-IL-2 Ab or anti-IL-2 receptor Ab. Thus TILs transduced with IL-2 gene can proliferate through the autocrine loop. However, the expression of IL-2 from TILs transduced with the IL-2 gene was downregulated after 2 to 3 weeks of G418 selection. Our study indicates the feasibility of transduction and expression of a truncated 480-bp IL-2 gene into TILs and the possibility of employing adoptive immunotherapy protocols using TILs modified with this IL-2 gene. JF - Journal of Immunotherapy AU - Yamaue, H AU - Kashmiri, SVS AU - De Filippi, R AU - Nieroda, C AU - Yannelli, J R AU - Tsang, Kwong Y AU - Schlom, J AD - Lab. Tumor Immunol. and Biol., NCI/NIH, Build. 10, Rm. 8B07, 9000 Rockville Pike, Bethesda, MD 20892, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 262 EP - 274 VL - 16 IS - 4 SN - 1053-8550, 1053-8550 KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - interleukin 2 KW - adoptive immunotherapy KW - lymphocytes T KW - cloning vectors KW - genes KW - infiltration KW - tumors KW - man KW - F 06818:Cancer immunotherapy KW - W3 33150:Cytokine based KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16732006?accountid=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=Enhanced+interleukin-2+production+in+human+tumor-infiltrating+lymphocytes+engineered+by+3%27-truncated+interleukin-2+gene&rft.au=Yamaue%2C+H%3BKashmiri%2C+SVS%3BDe+Filippi%2C+R%3BNieroda%2C+C%3BYannelli%2C+J+R%3BTsang%2C+Kwong+Y%3BSchlom%2C+J&rft.aulast=Yamaue&rft.aufirst=H&rft.date=1994-01-01&rft.volume=16&rft.issue=4&rft.spage=262&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immunotherapy&rft.issn=10538550&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - interleukin 2; adoptive immunotherapy; lymphocytes T; cloning vectors; infiltration; genes; tumors; man ER - TY - JOUR T1 - Enhanced immune responses and anti-tumor activity by baculovirus recombinant carcinoembryonic antigen (CEA) in mice primed with the recombinant vaccinia CEA AN - 16730249; 3718735 AB - Carcinoembryonic antigen (CEA), a glycosylated protein of Mr 180, is one of the most widely studied oncofetal antigens. A majority of gastrointestinal cancers as well as breast and non-small-cell lung carcinomas express CEA. CEA thus represents a potential target for immunotherapy of several carcinoma types. A recombinant vaccinia-CEA virus (rV-CEA) was previously shown to induce anti-tumor activity in an experimental murine model after three rV-CEA inoculations. However, because the majority of cancer patients have received a previous smallpox vaccination, a long-lasting immune memory and/or induced anamnestic responses against vaccinia proteins may prevent repetitive boosting with the recombinant vaccinia virus expressing CEA. Therefore, other types of vaccines may be required to boost the anti-CEA immune response: one such schema would be the use of purified CEA as a boost in hosts given one administration of rV-CEA. Commercially available sources of CEA are usually derived from liver metastases extracts and are sometimes contaminated with nonspecific cross-reactive antigen. We have previously generated a recombinant source of full-length human CEA using a baculovirus expression system (bV-CEA). bV-CEA was shown to be glycosylated CEA (nCEA). Moreover, bV-CEA was able to induce a humoral response against CEA present on human colorectal cancer cell lines. We have investigated here the effectiveness of bV-CEA and nCEA to boost both humoral and T-cell responses after a primary vaccination with the recombinant CEA vaccinia vaccine. The results indicate that the combination immunization regimen based on priming with rV-CEA followed by a bV-CEA boost is superior in the induction of immune responses and anti-tumor activity than using bV-CEA alone or one inoculation of rV-CEA as vaccine. The studies reported here thus provide evidence for the use of bV-CEA as a boost following primary immunization with rV-CEA. JF - Journal of Immunotherapy AU - Bei, R AU - Kantor, J AU - Kashmiri, SVS AU - Abrams, S AU - Schlom, J AD - Lab. Tumor Immunol. and Biol., NCI/NIH, Build. 10, Rm. 8B07, 9000 Rockville Pike, Bethesda, MD 20892, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 275 EP - 282 VL - 16 IS - 4 SN - 1053-8550, 1053-8550 KW - mice KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - vaccinia virus KW - cloning vectors KW - carcinoembryonic antigen KW - immune response KW - man KW - W 30965:Miscellaneous, Reviews KW - F 06814:Tumor antigens KW - W3 33180:Gene based (protocols, clinical trials, and animal models) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16730249?accountid=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=Enhanced+immune+responses+and+anti-tumor+activity+by+baculovirus+recombinant+carcinoembryonic+antigen+%28CEA%29+in+mice+primed+with+the+recombinant+vaccinia+CEA&rft.au=Bei%2C+R%3BKantor%2C+J%3BKashmiri%2C+SVS%3BAbrams%2C+S%3BSchlom%2C+J&rft.aulast=Bei&rft.aufirst=R&rft.date=1994-01-01&rft.volume=16&rft.issue=4&rft.spage=275&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immunotherapy&rft.issn=10538550&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - cloning vectors; carcinoembryonic antigen; immune response; man; vaccinia virus ER - TY - JOUR T1 - Murine retroviral vector that induces long-term expression of HIV-1 envelope protein AN - 16727535; 3715675 AB - A retroviral vector was constructed that induces long-term expression of human immunodeficiency virus type 1 (HIV-1) rev, vpu and env genes. The vector contains the neo gene and a cytomegalovirus (CMV) immediate early promoter followed by HIV-1 sequence. When HeLa cells were infected with viral stocks derived from this vector, about 25% of the resulting G418-resistant clones expressed HIV-1 envelope protein (Env), easily detectable by Western blot analysis, metabolic labelling, and syncytium formation after co-cultivation with HeLa-CD4 cells. In most cases the level of Env expression was higher than in a T cell line (H9) chronically infected with HIV-1. Env-expressing HeLa cell lines also expressed Rev, detected by transfection with a Rev-dependent CAT gene construct, and Vpu, detected by immunoprecipitation with a Vpu-specific antiserum. The 75% of G418-resistant HeLa cell lines that did not express Env were found to contain proviruses that had undergone deletion of env sequences corresponding to a known intron; presumably these cell lines arose as a result of infection with virions derived from spliced RNAs. This vector should be useful for studying non-transient effects of HIV Env, Rev and Vpu in tissue culture, and for the production of Env- and/or Rev-expressing cell lines. JF - Journal of Virological Methods AU - Fujita, K AU - Maldarelli, F AU - Purcell, DFJ AU - Silver, J AD - Lab. Mol. Microbiol., NIAID/NIH, Build. 4, Room 338, Bethesda, MD 20892, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 293 EP - 312 VL - 50 IS - 1-3 SN - 0166-0934, 0166-0934 KW - env gene KW - neo gene KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Virology & AIDS Abstracts KW - vectors KW - deletion KW - capsid protein KW - transfection KW - human immunodeficiency virus 1 KW - V 22002:AIDS: Molecular and in vitro aspects KW - W 30965:Miscellaneous, Reviews KW - W3 33130:Genetic based (PCR, etc.) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16727535?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Virological+Methods&rft.atitle=Murine+retroviral+vector+that+induces+long-term+expression+of+HIV-1+envelope+protein&rft.au=Fujita%2C+K%3BMaldarelli%2C+F%3BPurcell%2C+DFJ%3BSilver%2C+J&rft.aulast=Fujita&rft.aufirst=K&rft.date=1994-01-01&rft.volume=50&rft.issue=1-3&rft.spage=293&rft.isbn=&rft.btitle=&rft.title=Journal+of+Virological+Methods&rft.issn=01660934&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - deletion; vectors; capsid protein; transfection; human immunodeficiency virus 1 ER - TY - JOUR T1 - The use of colony-stimulating factors as bone marrow support for systemic anticancer chemotherapy AN - 16726660; 3715729 AB - Colony-stimulating factors (CSFs) are proteins that play normal roles in human hematopoietic physiology. Many of these factors have been cloned and sequenced. This has led to recombinant DNA technology that now allows for production of large quantities of pharmacologically pure compounds. Granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) are two such compounds that have been approved by the US Food and Drug Administration for human use in specific medical circumstances. This article summarizes the experience of one institution in using these two CSFs and adds brief commentary on four other CSFs that are expected to come to general use in the near future-interleukin-1, interleukin-3, interleukin-6, and erythropoietin. Both G-CSF and GM-CSF are effective in protecting patients from the leukotoxic effects of cancer chemotherapy, but GM-CSF appears to have a comparatively narrow "dosing window," wherein the agent is effective and tolerable. Future studies should address combining these agents with platelet protective compounds to improve patient safety. JF - Journal of the National Medical Association AU - Reed, E AD - Gynecol. Oncol. Sect., Med. Branch, NCI/NIH, Build. 10, Rm. 12N226, Bethesda, MD 20892, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 459 EP - 464 VL - 86 IS - 6 SN - 0027-9684, 0027-9684 KW - colony-stimulating factors KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - chemotherapy KW - man KW - bone marrow KW - W3 33150:Cytokine based KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16726660?accountid=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+Medical+Association&rft.atitle=The+use+of+colony-stimulating+factors+as+bone+marrow+support+for+systemic+anticancer+chemotherapy&rft.au=Reed%2C+E&rft.aulast=Reed&rft.aufirst=E&rft.date=1994-01-01&rft.volume=86&rft.issue=6&rft.spage=459&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+National+Medical+Association&rft.issn=00279684&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 - man; chemotherapy; bone marrow ER - TY - JOUR T1 - Management of infections in neutropenic patients: New opportunities and emerging challenges AN - 16726645; 3715357 AB - The approach to infection management in the neutropenic host is being refined as new antimicrobial agents and strategies aimed at augmenting various components of host competence are entering the realm of clinical investigation. To this end, diverse hematopoietic growth factors are being tested for their abilities to enhance cellular and humoral host defenses directed against bacterial and, most recently, fungal infections in the hematopoietically compromised patient. Additional novel antifungal approaches include new vehicles for local and systemic amphotericin B administration, for example aerosolized and lipid-based preparations. These are designed to deliver higher concentrations of the drug to sites of active infection and, at the same time, to spare the host from the well documented amphotericin-B-related multiorgan toxicities. The emergence of resistant pathogens, exemplified by vancomycin-resistant enterococci, challenges the current therapeutic armamentarium and will be addressed only through the development of structurally and functionally novel antibodies. JF - Current Opinion in Infectious Diseases AU - Karp, JE AU - Merz, W G AU - Dick, J D AD - NCI, 9000 Rockville Pike, Build. 31, Rm. 11A29, Bethesda, MD 20892, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 430 EP - 433 VL - 7 IS - 4 SN - 0951-7375, 0951-7375 KW - amphotericin B KW - Microbiology Abstracts C: Algology, Mycology & Protozoology; Microbiology Abstracts B: Bacteriology KW - antifungal agents KW - neutropenia KW - bacteremia KW - immunity KW - hosts KW - growth factors KW - antimicrobial agents KW - J 02855:Human Bacteriology: Others KW - K 03087:Fungi: human UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16726645?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+Opinion+in+Infectious+Diseases&rft.atitle=Management+of+infections+in+neutropenic+patients%3A+New+opportunities+and+emerging+challenges&rft.au=Karp%2C+JE%3BMerz%2C+W+G%3BDick%2C+J+D&rft.aulast=Karp&rft.aufirst=JE&rft.date=1994-01-01&rft.volume=7&rft.issue=4&rft.spage=430&rft.isbn=&rft.btitle=&rft.title=Current+Opinion+in+Infectious+Diseases&rft.issn=09517375&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 - bacteremia; hosts; neutropenia; antimicrobial agents; antifungal agents; growth factors; immunity ER - TY - JOUR T1 - Alcohol consumption during pregnancy and infant birth weight AN - 16719047; 3634546 AB - Heavy maternal alcohol consumption during pregnancy has been consistently linked to decreased infant birth weight but the effects of low and moderate levels of drinking on infant birth weight remain unclear. This study addresses the relationship of low to moderate alcohol consumption and birth weight in a nationally representative cohort sample (National Longitudinal Survey of Youth, n = 4409 births). Statistical methods that account for the complex sample design were used in the analysis. Multiple linear regression and logistic regression were used to adjust the relationship between drinking and birth weight for relevant covariates. Results of this study revealed a nonstatistically significant trend in the direction of greater numbers of low-birth-weight babies born to mothers who drank more frequently during pregnancy. A significant interaction between drinking and smoking was found in which the negative effects on birth weight of smoking were less for those women who drank more heavily (P = 0.046). JF - Annals of Epidemiology AU - Faden, V B AU - Graubard, B I AD - Div. Biometry and Epidemiol., NIAAA/NIH, 5600 Fishers Lane, Rm. 14C26, Rockville, MD 20857, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 279 EP - 284 VL - 4 IS - 4 SN - 1047-2797, 1047-2797 KW - alcohol KW - ethanol KW - birth weight KW - Toxicology Abstracts; Risk Abstracts KW - statistical analysis KW - smoking KW - pregnancy KW - infants KW - R2 23060:Medical and environmental health KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16719047?accountid=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=Annals+of+Epidemiology&rft.atitle=Alcohol+consumption+during+pregnancy+and+infant+birth+weight&rft.au=Faden%2C+V+B%3BGraubard%2C+B+I&rft.aulast=Faden&rft.aufirst=V&rft.date=1994-01-01&rft.volume=4&rft.issue=4&rft.spage=279&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 revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - alcohol; pregnancy; infants; statistical analysis; smoking; ethanol; birth weight ER - TY - JOUR T1 - Taxonomic descriptions of eight new non-sterol-requiring mollicutes assigned to the genus Mesoplasma AN - 16708578; 3700924 AB - Twenty mollicute strains isolated primarily from insect hosts were characterized and arranged into eight new species in the genus Mesoplasma. Morphological examination of the organisms by electron and dark-field microscopic techniques revealed that the cells of each strain were small, nonhelical, nonmotile, pleomorphic, and coccoid and that each cell was surrounded by a single cytoplasmic membrane with no evidence of a cell wall. Although the new mollicutes grew well in media containing horse or fetal bovine serum, growth in serum-free or cholesterol-free medium occurred only when the medium contained 0.04% polyoxyethylene sorbitan (Tween 80). The optimum temperature for growth was usually 30 degree C, but multiplication generally occurred over a temperature range of 10 to 32 degree C. All strains catabolized glucose. Most strains did not hydrolyze arginine or urea, although three related strains isolated from fireflies (the strain PUPA-2 super(T) [T = type strain] group) did hydrolyze arginine. The genome sizes ranged from 825 to 930 kbp, and the DNA base compositions (guanine-plus-cytosine contents) ranged from 26.5 to 31.6 mol%. The proposed type strains of the eight new species were not serologically related to the type strains of four other Mesoplasma species, five Entomoplasma species, 11 Acholeplasma species, and 100 Mycoplasma species and subspecies. Strain PS-1 (= ATCC 49582) is the type strain of Mesoplasma pleciae sp. nov., strain PUPA-2 (= ATCC 49581) is the type strain of Mesoplasma photuris sp. nov., strain YJS (= ATCC 43706) is the type strain of Mesoplasma syrphidae sp. nov., strain CHPA-2 (= ATCC 49578) is the type strain of Mesoplasma chauliocola sp. nov., strain ELCA-2 (= ATCC 49579) is the type strain of Mesoplasma corruscae sp. nov., strain GRUA-1 (= ATCC 49580) is the type strain of Mesoplasma grammopterae sp. nov., strain BARC 779 (= ATCC 49583) is the type strain of Mesoplasma coleopterae sp. nov., and strain BARC 857 (= ATCC 49584) is the type strain of Mesoplasma tabanidae sp. nov. JF - International Journal of Systematic Bacteriology AU - Tully, J G AU - Whitcomb, R F AU - Hackett, K J AU - Rose, D L AU - Henegar, R B AU - Bove, J M AU - Carle, P AU - Williamson, D L AU - Clark, T B AD - Mycoplasma Sect., NIAID, Bldg. 550, Frederick Cancer Res. Dev. Cent., Frederick, MD 21702, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 685 EP - 693 VL - 44 IS - 4 SN - 0020-7713, 0020-7713 KW - Mesoplasma KW - Mesoplasma pleciae sp.nov KW - Mesoplasma photuris sp.nov. KW - Mesoplasma syrphidae sp.nov. KW - Mesoplasma chauliorola sp.nov. KW - Mesoplasma corruscae sp.nov. KW - Mesoplasma grammopterae sp.nov. KW - Mesoplasma coleopterae sp.nov. KW - Mesoplasma tabanidae sp.nov. KW - Microbiology Abstracts B: Bacteriology KW - systematics KW - taxonomy KW - J 02710:Identification, taxonomy and typing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16708578?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+Journal+of+Systematic+Bacteriology&rft.atitle=Taxonomic+descriptions+of+eight+new+non-sterol-requiring+mollicutes+assigned+to+the+genus+Mesoplasma&rft.au=Tully%2C+J+G%3BWhitcomb%2C+R+F%3BHackett%2C+K+J%3BRose%2C+D+L%3BHenegar%2C+R+B%3BBove%2C+J+M%3BCarle%2C+P%3BWilliamson%2C+D+L%3BClark%2C+T+B&rft.aulast=Tully&rft.aufirst=J&rft.date=1994-01-01&rft.volume=44&rft.issue=4&rft.spage=685&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Systematic+Bacteriology&rft.issn=00207713&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 - taxonomy; systematics ER - TY - JOUR T1 - Acholeplasma brassicae sp. nov. and Acholeplasma palmae sp. nov., two non-sterol-requiring mollicutes from plant surfaces AN - 16708405; 3700926 AB - Two mollicutes (strains 0502 super(T) [T = type strain] and J233 super(T)), which were isolated from the surfaces of broccoli (Brassica oleracea var. italica) plants or the crown tissues of the coconut palm (Cocos nucifera), were capable of sustained growth in serum-free (or cholesterol-free) mycoplasma broth media. Examination by electron and dark-field microscopic techniques revealed that the cells of each strain were small, nonhelical, nonmotile, pleomorphic, and coccoid and that each cell was surrounded by a single cytoplasmic membrane. No evidence of a cell wall was found. The organisms were filterable and grew rapidly in most conventional mycoplasma culture medium formulations containing horse or fetal bovine sera under either aerobic or anaerobic conditions. The optimum temperature for growth of both organisms was 30 degree C, but multiplication occurred over a temperature range from 18 to 37 degree C. Both strains catabolized glucose, but did not hydrolyze arbutin, arginine, or urea. The genome size of strain 0502 super(T) was 1,215 kbp, and the DNA base composition (guanine-plus-cytosine content) was 35.5 mol%. The genome size of strain J233 super(T) was 1,610 kbp, and the DNA base composition was 30.0 mol%. The two isolates were not serologically related to each other or to the type strains of 11 previously described Acholeplasma species. Strain 0502 (= ATCC 49388) is the type strain of Acholeplasma brassicae sp. nov., and strain J233 (= ATCC 49389) is the type strain of Acholeplasma palmae sp. nov. JF - International Journal of Systematic Bacteriology AU - Tully, J G AU - Whitcomb, R F AU - Rose, D L AU - Bove, J M AU - Carle, P AU - Somerson, N L AU - Williamson, D L AU - Eden-Green, S AD - Mycoplasma Sect., NIAID, Build. 550, Frederick Cancer Res. Dev. Cent., Frederick, MD 21702, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 680 EP - 684 VL - 44 IS - 4 SN - 0020-7713, 0020-7713 KW - Acholeplasma brassicae sp.nov. KW - Acholeplasma palmae sp.nov. KW - Coco nucifera KW - Brassica deracea italica KW - Microbiology Abstracts B: Bacteriology KW - phylloplane KW - systematics KW - taxonomy KW - J 02710:Identification, taxonomy and typing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16708405?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+Journal+of+Systematic+Bacteriology&rft.atitle=Acholeplasma+brassicae+sp.+nov.+and+Acholeplasma+palmae+sp.+nov.%2C+two+non-sterol-requiring+mollicutes+from+plant+surfaces&rft.au=Tully%2C+J+G%3BWhitcomb%2C+R+F%3BRose%2C+D+L%3BBove%2C+J+M%3BCarle%2C+P%3BSomerson%2C+N+L%3BWilliamson%2C+D+L%3BEden-Green%2C+S&rft.aulast=Tully&rft.aufirst=J&rft.date=1994-01-01&rft.volume=44&rft.issue=4&rft.spage=680&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Systematic+Bacteriology&rft.issn=00207713&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 - phylloplane; taxonomy; systematics ER - TY - JOUR T1 - Sex differences in morbidity among respondents classified as alcohol abusers and/or dependent: Results of a national survey AN - 16707396; 3700270 AB - To date, none of the studies on gender differences in physical morbidity have focused on persons classified as DSM-III-R alcohol abusers and/or dependent in the general population. This Data Note presents data from a nationally representative survey on drinking practices and related problems for the purpose of examining gender differences in physical morbidity among respondents receiving these diagnoses. Results indicated that for certain major sociodemographic subgroups of the population, gender differences in morbidity were significant. The female-to-male odds ratios of these subgroups generally varied within the range of 1.5 and 2.0, reflecting about two times greater odds of experiencing morbid conditions for females when compared to males. JF - Addiction AU - Chou, S P AD - NIAAA, Div. Biometry and Epidemiol., 5600 Fishers Ln., Room 14C-26, Rockville, MD 20857, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 87 EP - 93 VL - 89 IS - 1 SN - 0965-2140, 0965-2140 KW - ethanol KW - Toxicology Abstracts KW - sex differences KW - morbidity KW - man KW - alcoholism KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16707396?accountid=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=Addiction&rft.atitle=Sex+differences+in+morbidity+among+respondents+classified+as+alcohol+abusers+and%2For+dependent%3A+Results+of+a+national+survey&rft.au=Chou%2C+S+P&rft.aulast=Chou&rft.aufirst=S&rft.date=1994-01-01&rft.volume=89&rft.issue=1&rft.spage=87&rft.isbn=&rft.btitle=&rft.title=Addiction&rft.issn=09652140&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 - sex differences; morbidity; man; alcoholism ER - TY - JOUR T1 - Locus coeruleus lesions potentiate neurotoxic effects of MPTP in dopaminergic neurons of the substantia nigra AN - 16704635; 3697800 AB - The observation that Parkinson's disease (PD) is associated with locus coeruleus (LC) noradrenergic neuronal degeneration suggests that the LC noradrenergic system may be involved in the pathogenesis and natural progression of the destruction of the substantia nigra (SN) dopaminergic neurons in Parkinson's disease. The relationship of these two systems was examined by injection of subtoxic doses of MPTP into unilateral LC 6-hydroxydopamine (6-OHDA) lesioned mice. A significant loss of dopaminergic cells was only found in the SN on the side of the LC lesions. The results suggest that the LC may have protective effects on SN dopaminergic neurons. JF - Brain Research AU - Bing, Guoying AU - Zhang, Yi AU - Watanabe, Y AU - McEwen, B S AU - Stone, E A AD - NIEHS/NIH, P.O. Box 12233, MD E1-01, Research Triangle Park, NC 27709, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 261 EP - 265 VL - 668 IS - 1-2 SN - 0006-8993, 0006-8993 KW - MPTP KW - dopamine KW - mice KW - Toxicology Abstracts; CSA Neurosciences Abstracts KW - lesions KW - neurotoxicity KW - locus coeruleus KW - substantia nigra KW - N3 11104:Mammals (except primates) KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16704635?accountid=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=Brain+Research&rft.atitle=Locus+coeruleus+lesions+potentiate+neurotoxic+effects+of+MPTP+in+dopaminergic+neurons+of+the+substantia+nigra&rft.au=Bing%2C+Guoying%3BZhang%2C+Yi%3BWatanabe%2C+Y%3BMcEwen%2C+B+S%3BStone%2C+E+A&rft.aulast=Bing&rft.aufirst=Guoying&rft.date=1994-01-01&rft.volume=668&rft.issue=1-2&rft.spage=261&rft.isbn=&rft.btitle=&rft.title=Brain+Research&rft.issn=00068993&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 - locus coeruleus; lesions; neurotoxicity; substantia nigra ER - TY - JOUR T1 - Gene targeting constructs: Effects of vector topology on co-expression efficiency of positive and negative selectable marker genes AN - 16703350; 3741186 AB - Targeting of DNA into specific chromosomal loci often involves the use of a negative selectable marker gene to enrich for cell clones that have undergone homologous recombination. In this study we asked if the arrangement of the positive and negative markers in 'knockout' constructs can influence the expression of a lacZ gene that was used as a negative marker. We show that constructs which differ only in their topology have vastly different co-expression efficiencies. The site of DNA linearization was critical. While linearizing at the 5'-end of the lacZ gene was compatible with efficient lacZ expression, linearizing at the 3'-end was always detrimental. We also demonstrate that the topology of the template was more important than the promoter used to drive lacZ expression. JF - Biochemical and Biophysical Research Communications AU - Zimmer, A AU - Reynolds, K AD - Unit on Dev. Biol., Lab. Cell Biol., NIMH, Bethesda, MD 20892, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 943 EP - 949 VL - 201 IS - 2 SN - 0006-291X, 0006-291X KW - Biotechnology and Bioengineering Abstracts; Biochemistry Abstracts 2: Nucleic Acids; Medical and Pharmaceutical Biotechnology Abstracts KW - cloning vectors KW - gene expression KW - genetic markers KW - N 14682:Cloning vectors KW - W 30965:Miscellaneous, Reviews KW - W3 33055:Genetic engineering (general) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16703350?accountid=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=Biochemical+and+Biophysical+Research+Communications&rft.atitle=Gene+targeting+constructs%3A+Effects+of+vector+topology+on+co-expression+efficiency+of+positive+and+negative+selectable+marker+genes&rft.au=Zimmer%2C+A%3BReynolds%2C+K&rft.aulast=Zimmer&rft.aufirst=A&rft.date=1994-01-01&rft.volume=201&rft.issue=2&rft.spage=943&rft.isbn=&rft.btitle=&rft.title=Biochemical+and+Biophysical+Research+Communications&rft.issn=0006291X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - cloning vectors; gene expression; genetic markers ER - TY - JOUR T1 - Biochemical and pharmacological factors causing induction and suppression of germination of Trichosporon beigelii AN - 16685796; 3689882 AB - Trichosporon beigelii is an emerging fungal pathogen, which is morphologically characterized by blastoconidia, arthroconidia and hyphae. The non-hyphal forms of T. beigelii germinate to form hyphae in plasma in vitro and in tissues in vivo, suggesting possible pathophysiological significance of this process. Little is known, however, about the mechanisms of germination of T. beigelii. We therefore studied relevant biochemical and pharmacological factors that may regulate germination of T. beigelii. Germination was significantly enhanced by temperature at 37 degree C, chemically defined cell culture media such as RPMI-1640, plasma, physiological pH, N-acetylglucosamine and proline. N-acetylglucosamine was equivalent to proline in inducing germination. Germination was suppressed by high concentrations of glucose, increasing inocula, low pH, and amphotericin B at achievable serum concentrations. Thus, many of the factors regulating germination of T. beigelii appear to be similar to those for Candida albicans. JF - Journal of Medical & Veterinary Mycology AU - Walsh, T J AU - Kelly, P AU - Peebles, R AU - Lee, J AU - Lecciones, J AU - Pizzo, P A AD - Infect. Dis. Sect., NCI, Build. 10, Room 13N240, Bethesda, MD 20892, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 123 EP - 132 VL - 32 IS - 2 SN - 0268-1218, 0268-1218 KW - amphotericin B KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Microbiology Abstracts C: Algology, Mycology & Protozoology KW - Trichosporon beigelii KW - pH KW - germination KW - A 01067:Antifungal & fungicidal KW - K 03063:Effects of physical & chemical factors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16685796?accountid=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+Medical+%26+Veterinary+Mycology&rft.atitle=Biochemical+and+pharmacological+factors+causing+induction+and+suppression+of+germination+of+Trichosporon+beigelii&rft.au=Walsh%2C+T+J%3BKelly%2C+P%3BPeebles%2C+R%3BLee%2C+J%3BLecciones%2C+J%3BPizzo%2C+P+A&rft.aulast=Walsh&rft.aufirst=T&rft.date=1994-01-01&rft.volume=32&rft.issue=2&rft.spage=123&rft.isbn=&rft.btitle=&rft.title=Journal+of+Medical+%26+Veterinary+Mycology&rft.issn=02681218&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 - Trichosporon beigelii; germination; pH ER - TY - JOUR T1 - Need for new standards to prevent deposition in wastewater sewers AN - 16681799; 3692102 AB - Both self-cleansing-velocity and minimum-shear-stress approaches have been used to investigate the effect of the relative flow depth in a sewer as an important factor influencing the buildup of deposits in a sewer designed for full flow. Each of the approaches indicates favorable deposit-free flow conditions for sewers with relative-normal flow depths ranging between 0.5 and 1.0. For relative flow depths well below 0.5 the same sewers show a strong tendency to form deposits. Nomographs have been developed for circular sewers partially clogged by deposits for easier computations of flow depths. Shear stresses in partially clogged sewers have been computed and discussed in relation to deposit thickness; the study here is limited to initiation criterion only. JF - Journal of Environmental Engineering AU - Nalluri, C AU - Dabrowski, W AD - Dep. Civ. Eng., Univ. Newcastle upon Tyne NEI 7RU, UK Y1 - 1994 PY - 1994 DA - 1994 SP - 1032 EP - 1043 VL - 120 IS - 5 SN - 0733-9372, 0733-9372 KW - flow KW - suspended sediments KW - storm water KW - Pollution Abstracts; Water Resources Abstracts KW - wastewater KW - standards KW - flow rates KW - sewers KW - sediments KW - P 2000:FRESHWATER POLLUTION KW - SW 0870:Erosion and sedimentation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16681799?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Apollution&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Environmental+Engineering&rft.atitle=Need+for+new+standards+to+prevent+deposition+in+wastewater+sewers&rft.au=Nalluri%2C+C%3BDabrowski%2C+W&rft.aulast=Nalluri&rft.aufirst=C&rft.date=1994-01-01&rft.volume=120&rft.issue=5&rft.spage=1032&rft.isbn=&rft.btitle=&rft.title=Journal+of+Environmental+Engineering&rft.issn=07339372&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 - standards; sewers; wastewater; sediments; flow; suspended sediments; storm water; flow rates ER - TY - JOUR T1 - Inhibition of HIV-1 integrase by flavones, caffeic acid phenethyl ester (CAPE) and related compounds AN - 16681323; 3693474 AB - The inhibition of HIV-1 integrase by flavones and related compounds was investigated biochemically and by means of structure-activity relationships. Purified enzyme and synthetic oligonucleotides were used to assay for three reactions catalyzed by integrase: (1) processing of 3' termini by cleavage of the terminal dinucleotide; (2) strand transfer, which models the integration step; and (3) "disintegration," which models the reversal of the strand transfer reaction. Inhibitions of all three reactions by flavones generally occurred in parallel, but caffeic acid phenethyl ester (CAPE) appeared to inhibit reaction 2 selectively. CAPE, however, inhibited reactions 1 and 3 effectively when preincubated with the enzyme, suggesting that this compound differs from the flavones primarily in requiring more time to block the enzyme. The core integrase fragment consisting of amino acids 50-212 retained the ability to catalyse reaction 3, and flavones and CAPE retained the ability to inhibit. Hence, the putative zinc-finger region that is deleted in this fragment is probably not the target of inhibition. Inhibition by flavones usually required the presence of at least one ortho pair of phenolic hydroxyl groups and at least one or two additional hydroxyl groups. Potency was enhanced by the presence of additional hydroxyl groups, especially when present in ortho pairs or in adjacent groups of three. Inhibitory activity was reduced or eliminated by methoxy or glycosidic substitutions or by saturation of the 2,3 double bond. These structure-activity findings for flavones were generally concordant with those previously reported for reverse transcriptase and topoisomerase II. These findings are discussed in the context of a review of the effects of flavones on various enzymes, the possible mechanisms of inhibition, and the potential for building upon a general pharmacophore to generate target specificity. JF - Biochemical Pharmacology AU - Fesen, M R AU - Pommier, Y AU - Leteurtre, F AU - Hiroguchi, S AU - Yung, J AU - Kohn, K W AD - Lab. Mol. Pharmacol., Build. 37, Rm. 5C25, NCI/NIH, Bethesda, MD 20892, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 595 EP - 608 VL - 48 IS - 3 SN - 0006-2952, 0006-2952 KW - integrase KW - flavone KW - caffeic acid phenethyl ester KW - oligodeoxyribonucleotides KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Virology & AIDS Abstracts KW - antiviral agents KW - human immunodeficiency virus 1 KW - V 22002:AIDS: Molecular and in vitro aspects KW - A 01068:Antiviral & viricidal UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16681323?accountid=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=Biochemical+Pharmacology&rft.atitle=Inhibition+of+HIV-1+integrase+by+flavones%2C+caffeic+acid+phenethyl+ester+%28CAPE%29+and+related+compounds&rft.au=Fesen%2C+M+R%3BPommier%2C+Y%3BLeteurtre%2C+F%3BHiroguchi%2C+S%3BYung%2C+J%3BKohn%2C+K+W&rft.aulast=Fesen&rft.aufirst=M&rft.date=1994-01-01&rft.volume=48&rft.issue=3&rft.spage=595&rft.isbn=&rft.btitle=&rft.title=Biochemical+Pharmacology&rft.issn=00062952&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - human immunodeficiency virus 1; antiviral agents ER - TY - JOUR T1 - The cheetah's conservation controversy AN - 16672356; 3686968 JF - Conservation Biology AU - O'Brien, S J AD - Lab. Viral Carcinog., NCI-FCRDC Program, Frederick, MD 21702, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 1153 EP - 1155 VL - 8 IS - 4 SN - 0888-8892, 0888-8892 KW - Genetics Abstracts; Ecology Abstracts KW - population genetics KW - conservation KW - Acinonyx jubatus KW - G 07270:Ecological genetics KW - D 04672:Mammals KW - D 04705:Conservation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16672356?accountid=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=Conservation+Biology&rft.atitle=The+cheetah%27s+conservation+controversy&rft.au=O%27Brien%2C+S+J&rft.aulast=O%27Brien&rft.aufirst=S&rft.date=1994-01-01&rft.volume=8&rft.issue=4&rft.spage=1153&rft.isbn=&rft.btitle=&rft.title=Conservation+Biology&rft.issn=08888892&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 - Acinonyx jubatus; conservation; population genetics ER - TY - JOUR T1 - Localization of cannabinoid receptors and nonsaturable high-density cannabinoid binding sites in peripheral tissues of the rat: Implications for receptor-mediated immune modulation by cannabinoids AN - 16668512; 3678831 AB - [ super(3)H]CP-55,940, a high-affinity cannabinoid receptor ligand, was used for in vitro binding and autoradiography in peripheral tissues in the rat. Specific cannabinoid receptor binding was found to be restricted to components of the immune system, i.e., spleen, lymph nodes and Peyer's patches. Displacement studies showed that this binding is identical (similar K sub(d) and structure-activity profile) to that in brain. Cannabinoid receptors in the immune system are confined to B lymphocyte-enriched areas, i.e., the marginal zone of the spleen, cortex of the lymph nodes and nodular corona of Peyer's patches. Specific binding is absent in T lymphocyte-enriched areas, such as the thymus and periarteriolar lymphatic sheaths of the spleen. Certain macrophage-enriched areas, i.e., liver and lung, lack specific binding. Thus, the single peripheral cell type that may contain cannabinoid receptors is the B lymphocyte. Numerous sites have dense binding that could not be displaced by excess unlabeled drug. These nonspecific sites were found in the liver, adrenal glands and sebaceous glands, which are high in fat content, and in the heart, pancreas, components of the male and female reproductive systems and the epithelium of the esophagus. JF - Journal of Pharmacology and Experimental Therapeutics AU - Lynn, AB AU - Herkenham, M AD - Sect. Funct. Neuroanat., NIMH, Build. 36, Rm. 2D-15, Bethesda, MD 20892, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 1612 EP - 1623 VL - 268 IS - 3 SN - 0022-3565, 0022-3565 KW - cannabinoid receptors KW - rats KW - Delta super(9)-THC KW - Delta super(9)-tetrahydrocannabinol KW - Toxicology Abstracts; CSA Neurosciences Abstracts KW - immune system KW - binding KW - N3 11106:Neurobiology of drug abuse KW - N3 11110:Neuroimmunology KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16668512?accountid=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+Pharmacology+and+Experimental+Therapeutics&rft.atitle=Localization+of+cannabinoid+receptors+and+nonsaturable+high-density+cannabinoid+binding+sites+in+peripheral+tissues+of+the+rat%3A+Implications+for+receptor-mediated+immune+modulation+by+cannabinoids&rft.au=Lynn%2C+AB%3BHerkenham%2C+M&rft.aulast=Lynn&rft.aufirst=AB&rft.date=1994-01-01&rft.volume=268&rft.issue=3&rft.spage=1612&rft.isbn=&rft.btitle=&rft.title=Journal+of+Pharmacology+and+Experimental+Therapeutics&rft.issn=00223565&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 - binding; immune system ER - TY - JOUR T1 - Isolation and characterization of a chimpanzee monoclonal antibody to the G glycoprotein of human respiratory syncytial virus AN - 16668413; 3683698 AB - Respiratory syncytial virus (RSV) is the most common cause of serious lower respiratory tract disease in infants and young children. In this study a hybridoma line secreting a chimpanzee monoclonal antibody that neutralizes RSV was isolated. Two chimpanzees were immunized with recombinant vaccinia viruses that express the RSV F or G surface glycoprotein and 1 month later were infected intranasally with the wild-type RSV strain A2. Peripheral blood lymphocytes obtained from the animals were transformed with Epstein-Barr virus, and lymphoblastoid cell lines that secreted anti-RSV antibodies were identified by an RSV antigen-binding enzyme-linked immunosorbent assay. Supernatants from RSV antibody-secreting lymphoblastoid cell lines were tested for in vitro virus neutralization before being fused to the heteromyeloma cell GLI-H7. A chimpanzee antibody [immunoglobulin G3( lambda ) subclass] produced from a hybridoma line designated E1.4/2 was shown to bind to the RSV G glycoprotein and neutralize a panel of subgroup A viruses, but not subgroup B viruses, at low (nanomolar) concentrations. Mice passively immunized with this antibody were partially resistant to RSV strain A2 challenge. The usefulness of such antibodies in immunoprophylaxis and immunotherapy of RSV infection is discussed. JF - Clinical and Diagnostic Laboratory Immunology AU - Crowe, JE Jr AU - Cheung, PYK AU - Wallace, E F AU - Chanock, R M AU - Larrick, J W AU - Murphy, B R AU - Fry, K AD - Resp. Viruses Sect., Lab. Infect. Dis., NIAID/NIH, Build. 7, Rm. 106, 9000 Rockville Pike, Bethesda, MD 20892, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 701 EP - 706 VL - 1 IS - 6 SN - 1071-412X, 1071-412X KW - glycoprotein G KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts; Virology & AIDS Abstracts KW - respiratory syncytial virus KW - monoclonal antibodies KW - Pan troglodytes KW - W3 33375:Antibodies KW - V 22091:Immunological techniques & reagents KW - W 30965:Miscellaneous, Reviews KW - F 06800:Viruses UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16668413?accountid=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=Clinical+and+Diagnostic+Laboratory+Immunology&rft.atitle=Isolation+and+characterization+of+a+chimpanzee+monoclonal+antibody+to+the+G+glycoprotein+of+human+respiratory+syncytial+virus&rft.au=Crowe%2C+JE+Jr%3BCheung%2C+PYK%3BWallace%2C+E+F%3BChanock%2C+R+M%3BLarrick%2C+J+W%3BMurphy%2C+B+R%3BFry%2C+K&rft.aulast=Crowe&rft.aufirst=JE&rft.date=1994-01-01&rft.volume=1&rft.issue=6&rft.spage=701&rft.isbn=&rft.btitle=&rft.title=Clinical+and+Diagnostic+Laboratory+Immunology&rft.issn=1071412X&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 - monoclonal antibodies; respiratory syncytial virus; Pan troglodytes ER - TY - JOUR T1 - Prolonged clinical latency and survival of macaques given a whole inactivated simian immunodeficiency virus vaccine AN - 16660081; 3670006 AB - Simian immunodeficiency virus (SIV) infection of macaques is a useful and relevant model for evaluating candidate human immunodeficiency virus (HIV) vaccines. One important feature of this model is that SIV vaccines can be evaluated for their ability to prevent infection as well as to prevent or delay the onset of AIDS. In the present study, a group of macaques was vaccinated with whole inactivated SIV and challenged with peripheral blood mononuclear cells from an SIV-infected macaque. This challenge represented a rigorous and realistic test of the immunization protocol. All macaques became infected after challenge; however, immunized animals survived significantly longer than naive controls. These data suggest that similar vaccines administered to humans at risk for HIV-1 infection might delay or prevent AIDS even if the vaccine failed to prevent infection. JF - Journal of Infectious Diseases AU - Hirsch, V M AU - Goldstein, S AU - Hynes, NA AU - Elkins, W R AU - London, W T AU - Zack, P M AU - Montefiori, D AU - Johnson, PR AD - NIAID/Twinbrook II Facility, 12441 Parklawn Dr., Rockville, MD 20852, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 51 EP - 59 VL - 170 IS - 1 SN - 0022-1899, 0022-1899 KW - Biotechnology and Bioengineering Abstracts; Immunology Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Virology & AIDS Abstracts KW - inactivation KW - immunization KW - vaccines KW - simian immunodeficiency virus KW - Macaca KW - human immunodeficiency virus KW - immunity KW - animal models KW - acquired immune deficiency syndrome KW - W3 33365:Vaccines (other) KW - F 06807:Active immunization KW - V 22003:AIDS: Immunological aspects KW - W 30965:Miscellaneous, Reviews KW - F 06800:Viruses KW - F 06856:Animal UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16660081?accountid=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+Infectious+Diseases&rft.atitle=Prolonged+clinical+latency+and+survival+of+macaques+given+a+whole+inactivated+simian+immunodeficiency+virus+vaccine&rft.au=Hirsch%2C+V+M%3BGoldstein%2C+S%3BHynes%2C+NA%3BElkins%2C+W+R%3BLondon%2C+W+T%3BZack%2C+P+M%3BMontefiori%2C+D%3BJohnson%2C+PR&rft.aulast=Hirsch&rft.aufirst=V&rft.date=1994-01-01&rft.volume=170&rft.issue=1&rft.spage=51&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 - 2011-12-14 N1 - SubjectsTermNotLitGenreText - immunization; inactivation; vaccines; immunity; animal models; acquired immune deficiency syndrome; simian immunodeficiency virus; human immunodeficiency virus; Macaca ER - TY - JOUR T1 - Purification and properties of the Escherichia coli K-12 NAD-dependent nucleotide diphosphosugar epimerase, ADP-L-glycero-D-mannoheptose 6-epimerase AN - 16657771; 3659526 AB - The Escherichia coli K-12 NAD-dependent nucleotide-diphosphosugar epimerase, ADP-L-glycero-D-mannoheptose 6-epimerase, catalyzes the conversion of ADP-D-glycero-D-mannoheptose to ADP-L-glycero-D-mannoheptose. ADP-L-glycero-D-mannoheptose is a key intermediate of lipopolysaccharide inner core biosynthesis in several genera of Gram-negative bacteria. Sedimentation equilibrium and sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the purified epimerase revealed that the native enzyme has a molecular mass of 240 kDa and a subunit molecular weight of 37,000 plus or minus 3,000. Lectin binding studies of the purified epimerase indicated that the protein is glycosylated. There was 1 mol of tightly bound NAD super(+) per enzyme subunit. Variable but small fractions of purified preparations of epimerase are highly fluorescent and contain NADH. The native enzyme can be resolved into apoenzyme and NAD super(+) by acidic ammonium sulfate precipitation. The catalytic activity can be reconstituted with the addition of NAD super(+) to the apoenzyme. Optimum pH range for enzyme activity is broad, between 5.5 and 9.5. It exhibits a temperature optimum at 42 degree C. The K sub(m) and V sub(max) for the substrate is 0.1 mM and 46 mu mol 30 min super(-1) mg super(-1), respectively. The native enzyme displays UV and fluorescence spectra that are consistent with the presence of enzyme bound NAD super(+). CD spectra of the holoepimerase indicate 11% alpha -helical and 36% beta -sheet structures. JF - Journal of Biological Chemistry AU - Ding, Li AU - Seto, B L AU - Ahmed, SA AU - Coleman, WG Jr AD - Sect. Pharmacol., Lab. Biochem. Pharmacol., NIDDK, Build. 8, Rm. 2A-03, Bethesda, MD 20892, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 24384 EP - 24390 VL - 269 IS - 39 SN - 0021-9258, 0021-9258 KW - ADP-L-glycero-D-mannoheptose-6-epimerase KW - Microbiology Abstracts B: Bacteriology KW - Escherichia coli KW - J 02728:Enzymes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16657771?accountid=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=Purification+and+properties+of+the+Escherichia+coli+K-12+NAD-dependent+nucleotide+diphosphosugar+epimerase%2C+ADP-L-glycero-D-mannoheptose+6-epimerase&rft.au=Ding%2C+Li%3BSeto%2C+B+L%3BAhmed%2C+SA%3BColeman%2C+WG+Jr&rft.aulast=Ding&rft.aufirst=Li&rft.date=1994-01-01&rft.volume=269&rft.issue=39&rft.spage=24384&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 ER - TY - JOUR T1 - Flow cytometric detection of DNA tumor virus nuclear oncogene products in unfixed cells: Saponin FACS of viral oncogene products AN - 16656292; 3662532 AB - Immunofluorescent analysis is a standard method for detecting DNA virus oncoproteins in transformed cells. Here we demonstrate the detection of DNA virus nuclear oncoproteins by flow cytometry of unfixed cells, after saponin permeabilization. This method could be of value in the evaluation and quantitation of oncogene products in transformed cells. JF - Journal of Virological Methods AU - Eyler, Y L AU - Lantz, L M AU - Lewis, AM Jr AD - Lab. Immunopathol., NIAID/NIH, Build. 7, Rm. 303, 9000 Rockville Pike, Bethesda, MD, 20892, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 23 EP - 27 VL - 46 IS - 1 SN - 0166-0934, 0166-0934 KW - saponin KW - Biotechnology and Bioengineering Abstracts; Oncogenes & Growth Factors Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Virology & AIDS Abstracts KW - detection KW - oncogenes KW - quantitation KW - DNA tumor viruses KW - transformed cells KW - immunofluorescence KW - flow cytometry KW - gene products KW - V 22091:Immunological techniques & reagents KW - W 30965:Miscellaneous, Reviews KW - W3 33250:Methods: Others KW - B 26250:Papovaviruses UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16656292?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Virological+Methods&rft.atitle=Flow+cytometric+detection+of+DNA+tumor+virus+nuclear+oncogene+products+in+unfixed+cells%3A+Saponin+FACS+of+viral+oncogene+products&rft.au=Eyler%2C+Y+L%3BLantz%2C+L+M%3BLewis%2C+AM+Jr&rft.aulast=Eyler&rft.aufirst=Y&rft.date=1994-01-01&rft.volume=46&rft.issue=1&rft.spage=23&rft.isbn=&rft.btitle=&rft.title=Journal+of+Virological+Methods&rft.issn=01660934&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - detection; oncogenes; quantitation; DNA tumor viruses; transformed cells; flow cytometry; immunofluorescence; gene products ER - TY - JOUR T1 - Moderate low birth weight and infectious disease mortality during infancy and childhood AN - 16648448; 3654103 AB - The purpose of this study was to determine whether moderately low birth weight, singleton babies without congenital anomalies are at increased risk for postperinatal infectious disease mortality. The study cohort consisted of 54,795 live births assembled at 12 medical school-affiliated hospitals in different regions of the United States between 1959 and 1966 and followed prospectively. After exclusions of multiple gestation births, very low birth weight births, births with major congenital anomalies, and first-week deaths, 51,931 children remained for analysis. Postperinatal infectious disease mortality was assessed through age 7 years. Moderately low birth weight infants and children were at increased risk of infectious disease mortality. The risk persisted among those whose deaths met our strictest criteria for infectious etiology and was sustained beyond infancy throughout the age interval under analysis. Among those with moderate low birth weight, there was an increased risk among those with preterm birth but not among those who were born small-for-gestational age. The data suggest that moderate low birth weight renders individuals vulnerable to infectious disease mortality during both infancy and childhood. JF - American Journal of Epidemiology AU - Read, J S AU - Clemens, J D AU - Klebanoff, MA AD - DESPR-NICHD-NIH, 6100 Executive Blvd., Rm. 7B03, Bethesda, MD 20892, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 721 EP - 733 VL - 140 IS - 8 SN - 0002-9262, 0002-9262 KW - infectious diseases KW - low-birth-weight KW - Health & Safety Science Abstracts KW - mortality KW - children KW - infants KW - H SM3.3:HAZARD DETERMINATION UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16648448?accountid=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=American+Journal+of+Epidemiology&rft.atitle=Moderate+low+birth+weight+and+infectious+disease+mortality+during+infancy+and+childhood&rft.au=Read%2C+J+S%3BClemens%2C+J+D%3BKlebanoff%2C+MA&rft.aulast=Read&rft.aufirst=J&rft.date=1994-01-01&rft.volume=140&rft.issue=8&rft.spage=721&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 N1 - SubjectsTermNotLitGenreText - mortality; infants; children ER - TY - JOUR T1 - Bacterial endotoxins and pathogenesis of gram-negative infections: Current status and future direction AN - 16642697; 3642579 AB - 100 years after the discovery of a bacterial 'endotoxin', 50 years after the introduction of antibiotics and 25 years after the routine use of intensive care units to support septic shock patients, Gram-negative infections continue to account for significant morbidity and mortality. In the coming decade, basic research on the structure/function of LPS, the cytokine cascade, and receptor-mediated intracellular signalling responses to LPS and cytokines will provide a greater understanding of the molecular, cellular and systemic responses to endotoxin and infection. New therapeutic agents now emerging from research, and better designed clinical trials to assess those agents will contribute to the next significant decline in sepsis- and shock-related morbidity and mortality. This article summarizes the findings of a workshop convened at the National Institutes of Health (NIH) to examine current research on endotoxin and Gram-negative septic shock. JF - Journal of Endotoxin Research AU - Morrison, D C AU - Danner, R L AU - Dinarello, CA AU - Munford, R S AU - Natanson, C AU - Pollack, M AU - Spitzer, J J AU - Ulevitch, R J AU - Vogel, S N AU - McSweegan, E AD - Bacteriol. and Mycol. Div., NIAID/NIH, Solar Build., Room 3A-32, Bethesda, MD 20892, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 71 EP - 83 VL - 1 IS - 2 SN - 0968-0519, 0968-0519 KW - cytokines KW - Microbiology Abstracts B: Bacteriology KW - structure-activity relationships KW - endotoxins KW - septic shock KW - mortality KW - pathogenesis KW - gram-negative bacteria KW - J 02823:In vitro and in vivo effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16642697?accountid=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+Endotoxin+Research&rft.atitle=Bacterial+endotoxins+and+pathogenesis+of+gram-negative+infections%3A+Current+status+and+future+direction&rft.au=Morrison%2C+D+C%3BDanner%2C+R+L%3BDinarello%2C+CA%3BMunford%2C+R+S%3BNatanson%2C+C%3BPollack%2C+M%3BSpitzer%2C+J+J%3BUlevitch%2C+R+J%3BVogel%2C+S+N%3BMcSweegan%2C+E&rft.aulast=Morrison&rft.aufirst=D&rft.date=1994-01-01&rft.volume=1&rft.issue=2&rft.spage=71&rft.isbn=&rft.btitle=&rft.title=Journal+of+Endotoxin+Research&rft.issn=09680519&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 - gram-negative bacteria; endotoxins; pathogenesis; mortality; septic shock; structure-activity relationships ER - TY - JOUR T1 - Dietary factors and non-Hodgkin's lymphoma in Nebraska (United States) AN - 16641071; 3652620 AB - Little is known about dietary factors and non-Hodgkin's lymphoma (NHL) risk, although high intakes of animal protein and milk have been associated with NHL in two previous studies. As part of a population-based case-control study of agricultural and other risk factors for NHL in eastern Nebraska (USA), we examined the self- and proxy-reported frequency of consumption of 30 food items by 385 White men and women with NHL and 1,432 controls. Animal protein intake was not associated significantly with the risk of NHL, however, there was a nonsignificantly elevated risk of NHL among men with high milk consumption. Vitamin C, carotene, citrus fruit, and dark green vegetable intakes were inversely significantly related to the risk of NHL for men, but not for women. Among men, the odds ratios for the highest quartiles of both vitamin C and carotene intake were 0.6 (95% confidence intervals = 0.3-1.0). There were no meaningful differences in the associations of nutrient intakes and NHL risk between B- and T-cell lymphomas and histologic types. Risks for low intakes of vitamin C and carotene were greater among men and women with a family history of cancer, particularly a history of lymphatic or hematopoietic cancer among first-degree relatives. JF - Cancer Causes & Control AU - Ward, M H AU - Zahm, SH AU - Weisenburger, D D AU - Gridley, G AU - Cantor, K P AU - Saal, R C AU - Blair, A AD - Environ. Epidemiol. Branch, NCI, EPN Room 418, Bethesda, MD 20892, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 422 EP - 432 VL - 5 IS - 5 SN - 0957-5243, 0957-5243 KW - foods KW - vitamins KW - non-Hodgkin's lymphoma KW - Risk Abstracts; Health & Safety Science Abstracts KW - diets KW - nutrients KW - milk KW - USA, Nebraska KW - proteins KW - cancer KW - R2 23060:Medical and environmental health KW - H SM10.21:CANCER UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16641071?accountid=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=Dietary+factors+and+non-Hodgkin%27s+lymphoma+in+Nebraska+%28United+States%29&rft.au=Ward%2C+M+H%3BZahm%2C+SH%3BWeisenburger%2C+D+D%3BGridley%2C+G%3BCantor%2C+K+P%3BSaal%2C+R+C%3BBlair%2C+A&rft.aulast=Ward&rft.aufirst=M&rft.date=1994-01-01&rft.volume=5&rft.issue=5&rft.spage=422&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 - USA, Nebraska; diets; proteins; milk; cancer; nutrients ER - TY - JOUR T1 - Architectural elements in nucleoprotein complexes: Interchangeability of specific and non-specific DNA binding proteins AN - 16638508; 3648810 AB - Integration host factor (IHF) is required in lambda site-specific recombination to deform the DNA substrates into conformations active for recombination. HU, a homolog of IHF, can also deform DNA but binds without any apparent sequence specificity. We demonstrate that HU can replace IHF by cooperating with the recombinase protein, integrase, to generate a stable and specific complex with electrophoretic mobility and biochemical activity very close to the complex formed by IHF and integrase. The eukaryotic HMG1 and HMG2 proteins differ entirely in structure from HU but they also bind DNA non-specifically and induce or stabilize deformed DNA. We show that the eukaryotic HMG1 and HMG2 proteins cooperate with integrase at least as well as does HU to make a defined structure. We also find that the eukaryotic core histone dimer H2A-H2B can replace IHF, suggesting that the histone dimer is functional outside the context of a nucleosome. HU and the HMG proteins not only contribute to the formation of stable complexes, but they can at least partially replace IHF for the integrative and excisive recombination reactions. The results, together with the analysis of nucleoprotein complexes made with damaged recombination sites, lead us to conclude that the cooperation between HU and integrase does not depend on protein-protein contacts. Rather, cooperation is manifested through building of higher order structures and depends on the capacity of the non-specific DNA binding proteins to bend DNA. While all these non-specific binding proteins appear to fulfil the same bending function, they do so with different efficiencies. This probably reflects subtle structural differences between the assembled complexes. JF - EMBO Journal AU - Segall, A M AU - Goodman, S D AU - Nash, HA AD - Lab. Mol. Biol., NIMH, Bethesda, MD 20892-4034, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 4536 EP - 4548 VL - 13 IS - 19 SN - 0261-4189, 0261-4189 KW - integration host factor KW - histones KW - high mobility group protein 1 KW - high mobility group protein 2 KW - integrase KW - Microbiology Abstracts B: Bacteriology; Virology & AIDS Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - DNA-binding protein KW - phage lambda KW - nucleoproteins KW - Escherichia coli KW - N 14920:Chromatin & chromosomes KW - J 02727:Amino acids, peptides and proteins KW - V 22031:Viral nucleic acids UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16638508?accountid=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=Architectural+elements+in+nucleoprotein+complexes%3A+Interchangeability+of+specific+and+non-specific+DNA+binding+proteins&rft.au=Segall%2C+A+M%3BGoodman%2C+S+D%3BNash%2C+HA&rft.aulast=Segall&rft.aufirst=A&rft.date=1994-01-01&rft.volume=13&rft.issue=19&rft.spage=4536&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 - phage lambda; Escherichia coli; nucleoproteins; DNA-binding protein ER - TY - JOUR T1 - Nucleotide sequence and analysis of the gene in Borrelia burgdorferi encoding the immunogenic P39 antigen AN - 16638139; 3648927 AB - The P39 antigen is a specific, highly conserved, and immunogenic protein of Lyme disease spirochetes, Borrelia burgdorferi sensu lato. The nucleotide sequence of the gene encoding this protein was determined and found to be the first of two tandemly arranged open reading frames located on the spirochete's chromosome. These two open reading frames were designated bmpA for the gene encoding P39 and bmpB for the gene encoding the putative protein ORF2 encoded by the second open reading frame. The nucleic acid sequence identity for the two open reading frames was 62% while their deduced amino acid sequences were 52% identical. Comparison to sequence data bases demonstrated that the deduced amino acid sequences of both P39 and ORF2 were homologous to TmpC, a putative outer or cytoplasmic membrane lipoprotein of the syphilis spirochete, Treponema pallidum. JF - FEMS Microbiology Letters AU - Simpson, W J AU - Cieplak, W AU - Schrumpf, ME AU - Barbour, A G AU - Schwan, T G AD - Rocky Mountain Lab., NIAID/NIH, Hamilton, MT 59840, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 381 EP - 388 VL - 119 IS - 3 SN - 0378-1097, 0378-1097 KW - P39 antigen KW - bmpA gene KW - bmpB gene KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Biochemistry Abstracts 2: Nucleic Acids; Genetics Abstracts; Microbiology Abstracts B: Bacteriology KW - nucleotide sequence KW - Borrelia burgdorferi KW - genes KW - Lyme disease KW - N 14640:Structure & sequence KW - J 02725:DNA KW - G 07320:Bacterial genetics KW - W3 33385:DNA/RNA KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16638139?accountid=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=Nucleotide+sequence+and+analysis+of+the+gene+in+Borrelia+burgdorferi+encoding+the+immunogenic+P39+antigen&rft.au=Simpson%2C+W+J%3BCieplak%2C+W%3BSchrumpf%2C+ME%3BBarbour%2C+A+G%3BSchwan%2C+T+G&rft.aulast=Simpson&rft.aufirst=W&rft.date=1994-01-01&rft.volume=119&rft.issue=3&rft.spage=381&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 - 2011-12-14 N1 - SubjectsTermNotLitGenreText - nucleotide sequence; genes; Lyme disease; Borrelia burgdorferi ER - TY - JOUR T1 - Laboratory and preliminary clinical characterization of Vi capsular polysaccharide-protein conjugate vaccines AN - 16633275; 3636480 AB - To improve its immunogenicity for children and adults and to make it suitable for routine immunization of infants against typhoid fever, the capsular polysaccharide of Salmonella typhi (Vi) was bound to the B subunit of the heat-labile toxin (LT-B) of Escherichia coli or the recombinant exoprotein A (rEPA) of Pseudomonas aeruginosa. The conjugates elicited higher levels of antibodies (micrograms per milliliter of serum) in mice and in guinea pigs than did Vi and, unlike Vi alone, elicited booster antibody responses in both species. In adult volunteers, Vi-LT-B and Vi-rEPA, respectively, elicited higher levels of antibodies than Vi alone after the first injection (4.74 versus 1.77 and 4.91 versus 1.77) and 26 weeks later (2.32 and 2.69 versus 0.54); a second injection of the conjugates did not elicit a booster response of Vi antibodies. None of the 51 vaccinees had fever or significant local reactions. Vi-rEPA elicited slightly higher levels of Vi antibodies than did Vi-LT-B at all intervals after injection, but these differences were not significant. Each conjugate elicited antibodies to its carrier protein. The antibody responses elicited in adults by Vi bound to LT-B and rEPA are similar to those of other polysaccharide-protein conjugates. These conjugates promise to be an improved Vi vaccine. Studies of Vi conjugates with adults and infants in areas where typhoid is endemic are planned. JF - Infection and Immunity AU - Szu, S C AU - Taylor, D N AU - Trofa, A C AU - Clements, J D AU - Shiloach, J AU - Sadoff, J C AU - Bryla, DA AU - Robbins, J B AD - NICHD, Build. 6, Rm. 145, NIH, Bethesda, MD 20892, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 4440 EP - 4444 VL - 62 IS - 10 SN - 0019-9567, 0019-9567 KW - carrier proteins KW - guinea-pigs KW - mice KW - polysaccharides KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts; Microbiology Abstracts B: Bacteriology KW - typhoid fever KW - vaccines KW - conjugation KW - Salmonella typhi KW - Escherichia coli KW - characterization KW - capsules KW - Pseudomonas aeruginosa KW - man KW - enterotoxins KW - W3 33365:Vaccines (other) KW - J 02834:Vaccination and immunization KW - F 06807:Active immunization KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16633275?accountid=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=Laboratory+and+preliminary+clinical+characterization+of+Vi+capsular+polysaccharide-protein+conjugate+vaccines&rft.au=Szu%2C+S+C%3BTaylor%2C+D+N%3BTrofa%2C+A+C%3BClements%2C+J+D%3BShiloach%2C+J%3BSadoff%2C+J+C%3BBryla%2C+DA%3BRobbins%2C+J+B&rft.aulast=Szu&rft.aufirst=S&rft.date=1994-01-01&rft.volume=62&rft.issue=10&rft.spage=4440&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - typhoid fever; vaccines; conjugation; characterization; capsules; man; enterotoxins; Salmonella typhi; Escherichia coli; Pseudomonas aeruginosa ER - TY - JOUR T1 - Maternal smoking during lactation: Relation to infant size at one year of age AN - 16623105; 3653722 AB - This study was conducted to test the hypothesis that breast-fed infants of smokers are smaller in size at 1 year of age than breast-fed infants of nonsmokers. Three groups of infants were selected from all singletons born to women who were seen for prenatal care in their 6th month of pregnancy at a health maintenance organization in Seattle, Washington, between January 1982 and April 1983. Breast-fed infants of smokers (n = 74) were compared with breast-fed infants of nonsmokers (n = 195) and with bottle-fed infants of smokers (n = 64). Mothers are interviewed at 1 and 3 months after delivery; both the mother and the infant were seen at 1 year. Among breast feeders, smokers' infants were twice as likely as nonsmokers' infants to have body mass more than 1 standard deviation above the mean (relative risk = 2.04, 95% confidence interval 1.15-3.61). This relation persisted after control for gestational age and weight at birth, length of lactation, mother's size and diet, exposure to other drugs in breast milk, and all other variables measured in this study. Every 10 cigarettes smoked while breast feeding predicted an additional 3% infant body mass at 1 year. In summary, breast-fed infants of smokers in this study gained more weight after birth than the other two groups; at 1 year of age, they were heavier and had significantly higher body mass. Reasons for this paradoxical finding are explored. JF - American Journal of Epidemiology AU - Little, R E AU - Lambert, MD III AU - Worthington-Roberts, B AU - Ervin, CH AD - NIEHS, A3-05, P.O. Box 12233, Research Triangle Park, NC 27709, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 544 EP - 554 VL - 140 IS - 6 SN - 0002-9262, 0002-9262 KW - lactation KW - weight KW - breast feeding KW - man KW - Toxicology Abstracts; Risk Abstracts; Health & Safety Science Abstracts KW - passive smoking KW - smoking KW - infants KW - epidemiology KW - growth KW - H SE4.26:DRUGS AND ALCOHOL KW - R2 23060:Medical and environmental health KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16623105?accountid=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+Epidemiology&rft.atitle=Maternal+smoking+during+lactation%3A+Relation+to+infant+size+at+one+year+of+age&rft.au=Little%2C+R+E%3BLambert%2C+MD+III%3BWorthington-Roberts%2C+B%3BErvin%2C+CH&rft.aulast=Little&rft.aufirst=R&rft.date=1994-01-01&rft.volume=140&rft.issue=6&rft.spage=544&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 N1 - SubjectsTermNotLitGenreText - infants; growth; smoking; epidemiology; passive smoking; lactation; weight; breast feeding; man ER - TY - JOUR T1 - Heterosexual transmission of human immunodeficiency virus type 1 from transfusion recipients to their sex partners AN - 16620723; 3649804 AB - Using lookback procedures and other methods, we identified and then prospectively followed human immunodeficiency virus type 1 (HIV-1)-infected transfusion recipients and their sex partners to determine AIDS incidence and risks of heterosexual transmission of HIV-1. At enrollment, 7 of 32 (21.9%) female partners of male recipients were themselves infected with HIV-1, as compared with none of 14 male partners of female recipients (p = 0.08). No additional episodes of transmission were observed. The prevalence of advanced immunodeficiency at enrollment was similar in male and female recipients. Male recipients with advanced immunodeficiency (CD4+ lymphocyte count less than or equal to 0.20 x 10 super(9)/L or a history of clinical AIDS) at enrollment were more likely to have infected their female partners (odds ratio = 7.9; p = 0.03) than men with neither condition. Similarly, AIDS-free survival, as estimated by the product-limit method, was lower among male transmitters than among male nontransmitters (p = 0.01). Transmission was not associated with frequency of unprotected vaginal intercourse. Our data suggest that HIV-1-infected men who develop immunodeficiency rapidly are more likely to infect their sex partners and that the greater efficiency of male-to-female HIV-1 transmission is not explained by a greater number of sexual contacts or more advanced immunodeficiency in index subjects. JF - JAIDS Journal of Acquired Immune Deficiency Syndromes AU - O'Brien, T R AU - Busch, M P AU - Donegan, E AU - Ward, J W AU - Wong, L AU - Samson, S M AU - Perkins, HA AU - Altman, R AU - Stoneburner, R L AU - Holmberg, S D AD - NCI/NIH, Exec. Plaza North Build., Room 434, 6130 Exec. Blvd., Rockville, MD 20852, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 705 EP - 710 VL - 7 IS - 7 SN - 0894-9255, 0894-9255 KW - infection KW - transmission (sexual) KW - heterosexuality KW - blood transfusion KW - sexually transmitted diseases KW - Risk Abstracts; Health & Safety Science Abstracts; Virology & AIDS Abstracts KW - human immunodeficiency virus 1 KW - epidemiology KW - H SM10.43:HIV/AIDS KW - V 22005:AIDS: Epidemiological aspects KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16620723?accountid=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=JAIDS+Journal+of+Acquired+Immune+Deficiency+Syndromes&rft.atitle=Heterosexual+transmission+of+human+immunodeficiency+virus+type+1+from+transfusion+recipients+to+their+sex+partners&rft.au=O%27Brien%2C+T+R%3BBusch%2C+M+P%3BDonegan%2C+E%3BWard%2C+J+W%3BWong%2C+L%3BSamson%2C+S+M%3BPerkins%2C+HA%3BAltman%2C+R%3BStoneburner%2C+R+L%3BHolmberg%2C+S+D&rft.aulast=O%27Brien&rft.aufirst=T&rft.date=1994-01-01&rft.volume=7&rft.issue=7&rft.spage=705&rft.isbn=&rft.btitle=&rft.title=JAIDS+Journal+of+Acquired+Immune+Deficiency+Syndromes&rft.issn=08949255&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - human immunodeficiency virus 1; epidemiology; sexually transmitted diseases; infection; transmission (sexual); heterosexuality; blood transfusion ER - TY - JOUR T1 - Surface plasmon resonance based methods for measuring the kinetics and binding affinities of biomolecular interactions AN - 16618392; 3646551 AB - Surface plasmon resonance is emerging as the method of choice to study biomolecular interactions between macromolecules because it allows the observation of real-time kinetics for these processes. The method is currently being applied to the study of antigen-antibody interactions, protein-DNA interactions, receptor SH2 domain-phosphotyrosine peptide interactions and receptor-ligand interactions. JF - Current Opinion in Biotechnology AU - Fisher, R J AU - Fivash, M AD - Lab. Cell. Biochem., PRI/DynCorp, P.O. Box B, NCI-Frederick Cancer Res. Dev. Cent., Frederick, MD 21702-1201, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 389 EP - 395 VL - 5 IS - 4 SN - 0958-1669, 0958-1669 KW - interactions KW - surface plasmon resonance KW - Biotechnology and Bioengineering Abstracts; Agricultural and Environmental Biotechnology Abstracts KW - measuring techniques KW - antigen-antibody interactions KW - binding KW - molecules KW - kinetics KW - W2 32250:Others KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16618392?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+Opinion+in+Biotechnology&rft.atitle=Surface+plasmon+resonance+based+methods+for+measuring+the+kinetics+and+binding+affinities+of+biomolecular+interactions&rft.au=Fisher%2C+R+J%3BFivash%2C+M&rft.aulast=Fisher&rft.aufirst=R&rft.date=1994-01-01&rft.volume=5&rft.issue=4&rft.spage=389&rft.isbn=&rft.btitle=&rft.title=Current+Opinion+in+Biotechnology&rft.issn=09581669&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 - antigen-antibody interactions; measuring techniques; molecules; binding; kinetics ER - TY - JOUR T1 - Structural characterization of Pseudomonas 7A glutaminase-asparaginase AN - 16615765; 3648962 AB - The amino acid sequence and a 2-angstrom-resolution crystallographic structure of Pseudomonas 7A glutaminase-asparaginase (PGA) have been determined. PGA, which belongs to the family of tetrameric bacterial amidohydrolases, deamidates glutamine and asparagine. The amino acid sequence of PGA has a high degree of similarity to the sequences of other members of the family. PGA has the same fold as other bacterial amidohydrolases, with the exception of the position of a 20-residue loop that forms part of the active site. In the PGA structure presented here, the active site loop is observed clearly in only one monomer, in an open position, with a conformation different from that observed for other amidohydrolases. In the other three monomers the loop is disordered and cannot be traced. This phenomenon is probably a direct consequence of a very low occupancy of product(s) of the enzymatic reaction bound in the active sites of PGA in these crystals. The active sites are composed of a rigid part and the flexible loop. The rigid part consists of the residues directly involved in the catalytic reaction as well as residues that assist in orienting the substrate. Two residues that are important for activity reside on the flexible loop. We suggest that the flexible loops actively participate in the transport of substrate and product molecules through the amidohydrolase active sites and participate in orienting the substrate molecules properly in relation to the catalytic residues. JF - Biochemistry (Washington) AU - Lubkowski, J AU - Wlodawer, A AU - Ammon, H L AU - Copeland, T D AU - Swain, AL AD - Macromol. Struct. Lab. and Spec. Program in Protein Chem., NCI-FCRDC, ABL-Basic Res. Program, Frederick, MD 21702-1201, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 10257 EP - 10265 VL - 33 IS - 34 SN - 0006-2960, 0006-2960 KW - glutaminase-asparaginase KW - Microbiology Abstracts B: Bacteriology KW - X-ray crystallography KW - active sites KW - crystal structure KW - Pseudomonas KW - J 02728:Enzymes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16615765?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemistry+%28Washington%29&rft.atitle=Structural+characterization+of+Pseudomonas+7A+glutaminase-asparaginase&rft.au=Lubkowski%2C+J%3BWlodawer%2C+A%3BAmmon%2C+H+L%3BCopeland%2C+T+D%3BSwain%2C+AL&rft.aulast=Lubkowski&rft.aufirst=J&rft.date=1994-01-01&rft.volume=33&rft.issue=34&rft.spage=10257&rft.isbn=&rft.btitle=&rft.title=Biochemistry+%28Washington%29&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Pseudomonas; crystal structure; X-ray crystallography; active sites ER - TY - JOUR T1 - Risk factors for esophageal cancer in Shanghai, China. II. Role of diet and nutrients AN - 16615487; 3636866 AB - A population-based case-control study of esophageal cancer (902 cases, 1,552 controls) in Shanghai, China, investigated the etiologic role of diet. After adjustment for cigarette smoking, alcohol consumption and other risk factors, increasing consumption of fruits, dark orange vegetables and beef or mutton was associated with statistically significant decreasing trends in risk for esophageal cancer. In general, risks were about 40% lower among those in the upper vs. lower quartiles of intake of these foods. Fivefold increases in risk were observed among those who consumed burning hot soup or porridge, with smaller excesses for preserved vegetables, salty and deep fried foods. Nutrient analysis revealed that increased dietary intake of protein, carotene, vitamins C and E and riboflavin was associated with reduced esophageal cancer risk. Our findings support the notion that the reported temporal increases in the per capita consumption of fruits, vegetables and animal products contribute to the substantial reduction in the incidence of esophageal cancer in Shanghai, particularly since cigarette and alcohol use has not decreased. JF - International Journal of Cancer AU - Gao, Yu-Tang AU - McLaughlin, J K AU - Gridley, G AU - Blot, W J AU - Ji, Bu-Tian AU - Dai, Qi AU - Fraumeni, JF Jr AD - NCI, 6130 Executive Blvd., Room 415, Rockville, MD 20852, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 197 EP - 202 VL - 58 IS - 2 SN - 0020-7136, 0020-7136 KW - foods KW - esophagus KW - Toxicology Abstracts; Risk Abstracts KW - etiology KW - diets KW - nutrients KW - food KW - China, People's Rep., Shanghai KW - cancer KW - X 24120:Food, additives & contaminants KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16615487?accountid=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=International+Journal+of+Cancer&rft.atitle=Risk+factors+for+esophageal+cancer+in+Shanghai%2C+China.+II.+Role+of+diet+and+nutrients&rft.au=Gao%2C+Yu-Tang%3BMcLaughlin%2C+J+K%3BGridley%2C+G%3BBlot%2C+W+J%3BJi%2C+Bu-Tian%3BDai%2C+Qi%3BFraumeni%2C+JF+Jr&rft.aulast=Gao&rft.aufirst=Yu-Tang&rft.date=1994-01-01&rft.volume=58&rft.issue=2&rft.spage=197&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Cancer&rft.issn=00207136&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - China, People's Rep., Shanghai; cancer; diets; nutrients; etiology; food; esophagus ER - TY - JOUR T1 - Administration of recombinant human IL-7 to mice alters the composition of B-lineage cells and T cell subsets, enhances T cell function, and induces regression of established metastases AN - 16612996; 3640819 AB - These studies investigate the effects of exogenously administered recombinant human IL-7 (rhIL-7) on mouse leukocyte subsets in vivo in normal and tumor-bearing mice. The administration of rhIL-7 to normal mice caused a pronounced leukocytosis (three- to fivefold increase over background) in the spleen and lymph nodes, with B-lineage and T cells, NK cells, and macrophages all being increased. CD8 super(+) T cells increased disproportionately, such that the CD4 to CD8 ratio decreased dramatically. The rhIL-7-induced effects were dose-dependent, increased with duration of treatment, and were reversible after cessation of rhIL-7 administration. The results demonstrate that the administration of rhIL-7 to mice profoundly increases the number of B and T cells, and reduces the number of pulmonary metastases. The results also suggest that IL-7 may be useful for restoring lymphoid subsets in immunosuppressed hosts and in enhancing T cell-mediated immune responses. Such effects may be useful in the treatment of microbial diseases and cancer. JF - Journal of Immunology AU - Komschlies, K L AU - Gregorio, T A AU - Gruys, ME AU - Back, T C AU - Faltynek, C R AU - Wiltrout, R H AD - Biol. Carcinogen. and Dev. Program, Program Resources, Inc./DynCorp, NCI-FCRDC, Build. 560, Rm. 31-93, Frederick, MD 21702-1201, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 5776 EP - 5784 VL - 152 IS - 12 SN - 0022-1767, 0022-1767 KW - mice KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - response KW - lymphocytes T KW - interleukin 7 KW - immunotherapy KW - metastases KW - regression KW - kidney KW - lymphocytes B KW - man KW - carcinoma KW - F 06818:Cancer immunotherapy KW - W3 33160:Antibody based KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16612996?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Immunology&rft.atitle=Administration+of+recombinant+human+IL-7+to+mice+alters+the+composition+of+B-lineage+cells+and+T+cell+subsets%2C+enhances+T+cell+function%2C+and+induces+regression+of+established+metastases&rft.au=Komschlies%2C+K+L%3BGregorio%2C+T+A%3BGruys%2C+ME%3BBack%2C+T+C%3BFaltynek%2C+C+R%3BWiltrout%2C+R+H&rft.aulast=Komschlies&rft.aufirst=K&rft.date=1994-01-01&rft.volume=152&rft.issue=12&rft.spage=5776&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immunology&rft.issn=00221767&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - response; lymphocytes T; interleukin 7; metastases; immunotherapy; regression; kidney; lymphocytes B; man; carcinoma ER - TY - JOUR T1 - In vitro and ex vivo effects of cyclosporin A on phagocytic host defenses against Aspergillus fumigatus AN - 16601724; 3669848 AB - Because cyclosporin A (CsA) is extensively used as an immunosuppressive agent, its effects on phagocytic defenses against Aspergillus fumigatus were studied in vitro and ex vivo. After incubation with 10 to 250 ng of CsA per ml at 37 degree C for 60 min, polymorphonuclear leukocytes (PMNs) exhibited unaltered superoxide anion (O sub(2) super(-)) production in response to phorbol myristate acetate and N-formylmethionyl leucyl phenylalanine, whereas greater than or equal to 500 ng/ml significantly suppressed it (P < 0.01). Moreover, at <250 ng of CsA per ml, PMNs exhibited no change in their capacity to damage unopsonized hyphae of A. fumigatus compared with controls, whereas at greater than or equal to 250 ng/ml, CsA suppressed the function (P < 0.01). Although neither CsA (250 ng/ml) nor hydrocortisone (10 mu g/ml) suppressed PMN O sub(2) super(-) production in response to phorbol myristate acetate and N-formylmethionyl leucyl phenylalanine, combination of the two agents reduced the function compared with that at the baseline (P < 0.05). Incubation of monocytes with 100 ng of CsA per ml for 1 or 2 days suppressed their antihyphal activity. No essential change in phagocytic activity of monocyte-derived macrophages (MDMs) against A. fumigatus conidia, tested as the percentage of phagocytosing MDMs and average number of MDM-associated conidia, was detected after 2 or 4 days of incubation with 10 to 1,000 ng of CsA per ml. Furthermore, in rabbits treated with CsA (up to 20 mg/kg of body weight per day intravenously for 7 days), neither O sub(2) super(-) production and hyphal damage caused by PMNs or monocytes against hyphae nor phagocytosis of conidia by pulmonary alveolar macrophages was significantly suppressed. Thus, these results demonstrated that CsA within therapeutically relevant concentrations does not suppress antifungal activity of phagocytes except that of circulating monocytes. However, it may induce significant immunosuppression of phagocytes' antifungal function at relatively high concentrations in vitro, especially when combined with corticosteroids. JF - Antimicrobial Agents & Chemotherapy AU - Roilides, E AU - Robinson, T AU - Sein, T AU - Pizzo, P A AU - Walsh, T J AD - Pediatric Branch, NCI, Bldg. 10, Rm. 13N240, Bethesda, MD 20892, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 2883 EP - 2888 VL - 38 IS - 12 SN - 0066-4804, 0066-4804 KW - cyclosporin A KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Microbiology Abstracts C: Algology, Mycology & Protozoology KW - immunosuppression KW - Aspergillus fumigatus KW - host range KW - activity KW - A 01067:Antifungal & fungicidal KW - K 03063:Effects of physical & chemical factors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16601724?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologya&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antimicrobial+Agents+%26+Chemotherapy&rft.atitle=In+vitro+and+ex+vivo+effects+of+cyclosporin+A+on+phagocytic+host+defenses+against+Aspergillus+fumigatus&rft.au=Roilides%2C+E%3BRobinson%2C+T%3BSein%2C+T%3BPizzo%2C+P+A%3BWalsh%2C+T+J&rft.aulast=Roilides&rft.aufirst=E&rft.date=1994-01-01&rft.volume=38&rft.issue=12&rft.spage=2883&rft.isbn=&rft.btitle=&rft.title=Antimicrobial+Agents+%26+Chemotherapy&rft.issn=00664804&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Aspergillus fumigatus; activity; host range; immunosuppression ER - TY - JOUR T1 - Cohort study among workers exposed to benzene in China: I. General methods and resources AN - 16599493; 3660077 AB - Benzene is recognized internationally as a leukemogen, but the available data to clarify dose-response relationships and examine risks of malignancies other than leukemia are sparse. A collaborative study was therefore carried out to expand on a previous retrospective cohort mortality study of Chinese benzene-exposed workers. Methods and resources used in the 16-year follow-up of 74,828 benzene-exposed and 35,805 unexposed workers employed for any length of time during 1972-1987 in 712 factories in 12 cities in China are described. Details are provided of the study organization, assessment of benzene exposures since 1949, characterization of factories and workers by exposure status, city, and sex, identification and confirmation of cancers and other deaths, and quality control procedures. The distinguishing features of the study are discussed in relation to earlier cohort studies, and study limitations as well as strengths are presented. JF - American Journal of Industrial Medicine AU - Yin, S-N AU - Linet AU - Hayes, R B AU - Li, G-L AU - Dosemeci, M AU - Wang, Y-Z AU - Chow, W-H AU - Jiang, Z-L AU - Wacholder, S AU - Zhang, W-U AD - Epidemiol. and Biostat. Prog., NCI, EPN 415, Rockville, MD 20892, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 383 EP - 400 VL - 26 IS - 3 SN - 0271-3586, 0271-3586 KW - benzene KW - factories KW - man KW - Toxicology Abstracts; Health & Safety Science Abstracts KW - historical account KW - leukemia KW - occupational exposure KW - dose-response effects KW - industries KW - China, People's Rep. KW - cancer KW - H SI6.3:HAZARD DETERMINATION KW - H SM10.21:CANCER KW - X 24152:Chronic exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16599493?accountid=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+Industrial+Medicine&rft.atitle=Cohort+study+among+workers+exposed+to+benzene+in+China%3A+I.+General+methods+and+resources&rft.au=Yin%2C+S-N%3BLinet%3BHayes%2C+R+B%3BLi%2C+G-L%3BDosemeci%2C+M%3BWang%2C+Y-Z%3BChow%2C+W-H%3BJiang%2C+Z-L%3BWacholder%2C+S%3BZhang%2C+W-U&rft.aulast=Yin&rft.aufirst=S-N&rft.date=1994-01-01&rft.volume=26&rft.issue=3&rft.spage=383&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 - China, People's Rep.; benzene; occupational exposure; leukemia; cancer; dose-response effects; historical account; factories; industries; man ER - TY - JOUR T1 - Comparative tolerability profiles of the newer versus older antidepressants AN - 16593765; 3647644 AB - Although the standard tricyclic antidepressants (TCAs) are generally effective in the treatment of depression, they can cause several troublesome adverse effects. Chief among these are their anticholinergic actions, which range from annoying dryness of the mouth and constipation to potentially dangerous urinary retention and confusion or delirium in the ill and elderly. Cardiovascular effects of TCAs include orthostatic hypotension, tachycardia and cardiac conduction slowing. Many TCAs are sedating and promote weight gain. Also problematic is the potential lethality of TCAs in overdose. The continual introduction of a host of new antidepressants over the past 15 years has provided an opportunity to improve the benefit-risk ratio for many patients by reducing medication-related toxicity. Selective serotonin reuptake inhibitors (SSRIs) and amfebutamone (bupropion), among others, are examples of effective antidepressants free of tricyclic-like anticholinergic, cardiovascular, sedating and appetite/weight-increasing effects. However, the new-generation drugs also present adverse effects of their own, including gastrointestinal distress, agitation and drug-drug interactions in the case of the SSRIs, and the risk of seizures or psychosis in amfebutamone recipients. JF - Drug Safety AU - Rudorfer, M V AU - Manji, H K AU - Potter, W Z AD - Sect. Clin. Pharmacol., Exp. Ther. Branch, NIMH/NIH, Build. 10, Room 2D46, 9000 Rockville Pike, Bethesda, MD 20892, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 47 EP - 65 VL - 10 IS - 1 SN - 0114-5916, 0114-5916 KW - Toxicology Abstracts KW - side effects KW - antidepressants KW - tricyclic antidepressants KW - man KW - X 24113:Side effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16593765?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Drug+Safety&rft.atitle=Comparative+tolerability+profiles+of+the+newer+versus+older+antidepressants&rft.au=Rudorfer%2C+M+V%3BManji%2C+H+K%3BPotter%2C+W+Z&rft.aulast=Rudorfer&rft.aufirst=M&rft.date=1994-01-01&rft.volume=10&rft.issue=1&rft.spage=47&rft.isbn=&rft.btitle=&rft.title=Drug+Safety&rft.issn=01145916&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 - tricyclic antidepressants; side effects; man; antidepressants ER - TY - JOUR T1 - The cytotoxicity of thioguanine vs mercaptopurine in acute lymphoblastic leukemia AN - 16587378; 3677323 AB - The use of mercaptopurine (MP) rather than thioguanine (TG) in the treatment of childhood acute lymphoblastic leukemia (ALL) has occurred for historical reasons, but does not have a pharmacologic basis. The purpose of this study was to begin to address whether TG would be more efficacious than MP in the treatment of childhood ALL. Pre-clinical cytotoxicity studies were performed using human leukemic cell lines and leukemic cells from patients with ALL. First, the concentration-survival curves for MP and TG in three human leukemic cell lines (MOLT-4, CCRF-CEM and Wilson) were determined. The second group of experiments determined the concentration-time dependence for cytotoxicity of MP and TG. The final group of experiments compared the in vitro cytotoxicity of MP to TG in leukemic cells from patients with ALL. The thiopurines displayed classical anti-metabolite cytotoxicity profiles, exhibiting a cytotoxicity threshold concentration and demonstrating an increase in cell kill with prolongation of exposure to the drug. For MP, the cytotoxicity threshold was approximately 1 mu M, with maximum cytotoxicity occurring with 10 mu M concentrations. For TG, the threshold was only 0.05 mu M with maximum cytotoxicity occurring at 0.5 mu M. Exposure to MP for more than 8 h was necessary to produce cytotoxicity, whereas exposures as short as 4 h were required for TG. Leukemic cells from children with ALL were also more sensitive to TG than to MP. The median IC sub(50) for TG (20 mu M) was significantly lower than that for MP ( greater than or equal to 206 mu M). The data presented here provide a strong rationale for evaluating TG in place of MP in the treatment of childhood ALL. The more direct intracellular activation pathway, higher potency, and shorter duration of drug exposure necessary for cytotoxicity all suggest that TG may have an advantage over MP. JF - Leukemia Research AU - Adamson, P C AU - Poplack, D G AU - Balis, F M AD - Pharmacol. and Exp. Ther. Sect., Pediatr. Branch, NCI, Build. 10, Rm. 13N240, 9000 Rockville Pike, Bethesda, MD 20892, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 805 EP - 810 VL - 18 IS - 11 SN - 0145-2126, 0145-2126 KW - thioguanine KW - mercaptopurine KW - Toxicology Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - cytotoxicity KW - acute lymphatic leukemia KW - man KW - X 24117:Biochemistry KW - N 14120:Biological properties UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16587378?accountid=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=Leukemia+Research&rft.atitle=The+cytotoxicity+of+thioguanine+vs+mercaptopurine+in+acute+lymphoblastic+leukemia&rft.au=Adamson%2C+P+C%3BPoplack%2C+D+G%3BBalis%2C+F+M&rft.aulast=Adamson&rft.aufirst=P&rft.date=1994-01-01&rft.volume=18&rft.issue=11&rft.spage=805&rft.isbn=&rft.btitle=&rft.title=Leukemia+Research&rft.issn=01452126&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 - cytotoxicity; acute lymphatic leukemia; man ER - TY - JOUR T1 - Quantitative analysis of viral burden in tissues from adults and children with symptomatic human immunodeficiency virus type 1 infection assessed by polymerase chain reaction AN - 16586746; 3670891 AB - The amount of human immunodeficiency virus type 1 (HIV-1) in various tissues was investigated by polymerase chain reaction (PCR) in 16 patients with end-stage HIV-1 infection and 7 patients with symptomatic but less advanced disease. During postmortem study of the 16 end-stage patients, HIV-1 DNA was found most often in lymph nodes and the spleen (both 100%), lung (93.8%), and colon (87.5%). Biopsied lymph nodes from the 7 symptomatic patients contained substantially higher copy numbers of HIV-1 RNA and DNA than did peripheral blood mononuclear cells (PBMC). Plasma viral RNA levels correlated significantly with the amount of HIV-1 RNA in PBMC (r super(2) = .86, P = .0025) but not with the level of viral RNA in lymph nodes in patients with symptomatic HIV-1 infection. These data suggest that although lymph nodes represent the main site for HIV-1 infection and replication, the level of circulating viral burden may not be solely determined by the magnitude of active HIV-1 replication in lymph nodes. JF - Journal of Infectious Diseases AU - Sei, S AU - Kleiner, DE AU - Kopp, J B AU - Chandra, R AU - Klotman, P E AU - Yarchoan, R AU - Pizzo, P A AU - Mitsuya, H AD - NCI/NIH, Bldg. 10, Room 13N240, 9000 Rockville Pike, Bethesda, MD 20892, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 325 EP - 333 VL - 170 IS - 2 SN - 0022-1899, 0022-1899 KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Virology & AIDS Abstracts KW - nucleotide sequence KW - pediatrics KW - lymphocytes KW - human immunodeficiency virus 1 KW - lymph nodes KW - quantitation KW - infection KW - DNA KW - autopsy KW - man KW - adolescence KW - W 30965:Miscellaneous, Reviews KW - V 22004:AIDS: Clinical aspects KW - W3 33130:Genetic based (PCR, etc.) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16586746?accountid=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+Infectious+Diseases&rft.atitle=Quantitative+analysis+of+viral+burden+in+tissues+from+adults+and+children+with+symptomatic+human+immunodeficiency+virus+type+1+infection+assessed+by+polymerase+chain+reaction&rft.au=Sei%2C+S%3BKleiner%2C+DE%3BKopp%2C+J+B%3BChandra%2C+R%3BKlotman%2C+P+E%3BYarchoan%2C+R%3BPizzo%2C+P+A%3BMitsuya%2C+H&rft.aulast=Sei&rft.aufirst=S&rft.date=1994-01-01&rft.volume=170&rft.issue=2&rft.spage=325&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 - 2011-12-14 N1 - SubjectsTermNotLitGenreText - nucleotide sequence; pediatrics; lymphocytes; lymph nodes; quantitation; DNA; infection; autopsy; man; adolescence; human immunodeficiency virus 1 ER - TY - JOUR T1 - Demonstration of human T lymphotropic virus type I (HTLV-I)-specific T cell responses from seronegative and polymerase chain reaction-negative persons exposed to HTLV-I AN - 16586362; 3670930 AB - Human T lymphotropic virus type I (HTLV-I) is a human retrovirus etiologically linked to adult T cell leukemia and the progressive chronic neurologic disease HTLV-I-associated myelopathy/tropical spastic paraparesis. Described is a method that measures the production of interleukin-2 from HTLV-I synthetic peptide-stimulated peripheral blood lymphocytes (PBL) of HTLV-I-infected persons. The peptides correspond to immunogenic regions of the HTLV-I Env and Tax proteins. Significantly, this assay demonstrated T cell responses to these HTLV-I peptides from coded PBL samples in 7 of 19 HTLV-I-seronegative polymerase chain reaction-negative persons known to have been exposed to HTLV-I but in none of 16 matched controls without risk factors for exposure (P = .007). The implications of this finding are discussed. JF - Journal of Infectious Diseases AU - Nishimura, M AU - Kermode, A G AU - Clerici, M AU - Shearer, G M AU - Berzofsky, JA AU - Uchiyama, T AU - Wiktor, S Z AU - Pate, E AU - Jacobson, S AD - NIH/NINDS, Bldg. 10, Room 5B-16, Bethesda, MD 20892, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 334 EP - 348 VL - 170 IS - 2 SN - 0022-1899, 0022-1899 KW - T cell leukemia virus I KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Virology & AIDS Abstracts KW - interleukin 2 KW - nucleotide sequence KW - detection KW - lymphocytes T KW - immune response (cell-mediated) KW - antibodies KW - man KW - V 22099:Immune response & immune mechanisms KW - W3 33240:Immunology KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16586362?accountid=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+Infectious+Diseases&rft.atitle=Demonstration+of+human+T+lymphotropic+virus+type+I+%28HTLV-I%29-specific+T+cell+responses+from+seronegative+and+polymerase+chain+reaction-negative+persons+exposed+to+HTLV-I&rft.au=Nishimura%2C+M%3BKermode%2C+A+G%3BClerici%2C+M%3BShearer%2C+G+M%3BBerzofsky%2C+JA%3BUchiyama%2C+T%3BWiktor%2C+S+Z%3BPate%2C+E%3BJacobson%2C+S&rft.aulast=Nishimura&rft.aufirst=M&rft.date=1994-01-01&rft.volume=170&rft.issue=2&rft.spage=334&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 - 2011-12-14 N1 - SubjectsTermNotLitGenreText - nucleotide sequence; interleukin 2; detection; lymphocytes T; immune response (cell-mediated); antibodies; man ER - TY - JOUR T1 - Isolation, characterization, and expression in Escherichia coli of the Pseudomonas aeruginosa rhlAB genes encoding a rhamnosyltransferase involved in rhamnolipid biosurfactant synthesis AN - 16578911; 3665552 AB - Transposon Tn5-GM-induced mutant strains of Pseudomonas aeruginosa which are unable to produce rhamnolipid biosurfactants and lack rhamnosyltransferase activity have been isolated. The DNA regions flanking the transposon were cloned and used as specific probes for the isolation of the corresponding wild-type genes from a P. aeruginosa wild-type cosmid gene library. Single cosmid clones capable of restoring rhamnolipid synthesis in the mutant strains were isolated and further subcloned and sequenced, resulting in the identification of two genes (rhlAB) which are organized as an operon upstream of the previously identified rhlR regulatory gene. The RhlA protein (32.5 kDa) harbors a putative signal sequence, suggesting that this protein is located in the periplasm, while the RhlB protein (47 kDa) contains at least two putative membrane-spanning domains. JF - Journal of Biological Chemistry AU - Ochsner, U A AU - Fiechter, A AU - Reiser, J AD - NIH, NINDS, Build. 10, Rm. 3D04, Bethesda, MD 20892, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 19787 EP - 19795 VL - 269 IS - 31 SN - 0021-9258, 0021-9258 KW - rhamnosyltransferase KW - rhlAB gene KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - nucleotide sequence KW - amino acid sequence KW - surfactants KW - prediction KW - Pseudomonas aeruginosa KW - N 14640:Structure & sequence KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16578911?accountid=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=Isolation%2C+characterization%2C+and+expression+in+Escherichia+coli+of+the+Pseudomonas+aeruginosa+rhlAB+genes+encoding+a+rhamnosyltransferase+involved+in+rhamnolipid+biosurfactant+synthesis&rft.au=Ochsner%2C+U+A%3BFiechter%2C+A%3BReiser%2C+J&rft.aulast=Ochsner&rft.aufirst=U&rft.date=1994-01-01&rft.volume=269&rft.issue=31&rft.spage=19787&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 - Pseudomonas aeruginosa; nucleotide sequence; amino acid sequence; prediction; surfactants ER - TY - JOUR T1 - Treatment and developmental therapeutics of Mycobacterium tuberculosis infections AN - 16569043; 3646320 AB - Tuberculosis still remains a serious health problem in many regions of the world, especially in developing nations. With the spread of AIDS and the increase in the number of immunocompromised patients, the problem of tuberculosis has been greatly exacerbated because of the susceptibility of such patients to mycobacteria. Currently, chemotherapy using multiple drug regimens with isoniazid, rifampin, streptomycin, pyrazinamide, and ethambutol is the recommended treatment for tuberculosis. The presence of drug resistance is still a major concern and new generations of more effective antimycobacterial agents (antibiotics, fluoroquinolone derivatives) are the subject of active investigation. The search for novel strategies to cure tuberculosis led to studies exploring the role of cytokines in host defenses and the application of adoptive immunotherapy. New and improved methodology for in vitro and in vivo screening of antimycobacterial activity has also been reported. JF - International Journal of Antimicrobial Agents AU - St. Georgiev, V AD - NIAID/NIH, Solar Build., Room 4C-04, Bethesda, MD 20892, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 157 EP - 173 VL - 4 IS - 3 SN - 0924-8579, 0924-8579 KW - isoniazid KW - rifampin KW - Microbiology Abstracts B: Bacteriology KW - BCG KW - treatment KW - immunotherapy KW - drug resistance KW - infection KW - antibacterial agents KW - Mycobacterium tuberculosis KW - J 02845:Ear, nose and respiratory tract UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16569043?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+Journal+of+Antimicrobial+Agents&rft.atitle=Treatment+and+developmental+therapeutics+of+Mycobacterium+tuberculosis+infections&rft.au=St.+Georgiev%2C+V&rft.aulast=St.+Georgiev&rft.aufirst=V&rft.date=1994-01-01&rft.volume=4&rft.issue=3&rft.spage=157&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Antimicrobial+Agents&rft.issn=09248579&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 tuberculosis; infection; antibacterial agents; treatment; drug resistance; immunotherapy; BCG ER - TY - JOUR T1 - Risk factors for esophageal cancer in Shanghai, China. I. Role of cigarette smoking and alcohol drinking AN - 16568292; 3636885 AB - A population-based case-control study of esophageal cancer was conducted in urban Shanghai involving interviews with 902 cases and 1,552 controls. Risk of esophageal cancer was increased among tobacco smokers and alcohol drinkers. Odds ratios (OR) for smoking were 2.1 and 1.6 for men and women, respectively, and increased with number of cigarettes smoked per day, duration of smoking, number of pack-years and decreasing age at start of smoking. For men who were current alcohol drinkers OR was 1.4, with the excess risk primarily among heavy drinkers. Few women drank alcoholic beverages. The combined effect of heavy smoking and drinking among men was pronounced: OR was 12.0 for those who smoked more than 1 pack per day and drank more than 750 g of ethanol per week. The relation with smoking appeared stronger for cancers of the middle and lower thirds of the esophagus than for the upper third, while patterns of risk for squamous cell carcinoma and adenocarcinoma were similar. Heavy drinking affected all 3 subsites, with increased risks mainly limited to squamous cell carcinoma. Cigarette smoking and alcohol drinking combined accounted for almost 50% of all esophageal cancers among men in Shanghai; among women, 14% of cases were attributed to smoking. Our study confirms that smoking and drinking are important risk factors for esophageal cancer in China, thereby paralleling findings from developed countries. JF - International Journal of Cancer AU - Gao, Yu-Tang AU - McLaughlin, J K AU - Blot, W J AU - Ji, Bu-Tian AU - Benichou, J AU - Dai, Qi AU - Fraumeni, JF Jr AD - NCI, 6130 Executive Blvd., Room 415, Rockville, MD 20852, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 192 EP - 196 VL - 58 IS - 2 SN - 0020-7136, 0020-7136 KW - alcohol KW - ethanol KW - esophagus KW - Toxicology Abstracts; Risk Abstracts KW - cigarette smoking KW - statistical analysis KW - China, People's Rep., Shanghai KW - cancer KW - R2 23060:Medical and environmental health KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16568292?accountid=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=International+Journal+of+Cancer&rft.atitle=Risk+factors+for+esophageal+cancer+in+Shanghai%2C+China.+I.+Role+of+cigarette+smoking+and+alcohol+drinking&rft.au=Gao%2C+Yu-Tang%3BMcLaughlin%2C+J+K%3BBlot%2C+W+J%3BJi%2C+Bu-Tian%3BBenichou%2C+J%3BDai%2C+Qi%3BFraumeni%2C+JF+Jr&rft.aulast=Gao&rft.aufirst=Yu-Tang&rft.date=1994-01-01&rft.volume=58&rft.issue=2&rft.spage=192&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Cancer&rft.issn=00207136&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - China, People's Rep., Shanghai; cancer; cigarette smoking; statistical analysis; alcohol; ethanol; esophagus ER - TY - JOUR T1 - Recent advances in the management of AIDS-related opportunistic infections AN - 15661660; 3953496 AB - Secondary infections remain the leading cause of death in patients with the acquired immunodeficiency syndrome (AIDS). Dealing with the rapidly evolving spectrum of infectious problems seen in patients with AIDS requires knowledge of current therapeutic and prophylactic strategies. Through an extensive preclinical trials network supported by both industry and government, an increasing number of new agents are being identified and rapidly moved into clinical trials. Several agents are now available to treat diseases caused by Pneumocystis carinii, and corticosteroids have become a useful adjunct to antimicrobial agents in the treatment of P. carinii pneumonia. Although the treatment of toxoplasmosis remains a challenge, alternatives to sulfadiazine and pyrimethamine are now available. Mycobacterial infections, particularly with Mycobacterium tuberculosis, have become an increasing problem for patients with AIDS, and both old and new combination drug regimens are being used. Cytomegalovirus disease, until recently an untreatable problem, can now at least be partially managed with antiviral agents. The use of more complete prophylactic regimens may decrease the morbidity and mortality from opportunistic infections. JF - Annals of Internal Medicine AU - Lane, H C AU - Laughon, B E AU - Falloon, J AU - Kovacs, JA AU - Davey, RT Jr AU - Polis, MA AU - Masur, H AD - NIAID/NIH, Bldg. 10, Rm. 11B09, Bethesda, MD 20892, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 945 EP - 955 VL - 120 IS - 11 SN - 0003-4819, 0003-4819 KW - Microbiology Abstracts B: Bacteriology; Microbiology Abstracts C: Algology, Mycology & Protozoology; Virology & AIDS Abstracts KW - opportunist infection KW - Pneumocystis carinii KW - treatment KW - mortality KW - pneumonia KW - acquired immune deficiency syndrome KW - Mycobacterium tuberculosis KW - K 03087:Fungi: human KW - J 02845:Ear, nose and respiratory tract KW - V 22004:AIDS: Clinical aspects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15661660?accountid=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=Annals+of+Internal+Medicine&rft.atitle=Recent+advances+in+the+management+of+AIDS-related+opportunistic+infections&rft.au=Lane%2C+H+C%3BLaughon%2C+B+E%3BFalloon%2C+J%3BKovacs%2C+JA%3BDavey%2C+RT+Jr%3BPolis%2C+MA%3BMasur%2C+H&rft.aulast=Lane&rft.aufirst=H&rft.date=1994-01-01&rft.volume=120&rft.issue=11&rft.spage=945&rft.isbn=&rft.btitle=&rft.title=Annals+of+Internal+Medicine&rft.issn=00034819&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Pneumocystis carinii; Mycobacterium tuberculosis; acquired immune deficiency syndrome; opportunist infection; treatment; pneumonia; mortality ER - TY - JOUR T1 - Synthesis of the methyl alpha -glycoside of the intracatenary disaccharide repeating unit of the O-polysaccharide of Vibrio cholerae O:1. A comparison of two assembly strategies AN - 15610664; 3925593 AB - The two strategies engaged in the construction of the title disaccharide 17 comprise: 1. assembly of a diamino disaccharide and its N-acylation using chiral reagents to introduce the 4-(-3-deoxy-L-glycero-tetronyl) group followed by deprotection and 2. preparation of a glycosyl acceptor and a glycosyl donor both having the chiral 3-deoxy-L-glycero-tetronamido group already in place, their condensation to give a fully substituted disaccharide, and deprotection. Accordingly, the crystalline diamino disaccharide methyl 2-O-(amino-3-O-benzyl 4,6-dideoxy- alpha -D-mannopyranosyl) 4-amino-3-O-benzyl-4,6 -dideoxy alpha -D-mannopyranoside, (14), was prepared from the known [Bundle D. R. et al., Carbohydr. Res., 174, 239 (1988)] diazido disaccharide 12, and treated with the lactone 30, or its acetylated or benzylated analogs 31 and 32, respectively, as the N-acylating reagents. Subsequent deprotection of the respective products applying standard chemistry gave 17. Alternatively, the methyl alpha -glycoside of the monomeric intracatenary repeating unit of Vibrio cholerae O:1 (2) was converted to the fully benzoylated glycosyl chloride 26, and the latter glycosyl donor was condensed with methyl 3-O-benzyl-4,6-dideoxy 4-(2,4-di-O-benzoyl 3-deoxy-L-glycero-tetronamido) alpha - D-mannopyranoside (24), to give the corresponding fully protected derivative 27. Deprotection then readily gave 17. It appears that the title disaccharide can be most efficiently synthesized using synthons 24 and 26. The lactones 30 and 32 appear to be promising acylating reagents for the introduction of the 3-deoxy-L-glycero-tetronamido group when higher oligosaccharides in this series will be synthesized via their (poly)amino precursors. JF - Journal of Carbohydrate Chemistry AU - Gotoh, M AU - Kovac, P AD - NIDDK, Natl. Inst. Health, Bethesda, MD 20892, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 1193 EP - 1213 VL - 13 IS - 8 SN - 0732-8303, 0732-8303 KW - methyl alpha -glycoside KW - disaccharides KW - polysaccharides KW - Microbiology Abstracts B: Bacteriology KW - Vibrio cholerae KW - J 02730:Carbohydrates UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15610664?accountid=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+Carbohydrate+Chemistry&rft.atitle=Synthesis+of+the+methyl+alpha+-glycoside+of+the+intracatenary+disaccharide+repeating+unit+of+the+O-polysaccharide+of+Vibrio+cholerae+O%3A1.+A+comparison+of+two+assembly+strategies&rft.au=Gotoh%2C+M%3BKovac%2C+P&rft.aulast=Gotoh&rft.aufirst=M&rft.date=1994-01-01&rft.volume=13&rft.issue=8&rft.spage=1193&rft.isbn=&rft.btitle=&rft.title=Journal+of+Carbohydrate+Chemistry&rft.issn=07328303&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Vibrio cholerae ER - TY - JOUR T1 - Effect of L-ascorbic acid pretreatment on cadmium toxicity in the male Fischer (F344/NCr) rat. AN - 76213968; 8303714 AB - Some studies have indicated that cadmium-induced lethality and selective injurious effects to specific tissues, such as testes or liver, can be prevented by pretreatment with the antioxidant L-ascorbic acid (ascorbic acid). However, the basis of this tolerance is unclear. We examined the effects of ascorbic acid pretreatment on cadmium toxicity in male Fischer (F344/NCr) rats. Cadmium treatment alone (25 mumol CdCl2/kg, s.c.) proved lethal, causing a 93% mortality within 72 h, but in rats pretreated with ascorbic acid (2 g/kg, s.c. 24, 12 and 1 h) cadmium-induced lethality was nearly prevented. Hepatic lesions, including hepatocellular necrosis, induced by cadmium were at least partially ameliorated by ascorbic acid pretreatment. Ascorbic acid pretreatment had no effect on cadmium-induced testicular lesions nor on cadmium content in testes, liver, kidney and urine. Ascorbic acid alone modestly increased hepatic metallothionein (MT), but not renal MT and had no effect on induction of hepatic or renal MT by cadmium. In contrast to liver and kidney, testicular cadmium-binding protein (TCBP) in rats exposed to cadmium alone decreased markedly. Moreover, the level of TCBP decreased unexpectedly in ascorbic acid pretreated rats as compared with control. These results indicate that ascorbic acid pretreatment decreases the toxicity of cadmium in the rat without markedly modifying its toxicokinetics or markedly stimulating MT synthesis. JF - Toxicology AU - Shiraishi, N AU - Uno, H AU - Waalkes, M P AD - Inorganic Carcinogenesis Section, National Cancer Institute, Frederick Cancer Research and Development Center, MD 21702-1201. Y1 - 1993/12/31/ PY - 1993 DA - 1993 Dec 31 SP - 85 EP - 100 VL - 85 IS - 2-3 SN - 0300-483X, 0300-483X KW - Oligonucleotide Probes KW - 0 KW - RNA, Messenger KW - cadmium-binding protein KW - Metallothionein KW - 9038-94-2 KW - L-Lactate Dehydrogenase KW - EC 1.1.1.27 KW - Ascorbic Acid KW - PQ6CK8PD0R KW - Index Medicus KW - Animals KW - Kidney -- metabolism KW - Testis -- metabolism KW - Metallothionein -- biosynthesis KW - Kidney -- drug effects KW - Liver -- metabolism KW - Metallothionein -- genetics KW - Tissue Distribution KW - Rats KW - Rats, Inbred F344 KW - Base Sequence KW - Testis -- drug effects KW - RNA, Messenger -- metabolism KW - Liver -- drug effects KW - L-Lactate Dehydrogenase -- blood KW - Molecular Sequence Data KW - Male KW - Ascorbic Acid -- pharmacology KW - Cadmium Poisoning -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76213968?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Effect+of+L-ascorbic+acid+pretreatment+on+cadmium+toxicity+in+the+male+Fischer+%28F344%2FNCr%29+rat.&rft.au=Shiraishi%2C+N%3BUno%2C+H%3BWaalkes%2C+M+P&rft.aulast=Shiraishi&rft.aufirst=N&rft.date=1993-12-31&rft.volume=85&rft.issue=2-3&rft.spage=85&rft.isbn=&rft.btitle=&rft.title=Toxicology&rft.issn=0300483X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-03-09 N1 - Date created - 1994-03-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Biochemical analysis of Escherichia coli selenophosphate synthetase mutants. Lysine 20 is essential for catalytic activity and cysteine 17/19 for 8-azido-ATP derivatization. AN - 76141477; 8262938 AB - A labile selenium donor compound, selenophosphate, is formed from selenide and ATP by selenophosphate synthetase. A cysteine residue (Cys-17) that is essential for catalytic activity of the enzyme (Kim, I.Y., Veres, Z., and Stadtman, T. C. (1992) J. Biol. Chem. 267, 19650-19654) is located in a glycine-rich segment near the N terminus of the protein. The possibility that this peptide sequence (HGAGCGCK) defines the ATP-binding site of the enzyme, as does a conserved ATP or GTP binding sequence (GXXXXGKS/T) found in several other proteins, was tested by site-specific mutagenesis. Thus His-13 and Gly-18 were changed to Asn and Val, respectively, and Lys-20 to Arg or Gln. Catalytic activity was markedly decreased by mutation of Lys-20 to Arg and abolished by mutation of Lys-20 to Gln. The mutation of Cys-19 and His-13 did not substantially alter the ATP Km and Vmax values, whereas the Gly-18 mutation resulted in a 4-fold increase in the ATP Km value compared with that of the wild type. ATP binding properties of the mutant enzymes were determined using Mn-[32P]ATP or Mn-[14C]ATP and gel filtration. Photoaffinity labeling of the proteins with [gamma-32P]8-azido-ATP showed that all mutant enzymes could be labeled with the ATP analog except those in which Cys-17 or Cys-19 were replaced with serine. JF - The Journal of biological chemistry AU - Kim, I Y AU - Veres, Z AU - Stadtman, T C AD - Laboratory of Biochemistry, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/12/25/ PY - 1993 DA - 1993 Dec 25 SP - 27020 EP - 27025 VL - 268 IS - 36 SN - 0021-9258, 0021-9258 KW - Affinity Labels KW - 0 KW - Azides KW - Bacterial Proteins KW - Drosophila Proteins KW - Metals KW - 8-azidoadenosine 5'-triphosphate KW - 53696-59-6 KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - Phosphotransferases KW - EC 2.7.- KW - selenophosphate synthetase KW - EC 2.7.9.3 KW - Lysine KW - K3Z4F929H6 KW - Cysteine KW - K848JZ4886 KW - Index Medicus KW - Metals -- pharmacology KW - Base Sequence KW - Adenosine Triphosphate -- analogs & derivatives KW - Adenosine Triphosphate -- metabolism KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Substrate Specificity KW - Azides -- chemistry KW - Catalysis KW - Adenosine Triphosphate -- chemistry KW - Mutagenesis, Site-Directed KW - Cysteine -- metabolism KW - Bacterial Proteins -- genetics KW - Bacterial Proteins -- antagonists & inhibitors KW - Cysteine -- genetics KW - Bacterial Proteins -- metabolism KW - Escherichia coli -- enzymology KW - Lysine -- genetics KW - Lysine -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76141477?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Biochemical+analysis+of+Escherichia+coli+selenophosphate+synthetase+mutants.+Lysine+20+is+essential+for+catalytic+activity+and+cysteine+17%2F19+for+8-azido-ATP+derivatization.&rft.au=Kim%2C+I+Y%3BVeres%2C+Z%3BStadtman%2C+T+C&rft.aulast=Kim&rft.aufirst=I&rft.date=1993-12-25&rft.volume=268&rft.issue=36&rft.spage=27020&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 - 1994-01-27 N1 - Date created - 1994-01-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - p53: at the crossroads of molecular carcinogenesis and risk assessment. AN - 76116310; 8266092 JF - Science (New York, N.Y.) AU - Harris, C C AD - Laboratory of Human Carcinogenesis, Division of Cancer Etiology, National Cancer Institute, Bethesda, MD 20892. Y1 - 1993/12/24/ PY - 1993 DA - 1993 Dec 24 SP - 1980 EP - 1981 VL - 262 IS - 5142 SN - 0036-8075, 0036-8075 KW - p53 KW - Codon KW - 0 KW - Index Medicus KW - Risk KW - Animals KW - Codon -- genetics KW - Humans KW - Genes, p53 KW - Mutation KW - Neoplasms -- genetics KW - Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76116310?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Science+%28New+York%2C+N.Y.%29&rft.atitle=p53%3A+at+the+crossroads+of+molecular+carcinogenesis+and+risk+assessment.&rft.au=Harris%2C+C+C&rft.aulast=Harris&rft.aufirst=C&rft.date=1993-12-24&rft.volume=262&rft.issue=5142&rft.spage=1980&rft.isbn=&rft.btitle=&rft.title=Science+%28New+York%2C+N.Y.%29&rft.issn=00368075&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-01-21 N1 - Date created - 1994-01-21 N1 - Date revised - 2017-01-13 N1 - Gene symbol - p53 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cloning and organization of the abc and mdl genes of Escherichia coli: relationship to eukaryotic multidrug resistance. AN - 76167916; 7904973 AB - Using degenerate oligodeoxyribonucleotides from conserved regions of the gene family encoding ATP-binding domain of the active transporter, two new Escherichia coli genes were identified. The first of the genes, named mdl (multidrug resistance-like), is located at min 10.2 of the E. coli chromosome and encodes two ATP-binding motifs and two hydrophobic (transmembrane) domains. The ATP-binding domains of mdl show 35-38% amino acid (aa) identity with members of the eukaryotic P-glycoprotein/multidrug resistance family. To date, 25 members of the ATP-transporter/permease gene family have been characterized in E. coli. Comparison of the ATP-binding domains from this family indicates that mdl is part of a distinct subfamily of sequences that includes hlyB, msbA, and cvaB. Gene-disruption studies revealed that mdl is not essential for cell growth. The second open reading frame, named abc (ATP-binding cassette), is located at min 4.9 of the chromosome, encodes a single ATP-binding domain, and is most homologous to ftsE, a cell division control gene of E. coli. The abc gene product also shows aa sequence homology to several E. coli permeases. JF - Gene AU - Allikmets, R AU - Gerrard, B AU - Court, D AU - Dean, M AD - Laboratory of Viral Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, MD 21702. Y1 - 1993/12/22/ PY - 1993 DA - 1993 Dec 22 SP - 231 EP - 236 VL - 136 IS - 1-2 SN - 0378-1119, 0378-1119 KW - HuMDR1 KW - abc KW - mdl KW - Bacterial Proteins KW - 0 KW - Carrier Proteins KW - DNA, Bacterial KW - Escherichia coli Proteins KW - Membrane Glycoproteins KW - Membrane Proteins KW - P-Glycoprotein KW - mdlB protein, E coli KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - Index Medicus KW - Base Sequence KW - Humans KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Membrane Proteins -- genetics KW - Chromosome Mapping KW - Membrane Glycoproteins -- genetics KW - Cloning, Molecular KW - Genes, Bacterial KW - Bacterial Proteins -- genetics KW - Carrier Proteins -- genetics KW - Drug Resistance, Microbial -- genetics KW - Escherichia coli -- drug effects KW - Escherichia coli -- genetics KW - ATP-Binding Cassette Transporters UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76167916?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cloning+and+organization+of+the+abc+and+mdl+genes+of+Escherichia+coli%3A+relationship+to+eukaryotic+multidrug+resistance.&rft.au=Allikmets%2C+R%3BGerrard%2C+B%3BCourt%2C+D%3BDean%2C+M&rft.aulast=Allikmets&rft.aufirst=R&rft.date=1993-12-22&rft.volume=136&rft.issue=1-2&rft.spage=231&rft.isbn=&rft.btitle=&rft.title=Gene&rft.issn=03781119&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-03-01 N1 - Date created - 1994-03-01 N1 - Date revised - 2017-01-13 N1 - Gene symbol - HuMDR1; abc; mdl N1 - Genetic sequence - Z15047; GENBANK; L15362; L08626; X72987; L08627; X72988; Z15048; X72989; L15363; L24529 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - LINE-1: a human transposable element. AN - 76150696; 8276257 AB - Among the 10(5) LINE-1 sequences (L1Hs) in the human genome are one or more 6-kb segments that are active retrotransposons. Expression of these retrotransposons appears to be favored in cells of germ line origin, as well as in some other tumor cells of epithelial origin. In such cells, the product of the first L1Hs open reading frame (ORF), a protein called p40, is detectable; p40 has no apparent similarity to gag proteins, but contains a leucine zipper region which may be responsible for the occurrence of p40 multimers. Transcription of L1Hs initiates at residue 1 although the transcriptional regulatory regions are downstream in the first 670 bp of the 5' untranslated region; deletion of a YY1-binding site in the first 20 bp reduces transcription by fivefold. Translation of the second ORF, which encodes reverse transcriptase, is independent of the translation of the frame encoding p40. JF - Gene AU - Singer, M F AU - Krek, V AU - McMillan, J P AU - Swergold, G D AU - Thayer, R E AD - Laboratory of Biochemistry, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/12/15/ PY - 1993 DA - 1993 Dec 15 SP - 183 EP - 188 VL - 135 IS - 1-2 SN - 0378-1119, 0378-1119 KW - DNA Transposable Elements KW - 0 KW - DNA-Binding Proteins KW - Proteins KW - Transcription Factors KW - L1Hs-encoded protein p40, human KW - 148349-28-4 KW - Index Medicus KW - Teratocarcinoma KW - Protein Biosynthesis KW - Animals KW - Tumor Cells, Cultured KW - Organ Specificity -- genetics KW - Open Reading Frames KW - Humans KW - Molecular Sequence Data KW - Transcription, Genetic KW - Mice KW - Amino Acid Sequence KW - Leucine Zippers KW - Transcription Factors -- genetics KW - Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76150696?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=LINE-1%3A+a+human+transposable+element.&rft.au=Singer%2C+M+F%3BKrek%2C+V%3BMcMillan%2C+J+P%3BSwergold%2C+G+D%3BThayer%2C+R+E&rft.aulast=Singer&rft.aufirst=M&rft.date=1993-12-15&rft.volume=135&rft.issue=1-2&rft.spage=183&rft.isbn=&rft.btitle=&rft.title=Gene&rft.issn=03781119&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-02-10 N1 - Date created - 1994-02-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Flavonol-stimulated efflux of 7,12-dimethylbenz(a)anthracene in multidrug-resistant breast cancer cells. AN - 76127867; 7903198 AB - We used a series of P-glycoprotein (P-gp) expressing multidrug-resistant (MDR) cells, developed from human breast cancer MCF-7 cells by exposure to Adriamycin, to investigate the effects of flavonoids on P-gp-mediated efflux mechanisms for chemical carcinogens. We previously showed that MDR cells derived from exposure to Adriamycin are cross-resistant to a chemical carcinogen, benzo(a)pyrene, due to its cellular efflux by the P-gp-mediated putative drug efflux pump. Our current studies extended this observation to another polycyclic aromatic hydrocarbon, 7,12-dimethylbenz(a)anthracene, known to induce mammary tumors in animals. In our attempt to find naturally occurring dietary compounds which may stimulate the P-gp-mediated efflux of carcinogens, we found that certain flavonols, kaempferol, quercetin, and galangin, are potent stimulators of the P-gp-mediated efflux of 7,12-dimethylbenz(a)-anthracene. The increased efflux decreased the cellular burden of 7,12-dimethylbenz(a)anthracene. Since these flavonol compounds are widely distributed in fruits and vegetables, their stimulatory effect on P-gp may be a mechanism relevant to carcinogenesis and the observed lowered cancer risk in humans with higher dietary intake of fruits and vegetables. JF - Cancer research AU - Phang, J M AU - Poore, C M AU - Lopaczynska, J AU - Yeh, G C AD - Laboratory of Nutritional and Molecular Regulation, National Cancer Institute, NIH, Frederick, Maryland 21702. Y1 - 1993/12/15/ PY - 1993 DA - 1993 Dec 15 SP - 5977 EP - 5981 VL - 53 IS - 24 SN - 0008-5472, 0008-5472 KW - Carrier Proteins KW - 0 KW - Flavonoids KW - Flavonols KW - Membrane Glycoproteins KW - P-Glycoprotein KW - 9,10-Dimethyl-1,2-benzanthracene KW - 57-97-6 KW - Index Medicus KW - Tumor Cells, Cultured KW - Membrane Glycoproteins -- physiology KW - Humans KW - Drug Resistance KW - Carrier Proteins -- physiology KW - Diet KW - Female KW - Breast Neoplasms -- metabolism KW - Flavonoids -- pharmacology KW - 9,10-Dimethyl-1,2-benzanthracene -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76127867?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Flavonol-stimulated+efflux+of+7%2C12-dimethylbenz%28a%29anthracene+in+multidrug-resistant+breast+cancer+cells.&rft.au=Phang%2C+J+M%3BPoore%2C+C+M%3BLopaczynska%2C+J%3BYeh%2C+G+C&rft.aulast=Phang&rft.aufirst=J&rft.date=1993-12-15&rft.volume=53&rft.issue=24&rft.spage=5977&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 - 1994-01-24 N1 - Date created - 1994-01-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Expression of an oncogenic rasHa gene in murine keratinocytes induces tyrosine phosphorylation and reduced activity of protein kinase C delta. AN - 76119926; 8253722 AB - Murine keratinocytes expressing an oncogenic rasHa gene produce benign tumors in vivo and demonstrate altered responses to phorbol esters in vitro. Cultured keratinocytes transduced with the v-rasHa gene (v-rasHa keratinocytes) are resistant to Ca(2+)-induced terminal differentiation, a process that is dependent on protein kinase C (PKC) activation in normal keratinocytes. Five PKC isoforms expressed in keratinocytes (alpha, delta, epsilon, zeta, and eta) were examined for quantitative or qualitative changes in v-rasHa-transformed cells. No quantitative changes were detected, but PKC delta was tyrosine-phosphorylated in v-rasHa keratinocytes and in benign neoplastic keratinocyte cell lines expressing an activated allele of the c-rasHa gene. Analysis of phosphorylated and non-phosphorylated forms of PKC delta from keratinocytes indicated that phosphorylated PKC delta was not stimulated by phorbol ester treatment. The protein kinase inhibitor staurosporine was able to induce differentiation in v-rasHa keratinocytes and benign tumor cell lines, and concomitantly tyrosine phosphorylation of PKC delta decreased. This interaction between tyrosine kinases and PKC delta in cells expressing an oncogenic rasHa gene may represent a molecular block to differentiation in neoplastic keratinocytes. JF - The Journal of biological chemistry AU - Denning, M F AU - Dlugosz, A A AU - Howett, M K AU - Yuspa, S H AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1993/12/15/ PY - 1993 DA - 1993 Dec 15 SP - 26079 EP - 26081 VL - 268 IS - 35 SN - 0021-9258, 0021-9258 KW - rasHa KW - Tyrosine KW - 42HK56048U KW - Protein Kinase C KW - EC 2.7.11.13 KW - Index Medicus KW - Animals KW - Phosphorylation KW - Cells, Cultured KW - Mice KW - Mice, Inbred BALB C KW - Protein Kinase C -- metabolism KW - Genes, ras KW - Protein Kinase C -- antagonists & inhibitors KW - Keratinocytes -- metabolism KW - Tyrosine -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76119926?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Expression+of+an+oncogenic+rasHa+gene+in+murine+keratinocytes+induces+tyrosine+phosphorylation+and+reduced+activity+of+protein+kinase+C+delta.&rft.au=Denning%2C+M+F%3BDlugosz%2C+A+A%3BHowett%2C+M+K%3BYuspa%2C+S+H&rft.aulast=Denning&rft.aufirst=M&rft.date=1993-12-15&rft.volume=268&rft.issue=35&rft.spage=26079&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 - 1994-01-13 N1 - Date created - 1994-01-13 N1 - Date revised - 2017-01-13 N1 - Gene symbol - rasHa N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - An early response of an AP1-junD complex during T-cell activation. AN - 76113141; 8253775 AB - Activated T-cell extracts contain an activity (T-AP1) composed of at least two dissociable protein components which bind to the AP1 consensus sequence in the enhancer of the gibbon ape leukemia virus (GALV)-LTR (GALV-TRE). This activity is inducible by 12-O-tetradecanoyl-phorbol-14-acetate (TPA) even in the presence of protein synthesis inhibitors. Although one component of this complex (CORE) is related immunologically and biochemically to junD, it nevertheless displays significant biochemical properties which distinguish CORE from recombinant junD. The second component of the complex, flowthrough, interacts more efficiently with CORE than with recombinant junD. GALV-TRE enhancer activity is increased within 2 h in vivo with T cells treated with TPA in the presence of protein synthesis inhibitors; this increase in enhancer activity is paralleled by the increased GALV-TRE-mediated transcriptional activity present in extracts of these cells. Purified T-cell junD activates GALV-TRE-driven RNA synthesis in vitro. The rapidity and the protein synthesis-independent nature of TPA-induced T-AP1 activation suggests that this complex is involved in the earliest stages of T-cell activation. JF - The Journal of biological chemistry AU - Farina, A R AU - Davis-Smyth, T AU - Gardner, K AU - Levens, D AD - Laboratory of Pathology, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1993/12/15/ PY - 1993 DA - 1993 Dec 15 SP - 26466 EP - 26475 VL - 268 IS - 35 SN - 0021-9258, 0021-9258 KW - Oligodeoxyribonucleotides KW - 0 KW - Proto-Oncogene Proteins c-jun KW - Cycloheximide KW - 98600C0908 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - HeLa Cells KW - Humans KW - Protein Processing, Post-Translational KW - Mice KW - Transcription, Genetic KW - Base Sequence KW - Tumor Cells, Cultured KW - Cycloheximide -- pharmacology KW - Enhancer Elements, Genetic KW - Molecular Sequence Data KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Lymphocyte Activation KW - T-Lymphocytes -- metabolism KW - Proto-Oncogene Proteins c-jun -- genetics KW - Proto-Oncogene Proteins c-jun -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76113141?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=An+early+response+of+an+AP1-junD+complex+during+T-cell+activation.&rft.au=Farina%2C+A+R%3BDavis-Smyth%2C+T%3BGardner%2C+K%3BLevens%2C+D&rft.aulast=Farina&rft.aufirst=A&rft.date=1993-12-15&rft.volume=268&rft.issue=35&rft.spage=26466&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 - 1994-01-13 N1 - Date created - 1994-01-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Translation of the human LINE-1 element, L1Hs. AN - 76109544; 8265584 AB - Full-length RNA transcribed from the human LINE-1 (L1) element L1 Homo sapiens (L1Hs) has a 900-nt, G+C-rich, 5'-untranslated region (UTR). The 5' UTR is followed by two long open reading frames, ORF1 and ORF2, which are separated from each other by an inter-ORF region of 33 nt that includes two or three in-frame stop codons. We examine here the mechanism(s) by which the translation of L1Hs ORF1 and ORF2 is initiated. A stable hairpin structure (delta G = -74.8 kcal/mol), inserted at nt 661 of the 5' UTR, caused a 3- to 8-fold decrease in the in vitro and in vivo translation of either a lacZ reporter gene for ORF1 or the ORF1 polypeptide product, p40, but translation of a lacZ reporter gene in ORF2 was increased. The results are compatible with a model for ORF1 translation initiation in which the majority of ribosomes scan from a point 5' of nt 661 but suggest that ORF2 is not translated by attached ribosomes that reinitiate after the termination of ORF1 translation. Our data are compatible with a model whereby the translation of L1Hs ORF2 is initiated internally. JF - Proceedings of the National Academy of Sciences of the United States of America AU - McMillan, J P AU - Singer, M F AD - Laboratory of Biochemistry, National Cancer Institute, Bethesda, MD 20892. Y1 - 1993/12/15/ PY - 1993 DA - 1993 Dec 15 SP - 11533 EP - 11537 VL - 90 IS - 24 SN - 0027-8424, 0027-8424 KW - Codon KW - 0 KW - Oligodeoxyribonucleotides KW - RNA, Messenger KW - beta-Galactosidase KW - EC 3.2.1.23 KW - Index Medicus KW - Animals KW - Blotting, Northern KW - Codon -- genetics KW - Open Reading Frames KW - Humans KW - Transcription, Genetic KW - Nucleic Acid Conformation KW - Base Sequence KW - Genes KW - RNA, Messenger -- metabolism KW - Transfection KW - Restriction Mapping KW - Molecular Sequence Data KW - Calorimetry KW - beta-Galactosidase -- biosynthesis KW - Repetitive Sequences, Nucleic Acid KW - Cell Line KW - Mutagenesis, Insertional KW - Protein Biosynthesis KW - Hominidae -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76109544?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Translation+of+the+human+LINE-1+element%2C+L1Hs.&rft.au=McMillan%2C+J+P%3BSinger%2C+M+F&rft.aulast=McMillan&rft.aufirst=J&rft.date=1993-12-15&rft.volume=90&rft.issue=24&rft.spage=11533&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 - 1994-01-21 N1 - Date created - 1994-01-21 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - M80343; GENBANK N1 - SuppNotes - Cited By: EMBO J. 1990 Apr;9(4):1177-85 [1691094] Mol Cell Biol. 1989 Nov;9(11):5134-42 [2601712] Proc Natl Acad Sci U S A. 1990 Sep;87(18):6990-4 [1698287] Mol Cell Biol. 1990 Dec;10(12):6718-29 [1701022] Trends Biochem Sci. 1990 Dec;15(12):477-83 [2077688] J Cell Biol. 1991 Nov;115(4):887-903 [1955461] Science. 1991 Dec 20;254(5039):1805-8 [1662412] Science. 1991 Dec 20;254(5039):1808-10 [1722352] Cancer Res. 1992 Feb 1;52(3):643-5 [1310068] Oncogene. 1992 Mar;7(3):507-10 [1312702] Adv Virus Res. 1992;41:193-239 [1575083] Mol Cell Biol. 1992 Sep;12(9):4242-8 [1380649] J Biol Chem. 1992 Oct 5;267(28):19765-8 [1328181] Cancer. 1993 Apr 1;71(7):2383-6 [8384068] Nature. 1970 Aug 15;227(5259):680-5 [5432063] J Biol Chem. 1977 Feb 25;252(4):1181-8 [190222] Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7 [271968] Nucleic Acids Res. 1980 Dec 20;8(24):6113-28 [6258162] Nucleic Acids Res. 1981 Jan 10;9(1):133-48 [6163133] Lab Invest. 1984 Feb;50(2):147-62 [6694356] Proc Natl Acad Sci U S A. 1985 Sep;82(18):6050-4 [2412228] EMBO J. 1986 Dec 1;5(12):3133-42 [3102226] Mol Cell Biol. 1987 Aug;7(8):2745-52 [3670292] Genomics. 1987 Oct;1(2):113-25 [3692483] Mol Cell Biol. 1988 Apr;8(4):1385-97 [2454389] Nature. 1988 Jul 28;334(6180):320-5 [2839775] Cell. 1989 Jan 13;56(1):85-92 [2463093] Nature. 1989 Jan 26;337(6205):364-8 [2463489] J Cell Biol. 1989 Feb;108(2):229-41 [2645293] Q Rev Biol. 1989 Mar;64(1):1-30 [2469098] Annu Rev Microbiol. 1989;43:403-34 [2552899] Biotechniques. 1990 May;8(5):528-35 [2357375] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Glucocorticoid therapy for immune-mediated diseases: basic and clinical correlates. AN - 76040342; 8239251 AB - Glucocorticoids are pleiotropic hormones that at pharmacologic doses prevent or suppress inflammation and other immunologically mediated processes. At the molecular level, glucocorticoids form complexes with specific receptors that migrate to the nucleus where they interact with selective regulatory sites within DNA; this results in positive and negative modulation of several genes involved in inflammatory and immune responses. At the cellular level, glucocorticoids inhibit the access of leukocytes to inflammatory sites; interfere with the functions of leukocytes, endothelial cells, and fibroblasts; and suppress the production and the effects of humoral factors involved in the inflammatory response. Clinically, several modes of glucocorticoid administration are used, depending on the disease process, the organ involved, and the extent of involvement. High doses of daily glucocorticoids are usually required in patients with severe diseases involving major organs, whereas alternate-day regimens may be used in patients with less aggressive diseases. Intravenous glucocorticoids (pulse therapy) are frequently used to initiate therapy in patients with rapidly progressive, immunologically mediated diseases. The benefits of glucocorticoid therapy can easily be offset by severe side effects; even with the greatest care, side effects may occur. Moreover, for certain complications (for example, infection diathesis, peptic ulcer, osteoporosis, avascular necrosis, and atherosclerosis), other drug toxicities and pathogenic factors overlap with glucocorticoid effects. Minimizing the incidence and severity of glucocorticoid-related side effects requires carefully decreasing the dose; using adjunctive disease-modifying immunosuppressive and anti-inflammatory agents; and taking general preventive measures. JF - Annals of internal medicine AU - Boumpas, D T AU - Chrousos, G P AU - Wilder, R L AU - Cupps, T R AU - Balow, J E AD - National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/12/15/ PY - 1993 DA - 1993 Dec 15 SP - 1198 EP - 1208 VL - 119 IS - 12 SN - 0003-4819, 0003-4819 KW - Glucocorticoids KW - 0 KW - Abridged Index Medicus KW - Index Medicus KW - Humans KW - Cells -- drug effects KW - Immune System Diseases -- drug therapy KW - Glucocorticoids -- adverse effects KW - Glucocorticoids -- therapeutic use KW - Glucocorticoids -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76040342?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+internal+medicine&rft.atitle=Glucocorticoid+therapy+for+immune-mediated+diseases%3A+basic+and+clinical+correlates.&rft.au=Boumpas%2C+D+T%3BChrousos%2C+G+P%3BWilder%2C+R+L%3BCupps%2C+T+R%3BBalow%2C+J+E&rft.aulast=Boumpas&rft.aufirst=D&rft.date=1993-12-15&rft.volume=119&rft.issue=12&rft.spage=1198&rft.isbn=&rft.btitle=&rft.title=Annals+of+internal+medicine&rft.issn=00034819&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-12-17 N1 - Date created - 1993-12-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Differential susceptibilities of the prosthetic heme of hemoglobin-based red cell substitutes. Implications in the design of safer agents. AN - 76143510; 8274164 AB - One approach to the development of an effective red cell substitute has been chemical modification of human hemoglobin to optimize oxygen transport and plasma half-life. Human hemoglobin A0 and two of these modified hemoglobins, one prepared from the cross-linking of the alpha-chains at lysine residue 99 by bis(3,5-dibromosalicyl)fumarate (Hb-DBBF) and the other by acylation of lysine residue 82 of the beta-chain by mono-(3,5-dibromosalicyl)fumarate (Hb-FMDA), were tested by HPLC for their susceptibility to oxidative damage caused by H2O2. Such oxidative insult may occur during ischemia and reperfusion of tissues after transfusion of red cell substitutes to patients with hypovolemic shock and trauma. Hb-DBBF was extremely susceptible to damage of its heme and protein moieties with stoichiometric amounts of H2O2, whereas Hb-FMDA was highly resistant, even at 10-fold molar excess and at an acidic pH of 4.7. Hemoglobin A0 was of intermediate susceptibility, exhibiting alteration of heme and protein moieties at acidic but not neutral pH. Since the degradation of heme can release the potentially toxic agent iron, Hb-FMDA may be a more promising candidate than Hb-DBBF for development as a red cell substitute. A similar approach may be used to assess the susceptibility of other hemoglobin-based red cell substitutes to oxidative damage in order to determine the molecular basis of heme and protein alteration. JF - Biochemical pharmacology AU - Osawa, Y AU - Darbyshire, J F AU - Meyer, C A AU - Alayash, A I AD - Laboratory of Chemical Pharmacology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/12/14/ PY - 1993 DA - 1993 Dec 14 SP - 2299 EP - 2305 VL - 46 IS - 12 SN - 0006-2952, 0006-2952 KW - Blood Substitutes KW - 0 KW - Cross-Linking Reagents KW - Hemoglobins KW - bis(3,5-dibromosalicyl)fumarate KW - 0E07K30TXY KW - Heme KW - 42VZT0U6YR KW - mono(3,5-dibromosalicyl)fumarate KW - 93705-06-7 KW - Hydrogen Peroxide KW - BBX060AN9V KW - Aspirin KW - R16CO5Y76E KW - Oxygen KW - S88TT14065 KW - Index Medicus KW - Oxidation-Reduction KW - Aspirin -- chemistry KW - Oxygen -- metabolism KW - Humans KW - Aspirin -- analogs & derivatives KW - Hydrogen Peroxide -- pharmacology KW - Biological Transport KW - Drug Design KW - Hemoglobins -- drug effects KW - Hemoglobins -- metabolism KW - Heme -- chemistry KW - Erythrocytes KW - Hemoglobins -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76143510?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+pharmacology&rft.atitle=Differential+susceptibilities+of+the+prosthetic+heme+of+hemoglobin-based+red+cell+substitutes.+Implications+in+the+design+of+safer+agents.&rft.au=Osawa%2C+Y%3BDarbyshire%2C+J+F%3BMeyer%2C+C+A%3BAlayash%2C+A+I&rft.aulast=Osawa&rft.aufirst=Y&rft.date=1993-12-14&rft.volume=46&rft.issue=12&rft.spage=2299&rft.isbn=&rft.btitle=&rft.title=Biochemical+pharmacology&rft.issn=00062952&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-01-31 N1 - Date created - 1994-01-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular mechanism of colchicine action: induced local unfolding of beta-tubulin. AN - 76102157; 8257691 AB - Colchicine, the classic antimitotic poison, disrupts cell division by preventing proper assembly of microtubules in the mitotic spindle. Colchicine is known to act by binding to tubulin, the heterodimeric subunit of microtubules. How this binding to tubulin changes the structure of the protein and results in polymerization poisoning has not been characterized. The structural locus of spectroscopically detected conformational changes induced by colchicine is unknown. We report here that colchicine induces the unfolding of a small region in the carboxyl-terminal region of beta-tubulin, around Arg-390. This unfolding is detected by proteolysis with trypsin and chymotrypsin. Chymotrypsin cleaves this region after Phe-389, and trypsin cleaves after Lys-392. The unfolded region appears to be the carboxyl end of an amphipathic helix in the absence of colchicine, and we propose that this unfolding prevents contacts necessary for assembly. Our results suggest that beta-tubulin is exposed on the growing end of the microtubule, which provides a mechanism for coupling GTP hydrolysis to polymerization. JF - Biochemistry AU - Sackett, D L AU - Varma, J K AD - Laboratory of Biochemical Pharmacology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/12/14/ PY - 1993 DA - 1993 Dec 14 SP - 13560 EP - 13565 VL - 32 IS - 49 SN - 0006-2960, 0006-2960 KW - Peptide Fragments KW - 0 KW - Tubulin KW - Guanosine Diphosphate KW - 146-91-8 KW - Guanosine Triphosphate KW - 86-01-1 KW - Chymotrypsin KW - EC 3.4.21.1 KW - Trypsin KW - EC 3.4.21.4 KW - GTP Phosphohydrolases KW - EC 3.6.1.- KW - Colchicine KW - SML2Y3J35T KW - Index Medicus KW - Peptide Fragments -- metabolism KW - Chymotrypsin -- metabolism KW - Animals KW - Immunoblotting KW - Protein Structure, Secondary KW - Guanosine Diphosphate -- metabolism KW - Brain Chemistry KW - Microtubules -- metabolism KW - Amino Acid Sequence KW - Microtubules -- drug effects KW - Binding Sites KW - Guanosine Triphosphate -- metabolism KW - Rats KW - Peptide Fragments -- chemistry KW - GTP Phosphohydrolases -- metabolism KW - Molecular Sequence Data KW - Trypsin -- metabolism KW - Colchicine -- pharmacology KW - Tubulin -- chemistry KW - Protein Folding KW - Tubulin -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76102157?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Molecular+mechanism+of+colchicine+action%3A+induced+local+unfolding+of+beta-tubulin.&rft.au=Sackett%2C+D+L%3BVarma%2C+J+K&rft.aulast=Sackett&rft.aufirst=D&rft.date=1993-12-14&rft.volume=32&rft.issue=49&rft.spage=13560&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-01-19 N1 - Date created - 1994-01-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Expression and V(D)J recombination activity of mutated RAG-1 proteins. AN - 76159364; 8284210 AB - The products of the RAG-1 and RAG-2 genes are essential for the recombination of the DNA encoding the antigen receptors of the developing immune system. Little is known of the specific role these genes play. We have explored the sequences encoding mouse RAG-1 by deleting large parts of the gene and by introducing local sequence changes. We find that a RAG-1 gene with 40% of the coding region deleted still retains its recombination function. In addition, a series of small deletions within the strongly conserved remaining 60% of the coding region was tested. Nine out of ten of these prove unable to provide RAG-1 activity, but one is quite active. Certain peptide sequences were also specifically targeted for mutagenesis. The RAG-1 protein generated from this expression system is transported to the nucleus and is degraded with a 15 minute half-life. The fate of the proteins made by the deletion mutants were also assessed. Transport of RAG-1 protein to the nucleus was found even with the most extensive deletions studied. The functionality of the deleted proteins is discussed with relation to an alignment of RAG-1 sequences from five animal species. JF - Nucleic acids research AU - Sadofsky, M J AU - Hesse, J E AU - McBlane, J F AU - Gellert, M AD - Laboratory of Molecular Biology, NIDDK, NIH, Bethesda, MD 20892. Y1 - 1993/12/11/ PY - 1993 DA - 1993 Dec 11 SP - 5644 EP - 5650 VL - 21 IS - 24 SN - 0305-1048, 0305-1048 KW - RAG-1 KW - Homeodomain Proteins KW - 0 KW - Proteins KW - RAG-1 protein KW - 128559-51-3 KW - DNA KW - 9007-49-2 KW - DNA Topoisomerases, Type I KW - EC 5.99.1.2 KW - Index Medicus KW - 3T3 Cells KW - Animals KW - Cell Nucleus -- metabolism KW - Humans KW - Biological Transport KW - Amino Acid Sequence KW - Mice KW - Precipitin Tests KW - Base Sequence KW - Molecular Sequence Data KW - Cell Line, Transformed KW - Sequence Homology, Amino Acid KW - DNA Topoisomerases, Type I -- metabolism KW - Genes, RAG-1 KW - Proteins -- metabolism KW - Proteins -- genetics KW - Mutation KW - Gene Rearrangement, B-Lymphocyte UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76159364?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nucleic+acids+research&rft.atitle=Expression+and+V%28D%29J+recombination+activity+of+mutated+RAG-1+proteins.&rft.au=Sadofsky%2C+M+J%3BHesse%2C+J+E%3BMcBlane%2C+J+F%3BGellert%2C+M&rft.aulast=Sadofsky&rft.aufirst=M&rft.date=1993-12-11&rft.volume=21&rft.issue=24&rft.spage=5644&rft.isbn=&rft.btitle=&rft.title=Nucleic+acids+research&rft.issn=03051048&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-02-14 N1 - Date created - 1994-02-14 N1 - Date revised - 2017-01-13 N1 - Gene symbol - RAG-1 N1 - SuppNotes - Cited By: Cell. 1992 Mar 6;68(5):855-67 [1547487] J Biol Chem. 1991 Oct 25;266(30):19867-70 [1939050] Annu Rev Immunol. 1992;10:359-83 [1590991] Nucleic Acids Res. 1992 May 11;20(9):2233-9 [1317548] Annu Rev Genet. 1992;26:425-46 [1482120] Int Immunol. 1993 Feb;5(2):231-2 [8452820] Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6100-4 [8327489] Mol Immunol. 1993 Aug;30(11):1021-32 [8350872] Cell. 1992 Mar 6;68(5):869-77 [1547488] J Mol Biol. 1967 Jun 14;26(2):365-9 [4291934] Mol Cell Biol. 1982 Sep;2(9):1044-51 [6960240] EMBO J. 1984 Jun;3(6):1209-19 [6086308] Mol Cell Biol. 1985 Dec;5(12):3610-6 [3915782] Cell. 1987 Jun 19;49(6):775-83 [3495343] Nature. 1987 Oct 29-Nov 4;329(6142):840-2 [3313052] Cell. 1988 Apr 8;53(1):107-15 [3349523] Nucleic Acids Res. 1989 May 25;17(10):3959-71 [2786626] Cell. 1989 Dec 22;59(6):1035-48 [2598259] Science. 1990 Jun 22;248(4962):1517-23 [2360047] Cell. 1990 Aug 10;62(3):403-6 [2165864] Cell. 1991 Jan 11;64(1):201-8 [1986866] Erratum In: Nucleic Acids Res. 1994 Feb 11;22(3):550 [8127702] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Upstream sequences of the myogenin gene convey responsiveness to skeletal muscle denervation in transgenic mice. AN - 19621836; 8727714 AB - Myogenin, as well as other MyoD-related skeletal muscle-specific transcription factors, regulate a large number of skeletal muscle genes during myogenic differentiation. During later development, innervation suppresses myogenin expression in the fetal hind limb musculature. Denervation of skeletal muscle reverses the effects of the nerve, and results in the reactivation of myogenin expression, as well as of other embryonic muscle proteins. Here we report that myogenin upstream sequences confer tissue- and developmental-specific expression in transgenic mice harboring a myogenin/chloramphenicol acetyltransferase (CAT) reporter construct. Using in situ hybridization to analyze serial sections of E12.5 embryos, we found colocalization of CAT and endogenous myogenin transcripts in the primordial muscle of the head and limbs, in the intercostal muscle masses, and in the most caudal somites. Later in development, we observed that the expression of the transgene and endogenous myogenin gene continued to be restricted to skeletal muscle but decreased shortly after birth; a period that coincides with the innervation of secondary myotubes. Furthermore, denervation of the mouse hind limbs induced a 10-fold accumulation of CAT and endogenous myogenin transcripts by 1 day after sciatic nerve resection; a 25-fold increase was observed by 4 days after denervation. Interestingly, we observed that the accumulation of CAT enzyme activity lagged considerably with respect to the increase in CAT transcripts. Our results indicate that the cis-acting elements that temporally and spatially confine transcription of the gene during embryonic development, and that mediate the responses to innervation and denervation of muscle, lie within the upstream sequences analyzed in these studies. Images JF - Nucleic Acids Research AU - Buonanno, A AU - Edmondson, D G AU - Hayes, W P AD - Laboratory of Developmental Neurobiology, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/12/11/ PY - 1993 DA - 1993 Dec 11 SP - 5684 EP - 5693 PB - Oxford University Press, Oxford Journals, Great Clarendon Street VL - 21 IS - 24 SN - 0305-1048, 0305-1048 KW - Genetics Abstracts; Biotechnology and Bioengineering Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - Innervation KW - myogenin KW - Sciatic nerve KW - Head KW - Transgenic mice KW - Denervation KW - Fetuses KW - Birth KW - Nerves KW - Differentiation KW - Chloramphenicol O-acetyltransferase KW - Embryogenesis KW - Limbs KW - Transcription factors KW - somites KW - Myotubes KW - Embryos KW - Skeletal muscle KW - Myogenin gene KW - W 30925:Genetic Engineering KW - N 14835:Protein-Nucleic Acids Association KW - G 07730:Development & Cell Cycle UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19621836?accountid=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=Nucleic+Acids+Research&rft.atitle=Upstream+sequences+of+the+myogenin+gene+convey+responsiveness+to+skeletal+muscle+denervation+in+transgenic+mice.&rft.au=Buonanno%2C+A%3BEdmondson%2C+D+G%3BHayes%2C+W+P&rft.aulast=Buonanno&rft.aufirst=A&rft.date=1993-12-11&rft.volume=21&rft.issue=24&rft.spage=5684&rft.isbn=&rft.btitle=&rft.title=Nucleic+Acids+Research&rft.issn=03051048&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2008-12-01 N1 - Last updated - 2015-03-27 N1 - SubjectsTermNotLitGenreText - Innervation; myogenin; Sciatic nerve; Head; Denervation; Transgenic mice; Fetuses; Nerves; Birth; Differentiation; Embryogenesis; Chloramphenicol O-acetyltransferase; Limbs; somites; Transcription factors; Myotubes; Skeletal muscle; Embryos; Myogenin gene ER - TY - JOUR T1 - Fluoxetine and desipramine selectively attenuate 2'-NH2-MPTP-induced depletions in serotonin and norepinephrine. AN - 76237473; 8112382 AB - We recently reported that the novel MPTP analog 1-methyl-4-(2'-aminophenyl)-1,2,3,6-tetrahydropyridine (2'-NH2-MPTP) administered to C57BL/6 mice produced substantial decreases in forebrain serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), and norepinephrine, with negligible effects on brain dopamine or dopamine metabolites. In the present report, we confirm and extend our original results to include dose-response data and the effect of selective uptake inhibition on the levels of monoamine neurotransmitters in various regions of the mouse brain following treatment with 2'-NH2-MPTP. In a dose-ranging study, 2'-NH2-MPTP (10 mg/kg x 4) produced a 25-30% reduction in frontal cortex 5-HT, 5-HIAA, and norepinephrine. When 4 x 20 mg/kg 2'-NH2-MPTP was administered, 70-75% reductions in 5-HT, 5-HIAA, and norepinephrine in both frontal cortex and hippocampus were seen 1 week after treatment. No changes in dopamine were found in striatum or in any of the other brain regions examined at either dose. Doses of 40 and 60 mg/kg were lethal shortly after a single injection. In mice receiving either fluoxetine or desipramine (10 mg/kg) prior to 2'-NH2-MPTP (20 mg/kg x 4), decreases in 5-HT and norepinephrine, respectively, were significantly attenuated by approximately 30-40%. These data suggest that 2'-NH2-MPTP acts in a dose-dependent manner and that the serotonergic and noradrenergic uptake systems are involved in the mechanism by which 2'-NH2-MPTP causes selective deficits in cortical and hippocampal 5-HT and norepinephrine. JF - European journal of pharmacology AU - Andrews, A M AU - Murphy, D L AD - Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, MD 20892. Y1 - 1993/12/07/ PY - 1993 DA - 1993 Dec 07 SP - 215 EP - 221 VL - 250 IS - 2 SN - 0014-2999, 0014-2999 KW - Carrier Proteins KW - 0 KW - Membrane Glycoproteins KW - Membrane Transport Proteins KW - Nerve Tissue Proteins KW - Neurotransmitter Uptake Inhibitors KW - Norepinephrine Plasma Membrane Transport Proteins KW - Serotonin Plasma Membrane Transport Proteins KW - Serotonin Uptake Inhibitors KW - Slc6a2 protein, mouse KW - Slc6a4 protein, mouse KW - Symporters KW - Fluoxetine KW - 01K63SUP8D KW - 1-methyl-4-(2'-aminophenyl)-1,2,3,6-tetrahydropyridine KW - 108114-93-8 KW - Serotonin KW - 333DO1RDJY KW - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine KW - 9P21XSP91P KW - Desipramine KW - TG537D343B KW - Norepinephrine KW - X4W3ENH1CV KW - Index Medicus KW - Behavior, Animal -- drug effects KW - Animals KW - Carrier Proteins -- metabolism KW - Body Temperature -- drug effects KW - Dose-Response Relationship, Drug KW - Neurotransmitter Uptake Inhibitors -- pharmacology KW - Brain Chemistry -- drug effects KW - Mice, Inbred C57BL KW - Mice KW - Serotonin Uptake Inhibitors -- pharmacology KW - Chromatography, High Pressure Liquid KW - Membrane Glycoproteins -- metabolism KW - Fluoxetine -- pharmacology KW - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine -- analogs & derivatives KW - Desipramine -- pharmacology KW - Norepinephrine -- metabolism KW - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine -- pharmacology KW - Serotonin -- metabolism KW - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76237473?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+pharmacology&rft.atitle=Fluoxetine+and+desipramine+selectively+attenuate+2%27-NH2-MPTP-induced+depletions+in+serotonin+and+norepinephrine.&rft.au=Andrews%2C+A+M%3BMurphy%2C+D+L&rft.aulast=Andrews&rft.aufirst=A&rft.date=1993-12-07&rft.volume=250&rft.issue=2&rft.spage=215&rft.isbn=&rft.btitle=&rft.title=European+journal+of+pharmacology&rft.issn=00142999&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-03-25 N1 - Date created - 1994-03-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Structure/function studies of HIV-1(1) reverse transcriptase: dimerization-defective mutant L289K. AN - 76088830; 7694651 AB - Virion-derived HIV-1 reverse transcriptase (RT) has subunits of molecular mass 66 and 51 kDa (p66 and p51, respectively) in an approximately 1:1 ratio. Since enzyme activity appears to depend on dimerization of these subunits, identification of critical regions of primary sequence required for proper dimerization could lead to potential targets for antiviral therapy. A central region of primary sequence contains a leucine hepta-repeat motif from leucine 282 to leucine 310 that has been suggested to be involved in dimerization [Baillon, J. G., Nashed, N. T., Kumar, A., Wilson, S. H., & Jerina, D. M. (1991) New Biol. 3, 1015-1019]. A region including this hepta-repeat was recently shown to be involved in protein-protein interactions required for dimerization [Becerra, S. P., Kumar, A., Lewis, M. S., Widen, S. G., Abbotts, J., Karawya, E. M., Hughes, S. H., Shiloach, J., & Wilson, S. H. (1991) Biochemistry 30, 11708-11719]. To investigate the role of this repeat motif in dimerization, we performed site-directed mutagenesis of these leucine residues from position 282 to position 310. Mutations were introduced into p66 and p51 RT coding sequences, and the individually purified RT subunit polypeptides were compared with wild-type polypeptides for dimerization. Physical characterization of the purified mutant peptides was conducted by circular dichroism analysis. Binding between p66 and p51 was studied by gel filtration, ultracentrifugation, and CD analysis. L289K-p66 was unable to dimerize with itself and wild-type or L289K-p51. The leucine repeat motif in the p66 subunit appears to be critical in formation of the heterodimer.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Biochemistry AU - Goel, R AU - Beard, W A AU - Kumar, A AU - Casas-Finet, J R AU - Strub, M P AU - Stahl, S J AU - Lewis, M S AU - Bebenek, K AU - Becerra, S P AU - Kunkel, T A AD - Laboratory of Biochemistry, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/12/07/ PY - 1993 DA - 1993 Dec 07 SP - 13012 EP - 13018 VL - 32 IS - 48 SN - 0006-2960, 0006-2960 KW - Macromolecular Substances KW - 0 KW - HIV Reverse Transcriptase KW - EC 2.7.7.49 KW - RNA-Directed DNA Polymerase KW - Leucine KW - GMW67QNF9C KW - Index Medicus KW - AIDS/HIV KW - Protein Structure, Secondary KW - Circular Dichroism KW - Amino Acid Sequence KW - Leucine -- chemistry KW - Ultracentrifugation KW - Protein Binding KW - Structure-Activity Relationship KW - Mutagenesis, Site-Directed KW - Chromatography, Gel KW - Molecular Sequence Data KW - Repetitive Sequences, Nucleic Acid KW - RNA-Directed DNA Polymerase -- chemistry KW - HIV-1 -- enzymology KW - RNA-Directed DNA Polymerase -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76088830?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Structure%2Ffunction+studies+of+HIV-1%281%29+reverse+transcriptase%3A+dimerization-defective+mutant+L289K.&rft.au=Goel%2C+R%3BBeard%2C+W+A%3BKumar%2C+A%3BCasas-Finet%2C+J+R%3BStrub%2C+M+P%3BStahl%2C+S+J%3BLewis%2C+M+S%3BBebenek%2C+K%3BBecerra%2C+S+P%3BKunkel%2C+T+A&rft.aulast=Goel&rft.aufirst=R&rft.date=1993-12-07&rft.volume=32&rft.issue=48&rft.spage=13012&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-01-06 N1 - Date created - 1994-01-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cloning of Chinese hamster DNA topoisomerase I cDNA and identification of a single point mutation responsible for camptothecin resistance. AN - 76075965; 8244980 AB - A camptothecin-resistant (DC3F/C-10) Chinese hamster cell line that contains a catalytically altered and camptothecin (CPT)-resistant DNA topoisomerase I (top 1) (Tanizawa, A., and Pommier, Y. (1992) Cancer Res. 52, 1848-1854) and the parent cell line (DC3F) were used to compare top 1 mRNAs and cDNAs. Northern blot analysis showed a single 4.1-kilobase band without quantitative reduction between the two cell lines. We have cloned and sequenced top 1 cDNAs. DC3F and DC3F/C-10 top 1 c-DNA are 3591 and 3626 base pair long, respectively, and encode 767 amino acids. The homology of deduced amino acid sequences between Chinese hamster and mouse or human top 1 are 98.1 and 96.7, respectively. cDNAs from DC3F/C-10 and DC3F cells differ by a single base point mutation (G to A) which results in an amino acid change from Gly505 to Ser (Gly505-->Ser). G505 corresponds to Gly503 of human top 1 cDNA and is located 220 amino acids away from the presumed catalytic Tyr725. The point mutation in the Chinese hamster top 1 is located in a region that is highly conserved among all cloned top 1 cDNAs (plant ATH, vaccinia virus, Shope fibroma virus, Drosophila, Saccharomyces cerevisiae, Schizosaccharomyces pombe, mouse, and Human). A mutation of Asp533 to Gly in this same region has been shown to confer CPT resistance for human top 1. Chinese hamster top 1 protein with a Gly505-->Ser mutation that was expressed in bacteria was resistant to CPT, indicating that this single base mutation is involved in CPT resistance. Our results suggest that the highly conserved region around Gly505 plays an important role in the interactions among top 1, DNA, and CPT. JF - The Journal of biological chemistry AU - Tanizawa, A AU - Beitrand, R AU - Kohlhagen, G AU - Tabuchi, A AU - Jenkins, J AU - Pommier, Y AD - Laboratory of Molecular Pharmacology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/12/05/ PY - 1993 DA - 1993 Dec 05 SP - 25463 EP - 25468 VL - 268 IS - 34 SN - 0021-9258, 0021-9258 KW - DNA Primers KW - 0 KW - DNA, Complementary KW - Recombinant Proteins KW - Serine KW - 452VLY9402 KW - DNA Topoisomerases, Type I KW - EC 5.99.1.2 KW - Glycine KW - TE7660XO1C KW - Camptothecin KW - XT3Z54Z28A KW - Index Medicus KW - Viruses -- enzymology KW - Animals KW - Recombinant Proteins -- biosynthesis KW - Cricetulus KW - Drosophila melanogaster -- genetics KW - Humans KW - Mice KW - Amino Acid Sequence KW - Saccharomyces cerevisiae -- enzymology KW - Drosophila melanogaster -- enzymology KW - Cloning, Molecular KW - Saccharomyces cerevisiae -- genetics KW - Arabidopsis -- enzymology KW - Polymerase Chain Reaction KW - Arabidopsis -- genetics KW - Base Sequence KW - Conserved Sequence KW - Recombinant Proteins -- metabolism KW - Lung KW - Molecular Sequence Data KW - Viruses -- genetics KW - Sequence Homology, Amino Acid KW - Cell Line KW - Cricetinae KW - Drug Resistance -- genetics KW - DNA, Complementary -- metabolism KW - Camptothecin -- toxicity KW - Point Mutation KW - DNA Topoisomerases, Type I -- biosynthesis KW - DNA Topoisomerases, Type I -- genetics KW - DNA Topoisomerases, Type I -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76075965?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cloning+of+Chinese+hamster+DNA+topoisomerase+I+cDNA+and+identification+of+a+single+point+mutation+responsible+for+camptothecin+resistance.&rft.au=Tanizawa%2C+A%3BBeitrand%2C+R%3BKohlhagen%2C+G%3BTabuchi%2C+A%3BJenkins%2C+J%3BPommier%2C+Y&rft.aulast=Tanizawa&rft.aufirst=A&rft.date=1993-12-05&rft.volume=268&rft.issue=34&rft.spage=25463&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 - 1994-01-04 N1 - Date created - 1994-01-04 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - Z21624; GENBANK; Z21625 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Activation of phospholipase C-beta 2 mutants by G protein alpha q and beta gamma subunits. AN - 76075032; 8245028 AB - The beta- but not the gamma- and delta-type isozymes of inositol phospholipid-specific phospholipase C (PLC) are activated by G protein alpha q and beta gamma subunits. The beta-type PLC isozymes differ from other isozymes in that they contain a long carboxyl-terminal region downstream of the Y catalytic domain and a region rich in acidic amino acids between the two separated X and Y catalytic domains. To determine the sites on PLC-beta 2 that participate in the interaction of the enzyme with alpha q and beta gamma subunits, we introduced specific truncations and substitutions in the PLC-beta 2 cDNA at positions corresponding to the carboxyl-terminal and acidic amino acid-rich regions, respectively. After transient expression of these cDNA clones in CV-1 cells, the mutant enzymes were partially purified and their capacity to be activated by alpha q and beta gamma subunits determined. Substitution of glutamine residues for three or all seven of a stretch of consecutive glutamic acids in the acidic domain of PLC-beta 2 affected neither alpha q- nor beta gamma-dependent activation significantly. Carboxyl-terminal truncation to residue Gly-934 or to residue Ala-867 resulted in enzymes that were activated by beta gamma but not by alpha q. This result suggests that the carboxyl-terminal region of PLC-beta 2 is required for activation by alpha q, and that beta gamma subunits interact with a different region of the enzyme. Thus, alpha q and beta gamma subunits may independently modulate a single PLC-beta 2 molecule concurrently. JF - The Journal of biological chemistry AU - Lee, S B AU - Shin, S H AU - Hepler, J R AU - Gilman, A G AU - Rhee, S G AD - Laboratory of Biochemistry, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/12/05/ PY - 1993 DA - 1993 Dec 05 SP - 25952 EP - 25957 VL - 268 IS - 34 SN - 0021-9258, 0021-9258 KW - DNA Primers KW - 0 KW - Isoenzymes KW - Macromolecular Substances KW - Phosphatidylinositol 4,5-Diphosphate KW - Phosphatidylinositol Phosphates KW - Recombinant Proteins KW - Phosphoric Diester Hydrolases KW - EC 3.1.4.- KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - Phosphatidylinositol Diacylglycerol-Lyase KW - EC 4.6.1.13 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Animals KW - Enzyme Activation KW - Humans KW - Phosphatidylinositol Phosphates -- metabolism KW - Amino Acid Sequence KW - Calcium -- pharmacology KW - Cloning, Molecular KW - Mutagenesis, Site-Directed KW - Recombinant Proteins -- isolation & purification KW - Base Sequence KW - Transfection KW - Recombinant Proteins -- metabolism KW - Kinetics KW - Molecular Sequence Data KW - Cell Line KW - Phosphoric Diester Hydrolases -- genetics KW - Isoenzymes -- isolation & purification KW - Phosphoric Diester Hydrolases -- isolation & purification KW - GTP-Binding Proteins -- metabolism KW - Phosphoric Diester Hydrolases -- metabolism KW - Isoenzymes -- genetics KW - Isoenzymes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76075032?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Activation+of+phospholipase+C-beta+2+mutants+by+G+protein+alpha+q+and+beta+gamma+subunits.&rft.au=Lee%2C+S+B%3BShin%2C+S+H%3BHepler%2C+J+R%3BGilman%2C+A+G%3BRhee%2C+S+G&rft.aulast=Lee&rft.aufirst=S&rft.date=1993-12-05&rft.volume=268&rft.issue=34&rft.spage=25952&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 - 1994-01-04 N1 - Date created - 1994-01-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Abolition of anaphylaxis by targeted disruption of the high affinity immunoglobulin E receptor alpha chain gene. AN - 76114364; 8252632 AB - Mast cells and basophils, which are activated by immunoglobulin E (IgE) and allergen, play a prominent role in anaphylaxis. However, they express at least three types of IgE receptor, including the high affinity IgE receptor (Fc epsilon RI). The relative contribution of these IgE receptors, and possibly other receptors such as Fc epsilon RII/CD23 and Mac-2, to the genesis of in vivo anaphylaxis is still unclear. To address this question, we have generated Fc epsilon RI-deficient mice. These mice appear normal and express a normal number of mast cells, but they are resistant to cutaneous and systemic anaphylaxis. These data demonstrate that Fc epsilon RI is necessary for the initiation of IgE-dependent anaphylactic reactions. Therefore, interfering with its function should be an effective means of treating allergy, regardless of the allergen specificity. JF - Cell AU - Dombrowicz, D AU - Flamand, V AU - Brigman, K K AU - Koller, B H AU - Kinet, J P AD - Molecular Allergy and Immunology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland 20852. Y1 - 1993/12/03/ PY - 1993 DA - 1993 Dec 03 SP - 969 EP - 976 VL - 75 IS - 5 SN - 0092-8674, 0092-8674 KW - DNA Primers KW - 0 KW - Receptors, IgE KW - Receptors, IgG KW - Serotonin KW - 333DO1RDJY KW - Index Medicus KW - Animals KW - Mast Cells -- immunology KW - Base Sequence KW - Receptors, IgG -- metabolism KW - Molecular Sequence Data KW - Mice KW - Flow Cytometry KW - B-Lymphocytes -- metabolism KW - Serotonin -- metabolism KW - Mutagenesis, Insertional KW - Mice, Knockout KW - DNA Primers -- chemistry KW - Receptors, IgE -- metabolism KW - Receptors, IgE -- genetics KW - Receptors, IgE -- immunology KW - Passive Cutaneous Anaphylaxis -- immunology KW - Anaphylaxis -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76114364?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cell&rft.atitle=Abolition+of+anaphylaxis+by+targeted+disruption+of+the+high+affinity+immunoglobulin+E+receptor+alpha+chain+gene.&rft.au=Dombrowicz%2C+D%3BFlamand%2C+V%3BBrigman%2C+K+K%3BKoller%2C+B+H%3BKinet%2C+J+P&rft.aulast=Dombrowicz&rft.aufirst=D&rft.date=1993-12-03&rft.volume=75&rft.issue=5&rft.spage=969&rft.isbn=&rft.btitle=&rft.title=Cell&rft.issn=00928674&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-01-10 N1 - Date created - 1994-01-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regional differences in rat brain dopamine transporter binding: function of time after chronic cocaine. AN - 76367535; 9377588 AB - Chronic administration of cocaine to rats has been shown to produce a persistent decrease in dopamine (DA) and its metabolites in the brain and periphery. To further explore the alterations in the DA system following repeated administration of cocaine, we studied the regional differences in DA transporter binding as a function of time after the last injection of cocaine. Two groups of rats were treated with cocaine (10 mg/kg twice a day) or saline for 7 days. Rats were sacrificed 1, 2, 3, 6, and 12 weeks after the last injection. The corpus striatum and the frontal cortex were dissected and assayed with [3H]GBR 12935 for DA transporter binding. Time-related differences were observed in the frontal cortex but not in the striatum of the saline-treated control rats. Cocaine treatment prevented the time-dependent increase in Bmax over the course of 6 weeks, but not over the course of 12 weeks following withdrawal. Although there was no difference between the cocaine- and saline-treated group in the striatum at any of the time points, cocaine in the frontal cortex produced a 33% reduction in Bmax during weeks 2 and 3 and a 57% reduction in Bmax at week 6 of withdrawal; the reduction persisted for > or = 12 weeks. The KD was not affected by cocaine or time in either brain region. These findings may be functionally related to cocaine craving because the DA transporter has been identified as the neuronal structure and the medial prefrontal cortex as the anatomical site mediating cocaine reinforcement. JF - Clinical neuropharmacology AU - Hitri, A AU - Wyatt, R J AD - Neuropsychiatry Branch, NIMH Neurosciences Center, Washington, D.C., USA. Y1 - 1993/12// PY - 1993 DA - December 1993 SP - 525 EP - 539 VL - 16 IS - 6 SN - 0362-5664, 0362-5664 KW - Carrier Proteins KW - 0 KW - Dopamine Plasma Membrane Transport Proteins KW - Membrane Glycoproteins KW - Membrane Transport Proteins KW - Narcotics KW - Nerve Tissue Proteins KW - Piperazines KW - 1-(2 (diphenylmethoxy)ethyl)-4-(3-phenylpropyl)piperazine KW - 9J9974WIBA KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Neostriatum -- metabolism KW - Substance Withdrawal Syndrome -- metabolism KW - Prefrontal Cortex -- metabolism KW - Kinetics KW - Neostriatum -- drug effects KW - Brain -- anatomy & histology KW - Prefrontal Cortex -- drug effects KW - Piperazines -- metabolism KW - Male KW - Carrier Proteins -- metabolism KW - Brain Chemistry -- drug effects KW - Narcotics -- adverse effects KW - Cocaine -- pharmacology KW - Narcotics -- pharmacology KW - Cocaine -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76367535?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+neuropharmacology&rft.atitle=Regional+differences+in+rat+brain+dopamine+transporter+binding%3A+function+of+time+after+chronic+cocaine.&rft.au=Hitri%2C+A%3BWyatt%2C+R+J&rft.aulast=Hitri&rft.aufirst=A&rft.date=1993-12-01&rft.volume=16&rft.issue=6&rft.spage=525&rft.isbn=&rft.btitle=&rft.title=Clinical+neuropharmacology&rft.issn=03625664&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-11-10 N1 - Date created - 1997-11-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Absence of morphologic correlation between chemical toxicity and chemical carcinogenesis. AN - 76289475; 8013424 AB - The experimental data set used to evaluate site-specific histopathologic correspondence between the morphologic end points of toxicity and carcinogenicity comprises 130 chemical carcinogenesis studies. Nearly 1500 sex-species-exposure-group experiments were evaluated for a) evidence of toxicity or/and carcinogenicity, b) dose-response relationships, c) site-specific correlations of toxicity and carcinogenicity, and d) correspondence with Salmonella mutagenicity. The major conclusions are that chemicals evaluated for long-term toxicity and carcinogenicity in experimental animals divide typically and consistently into three categories: a) chemicals causing organ toxicity without cancer, b) chemicals causing site-specific cancer with no associated toxicity, and c) chemicals causing both toxicity and cancer in the same organ. Few chemicals overall (and none in this data set) fit the remaining group that cause neither toxicity nor carcinogenicity under these protocol conditions. Mutagenicity exhibited no consistent pattern with any of these groupings. Only 7 of 53 "positive" chemicals had target organ toxicity at all sites of carcinogenicity. Just three chemicals showed carcinogenic effects at the highest exposure concentrations without supporting evidence of tumors at the lower levels. From these comparative morphological analyses, and for almost all cases, available data do not support a correlation between chemically induced toxicity or regenerative phenomena and carcinogenicity. Consequently, until scientific knowledge about molecular mechanisms of chemical carcinogenesis becomes better understood and generally accepted, attempts to use toxicity findings to modify risk assessment processes will be fraught with uncertainty and thus could have a negative impact on public health. JF - Environmental health perspectives AU - Huff, J AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1993/12// PY - 1993 DA - December 1993 SP - 45 EP - 53 VL - 101 Suppl 5 SN - 0091-6765, 0091-6765 KW - Carcinogens KW - 0 KW - Mutagens KW - Index Medicus KW - Rats KW - Animals KW - Humans KW - Databases, Factual KW - Carcinogenicity Tests KW - Mutagens -- toxicity KW - Liver Neoplasms, Experimental -- chemically induced KW - Mice KW - Male KW - Female KW - Neoplasms -- pathology KW - Neoplasms -- chemically induced KW - Carcinogens -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76289475?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Absence+of+morphologic+correlation+between+chemical+toxicity+and+chemical+carcinogenesis.&rft.au=Huff%2C+J&rft.aulast=Huff&rft.aufirst=J&rft.date=1993-12-01&rft.volume=101+Suppl+5&rft.issue=&rft.spage=45&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 - 1994-07-22 N1 - Date created - 1994-07-22 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Environ Mol Mutagen. 1992;19(3):209-22 [1572344] Scand J Work Environ Health. 1992;18 Suppl 1:31-7 [1411375] Annu Rev Pharmacol Toxicol. 1979;19:511-30 [378109] J Environ Pathol Toxicol. 1979 Dec;3(1-2):281-7 [547015] Med Lav. 1979 Sep-Oct;70(5):352-7 [554913] Am J Ind Med. 1982;3(1):11-6 [7124739] J Natl Cancer Inst. 1984 Apr;72(4):929-40 [6584668] Cancer Res. 1984 May;44(5):2244-50 [6370426] Scand J Work Environ Health. 1992;18 Suppl 1:64-73 [1411382] Scand J Work Environ Health. 1992;18 Suppl 1:74-82 [1411383] Scand J Work Environ Health. 1992;18 Suppl 1:83-9 [1411384] Environ Health Perspect. 1993 Apr;100:201-10 [8354167] Environ Health Perspect. 1993 Apr;100:9-20 [8354184] Environ Health Perspect. 1993 Dec;101 Suppl 5:115-20 [7516872] Environ Health Perspect. 1993 Dec;101 Suppl 5:121-4 [8013398] Environ Health Perspect. 1993 Dec;101 Suppl 5:125-35 [8013399] Environ Health Perspect. 1993 Dec;101 Suppl 5:149-51 [8013403] Environ Health Perspect. 1993 Dec;101 Suppl 5:253-7 [8013416] Environ Health Perspect. 1993 Dec;101 Suppl 5:271-6 [8013420] Environ Health Perspect. 1993 Dec;101 Suppl 5:3-7 [7912189] Environ Health Perspect. 1991 Jun;93:247-70 [1773796] Mol Carcinog. 1991;4(6):420-40 [1793481] Mol Carcinog. 1992;5(1):2-3 [1543538] Carcinogenesis. 1992 Mar;13(3):409-15 [1547531] Cancer Res. 1992 Apr 15;52(8):2357-61 [1559239] Science. 1985 Feb 1;227(4686):548-9 [3966163] Environ Mutagen. 1985;7(4):427-8 [4054069] Carcinogenesis. 1986 Nov;7(11):1853-63 [3769134] Arch Toxicol Suppl. 1987;10:10-26 [3555413] Annu Rev Public Health. 1987;8:355-85 [3555527] Cancer Lett. 1987 Oct 30;37(2):125-32 [3677049] Carcinogenesis. 1988 Nov;9(11):2045-52 [3052903] Cancer Metastasis Rev. 1989 Jun;8(1):1-22 [2667783] Jpn J Cancer Res. 1989 Sep;80(9):795-807 [2513295] Science. 1990 Aug 31;249(4972):970-1 [2136249] Environ Health Perspect. 1990 Jun;86:313-21 [2205492] Cancer Res. 1990 Oct 15;50(20):6592-9 [2208121] Cancer Res. 1990 Nov 1;50(21):6769-71 [2208140] Science. 1991 Jan 25;251(4992):387-8 [1989073] Mutat Res. 1991 May;257(3):229-306 [1707500] Cell Biol Toxicol. 1991 Jan;7(1):67-94 [2054688] Annu Rev Pharmacol Toxicol. 1991;31:621-52 [2064387] Cancer Res. 1992 Jan 15;52(2):249-53 [1728397] Environ Health Perspect. 1991 Dec;96:23-31 [1820269] FASEB J. 1992 Jun;6(9):2698-706 [1612294] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Relationship between the time of sustained ethyl acrylate forestomach hyperplasia and carcinogenicity. AN - 76289420; 8013421 AB - Chronic administration of ethyl acrylate (EA) by gavage at 100 or 200 mg/kg/day resulted in a significant dose-dependent increase in the incidence of forestomach (FS) squamous cell papillomas and carcinomas in both sexes of F344 rats and B6C3F1 mice. Subsequent work in this laboratory was designed to investigate the relationship between EA-induced FS hyperplasia and carcinogenicity. Current studies have focused on determining the time required for sustained FS hyperplasia to produce neoplastic transformation. Results of these studies demonstrated that gavage administration of EA to male F344 rats at 200 mg/kg/day for 6 or 12 months caused a sustained increase in FS epithelial hyperplasia for as long as exposure to EA continued. However, FS hyperplasia regressed, and no neoplasms developed when animals receiving EA for 6 months were allowed to recover until they were sacrificed at 24 months of age. In contrast, rats treated for 12 months and allowed 9 months recovery developed FS squamous cell carcinomas (3/13) and papillomas (1/13) for a combined incidence of 4/13. No gross lesions were detected in the liver of any of the rats treated with EA or corn oil vehicle, confirming the tissue specificity in the relationship between EA-induced FS hyperplasia and carcinogenesis. In conclusion, the present work has demonstrated that FS hyperplasia is selectively sustained at the site of EA-induced carcinogenicity for as long as EA is administered and has also demonstrated a temporal relationship between FS mucosal hyperplasia and the development of FS neoplasia by EA.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Environmental health perspectives AU - Ghanayem, B I AU - Sanchez, I M AU - Maronpot, R R AU - Elwell, M R AU - Matthews, H B AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1993/12// PY - 1993 DA - December 1993 SP - 277 EP - 279 VL - 101 Suppl 5 SN - 0091-6765, 0091-6765 KW - Acrylates KW - 0 KW - Carcinogens KW - Mutagens KW - ethyl acrylate KW - 71E6178C9T KW - Index Medicus KW - Administration, Oral KW - Animals KW - Carcinogens -- toxicity KW - Cell Division -- drug effects KW - Carcinoma, Squamous Cell -- chemically induced KW - Mutagens -- toxicity KW - Mice KW - Organ Specificity KW - Rats KW - Rats, Inbred F344 KW - Hyperplasia KW - Papilloma -- chemically induced KW - Female KW - Male KW - Stomach -- pathology KW - Stomach Neoplasms -- chemically induced KW - Acrylates -- toxicity KW - Acrylates -- administration & dosage KW - Stomach -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76289420?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Relationship+between+the+time+of+sustained+ethyl+acrylate+forestomach+hyperplasia+and+carcinogenicity.&rft.au=Ghanayem%2C+B+I%3BSanchez%2C+I+M%3BMaronpot%2C+R+R%3BElwell%2C+M+R%3BMatthews%2C+H+B&rft.aulast=Ghanayem&rft.aufirst=B&rft.date=1993-12-01&rft.volume=101+Suppl+5&rft.issue=&rft.spage=277&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 - 1994-07-22 N1 - Date created - 1994-07-22 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Toxicol Appl Pharmacol. 1985 Sep 15;80(2):336-44 [4024123] Toxicol Appl Pharmacol. 1986 May;83(3):576-83 [3518156] Carcinogenesis. 1986 Aug;7(8):1285-9 [3731382] Cancer Lett. 1986 Sep;32(3):271-8 [3768853] Cancer Res. 1988 Dec 1;48(23):6739-44 [3180084] Toxicology. 1988 Dec 30;53(2-3):251-68 [3212786] Toxicol Appl Pharmacol. 1985 Sep 15;80(2):323-35 [4024122] Cancer Res. 1991 Dec 15;51(24):6493-505 [1742722] Toxicol Pathol. 1991;19(3):273-9 [1723532] Mutat Res. 1984 Mar;135(3):189-91 [6424006] Mutat Res. 1984 Aug-Sep;137(2-3):95-102 [6381999] J Toxicol Environ Health. 1984;14(2-3):115-20 [6153064] Drug Chem Toxicol. 1985;8(1-2):1-42 [4017897] Mutagenesis. 1989 Jul;4(4):283-5 [2674606] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Site-specific cell proliferation in renal tubular cells by the renal tubular carcinogen tris(2,3-dibromopropyl)phosphate. AN - 76288764; 8013416 AB - Our laboratory has been examining the mechanisms whereby chemicals are mutagenic in short-term in-vitro assays yet are not carcinogenic in 2-year rodent bioassays. Previous studies indicated that mutagenic carcinogens increased the amount of cell turnover in the target organ, but that mutagenic noncarcinogens failed to do so. The present study compares the incidence of cell proliferation in specific regions of the kidney, which is the site of carcinogenicity, with cell proliferation induced in a nontarget tissue, the liver, by the mutagenic renal tubular carcinogen tris(2,3-dibromopropyl)phosphate (TRIS). Renal tubular adenocarcinoma induced by TRIS was the only tumor type identified in male F344 rats, and it was localized in the outer medulla. Male F344 rats were fed a diet containing 0, 50, or 100 ppm TRIS for 14 days. These doses were identical to the doses given in the National Toxicology Program cancer bioassay. Replicating cells were labeled with bromodeoxyuridine administered by an osmotic minipump and identified in tissue sections from liver and kidney using immunohistochemical techniques. Examination of liver sections showed no chemically related increases in cell proliferation above control for either dose group. However, in the kidney, TRIS induced significant cell proliferation that was localized in the renal outer medulla region, the target area for carcinogenesis. The labeling index (number of labeled cells/total number of cells counted) in the kidneys of TRIS-exposed rats was increased approximately 4-fold in the outer medulla and was not increased in the cortex or inner medulla. The results of this study suggest an association between the chemically-induced renal cell proliferation and the renal carcinogenicity of TRIS. JF - Environmental health perspectives AU - Cunningham, M L AU - Elwell, M R AU - Matthews, H B AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1993/12// PY - 1993 DA - December 1993 SP - 253 EP - 257 VL - 101 Suppl 5 SN - 0091-6765, 0091-6765 KW - Carcinogens KW - 0 KW - Organophosphates KW - tris(2,3-dibromopropyl)phosphate KW - 126-72-7 KW - Index Medicus KW - Animals KW - Liver -- pathology KW - Cocarcinogenesis KW - Carcinoma, Renal Cell -- chemically induced KW - Kidney Neoplasms -- chemically induced KW - Carcinogens -- toxicity KW - Organ Specificity KW - Rats KW - Rats, Inbred F344 KW - Mutagenicity Tests KW - Liver -- drug effects KW - In Vitro Techniques KW - Carcinogenicity Tests KW - Male KW - Kidney Tubules -- pathology KW - Kidney Tubules -- drug effects KW - Organophosphates -- toxicity KW - Cell Division -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76288764?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Site-specific+cell+proliferation+in+renal+tubular+cells+by+the+renal+tubular+carcinogen+tris%282%2C3-dibromopropyl%29phosphate.&rft.au=Cunningham%2C+M+L%3BElwell%2C+M+R%3BMatthews%2C+H+B&rft.aulast=Cunningham&rft.aufirst=M&rft.date=1993-12-01&rft.volume=101+Suppl+5&rft.issue=&rft.spage=253&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 - 1994-07-22 N1 - Date created - 1994-07-22 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Science. 1977 Jan 7;195(4273):76-8 [318761] Nature. 1978 Sep 7;275(5675):60-2 [683342] Science. 1987 May 22;236(4804):933-41 [3554512] Lab Invest. 1987 Nov;57(5):564-77 [3682766] Mutat Res. 1988 Jan;204(1):17-115 [3277047] Cancer Res. 1988 Dec 1;48(23):6739-44 [3180084] Toxicol Appl Pharmacol. 1991 Sep 15;110(3):505-13 [1949017] Toxicol Appl Pharmacol. 1989 Sep 15;100(3):398-410 [2551075] Cancer Lett. 1989 Oct;47(3):163-7 [2699723] Science. 1990 Aug 31;249(4972):1007-11 [2204108] Proc Natl Acad Sci U S A. 1990 Oct;87(19):7772-6 [2217209] Toxicol Appl Pharmacol. 1991 Mar 1;107(3):562-7 [2000642] Environ Mol Mutagen. 1990;16 Suppl 18:32-54 [2091923] Toxicol Appl Pharmacol. 1988 Nov;96(2):367-79 [2461605] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Renal cell cancer and exposure to gasoline: a review. AN - 76286619; 8020434 AB - A review of the epidemiology of renal cell cancer is presented. Risk factors for renal cell cancer such as cigarette smoking, obesity, diet, and use of analgesics and prescription diuretics are examined. Although uncommon, occupational risk factors are also reviewed. Studies examining gasoline exposure and renal cell cancer are evaluated, including investigations recently presented at a meeting on this topic. Overall, most studies find no link between gasoline exposure and renal cell cancer; moreover, the experimental evidence that initiated the health concern is no longer considered relevant to humans. Positive associations, however, reported in two recent studies prevent a firm conclusion of no risk for this exposure. JF - Environmental health perspectives AU - McLaughlin, J K AD - National Cancer Institute, Division of Cancer Etiology, Rockville, MD 20852. Y1 - 1993/12// PY - 1993 DA - December 1993 SP - 111 EP - 114 VL - 101 Suppl 6 SN - 0091-6765, 0091-6765 KW - Gasoline KW - 0 KW - Index Medicus KW - Risk Factors KW - Humans KW - Incidence KW - Male KW - Female KW - Occupational Exposure KW - Carcinoma, Renal Cell -- chemically induced KW - Kidney Neoplasms -- chemically induced KW - Gasoline -- adverse effects KW - Occupational Diseases -- epidemiology KW - Kidney Neoplasms -- epidemiology KW - Occupational Diseases -- chemically induced KW - Carcinoma, Renal Cell -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76286619?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Renal+cell+cancer+and+exposure+to+gasoline%3A+a+review.&rft.au=McLaughlin%2C+J+K&rft.aulast=McLaughlin&rft.aufirst=J&rft.date=1993-12-01&rft.volume=101+Suppl+6&rft.issue=&rft.spage=111&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 - 1994-08-04 N1 - Date created - 1994-08-04 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Environ Health Perspect. 1993 Dec;101 Suppl 6:77-84 [8020451] Int J Cancer. 1992 Aug 19;52(1):1-6 [1379993] Cancer. 1976 Apr;37(4):1782-7 [769938] Am J Public Health. 1979 May;69(5):508-11 [434285] Ann N Y Acad Sci. 1979;330:91-116 [294225] J Occup Med. 1980 Aug;22(8):542-4 [7400867] Am J Public Health. 1981 Mar;71(3):305-7 [7468868] J Natl Cancer Inst. 1984 Feb;72(2):275-84 [6582315] Am J Public Health. 1984 Nov;74(11):1278-80 [6496825] J Occup Med. 1985 Jun;27(6):398-9 [4020495] J Occup Med. 1985 Sep;27(9):672-4 [4045578] Natl Cancer Inst Monogr. 1985 Dec;69:213-5 [3834335] J Natl Cancer Inst. 1986 Aug;77(2):351-6 [3461197] Environ Res. 1987 Apr;42(2):353-61 [3569176] Br J Ind Med. 1987 Jun;44(6):396-401 [3606968] J Occup Med. 1987 Jun;29(6):535-41 [3612328] Scand J Work Environ Health. 1987 Dec;13(6):493-504 [3433051] J Natl Cancer Inst. 1988 May 4;80(5):378 [3357203] Arch Environ Health. 1988 May-Jun;43(3):238-41 [3382249] Int J Cancer. 1988 Jul 15;42(1):13-6 [3391702] Am J Ind Med. 1989;15(3):283-310 [2929617] Cancer Detect Prev. 1988;13(3-4):263-79 [3266567] Br J Ind Med. 1989 Nov;46(11):823-4 [2511925] Br J Ind Med. 1990 Mar;47(3):162-8 [2328223] Public Health Rep. 1990 Sep-Oct;105(5):535-7 [2120735] Int J Epidemiol. 1990 Dec;19(4):832-8 [2084009] Epidemiology. 1990 Nov;1(6):430-40 [2090280] Cancer Causes Control. 1990 Sep;1(2):125-31 [2102282] Cancer Causes Control. 1990 Sep;1(2):133-41 [2102283] Br J Ind Med. 1991 Aug;48(8):515-30 [1878308] Scand J Work Environ Health. 1991 Aug;17(4):231-9 [1925434] Am J Epidemiol. 1991 Nov 1;134(9):942-7 [1951291] Am J Epidemiol. 1992 May 1;135(9):1019-28 [1595688] J Occup Med. 1972 Aug;14(8):621-9 [4673324] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cell cycle controls: potential targets for chemical carcinogens? AN - 76284093; 8013430 AB - The progression of the cell cycle is controlled by the action of both positive and negative growth regulators. The key players in this activity include a family of cyclins and cyclin-dependent kinases, which are themselves regulated by other kinases and phosphatases. Maintenance of balanced cell cycle controls may be directly linked to genomic stability. Loss of the check-points involved in cell cycle control may result in unrepaired DNA damage during DNA synthesis or mitosis leading to genetic mutations and contributing to carcinogenesis. JF - Environmental health perspectives AU - Afshari, C A AU - Barrett, J C AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1993/12// PY - 1993 DA - December 1993 SP - 9 EP - 14 VL - 101 Suppl 5 SN - 0091-6765, 0091-6765 KW - Carcinogens KW - 0 KW - Proteins KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Animals KW - Neoplasms -- pathology KW - DNA Damage KW - Humans KW - Neoplasms -- chemically induced KW - DNA -- biosynthesis KW - Proteins -- physiology KW - Cell Cycle -- physiology KW - Carcinogens -- toxicity KW - Cell Cycle -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76284093?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cell+cycle+controls%3A+potential+targets+for+chemical+carcinogens%3F&rft.au=Afshari%2C+C+A%3BBarrett%2C+J+C&rft.aulast=Afshari&rft.aufirst=C&rft.date=1993-12-01&rft.volume=101+Suppl+5&rft.issue=&rft.spage=9&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 - 1994-07-22 N1 - Date created - 1994-07-22 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cell. 1992 Nov 13;71(4):587-97 [1423616] Proc Natl Acad Sci U S A. 1993 Feb 1;90(3):1112-6 [8430082] Nature. 1987 May 7-13;327(6117):31-5 [3553962] Cell. 1987 Jul 17;50(2):319-25 [3297353] EMBO J. 1987 Nov;6(11):3507-14 [3322810] Proc Natl Acad Sci U S A. 1988 Mar;85(6):1768-71 [3126494] Nature. 1988 Jun 16;333(6174):676-9 [3287181] Differentiation. 1989 Mar;40(1):36-41 [2663576] Cell. 1989 Jul 14;58(1):193-203 [2473839] Cancer Res. 1989 Oct 15;49(20):5489-96 [2676144] Nature. 1989 Nov 2;342(6245):39-45 [2682257] Science. 1989 Nov 3;246(4930):603-8 [2683075] Science. 1989 Nov 3;246(4930):614-21 [2683077] Science. 1989 Nov 3;246(4930):629-34 [2683079] Annu Rev Cell Biol. 1989;5:341-96 [2574592] Nature. 1990 Feb 8;343(6258):555-7 [1967822] Cell. 1990 Feb 23;60(4):665-73 [2406029] Cell. 1990 Mar 9;60(5):791-801 [2178776] Nature. 1990 Apr 5;344(6266):503-8 [2138713] Cell. 1990 Jun 1;61(5):743-52 [2160858] Proc Natl Acad Sci U S A. 1990 Jul;87(14):5397-401 [2164683] Nature. 1990 Aug 23;346(6286):760-3 [2143810] Science. 1990 Nov 9;250(4982):786-91 [2173140] Cell. 1988 Jul 1;54(1):17-26 [3289755] N Engl J Med. 1988 Sep 1;319(9):525-32 [2841597] Carcinogenesis. 1988 Nov;9(11):2045-52 [3052903] Nature. 1988 Dec 22-29;336(6201):738-44 [2462672] Cell. 1989 Apr 21;57(2):253-63 [2649251] Carcinogenesis. 1989 May;10(5):847-50 [2565171] Cell. 1989 Jun 2;57(5):775-86 [2470513] Nature. 1991 Feb 28;349(6312):808-11 [1825699] Proc Natl Acad Sci U S A. 1991 Mar 1;88(5):1636-40 [2000373] Cell. 1991 Mar 22;64(6):1111-22 [1706223] EMBO J. 1991 Apr;10(4):857-64 [2009861] EMBO J. 1991 Apr;10(4):865-75 [1849074] Nature. 1991 Apr 11;350(6318):512-5 [1826542] Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3377-81 [2014258] EMBO J. 1991 May;10(5):1255-63 [1850698] Mol Cell Biol. 1990 Dec;10(12):6554-64 [2247073] Cancer Res. 1990 Dec 1;50(23):7415-21 [2174724] Nature. 1991 Jan 10;349(6305):132-8 [1846030] Science. 1990 Dec 14;250(4987):1573-6 [1703321] EMBO J. 1991 Feb;10(2):305-16 [1846803] Nature. 1991 Jan 31;349(6308):388-93 [1992340] J Cell Biol. 1991 Feb;112(4):523-33 [1825210] Cell. 1991 Oct 4;67(1):197-211 [1913817] Cancer Res. 1991 Nov 1;51(21):6010-3 [1933864] Cancer Res. 1991 Dec 1;51(23 Pt 1):6304-11 [1933891] Mol Cell Biol. 1991 Dec;11(12):6177-84 [1944283] EMBO J. 1991 Dec;10(13):4279-90 [1756735] EMBO J. 1991 Dec;10(13):4301-9 [1756737] Cell. 1991 Dec 20;67(6):1169-79 [1836977] Proc Natl Acad Sci U S A. 1974 Apr;71(4):1286-90 [4524638] Bacteriol Rev. 1974 Jun;38(2):164-98 [4599449] Nature. 1982 Dec 23;300(5894):706-9 [6757758] EMBO J. 1991 Jun;10(6):1545-54 [1709096] Cell. 1991 May 17;65(4):691-9 [1827756] Cell. 1991 May 17;65(4):701-13 [1827757] J Biol Chem. 1991 Jun 5;266(16):10031-4 [1645333] Nature. 1991 May 16;351(6323):242-5 [1828290] Cell. 1991 Jun 14;65(6):921-3 [2044152] EMBO J. 1991 Aug;10(8):2069-75 [2065655] New Biol. 1991 Mar;3(3):259-69 [1715184] Cell. 1991 Aug 23;66(4):731-42 [1652371] Nature. 1991 Sep 5;353(6339):80-3 [1840647] Nature. 1991 Sep 12;353(6340):174-7 [1653904] Cell. 1991 Sep 20;66(6):1197-206 [1833066] Cell. 1991 Sep 20;66(6):1207-16 [1833067] Cell. 1991 Sep 20;66(6):1217-28 [1833068] Cell. 1991 Dec 20;67(6):1181-94 [1836978] Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11012-6 [1722313] DNA Seq. 1990;1(1):49-54 [2132958] Cell. 1992 Jan 10;68(1):167-76 [1310073] Cell. 1992 Jan 24;68(2):323-32 [1310257] Cell. 1992 Feb 7;68(3):407-10 [1310893] Mol Cell Biol. 1992 Mar;12(3):971-80 [1545827] Science. 1992 Feb 28;255(5048):1144-7 [1312258] EMBO J. 1992 Mar;11(3):961-71 [1312467] Nature. 1992 Mar 26;356(6367):353-5 [1549179] Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):2824-8 [1532660] Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):2917-21 [1372994] Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):3093-7 [1372997] EMBO J. 1992 May;11(5):1797-804 [1582409] Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7491-5 [1323840] Cell. 1992 Sep 18;70(6):923-35 [1356076] Cell. 1992 Sep 18;70(6):937-48 [1525830] Science. 1992 Sep 18;257(5077):1689-94 [1388288] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Using cell replication data in mathematical modeling in carcinogenesis. AN - 76282352; 8013428 AB - Risk estimation involves the application of quantitative models of dose versus response to carcinogenicity data. Recent advances in biology, computing, and mathematics have led to the application of mathematically complicated, mechanistically based models of carcinogenesis to the estimation of risks. This paper focuses on two aspects of this application, distinguishing between models using available data and the development of new models to keep pace with research developments. JF - Environmental health perspectives AU - Portier, C J AU - Kopp-Schneider, A AU - Sherman, C D AD - Risk Methodology Section, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1993/12// PY - 1993 DA - December 1993 SP - 79 EP - 86 VL - 101 Suppl 5 SN - 0091-6765, 0091-6765 KW - Carcinogens KW - 0 KW - Index Medicus KW - Risk KW - Animals KW - Biometry KW - Cocarcinogenesis KW - Neoplastic Stem Cells -- pathology KW - Humans KW - Carcinogens -- toxicity KW - Mathematics KW - Neoplasms -- pathology KW - Models, Biological KW - Neoplasms -- etiology KW - Cell Division UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76282352?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Using+cell+replication+data+in+mathematical+modeling+in+carcinogenesis.&rft.au=Portier%2C+C+J%3BKopp-Schneider%2C+A%3BSherman%2C+C+D&rft.aulast=Portier&rft.aufirst=C&rft.date=1993-12-01&rft.volume=101+Suppl+5&rft.issue=&rft.spage=79&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 - 1994-07-22 N1 - Date created - 1994-07-22 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cell. 1990 Jun 1;61(5):759-67 [2188735] Acta Pathol Microbiol Scand. 1952;30(1):21-53 [14933039] Risk Anal. 1991 Sep;11(3):535-43 [1947359] Fundam Appl Toxicol. 1991 Oct;17(3):601-13 [1794662] Carcinogenesis. 1992 Jun;13(6):973-8 [1600619] Fundam Appl Toxicol. 1993 Jan;20(1):48-56 [8381755] Cancer Res. 1977 Oct;37(10):3475-83 [908002] J Natl Cancer Inst. 1980 Apr;64(4):977-89 [6929006] J Natl Cancer Inst. 1980 Sep;65(3):559-69 [6931935] J Toxicol Environ Health. 1983 Jul;12(1):1-19 [6631999] Fundam Appl Toxicol. 1984 Dec;4(6):949-59 [6519375] EMBO J. 1984 Dec 1;3(12):2943-6 [6098458] Cancer Res. 1986 Sep;46(9):4372-8 [3731095] Cell. 1987 May 22;49(4):465-75 [3032456] Cell. 1988 Apr 22;53(2):173-4 [3282673] Environ Health Perspect. 1987 Dec;76:125-31 [3447890] N Engl J Med. 1988 Sep 1;319(9):525-32 [2841597] Risk Anal. 1988 Sep;8(3):383-92 [3201016] J Toxicol Environ Health. 1989;27(1):21-45 [2724366] Science. 1990 Jan 5;247(4938):12-3 [2403692] Biometrics. 1989 Dec;45(4):1259-63 [2611323] Fundam Appl Toxicol. 1989 Oct;13(3):533-44 [2612786] Fundam Appl Toxicol. 1990 Apr;14(3):444-60 [2340975] Carcinogenesis. 1990 Aug;11(8):1271-8 [2143703] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cell proliferation not associated with carcinogenesis in rodents and humans. AN - 76282132; 8013399 AB - Cell proliferation has often been found to be associated with carcinogenesis in rodents and humans at different stages of the multistage carcinogenesis process. The multistage process includes initiation, promotion, and progression phases. At each phase, increasing the normal level of cell turnover of target cells may enhance carcinogenesis. However, we present evidence that normal levels of cell turnover, or increasing the rate of cell turnover at these different stages, do not necessarily lead to enhanced carcinogenesis. In normal tissues, the length of the cell cycle depends on the age of the host and varies from tissue to tissue. Tissues with normal short cell cycles, such as intestine and bone marrow, do not show a high rate of spontaneous tumors in most species. Cells with higher turnover should be more susceptible to carcinogens at the initiation stage of carcinogenesis if cell proliferation per se causes cancer and if these cells or their progeny survive. Cancer in humans is more often associated with specific etiological factors rather than with the natural proliferative rate of specific tissues. For many tissues of humans and rodents, age-related diseases develop in a progressive, irreversible manner. Often, naturally occurring chronic degenerative and inflammatory changes in a tissue (e.g., kidney, liver, heart, reproductive tract) lead to chronic regeneration of the damaged tissue. Yet, cancer is rarely found in these tissues. In rodent carcinogenesis experiments, chronic toxic lesions, accompanied by increases in normal levels of cell turnover, have sometimes been observed in target organs of nongenotoxic carcinogens. More often, however, organ-specific nongenotoxic toxins are not carcinogens. These toxins include compounds toxic for the liver, kidney, and nasal cavity. In 19 inhalation bioassays conducted by the National Toxicology Program, 5/5 nasal carcinogens and 12/14 nasal noncarcinogens caused nasal lesions usually associated with chronic cell proliferation. Although cell proliferation may contribute to multistage carcinogenesis, cell proliferation is not necessarily a tumor promoter or cocarcinogen. JF - Environmental health perspectives AU - Ward, J M AU - Uno, H AU - Kurata, Y AU - Weghorst, C M AU - Jang, J J AD - Tumor Pathology and Pathogenesis Section, National Cancer Institute, Frederick, MD 21702-1201. Y1 - 1993/12// PY - 1993 DA - December 1993 SP - 125 EP - 135 VL - 101 Suppl 5 SN - 0091-6765, 0091-6765 KW - Carcinogens KW - 0 KW - Index Medicus KW - Animals KW - Kidney Neoplasms -- pathology KW - Urinary Bladder Neoplasms -- pathology KW - Urinary Bladder Neoplasms -- etiology KW - Cocarcinogenesis KW - Humans KW - Carcinogens -- toxicity KW - Mice KW - Rats KW - Hyperplasia KW - Liver Neoplasms -- pathology KW - Nose Neoplasms -- pathology KW - Nose Neoplasms -- etiology KW - Aging -- pathology KW - Kidney Neoplasms -- etiology KW - Liver Neoplasms -- etiology KW - Female KW - Male KW - Neoplasms -- pathology KW - Neoplasms -- etiology KW - Cell Division UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76282132?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cell+proliferation+not+associated+with+carcinogenesis+in+rodents+and+humans.&rft.au=Ward%2C+J+M%3BUno%2C+H%3BKurata%2C+Y%3BWeghorst%2C+C+M%3BJang%2C+J+J&rft.aulast=Ward&rft.aufirst=J&rft.date=1993-12-01&rft.volume=101+Suppl+5&rft.issue=&rft.spage=125&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 - 1994-07-22 N1 - Date created - 1994-07-22 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Natl Cancer Inst. 1981 Aug;67(2):473-9 [6943384] Carcinogenesis. 1989 Sep;10(9):1651-6 [2766457] Toxicol Appl Pharmacol. 1983 Apr;68(2):161-76 [6857658] Cancer Res. 1983 Sep;43(9):4454-7 [6871876] Carcinogenesis. 1983;4(7):895-9 [6135514] Toxicol Appl Pharmacol. 1984 Feb;72(2):292-303 [6695376] Cancer Lett. 1984 May;23(1):29-37 [6744233] Carcinogenesis. 1985 Sep;6(9):1255-9 [2863006] Proc Natl Acad Sci U S A. 1990 Oct;87(19):7777-81 [2217210] Cancer Res. 1990 Dec 1;50(23):7415-21 [2174724] Crit Rev Oncol Hematol. 1990;10(3):283-303 [2257089] Carcinogenesis. 1990 Dec;11(12):2149-56 [2148284] Science. 1991 Jan 25;251(4992):387-8 [1989073] J Dermatol Sci. 1990 Nov;1(6):441-6 [2288899] Toxicol Appl Pharmacol. 1991 Mar 1;107(3):562-7 [2000642] Cancer Lett. 1991 May 1;57(2):95-101 [1851054] Exp Pathol. 1990;40(3):125-38 [2097173] Annu Rev Pharmacol Toxicol. 1991;31:253-87 [2064376] Mod Pathol. 1991 May;4(3):371-82 [2068065] Carcinogenesis. 1991 Sep;12(9):1557-61 [1893515] Cancer Res. 1991 Dec 15;51(24):6493-505 [1742722] Toxicol Appl Pharmacol. 1991 Dec;111(3):375-87 [1720906] Toxicol Appl Pharmacol. 1991 Dec;111(3):409-21 [1746023] Cancer Res. 1992 Jan 15;52(2):249-53 [1728397] Environ Health Perspect. 1991 Jun;93:247-70 [1773796] Mol Carcinog. 1991;4(6):420-40 [1793481] FASEB J. 1992 Jun;6(9):2698-706 [1612294] Cancer. 1957 Jul-Aug;10(4):645-54 [13472598] Int Rev Exp Pathol. 1969;7:1-30 [4885801] Acta Pathol Microbiol Scand A. 1973 May;81(3):359-65 [4767228] Toxicol Appl Pharmacol. 1989 Dec;101(3):414-31 [2481346] N Engl J Med. 1990 Apr 19;322(16):1093-7 [2320078] J Am Acad Dermatol. 1990 Jun;22(6 Pt 1):1056-60 [2370331] Science. 1990 Aug 31;249(4972):1007-11 [2204108] Science. 1990 Aug 31;249(4972):970-1 [2136249] Environ Health Perspect. 1990 Jun;86:27-36 [2401263] Cancer Res. 1974 May;34(5):920-6 [4842806] J Natl Cancer Inst. 1974 Aug;53(2):335-40 [4843266] Cancer Res. 1980 Sep;40(9):3398-402 [7427950] Urology. 1981 Mar;17(Suppl 3):11-6 [6163241] Environ Health Perspect. 1986 Mar;65:279-91 [3709454] J Natl Cancer Inst. 1986 Aug;77(2):573-82 [3461216] Cancer Res. 1986 Dec;46(12 Pt 1):6349-52 [3779651] Fundam Appl Toxicol. 1986 Oct;7(3):376-86 [3781128] J Natl Cancer Inst. 1986 Dec;77(6):1261-5 [3467116] Jpn J Cancer Res. 1987 Sep;78(9):879-82 [3117745] Lab Invest. 1987 Nov;57(5):564-77 [3682766] Cancer Res. 1988 Mar 15;48(6):1658-62 [3345534] Cancer Res. 1988 Apr 15;48(8):1996-2004 [2450643] J Natl Cancer Inst. 1988 Jul 20;80(10):772-4 [3385783] Carcinogenesis. 1988 Nov;9(11):2045-52 [3052903] Toxicology. 1988 Nov 30;52(3):237-52 [3188037] Toxicol Appl Pharmacol. 1988 Dec;96(3):494-506 [3206528] Vet Pathol. 1989 Jan;26(1):6-10 [2913704] Fundam Appl Toxicol. 1989 Jan;12(1):163-71 [2925015] Fundam Appl Toxicol. 1989 Apr;12(3):418-31 [2731657] J Natl Cancer Inst. 1983 Feb;70(2):343-52 [6571941] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Comparison of proliferating cell nuclear antigen to tritiated thymidine as a marker of proliferating hepatocytes in rats. AN - 76280379; 7912186 AB - Proliferating cell nuclear antigen (PCNA), an endogenous nuclear protein, has recently been used to identify replicating cells. PCNA was compared to tritiated thymidine ([3H]-TdR), a reliable and accurate exogenous labeling agent, to ascertain if PCNA gives comparable results for quantitative cell proliferation. Male F344 rats were treated with a single dose of 500 mg/kg 4-acetylaminofluorene (4-AAF), a known liver mitogen. Rats (n = 5) were euthanized and necropsied at 6, 12, 18, 24, 36, 48, 96, or 192 hr after treatment. Two hours before necropsy, rats were pulsed-dosed with [3H]-TdR (2 mCi/kg body weight). Livers were sectioned, autoradiography performed, and labeling indexes (LI), a measurement of the percentage of S-phase hepatocytes, determined. One and a half years after the completion of this study, the archival paraffin blocks of the liver tissue were sectioned and stained for PCNA by an immunohistochemical procedure. Immunocytochemical staining patterns of proliferating cell nuclear antigen antigen expression permitted the recognition of G1, S, G2, M, and quiescent cells. PCNA LI, generated by scoring only cells exhibiting S-phase staining patterns, was compared to the pulse [3H]-TdR LI for each animal. Similar periportal staining patterns of S-phase nuclei were detected by both markers. The [3H]-TdR LI and the PCNA LI exhibited a peak at 24 hr of approximately the same magnitude. However, while the [3H]-TdR LI had returned to near baseline at the 48-hr time point, the PCNA LI remained elevated until the 96-hr time point. This sustained elevation of the PCNA index cannot be explained at this time.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Environmental health perspectives AU - Foley, J AU - Ton, T AU - Maronpot, R AU - Butterworth, B AU - Goldsworthy, T L AD - National Institute of Environmental Health Sciences, Resaerch Triangle Park, NC 27709. Y1 - 1993/12// PY - 1993 DA - December 1993 SP - 199 EP - 205 VL - 101 Suppl 5 SN - 0091-6765, 0091-6765 KW - Biomarkers KW - 0 KW - Nuclear Proteins KW - Proliferating Cell Nuclear Antigen KW - Tritium KW - 10028-17-8 KW - 2-Acetylaminofluorene KW - 9M98QLJ2DL KW - Thymidine KW - VC2W18DGKR KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - 2-Acetylaminofluorene -- toxicity KW - Cell Cycle -- physiology KW - Immunohistochemistry KW - Male KW - Thymidine -- metabolism KW - Liver -- cytology KW - Liver -- drug effects KW - Cell Division -- physiology KW - Liver -- metabolism KW - Nuclear Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76280379?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Comparison+of+proliferating+cell+nuclear+antigen+to+tritiated+thymidine+as+a+marker+of+proliferating+hepatocytes+in+rats.&rft.au=Foley%2C+J%3BTon%2C+T%3BMaronpot%2C+R%3BButterworth%2C+B%3BGoldsworthy%2C+T+L&rft.aulast=Foley&rft.aufirst=J&rft.date=1993-12-01&rft.volume=101+Suppl+5&rft.issue=&rft.spage=199&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 - 1994-07-22 N1 - Date created - 1994-07-22 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Histopathology. 1991 Mar;18(3):221-7 [1675189] Am J Pathol. 1991 May;138(5):1165-72 [1673821] Cancer Lett. 1991 Sep;59(3):251-6 [1680544] J Pathol. 1991 Dec;165(4):349-54 [1783954] J Pathol. 1991 Dec;165(4):356-7 [1686057] Environ Health Perspect. 1993 Dec;101 Suppl 5:211-8 [7912188] Cancer Lett. 1980 Aug;10(2):95-107 [7459837] Mutat Res. 1984 Feb;130(1):53-61 [6694655] EMBO J. 1985 Mar;4(3):655-61 [2861088] Exp Cell Res. 1986 Sep;166(1):209-19 [2874992] Nature. 1987 Apr 2-8;326(6112):515-7 [2882423] Nature. 1987 Apr 2-8;326(6112):517-20 [2882424] Proc Natl Acad Sci U S A. 1987 Mar;84(6):1575-9 [2882507] Arch Pathol Lab Med. 1987 Sep;111(9):841-5 [2888448] Am J Pathol. 1989 Apr;134(4):733-9 [2565087] Cell Tissue Kinet. 1989 Sep;22(5):383-92 [2575456] J Cell Sci. 1990 Jan;95 ( Pt 1):1-4 [1972157] J Cell Sci. 1990 May;96 ( Pt 1):121-9 [1695635] J Histochem Cytochem. 1991 Jan;39(1):23-30 [1670579] Cell Tissue Kinet. 1990 Nov;23(6):505-22 [2276170] Cell Biol Int Rep. 1990 Sep;14(9):765-74 [1980636] Am J Pathol. 1991 Jun;138(6):1471-7 [1675840] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Detecting proliferating cell nuclear antigen in archival rodent tissues. AN - 76274840; 7912187 AB - The detection of proliferating cell nuclear antigen (PCNA), an endogenous cell replication marker, has lacked sensitivity in paraffin-embedded archival tissues fixed in formalin. An enhanced immunohistochemical procedure to detect PCNA has been successfully applied to rat and mouse tissues. Tissue sections are heated in a microwave oven in the presence of an antigen-retrieval solution of heavy-metal salts. Positive immunostaining of S-phase cells, an indication of DNA replicative activity, has been consistently obtained in tissues fixed for more than 24 months in formalin and in paraffin blocks stored for up to 19 months. Use of this technique will allow retrospective staining of rodent tissues from previously conducted toxicity and carcinogenicity studies. JF - Environmental health perspectives AU - Greenwell, A AU - Foley, J F AU - Maronpot, R R AD - National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1993/12// PY - 1993 DA - December 1993 SP - 207 EP - 209 VL - 101 Suppl 5 SN - 0091-6765, 0091-6765 KW - Biomarkers KW - 0 KW - Nuclear Proteins KW - Proliferating Cell Nuclear Antigen KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Kidney -- metabolism KW - Cell Division -- physiology KW - S Phase KW - Liver -- metabolism KW - Mice KW - Tissue Distribution KW - DNA Replication KW - Immunohistochemistry -- methods KW - Nuclear Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76274840?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Detecting+proliferating+cell+nuclear+antigen+in+archival+rodent+tissues.&rft.au=Greenwell%2C+A%3BFoley%2C+J+F%3BMaronpot%2C+R+R&rft.aulast=Greenwell&rft.aufirst=A&rft.date=1993-12-01&rft.volume=101+Suppl+5&rft.issue=&rft.spage=207&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 - 1994-07-22 N1 - Date created - 1994-07-22 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Leuk Res. 1984;8(2):143-57 [6143860] Cancer Lett. 1991 Sep;59(3):251-6 [1680544] Nature. 1987 Apr 2-8;326(6112):515-7 [2882423] FEBS Lett. 1987 Aug 10;220(1):1-7 [2886367] Proc Natl Acad Sci U S A. 1988 Oct;85(20):7506-10 [2902631] Am J Pathol. 1989 Apr;134(4):733-9 [2565087] Cell Tissue Res. 1989 Apr;256(1):167-73 [2565770] Cell Tissue Kinet. 1989 Sep;22(5):383-92 [2575456] Science. 1990 Aug 31;249(4972):1007-11 [2204108] Science. 1990 Aug 31;249(4972):970-1 [2136249] Proc Natl Acad Sci U S A. 1990 Oct;87(19):7772-6 [2217209] Science. 1991 Jan 25;251(4992):387-8 [1989073] J Pathol. 1990 Dec;162(4):285-94 [1981239] J Histochem Cytochem. 1991 Jun;39(6):741-8 [1709656] Exp Cell Res. 1986 Sep;166(1):209-19 [2874992] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - MK-801 and memantine protect cultured neurons from glutamate toxicity induced by glutamate carboxypeptidase-mediated cleavage of methotrexate. AN - 76271358; 7910141 AB - Cleavage of methotrexate into glutamate and diaminomethylpteroate by intrathecal glutamate carboxypeptidase is a new approach to the treatment of acute methotrexate neurotoxicity. The simulation of glutamate carboxypeptidase rescue from high-dose methotrexate in neuron astrocyte cocultures of rat cerebellum or cerebral cortex resulted in a selective, concentration-dependent neurotoxicity. The neurotoxicity was caused by the enzymatic release of glutamate from methotrexate at lower concentrations of methotrexate, and by both glutamate and diaminomethylpteroate at concentrations of methotrexate exceeding 200 microM. The good neuroprotection afforded by MK-801 and memantine suggested that glutamate toxicity was mediated by N-methyl-D-aspartate receptors. Methotrexate alone was not toxic to astrocytes, neurons, or the neurite networking. [3H]thymidine and [3H]deoxyuridine incorporation studies showed that astrocyte proliferation in the presence of methotrexate was maintained by the reutilization of pyrimidine bases for DNA synthesis. N-methyl-D-asparate receptor antagonists should be coadministered in future experimental and clinical trials examining intrathecal glutamate carboxypeptidase rescue of methotrexate toxicity. JF - European journal of pharmacology AU - Weller, M AU - Marini, A M AU - Finiels-Marlier, F AU - Martin, B AU - Paul, S M AD - Section on Molecular Pharmacology, National Institute of Mental Health, Bethesda, MD. Y1 - 1993/12/01/ PY - 1993 DA - 1993 Dec 01 SP - 303 EP - 312 VL - 248 IS - 4 SN - 0014-2999, 0014-2999 KW - Excitatory Amino Acid Antagonists KW - 0 KW - Glutamates KW - Glutamic Acid KW - 3KX376GY7L KW - Dizocilpine Maleate KW - 6LR8C1B66Q KW - Carboxypeptidases KW - EC 3.4.- KW - glutamate carboxypeptidase KW - EC 3.4.17.11 KW - Memantine KW - W8O17SJF3T KW - Methotrexate KW - YL5FZ2Y5U1 KW - Index Medicus KW - Animals KW - Cerebral Cortex -- cytology KW - Cerebral Cortex -- drug effects KW - Drug Interactions KW - Astrocytes -- drug effects KW - Rats KW - Rats, Sprague-Dawley KW - Cerebellum -- cytology KW - Cells, Cultured KW - Cerebellum -- drug effects KW - Astrocytes -- pathology KW - Carboxypeptidases -- pharmacology KW - Neurons -- drug effects KW - Memantine -- pharmacology KW - Brain -- drug effects KW - Methotrexate -- metabolism KW - Glutamates -- toxicity KW - Methotrexate -- toxicity KW - Neurons -- pathology KW - Dizocilpine Maleate -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76271358?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+pharmacology&rft.atitle=MK-801+and+memantine+protect+cultured+neurons+from+glutamate+toxicity+induced+by+glutamate+carboxypeptidase-mediated+cleavage+of+methotrexate.&rft.au=Weller%2C+M%3BMarini%2C+A+M%3BFiniels-Marlier%2C+F%3BMartin%2C+B%3BPaul%2C+S+M&rft.aulast=Weller&rft.aufirst=M&rft.date=1993-12-01&rft.volume=248&rft.issue=4&rft.spage=303&rft.isbn=&rft.btitle=&rft.title=European+journal+of+pharmacology&rft.issn=00142999&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-06-15 N1 - Date created - 1994-06-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Use of omeprazole in Zollinger-Ellison syndrome: a prospective nine-year study of efficacy and safety. AN - 76271169; 8161665 AB - H+, K(+)-ATPase inhibitors such as omeprazole are the antisecretory agents of choice for the management of gastric acid hypersecretory states, including the Zollinger-Ellison syndrome. However, long-term follow-up data on the overall efficacy and safety of these agents in large numbers of patients are lacking. In the current study we examined the long-term efficacy and safety of omeprazole in 116 patients with Zollinger-Ellison syndrome treated with oral omeprazole at a single centre for up to 114 months (mean +/- S.E.M. = 38 +/- 3 months). The initial omeprazole maintenance dose was established according to the acute upward dose titration method in 89/116 patients (77%). Gastric acid output was effectively controlled using 60 mg of omeprazole once daily in 41/89 patients (46%) and 22/89 patients (25%) required twice daily omeprazole therapy. The mean ranitidine equivalent dose for patients who required 60 mg omeprazole once daily (2.5 +/- 0.2 g/day) was significantly lower than the mean ranitidine equivalent dose for patients who required more than 60 mg omeprazole once daily (4.3 +/- 0.3 g/day). Long-term omeprazole maintenance therapy was discontinued in 36/116 patients (31%) but in no cases was discontinuation due either to drug-induced side-effects or uncontrolled gastric acid output. Fasting serum gastrin levels were significantly elevated above pre-treatment levels at only one time point during follow-up and were likely due to tumour growth rather than a drug effect. The final long-term omeprazole maintenance doses were lower than the initial doses but correlated closely with the pre-omeprazole basal acid output (r = 0.41, P < 0.001) and ranitidine equivalent dose requirements (r = 0.49, P < 0.001). We conclude that omeprazole effectively and safely controls gastric acid hypersecretion in all patients with Zollinger-Ellison syndrome for up to nine years without evidence by tachyphylaxis. JF - Alimentary pharmacology & therapeutics AU - Metz, D C AU - Strader, D B AU - Orbuch, M AU - Koviack, P D AU - Feigenbaum, K M AU - Jensen, R T AD - Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/12// PY - 1993 DA - December 1993 SP - 597 EP - 610 VL - 7 IS - 6 SN - 0269-2813, 0269-2813 KW - Gastrins KW - 0 KW - Ranitidine KW - 884KT10YB7 KW - Omeprazole KW - KG60484QX9 KW - Index Medicus KW - Administration, Oral KW - Ranitidine -- administration & dosage KW - Dose-Response Relationship, Drug KW - Humans KW - Gastrins -- blood KW - Aged KW - Prospective Studies KW - Ranitidine -- therapeutic use KW - Adult KW - Follow-Up Studies KW - Middle Aged KW - Adolescent KW - Female KW - Male KW - Omeprazole -- pharmacology KW - Zollinger-Ellison Syndrome -- drug therapy KW - Omeprazole -- adverse effects KW - Omeprazole -- therapeutic use KW - Omeprazole -- administration & dosage KW - Gastric Acid -- secretion UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76271169?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Alimentary+pharmacology+%26+therapeutics&rft.atitle=Use+of+omeprazole+in+Zollinger-Ellison+syndrome%3A+a+prospective+nine-year+study+of+efficacy+and+safety.&rft.au=Metz%2C+D+C%3BStrader%2C+D+B%3BOrbuch%2C+M%3BKoviack%2C+P+D%3BFeigenbaum%2C+K+M%3BJensen%2C+R+T&rft.aulast=Metz&rft.aufirst=D&rft.date=1993-12-01&rft.volume=7&rft.issue=6&rft.spage=597&rft.isbn=&rft.btitle=&rft.title=Alimentary+pharmacology+%26+therapeutics&rft.issn=02692813&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-05-25 N1 - Date created - 1994-05-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The fourth United States-Japan meeting on the toxicological characterization of environmental chemicals. AN - 76266158; 8143598 JF - Environmental health perspectives AU - Damstra, T AU - Kurokawa, Y AD - National Institute of Environmental Health Sciences, Research Triange Park, NC 27709. Y1 - 1993/12// PY - 1993 DA - December 1993 SP - 644 EP - 649 VL - 101 IS - 7 SN - 0091-6765, 0091-6765 KW - Environmental Pollutants KW - 0 KW - Index Medicus KW - United States KW - Animals KW - Testis -- drug effects KW - Reproduction -- drug effects KW - Fishes KW - Carcinogenicity Tests KW - Anura KW - Guidelines as Topic KW - Drug Evaluation, Preclinical KW - Drosophila KW - Male KW - Japan KW - Growth -- drug effects KW - Female KW - Environmental Pollutants -- toxicity KW - International Cooperation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76266158?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+fourth+United+States-Japan+meeting+on+the+toxicological+characterization+of+environmental+chemicals.&rft.au=Damstra%2C+T%3BKurokawa%2C+Y&rft.aulast=Damstra&rft.aufirst=T&rft.date=1993-12-01&rft.volume=101&rft.issue=7&rft.spage=644&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 - 1994-05-05 N1 - Date created - 1994-05-05 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Soc Exp Biol Med. 1970 Oct;135(1):51-4 [5475623] Environ Health Perspect. 1993 Apr;100:269-82 [8354175] Arch Environ Contam Toxicol. 1981;10(3):371-91 [7259304] J Embryol Exp Morphol. 1983 Apr;74:133-42 [6411849] Toxicol Appl Pharmacol. 1984 Feb;72(2):364-71 [6695380] Regul Toxicol Pharmacol. 1985 Sep;5(3):294-313 [3903881] Hum Toxicol. 1988 Sep;7(5):405-10 [3192224] Teratog Carcinog Mutagen. 1988;8(5):251-63 [2905834] Science. 1989 Oct 20;246(4928):352-8 [2678474] Fundam Appl Toxicol. 1989 Nov;13(4):747-77 [2620795] Fundam Appl Toxicol. 1990 May;14(4):720-33 [2361573] Toxicol Pathol. 1990;18(1 Pt 2):186-92 [2195638] Toxicol Pathol. 1990;18(2):239-46 [1697977] Environ Health Perspect. 1990 Jul;87:301-7 [2269235] Environ Health Perspect. 1991 Aug;94:255-9 [1683283] Fundam Appl Toxicol. 1992 Jan;18(1):89-95 [1601214] J Biomed Mater Res. 1992 Mar;26(3):339-56 [1613025] Fundam Appl Toxicol. 1992 Aug;19(2):186-96 [1516774] Regul Toxicol Pharmacol. 1992 Aug;16(1):73-80 [1410657] Environ Health Perspect. 1992 Nov;98:281-6 [1486859] J Toxicol Environ Health. 1979 Jul;5(4):699-709 [490681] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Preliminary controlled trial of nimodipine in ultra-rapid cycling affective dysregulation. AN - 76265807; 8177920 AB - We report the initial results of the first controlled double-blind trial of nimodipine, a calcium channel antagonist, in the acute and prophylactic treatment of patients with treatment-refractory affective dysregulation. Active drug nimodipine (A) was substituted for placebo (B) in 12 patients. Patients were studied in a B-A-B design, with 3 of the 12 patients rechallenged with active drug in a B-A-B-A design (patients 9, 10, and 11). Five of the nine patients who completed the drug trial responded. One of three patients suffering from ultra-ultra-rapid (ultradian) cycling bipolar II disorder (patient 6) showed an essentially complete response; the other two ultradian patients (patients 4 and 9) showed evidence of a partial response on manic and depressive oscillations, one of which was confirmed in a B-A-B-A design. Only one of five less rapidly, but continuously cycling patients showed an excellent response (patient 10), and this was confirmed in a B-A-B-A design. The one patient who had recurrent brief depression (patient 11) showed a complete resolution of severe depressive recurrences, with response re-confirmed in an extended prophylactic trial with a B-A-B-A design. In the eight patients who completed self-ratings, nimodipine was associated with a significant reduction in the magnitude of mood fluctuations compared with the baseline placebo condition. Further clinical study of nimodipine, a calcium channel blocker with a unique profile of behavioral and anticonvulsant properties, appears warranted in patients with treatment-refractory affective illness characterized by recurrent brief depression and ultradian cycling. JF - Psychiatry research AU - Pazzaglia, P J AU - Post, R M AU - Ketter, T A AU - George, M S AU - Marangell, L B AD - Biological Psychiatry Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/12// PY - 1993 DA - December 1993 SP - 257 EP - 272 VL - 49 IS - 3 SN - 0165-1781, 0165-1781 KW - Nimodipine KW - 57WA9QZ5WH KW - Index Medicus KW - Drug Administration Schedule KW - Psychiatric Status Rating Scales KW - Double-Blind Method KW - Dose-Response Relationship, Drug KW - Humans KW - Adult KW - Periodicity KW - Middle Aged KW - Recurrence KW - Male KW - Female KW - Nimodipine -- adverse effects KW - Depressive Disorder -- psychology KW - Bipolar Disorder -- drug therapy KW - Nimodipine -- therapeutic use KW - Depressive Disorder -- drug therapy KW - Bipolar Disorder -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76265807?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psychiatry+research&rft.atitle=Preliminary+controlled+trial+of+nimodipine+in+ultra-rapid+cycling+affective+dysregulation.&rft.au=Pazzaglia%2C+P+J%3BPost%2C+R+M%3BKetter%2C+T+A%3BGeorge%2C+M+S%3BMarangell%2C+L+B&rft.aulast=Pazzaglia&rft.aufirst=P&rft.date=1993-12-01&rft.volume=49&rft.issue=3&rft.spage=257&rft.isbn=&rft.btitle=&rft.title=Psychiatry+research&rft.issn=01651781&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-06-09 N1 - Date created - 1994-06-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dopamine D2 and serotonin S2 receptors in susceptibility to methamphetamine psychosis detected by positron emission tomography. AN - 76263125; 8177922 AB - Positron emission tomography (PET) was used to assess the role of dopamine D2 receptors in the striatum and serotonin S2 receptors in the frontal cortex in the susceptibility to methamphetamine-induced psychosis. Subjects were six men who had previously experienced methamphetamine psychosis (methamphetamine subjects) and 10 age- and sex-matched control subjects. The radiotracer used was 11C-N-methylspiperone. Although binding availability, assessed by dynamic analysis, in the two regions did not differ between the two groups, the ratio of binding availability in the striatum to that in the frontal cortex significantly decreased in the methamphetamine subjects as compared with the control subjects. These findings suggest that an imbalance in the activity of these two receptors may be related to the susceptibility to methamphetamine psychosis. JF - Psychiatry research AU - Iyo, M AU - Nishio, M AU - Itoh, T AU - Fukuda, H AU - Suzuki, K AU - Yamasaki, T AU - Fukui, S AU - Tateno, Y AD - Division of Drug Dependence, National Institute of Mental Health, Chiba, Japan. Y1 - 1993/12// PY - 1993 DA - December 1993 SP - 217 EP - 231 VL - 50 IS - 4 SN - 0165-1781, 0165-1781 KW - Receptors, Dopamine D2 KW - 0 KW - Receptors, Serotonin KW - Methamphetamine KW - 44RAL3456C KW - Spiperone KW - 4X6E73CJ0Q KW - 3-N-methylspiperone KW - 87539-19-3 KW - Index Medicus KW - Substance-Related Disorders -- physiopathology KW - Frontal Lobe -- physiopathology KW - Frontal Lobe -- drug effects KW - Humans KW - Adult KW - Substance-Related Disorders -- diagnostic imaging KW - Radioligand Assay KW - Spiperone -- analogs & derivatives KW - Male KW - Receptors, Serotonin -- physiology KW - Receptors, Serotonin -- drug effects KW - Cerebral Cortex -- drug effects KW - Psychoses, Substance-Induced -- diagnostic imaging KW - Methamphetamine -- adverse effects KW - Receptors, Dopamine D2 -- physiology KW - Cerebral Cortex -- diagnostic imaging KW - Cerebral Cortex -- physiopathology KW - Corpus Striatum -- diagnostic imaging KW - Corpus Striatum -- physiopathology KW - Psychoses, Substance-Induced -- physiopathology KW - Tomography, Emission-Computed KW - Corpus Striatum -- drug effects KW - Receptors, Dopamine D2 -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76263125?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psychiatry+research&rft.atitle=Dopamine+D2+and+serotonin+S2+receptors+in+susceptibility+to+methamphetamine+psychosis+detected+by+positron+emission+tomography.&rft.au=Iyo%2C+M%3BNishio%2C+M%3BItoh%2C+T%3BFukuda%2C+H%3BSuzuki%2C+K%3BYamasaki%2C+T%3BFukui%2C+S%3BTateno%2C+Y&rft.aulast=Iyo&rft.aufirst=M&rft.date=1993-12-01&rft.volume=50&rft.issue=4&rft.spage=217&rft.isbn=&rft.btitle=&rft.title=Psychiatry+research&rft.issn=01651781&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-06-09 N1 - Date created - 1994-06-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interleukin-1 and tumor necrosis factor-alpha as radio- and chemoprotectors of bone marrow. AN - 76262870; 8136738 AB - Administration of interleukin 1 (IL-1) or tumor necrosis factor-alpha (TNF alpha) protects bone marrow precursor cells (BMPC) from ionizing radiation and antineoplastic drugs. The time of injection is critical: the best protective results being obtained when cytokines are given around 24h prior to the induced injury. Multiple daily cytokine injections that precede irradiation or drug administration are more effective than single ones although single doses are quite effective at increasing survival in mice. Protection is positively correlated with both rapid granulocyte recovery and BMPC survival. Mechanisms involved in BMPC radioprotection include: (1) push to the S/G2 + M or arrest in the G0 phases of the cell cycle by IL-1 or TNF alpha, respectively, and (2) induction of mitochondrial manganous superoxide dismutase synthesis. For BMPC chemoprotection, proposed mechanisms are: (1) increase of aldehyde dehydrogenase synthesis, and (2) modulation of multiple-drug resistant gene expression. Stimulation of glutathione synthesis in BMPC could be operating in both radio- and chemoprotection. These findings point to the relevance of IL-1 or TNF alpha in cancer therapy as a means of reducing BMPC sensitivity to cytoreductive drugs or irradiation (including radioimmunotherapy) as well as in in vitro tumor cell purging with drugs in autologous BMT. Prior administration of these cytokines should be also considered for people in imminent danger of exposure to radiation. JF - Bone marrow transplantation AU - Dalmau, S R AU - Freitas, C S AU - Tabak, D G AD - Department of Immunology, National Cancer Institute, Rio de Janeiro, Brazil. Y1 - 1993/12// PY - 1993 DA - December 1993 SP - 551 EP - 563 VL - 12 IS - 6 SN - 0268-3369, 0268-3369 KW - Antineoplastic Agents KW - 0 KW - Interleukin-1 KW - Radiation-Protective Agents KW - Tumor Necrosis Factor-alpha KW - Index Medicus KW - Animals KW - Radiation Injuries -- prevention & control KW - Humans KW - Hematopoietic Stem Cells -- cytology KW - Radiation-Protective Agents -- pharmacology KW - Neoplasms -- therapy KW - Antineoplastic Agents -- adverse effects KW - Hematopoietic Stem Cells -- drug effects KW - Bone Marrow Cells KW - Cell Survival -- drug effects KW - In Vitro Techniques KW - Cell Survival -- radiation effects KW - Colony-Forming Units Assay KW - Hematopoietic Stem Cells -- radiation effects KW - Antineoplastic Agents -- antagonists & inhibitors KW - Interleukin-1 -- pharmacology KW - Tumor Necrosis Factor-alpha -- administration & dosage KW - Interleukin-1 -- administration & dosage KW - Tumor Necrosis Factor-alpha -- pharmacology KW - Tumor Necrosis Factor-alpha -- adverse effects KW - Bone Marrow -- radiation effects KW - Bone Marrow -- drug effects KW - Interleukin-1 -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76262870?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Bone+marrow+transplantation&rft.atitle=Interleukin-1+and+tumor+necrosis+factor-alpha+as+radio-+and+chemoprotectors+of+bone+marrow.&rft.au=Dalmau%2C+S+R%3BFreitas%2C+C+S%3BTabak%2C+D+G&rft.aulast=Dalmau&rft.aufirst=S&rft.date=1993-12-01&rft.volume=12&rft.issue=6&rft.spage=551&rft.isbn=&rft.btitle=&rft.title=Bone+marrow+transplantation&rft.issn=02683369&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-04-25 N1 - Date created - 1994-04-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dose response for TCDD promotion of hepatocarcinogenesis in rats initiated with DEN: histologic, biochemical, and cell proliferation endpoints. AN - 76262458; 8143597 AB - The present study examines the dose-response relationship for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) promotion of histologic and biochemical parameters by using a two-stage model for hepatocarcinogenesis in female Sprague-Dawley rats initiated with a single intraperitoneal dose of 175 mg of diethylnitrosamine (DEN)/kg body weight at 70 days of age. Starting 2 weeks after initiation, treatment groups of 8-10 rats were given TCDD by gavage in corn oil once every 2 weeks for 30 weeks. Doses were 3.5, 10.7, 35.7, and 125 ng TCDD/kg body weight/day. A significant body weight reduction was present in the noninitiated group that received 125 ng TCDD. Relative liver weight was statistically increased in initiated rats treated with > or = 10.7 ng TCDD and in noninitiated rats treated with > or = 35.7 ng TCDD. Histopathologic evidence of cytotoxicity was dose-related in all TCDD-treated groups. There was a statistically significant dose response in the bromodeoxyuridine (BrdU) S-phase labeling index (LI) in the DEN-initiated rats (p < 0.01) and a marginally significant trend in the saline-treated rats (p = 0.10), but proliferating cell nuclear antigen S-phase LI and growth fraction within altered hepatic foci showed no increase. Among the DEN-initiated groups there was a significant increase in glutathione S-transferase altered hepatic foci stereological parameters in the 125 ng TCDD group. This study demonstrates that dose-response relationships for TCDD's effects on cell proliferation growth of altered hepatic foci are different from previously reported effects on P450 gene expression, indicating that different biological or biochemical responses may exhibit different dose-response relationships.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Environmental health perspectives AU - Maronpot, R R AU - Foley, J F AU - Takahashi, K AU - Goldsworthy, T AU - Clark, G AU - Tritscher, A AU - Portier, C AU - Lucier, G AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1993/12// PY - 1993 DA - December 1993 SP - 634 EP - 642 VL - 101 IS - 7 SN - 0091-6765, 0091-6765 KW - Isoenzymes KW - 0 KW - Polychlorinated Dibenzodioxins KW - Diethylnitrosamine KW - 3IQ78TTX1A KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Index Medicus KW - Osmolar Concentration KW - Animals KW - Liver -- pathology KW - Placenta -- enzymology KW - Dose-Response Relationship, Drug KW - Glutathione Transferase -- metabolism KW - Liver -- metabolism KW - Organ Size KW - Isoenzymes -- metabolism KW - Rats KW - Body Weight KW - Rats, Sprague-Dawley KW - Female KW - Cell Division KW - Liver Neoplasms, Experimental -- pathology KW - Liver Neoplasms, Experimental -- chemically induced KW - Polychlorinated Dibenzodioxins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76262458?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Dose+response+for+TCDD+promotion+of+hepatocarcinogenesis+in+rats+initiated+with+DEN%3A+histologic%2C+biochemical%2C+and+cell+proliferation+endpoints.&rft.au=Maronpot%2C+R+R%3BFoley%2C+J+F%3BTakahashi%2C+K%3BGoldsworthy%2C+T%3BClark%2C+G%3BTritscher%2C+A%3BPortier%2C+C%3BLucier%2C+G&rft.aulast=Maronpot&rft.aufirst=R&rft.date=1993-12-01&rft.volume=101&rft.issue=7&rft.spage=634&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 - 1994-05-05 N1 - Date created - 1994-05-05 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Mutat Res. 1977-1978;47(3-4):141-60 [99649] Carcinogenesis. 1992 Mar;13(3):501-3 [1347716] Cancer Res. 1979 Sep;39(9):3341-4 [476664] Cancer Res. 1980 Oct;40(10):3616-20 [6108157] Cancer Res. 1982 Feb;42(2):465-72 [6120037] Nature. 1982 Nov 18;300(5889):271-3 [7144882] Cancer Res. 1983 Mar;43(3):1261-8 [6825098] Fundam Appl Toxicol. 1993 Jan;20(1):48-56 [8381755] Carcinogenesis. 1993 May;14(5):811-7 [8099314] Toxicol Appl Pharmacol. 1993 May;120(1):138-54 [8511776] Proc Natl Acad Sci U S A. 1984 Dec;81(23):7407-11 [6095293] Toxicol Appl Pharmacol. 1985 Feb;77(2):251-9 [2579474] Carcinogenesis. 1985 Sep;6(9):1261-9 [2863007] Arch Toxicol. 1985 Aug;57(3):147-58 [3904674] Fundam Appl Toxicol. 1986 Feb;6(2):364-71 [3084326] Crit Rev Toxicol. 1986;17(1):61-89 [3527567] Toxicol Pathol. 1986;14(2):263-73 [3764323] Carcinogenesis. 1986 Nov;7(11):1797-803 [2876784] Toxicol Appl Pharmacol. 1987 Feb;87(2):306-14 [3029898] Carcinogenesis. 1987 Oct;8(10):1491-9 [2888545] Toxicol Lett. 1988 Jul;42(1):5-14 [2838937] Jpn J Cancer Res. 1988 May;79(5):556-72 [3136107] Carcinogenesis. 1988 Nov;9(11):1935-41 [3141074] Arch Toxicol. 1988;62(5):359-68 [3242446] Cancer Res. 1990 Feb 1;50(3):472-9 [1967547] Toxicol Pathol. 1989;17(4 Pt 1):630-41 [2629099] Toxicol Pathol. 1989;17(4 Pt 1):663-72; discussion 673-4 [2697941] Science. 1990 Aug 31;249(4972):1007-11 [2204108] Cancer Res. 1991 Mar 1;51(5):1391-7 [1671757] Cell Biol Toxicol. 1991 Jan;7(1):67-94 [2054688] Fundam Appl Toxicol. 1991 Apr;16(3):525-47 [1855624] Carcinogenesis. 1992 Mar;13(3):453-6 [1547536] Toxicol Appl Pharmacol. 1978 Nov;46(2):279-303 [734660] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cytochrome P450 and monoclonal antibodies. AN - 76262450; 8127919 JF - Pharmacological reviews AU - Gelboin, H V AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/12// PY - 1993 DA - December 1993 SP - 413 EP - 453 VL - 45 IS - 4 SN - 0031-6997, 0031-6997 KW - Antibodies, Monoclonal KW - 0 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Index Medicus KW - Animals KW - Humans KW - Immunohistochemistry KW - Cytochrome P-450 Enzyme System -- analysis KW - Antibodies, Monoclonal -- isolation & purification KW - Cytochrome P-450 Enzyme System -- immunology KW - Antibodies, Monoclonal -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76262450?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+reviews&rft.atitle=Cytochrome+P450+and+monoclonal+antibodies.&rft.au=Gelboin%2C+H+V&rft.aulast=Gelboin&rft.aufirst=H&rft.date=1993-12-01&rft.volume=45&rft.issue=4&rft.spage=413&rft.isbn=&rft.btitle=&rft.title=Pharmacological+reviews&rft.issn=00316997&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-04-14 N1 - Date created - 1994-04-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The misuse of analysis of variance to detect synergy in combination drug studies. AN - 76254696; 8121692 AB - Drug combination studies often examine the possibility of synergy between drugs. Synergy is defined as an effect of a combination of drugs greater than that expected from the effects of the drugs given individually. One technique used by several investigators is the use of analysis of variance (ANOVA) to determine synergy. In this discussion, the argument is made that due to the pharmacology of drug combination studies the conditions necessary to support the use of ANOVA to detect synergy are typically not met. Therefore, the ANOVA technique is invalid for these drug combination studies. JF - Pain AU - Caudle, R M AU - Williams, G M AD - Neurobiology and Anesthesiology Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/12// PY - 1993 DA - December 1993 SP - 313 EP - 317 VL - 55 IS - 3 SN - 0304-3959, 0304-3959 KW - Receptors, Drug KW - 0 KW - Index Medicus KW - Receptors, Drug -- drug effects KW - Dose-Response Relationship, Drug KW - Kinetics KW - Research Design KW - Analysis of Variance KW - Drug Synergism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76254696?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pain&rft.atitle=The+misuse+of+analysis+of+variance+to+detect+synergy+in+combination+drug+studies.&rft.au=Caudle%2C+R+M%3BWilliams%2C+G+M&rft.aulast=Caudle&rft.aufirst=R&rft.date=1993-12-01&rft.volume=55&rft.issue=3&rft.spage=313&rft.isbn=&rft.btitle=&rft.title=Pain&rft.issn=03043959&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-04-05 N1 - Date created - 1994-04-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Comparison of DSM-III-R and draft DSM-IV alcohol abuse and dependence in a general population sample. AN - 76252847; 8130711 AB - The purpose of this Data Note was to compare DSM-III-R and Draft DSM-IV formulations of alcohol use disorders in terms of prevalence and overlap in a representative sample of the United States general population. The prevalence of DSM-III-R and DSM-IV alcohol abuse and dependence combined were strikingly similar, despite discrepancies in the separate component diagnoses of abuse and dependence. The major finding of this study showed a reversal of the abuse-to-dependence ratio associated with the DSM-IV classification. Unlike previous surveys using DSM-III-R definitions, the prevalence of DSM-IV abuse exceeded that of dependence in this general population sample. Reasons for this discrepancy were discussed in terms of the differences in the number and content of abuse and dependence criteria and the relationship between abuse and dependence categories. The need for an explicit statement justifying the changes in the DSM-IV classification is highlighted. JF - Addiction (Abingdon, England) AU - Grant, B F AD - Division of Biometry and Epidemiology, National Institute on Alcohol Abuse and Alcoholism, Rockville, MD 20857. Y1 - 1993/12// PY - 1993 DA - December 1993 SP - 1709 EP - 1716 VL - 88 IS - 12 SN - 0965-2140, 0965-2140 KW - Index Medicus KW - Sex Factors KW - Humans KW - Continental Population Groups KW - Adult KW - Aged KW - Middle Aged KW - Adolescent KW - United States -- epidemiology KW - Male KW - Female KW - Prevalence KW - Substance-Related Disorders -- diagnosis KW - Psychiatric Status Rating Scales KW - Alcoholism -- epidemiology KW - Alcoholism -- diagnosis KW - Substance-Related Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76252847?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Comparison+of+DSM-III-R+and+draft+DSM-IV+alcohol+abuse+and+dependence+in+a+general+population+sample.&rft.au=Grant%2C+B+F&rft.aulast=Grant&rft.aufirst=B&rft.date=1993-12-01&rft.volume=88&rft.issue=12&rft.spage=1709&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 - 1994-04-18 N1 - Date created - 1994-04-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Adverse effects of antipsychotic drugs. AN - 76244868; 7907481 AB - Since the introduction of chlorpromazine in the 1950s, neuroleptic medications have been the mainstay of treatment of schizophrenia and other psychotic disorders. These medications do not always lead to complete remission of symptoms but they have allowed many patients to lead more productive and satisfying lives away from the restrictions of chronic hospitalisation. However, neuroleptics are associated with a number of adverse effects that can compromise their effectiveness. Extrapyramidal adverse effects include acute dystonic reactions, neuroleptic-induced Parkinsonism and akathisia. They can often be treated with neuroleptic dose reduction, addition of anticholinergic or beta-blocking agents, or medication change. Later-onset movement disorders such as tardive dyskinesia or dystonia require careful evaluation and may be treated with dose reduction or change of neuroleptic to an atypical agent. Potentially fatal reactions such as agranulocytosis and neuroleptic malignant syndrome can rarely occur and often require significant medical intervention. Clozapine offers some advantages over 'typical' neuroleptics but has a unique adverse effect profile which includes agranulocytosis. JF - Drug safety AU - Malhotra, A K AU - Litman, R E AU - Pickar, D AD - Experimental Therapeutics Branch, National Institute of Mental Health, Bethesda, Maryland. Y1 - 1993/12// PY - 1993 DA - December 1993 SP - 429 EP - 436 VL - 9 IS - 6 SN - 0114-5916, 0114-5916 KW - Antipsychotic Agents KW - 0 KW - Clozapine KW - J60AR2IKIC KW - Index Medicus KW - Parkinson Disease, Secondary -- chemically induced KW - Neuroleptic Malignant Syndrome -- etiology KW - Akathisia, Drug-Induced KW - Parasympathetic Nervous System -- drug effects KW - Humans KW - Dystonia -- chemically induced KW - Dyskinesia, Drug-Induced KW - Clozapine -- adverse effects KW - Antipsychotic Agents -- adverse effects KW - Basal Ganglia Diseases -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76244868?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Drug+safety&rft.atitle=Adverse+effects+of+antipsychotic+drugs.&rft.au=Malhotra%2C+A+K%3BLitman%2C+R+E%3BPickar%2C+D&rft.aulast=Malhotra&rft.aufirst=A&rft.date=1993-12-01&rft.volume=9&rft.issue=6&rft.spage=429&rft.isbn=&rft.btitle=&rft.title=Drug+safety&rft.issn=01145916&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-04-21 N1 - Date created - 1994-04-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interleukin-6 and interleukin-8 production by mononuclear cells of chronic alcoholics during treatment. AN - 76240445; 8116830 AB - Chronic alcohol consumption has been associated with suppression of a number of immune parameters. This study was designed to investigate the relationship between chronic alcohol ingestion and cessation with respect to release of interleukin-6 (IL-6) and interleukin-8 (IL-8) using highly specific and sensitive ELISA assays, as well as a functional assay, natural killer cell cytotoxic activity. ELISAs were developed to determine the amount of IL-6 and IL-8 release by peripheral blood mononuclear cells (PBMCs). Two groups of subjects were recruited: young (18-22 years old), nonalcoholic users (controls) and long-term alcoholics (35-55 years old). Blood samples were collected at time 0 from all subjects and from alcoholics 28 days after treatment had begun and alcohol use had ceased. Then mitogen-stimulated release of cytokines by peripheral blood cells was determined. The abstaining controls, and the alcoholics, after 30 days of abstinence, tended to produce lower amounts of IL-6 and IL-8, although these differences were not statistically significant. Natural killer cell activity was not statistically different between the young groups, yet appeared to increase once alcohol use discontinued. Some of the cells from the controls (abstainers) were incubated with ethanol (EtOH). Its content in sealed wells was measured after the time of incubation of PBMCs. When EtOH was serially diluted in plates, some well-well diffusion was noted, but the maximum concentration of EtOH never fell below 0.3% from an initial concentration of 0.5%, and at no time was the EtOH concentration gradient completely lost, even after 66 hr of incubation.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Alcoholism, clinical and experimental research AU - Martinez, F AU - Thomas, N M AU - Darban, H AU - Cox, T J AU - Wood, S AU - Watson, R R AD - Department of Family and Community Medicine, NIAAA Alcohol Research Center, University of Arizona, Tucson 85724. Y1 - 1993/12// PY - 1993 DA - December 1993 SP - 1193 EP - 1197 VL - 17 IS - 6 SN - 0145-6008, 0145-6008 KW - Interleukin-6 KW - 0 KW - Interleukin-8 KW - Index Medicus KW - Liver Diseases, Alcoholic -- rehabilitation KW - Humans KW - Adult KW - Alcohol Drinking -- adverse effects KW - Enzyme-Linked Immunosorbent Assay KW - Adolescent KW - Male KW - Killer Cells, Natural -- immunology KW - Killer Cells, Natural -- drug effects KW - Liver Diseases, Alcoholic -- immunology KW - Alcohol Drinking -- immunology KW - Alcoholism -- rehabilitation KW - Interleukin-6 -- blood KW - Alcohol Withdrawal Delirium -- rehabilitation KW - Alcohol Withdrawal Delirium -- immunology KW - Monocytes -- immunology KW - Monocytes -- drug effects KW - Alcoholism -- immunology KW - Interleukin-8 -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76240445?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Interleukin-6+and+interleukin-8+production+by+mononuclear+cells+of+chronic+alcoholics+during+treatment.&rft.au=Martinez%2C+F%3BThomas%2C+N+M%3BDarban%2C+H%3BCox%2C+T+J%3BWood%2C+S%3BWatson%2C+R+R&rft.aulast=Martinez&rft.aufirst=F&rft.date=1993-12-01&rft.volume=17&rft.issue=6&rft.spage=1193&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 - 1994-03-31 N1 - Date created - 1994-03-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - CAGE as a predictor of hazardous alcohol consumption in U.S. Army personnel. AN - 76238868; 8116828 AB - Sensitivities, specificities, and odds ratios for hazardous drinking for various cut scores on the CAGE are computed for a large sample active duty Army personnel. Contrasts on these properties are made between the standard CAGE and a "modified CAGE" consisting of standard CAGE items and two other items dealing with problematic drinking. The role of demographic variables--gender, ethnicity, marital status, rank category, and age in mediating relationships of both versions of the screening test to hazardous drinking--is also explored. At a cutoff score of one endorsed item, odds ratios were highest for female personnel and commissioned officers. JF - Alcoholism, clinical and experimental research AU - Fertig, J B AU - Allen, J P AU - Cross, G M AD - Treatment Research Branch, National Institute on Alcohol Abuse and Alcoholism, Rockville, MD 20857. Y1 - 1993/12// PY - 1993 DA - December 1993 SP - 1184 EP - 1187 VL - 17 IS - 6 SN - 0145-6008, 0145-6008 KW - Index Medicus KW - Reproducibility of Results KW - Risk Factors KW - Humans KW - Adult KW - Alcohol Drinking -- psychology KW - Alcohol Drinking -- adverse effects KW - Adolescent KW - Psychometrics KW - Male KW - Female KW - Personality Inventory -- statistics & numerical data KW - Alcoholism -- diagnosis KW - Military Personnel -- psychology KW - Alcoholism -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76238868?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=CAGE+as+a+predictor+of+hazardous+alcohol+consumption+in+U.S.+Army+personnel.&rft.au=Fertig%2C+J+B%3BAllen%2C+J+P%3BCross%2C+G+M&rft.aulast=Fertig&rft.aufirst=J&rft.date=1993-12-01&rft.volume=17&rft.issue=6&rft.spage=1184&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 - 1994-03-31 N1 - Date created - 1994-03-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evolution by DNA turnover in the control region of vertebrate mitochondrial DNA. AN - 76236411; 8118214 AB - The control region of animal mitochondrial DNA is heterogeneous, including both highly conserved and highly variable sequences. Within the variable regions, variable number tandem repeat sequences have been described for numerous species. Repeats at one location, just upstream of the origin of replication, show an unprecedented level of length variation in somatic tissue. Recent comparison of these sequences in different species indicates a pattern of DNA turnover acting at different rates and over motifs of various sizes. JF - Current opinion in genetics & development AU - Hoelzel, A R AD - Laboratory of Viral Carcinogenesis, National Cancer Institute, Frederick, Maryland 21702. Y1 - 1993/12// PY - 1993 DA - December 1993 SP - 891 EP - 895 VL - 3 IS - 6 SN - 0959-437X, 0959-437X KW - DNA, Mitochondrial KW - 0 KW - Index Medicus KW - Animals KW - Humans KW - Vertebrates KW - Regulatory Sequences, Nucleic Acid KW - Biological Evolution KW - DNA, Mitochondrial -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76236411?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+genetics+%26+development&rft.atitle=Evolution+by+DNA+turnover+in+the+control+region+of+vertebrate+mitochondrial+DNA.&rft.au=Hoelzel%2C+A+R&rft.aulast=Hoelzel&rft.aufirst=A&rft.date=1993-12-01&rft.volume=3&rft.issue=6&rft.spage=891&rft.isbn=&rft.btitle=&rft.title=Current+opinion+in+genetics+%26+development&rft.issn=0959437X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-04-05 N1 - Date created - 1994-04-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Taxol: a case study. AN - 76235877; 7906612 AB - Taxol is a novel antineoplastic agent that has demonstrated significant activity in ovarian carcinoma. Clinical trials are now underway to determine its use in combination with other chemotherapeutic agents, cytokines, and other cancers. The purpose of this article is to review clinical trials using Taxol and relevant nursing care for patients receiving this drug. The nursing implications for Taxol's administration, side effects, and toxicities are also presented. Knowledge of Taxol allows the nurse to provide optimal nursing care and to create appropriate patient care and teaching plans. JF - Cancer nursing AU - DeLaPena, L B AU - Pyron, S AU - Nichols, J AD - Cancer Nursing Service, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/12// PY - 1993 DA - December 1993 SP - 423 EP - 430 VL - 16 IS - 6 SN - 0162-220X, 0162-220X KW - Paclitaxel KW - P88XT4IS4D KW - Index Medicus KW - Nursing KW - Humans KW - Adult KW - Clinical Trials as Topic KW - Female KW - Paclitaxel -- administration & dosage KW - Paclitaxel -- adverse effects KW - Ovarian Neoplasms -- nursing KW - Patient Care Planning UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76235877?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+nursing&rft.atitle=Taxol%3A+a+case+study.&rft.au=DeLaPena%2C+L+B%3BPyron%2C+S%3BNichols%2C+J&rft.aulast=DeLaPena&rft.aufirst=L&rft.date=1993-12-01&rft.volume=16&rft.issue=6&rft.spage=423&rft.isbn=&rft.btitle=&rft.title=Cancer+nursing&rft.issn=0162220X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-03-30 N1 - Date created - 1994-03-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Coordinate regulation of collagen II(alpha 1) and H19 expression in immortalized hamster cells. AN - 76234348; 8117615 AB - Loss of tumor suppressor gene function is essential in the multistep progression of cells to neoplasia. Immortalized cells were established by carcinogen treatment of Syrian hamster embryo cells. At early passages, these nontumorigenic cells retained the ability to suppress tumorigenicity in cell hybrids with malignant cells. Upon passage and subcloning of these suppressor-positive (supB+) cells, variant clones that had lost tumor suppressor activity were isolated. These suppressor-negative (supB-) clones remained nontumorigenic. The mRNAs encoding collagen II(alpha 1a), a chondrocyte differentiation marker, and H19, a developmentally controlled gene, were more abundant in supB+ cells than in supB- cells. Nuclear run-on analysis indicated that the transcription of these genes is differentially regulated. Transient transfection experiments revealed that a cis-acting element in the rat collagen II 5' flanking sequences directs differentially regulated transcription. Gel retention analysis demonstrated the presence of a nuclear DNA-binding factor(s) that specifically recognizes a DNA sequence common to both the rat collagen II sequences and the mouse H19 enhancer. In one set of clones, transcriptional regulation could account for differential collagen II and H19 expression in supB+ and supB- cells. In another set of clones, posttranscriptional controls are responsible for the decreased expression of these genes in supB- cells. The emergence of two independent mechanisms that cause differential expression of collagen II and H19 related to tumor suppressor loss suggests that coordinate regulation of these genes, or others regulated by common mechanisms, may be important in tumor suppression. JF - Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research AU - Owen, R D AU - Hosoi, J AU - Montgomery, J C AU - Wiseman, R AU - Barrett, J C AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina 27709. Y1 - 1993/12// PY - 1993 DA - December 1993 SP - 1013 EP - 1021 VL - 4 IS - 12 SN - 1044-9523, 1044-9523 KW - H19 KW - DNA-Binding Proteins KW - 0 KW - Collagen KW - 9007-34-5 KW - Index Medicus KW - Phenotype KW - Animals KW - Base Sequence KW - Cells, Cultured KW - Molecular Sequence Data KW - DNA-Binding Proteins -- physiology KW - Cell Line, Transformed KW - Cricetinae KW - Collagen -- genetics KW - Gene Expression Regulation, Neoplastic -- physiology KW - Transcription, Genetic KW - Collagen -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76234348?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cell+growth+%26+differentiation+%3A+the+molecular+biology+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=Coordinate+regulation+of+collagen+II%28alpha+1%29+and+H19+expression+in+immortalized+hamster+cells.&rft.au=Owen%2C+R+D%3BHosoi%2C+J%3BMontgomery%2C+J+C%3BWiseman%2C+R%3BBarrett%2C+J+C&rft.aulast=Owen&rft.aufirst=R&rft.date=1993-12-01&rft.volume=4&rft.issue=12&rft.spage=1013&rft.isbn=&rft.btitle=&rft.title=Cell+growth+%26+differentiation+%3A+the+molecular+biology+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10449523&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-04-06 N1 - Date created - 1994-04-06 N1 - Date revised - 2017-01-13 N1 - Gene symbol - H19 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Specific induction of hepatic cytochrome P4501a-2 in C57BL/6 and DBA/2 mice treated with 2-amino-3-methylimidazo[4,5-f]quinoline (IQ). AN - 76234130; 8114061 AB - The food mutagen/carcinogen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) is activated by cytochrome p4501a-2 via N-hydroxylation; various P450s may contribute to detoxification via ring hydroxylation. Alterations in P450 levels by IQ treatment might therefore influence its toxicity. To examine the role of Ah locus genotype on the biochemical effects of IQ, C57BL/6 (AhbAhb; p450Ia-1/2 inducible) and DBA/2 (AhdAhd, noninducible) mice of both sexes were given IQ at varying doses, with different vehicles and routes of administration. Livers taken after 24 hours were assessed for total cytochrome p450 and activities of ethoxyresorufin-O-deethylase (EROD, a p4501a-1 activity, inducible in Ahb mice), methoxyresorufin-O-demethylase (MROD, a p4501a-2 activity), and benzyloxyresorufin-O-dealkylase (BzROD, an activity of p4502b). There was little effect on total cytochrome p450, but all three enzyme activities were often induced, a maximum of 2.5-fold, in both sexes and in DBA/2 as well as C57BL/6 mice. However, Western immunoblot analysis with monoclonal antibodies demonstrated an increase only in p4501a-2 protein. p4501a-1 remained undetectable. A monoclonal antibody to p4502-b recognized one protein band in liver microsomes from males and two bands in female mice of both strains. Amounts of these proteins were not altered by IQ treatment. Thus, IQ specifically, if moderately, induces its activating enzyme, p4501a-2, in a process that was not clearly related to Ah responsiveness. JF - Journal of biochemical toxicology AU - Nerurkar, P V AU - Anderson, L M AU - Snyderwine, E G AU - Park, S S AU - Thorgeirsson, S S AU - Rice, J M AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick, MD 21702-1201. Y1 - 1993/12// PY - 1993 DA - December 1993 SP - 175 EP - 186 VL - 8 IS - 4 SN - 0887-2082, 0887-2082 KW - Mutagens KW - 0 KW - Quinolines KW - 2-amino-3-methylimidazo(4,5-f)quinoline KW - 30GL3D3T0G KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Oxidoreductases KW - EC 1.- KW - methoxyresorufin-O-demethylase KW - Cytochrome P-450 CYP1A1 KW - EC 1.14.14.1 KW - Cytochrome P-450 CYP2B1 KW - Index Medicus KW - Animals KW - Blotting, Western KW - Mice, Inbred C57BL KW - Enzyme Induction KW - Mice KW - Oxidoreductases -- drug effects KW - Male KW - Female KW - Mice, Inbred DBA KW - Quinolines -- toxicity KW - Liver -- enzymology KW - Mutagens -- toxicity KW - Cytochrome P-450 Enzyme System -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76234130?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+biochemical+toxicology&rft.atitle=Specific+induction+of+hepatic+cytochrome+P4501a-2+in+C57BL%2F6+and+DBA%2F2+mice+treated+with+2-amino-3-methylimidazo%5B4%2C5-f%5Dquinoline+%28IQ%29.&rft.au=Nerurkar%2C+P+V%3BAnderson%2C+L+M%3BSnyderwine%2C+E+G%3BPark%2C+S+S%3BThorgeirsson%2C+S+S%3BRice%2C+J+M&rft.aulast=Nerurkar&rft.aufirst=P&rft.date=1993-12-01&rft.volume=8&rft.issue=4&rft.spage=175&rft.isbn=&rft.btitle=&rft.title=Journal+of+biochemical+toxicology&rft.issn=08872082&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-03-28 N1 - Date created - 1994-03-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cancer mortality among jewelry workers. AN - 76232783; 8311104 AB - Mortality was investigated for the years 1950-1980 for 1,009 male members of a New York jewelry workers union, and for the years 1984-1989 among 919 men and 605 women identified as jewelry workers on death certificates from 24 states. Malignant neoplasms were excessive for male union members (proportional mortality ratio [PMR] = 1.17; 95% confidence interval [CI]: 1.02-1.33) and female jeweler deaths from the 24 states (PMR = 1.24; 95% CI: 1.07-1.42). Deaths due to nonmalignant causes were not unusual, except for excesses, in union males, of the circulatory system (PMR = 1.10; 95% CI: 1.02-1.19), including arteriosclerotic heart disease (PMR = 1.25; 95% CI: 1.14-1.37) and rheumatic heart disease (PMR = 3.02; 95% CI: 1.94-4.50). Cancers of the digestive tract were proportionally elevated among union males (proportional cancer mortality rate [PMR] = 1.13; 95% CI: 0.89-1.41) and among deaths from the 24 states (PCMR = 1.22; 95% CI: 1.01-1.47). For the 24 states, excesses for digestive cancer were found for both males (PCMR = 1.19; 95% CI: 0.90-1.54) and females (PCMR = 1.26; 95% CI: 0.96-1.62). Regarding specific sites in the digestive tract, colon cancer excesses were found in union males (PCMR = 1.53: 95% CI: 1.05-2.15), and for men (PCMR = 1.27; 95% CI: 0.82-1.88) and women (PCMR = 1.36; 95% CI: 0.92-3.27) in 24 states.(ABSTRACT TRUNCATED AT 250 WORDS) JF - American journal of industrial medicine AU - Hayes, R B AU - Dosemeci, M AU - Riscigno, M AU - Blair, A AD - Environmental Epidemiology Branch, National Cancer Institute, Bethesda, MD 20892. Y1 - 1993/12// PY - 1993 DA - December 1993 SP - 743 EP - 751 VL - 24 IS - 6 SN - 0271-3586, 0271-3586 KW - Metals KW - 0 KW - Solvents KW - Index Medicus KW - Occupational Exposure KW - Cardiovascular Diseases -- mortality KW - Sex Factors KW - Humans KW - Male KW - Female KW - Proportional Hazards Models KW - Neoplasms -- mortality KW - Metallurgy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76232783?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+industrial+medicine&rft.atitle=Cancer+mortality+among+jewelry+workers.&rft.au=Hayes%2C+R+B%3BDosemeci%2C+M%3BRiscigno%2C+M%3BBlair%2C+A&rft.aulast=Hayes&rft.aufirst=R&rft.date=1993-12-01&rft.volume=24&rft.issue=6&rft.spage=743&rft.isbn=&rft.btitle=&rft.title=American+journal+of+industrial+medicine&rft.issn=02713586&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-03-15 N1 - Date created - 1994-03-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Drug users' self-reports of behaviors and affective states under the influence of alcohol. AN - 76223017; 8307666 AB - This study tested a modified version of the Alcohol-Related Behavior Questionnaire (ARBQ) to investigate the influence of alcohol on negative mood states. The ARBQ asked subjects (substance users and those not misusing drugs or alcohol) to recall various moods and behaviors under three drug conditions: sober, drinking, and drunk. Tests of the ARBQ subscales provided support for its reliability and validity. Scale scores measuring negative affect increased as levels of recalled alcohol intake increased, suggesting that larger amounts of alcohol produced more negative and aggressive feelings. Alcohol-dependent subjects reported more anger and aggression with increasing levels of alcohol intake than nonproblem drinkers. These data further indicated that, among those with alcohol dependence, a history of childhood aggression is an important predictor of negative behaviors and feelings associated with alcohol intake. Among other groups of drug users, a diagnosis of antisocial personality was relatively more important. JF - The International journal of the addictions AU - Fishbein, D H AU - Jaffe, J H AU - Synder, F R AU - Haertzen, C A AU - Hickey, J E AD - Addiction Research Center, National Institute on Drug Abuse, Baltimore, Maryland 21224. Y1 - 1993/12// PY - 1993 DA - December 1993 SP - 1565 EP - 1585 VL - 28 IS - 14 SN - 0020-773X, 0020-773X KW - Psychotropic Drugs KW - 0 KW - Street Drugs KW - Index Medicus KW - Aggression -- drug effects KW - Hostility KW - Risk Factors KW - Humans KW - Depression -- psychology KW - Adult KW - Retrospective Studies KW - Personality Inventory KW - Personality Development KW - Antisocial Personality Disorder -- psychology KW - Male KW - Affect -- drug effects KW - Social Behavior KW - Alcohol Drinking -- adverse effects KW - Substance-Related Disorders -- psychology KW - Alcoholism -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76223017?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+International+journal+of+the+addictions&rft.atitle=Drug+users%27+self-reports+of+behaviors+and+affective+states+under+the+influence+of+alcohol.&rft.au=Fishbein%2C+D+H%3BJaffe%2C+J+H%3BSynder%2C+F+R%3BHaertzen%2C+C+A%3BHickey%2C+J+E&rft.aulast=Fishbein&rft.aufirst=D&rft.date=1993-12-01&rft.volume=28&rft.issue=14&rft.spage=1565&rft.isbn=&rft.btitle=&rft.title=The+International+journal+of+the+addictions&rft.issn=0020773X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-03-15 N1 - Date created - 1994-03-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cancer among migrant and seasonal farmworkers: an epidemiologic review and research agenda. AN - 76222712; 8311105 AB - There are an estimated three million hired migrant and seasonal farmworkers in the United States. Adults and children may be exposed to mutagenic and potentially carcinogenic pesticides during planting, weeding, thinning, and harvesting crops. Field conditions that provide little opportunity to wash skin or clothing to minimize pesticide absorption may intensify exposure. Little is known, however, about the occurrence of cancer in migrant or seasonal farmworkers. Most cancer epidemiologic research on agricultural populations has focussed on farm owner/operators. The few studies that have evaluated cancer in farmworkers suggest that, like farm owner/operators, they may be experiencing excesses of multiple myeloma and cancers of the stomach, prostate, and testis. A few studies suggest that the farmworkers may differ from farmers by experiencing excesses of cancers of the buccal cavity and pharynx, lung, and liver. Cervical cancer was elevated in female farmworkers in one study. Descriptive data and etiologic research on cancer among farmworkers and family members are urgently needed. Feasibility evaluations, however, should precede etiologic investigations because of possible difficulties in studying this population of workers. Issues that need to be evaluated include assessing where and when farmworkers and family members are diagnosed and/or treated for malignancies, the ability of farmworkers to provide histories of crops, locations, and years worked and living conditions, the ability of agricultural experts to determine likely pesticide exposures based on such farmworkers' histories, the ability to obtain information on potential confounding factors, the ability to recontact or determine vital status of specific farmworkers over time, the suitability of conducting studies in home-base vs. upstream counties, and the ability to study agriculturally related malignancies in persons who have left farm work before the disease occurs. JF - American journal of industrial medicine AU - Zahm, S H AU - Blair, A AD - Occupational Studies Section, National Cancer Institute, Rockville, MD. Y1 - 1993/12// PY - 1993 DA - December 1993 SP - 753 EP - 766 VL - 24 IS - 6 SN - 0271-3586, 0271-3586 KW - Pesticides KW - 0 KW - Index Medicus KW - Risk KW - Sex Factors KW - Humans KW - Seasons KW - Cohort Studies KW - Adult KW - Case-Control Studies KW - Child KW - United States -- epidemiology KW - Male KW - Female KW - Occupational Exposure KW - Agricultural Workers' Diseases -- mortality KW - Neoplasms -- mortality KW - Agricultural Workers' Diseases -- epidemiology KW - Neoplasms -- epidemiology KW - Transients and Migrants UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76222712?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+industrial+medicine&rft.atitle=Cancer+among+migrant+and+seasonal+farmworkers%3A+an+epidemiologic+review+and+research+agenda.&rft.au=Zahm%2C+S+H%3BBlair%2C+A&rft.aulast=Zahm&rft.aufirst=S&rft.date=1993-12-01&rft.volume=24&rft.issue=6&rft.spage=753&rft.isbn=&rft.btitle=&rft.title=American+journal+of+industrial+medicine&rft.issn=02713586&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-03-15 N1 - Date created - 1994-03-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Prevention of sexually transmitted infections. Physical and chemical barrier methods. AN - 76221549; 8106732 AB - Barrier contraceptives, including mechanical methods, chemical methods, and combinations thereof, have the potential to decrease the spread of STDs, are inexpensive, and do not have any systemic effects. Currently, the concerns that the efficacy of latex condoms is limited because they are not consistently used, they can break, may cause allergies, and have a limited shelf-life has led to the development of condoms made of other materials such as polyurethane. Spermicides using nonoxynol-9 as their active ingredient have been shown to be effective in preventing the transmission of some STDs such as gonorrhea and chlamydia. In the absence of well-controlled studies of nonoxynol-9 efficacy against HIV, questions have been raised that some formulations, high doses, or frequent use may be associated with genital tract irritation, and possibly, enhancement of HIV transmission. Because heterosexual transmission will continue to be the major route of HIV transmission worldwide, the development and consistent use of a chemical or mechanical barrier during intercourse may be the best way to decrease the spread of HIV. JF - Infectious disease clinics of North America AU - Stratton, P AU - Alexander, N J AD - National Institute of Child Health and Human Development/Center for Population Research/Contraceptive Development Branch, National Institutes of Health, Bethesda, Maryland. Y1 - 1993/12// PY - 1993 DA - December 1993 SP - 841 EP - 859 VL - 7 IS - 4 SN - 0891-5520, 0891-5520 KW - Spermatocidal Agents KW - 0 KW - Index Medicus KW - Humans KW - Male KW - Female KW - Condoms KW - Sexually Transmitted Diseases -- prevention & control KW - Contraceptive Devices, Female UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76221549?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Infectious+disease+clinics+of+North+America&rft.atitle=Prevention+of+sexually+transmitted+infections.+Physical+and+chemical+barrier+methods.&rft.au=Stratton%2C+P%3BAlexander%2C+N+J&rft.aulast=Stratton&rft.aufirst=P&rft.date=1993-12-01&rft.volume=7&rft.issue=4&rft.spage=841&rft.isbn=&rft.btitle=&rft.title=Infectious+disease+clinics+of+North+America&rft.issn=08915520&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-03-22 N1 - Date created - 1994-03-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Brain vessels near muscle autografts are sites for entry of isogeneic macrophages into brain. AN - 76164226; 7507059 AB - An autograft of skeletal muscle on rat dorsal medulla is a permanent opening in the blood-brain barrier to solutes. Is the graft also a site for the entry of exogenous, isogeneic leukocytes? Five weeks after inserting the graft, peritoneal macrophages (M phi) from inbred Fischer rats were activated by phorbol myristate acetate, labeled with a fluorescent dye, and infused as a bolus of about 2 x 10(6) cells into the axillary artery of Fischer hosts. The cells circulated for 2 h. The brains were then fixed, frozen, and sectioned. Only when M phi had been activated and a muscle autograft inserted did appreciable numbers of M phi enter the medulla. Nonactivated M phi invaded the grafts but very few entered the brain at 2 h. In rats with gel foam grafts, only a few activated M phi invaded gel and brain. Before entering tissues, M phi must adhere to the lumenal face of vessels. Cell adhesion molecules, e.g., I-CAM-1 and its ligand adhesion molecule, leukocyte function antigen (LFA-1), are known to mediate adhesion. I-CAM-1, detected immunohistochemically, increased in graft vessels and in nearby brain vessels. The rise may have been mediated by cytokines, interleukin-6, and tumor necrosis factor-beta, found in the grafts. LFA-1, however, assayed by fluorescence-activated cell sorting, was on both activated and nonactivated, exogenous M phi. Thus, M phi-endothelial attachment may have involved other adhesion molecules, e.g., selectins. The autograft also induced major histocompatibility complex class I on microglia and classes I and II on brain vessels near the graft. These vessels, by expressing adhesion molecules, are entry routes into brain for activated, isogeneic leukocytes that can then migrate for a limited distance of 1-2 mm in an otherwise intact brain. JF - Experimental neurology AU - Ishihara, S AU - Sawada, M AU - Chang, L AU - Kim, J M AU - Brightman, M AD - Laboratory of Neurobiology, NINDS, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/12// PY - 1993 DA - December 1993 SP - 219 EP - 230 VL - 124 IS - 2 SN - 0014-4886, 0014-4886 KW - Antibodies, Monoclonal KW - 0 KW - Cell Adhesion Molecules KW - Lymphocyte Function-Associated Antigen-1 KW - Lymphotoxin-alpha KW - Intercellular Adhesion Molecule-1 KW - 126547-89-5 KW - Interferon-gamma KW - 82115-62-6 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Lymphotoxin-alpha -- metabolism KW - Cell Movement KW - Muscle, Smooth, Vascular -- physiology KW - Animals KW - Lymphocyte Function-Associated Antigen-1 -- analysis KW - Macrophage Activation KW - Lymphotoxin-alpha -- analysis KW - Lymphocyte Function-Associated Antigen-1 -- biosynthesis KW - Transplantation, Isogeneic KW - Cell Adhesion Molecules -- analysis KW - Capillaries -- physiology KW - Rats KW - Rats, Inbred F344 KW - Cerebellum -- blood supply KW - Interferon-gamma -- metabolism KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Neovascularization, Pathologic KW - Cell Adhesion Molecules -- biosynthesis KW - Immunohistochemistry KW - Interferon-gamma -- analysis KW - Male KW - Cell Adhesion KW - Macrophages, Peritoneal -- physiology KW - Macrophages, Peritoneal -- transplantation KW - Muscles -- transplantation KW - Medulla Oblongata -- blood supply KW - Cerebral Ventricles -- physiology KW - Transplantation, Autologous -- physiology KW - Macrophages, Peritoneal -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76164226?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Brain+vessels+near+muscle+autografts+are+sites+for+entry+of+isogeneic+macrophages+into+brain.&rft.au=Ishihara%2C+S%3BSawada%2C+M%3BChang%2C+L%3BKim%2C+J+M%3BBrightman%2C+M&rft.aulast=Ishihara&rft.aufirst=S&rft.date=1993-12-01&rft.volume=124&rft.issue=2&rft.spage=219&rft.isbn=&rft.btitle=&rft.title=Experimental+neurology&rft.issn=00144886&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-02-18 N1 - Date created - 1994-02-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of X irradiation on the function of rat salivary glands at 3 and 40 days. AN - 76152659; 8278581 AB - The purpose of this study was to examine the effects of different doses of X irradiation on the major rat salivary glands. The flow rates of the salivary glands were measured simultaneously in both parotid and submandibular glands of mature male Wistar rats at 3 and 40 days after head and neck irradiation with single doses of 2.5, 5, 7.5, 10, or 15 Gy. The parotid and submandibular glands were weighed at the time of saliva collection and total body weight was obtained weekly. Significant reductions in parotid salivary flow at 3 days and parotid and submandibular flow at 40 days were found. Diminished saliva output was dose-dependent and significantly reduced at radiation exposures of 7.5 Gy and greater. Submandibular function deteriorated between 3 and 40 days and the extent of hypofunction was comparable to the parotid gland at the latter time. Parotid and submandibular gland weights were reduced by irradiation in a dose-dependent manner at both 3 and 40 days. The effects were similar for both glands at the latter time. Total body weight was also reduced by the head and neck irradiation in a dose-dependent manner. There was significant mortality in the group receiving 15 Gy irradiation between 7 and 14 days after irradiation. The results demonstrate that parotid and submandibular glands may be affected comparably by equal doses of head and neck irradiation when examined at later times. In the period immediately after irradiation, there are significant differences in the responses of the major salivary glands. JF - Radiation research AU - Nagler, R M AU - Baum, B J AU - Fox, P C AD - Clinical Investigations and Patient Care Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/12// PY - 1993 DA - December 1993 SP - 392 EP - 396 VL - 136 IS - 3 SN - 0033-7587, 0033-7587 KW - Index Medicus KW - Space life sciences KW - Rats KW - Animals KW - X-Rays KW - Body Weight -- radiation effects KW - Rats, Wistar KW - Organ Size -- radiation effects KW - Dose-Response Relationship, Radiation KW - Time Factors KW - Male KW - Salivary Glands -- radiation effects KW - Salivary Glands -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76152659?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Effects+of+X+irradiation+on+the+function+of+rat+salivary+glands+at+3+and+40+days.&rft.au=Nagler%2C+R+M%3BBaum%2C+B+J%3BFox%2C+P+C&rft.aulast=Nagler&rft.aufirst=R&rft.date=1993-12-01&rft.volume=136&rft.issue=3&rft.spage=392&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 - 1994-02-10 N1 - Date created - 1994-02-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Enzyme-kinetic and immunochemical characteristics of mouse cDNA-expressed, microsomal, and purified CYP1A1 and CYP1A2. AN - 76152572; 8274012 AB - Kinetics of benzo[alpha]pyrene hydroxylase (AHH), 7-methoxyresorufin o-demethylase (MROD), and 7-ethoxyresorufin o-deethylase (EROD) were estimated in microsomes of Hep G2 cells infected with a recombinant vaccinia virus bearing mouse CYP1A1 or CYP1A2 cDNAs. The kcat and Km values obtained were compared with those of liver microsomal and purified mouse CYP1A1 and CYP1A2. In the matter of AHH activity, the kcat CYP1A1/CYP1A2 ratios were 21.2, 12.3, and 1.5 for expressed, microsomal, and purified CYPs, respectively. As to MROD activity, the kcat CYP1A2/CYP1A1 ratio was 3.0 for both expressed and microsomal CYPs and was 8.0 for purified CYPs. As regards EROD activity, the kcat CYP1A2/CYP1A1 ratios were 1.0, 1.1, and 6.25 for expressed, microsomal, and purified CYPs, respectively. Whereas furafylline displayed an isozyme-specific inhibition of CYP1A2-catalyzing MROD and EROD activities, alpha-naphthoflavone was an equally strong inhibitor of AHH activity of the CYP1A1s and MROD activities of the CYP1A2s. Immunodepleted polyclonal anti-CYP1A1(-A2) and anti-CYP1A2(-A1) showed an isozyme-specific immunoblotting and inhibition of mouse CYP1A1 and CYP1A2 while monoclonal antibody (Mab) 1-7-1 displayed a striking difference between its immunoblotting and inhibitory effects. Western blot/densitometry analysis revealed a 4.8 times lower binding of Mab 1-7-1 to cDNA-expressed CYP1A2 than to CYP1A1. The results demonstrate the reliability of the vaccinia virus expression system for studies on the enzymology of mouse CYP1A1 and CYP1A2. JF - Archives of biochemistry and biophysics AU - Tsyrlov, I B AU - Goldfarb, I S AU - Gelboin, H V AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/12// PY - 1993 DA - December 1993 SP - 259 EP - 266 VL - 307 IS - 2 SN - 0003-9861, 0003-9861 KW - Antibodies, Monoclonal KW - 0 KW - Benzoflavones KW - DNA, Complementary KW - Isoenzymes KW - Recombinant Proteins KW - alpha-naphthoflavone KW - 604-59-1 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Theophylline KW - C137DTR5RG KW - furafylline KW - C2087G0XX3 KW - Oxidoreductases KW - EC 1.- KW - Cytochrome P-450 CYP1A2 KW - EC 1.14.14.1 KW - Index Medicus KW - Vaccinia virus -- genetics KW - Animals KW - DNA, Complementary -- genetics KW - Humans KW - Multigene Family KW - Mice KW - Antibodies, Monoclonal -- pharmacology KW - Cloning, Molecular KW - Theophylline -- analogs & derivatives KW - Theophylline -- pharmacology KW - Recombinant Proteins -- metabolism KW - Recombinant Proteins -- immunology KW - Cell Line KW - Benzoflavones -- pharmacology KW - Oxidoreductases -- immunology KW - Oxidoreductases -- genetics KW - Oxidoreductases -- metabolism KW - Cytochrome P-450 Enzyme System -- genetics KW - Microsomes, Liver -- enzymology KW - Isoenzymes -- immunology KW - Cytochrome P-450 Enzyme System -- immunology KW - Cytochrome P-450 Enzyme System -- metabolism KW - Isoenzymes -- genetics KW - Isoenzymes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76152572?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Enzyme-kinetic+and+immunochemical+characteristics+of+mouse+cDNA-expressed%2C+microsomal%2C+and+purified+CYP1A1+and+CYP1A2.&rft.au=Tsyrlov%2C+I+B%3BGoldfarb%2C+I+S%3BGelboin%2C+H+V&rft.aulast=Tsyrlov&rft.aufirst=I&rft.date=1993-12-01&rft.volume=307&rft.issue=2&rft.spage=259&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 - 1994-01-28 N1 - Date created - 1994-01-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Single calcium channels and acetylcholine release at a presynaptic nerve terminal. AN - 76148769; 8274272 AB - The relationship between calcium influx and the gating of transmitter release was examined at the release face of a cholinergic presynaptic nerve terminal using a technique that allows the simultaneous recording of both calcium channels at the single-channel level and quantal acetylcholine secretion. Acetylcholine release occurred during large inward calcium currents through many simultaneously open channels but was also gated by very small calcium transients, admitting less than 200 ions, when only one channel was open at a time. These findings provide functional support for a highly structured model of the transmitter release face in which the synaptic vesicle release mechanism is closely tethered to one or more presynaptic calcium channels and the opening of only one of these may be sufficient to trigger quantal secretion. JF - Neuron AU - Stanley, E F AD - National Institute of Neurological Diseases and Stroke, Synaptic Mechanisms Section, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/12// PY - 1993 DA - December 1993 SP - 1007 EP - 1011 VL - 11 IS - 6 SN - 0896-6273, 0896-6273 KW - Barium Compounds KW - 0 KW - Calcium Channels KW - Chlorides KW - barium chloride KW - 0VK51DA1T2 KW - Tetrodotoxin KW - 4368-28-9 KW - Acetylcholine KW - N9YNS0M02X KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Ion Channel Gating KW - Animals KW - Chickens KW - In Vitro Techniques KW - Membrane Potentials -- physiology KW - Models, Neurological KW - Electrophysiology KW - Tetrodotoxin -- pharmacology KW - Time Factors KW - Barium Compounds -- pharmacology KW - Chlorides -- pharmacology KW - Nerve Endings -- physiology KW - Calcium -- metabolism KW - Acetylcholine -- metabolism KW - Synapses -- physiology KW - Calcium Channels -- physiology KW - Ganglia, Parasympathetic -- physiology KW - Calcium Channels -- drug effects KW - Neurons -- physiology KW - Acetylcholine -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76148769?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuron&rft.atitle=Single+calcium+channels+and+acetylcholine+release+at+a+presynaptic+nerve+terminal.&rft.au=Stanley%2C+E+F&rft.aulast=Stanley&rft.aufirst=E&rft.date=1993-12-01&rft.volume=11&rft.issue=6&rft.spage=1007&rft.isbn=&rft.btitle=&rft.title=Neuron&rft.issn=08966273&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-02-04 N1 - Date created - 1994-02-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Investigation of the role of G1/S cell cycle mediators in cellular senescence. AN - 76140045; 8262140 AB - Cellular senescence is a state of irreversible cell cycle arrest in which normal cells at the end of their lifespan fail to enter into DNA synthesis upon serum or growth factor stimulation. We examined whether proteins required for G1/S cell cycle progression were irreversibly down-regulated in senescent human fibroblasts. Both the 44- and 42-kDa forms of the MAP-kinase protein were expressed at similar levels in young and senescent cells. In contrast to young cells where both forms were phosphorylated on tyrosine in response to serum, the p42MAP-kinase was not tyrosine phosphorylated upon serum stimulation, whereas p44MAP-kinase was phosphorylated on tyrosine in serum-starved or serum-stimulated senescent cells. Examination of p53 protein in growing, quiescent, and senescent cells revealed no significant differences in levels between the different growth states. In contrast, cdk2 and cyclin A mRNAs were completely down-regulated in stimulated senescent fibroblasts, while the G1 cyclins, C, D1, and E mRNAs, were still expressed in stimulated senescent cells although at reduced levels compared to young cells. The expression of early G1 markers, but not late G1 markers, indicates that senescent cells may be blocked at a point in late G1. We investigated whether transfection of cyclin A, alone or in combination with cdc2, was sufficient for extension of lifespan or escape from senescence. Clones expressing the transfected human cyclin A or cdc2 genes senesced at a population doubling similar to controls, thereby showing that cyclin A or cdc2 expression alone was insufficient for escape from senescence. JF - Experimental cell research AU - Afshari, C A AU - Vojta, P J AU - Annab, L A AU - Futreal, P A AU - Willard, T B AU - Barrett, J C AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1993/12// PY - 1993 DA - December 1993 SP - 231 EP - 237 VL - 209 IS - 2 SN - 0014-4827, 0014-4827 KW - Cyclins KW - 0 KW - DNA Primers KW - RNA, Messenger KW - Tumor Suppressor Protein p53 KW - Protein Kinases KW - EC 2.7.- KW - Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - CDC2-CDC28 Kinases KW - EC 2.7.11.22 KW - CDK2 protein, human KW - Cyclin-Dependent Kinase 2 KW - Cyclin-Dependent Kinases KW - Mitogen-Activated Protein Kinase 1 KW - EC 2.7.11.24 KW - Index Medicus KW - Blotting, Northern KW - Humans KW - Gene Expression KW - RNA, Messenger -- genetics KW - Precipitin Tests KW - Polymerase Chain Reaction KW - Base Sequence KW - Blotting, Western KW - In Vitro Techniques KW - Molecular Sequence Data KW - Cell Line KW - Cyclins -- genetics KW - DNA Primers -- chemistry KW - Protein-Serine-Threonine Kinases -- metabolism KW - Cell Aging KW - Protein Kinases -- genetics KW - Protein-Tyrosine Kinases -- metabolism KW - Tumor Suppressor Protein p53 -- metabolism KW - Cell Cycle UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76140045?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Investigation+of+the+role+of+G1%2FS+cell+cycle+mediators+in+cellular+senescence.&rft.au=Afshari%2C+C+A%3BVojta%2C+P+J%3BAnnab%2C+L+A%3BFutreal%2C+P+A%3BWillard%2C+T+B%3BBarrett%2C+J+C&rft.aulast=Afshari&rft.aufirst=C&rft.date=1993-12-01&rft.volume=209&rft.issue=2&rft.spage=231&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 - 1994-01-24 N1 - Date created - 1994-01-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Complete cDNA sequence and cDNA-directed expression of CYP4A11, a fatty acid omega-hydroxylase expressed in human kidney. AN - 76134429; 8274222 AB - A cDNA was isolated from a human kidney lambda gt10 library using the rat CYP4A3 cDNA as a probe. The cDNA-deduced amino acid sequence encoded a protein of 519 amino acids that was designated CYP4A11 (Nelson et al., 1993) and exhibited 76%, 72%, 80%, and 53% similarities to rat CYP4A1, rat CYP4A3, rabbit CYP4A6, and human CYP4B1, respectively. The deduced amino-terminal amino acid sequence of this cDNA agreed with the amino-terminal amino acid sequence of a major P450 protein purified from human renal microsomes. A second variant form of CYP4A11 cDNA, designated CYP4A11v, was isolated from the same library and had a deletion of a single adenine residue, thereby extending the reading frame and resulting in a protein of 591 amino acids. CYP4A11v is probably encoded by a rare allelic variant of CYP4A11, since no mutant alleles were uncovered in 15 normal individuals, as determined by a polymerase chain reaction (PCR) diagnostic test. Baculovirus-mediated cDNA expression of CYP4A11 yielded a P450 protein having a lambda max of 452 nm when reduced and complexed with carbon monoxide. The expressed enzyme efficiently catalyzed omega-hydroxylation of lauric acid. No detectable activity was uncovered toward arachidonic acid and prostaglandin E1. The cDNA-expressed variant, CYP4A11v, was found to be unstable and not to efficiently metabolize lauric acid, as assessed by both baculovirus and monkey kidney COS cell cDNA expression systems. These studies indicate that CYP4A11 is a major fatty acid-metabolizing P450 that is expressed in human kidney. JF - DNA and cell biology AU - Imaoka, S AU - Ogawa, H AU - Kimura, S AU - Gonzalez, F J AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, Bethesda, MD 20892. Y1 - 1993/12// PY - 1993 DA - December 1993 SP - 893 EP - 899 VL - 12 IS - 10 SN - 1044-5498, 1044-5498 KW - CYP4A11 KW - DNA, Complementary KW - 0 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Mixed Function Oxygenases KW - EC 1.- KW - Cytochrome P-450 CYP4A KW - EC 1.14.15.3 KW - Index Medicus KW - Rats KW - Animals KW - Base Sequence KW - Spectrum Analysis KW - Humans KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Cloning, Molecular KW - Catalysis KW - Mixed Function Oxygenases -- metabolism KW - Cytochrome P-450 Enzyme System -- genetics KW - Kidney -- enzymology KW - Cytochrome P-450 Enzyme System -- metabolism KW - Mixed Function Oxygenases -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76134429?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=DNA+and+cell+biology&rft.atitle=Complete+cDNA+sequence+and+cDNA-directed+expression+of+CYP4A11%2C+a+fatty+acid+omega-hydroxylase+expressed+in+human+kidney.&rft.au=Imaoka%2C+S%3BOgawa%2C+H%3BKimura%2C+S%3BGonzalez%2C+F+J&rft.aulast=Imaoka&rft.aufirst=S&rft.date=1993-12-01&rft.volume=12&rft.issue=10&rft.spage=893&rft.isbn=&rft.btitle=&rft.title=DNA+and+cell+biology&rft.issn=10445498&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-02-08 N1 - Date created - 1994-02-08 N1 - Date revised - 2017-01-13 N1 - Gene symbol - CYP4A11 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Recombinant interleukin-6 activates the hypothalamic-pituitary-adrenal axis in humans. AN - 76128574; 8263159 AB - The inflammatory cytokines, tumor necrosis factor-alpha, interleukin-1 alpha and -beta (IL-1 alpha and -beta), and IL-6 can activate the hypothalamic-pituitary-adrenal (HPA) axis. Tumor necrosis factor-alpha and IL-1 have been tested in both experimental animals and humans, but their administration has been limited by significant toxicity, mainly severe hypotension. IL-6, on the other hand, has demonstrated modest toxicity in animals. We evaluated the ability of recombinant IL-6 to stimulate the human HPA axis in patients with cancer and a good performance status, who received daily morning sc injections of 30 micrograms/kg IL-6 for 7 consecutive days, during the course of a phase I trial. IL-6 caused impressively marked and prolonged elevations of plasma ACTH and cortisol on the first day and blunted ACTH responses on the seventh day of treatment, perhaps as a result of increased baseline cortisol levels. The overall cortisol response, however, on the seventh day was of similar magnitude, suggesting that a new equilibrium in the feedback regulation of the HPA axis occurs with chronic IL-6 administration. The toxic effects of IL-6 were modest, suggesting that it might be useful for clinical testing of the HPA axis, as an alternative to the insulin tolerance test. JF - The Journal of clinical endocrinology and metabolism AU - Mastorakos, G AU - Chrousos, G P AU - Weber, J S AD - Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/12// PY - 1993 DA - December 1993 SP - 1690 EP - 1694 VL - 77 IS - 6 SN - 0021-972X, 0021-972X KW - Interleukin-6 KW - 0 KW - Recombinant Proteins KW - Adrenocorticotropic Hormone KW - 9002-60-2 KW - Corticotropin-Releasing Hormone KW - 9015-71-8 KW - Hydrocortisone KW - WI4X0X7BPJ KW - Abridged Index Medicus KW - Index Medicus KW - Corticotropin-Releasing Hormone -- blood KW - Recombinant Proteins -- pharmacology KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Corticotropin-Releasing Hormone -- pharmacology KW - Male KW - Hydrocortisone -- blood KW - Female KW - Adrenocorticotropic Hormone -- blood KW - Hypothalamo-Hypophyseal System -- drug effects KW - Interleukin-6 -- pharmacology KW - Pituitary-Adrenal System -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76128574?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Recombinant+interleukin-6+activates+the+hypothalamic-pituitary-adrenal+axis+in+humans.&rft.au=Mastorakos%2C+G%3BChrousos%2C+G+P%3BWeber%2C+J+S&rft.aulast=Mastorakos&rft.aufirst=G&rft.date=1993-12-01&rft.volume=77&rft.issue=6&rft.spage=1690&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 - 1994-01-24 N1 - Date created - 1994-01-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Catechol-O-methyltransferase inhibitor tolcapone prolongs levodopa/carbidopa action in parkinsonian patients. AN - 76124881; 8255478 AB - The wearing-off phenomenon frequently complicates levodopa therapy of Parkinson's disease (PD). These response fluctuations appear when intrasynaptic dopamine concentrations begin to reflect the swings in levodopa availability that attend standard dosing regimens. Drugs that prolong the biologic half-life of levodopa and dopamine should thus prove beneficial. We administered levodopa/carbidopa in combination with single oral doses of tolcapone (Ro 40-7592), an inhibitor of catechol-O-methyltransferase, under controlled conditions to 10 PD patients with the wearing-off phenomenon. Tolcapone prolonged the antiparkinson response to levodopa/carbidopa by about 67% at several doses ranging from 50 to 400 mg (p < 0.05). There was no significant change in the peak levodopa effect on parkinsonian signs or in the severity of dyskinesias. No dose-limiting adverse effects occurred. Multiple daily dosing with tolcapone would thus be expected to safely reduce the wearing-off phenomenon associated with levodopa/carbidopa therapy. JF - Neurology AU - Roberts, J W AU - Cora-Locatelli, G AU - Bravi, D AU - Amantea, M A AU - Mouradian, M M AU - Chase, T N AD - Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/12// PY - 1993 DA - December 1993 SP - 2685 EP - 2688 VL - 43 IS - 12 SN - 0028-3878, 0028-3878 KW - Benzophenones KW - 0 KW - Catechol O-Methyltransferase Inhibitors KW - Nitrophenols KW - Placebos KW - Levodopa KW - 46627O600J KW - tolcapone KW - CIF6334OLY KW - Carbidopa KW - MNX7R8C5VO KW - Abridged Index Medicus KW - Index Medicus KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Drug Synergism KW - Adolescent KW - Parkinson Disease, Secondary -- physiopathology KW - Parkinson Disease, Secondary -- metabolism KW - Benzophenones -- adverse effects KW - Levodopa -- pharmacokinetics KW - Levodopa -- therapeutic use KW - Carbidopa -- therapeutic use KW - Benzophenones -- therapeutic use KW - Parkinson Disease, Secondary -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76124881?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurology&rft.atitle=Catechol-O-methyltransferase+inhibitor+tolcapone+prolongs+levodopa%2Fcarbidopa+action+in+parkinsonian+patients.&rft.au=Roberts%2C+J+W%3BCora-Locatelli%2C+G%3BBravi%2C+D%3BAmantea%2C+M+A%3BMouradian%2C+M+M%3BChase%2C+T+N&rft.aulast=Roberts&rft.aufirst=J&rft.date=1993-12-01&rft.volume=43&rft.issue=12&rft.spage=2685&rft.isbn=&rft.btitle=&rft.title=Neurology&rft.issn=00283878&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-01-13 N1 - Date created - 1994-01-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Metabolism of the food-derived mutagen/carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in nonhuman primates. AN - 76123516; 8269621 AB - Metabolism of the food-derived heterocyclic amine mutagen/carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) was examined in cynomolgus monkeys. [3H]PhIP (50 mumol/kg, p.o.) was extensively metabolized, with only 1% of the dose excreted into the urine as parent compound. Four metabolites were isolated by HPLC and identified: PhIP-4'-O-glucuronide, PhIP-4'-sulfate, 4'-hydroxy-PhIP and a glucuronide conjugate of N-hydroxy-PhIP. All four metabolites were detected in urine, bile and plasma of monkeys. 4'-Hydroxy-PhIP and PhIP were found in feces. The major PhIP metabolite in urine, bile and plasma was PhIP-4'-sulfate. In urine this metabolite constituted approximately 64-72% of the radioactivity excreted. The clearance of PhIP and PhIP metabolites from plasma was rapid, with the largest elimination occurring within 8 h. Administration of nine consecutive daily doses of unlabeled PhIP (50 mumol/kg, p.o.) prior to administration of [3H]PhIP (50 mumol/kg, p.o.) did not alter the plasma clearance of radiolabeled PhIP or PhIP metabolites, suggesting that this multiple-dose regimen did not induce or alter PhIP metabolism. PhIP formed DNA adducts in white blood cells, as determined by the 32P-postlabeling method. The levels of PhIP-DNA adducts in blood appeared to peak 3 h after administering a single dose of PhIP (50 mumol/kg, p.o.) and were still detected 1 week after dosing. The presence of the glucuronide conjugate of N-hydroxy-PhIP in urine, bile and plasma, and the presence of PhIP-DNA adducts in white blood cells indicate that PhIP undergoes metabolic activation via N-hydroxylation in cynomolgus monkeys. The results suggest that PhIP is activated in vivo to genotoxic metabolites in nonhuman primates and thus is a potential carcinogen in this species. JF - Carcinogenesis AU - Snyderwine, E G AU - Buonarati, M H AU - Felton, J S AU - Turteltaub, K W AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, Bethesda, MD 20892. Y1 - 1993/12// PY - 1993 DA - December 1993 SP - 2517 EP - 2522 VL - 14 IS - 12 SN - 0143-3334, 0143-3334 KW - Carcinogens KW - 0 KW - Imidazoles KW - Mutagens KW - 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine KW - 909C6UN66T KW - Index Medicus KW - Body Fluids KW - Animals KW - Macaca fascicularis KW - Food KW - Feces KW - Male KW - Female KW - Chromatography, High Pressure Liquid KW - Carcinogens -- metabolism KW - Mutagens -- metabolism KW - Imidazoles -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76123516?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Metabolism+of+the+food-derived+mutagen%2Fcarcinogen+2-amino-1-methyl-6-phenylimidazo%5B4%2C5-b%5Dpyridine+%28PhIP%29+in+nonhuman+primates.&rft.au=Snyderwine%2C+E+G%3BBuonarati%2C+M+H%3BFelton%2C+J+S%3BTurteltaub%2C+K+W&rft.aulast=Snyderwine&rft.aufirst=E&rft.date=1993-12-01&rft.volume=14&rft.issue=12&rft.spage=2517&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-02-03 N1 - Date created - 1994-02-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Human T lymphocytes synthesize the 92 kDa type IV collagenase (gelatinase B). AN - 76116921; 8253876 AB - In order for T cells to exit the circulatory system, traverse the endothelial basement membrane, and arrive in target tissues, these cells must attach to and degrade basement membrane proteins. 12-O-tetradecanoylphorbol-13-acetate (TPA) has been shown to stimulate lymphoid cell adhesion to basement membrane components. We have used TPA to study the ability of human lymphoid cells to secrete type IV collagenases, enzymes capable of degrading basement membrane proteins. Here, we found that human primary T cells and H-9 lymphoid cells synthesize the 92 kDa type IV collagenase (gelatinase B) and TPA stimulates the synthesis and secretion of this protease. Peak TPA-stimulated gelatinase B secretion and mRNA accumulation were observed 9 hours after TPA treatment, while the peak adhesion to type IV collagen was observed only 3 hours after TPA treatment. The protein kinase C inhibitor, H-7, inhibited TPA-stimulated gelatinase B secretion. Both the primary T cells and H-9 lymphoid cells also expressed the mRNA for the tissue inhibitor of metalloproteinase-1 (TIMP-1). These data demonstrate that TPA-stimulated lymphoid cells adhere to type IV collagen and subsequently synthesize and secrete gelatinase B and TIMP-1. We conclude that lymphoid cell extravasation may involve cellular employment of adhesion mechanisms prior to degradation of the matrix, which is similar to the process of extravasation used by metastatic cells. JF - Journal of cellular physiology AU - Weeks, B S AU - Schnaper, H W AU - Handy, M AU - Holloway, E AU - Kleinman, H K AD - Laboratory of Developmental Biology, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/12// PY - 1993 DA - December 1993 SP - 644 EP - 649 VL - 157 IS - 3 SN - 0021-9541, 0021-9541 KW - Glycoproteins KW - 0 KW - Matrix Metalloproteinase Inhibitors KW - Neoplasm Proteins KW - Tissue Inhibitor of Metalloproteinases KW - Tissue Inhibitor of Metalloproteinase-2 KW - 127497-59-0 KW - Collagen KW - 9007-34-5 KW - Collagenases KW - EC 3.4.24.- KW - Gelatinases KW - Metalloendopeptidases KW - Matrix Metalloproteinase 2 KW - EC 3.4.24.24 KW - Matrix Metalloproteinase 9 KW - EC 3.4.24.35 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Neoplasm Proteins -- biosynthesis KW - Animals KW - Blotting, Northern KW - Glycoproteins -- biosynthesis KW - Collagen -- metabolism KW - Humans KW - Mice KW - Gelatinases -- biosynthesis KW - Cells, Cultured KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Metalloendopeptidases -- biosynthesis KW - Cell Adhesion KW - T-Lymphocytes -- cytology KW - Collagenases -- secretion KW - Collagenases -- biosynthesis KW - T-Lymphocytes -- secretion KW - T-Lymphocytes -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76116921?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+cellular+physiology&rft.atitle=Human+T+lymphocytes+synthesize+the+92+kDa+type+IV+collagenase+%28gelatinase+B%29.&rft.au=Weeks%2C+B+S%3BSchnaper%2C+H+W%3BHandy%2C+M%3BHolloway%2C+E%3BKleinman%2C+H+K&rft.aulast=Weeks&rft.aufirst=B&rft.date=1993-12-01&rft.volume=157&rft.issue=3&rft.spage=644&rft.isbn=&rft.btitle=&rft.title=Journal+of+cellular+physiology&rft.issn=00219541&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-01-13 N1 - Date created - 1994-01-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tolerance to the behavioral effects of chlordiazepoxide: pharmacological and biochemical selectivity. AN - 76116790; 8263795 AB - There is a dynamic interaction between a drug's pharmacological effects and the behavioral context in which it is administered. The present study evaluated the influence of behavioral processes on the development of tolerance and cross-tolerance to the rate-decreasing effects of chlordiazepoxide in rats. Sprague-Dawley rats responded under a fixed-ratio 30 schedule of food delivery. Different groups of rats received 18 mg/kg/day of chlordiazepoxide either before (PRE, n = 8) or after (POST, n = 10) daily experimental sessions for 8 weeks. Cumulative dose-response curves for chlordiazepoxide were obtained before and during chronic chlordiazepoxide administration and during chronic saline administration. Cumulative dose-response curves for midazolam, FG 7142 (N-methyl-beta-carboline-3-carboxamide) flumazenil, pentobarbital, caffeine, morphine and d-amphetamine were determined before, during and 4.5 to 5 months after chronic chlordiazepoxide administration. Group PRE developed tolerance to chlordiazepoxide, whereas group POST did not develop tolerance. Although cross-tolerance developed to midazolam in both groups, it was greater in group PRE. Both groups showed comparable sensitization to FG7142 and neither group showed a significant change in sensitivity to any of the other drugs. Biochemical studies of gamma-aminobutyric acid (GABA)-related functioning in groups of rats that received chronic chlordiazepoxide administration either before (BIO-PRE, n = 6) or after (BIO-POST, n = 6) daily sessions found that GABA-stimulated 36Cl-uptake increased in both cortical and cerebellar preparations. However, GABA sensitivity in cerebellar tissue was significantly lower in group BIO-PRE compared with group BIO-POST. Thus, behavioral tolerance to chlordiazepoxide was associated with both pharmacological and biochemical effects, which suggests a relationship between behavioral tolerance to benzodiazepines and changes in the functional state of the GABA-benzodiazepine receptor complex. JF - The Journal of pharmacology and experimental therapeutics AU - Sannerud, C A AU - Marley, R J AU - Serdikoff, S L AU - Alastra, A J AU - Cohen, C AU - Goldberg, S R AD - Behavioral Pharmacology and Genetics Section, National Institute on Drug Abuse, Baltimore, Maryland. Y1 - 1993/12// PY - 1993 DA - December 1993 SP - 1311 EP - 1320 VL - 267 IS - 3 SN - 0022-3565, 0022-3565 KW - Carbolines KW - 0 KW - Chlorides KW - Radioisotopes KW - Receptors, GABA-A KW - Caffeine KW - 3G6A5W338E KW - Flumazenil KW - 40P7XK9392 KW - Chlorine KW - 4R7X1O2820 KW - gamma-Aminobutyric Acid KW - 56-12-2 KW - FG 7142 KW - 60PO70N1BP KW - Chlordiazepoxide KW - 6RZ6XEZ3CR KW - Morphine KW - 76I7G6D29C KW - Amphetamine KW - CK833KGX7E KW - Pentobarbital KW - I4744080IR KW - Midazolam KW - R60L0SM5BC KW - Index Medicus KW - Sensitivity and Specificity KW - Animals KW - Dose-Response Relationship, Drug KW - gamma-Aminobutyric Acid -- pharmacology KW - Caffeine -- pharmacology KW - Midazolam -- pharmacology KW - Chlorides -- pharmacokinetics KW - Flumazenil -- pharmacology KW - Pentobarbital -- pharmacology KW - Morphine -- pharmacology KW - Stimulation, Chemical KW - Rats KW - Drug Tolerance KW - Rats, Sprague-Dawley KW - Receptors, GABA-A -- metabolism KW - Carbolines -- pharmacology KW - Amphetamine -- pharmacology KW - Chlorine -- pharmacokinetics KW - Male KW - Behavior, Animal -- drug effects KW - Chlordiazepoxide -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76116790?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Tolerance+to+the+behavioral+effects+of+chlordiazepoxide%3A+pharmacological+and+biochemical+selectivity.&rft.au=Sannerud%2C+C+A%3BMarley%2C+R+J%3BSerdikoff%2C+S+L%3BAlastra%2C+A+J%3BCohen%2C+C%3BGoldberg%2C+S+R&rft.aulast=Sannerud&rft.aufirst=C&rft.date=1993-12-01&rft.volume=267&rft.issue=3&rft.spage=1311&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 - 1994-01-27 N1 - Date created - 1994-01-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of verapamil on morphine-induced euphoria, analgesia and respiratory depression in humans. AN - 76115781; 8263800 AB - Organic calcium (Ca++) channel antagonists enhance opiate-induced analgesia and antagonize respiratory depression produced by morphine in rodents. Our preliminary data indicated that verapamil reduces the subjective effects of morphine in humans. We therefore assessed morphine-verapamil interactions in 12 experienced, male polydrug users with histories of heroin abuse by using a double-blind, cross-over study design. Treatments consisted of two drug infusions. Either verapamil, 2.5 or 10 mg, or saline was infused, 30 ml i.v. over 2 min; half way through this infusion either 10 mg of morphine or saline was infused, 3 ml i.v. over 10 sec, via a second catheter. Autonomic parameters, responsiveness to pain and subjective self-reports of mood and feeling state were measured over 4 hr. Analgesia was measured using a finger pressure test and hand immersion in ice water. Respiration was measured by using respiratory inductive plethysmography and transcutaneous CO2 levels. The Addiction Research Center Inventory (ARCI) was used to measure the subjective effects. Morphine had a liminal effect on pain threshold, but verapamil potentiated this effect to elevate pain threshold significantly. Verapamil did not affect the ability of morphine to increase pain endurance or to produce respiratory depression. Morphine produced positive affective responses, as demonstrated by elevated scores on the Morphine-Benzedrine Group subscale of the ARCI. Verapamil alone produced no effects on any ARCI subscales; however, 10 mg of verapamil significantly reduced morphine-elevated MBG scores over a 3-hr period. The results suggest the euphorigenic and analgesic effects of opioids may be differentiated by using Ca++ channel blockers. JF - The Journal of pharmacology and experimental therapeutics AU - Vaupel, D B AU - Lange, W R AU - London, E D AD - Neuroimaging and Drug Action Section, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland. Y1 - 1993/12// PY - 1993 DA - December 1993 SP - 1386 EP - 1394 VL - 267 IS - 3 SN - 0022-3565, 0022-3565 KW - Morphine KW - 76I7G6D29C KW - Verapamil KW - CJ0O37KU29 KW - Index Medicus KW - Analgesia KW - Pupil -- drug effects KW - Humans KW - Adult KW - Cardiovascular System -- drug effects KW - Drug Synergism KW - Male KW - Euphoria -- drug effects KW - Morphine -- adverse effects KW - Verapamil -- pharmacology KW - Respiration Disorders -- drug therapy KW - Respiration Disorders -- chemically induced KW - Morphine -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76115781?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Effects+of+verapamil+on+morphine-induced+euphoria%2C+analgesia+and+respiratory+depression+in+humans.&rft.au=Vaupel%2C+D+B%3BLange%2C+W+R%3BLondon%2C+E+D&rft.aulast=Vaupel&rft.aufirst=D&rft.date=1993-12-01&rft.volume=267&rft.issue=3&rft.spage=1386&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 - 1994-01-27 N1 - Date created - 1994-01-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Influence of previous exposure to levodopa on the interaction between dizocilpine and dopamine D1 and D2 agonists in rats with 6-hydroxydopamine-induced lesions. AN - 76113726; 7903390 AB - The potential antiparkinson activity of N-methyl-D-aspartate antagonists was investigated by examining the effects of dizocilpine (MK-801) on rats with 6-hydroxydopamine-induced lesions of the nigrostriatal pathway. MK-801, when administered alone to these animals, elicited ipsilateral rotation, which could be blocked by haloperidol. MK-801, at doses that did not produce rotation when given alone, inhibited the contralateral rotation produced by the D2 receptor agonist quinpirole but had no effect on the rotation induced by the D1 agonist SKF 38393 [(+-)-1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8- diolhydrochloride]. However, exposure to levodopa 3 days previously resulted in a subsensitive rotational response to SKF 38393 and this subsensitivity to the D1 agonist was reversed by MK-801. The subsensitive rotational response to SKF 38393 was not evident 7 days after exposure to levodopa and MK-801 had no effect on the response to SKF 38393 at this time. These data suggest that N-methyl-D-aspartate receptor blockade can exert differential effects on dopamine agonist-induced rotational behavior that depend on which dopamine receptor subtype is activated and the previous exposure of the animal to dopamine agonists. JF - The Journal of pharmacology and experimental therapeutics AU - Boldry, R C AU - Chase, T N AU - Engber, T M AD - Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland. Y1 - 1993/12// PY - 1993 DA - December 1993 SP - 1454 EP - 1459 VL - 267 IS - 3 SN - 0022-3565, 0022-3565 KW - Dopamine Agents KW - 0 KW - Receptors, Dopamine D1 KW - Receptors, Dopamine D2 KW - Levodopa KW - 46627O600J KW - N-Methylaspartate KW - 6384-92-5 KW - 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine KW - 67287-49-4 KW - Dizocilpine Maleate KW - 6LR8C1B66Q KW - Oxidopamine KW - 8HW4YBZ748 KW - Index Medicus KW - Rats KW - Behavior, Animal -- drug effects KW - Animals KW - Rats, Sprague-Dawley KW - Drug Interactions KW - Dose-Response Relationship, Drug KW - N-Methylaspartate -- antagonists & inhibitors KW - Motor Activity -- drug effects KW - 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine -- pharmacology KW - Parkinson Disease -- drug therapy KW - Male KW - Levodopa -- pharmacology KW - Receptors, Dopamine D1 -- physiology KW - Dopamine Agents -- pharmacology KW - Brain Diseases -- chemically induced KW - Receptors, Dopamine D2 -- drug effects KW - Receptors, Dopamine D1 -- drug effects KW - Receptors, Dopamine D2 -- physiology KW - Brain Diseases -- physiopathology KW - Dizocilpine Maleate -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76113726?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Influence+of+previous+exposure+to+levodopa+on+the+interaction+between+dizocilpine+and+dopamine+D1+and+D2+agonists+in+rats+with+6-hydroxydopamine-induced+lesions.&rft.au=Boldry%2C+R+C%3BChase%2C+T+N%3BEngber%2C+T+M&rft.aulast=Boldry&rft.aufirst=R&rft.date=1993-12-01&rft.volume=267&rft.issue=3&rft.spage=1454&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 - 1994-01-27 N1 - Date created - 1994-01-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Risk factors for cancers of the nasal cavity and paranasal sinuses among white men in the United States. AN - 76112691; 8256781 AB - A case-control analysis of cancer of the nasal cavity and sinuses was performed using data from the 1986 National Mortality Followback Survey. Data on cigarette smoking, alcohol consumption, usual diet, and other factors from 147 white men who died from nasal cancer and from 449 controls who died from other causes were compared. Cigarette smoking was related to an increased risk of nasal cancer, with a doubling of risk among heavy or long-term smokers and a reduction in risk among long-term quitters. Among nonsmokers, having a spouse who smoked was associated with a significantly elevated risk of nasal cancer. After adjustment for smoking, a significant dose-response relation was also noted between alcohol drinking and risk of nasal cancer. High consumption of salted/smoked foods was associated with elevated risk, and risk tended to decrease with increasing intake of vegetables. Associations were more pronounced for cigarette smoking and certain dietary items when the analysis was restricted to maxillary sinus cancer. The study confirms that cigarette smoking is a risk factor for nasal cancer, and provides further evidence that dietary factors may play a role in the etiology of this malignancy. JF - American journal of epidemiology AU - Zheng, W AU - McLaughlin, J K AU - Chow, W H AU - Chien, H T AU - Blot, W J AD - National Cancer Institute, Division of Cancer Etiology, Bethesda, MD. Y1 - 1993/12/01/ PY - 1993 DA - 1993 Dec 01 SP - 965 EP - 972 VL - 138 IS - 11 SN - 0002-9262, 0002-9262 KW - Tobacco Smoke Pollution KW - 0 KW - Index Medicus KW - Odds Ratio KW - Sex Factors KW - Humans KW - Alcohol Drinking -- adverse effects KW - Smoking -- adverse effects KW - Aged KW - Alcohol Drinking -- epidemiology KW - Smoking -- epidemiology KW - Diet -- adverse effects KW - Logistic Models KW - Risk Factors KW - Health Surveys KW - Tobacco Smoke Pollution -- adverse effects KW - Case-Control Studies KW - Middle Aged KW - United States -- epidemiology KW - Male KW - Paranasal Sinus Neoplasms -- etiology KW - Nose Neoplasms -- etiology KW - Paranasal Sinus Neoplasms -- mortality KW - Nose Neoplasms -- mortality KW - European Continental Ancestry Group -- statistics & numerical data UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76112691?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+epidemiology&rft.atitle=Risk+factors+for+cancers+of+the+nasal+cavity+and+paranasal+sinuses+among+white+men+in+the+United+States.&rft.au=Zheng%2C+W%3BMcLaughlin%2C+J+K%3BChow%2C+W+H%3BChien%2C+H+T%3BBlot%2C+W+J&rft.aulast=Zheng&rft.aufirst=W&rft.date=1993-12-01&rft.volume=138&rft.issue=11&rft.spage=965&rft.isbn=&rft.btitle=&rft.title=American+journal+of+epidemiology&rft.issn=00029262&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-01-13 N1 - Date created - 1994-01-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - p53 mutations in lung cancers from non-smoking atomic-bomb survivors. AN - 76112564; 7902903 AB - Tobacco smoke contains many carcinogens and has been linked with the development of lung cancer. We sequenced the conserved regions of the p53 tumour suppressor gene in lung cancers from 17 non-smokers from Hiroshima, Japan; 9 were atomic-bomb survivors. The mutations were predominantly transitions (all G:C to A:T); there were no G:C to T:A transversions. By contrast, lung cancers from 77 Japanese smokers have a predominance of G:C to T:A transversions in which the guanine residues occur on the non-transcribed DNA strand. These findings further implicate tobacco smoke carcinogens in the molecular pathogenesis of lung cancer. JF - Lancet (London, England) AU - Takeshima, Y AU - Seyama, T AU - Bennett, W P AU - Akiyama, M AU - Tokuoka, S AU - Inai, K AU - Mabuchi, K AU - Land, C E AU - Harris, C C AD - National Cancer Institute, National Institutes of Health, Bethesda, Maryland. PY - 1993 SP - 1520 EP - 1521 VL - 342 IS - 8886-8887 SN - 0140-6736, 0140-6736 KW - genes, p53 KW - Abridged Index Medicus KW - Index Medicus KW - Smoking KW - Humans KW - DNA Mutational Analysis KW - Adult KW - Retrospective Studies KW - Aged KW - Middle Aged KW - Japan KW - Genes, p53 KW - Nuclear Warfare KW - Lung Neoplasms -- genetics KW - Neoplasms, Radiation-Induced -- genetics KW - Mutation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76112564?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=p53+mutations+in+lung+cancers+from+non-smoking+atomic-bomb+survivors.&rft.au=Takeshima%2C+Y%3BSeyama%2C+T%3BBennett%2C+W+P%3BAkiyama%2C+M%3BTokuoka%2C+S%3BInai%2C+K%3BMabuchi%2C+K%3BLand%2C+C+E%3BHarris%2C+C+C&rft.aulast=Takeshima&rft.aufirst=Y&rft.date=1993-12-01&rft.volume=342&rft.issue=8886-8887&rft.spage=1520&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 - 1994-01-12 N1 - Date created - 1994-01-12 N1 - Date revised - 2017-01-13 N1 - Gene symbol - genes, p53 N1 - SuppNotes - Erratum In: Lancet 1994 May 21;343(8908):1302 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cytotoxic studies of paclitaxel (Taxol) in human tumour cell lines. AN - 76111931; 7903152 AB - The cytotoxicity of paclitaxel against eight human tumour cell lines has been studied with in vitro clonogenic assays. The fraction of surviving cells fell sharply after exposure for 24 h to paclitaxel concentrations ranging from 2 to 20 nM; the paclitaxel IC50 was found to range between 2.5 and 7.5 nM. Increasing the paclitaxel concentration above 50 nM, however, resulted in no additional cytotoxicity after a 24 h drug exposure. Cells incubated in very high concentrations of paclitaxel (10,000 nM) had an increase in survival compared with cells treated with lower concentrations of the drug. Prolonging the time of exposure of cells to paclitaxel from 24 to 72 h increased cytotoxicity from 5 to 200 fold in different cell lines. Exponentially growing cells were more sensitive to paclitaxel than were cells in the plateau phase of growth. Cremophor EL, the diluent in which the clinical preparation of paclitaxel is formulated, antagonised paclitaxel at concentrations of 0.135% (v/v). These data suggest that paclitaxel will be most effective clinically when there is prolonged exposure of tumour to the drug. Further, it appears that modest concentrations (i.e., 50 nM) should be as effective as higher concentrations of paclitaxel. Finally, we have noted that Cremophor EL is a biologically active diluent and, at high concentrations (0.135% v/v), can antagonise paclitaxel cytotoxicity. JF - British journal of cancer AU - Liebmann, J E AU - Cook, J A AU - Lipschultz, C AU - Teague, D AU - Fisher, J AU - Mitchell, J B AD - Radiation Oncology Branch, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1993/12// PY - 1993 DA - December 1993 SP - 1104 EP - 1109 VL - 68 IS - 6 SN - 0007-0920, 0007-0920 KW - cremophor EL KW - 6D4M1DAL6O KW - Paclitaxel KW - P88XT4IS4D KW - Glycerol KW - PDC6A3C0OX KW - Index Medicus KW - Ovarian Neoplasms -- metabolism KW - Adenocarcinoma -- metabolism KW - Pancreatic Neoplasms -- metabolism KW - HeLa Cells -- drug effects KW - Dose-Response Relationship, Drug KW - Humans KW - Astrocytoma -- metabolism KW - Breast Neoplasms -- metabolism KW - Cell Survival -- drug effects KW - Uterine Cervical Neoplasms -- metabolism KW - Glycerol -- analogs & derivatives KW - Colonic Neoplasms -- metabolism KW - Female KW - Glycerol -- pharmacology KW - Lung Neoplasms -- metabolism KW - Paclitaxel -- administration & dosage KW - Paclitaxel -- antagonists & inhibitors KW - Paclitaxel -- toxicity KW - Tumor Cells, Cultured -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76111931?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=British+journal+of+cancer&rft.atitle=Cytotoxic+studies+of+paclitaxel+%28Taxol%29+in+human+tumour+cell+lines.&rft.au=Liebmann%2C+J+E%3BCook%2C+J+A%3BLipschultz%2C+C%3BTeague%2C+D%3BFisher%2C+J%3BMitchell%2C+J+B&rft.aulast=Liebmann&rft.aufirst=J&rft.date=1993-12-01&rft.volume=68&rft.issue=6&rft.spage=1104&rft.isbn=&rft.btitle=&rft.title=British+journal+of+cancer&rft.issn=00070920&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-01-21 N1 - Date created - 1994-01-21 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nature. 1979 Feb 22;277(5698):665-7 [423966] Cancer Res. 1993 May 1;53(9):2066-70 [8097674] Cancer Res. 1981 Jun;41(6):2328-33 [7237431] J Natl Cancer Inst. 1981 Aug;67(2):437-43 [6943380] Pharmacol Ther. 1984;25(1):83-125 [6149569] Cancer Chemother Pharmacol. 1986;17(2):137-42 [2872974] Ann N Y Acad Sci. 1986;466:733-44 [2873780] Cancer Res. 1987 Feb 15;47(4):936-42 [3802100] Cancer Res. 1988 Jul 15;48(14):4093-100 [2898289] Cancer Res. 1989 Aug 15;49(16):4640-7 [2568175] Anal Biochem. 1989 May 15;179(1):1-7 [2667390] Ann Intern Med. 1989 Aug 15;111(4):273-9 [2569287] Cancer Res. 1990 Jul 15;50(14):4199-203 [2364376] J Natl Cancer Inst. 1990 Aug 1;82(15):1247-59 [1973737] J Natl Cancer Inst. 1991 Dec 18;83(24):1797-805 [1683908] Anticancer Res. 1991 Jul-Aug;11(4):1517-21 [1746908] J Clin Oncol. 1992 Sep;10(9):1485-91 [1355523] Biochem Biophys Res Commun. 1992 Aug 31;187(1):164-70 [1381586] Proc Natl Acad Sci U S A. 1980 Mar;77(3):1561-5 [6103535] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Motor response complications and the function of striatal efferent systems. AN - 76111344; 8264907 AB - Motor response complications eventually appear in most patients with advanced Parkinson's disease being treated with levodopa. The interval between onset of parkinsonism and emergence of these adverse events appears independent of the dose or the duration of therapy. Current evidence suggests that "wearing-off" fluctuations largely reflect the loss of normally functioning dopaminergic terminals, although postsynaptic alterations contribute somewhat to the underlying decline in the duration of levodopa's antiparkinsonian action. "On-off" fluctuations and peak-dose dyskinesias, on the other hand, appear to arise mainly as a consequence of postjunctional alterations that follow exposure to nonphysiologic intrasynaptic dopamine fluctuations in patients who have lost the buffering afforded by dopaminergic terminals. Studies in rats with 6-hydroxydopamine lesions indicate that striking functional alterations occur in striatal dopaminoceptive systems as a result of dopaminergic denervation and that levodopa replacement, particularly when given intermittently, fails to normalize these changes. To the extent that similar alterations contribute to the appearance of motor complications, the successful symptomatic therapy of Parkinson's disease may require continuous dopaminergic stimulation, as well as direct pharmacologic targeting of striatal dopaminoceptive systems. JF - Neurology AU - Chase, T N AU - Mouradian, M M AU - Engber, T M AD - Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/12// PY - 1993 DA - December 1993 SP - S23 EP - S27 VL - 43 IS - 12 Suppl 6 SN - 0028-3878, 0028-3878 KW - Levodopa KW - 46627O600J KW - Abridged Index Medicus KW - Index Medicus KW - Rats KW - Animals KW - Humans KW - Levodopa -- therapeutic use KW - Levodopa -- adverse effects KW - Corpus Striatum -- physiopathology KW - Corpus Striatum -- drug effects KW - Parkinson Disease -- physiopathology KW - Neurons, Efferent -- physiology KW - Muscles -- physiopathology KW - Parkinson Disease -- drug therapy KW - Neurons, Efferent -- drug effects KW - Muscles -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76111344?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurology&rft.atitle=Motor+response+complications+and+the+function+of+striatal+efferent+systems.&rft.au=Chase%2C+T+N%3BMouradian%2C+M+M%3BEngber%2C+T+M&rft.aulast=Chase&rft.aufirst=T&rft.date=1993-12-01&rft.volume=43&rft.issue=12+Suppl+6&rft.spage=S23&rft.isbn=&rft.btitle=&rft.title=Neurology&rft.issn=00283878&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-01-26 N1 - Date created - 1994-01-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - 2'-NH2-MPTP in Swiss Webster mice: evidence for long-term (6-month) depletions in cortical and hippocampal serotonin and norepinephrine, differential protection by selective uptake inhibitors or clorgyline and functional changes in central serotonin neurotransmission. AN - 76111041; 8263805 AB - The i.p. administration of 1-methyl-4-(2'-aminophenyl)-1,2,3,6-tetrahydropyridine (2'-NH2-MPTP; 4 x 20 mg/kg) to Swiss Webster mice caused substantial decreases in cortical and hippocampal 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid and norepinephrine (NE) measured 1 week post-treatment. Compared with the authors' previously reported results in C57BL/6 mice, these effects were significantly greater in hippocampus (80-90% vs. 60%) and of a similar magnitude in frontal cortex (60-75%). A long-term study showed that cortical and hippocampal 5-HT, 5-hydroxyindoleacetic acid and NE were still decreased 40% to 50% 6 months after treatment. Regional brain dopamine was essentially unchanged during the 6-month period. Pretreatment with the 5-HT-selective uptake inhibitors, fluoxetine or paroxetine, or with the NE-selective uptake inhibitor, desipramine, prevented decreases in cortical and hippocampal 5-HT and NE, respectively, 3 weeks after 2'-NH2-MPTP (4 x 20 mg/kg). In addition, pretreatment with the monoamine oxidase type-A inhibitor, clorgyline, also prevented the more modest decreases in 5-HT and NE caused by 4 x 15 mg/kg 2'-NH2-MPTP. Selegiline, a monoamine oxidase-B inhibitor, did not provide similar protection. Lastly, 2'-NH2-MPTP administered 3 weeks earlier, abolished hypothermia caused by the serotonin agonist, m-chlorophenylpiperazine, which provided preliminary evidence for an associated functional change in the central serotonergic system. Together, these data suggest that 2'-NH2-MPTP is a novel agent capable of producing long-lasting depletions in forebrain 5-HT and NE but not dopamine in two different strains of mice by some mechanisms that resemble those of the parent dopamine-depleting neurotoxin, MPTP. JF - The Journal of pharmacology and experimental therapeutics AU - Andrews, A M AU - Murphy, D L AD - Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, Maryland. Y1 - 1993/12// PY - 1993 DA - December 1993 SP - 1432 EP - 1439 VL - 267 IS - 3 SN - 0022-3565, 0022-3565 KW - Monoamine Oxidase Inhibitors KW - 0 KW - Neurotransmitter Uptake Inhibitors KW - Serotonin Receptor Agonists KW - Fluoxetine KW - 01K63SUP8D KW - 1-methyl-4-(2'-aminophenyl)-1,2,3,6-tetrahydropyridine KW - 108114-93-8 KW - Selegiline KW - 2K1V7GP655 KW - Serotonin KW - 333DO1RDJY KW - Paroxetine KW - 41VRH5220H KW - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine KW - 9P21XSP91P KW - Clorgyline KW - LYJ16FZU9Q KW - Desipramine KW - TG537D343B KW - Norepinephrine KW - X4W3ENH1CV KW - Index Medicus KW - Serotonin Receptor Agonists -- pharmacology KW - Animals KW - Selegiline -- pharmacology KW - Fluoxetine -- pharmacology KW - Desipramine -- pharmacology KW - MPTP Poisoning KW - Mice KW - Time Factors KW - Paroxetine -- pharmacology KW - Monoamine Oxidase Inhibitors -- pharmacology KW - Male KW - Cerebral Cortex -- drug effects KW - Serotonin -- physiology KW - Cerebral Cortex -- metabolism KW - Hippocampus -- physiology KW - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine -- metabolism KW - Synaptic Transmission -- drug effects KW - Hippocampus -- metabolism KW - Synaptic Transmission -- physiology KW - Hippocampus -- drug effects KW - Cerebral Cortex -- physiology KW - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine -- analogs & derivatives KW - Neurotransmitter Uptake Inhibitors -- pharmacology KW - Norepinephrine -- metabolism KW - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine -- pharmacology KW - Clorgyline -- pharmacology KW - Serotonin -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76111041?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=2%27-NH2-MPTP+in+Swiss+Webster+mice%3A+evidence+for+long-term+%286-month%29+depletions+in+cortical+and+hippocampal+serotonin+and+norepinephrine%2C+differential+protection+by+selective+uptake+inhibitors+or+clorgyline+and+functional+changes+in+central+serotonin+neurotransmission.&rft.au=Andrews%2C+A+M%3BMurphy%2C+D+L&rft.aulast=Andrews&rft.aufirst=A&rft.date=1993-12-01&rft.volume=267&rft.issue=3&rft.spage=1432&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 - 1994-01-27 N1 - Date created - 1994-01-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evidence of two levels of control of P1 oriR and host oriC replication origins by DNA adenine methylation. AN - 76109156; 8253669 AB - A mutant mini-P1 plasmid with increased copy number can be established in Dam- strains of Escherichia coli, where mini-P1 plasmid replication is normally blocked. Comparison of this plasmid and a plasmid driven by the host oriC replication origin showed that both origins are subject to control by methylation at two different levels. First, both origins appear to be subject to negative regulation acting at the level of hemimethylation. This probably involves the sequestration of the hemimethylated DNA produced by replication, as has been previously described for oriC. Second, both origins show a positive requirement for adenine methylation for efficient function in vivo. This conclusion is supported by the behavior of the P1 origin in an improved in vitro replication system. In vitro, where sequestration of hemimethylated DNA is not expected to occur, the hemimethylated P1 origin DNA was fully functional as a template. However, the activity of fully unmethylated DNA was severely restricted in comparison with that of either of the methylated forms. This in vitro uncoupling of the two effects of origin methylation suggests that two separate mechanisms are involved. JF - Journal of bacteriology AU - Abeles, A AU - Brendler, T AU - Austin, S AD - Laboratory of Chromosome Biology, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland 21701-1201. Y1 - 1993/12// PY - 1993 DA - December 1993 SP - 7801 EP - 7807 VL - 175 IS - 24 SN - 0021-9193, 0021-9193 KW - DNA, Bacterial KW - 0 KW - Site-Specific DNA-Methyltransferase (Adenine-Specific) KW - EC 2.1.1.72 KW - Adenine KW - JAC85A2161 KW - Index Medicus KW - Bacteriophage T4 -- enzymology KW - Blotting, Southern KW - Transformation, Genetic KW - Templates, Genetic KW - Repetitive Sequences, Nucleic Acid KW - Methylation KW - Mutagenesis KW - Escherichia coli -- metabolism KW - Adenine -- metabolism KW - DNA, Bacterial -- biosynthesis KW - Escherichia coli -- genetics KW - Site-Specific DNA-Methyltransferase (Adenine-Specific) -- metabolism KW - Plasmids KW - DNA Replication UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76109156?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+bacteriology&rft.atitle=Evidence+of+two+levels+of+control+of+P1+oriR+and+host+oriC+replication+origins+by+DNA+adenine+methylation.&rft.au=Abeles%2C+A%3BBrendler%2C+T%3BAustin%2C+S&rft.aulast=Abeles&rft.aufirst=A&rft.date=1993-12-01&rft.volume=175&rft.issue=24&rft.spage=7801&rft.isbn=&rft.btitle=&rft.title=Journal+of+bacteriology&rft.issn=00219193&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-01-10 N1 - Date created - 1994-01-10 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Bacteriol. 1989 Oct;171(10):5738-42 [2676991] Genetics. 1962 Sep;47:1219-24 [13955138] Mol Gen Genet. 1989 Oct;219(1-2):69-74 [2693949] J Bacteriol. 1990 Aug;172(8):4386-91 [2165477] Cold Spring Harb Symp Quant Biol. 1979;43 Pt 1:121-8 [383376] Cold Spring Harb Symp Quant Biol. 1979;43 Pt 1:139-45 [157832] Gene. 1979 May;6(1):23-8 [383576] Mol Gen Genet. 1979;177(1):65-72 [231729] Proc Natl Acad Sci U S A. 1981 Dec;78(12):7370-4 [6278471] Nucleic Acids Res. 1983 Feb 11;11(3):837-51 [6300769] Proc Natl Acad Sci U S A. 1983 Aug;80(15):4639-43 [6308634] J Mol Biol. 1983 Sep 15;169(2):373-87 [6225875] J Mol Biol. 1984 Mar 5;173(3):307-24 [6699914] J Mol Biol. 1984 Jun 15;176(1):155-9 [6330369] EMBO J. 1984 Dec 1;3(12):2863-71 [6098451] EMBO J. 1985 May;4(5):1319-26 [3891329] J Bacteriol. 1986 Mar;165(3):896-900 [3512529] J Biol Chem. 1986 Mar 15;261(8):3548-55 [3949778] Mol Gen Genet. 1986 Feb;202(2):246-50 [3010047] Proc Natl Acad Sci U S A. 1986 Jun;83(12):4423-7 [3520571] Mol Gen Genet. 1986 Oct;205(1):115-21 [3025553] J Mol Biol. 1986 Nov 20;192(2):275-85 [3560217] Proc Natl Acad Sci U S A. 1987 Mar;84(6):1482-6 [3550791] Proc Natl Acad Sci U S A. 1987 Jun;84(12):4171-5 [2438693] Cell. 1987 Sep 25;50(7):1071-9 [3304662] EMBO J. 1987 Oct;6(10):3185-9 [2826133] Cell. 1988 Jul 1;54(1):127-35 [2838178] Nucleic Acids Res. 1988 Jun 10;16(11):5067-73 [3290846] J Biol Chem. 1988 Aug 5;263(22):10625-32 [2839499] Gene. 1988 Dec 20;73(2):531-5 [2854098] Cell. 1990 Sep 7;62(5):967-79 [1697508] Cell. 1990 Sep 7;62(5):981-9 [2203541] Cell. 1990 Nov 30;63(5):1053-60 [2257623] J Bacteriol. 1991 Jul;173(13):3935-42 [2061278] J Bacteriol. 1991 Jul;173(14):4537-9 [2066345] J Mol Biol. 1989 Sep 5;209(1):79-90 [2478715] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Autocrine induction of c-fos expression in GT1 neuronal cells by gonadotropin-releasing hormone. AN - 76103566; 8243334 AB - Activation of GnRH receptors in GnRH neuronal (GT1-7) cells causes marked and transient increases in c-fos expression, with peak response at 30 min. GnRH and des-Gly10-[D-Ala6]GnRH N-ethylamide induced concentration-dependent c-fos responses with EC50s of approximately 0.1 and approximately 1 nM, respectively. GnRH action was mimicked by phorbol 12-myristate-13-acetate (PMA), but stimulation of Ca2+ entry by K(+)-induced depolarization and Bay K 8644 was much less effective. In protein kinase C-depleted cells, the c-fos response to GnRH was reduced to that elicited by increased Ca2+ entry, and the effect of PMA was abolished. Thus, GnRH-induced c-fos expression in GT1 cells appears to be mediated predominantly by protein kinase C, and to a lesser extent by Ca2+. These findings demonstrate that c-fos expression can be induced in a peptidergic neuron by activation of receptors for its neurosecretory product. It is possible that the expression of c-fos in GnRH hypothalamic neurons during the proestrous surge of gonadotropins could likewise be stimulated by a positive feedback action of GnRH on its neuronal receptors. JF - Endocrinology AU - Cesnjaj, M AU - Krsmanovic, L Z AU - Catt, K J 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. Y1 - 1993/12// PY - 1993 DA - December 1993 SP - 3042 EP - 3045 VL - 133 IS - 6 SN - 0013-7227, 0013-7227 KW - Proto-Oncogene Proteins c-fos KW - 0 KW - RNA, Messenger KW - Gonadotropin-Releasing Hormone KW - 33515-09-2 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Abridged Index Medicus KW - Index Medicus KW - Protein Kinase C -- antagonists & inhibitors KW - RNA, Messenger -- metabolism KW - Dose-Response Relationship, Drug KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Cell Line, Transformed KW - Neurons -- metabolism KW - Proto-Oncogene Proteins c-fos -- genetics KW - Neurons -- physiology KW - Gene Expression Regulation -- drug effects KW - Gonadotropin-Releasing Hormone -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76103566?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Autocrine+induction+of+c-fos+expression+in+GT1+neuronal+cells+by+gonadotropin-releasing+hormone.&rft.au=Cesnjaj%2C+M%3BKrsmanovic%2C+L+Z%3BCatt%2C+K+J%3BStojilkovic%2C+S+S&rft.aulast=Cesnjaj&rft.aufirst=M&rft.date=1993-12-01&rft.volume=133&rft.issue=6&rft.spage=3042&rft.isbn=&rft.btitle=&rft.title=Endocrinology&rft.issn=00137227&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-01-06 N1 - Date created - 1994-01-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Quinolinic acid in the cerebrospinal fluid of children with symptomatic human immunodeficiency virus type 1 disease: relationships to clinical status and therapeutic response. AN - 76098190; 8245522 AB - Quinolinic acid (QUIN) is a neurotoxin implicated in the neurologic deficits associated with human immunodeficiency virus type 1 (HIV-1) infection. Forty children with symptomatic HIV-1 disease had elevated (P < .001) cerebrospinal fluid (CSF) QUIN levels (55.8 +/- 8.9 nM) compared with controls (14.9 +/- 3.0 nM). Age-adjusted CSF QUIN concentrations in HIV-1-infected children were predicted by the general index of mental abilities (GIMA, from an age-appropriate intelligence test; r = -0.45, P < .01). Zidovudine therapy reduced CSF QUIN from 64.1 +/- 16.3 to 19.7 +/- 5.2 nM (P < .01; N = 16) and increased GIMA from 76.8 +/- 5.2 to 87.2 +/- 6.3 (P < .001). Encephalopathic HIV-1-infected patients had higher CSF QUIN levels than patients without encephalopathy (79.6 +/- 16.1 vs. 32.7 +/- 6.7 nM, P < .01). CSF QUIN concentrations were also higher (P < .001) in patients who died < or = 3 years after their baseline assessment, compared with those who were still alive. These results warrant further investigation of CSF QUIN in HIV-infected children as a mediator of neurologic dysfunction and a supplemental marker of neurologic disease, particularly when combined with measures of neurocognitive functioning. JF - The Journal of infectious diseases AU - Brouwers, P AU - Heyes, M P AU - Moss, H A AU - Wolters, P L AU - Poplack, D G AU - Markey, S P AU - Pizzo, P A AD - Pediatric Branch, National Cancer Institute, NIH Clinical Center, Bethesda, MD 20892. Y1 - 1993/12// PY - 1993 DA - December 1993 SP - 1380 EP - 1386 VL - 168 IS - 6 SN - 0022-1899, 0022-1899 KW - Zidovudine KW - 4B9XT59T7S KW - Quinolinic Acid KW - F6F0HK1URN KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Infant KW - Analysis of Variance KW - AIDS Dementia Complex -- cerebrospinal fluid KW - Humans KW - Child KW - Male KW - Female KW - Cognition KW - Child, Preschool KW - Zidovudine -- therapeutic use KW - Acquired Immunodeficiency Syndrome -- physiopathology KW - Quinolinic Acid -- cerebrospinal fluid KW - Acquired Immunodeficiency Syndrome -- drug therapy KW - Acquired Immunodeficiency Syndrome -- mortality KW - HIV-1 KW - Acquired Immunodeficiency Syndrome -- cerebrospinal fluid UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76098190?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Quinolinic+acid+in+the+cerebrospinal+fluid+of+children+with+symptomatic+human+immunodeficiency+virus+type+1+disease%3A+relationships+to+clinical+status+and+therapeutic+response.&rft.au=Brouwers%2C+P%3BHeyes%2C+M+P%3BMoss%2C+H+A%3BWolters%2C+P+L%3BPoplack%2C+D+G%3BMarkey%2C+S+P%3BPizzo%2C+P+A&rft.aulast=Brouwers&rft.aufirst=P&rft.date=1993-12-01&rft.volume=168&rft.issue=6&rft.spage=1380&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 - 1993-12-28 N1 - Date created - 1993-12-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In vivo ESR spin trapping evidence for hydroxyl radical-mediated toxicity of paraquat and copper in rats. AN - 76085197; 8248925 AB - The electron spin resonance (ESR) spin trapping technique was employed to study the role of Cu(II) in the generation of hydroxyl radical during paraquat (PQ2+) intoxication in rats. A secondary radical trapping technique was used for the detection of hydroxyl radical generated in vivo during copper-mediated PQ2+ toxicity. According to this technique (Burkitt and Mason, Proc. Natl. Acad. Sci. USA 88, 8440-8444, 1991), the hydroxyl radical generated reacts with dimethyl sulfoxide (DMSO) in vivo to form the methyl radical, which is then spin trapped by phenyl-N-tert-butylnitrone (PBN). The relatively stable methyl radical adduct of PBN was detected in the bile of rats 2 hr after treatment with simultaneous doses of CuSO4, PQ2+, PBN, and DMSO, whereas no radical adducts were detected in the absence of administered PQ2+. Bile samples were collected into Cu(I)- and Fe(II)-stabilizing agents in order to prevent the occurrence of radical adducts generated ex vivo in bile during its collection. The analysis of radical adducts excreted via the biliary route provide strong ESR evidence for the generation of the hydroxyl radical as a result of the known futile enzymatic redox cycling of PQ2+, with copper playing an essential mediatory role. No radical adducts were detected when either CuSO4 or PQ2+ was excluded. From a different perspective, in vivo copper-dependent hydroxyl radical generation could be said to be promoted by PQ2+. This is the first report of ESR evidence for this synergetic hydroxyl radical generation by copper and PQ2+ in a whole animal. JF - Toxicology and applied pharmacology AU - Kadiiska, M B AU - Hanna, P M AU - Mason, R P AD - National Institutes of Health, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1993/12// PY - 1993 DA - December 1993 SP - 187 EP - 192 VL - 123 IS - 2 SN - 0041-008X, 0041-008X KW - Hydroxyl Radical KW - 3352-57-6 KW - Copper KW - 789U1901C5 KW - Paraquat KW - PLG39H7695 KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Electron Spin Resonance Spectroscopy KW - Male KW - Hydroxyl Radical -- metabolism KW - Copper -- toxicity KW - Paraquat -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76085197?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=In+vivo+ESR+spin+trapping+evidence+for+hydroxyl+radical-mediated+toxicity+of+paraquat+and+copper+in+rats.&rft.au=Kadiiska%2C+M+B%3BHanna%2C+P+M%3BMason%2C+R+P&rft.aulast=Kadiiska&rft.aufirst=M&rft.date=1993-12-01&rft.volume=123&rft.issue=2&rft.spage=187&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 - 1994-01-05 N1 - Date created - 1994-01-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Paclitaxel for platinum-refractory ovarian cancer: results from the first 1,000 patients registered to National Cancer Institute Treatment Referral Center 9103. AN - 76082520; 7902426 AB - To provide an investigational drug, paclitaxel, now commercially available, to women with refractory ovarian cancer and to evaluate response and toxicity in these patients. Patients with platinum-refractory ovarian cancer, Eastern Cooperative Oncology Group (ECOG) performance status 0 to 3, at least three prior chemotherapy regimens, adequate hepatic and renal function, and no significant cardiac history were eligible. Patients were treated with paclitaxel 135 mg/m2 administered by 24-hour continuous intravenous infusion every 3 weeks. Leukopenia was the most frequent toxicity, with 78% of patients experiencing grade 3 or 4 toxicity. Other grade 3 and 4 toxicities were less common: fever (33%), infection (12%), thrombocytopenia (8%), vomiting (7%), cardiac (2%), neurologic (2%), and mucositis (1%). Fifteen treatment-related deaths (1.5%) were reported. The objective response rate was 22% (4% complete response [CR], 18% partial response; 95% confidence interval [CI] for overall response, 19% to 25%). The median time to progression from treatment initiation was 7.1 months in responding patients and 4.5 months for all patients. The median survival duration was 8.8 months. Paclitaxel has shown activity in women with platinum-refractory ovarian cancer, and it can be administered with an acceptable safety profile. Further research is needed to determine the optimal role of paclitaxel in the primary and salvage treatment of ovarian cancer. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Trimble, E L AU - Adams, J D AU - Vena, D AU - Hawkins, M J AU - Friedman, M A AU - Fisherman, J S AU - Christian, M C AU - Canetta, R AU - Onetto, N AU - Hayn, R AD - Clinical Investigation Branch, National Cancer Institute, Rockville, MD 20852. Y1 - 1993/12// PY - 1993 DA - December 1993 SP - 2405 EP - 2410 VL - 11 IS - 12 SN - 0732-183X, 0732-183X KW - Antineoplastic Agents KW - 0 KW - Platinum Compounds KW - Paclitaxel KW - P88XT4IS4D KW - Index Medicus KW - Life Tables KW - Infusions, Intravenous KW - Aged, 80 and over KW - Humans KW - Adult KW - Drug Resistance KW - Aged KW - Middle Aged KW - Platinum Compounds -- therapeutic use KW - Antineoplastic Agents -- therapeutic use KW - Female KW - Survival Analysis KW - Paclitaxel -- administration & dosage KW - Paclitaxel -- adverse effects KW - Carcinoma -- drug therapy KW - Paclitaxel -- therapeutic use KW - Ovarian Neoplasms -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76082520?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Paclitaxel+for+platinum-refractory+ovarian+cancer%3A+results+from+the+first+1%2C000+patients+registered+to+National+Cancer+Institute+Treatment+Referral+Center+9103.&rft.au=Trimble%2C+E+L%3BAdams%2C+J+D%3BVena%2C+D%3BHawkins%2C+M+J%3BFriedman%2C+M+A%3BFisherman%2C+J+S%3BChristian%2C+M+C%3BCanetta%2C+R%3BOnetto%2C+N%3BHayn%2C+R&rft.aulast=Trimble&rft.aufirst=E&rft.date=1993-12-01&rft.volume=11&rft.issue=12&rft.spage=2405&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 - 1993-12-23 N1 - Date created - 1993-12-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A human mitochondrial ATP-dependent protease that is highly homologous to bacterial Lon protease. AN - 76081160; 8248235 AB - We have cloned a human ATP-dependent protease that is highly homologous to members of the bacterial Lon protease family. The cloned gene encodes a protein of 963 amino acids with a calculated molecular mass of 106 kDa, slightly higher than that observed by Western blotting the protein from human tissues and cell lines (100 kDa). A single species of mRNA was found for this Lon protease in all human tissues examined. The protease is encoded in the nucleus, and the amino-terminal portion of the protein sequence contains a potential mitochondrial targeting presequence. Immunofluorescence microscopy suggested a predominantly mitochondrial localization for the Lon protease in cultured human cells. A truncated LON gene, in which translation was initiated at Met118 of the coding sequence, was expressed in Escherichia coli and produced a protease that degraded alpha-casein in vitro in an ATP-dependent manner and had other properties similar to E. coli Lon protease. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Wang, N AU - Gottesman, S AU - Willingham, M C AU - Gottesman, M M AU - Maurizi, M R AD - Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/12/01/ PY - 1993 DA - 1993 Dec 01 SP - 11247 EP - 11251 VL - 90 IS - 23 SN - 0027-8424, 0027-8424 KW - lon KW - DNA, Complementary KW - 0 KW - Escherichia coli Proteins KW - Heat-Shock Proteins KW - ATP-Dependent Proteases KW - EC 3.4.21.- KW - Serine Endopeptidases KW - Lon protein, E coli KW - EC 3.4.21.53 KW - Protease La KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Blotting, Western KW - Base Sequence KW - DNA, Complementary -- genetics KW - Sequence Alignment KW - Humans KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Tissue Distribution KW - Sequence Homology, Amino Acid KW - Structure-Activity Relationship KW - Cloning, Molecular KW - Heat-Shock Proteins -- metabolism KW - Genes KW - Serine Endopeptidases -- metabolism KW - Serine Endopeptidases -- genetics KW - Mitochondria -- enzymology KW - Serine Endopeptidases -- chemistry KW - Heat-Shock Proteins -- genetics KW - Heat-Shock Proteins -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76081160?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+human+mitochondrial+ATP-dependent+protease+that+is+highly+homologous+to+bacterial+Lon+protease.&rft.au=Wang%2C+N%3BGottesman%2C+S%3BWillingham%2C+M+C%3BGottesman%2C+M+M%3BMaurizi%2C+M+R&rft.aulast=Wang&rft.aufirst=N&rft.date=1993-12-01&rft.volume=90&rft.issue=23&rft.spage=11247&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 - 1994-01-04 N1 - Date created - 1994-01-04 N1 - Date revised - 2017-01-13 N1 - Gene symbol - lon N1 - Genetic sequence - U02389; GENBANK N1 - SuppNotes - Cited By: J Bacteriol. 1993 Apr;175(8):2271-7 [8468287] Microbiol Rev. 1992 Dec;56(4):592-621 [1480111] J Bacteriol. 1993 Jul;175(14):4545-9 [8331083] Nat Genet. 1993 Jul;4(3):256-67 [8358434] Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7 [271968] Proc Natl Acad Sci U S A. 1981 Aug;78(8):4728-32 [6458036] Proc Natl Acad Sci U S A. 1981 Aug;78(8):4931-5 [6458037] Proc Natl Acad Sci U S A. 1982 Mar;79(6):1869-73 [7043466] J Biol Chem. 1982 Oct 10;257(19):11673-9 [6749845] EMBO J. 1982;1(8):945-51 [6329717] J Biol Chem. 1985 Oct 5;260(22):12022-8 [3900067] J Biol Chem. 1985 Nov 25;260(27):14498-504 [3902833] J Bacteriol. 1985 Dec;164(3):1124-35 [2999072] J Mol Biol. 1986 May 5;189(1):113-30 [3537305] J Biol Chem. 1987 Feb 25;262(6):2696-703 [2950089] J Biol Chem. 1987 Apr 5;262(10):4477-85 [3549708] J Biol Chem. 1987 Apr 5;262(10):4508-15 [3549709] Proc Natl Acad Sci U S A. 1987 Aug;84(16):5550-4 [3303028] Mol Cell Biol. 1988 Feb;8(2):655-63 [2832732] J Biol Chem. 1988 Aug 25;263(24):11718-28 [3042779] Nucleic Acids Res. 1988 Aug 11;16(15):7583-600 [2970625] Eur J Biochem. 1989 Apr 1;180(3):535-45 [2653818] Proc Natl Acad Sci U S A. 1989 Jun;86(11):4056-60 [2657736] Annu Rev Genet. 1989;23:163-98 [2694929] Proc Natl Acad Sci U S A. 1990 May;87(9):3513-7 [2185473] J Biol Chem. 1990 Jul 25;265(21):12546-52 [2197276] Methods Enzymol. 1990;185:60-89 [2199796] Cell. 1990 Aug 24;62(4):611-4 [2201450] Biotechniques. 1991 Feb;10(2):202-4, 206, 208-9 [1676289] FEBS Lett. 1991 Aug 5;287(1-2):211-4 [1652461] J Biol Chem. 1991 Oct 25;266(30):19867-70 [1939050] Eur J Biochem. 1992 Jan 15;203(1-2):9-23 [1730246] Nature. 1992 Feb 13;355(6361):632-4 [1538749] J Bacteriol. 1992 Apr;174(7):2281-7 [1551846] Biochem J. 1992 Jun 15;284 ( Pt 3):609-20 [1622383] Annu Rev Biochem. 1992;61:1175-212 [1497308] Annu Rev Biochem. 1992;61:761-807 [1323239] Gene. 1992 Oct 21;120(2):197-206 [1398134] J Biol Chem. 1992 Nov 15;267(32):22699-702 [1429620] J Bacteriol. 1993 Jul;175(14):4538-44 [8331082] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - An extraintestinal, pathogenic isolate of Escherichia coli (O4/K54/H5) can produce a group 1 capsule which is divergently regulated from its constitutively produced group 2, K54 capsular polysaccharide. AN - 76079410; 8244930 AB - We are studying an O4/K54/H5 Escherichia coli bacteremic isolate (CP9) as a model pathogen for extraintestinal infection. Its group 2, K54 capsular polysaccharide is an important virulence determinant and confers serum resistance. In this study the effect of the group 1 capsule regulators, RcsA, RcsB, and Lon protease, on the regulation of CP9's capsular polysaccharides was assessed. It was established that in the presence of multicopy rcsA or with disruption of lon, CP9 can be induced to produce a group 1 capsule. RcsA, RcsB, and Lon are present in this K54 background and regulate group 1 capsule expression in a fashion similar to that described for K-12 strains. Two independent group 2 capsule gene protein fusions (cl1.29::TnphoA and cl1.137::TnphoA) were used to evaluate the effects of these regulators on group 2 K54 capsule production. Disruption of lon resulted in 1.9-fold (TR293 [cl1.29::TnphoA lon-146]) and 3.4-fold (TR1373 [cl1.137::TnphoA lon-146]) decreases in fusion activity at 28 degrees C, relative to the baseline level. However, decreases in fusion activity at 42 degrees C were only 1.2- and 1.4-fold, respectively. Inactivation of both lon and rcsA or lon and rcsB restored fusion activity to baseline levels at 28 degrees C, but only a partial restoration of activity was seen at higher temperatures. To assess whether these differences in fusion activity reflected a functional change in capsule production, the effects of 80% normal human serum (NHS) were tested against CP9 and TR93 (lon-146). Since the group 2 K54 capsule protects against the bactericidal activity of 80% NHS, a decrease in its production results in an increase in serum sensitivity. Viable counts of CP9 increased 10-fold in 80% NHS over 3 h at 28 degrees C, as expected. In contrast to CP9, TR93 (lon-146) incurred a 10-fold loss in viability under the same conditions. The levels of RcsA are increased in TR93 (lon 146) as consequence of lon disruption; therefore, these results in conjunction with the cl1::TnphoA protein fusion data establish RcsA as a negative regulator of the group 2 K54 capsular polysaccharide. Furthermore, these results also suggest existence of another Lon-sensitive negative regulator of group 2 K54 capsule production, which is active higher temperatures. JF - Journal of bacteriology AU - Russo, T A AU - Singh, G AD - Bacterial Pathogenesis Unit, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892. Y1 - 1993/12// PY - 1993 DA - December 1993 SP - 7617 EP - 7623 VL - 175 IS - 23 SN - 0021-9193, 0021-9193 KW - Antigens, Bacterial KW - 0 KW - Antigens, Surface KW - Bacterial Proteins KW - Escherichia coli Proteins KW - Heat-Shock Proteins KW - K antigens KW - Polysaccharides, Bacterial KW - RcsB protein, E coli KW - Recombinant Fusion Proteins KW - Transcription Factors KW - RcsB protein, Bacteria KW - 127737-30-8 KW - RcsA protein, E coli KW - 135688-02-7 KW - Alkaline Phosphatase KW - EC 3.1.3.1 KW - ATP-Dependent Proteases KW - EC 3.4.21.- KW - Serine Endopeptidases KW - Lon protein, E coli KW - EC 3.4.21.53 KW - Protease La KW - Index Medicus KW - Bacterial Proteins -- genetics KW - Serine Endopeptidases -- genetics KW - Virulence -- genetics KW - Blood Bactericidal Activity KW - Alkaline Phosphatase -- analysis KW - Mutagenesis, Insertional KW - Heat-Shock Proteins -- genetics KW - Genes, Regulator KW - Gene Expression Regulation, Bacterial KW - Escherichia coli -- immunology KW - Antigens, Bacterial -- biosynthesis KW - Escherichia coli -- genetics KW - Antigens, Surface -- biosynthesis KW - Antigens, Bacterial -- genetics KW - Antigens, Surface -- genetics KW - Polysaccharides, Bacterial -- biosynthesis KW - Bacterial Capsules -- chemistry KW - Escherichia coli -- pathogenicity KW - Bacterial Capsules -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76079410?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+bacteriology&rft.atitle=An+extraintestinal%2C+pathogenic+isolate+of+Escherichia+coli+%28O4%2FK54%2FH5%29+can+produce+a+group+1+capsule+which+is+divergently+regulated+from+its+constitutively+produced+group+2%2C+K54+capsular+polysaccharide.&rft.au=Russo%2C+T+A%3BSingh%2C+G&rft.aulast=Russo&rft.aufirst=T&rft.date=1993-12-01&rft.volume=175&rft.issue=23&rft.spage=7617&rft.isbn=&rft.btitle=&rft.title=Journal+of+bacteriology&rft.issn=00219193&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-01-03 N1 - Date created - 1994-01-03 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Bacteriol. 1988 Mar;170(3):1305-10 [2830235] Rev Infect Dis. 1987 Sep-Oct;9 Suppl 5:S517-26 [2446369] J Bacteriol. 1988 Jun;170(6):2599-611 [2836365] Infect Immun. 1990 Jan;58(1):222-7 [2403532] Can J Microbiol. 1989 Nov;35(11):994-9 [2482125] J Bacteriol. 1990 Feb;172(2):659-69 [2404948] Mol Microbiol. 1989 Oct;3(10):1349-59 [2693894] Mol Microbiol. 1989 Dec;3(12):1819-23 [2695750] FEMS Microbiol Lett. 1990 May;57(1-2):129-33 [2165964] Rev Infect Dis. 1990 Nov-Dec;12(6):1008-18 [2267481] Infect Immun. 1991 Feb;59(2):494-502 [1987069] J Bacteriol. 1991 Mar;173(5):1738-47 [1999391] Clin Microbiol Rev. 1991 Jan;4(1):80-128 [1672263] Mol Microbiol. 1991 Jul;5(7):1599-606 [1943696] J Bacteriol. 1992 Jan;174(1):8-16 [1729226] J Bacteriol. 1992 Feb;174(3):1063-7 [1732199] J Bacteriol. 1992 Sep;174(18):5910-5 [1522067] J Bacteriol. 1992 Dec;174(24):8016-22 [1459951] Clin Microbiol Rev. 1993 Jan;6(1):57-68 [8457980] Infect Immun. 1993 Aug;61(8):3578-82 [8392976] J Bacteriol. 1993 Sep;175(17):5384-94 [8366025] J Gen Microbiol. 1993 Aug;139(8):1707-14 [8409913] Mol Microbiol. 1993 Jul;9(2):357-64 [8412686] N Engl J Med. 1974 May 30;290(22):1216-20 [4133095] Nature. 1981 Feb 19;289(5799):696-8 [7007894] Infect Immun. 1983 Jul;41(1):54-60 [6408005] J Infect Dis. 1984 Feb;149(2):184-93 [6199436] J Bacteriol. 1984 Oct;160(1):184-91 [6090411] Carbohydr Res. 1985 Jun 15;139:261-71 [3896488] J Bacteriol. 1987 Mar;169(3):981-9 [3029041] J Bacteriol. 1987 Oct;169(10):4525-31 [2820930] J Gen Microbiol. 1987 Feb;133(2):331-40 [3309150] Adv Intern Med. 1988;33:231-52 [2830769] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Serotonin secretion from rat Leydig cells. AN - 76079400; 8243331 AB - In rat Leydig cells, serotonin (5HT) binds to 5HT2 receptors and stimulates the secretion of CRF which in turn acts as an inhibitor of gonadotropin-induced cAMP formation and androgen production. In the present study we defined the regulation of 5HT secretion in cultured Leydig cells. Adult Leydig cells secreted considerable quantities of 5HT (100-150 pg/10(6) cells per 10 min). The release of 5HT was acutely stimulated by hCG (ED50, 1.1 pM) with maximal stimulation at 10 pM hCG (160%). Forskolin also increased (+220%) 5HT release from cultures (ED50, 50 nM) while TPA was much less effective (+20%), indicating a major role for cAMP in gonadotropin-induced 5HT release. This was confirmed by the finding that 8-Br cAMP (1 mM) was an effective stimulus of 5HT release (+360%). Similar increases of 5HT release by hCG were observed in the absence of extracellular Ca2+. However, ionomycin was a potent stimulus of 5HT release, indicating that elevation of cytoplasmic [Ca2+] could also induce amine secretion. The 5HT content of Leydig cells ranged from 300 to 350 pg/10(6) cells, and decreased during stimulation of 5HT release. Also, immunohistochemical studies revealed specific staining of 5 HT in interstitial cells of the adult rat testis. These studies demonstrated that rat Leydig cells contain and secrete 5HT, and that 5HT release is stimulated by gonadotropin acting primarily through a cAMP-mediated mechanism. JF - Endocrinology AU - Tinajero, J C AU - Fabbri, A AU - Ciocca, D R AU - Dufau, M L AD - Section on Molecular Endocrinology, National Institute of Child Health and Human Development, National Institute of Health, Bethesda, MD 20892. Y1 - 1993/12// PY - 1993 DA - December 1993 SP - 3026 EP - 3029 VL - 133 IS - 6 SN - 0013-7227, 0013-7227 KW - Chorionic Gonadotropin KW - 0 KW - Colforsin KW - 1F7A44V6OU KW - 8-Bromo Cyclic Adenosine Monophosphate KW - 23583-48-4 KW - Serotonin KW - 333DO1RDJY KW - Ionomycin KW - 56092-81-0 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Calcium KW - SY7Q814VUP KW - Abridged Index Medicus KW - Index Medicus KW - Rats KW - Animals KW - Colforsin -- pharmacology KW - Chorionic Gonadotropin -- pharmacology KW - Dose-Response Relationship, Drug KW - Cells, Cultured KW - Calcium -- physiology KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Ionomycin -- pharmacology KW - 8-Bromo Cyclic Adenosine Monophosphate -- pharmacology KW - Male KW - Serotonin -- secretion KW - Leydig Cells -- secretion UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76079400?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Serotonin+secretion+from+rat+Leydig+cells.&rft.au=Tinajero%2C+J+C%3BFabbri%2C+A%3BCiocca%2C+D+R%3BDufau%2C+M+L&rft.aulast=Tinajero&rft.aufirst=J&rft.date=1993-12-01&rft.volume=133&rft.issue=6&rft.spage=3026&rft.isbn=&rft.btitle=&rft.title=Endocrinology&rft.issn=00137227&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-01-06 N1 - Date created - 1994-01-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Resistance to cyclopentenylcytosine in murine leukemia L1210 cells. AN - 76077655; 7694793 AB - Cyclopentenyl cytosine (CPEC) exhibits oncological activity in murine and human tumor cells and has now entered Phase I clinical trials. Its mode of action as an antitumor agent appears to be inhibition by its triphosphate (CPEC-TP) of CTP synthase, the enzyme which converts UTP to CTP. In an attempt to elucidate the mechanism of resistance to CPEC, a murine leukemia cell line resistant to CPEC (L1210/CPEC) was developed by N-methyl-N-nitro-N-nitrosoguanidine-induced mutagenesis and subsequent selection by cultivation of the L1210 cells in the presence of 2 microM CPEC. Resistant clones were maintained in CPEC-free medium for 6 generations before biochemical studies were performed. The resistant clone selected for further studies was approximately 13,000-fold less sensitive to growth inhibition by CPEC than the parental cells, and the concentration of CPEC required to deplete CTP in the resistant cells was 50-fold higher than in the sensitive cells. A comparison of the kinetic properties of CTP synthase from sensitive and resistant cells indicated alteration in the properties of the enzyme from the latter; the median inhibitory concentration for CPEC-TP increased from 2 to 14 microM, Km for UTP decreased from 126 to 50 microM, and Vmax increased 12-fold from 0.2 to 2.3 nmol/mg/min. Northern blot analyses of polyadenylated RNA from the resistant and sensitive cells indicated a 3-fold increase in transcripts of the CTP synthase gene in the resistant line. Consistent with these alterations in the properties of the enzyme, the resistant cells exhibited significantly expanded CTP and dCTP pools (4- 5-fold) when compared with the sensitive cells. No change was observed, however, in the properties of uridine-cytidine kinase, the enzyme responsible for the initial phosphorylation of CPEC; despite this, however, cellular uptake of CPEC was greatly decreased, and phosphorylation of CPEC and its incorporation into RNA were 10-fold less than in the parental cells. These latter observations are most readily explained by feedback inhibition by the increased CTP levels of the resistant cells of uridine-cytidine kinase and/or of the membrane transport process used for initial entry of CPEC. JF - Cancer research AU - Zhang, H AU - Cooney, D A AU - Zhang, M H AU - Ahluwalia, G AU - Ford, H AU - Johns, D G AD - Laboratory of Medicinal Chemistry, National Cancer Institute, NIH, Bethesda, Maryland 20892. Y1 - 1993/12/01/ PY - 1993 DA - 1993 Dec 01 SP - 5714 EP - 5720 VL - 53 IS - 23 SN - 0008-5472, 0008-5472 KW - Antineoplastic Agents KW - 0 KW - Cytidine KW - 5CSZ8459RP KW - RNA KW - 63231-63-0 KW - Cytidine Triphosphate KW - 65-47-4 KW - cyclopentenyl cytosine KW - 69MO0NDN8K KW - Ligases KW - EC 6.- KW - Carbon-Nitrogen Ligases KW - EC 6.3.- KW - CTP synthetase KW - EC 6.3.4.2 KW - Index Medicus KW - Ligases -- genetics KW - Animals KW - Tumor Cells, Cultured KW - Phosphorylation KW - RNA -- metabolism KW - Cytidine Triphosphate -- metabolism KW - Deamination KW - Ligases -- metabolism KW - Drug Resistance KW - Mice KW - Leukemia L1210 -- pathology KW - Cytidine -- pharmacology KW - Leukemia L1210 -- drug therapy KW - Cytidine -- metabolism KW - Cytidine -- analogs & derivatives KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76077655?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Resistance+to+cyclopentenylcytosine+in+murine+leukemia+L1210+cells.&rft.au=Zhang%2C+H%3BCooney%2C+D+A%3BZhang%2C+M+H%3BAhluwalia%2C+G%3BFord%2C+H%3BJohns%2C+D+G&rft.aulast=Zhang&rft.aufirst=H&rft.date=1993-12-01&rft.volume=53&rft.issue=23&rft.spage=5714&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 - 1994-01-03 N1 - Date created - 1994-01-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Neoadjuvant therapy in cancer treatment. AN - 76077228; 8242583 AB - Neoadjuvant therapy has come to play an increasingly prominent role in the treatment of cancer. Originally defined as systemic therapy given before local treatment, the concept has been extended to include radiation therapy given before surgery. Potential advantages include improved local and distant control, direct evaluation, and organ-sparing treatment. Potential disadvantages include increased toxicity and cost, potential delay in effective treatment, and obscuring of pathologic staging. Neoadjuvant therapy in cancer treatment may be viewed in three categories: tumors in which neoadjuvant treatment has been shown effective, thus becoming standard therapy; tumors in which it has been shown to facilitate organ-sparing, and tumors in which its utility has not been shown. For patients with osteogenic sarcoma, for example, preoperative chemotherapy and limb salvage therapy have become the standard of care. Response to chemotherapy, ascertained by histologic review of the surgical specimen, can be used to tailor postoperative chemotherapy. In patients with advanced laryngeal squamous cell carcinoma, neoadjuvant chemotherapy followed by radiation has permitted laryngeal preservation in a majority of patients without compromising overall survival. Phase II and III studies conducted in women with breast cancer have demonstrated promising results for neoadjuvant chemotherapy given before radiation therapy and/or surgery. Phase III studies to compare neoadjuvant therapy to standard therapy in patients with breast cancer are underway. For neoadjuvant therapy, as with other innovations in cancer treatment, it is crucial that a new strategy must be compared closely to standard therapy in terms of recurrence, survival, and impact on organ sparing, as well as quality of life and treatment costs. JF - Cancer AU - Trimble, E L AU - Ungerleider, R S AU - Abrams, J A AU - Kaplan, R S AU - Feigal, E G AU - Smith, M A AU - Carter, C L AU - Friedman, M A AD - National Cancer Institute, Bethesda, Maryland. Y1 - 1993/12/01/ PY - 1993 DA - 1993 Dec 01 SP - 3515 EP - 3524 VL - 72 IS - 11 Suppl SN - 0008-543X, 0008-543X KW - Antineoplastic Agents KW - 0 KW - Abridged Index Medicus KW - Index Medicus KW - Humans KW - Chemotherapy, Adjuvant KW - Neoplasms -- surgery KW - Neoplasms -- drug therapy KW - Neoplasms -- radiotherapy KW - Antineoplastic Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76077228?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Neoadjuvant+therapy+in+cancer+treatment.&rft.au=Trimble%2C+E+L%3BUngerleider%2C+R+S%3BAbrams%2C+J+A%3BKaplan%2C+R+S%3BFeigal%2C+E+G%3BSmith%2C+M+A%3BCarter%2C+C+L%3BFriedman%2C+M+A&rft.aulast=Trimble&rft.aufirst=E&rft.date=1993-12-01&rft.volume=72&rft.issue=11+Suppl&rft.spage=3515&rft.isbn=&rft.btitle=&rft.title=Cancer&rft.issn=0008543X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-12-27 N1 - Date created - 1993-12-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Lithium decreases membrane-associated protein kinase C in hippocampus: selectivity for the alpha isozyme. AN - 76071289; 8245981 AB - We investigated the effects of lithium on alterations in the amount and distribution of protein kinase C (PKC) in discrete areas of rat brain by using [3H]phorbol 12,13-dibutyrate quantitative autoradiography as well as western blotting. Chronic administration of lithium resulted in a significant decrease in membrane-associated PKC in several hippocampal structures, most notably the subiculum and the CA1 region. In contrast, only modest changes in [3H]phorbol 12,13-dibutyrate binding were observed in the various other cortical and subcortical structures examined. Immunoblotting using monoclonal anti-PKC antibodies revealed an isozyme-specific 30% decrease in hippocampal membrane-associated PKC alpha, in the absence of any changes in the labeling of either the beta (I/II) or gamma isozymes. These changes were observed only after chronic (4 week) treatment with lithium, and not after acute (5 days) treatment, suggesting potential clinical relevance. Given the critical role of PKC in regulating neuronal signal transduction, lithium's effects on PKC in the limbic system represent an attractive molecular mechanism for its efficacy in treating both poles of manic-depressive illness. In addition, the decreased hippocampal membrane-associated PKC observed in the present study offers a possible explanation for lithium-induced memory impairment. JF - Journal of neurochemistry AU - Manji, H K AU - Etcheberrigaray, R AU - Chen, G AU - Olds, J L AD - Section on Clinical Pharmacology, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/12// PY - 1993 DA - December 1993 SP - 2303 EP - 2310 VL - 61 IS - 6 SN - 0022-3042, 0022-3042 KW - Isoenzymes KW - 0 KW - Tritium KW - 10028-17-8 KW - Lithium Carbonate KW - 2BMD2GNA4V KW - Phorbol 12,13-Dibutyrate KW - 37558-16-0 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Phorbol 12,13-Dibutyrate -- metabolism KW - Pyramidal Tracts -- enzymology KW - Organ Specificity KW - Autoradiography KW - Male KW - Protein Kinase C -- metabolism KW - Brain -- enzymology KW - Lithium Carbonate -- pharmacology KW - Hippocampus -- enzymology KW - Isoenzymes -- metabolism KW - Hippocampus -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76071289?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Lithium+decreases+membrane-associated+protein+kinase+C+in+hippocampus%3A+selectivity+for+the+alpha+isozyme.&rft.au=Manji%2C+H+K%3BEtcheberrigaray%2C+R%3BChen%2C+G%3BOlds%2C+J+L&rft.aulast=Manji&rft.aufirst=H&rft.date=1993-12-01&rft.volume=61&rft.issue=6&rft.spage=2303&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 - 1993-12-23 N1 - Date created - 1993-12-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Gene therapy for human hemoglobinopathies. AN - 76065835; 8234372 AB - Gene transfer of human globin genes into human pluripotent stem cells via viral vectors may soon be realized. The high level of globin gene expression believed to be required for the treatment of severe hemoglobinopathies necessitated the inclusion of cis-acting sequences (LCR). Retroviral vectors containing the LCR elements are prone to rearrangement, low titer, and poor expression. Inclusion of a "minilocus" containing four HS sites linked to a globin gene resulted in higher expression in transplanted mice, but rearrangement of the provirus still occurs, and it is unclear what significance these experiments have with regard to human marrow stem cell transduction. Recombinant AAV is among the newest of genetic transfer vectors. This once obscure virus possesses unique properties that distinguish it from all other vectors. Its major advantage is the lack of pathogenicity in humans. Wild-type AAV has the unusual ability to selectively integrate into the mammalian genome at a specific region, thus reducing the concern for genomic disruption and insertional mutagenesis. The ability of AAV to carry regulatory elements without interference from the viral template may enable greater control of transferred gene expression. Disadvantages currently include the inferior packaging systems which yield low numbers of recombinant virions which are contaminated with wild-type adenovirus. The small AAV genome that can be packaged (approximately 5 kb) rules out its use for transfer of larger genes. Recombinant AAV viruses do not appear to demonstrate the same site-specific genomic integration as wild-type viruses. Elucidation of the mechanism of site-specific integration should prove useful in the development of safe vectors for gene transfer as well as provide insight into the nature of DNA recombination in humans. JF - Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.) AU - Walsh, C E AU - Liu, J M AU - Miller, J L AU - Nienhuis, A W AU - Samulski, R J AD - Clinical Hematology Branch, NHLBI/NIH, Bethesda, Maryland 20892. Y1 - 1993/12// PY - 1993 DA - December 1993 SP - 289 EP - 300 VL - 204 IS - 3 SN - 0037-9727, 0037-9727 KW - RNA, Messenger KW - 0 KW - Globins KW - 9004-22-2 KW - Index Medicus KW - Gene Transfer Techniques KW - Humans KW - Genetic Vectors KW - Transduction, Genetic KW - Recombination, Genetic KW - Dependovirus -- genetics KW - Gene Expression Regulation KW - Retroviridae -- genetics KW - RNA, Messenger -- genetics KW - Globins -- genetics KW - Genetic Therapy -- methods KW - Hemoglobinopathies -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76065835?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Society+for+Experimental+Biology+and+Medicine.+Society+for+Experimental+Biology+and+Medicine+%28New+York%2C+N.Y.%29&rft.atitle=Gene+therapy+for+human+hemoglobinopathies.&rft.au=Walsh%2C+C+E%3BLiu%2C+J+M%3BMiller%2C+J+L%3BNienhuis%2C+A+W%3BSamulski%2C+R+J&rft.aulast=Walsh&rft.aufirst=C&rft.date=1993-12-01&rft.volume=204&rft.issue=3&rft.spage=289&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+Society+for+Experimental+Biology+and+Medicine.+Society+for+Experimental+Biology+and+Medicine+%28New+York%2C+N.Y.%29&rft.issn=00379727&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-12-22 N1 - Date created - 1993-12-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hepatic stem cell compartment: activation and lineage commitment. AN - 76057178; 7694304 JF - Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.) AU - Thorgeirsson, S S AU - Evarts, R P AU - Bisgaard, H C AU - Fujio, K AU - Hu, Z AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1993/12// PY - 1993 DA - December 1993 SP - 253 EP - 260 VL - 204 IS - 3 SN - 0037-9727, 0037-9727 KW - Antibodies, Monoclonal KW - 0 KW - Desmin KW - Growth Substances KW - RNA, Messenger KW - alpha-Fetoproteins KW - Keratins KW - 68238-35-7 KW - 2-Acetylaminofluorene KW - 9M98QLJ2DL KW - gamma-Glutamyltransferase KW - EC 2.3.2.2 KW - Index Medicus KW - Keratins -- metabolism KW - Animals KW - 2-Acetylaminofluorene -- toxicity KW - gamma-Glutamyltransferase -- metabolism KW - Gene Expression KW - Desmin -- metabolism KW - RNA, Messenger -- genetics KW - Rats KW - Rats, Inbred F344 KW - Hepatectomy KW - alpha-Fetoproteins -- genetics KW - Male KW - Liver -- cytology KW - Stem Cells -- cytology KW - Liver Regeneration KW - Growth Substances -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76057178?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Society+for+Experimental+Biology+and+Medicine.+Society+for+Experimental+Biology+and+Medicine+%28New+York%2C+N.Y.%29&rft.atitle=Hepatic+stem+cell+compartment%3A+activation+and+lineage+commitment.&rft.au=Thorgeirsson%2C+S+S%3BEvarts%2C+R+P%3BBisgaard%2C+H+C%3BFujio%2C+K%3BHu%2C+Z&rft.aulast=Thorgeirsson&rft.aufirst=S&rft.date=1993-12-01&rft.volume=204&rft.issue=3&rft.spage=253&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+Society+for+Experimental+Biology+and+Medicine.+Society+for+Experimental+Biology+and+Medicine+%28New+York%2C+N.Y.%29&rft.issn=00379727&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-12-22 N1 - Date created - 1993-12-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Positron emission tomographic imaging of cardiac sympathetic innervation using 6-[18F]fluorodopamine: initial findings in humans. AN - 76053466; 8245356 AB - This study evaluated the safety, efficacy and validity of 6-[18F]fluorodopamine positron emission tomographic scanning of cardiac sympathetic innervation and function in humans. Positron emission tomography (PET) scans, arterial blood and urine were obtained after a 3-min intravenous infusion of 6-[18F]fluorodopamine (1 to 4 mCi, 188 to 809 mCi/mmol) in healthy volunteers, with or without pretreatment with oral desipramine to inhibit neuronal uptake of catecholamines. 6-[18F]Fluorodopamine PET scanning visualized the left ventricular myocardium. Blood pressure increased slightly and transiently. The estimated absorbed radiation dose to the main target organ, the wall of the urinary bladder, was 0.8 to 1.0 rad/mCi of injected 6-[18F]fluorodopamine. By 24 h after the injection, the main 6F-compound in urine was 6F-vanillymandelic acid, a metabolite of 6F-norepinephrine. Desipramine attenuated accumulation of myocardial 6-[18F]fluorodopamine-derived radioactivity and plasma 6F-dihydroxyphenylacetic acid. 6-[18F]Fluorodopamine produces negligible hemodynamic effects and acceptable radiation exposure at doses that visualize the left ventricular myocardium. Sympathetic nerves take up 6-[18F]fluorodopamine, which is translocated from the axoplasm into storage vesicles, where is it beta-hydroxylated to the fluorinated analogue of the sympathetic neurotransmitter norepinephrine. Therefore, the basis for visualization of myocardium after 6-[18F]fluorodopamine injection in humans is radiolabeling by 6-[18F]fluorodopamine and 6-[18F]fluoronorepinephrine of vesicles in sympathetic terminals. 6-[18F]Fluorodopamine PET scanning provides a novel means for assessing sympathetic innervation and function noninvasively in the human heart. JF - Journal of the American College of Cardiology AU - Goldstein, D S AU - Eisenhofer, G AU - Dunn, B B AU - Armando, I AU - Lenders, J AU - Grossman, E AU - Holmes, C AU - Kirk, K L AU - Bacharach, S AU - Adams, R AD - Clinical Neuroscience Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/12// PY - 1993 DA - December 1993 SP - 1961 EP - 1971 VL - 22 IS - 7 SN - 0735-1097, 0735-1097 KW - Drugs, Investigational KW - 0 KW - Fluorine Radioisotopes KW - 6-fluorodopamine KW - 59043-70-8 KW - Desipramine KW - TG537D343B KW - Dopamine KW - VTD58H1Z2X KW - Abridged Index Medicus KW - Index Medicus KW - Hemodynamics -- drug effects KW - Radiation Dosage KW - Desipramine -- pharmacology KW - Humans KW - Premedication KW - Adult KW - Aged KW - Middle Aged KW - Urinary Bladder -- radiation effects KW - Male KW - Dopamine -- analogs & derivatives KW - Heart -- innervation KW - Heart -- diagnostic imaging KW - Tomography, Emission-Computed KW - Sympathetic Nervous System -- diagnostic imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76053466?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+American+College+of+Cardiology&rft.atitle=Positron+emission+tomographic+imaging+of+cardiac+sympathetic+innervation+using+6-%5B18F%5Dfluorodopamine%3A+initial+findings+in+humans.&rft.au=Goldstein%2C+D+S%3BEisenhofer%2C+G%3BDunn%2C+B+B%3BArmando%2C+I%3BLenders%2C+J%3BGrossman%2C+E%3BHolmes%2C+C%3BKirk%2C+K+L%3BBacharach%2C+S%3BAdams%2C+R&rft.aulast=Goldstein&rft.aufirst=D&rft.date=1993-12-01&rft.volume=22&rft.issue=7&rft.spage=1961&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+American+College+of+Cardiology&rft.issn=07351097&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-12-28 N1 - Date created - 1993-12-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Rescue of an influenza A virus wild-type PB2 gene and a mutant derivative bearing a site-specific temperature-sensitive and attenuating mutation. AN - 76048146; 8230444 AB - Live attenuated influenza A virus vaccines are currently produced by the transfer of attenuating genes from a donor virus to new epidemic variants of influenza A virus, with the selection of reassortant viruses that possess the protective antigens (i.e., the two surface glycoproteins) of the epidemic virus and the attenuating genes from the donor virus. The previously studied attenuated donor viruses were produced by conventional methods such as passage of virus at low temperature or chemical mutagenesis. The present paper describes a new strategy for the generation of a donor virus bearing an attenuating, non-surface-glycoprotein gene. This strategy involves the introduction of attenuating mutations into the cDNA copy of the PB2 polymerase gene by site-directed mutagenesis, transfection of in vitro RNA transcripts of PB2 cDNA, and recovery of the transfected PB2 gene into an infectious virus. An avian-human influenza A virus PB2 single-gene reassortant virus (with an avian influenza A virus PB2 gene) that replicates efficiently in avian tissue but poorly in mammalian cells was used as a helper virus to rescue a transfected synthetic RNA derived from a human influenza A virus PB2 gene. The desired human influenza A virus mutant PB2 transfectant was favored in this situation because the avian influenza A virus PB2 gene restricts viral replication in mammalian cells in culture, the system used for rescue, thereby providing strong selection for the virus bearing the human influenza A virus PB2 gene. We validated the feasibility of this approach by rescuing the PB2 gene of the wild-type influenza A/Ann Arbor/6/60 virus and a mutant derivative that had a single amino acid substitution introduced at position 265 by site-directed mutagenesis. Previously, this amino acid substitution had been shown to specify both a temperature-sensitive (ts) and an attenuation (att) phenotype. The rescued mutant 265 PB2 transfectant virus exhibited the ts and att phenotypes, which confirms that these phenotypes were specified by this single amino acid substitution. The transfectant virus was immunogenic and protected hamsters from subsequent challenge with wild-type virus. The cDNA copy of this influenza A/Ann Arbor/6/60 virus mutant 265 PB2 gene will be used as a substrate for the introduction of additional attenuating mutations by site-directed mutagenesis. JF - Journal of virology AU - Subbarao, E K AU - Kawaoka, Y AU - Murphy, B R AD - Respiratory Viruses Section, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892. Y1 - 1993/12// PY - 1993 DA - December 1993 SP - 7223 EP - 7228 VL - 67 IS - 12 SN - 0022-538X, 0022-538X KW - Antibodies, Viral KW - 0 KW - PB2 protein, Influenzavirus A KW - Vaccines, Attenuated KW - Vaccines, Synthetic KW - Viral Proteins KW - RNA Replicase KW - EC 2.7.7.48 KW - Index Medicus KW - Virus Replication KW - Antibodies, Viral -- blood KW - Animals KW - Base Sequence KW - Transfection KW - Respiratory System -- microbiology KW - Recombination, Genetic KW - Molecular Sequence Data KW - Cricetinae KW - Viral Proteins -- genetics KW - Influenza A virus -- growth & development KW - Genes, Viral KW - Influenza A virus -- genetics KW - Mutation KW - Immunization UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76048146?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Rescue+of+an+influenza+A+virus+wild-type+PB2+gene+and+a+mutant+derivative+bearing+a+site-specific+temperature-sensitive+and+attenuating+mutation.&rft.au=Subbarao%2C+E+K%3BKawaoka%2C+Y%3BMurphy%2C+B+R&rft.aulast=Subbarao&rft.aufirst=E&rft.date=1993-12-01&rft.volume=67&rft.issue=12&rft.spage=7223&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 - 1993-12-21 N1 - Date created - 1993-12-21 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Virology. 1981 Jul 30;112(2):505-17 [7257183] J Virol. 1991 May;65(5):2711-3 [2016777] Infect Immun. 1982 Sep;37(3):1119-26 [7129631] J Virol. 1987 Sep;61(9):2857-63 [2441080] J Virol. 1988 Feb;62(2):488-95 [3336068] Virology. 1988 Dec;167(2):554-67 [2974219] J Virol. 1989 Dec;63(12):5142-52 [2585601] Cell. 1989 Dec 22;59(6):1107-13 [2598262] Proc Natl Acad Sci U S A. 1990 May;87(10):3802-5 [2339122] Proc Natl Acad Sci U S A. 1991 Jun 15;88(12):5177-81 [2052599] J Virol. 1992 Jan;66(1):399-404 [1370088] J Clin Microbiol. 1992 Mar;30(3):655-62 [1551982] J Virol. 1992 Aug;66(8):4647-53 [1378505] Virology. 1992 Nov;191(1):506-10 [1413525] J Virol. 1993 Apr;67(4):1761-4 [8445709] J Biochem Biophys Methods. 1981 Oct;5(4):219-28 [6171588] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In vivo control of NF-kappa B activation by I kappa B alpha. AN - 76027380; 8223478 AB - The transcription factor NF-kappa B is stored in the cytoplasm in complexes with the inhibitor protein I kappa B alpha. It has been shown in vitro that dissociation of I kappa B alpha from these complexes results in active NF-kappa B. In this report we show that lipopolysaccharide (LPS)-induced activation of B or pre-B cells results in loss of I kappa B alpha from NF-kappa B complexes in vivo. Many liberated NF-kappa B dimers reached the nucleus, where increased c-rel, p65 and p50 were detected by immunoblotting and by DNA binding assays. Some liberated dimers were retained in the cytoplasm, however, through binding to newly synthesized I kappa B alpha, a finding which strongly suggests (i) that the LPS-induced signal causes dissociation of complexes rather than preventing their association and (ii) that dissociation results from modification of I kappa B alpha and not of c-rel or p65. No effect of LPS treatment was detected on p105 or p100, which also retain rel family members in the cytoplasm. Quite unexpectedly, we also found that in unstimulated cells there is a constant ongoing process of degradation and replacement of complexed I kappa B alpha. We propose that this turnover results in the low level of active NF-kappa B presumably necessary even in the unstimulated cell, and that the high rate of synthesis of I kappa B alpha provides the ability to turn off NF-kappa B activity rapidly as soon as the activating signal ceases. JF - The EMBO journal AU - Rice, N R AU - Ernst, M K AD - Laboratory of Molecular Virology and Carcinogenesis, NCI-Frederick Cancer Research and Development Center, Frederick, MD 21702-1201. Y1 - 1993/12// PY - 1993 DA - December 1993 SP - 4685 EP - 4695 VL - 12 IS - 12 SN - 0261-4189, 0261-4189 KW - DNA-Binding Proteins KW - 0 KW - I-kappa B Proteins KW - Lipopolysaccharides KW - NF-kappa B KW - NFKBIA protein, human KW - Nfkbia protein, mouse KW - Proto-Oncogene Proteins KW - Proto-Oncogene Proteins c-rel KW - NF-KappaB Inhibitor alpha KW - 139874-52-5 KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Animals KW - Immunoblotting KW - DNA -- metabolism KW - Humans KW - Lipopolysaccharides -- pharmacology KW - Proto-Oncogene Proteins -- metabolism KW - Amino Acid Sequence KW - Mice KW - B-Lymphocytes -- metabolism KW - Base Sequence KW - Half-Life KW - Transfection KW - Molecular Sequence Data KW - Cell Line KW - NF-kappa B -- metabolism KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76027380?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=In+vivo+control+of+NF-kappa+B+activation+by+I+kappa+B+alpha.&rft.au=Rice%2C+N+R%3BErnst%2C+M+K&rft.aulast=Rice&rft.aufirst=N&rft.date=1993-12-01&rft.volume=12&rft.issue=12&rft.spage=4685&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 - 1993-12-21 N1 - Date created - 1993-12-21 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Virol. 1992 Jun;66(6):3758-67 [1533881] Mol Cell Biol. 1992 Feb;12(2):444-54 [1732726] Nature. 1992 Aug 13;358(6387):597-9 [1501714] Genes Dev. 1992 Oct;6(10):1899-913 [1340770] Cell. 1992 Oct 16;71(2):243-53 [1423592] EMBO J. 1993 Jan;12(1):201-11 [7679069] Int Rev Cytol. 1993;143:1-62 [8449662] Science. 1993 Mar 26;259(5103):1912-5 [8096091] Genes Dev. 1993 Apr;7(4):705-18 [8458581] Proc Natl Acad Sci U S A. 1993 Mar 15;90(6):2532-6 [8460169] Mol Cell Biol. 1993 Jun;13(6):3301-10 [8497253] J Biol Chem. 1993 Jun 5;268(16):11803-10 [8505309] Genes Dev. 1993 Jul;7(7A):1266-76 [8319912] Cell. 1990 Sep 7;62(5):1007-18 [2203531] Cell. 1990 Sep 7;62(5):1019-29 [2203532] J Biol Chem. 1990 Sep 5;265(25):15183-8 [2168404] Mol Cell Biol. 1990 Oct;10(10):5473-85 [2204816] Biochemistry. 1979 Feb 20;18(4):690-3 [84683] Proc Natl Acad Sci U S A. 1986 Jan;83(2):295-8 [3079910] Cell. 1986 Aug 29;46(5):705-16 [3091258] Cell. 1986 Dec 26;47(6):921-8 [3096580] Cell. 1988 Apr 22;53(2):211-7 [3129195] Mol Cell Biol. 1989 Jun;9(6):2424-30 [2548081] Genes Dev. 1989 Nov;3(11):1689-98 [2691328] Mol Cell Biol. 1990 May;10(5):2327-34 [2183031] Nature. 1990 Apr 12;344(6267):678-82 [2157987] Cell. 1990 Apr 20;61(2):255-65 [2184941] Mol Cell Biol. 1992 Feb;12(2):674-84 [1732739] Mol Cell Biol. 1992 Feb;12(2):685-95 [1531086] EMBO J. 1992 Jan;11(1):195-203 [1740105] EMBO J. 1992 Jan;11(1):205-13 [1740106] Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1529-33 [1542644] Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1875-9 [1542686] Genes Dev. 1992 May;6(5):745-60 [1577270] Genes Dev. 1992 May;6(5):775-87 [1577272] Cell. 1990 Nov 16;63(4):803-14 [2225078] Nature. 1990 Nov 1;348(6296):76-80 [2234062] Mol Cell Biol. 1991 Jan;11(1):259-66 [1986224] Proc Natl Acad Sci U S A. 1991 Feb 1;88(3):966-70 [1992489] Oncogene. 1990 Dec;5(12):1843-50 [2284104] Cell. 1991 Mar 8;64(5):961-9 [2001591] Science. 1991 Mar 22;251(5000):1490-3 [2006423] Proc Natl Acad Sci U S A. 1991 May 1;88(9):3715-9 [2023921] Oncogene. 1991 Apr;6(4):615-26 [1851550] EMBO J. 1991 Jul;10(7):1817-25 [2050119] Cell. 1991 Jun 28;65(7):1281-9 [1829648] Genes Dev. 1991 Aug;5(8):1464-76 [1907941] Nature. 1991 Aug 22;352(6337):733-6 [1876189] Science. 1991 Sep 13;253(5025):1268-71 [1891714] EMBO J. 1991 Dec;10(12):3805-17 [1935902] Nature. 1991 Dec 5;354(6352):395-8 [1956402] Cell. 1991 Dec 20;67(6):1075-87 [1760839] Oncogene. 1991 Dec;6(12):2203-10 [1766669] Mol Cell Biol. 1992 Jun;12(6):2898-908 [1588976] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cell proliferation and chemical carcinogenesis: symposium overview. AN - 21251144; 11703189 AB - Cancer, by definition, is a proliferative disease. The fundamental scientific issue explored at the international symposium "Cell Proliferation and Chemical Carcinogenesis" was the impact of chemically enhanced cell proliferation on the dynamic carcinogenic processes. This conference, held at the National Institute of Environmental Health Sciences January 14-16, 1992, provided an open forum for the exchange of new results, information, and ideas in four areas: a) general principles of cell division and carcinogenesis, b) critical evaluation of cell proliferation methodologies, c) cell proliferation and modeling of organ-specific carcinogenesis, and d) cell proliferation and human carcinogenesis. This overview summarizes key findings from that symposium. The general view expressed was that although cell proliferation is involved inextricably in the development of cancers, chemically enhanced cell division does not reliably predict carcinogenicity. Our knowledge of the multistep nature of carcinogenesis has advanced substantially during recent years; however, much still needs to be learned. A greater understanding of the cellular and molecular events in chemical carcinogenesis should improve all aspects of the overall risk assessment process, including extrapolations based on dose, species, and interindividual differences. JF - Environmental Health Perspectives AU - Melnick, R L AU - Huff, J AU - Barrett, J C AU - Maronpot, R R AU - Lucier, G AU - Portier, C J AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1993/12// PY - 1993 DA - Dec 1993 SP - 3 EP - 7 PB - US Government Printing Office, Superintendent of Documents, P.O. Box 371954 Pittsburgh PA 15250-7954 USA VL - 101 IS - Suppl 5 SN - 0091-6765, 0091-6765 KW - Health & Safety Science Abstracts; Risk Abstracts; Environment Abstracts KW - Risk assessment KW - Conferences KW - Carcinogenicity KW - Carcinogenesis KW - Environmental health KW - Cancer KW - H 12000:Epidemiology and Public Health KW - R2 23060:Medical and environmental health KW - ENA 02:Toxicology & Environmental Safety UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/21251144?accountid=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=Environmental+Health+Perspectives&rft.atitle=Cell+proliferation+and+chemical+carcinogenesis%3A+symposium+overview.&rft.au=Melnick%2C+R+L%3BHuff%2C+J%3BBarrett%2C+J+C%3BMaronpot%2C+R+R%3BLucier%2C+G%3BPortier%2C+C+J&rft.aulast=Melnick&rft.aufirst=R&rft.date=1993-12-01&rft.volume=101&rft.issue=Suppl+5&rft.spage=3&rft.isbn=&rft.btitle=&rft.title=Environmental+Health+Perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-01-01 N1 - Last updated - 2015-03-31 N1 - SubjectsTermNotLitGenreText - Risk assessment; Conferences; Carcinogenicity; Carcinogenesis; Environmental health; Cancer ER - TY - JOUR T1 - Antineoplastic drug resistance and breast cancer. AN - 76148716; 7904140 JF - Annals of the New York Academy of Sciences AU - Morrow, C S AU - Cowan, K H AD - Medical Breast Cancer Section, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1993/11/30/ PY - 1993 DA - 1993 Nov 30 SP - 289 EP - 312 VL - 698 SN - 0077-8923, 0077-8923 KW - Alkylating Agents KW - 0 KW - Antimetabolites, Antineoplastic KW - Antineoplastic Agents KW - Carrier Proteins KW - Membrane Glycoproteins KW - P-Glycoprotein KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Mixed Function Oxygenases KW - EC 1.- KW - Glutathione Transferase KW - EC 2.5.1.18 KW - DNA Topoisomerases, Type I KW - EC 5.99.1.2 KW - Index Medicus KW - Alkylating Agents -- therapeutic use KW - Mixed Function Oxygenases -- metabolism KW - Humans KW - Glutathione Transferase -- metabolism KW - Cytochrome P-450 Enzyme System -- metabolism KW - Antimetabolites, Antineoplastic -- therapeutic use KW - Female KW - DNA Topoisomerases, Type I -- metabolism KW - Breast Neoplasms -- drug therapy KW - Drug Resistance -- physiology KW - Carrier Proteins -- metabolism KW - Antineoplastic Agents -- metabolism KW - Breast Neoplasms -- metabolism KW - Antineoplastic Agents -- therapeutic use KW - Membrane Glycoproteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76148716?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Antineoplastic+drug+resistance+and+breast+cancer.&rft.au=Morrow%2C+C+S%3BCowan%2C+K+H&rft.aulast=Morrow&rft.aufirst=C&rft.date=1993-11-30&rft.volume=698&rft.issue=&rft.spage=289&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 - 1994-02-04 N1 - Date created - 1994-02-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Generation of a plasmid vector for deletion cloning by rapid multiple site-directed mutagenesis. AN - 76108326; 8244035 AB - The construction of a new plasmid vector, devoid of all MboI (GATC) and TspEI (AATT) restriction sites, is described. The lack of these two frequent-cutting restriction sites is a unique feature among plasmids. This new plasmid, pBRkanf1-, allows selective fragmentation of a cloned insert. As a result, the vector offers an alternative strategy to create overlapping and sequentially deleted subclones. In addition, the construction of the new plasmid required the development of a rapid and accurate multiple site-directed mutagenesis procedure. The mutagenesis method uses a combination of DNA amplification and chain extension by DNA polymerase. By this method, mutations are created progressively from one end of a DNA molecule to the other. JF - Gene AU - Bhat, K S AD - National Institutes of Health, Rocky Mountain Laboratories, Hamilton, MT 59840. Y1 - 1993/11/30/ PY - 1993 DA - 1993 Nov 30 SP - 83 EP - 87 VL - 134 IS - 1 SN - 0378-1119, 0378-1119 KW - DNA KW - 9007-49-2 KW - endodeoxyribonuclease TspEI KW - EC 3.1.21.- KW - Deoxyribonucleases, Type II Site-Specific KW - EC 3.1.21.4 KW - GATC-specific type II deoxyribonucleases KW - Index Medicus KW - Base Sequence KW - Genetic Vectors KW - Molecular Sequence Data KW - Mutagenesis, Site-Directed KW - Cloning, Molecular -- methods KW - Plasmids KW - Sequence Deletion UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76108326?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Generation+of+a+plasmid+vector+for+deletion+cloning+by+rapid+multiple+site-directed+mutagenesis.&rft.au=Bhat%2C+K+S&rft.aulast=Bhat&rft.aufirst=K&rft.date=1993-11-30&rft.volume=134&rft.issue=1&rft.spage=83&rft.isbn=&rft.btitle=&rft.title=Gene&rft.issn=03781119&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-01-05 N1 - Date created - 1994-01-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Facilitation of cocaine kindling by glucocorticoids in rats. AN - 76173285; 8287272 AB - We report that glucocorticoids significantly facilitated the development of cocaine-induced kindled seizures. These results suggest that glucocorticoids may have effects on the development of kindled seizures which are similar to those of the neuropeptide, corticotropin-releasing hormone (CRH), with which they show a close functional relationship. These results may be of interest in the light of data showing that glucocorticoids increase CRH expression in the central nucleus of the amygdala, which is an important site for the development of kindling. JF - Brain research AU - Kling, M A AU - Smith, M A AU - Glowa, J R AU - Pluznik, D AU - Demas, J AU - DeBellis, M D AU - Gold, P W AU - Schulkin, J AD - Clinical Neuroendocrinology Branch, NIMH, Bethesda, MD 20892. Y1 - 1993/11/26/ PY - 1993 DA - 1993 Nov 26 SP - 163 EP - 166 VL - 629 IS - 1 SN - 0006-8993, 0006-8993 KW - Dexamethasone KW - 7S5I7G3JQL KW - Cocaine KW - I5Y540LHVR KW - Corticosterone KW - W980KJ009P KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Stereotyped Behavior -- drug effects KW - Motor Activity -- drug effects KW - Drug Synergism KW - Male KW - Seizures -- chemically induced KW - Dexamethasone -- toxicity KW - Kindling, Neurologic -- drug effects KW - Seizures -- physiopathology KW - Cocaine -- toxicity KW - Corticosterone -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76173285?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Facilitation+of+cocaine+kindling+by+glucocorticoids+in+rats.&rft.au=Kling%2C+M+A%3BSmith%2C+M+A%3BGlowa%2C+J+R%3BPluznik%2C+D%3BDemas%2C+J%3BDeBellis%2C+M+D%3BGold%2C+P+W%3BSchulkin%2C+J&rft.aulast=Kling&rft.aufirst=M&rft.date=1993-11-26&rft.volume=629&rft.issue=1&rft.spage=163&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 - 1994-02-23 N1 - Date created - 1994-02-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - SpoU protein of Escherichia coli belongs to a new family of putative rRNA methylases. AN - 20181162; 8745836 JF - Nucleic Acids Research AU - Koonin, E V AU - Rudd, K E AD - National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894. Y1 - 1993/11/25/ PY - 1993 DA - 1993 Nov 25 SP - 5519 PB - Oxford University Press, Oxford Journals, Great Clarendon Street VL - 21 IS - 23 SN - 0305-1048, 0305-1048 KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - rRNA KW - Methylase KW - Escherichia coli KW - J 02310:Genetics & Taxonomy KW - N 14830:RNA UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20181162?accountid=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=Nucleic+Acids+Research&rft.atitle=SpoU+protein+of+Escherichia+coli+belongs+to+a+new+family+of+putative+rRNA+methylases.&rft.au=Koonin%2C+E+V%3BRudd%2C+K+E&rft.aulast=Koonin&rft.aufirst=E&rft.date=1993-11-25&rft.volume=21&rft.issue=23&rft.spage=5519&rft.isbn=&rft.btitle=&rft.title=Nucleic+Acids+Research&rft.issn=03051048&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2008-12-01 N1 - Last updated - 2015-03-27 N1 - SubjectsTermNotLitGenreText - rRNA; Methylase; Escherichia coli ER - TY - JOUR T1 - Effects of N6-cyclopentyl adenosine and 8-cyclopentyl-1,3-dipropylxanthine on N-methyl-D-aspartate induced seizures in mice. AN - 76172014; 8287913 AB - The effect of the adenosine A1 receptor agonist N6-cyclopentyladenosine (CPA) and antagonist 8-cyclopentyl-1,3-dipropylxanthine (CPX) on N-methyl-D-aspartate (NMDA)-evoked seizures was studied in C57BL/6 mice (20/group). Animals were injected i.p. either with CPA (0.5, 1, 2 mg/kg) or CPX (1, 2 mg/kg) 15 min prior to administration of NMDA (30, 60, 125 mg/kg). Administration of NMDA alone resulted in a complete locomotor arrest at 30 mg/kg, while clonic/tonic seizures and progressively increasing mortality were seen at higher doses. Prior administration of CPA resulted either in a delay of seizure onset and unchanged mortality (0.5 mg/kg CPA, 60 mg/kg NMDA) or in elimination of tonic episodes and a significant reduction in postictal mortality (1, 2 mg/kg CPA; 60, 125 mg/kg NMDA). Pretreatment with CPX at either 1 or 2 mg/kg eliminated locomotor depression in animals injected with NMDA at 30 mg/kg. At 60 mg/kg NMDA, the effect of CPX administration resulted in mortality equivalent to that seen with 125 mg/kg NMDA administered alone. The results indicate that A1 receptor agonists may protect against NMDA-evoked seizures and that the adenosine A1 receptor may be directly involved in these actions. JF - European journal of pharmacology AU - Von Lubitz, D K AU - Paul, I A AU - Carter, M AU - Jacobson, K A AD - Laboratory of Bioorganic Chemistry, NIH/NIDDK, Bethesda, MD 20892. Y1 - 1993/11/16/ PY - 1993 DA - 1993 Nov 16 SP - 265 EP - 270 VL - 249 IS - 3 SN - 0014-2999, 0014-2999 KW - Xanthines KW - 0 KW - N(6)-cyclopentyladenosine KW - 41552-82-3 KW - N-Methylaspartate KW - 6384-92-5 KW - 1,3-dipropyl-8-cyclopentylxanthine KW - 9PTP4FOI9E KW - Adenosine KW - K72T3FS567 KW - Index Medicus KW - Injections, Intraperitoneal KW - Animals KW - Drug Interactions KW - Survival Rate KW - Temperature KW - Mice, Inbred C57BL KW - Mice KW - Male KW - Seizures -- chemically induced KW - Adenosine -- pharmacology KW - Seizures -- mortality KW - Adenosine -- administration & dosage KW - Xanthines -- administration & dosage KW - Adenosine -- analogs & derivatives KW - N-Methylaspartate -- toxicity KW - Motor Activity -- drug effects KW - Seizures -- prevention & control KW - Xanthines -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76172014?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+pharmacology&rft.atitle=Effects+of+N6-cyclopentyl+adenosine+and+8-cyclopentyl-1%2C3-dipropylxanthine+on+N-methyl-D-aspartate+induced+seizures+in+mice.&rft.au=Von+Lubitz%2C+D+K%3BPaul%2C+I+A%3BCarter%2C+M%3BJacobson%2C+K+A&rft.aulast=Von+Lubitz&rft.aufirst=D&rft.date=1993-11-16&rft.volume=249&rft.issue=3&rft.spage=265&rft.isbn=&rft.btitle=&rft.title=European+journal+of+pharmacology&rft.issn=00142999&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-02-24 N1 - Date created - 1994-02-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transformation of NIH3T3 cells with ras oncogenes abrogates the retinoic acid induction of tissue transglutaminase. AN - 76087134; 7504461 AB - Retinoic acid greatly increases enzyme activity and mRNA expression of the tissue-type transglutaminase enzyme in NIH3T3 cells. This response is blocked in cells transformed with activated H-ras, K-ras or N-ras oncogenes, but not in pSVneo vector transfected cells. Lack of induction by RA of the tissue-type TGase in these ras-transformed fibroblasts suggests intersecting pathways between retinoid action and the ras oncogene. JF - Biochemical and biophysical research communications AU - Kosa, K AU - Meyers, K AU - De Luca, L M AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1993/11/15/ PY - 1993 DA - 1993 Nov 15 SP - 1025 EP - 1033 VL - 196 IS - 3 SN - 0006-291X, 0006-291X KW - HOX2 KW - K-ras KW - N-ras KW - ras KW - RNA, Messenger KW - 0 KW - Poly A KW - 24937-83-5 KW - Tretinoin KW - 5688UTC01R KW - RNA KW - 63231-63-0 KW - Glyceraldehyde-3-Phosphate Dehydrogenases KW - EC 1.2.1.- KW - Transglutaminases KW - EC 2.3.2.13 KW - Index Medicus KW - 3T3 Cells KW - Animals KW - Blotting, Northern KW - Glyceraldehyde-3-Phosphate Dehydrogenases -- biosynthesis KW - RNA, Messenger -- analysis KW - Gene Expression KW - Transcription, Genetic KW - RNA -- analysis KW - Mice KW - RNA, Messenger -- biosynthesis KW - Cloning, Molecular KW - Kirsten murine sarcoma virus KW - Poly A -- analysis KW - Transfection KW - Genetic Vectors KW - Kinetics KW - Enzyme Induction KW - Time Factors KW - Genes, ras KW - Tretinoin -- pharmacology KW - Transglutaminases -- biosynthesis KW - Cell Transformation, Neoplastic UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76087134?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+and+biophysical+research+communications&rft.atitle=Transformation+of+NIH3T3+cells+with+ras+oncogenes+abrogates+the+retinoic+acid+induction+of+tissue+transglutaminase.&rft.au=Kosa%2C+K%3BMeyers%2C+K%3BDe+Luca%2C+L+M&rft.aulast=Kosa&rft.aufirst=K&rft.date=1993-11-15&rft.volume=196&rft.issue=3&rft.spage=1025&rft.isbn=&rft.btitle=&rft.title=Biochemical+and+biophysical+research+communications&rft.issn=0006291X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-01-04 N1 - Date created - 1994-01-04 N1 - Date revised - 2017-01-13 N1 - Gene symbol - HOX2; K-ras; N-ras; ras N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Giant multilevel cation channels formed by Alzheimer disease amyloid beta-protein [A beta P-(1-40)] in bilayer membranes. AN - 76082088; 7504270 AB - We have recently shown that the Alzheimer disease 40-residue amyloid beta-protein [A beta P-(1-40)] can form cation-selective channels when incorporated into planar lipid bilayers by fusion of liposomes containing the peptide. Since A beta P-(1-40) comprises portions of the putative extracellular and membrane-spanning domains of the amyloid precursor protein (APP751), we suggested that the channel-forming property could be the underlying cause of amyloid neurotoxicity. The peptide has been proposed to occur in vivo in both membrane-bound and soluble forms, and we now report that soluble A beta P-(1-40) can also form similar channels in solvent-free lipid bilayers formed at the tip of a patch pipet, as well as in the planar lipid bilayer system. As in the case of liposome-mediated incorporation, the amyloid channel activity in the patch pipet exhibits multiple conductance levels between 40 and 400 pS, cation selectivity, and sensitivity to tromethamine (Tris). Further studies with A beta P channels incorporated into planar lipid bilayers from the liposome complex have also revealed that the channel activity can express spontaneous transitions to a much higher range of conductances between 400 and 4000 pS. Under these conditions, the amyloid channel continues to be cation selective. Amyloid channels were insensitive to nitrendipine at either conductance range. We calculate that if such channels were expressed in cells, the ensuing ion fluxes down their electrochemical potential gradients would be homeostatically dissipative. We therefore interpret these data as providing further support for the concept that cell death in Alzheimer disease may be due to amyloid ion-channel activity. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Arispe, N AU - Pollard, H B AU - Rojas, E AD - Laboratory of Cell Biology and Genetics, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/11/15/ PY - 1993 DA - 1993 Nov 15 SP - 10573 EP - 10577 VL - 90 IS - 22 SN - 0027-8424, 0027-8424 KW - Amyloid beta-Peptides KW - 0 KW - Cations KW - Ion Channels KW - Lipid Bilayers KW - Membrane Lipids KW - Membranes, Artificial KW - Nitrendipine KW - 9B627AW319 KW - Index Medicus KW - Membrane Lipids -- chemistry KW - Nitrendipine -- pharmacology KW - Ion Channel Gating KW - Electric Conductivity KW - In Vitro Techniques KW - Membrane Potentials KW - Lipid Bilayers -- chemistry KW - Ion Channels -- chemistry KW - Amyloid beta-Peptides -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76082088?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Giant+multilevel+cation+channels+formed+by+Alzheimer+disease+amyloid+beta-protein+%5BA+beta+P-%281-40%29%5D+in+bilayer+membranes.&rft.au=Arispe%2C+N%3BPollard%2C+H+B%3BRojas%2C+E&rft.aulast=Arispe&rft.aufirst=N&rft.date=1993-11-15&rft.volume=90&rft.issue=22&rft.spage=10573&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 - 1993-12-29 N1 - Date created - 1993-12-29 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nature. 1966 Jan 1;209(5018):109-10 [5927229] J Neurosci. 1993 Apr;13(4):1676-87 [8463843] Science. 1986 Jul 11;233(4760):184-90 [2425429] Science. 1987 Feb 20;235(4791):877-80 [3810169] Science. 1987 Feb 20;235(4791):880-4 [2949367] FEBS Lett. 1987 Jun 8;217(1):25-31 [2954851] EMBO J. 1988 Apr;7(4):949-57 [2900137] Brain Res. 1988 Nov 22;474(1):100-11 [3214703] Science. 1990 Oct 12;250(4978):279-82 [2218531] Prog Brain Res. 1990;86:257-67 [2150887] J Biol Chem. 1992 Jan 5;267(1):546-54 [1730616] Brain Res. 1991 Nov 1;563(1-2):311-4 [1786545] Science. 1992 Apr 10;256(5054):184-5 [1566067] J Mol Biol. 1992 Jun 20;225(4):1075-93 [1613791] Nature. 1992 Sep 24;359(6393):322-5 [1383826] Nature. 1992 Sep 24;359(6393):325-7 [1406936] Neurobiol Aging. 1992 Sep-Oct;13(5):537-42 [1461341] Neurobiol Aging. 1992 Sep-Oct;13(5):543-51 [1461342] Neurobiol Aging. 1992 Sep-Oct;13(5):615-6 [1461352] Proc Natl Acad Sci U S A. 1993 Jan 15;90(2):567-71 [8380642] Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):2092-6 [8446635] Proc Natl Acad Sci U S A. 1985 Jun;82(12):4245-9 [3159021] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Base selection, proofreading, and mismatch repair during DNA replication in Escherichia coli. AN - 76047148; 8226906 AB - The accuracy by which organisms duplicate their DNA is of considerable interest. At least three mechanisms operate, serially, to secure high fidelity: base selection, exonucleolytic proofreading, and postreplicative mismatch correction. To obtain insights into the efficiency and specificity of these steps in the bacterium Escherichia coli, we have performed DNA sequence analysis of mutations occurring in the bacterial lacI gene in a series of strains genetically disabled in one or more of these error avoidance pathways. The base selection efficiency was estimated from mutagenesis occurring in a mutDmutL strain, which is deficient in both proofreading (mutD5) and mismatch repair (mutL). The proofreading efficiency was derived comparing the mutD5 mutL strain to the mismatch repair-deficient mutL strain. The efficiency of mismatch repair was derived comparing the mutL strain to the wild-type strain. The results show that base selection discriminates against errors by 200,000-2,000,000-fold, proofreading by 40-200-fold, and mismatch repair by 20-400-fold, each depending on the type of error. Base selection and proofreading act more strongly against transversions than transitions, whereas mismatch repair does the opposite. The data are based on 866 sequenced lacI mutations in a target that allows the scoring of at least 127 different mutations in 76 distinct DNA sequence contexts in vivo. They may therefore have general significance. JF - The Journal of biological chemistry AU - Schaaper, R M AD - Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1993/11/15/ PY - 1993 DA - 1993 Nov 15 SP - 23762 EP - 23765 VL - 268 IS - 32 SN - 0021-9258, 0021-9258 KW - lacI KW - mutD KW - mutL KW - DNA, Bacterial KW - 0 KW - Index Medicus KW - Base Sequence KW - Molecular Sequence Data KW - Mutation KW - DNA Repair KW - Base Composition KW - DNA, Bacterial -- genetics KW - DNA, Bacterial -- biosynthesis KW - Escherichia coli -- genetics KW - DNA Replication UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76047148?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Base+selection%2C+proofreading%2C+and+mismatch+repair+during+DNA+replication+in+Escherichia+coli.&rft.au=Schaaper%2C+R+M&rft.aulast=Schaaper&rft.aufirst=R&rft.date=1993-11-15&rft.volume=268&rft.issue=32&rft.spage=23762&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 - 1993-12-13 N1 - Date created - 1993-12-13 N1 - Date revised - 2017-01-13 N1 - Gene symbol - lacI; mutD; mutL N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Increased palmitoylation of the Gs protein alpha subunit after activation by the beta-adrenergic receptor or cholera toxin. AN - 76045684; 8226908 AB - The alpha subunit of the heterotrimeric Gs protein that couples the beta-adrenergic receptor to adenylyl cyclase undergoes post-translational palmitoylation. We examined the dynamics of this modification of alpha s by metabolic labeling of COS and S49 lymphoma cells under different conditions. The endogenous alpha s proteins were immunoprecipitated with a peptide-specific antibody, separated by SDS-polyacrylamide gel electrophoresis, and analyzed by fluorography and densitometry. A pulse-chase study of COS cells incubated with [3H]palmitate or [35S]methionine showed that for alpha s the palmitate turnover (t1/2 approximately 50 min) was significantly faster than the protein degradation. Treatment of cells with 10 microM isoproterenol, a beta-adrenergic receptor agonist, in the presence of [3H]palmitate led to a rapid 4-10-fold increase in the palmitoylation of alpha s. This increase in palmitoylation was concentration-dependent (EC50 approximately 0.9 microM) and blocked by the antagonist propranolol. The mutant alpha s proteins in the unc and H21a S49 cell lines did not show an increase in [3H]palmitate incorporation with isoproterenol treatment. Cholera toxin treatment of COS cells increased the [3H]palmitate incorporation into the alpha s subunits. These data indicate that palmitoylation of the alpha s subunit is dynamic and regulated by activation of the alpha s subunit. JF - The Journal of biological chemistry AU - Degtyarev, M Y AU - Spiegel, A M AU - Jones, T L AD - Molecular Pathophysiology Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/11/15/ PY - 1993 DA - 1993 Nov 15 SP - 23769 EP - 23772 VL - 268 IS - 32 SN - 0021-9258, 0021-9258 KW - Palmitic Acids KW - 0 KW - Receptors, Adrenergic, beta KW - Palmitic Acid KW - 2V16EO95H1 KW - Cholera Toxin KW - 9012-63-9 KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - Index Medicus KW - Animals KW - Tumor Cells, Cultured KW - Cells, Cultured KW - Protein Processing, Post-Translational KW - Mutation KW - Lymphoma KW - Haplorhini KW - Receptors, Adrenergic, beta -- metabolism KW - Palmitic Acids -- metabolism KW - GTP-Binding Proteins -- metabolism KW - Cholera Toxin -- pharmacology KW - Receptors, Adrenergic, beta -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76045684?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Increased+palmitoylation+of+the+Gs+protein+alpha+subunit+after+activation+by+the+beta-adrenergic+receptor+or+cholera+toxin.&rft.au=Degtyarev%2C+M+Y%3BSpiegel%2C+A+M%3BJones%2C+T+L&rft.aulast=Degtyarev&rft.aufirst=M&rft.date=1993-11-15&rft.volume=268&rft.issue=32&rft.spage=23769&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 - 1993-12-13 N1 - Date created - 1993-12-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Oncogene activation of HIV-LTR-driven expression via the NF-kappa B binding sites. AN - 76108269; 8255780 AB - The Raf-1 proto-oncogene product is a highly regulated serine/threonine kinase that functions in signal transduction downstream from growth factor receptors and upstream from nuclear proto-oncogene products. Using a transient cotransfection assay we have found that activated Raf-1 activates expression from the HIV-LTR. Analysis of a series of 5' deletion and point mutations revealed the NF-kappa B motifs as the Raf-responsive element in the HIV-LTR. Moreover, Raf-BXB activated expression from heterologous promoters driven by the HIV NF-kappa B binding sites. In addition to Raf, we show that v-Src, v-H-Ras and v-Mos activate HIV-LTR expression through the NF-kappa B binding sites and v-H-Ras-induced HIV-LTR expression is mediated by Raf-1. These findings may have implications for the involvement of the cellular homologues of these oncogenes in the switch from latent to productive infection by HIV in response to T-cell activation. JF - Nucleic acids research AU - Bruder, J T AU - Heidecker, G AU - Tan, T H AU - Weske, J C AU - Derse, D AU - Rapp, U R AD - Viral Pathology Section, NCI-Frederick Cancer Research and Development Center, MD 21702-1201. Y1 - 1993/11/11/ PY - 1993 DA - 1993 Nov 11 SP - 5229 EP - 5234 VL - 21 IS - 22 SN - 0305-1048, 0305-1048 KW - NF-kappa B KW - 0 KW - Proto-Oncogene Proteins KW - Proto-Oncogene Proteins c-raf KW - EC 2.7.11.1 KW - Index Medicus KW - AIDS/HIV KW - Mutagenesis, Site-Directed KW - Animals KW - 3T3 Cells KW - Mice KW - Transcriptional Activation KW - Binding Sites KW - Oncogenes KW - Gene Expression Regulation, Viral KW - HIV Long Terminal Repeat -- genetics KW - Proto-Oncogene Proteins -- genetics KW - NF-kappa B -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76108269?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nucleic+acids+research&rft.atitle=Oncogene+activation+of+HIV-LTR-driven+expression+via+the+NF-kappa+B+binding+sites.&rft.au=Bruder%2C+J+T%3BHeidecker%2C+G%3BTan%2C+T+H%3BWeske%2C+J+C%3BDerse%2C+D%3BRapp%2C+U+R&rft.aulast=Bruder&rft.aufirst=J&rft.date=1993-11-11&rft.volume=21&rft.issue=22&rft.spage=5229&rft.isbn=&rft.btitle=&rft.title=Nucleic+acids+research&rft.issn=03051048&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-01-13 N1 - Date created - 1994-01-13 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cell. 1977 May;11(1):223-32 [194704] Science. 1992 Sep 4;257(5075):1404-7 [1326789] Cell. 1985 Jul;41(3):813-23 [2988790] Science. 1986 Nov 21;234(4779):988-92 [3490693] Nature. 1987 Apr 16-22;326(6114):711-3 [3031512] EMBO J. 1988 Aug;7(8):2475-83 [3142763] Proc Natl Acad Sci U S A. 1988 Dec;85(23):8855-9 [3057494] Mol Cell Biol. 1989 Feb;9(2):639-47 [2710120] Nature. 1989 May 4;339(6219):70-3 [2654643] Mol Cell Biol. 1989 May;9(5):2247-50 [2501665] Cold Spring Harb Symp Quant Biol. 1988;53 Pt 1:173-84 [2978288] EMBO J. 1989 Nov;8(11):3371-8 [2555163] J Biol Chem. 1989 Dec 15;264(35):20855-8 [2556385] J Virol. 1990 Apr;64(4):1616-24 [2157047] Nature. 1990 Mar 29;344(6265):463-6 [2157161] Mol Cell Biol. 1990 Jun;10(6):2503-12 [2188091] Cell. 1990 Jun 29;61(7):1271-6 [2364429] Cell. 1990 Sep 7;62(5):1007-18 [2203531] Cell. 1990 Sep 7;62(5):1019-29 [2203532] Nature. 1990 Nov 1;348(6296):76-80 [2234062] Nucleic Acids Res. 1990 Dec 25;18(24):7433-8 [2259632] Nature. 1991 Jan 31;349(6308):426-8 [1992343] Proc Natl Acad Sci U S A. 1991 Feb 15;88(4):1227-31 [1996324] Science. 1991 Mar 22;251(5000):1490-3 [2006423] Mol Cell Biol. 1991 May;11(5):2794-803 [1708096] Proc Natl Acad Sci U S A. 1991 May 1;88(9):3715-9 [2023921] Oncogene. 1991 Apr;6(4):495-500 [2030909] J Virol. 1991 Jul;65(7):3460-7 [1645777] Nature. 1991 Aug 22;352(6337):733-6 [1876189] Cell Growth Differ. 1991 May;2(5):235-43 [1888699] Nature. 1991 Oct 17;353(6345):670-4 [1922387] J Biol Chem. 1991 Nov 5;266(31):20594-7 [1939108] Mol Cell Biol. 1992 Feb;12(2):685-95 [1531086] Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):2922-6 [1372995] Genes Dev. 1992 Apr;6(4):545-56 [1313769] Trends Genet. 1992 Feb;8(2):61-6 [1566373] Cell Growth Differ. 1991 Dec;2(12):609-17 [1687313] J Virol. 1992 Jun;66(6):3616-23 [1316471] Mol Cell Biol. 1992 Aug;12(8):3507-13 [1630458] J Biol Chem. 1992 Aug 5;267(22):15281-4 [1639773] Nature. 1992 Jul 30;358(6385):417-21 [1322500] Oncogene. 1992 Sep;7(9):1867-73 [1386920] Mol Cell Biol. 1985 May;5(5):1073-83 [2582237] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Fidelity of DNA synthesis catalyzed by human DNA polymerase alpha and HIV-1 reverse transcriptase: effect of reaction pH. AN - 19797668; 8739469 AB - The accuracy of DNA synthesis catalyzed by the Thermus aquaticus DNA polymerase and the 3'-->5' exonuclease-deficient Klenow fragment of Escherichia coli DNA polymerase I varies as a function of reaction pH (Eckert, K.A. and Kunkel, T.A. (1990) Nucleic Acids Res. 18, 3739-3744; Eckert, K.A. and Kunkel, T.A. (1993) J. Biol. Chem. 268, 13462-13471). In the current study, we demonstrate that the fidelity of human DNA polymerase alpha increases 10-fold when the pH of the in vitro synthesis reaction is lowered from pH 8.6 to pH 6.1 (37 degrees C), as determined using a base substitution reversion assay to score polymerase errors within the lacZ alpha gene of bacteriophage M13mp2. Similarly, the base substitution fidelity of DNA-dependent DNA synthesis by the human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT) was improved nine-fold at pH 6.5 relative to pH 8.0 (37 degrees C). A detailed comparison of HIV-1 RT error specificity at neutral and low pH in a lacZ alpha forward mutation assay revealed that low pH suppresses both mispairing-mediated and misalignment-mediated mutations; however, the characteristic HIV-1 RT pattern of mutational hotspots at homopolymeric sequences is retained at the lower pH. Consistent with the presumption that these mutations result, in part, from increased termination of DNA synthesis within the hotspot sequences relative to other homopolymeric sequences, the HIV-1 RT termination pattern during processive DNA synthesis is not altered by low pH. The HIV-1 RT results are in agreement with our previous hypothesis that the observed increase in polymerase fidelity at low pH results from a decreased efficiency of continuing DNA synthesis from premutational DNA intermediates. Images JF - Nucleic Acids Research AU - Eckert, K A AU - Kunkel, T A AD - National Institute of Environmental Health Sciences, Laboratory of Molecular Genetics, Research Triangle Park, NC 27709. Y1 - 1993/11/11/ PY - 1993 DA - 1993 Nov 11 SP - 5212 EP - 5220 PB - Oxford University Press, Oxford Journals, Great Clarendon Street VL - 21 IS - 22 SN - 0305-1048, 0305-1048 KW - Microbiology Abstracts B: Bacteriology; Virology & AIDS Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - Phages KW - DNA biosynthesis KW - Nucleotide sequence KW - Reversion KW - Fidelity KW - nucleic acids KW - DNA-directed DNA polymerase KW - Human immunodeficiency virus 1 KW - Escherichia coli KW - RNA-directed DNA polymerase KW - Thermus aquaticus KW - pH effects KW - Mutation KW - J 02310:Genetics & Taxonomy KW - V 22360:AIDS and HIV KW - N 14820:DNA Metabolism & Structure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19797668?accountid=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=Nucleic+Acids+Research&rft.atitle=Fidelity+of+DNA+synthesis+catalyzed+by+human+DNA+polymerase+alpha+and+HIV-1+reverse+transcriptase%3A+effect+of+reaction+pH.&rft.au=Eckert%2C+K+A%3BKunkel%2C+T+A&rft.aulast=Eckert&rft.aufirst=K&rft.date=1993-11-11&rft.volume=21&rft.issue=22&rft.spage=5212&rft.isbn=&rft.btitle=&rft.title=Nucleic+Acids+Research&rft.issn=03051048&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2008-12-01 N1 - Last updated - 2015-03-27 N1 - SubjectsTermNotLitGenreText - Phages; DNA biosynthesis; Fidelity; nucleic acids; Nucleotide sequence; DNA-directed DNA polymerase; Reversion; RNA-directed DNA polymerase; Mutation; pH effects; Human immunodeficiency virus 1; Escherichia coli; Thermus aquaticus ER - TY - JOUR T1 - Characterization of a set of integration host factor mutants deficient for DNA binding. AN - 76057652; 8230206 AB - Integration host factor, IHF, is a sequence-specific DNA-binding and DNA-bending protein composed of two related but non-identical subunits. We report the isolation and characterization of hydroxylamine-induced loss-of-function mutations in the genes encoding the IHF subunits. To screen for mutants that preserve proper folding of IHF, clarified extracts were prepared from each mutant and were assayed for production of each subunit by immunoblotting and for formation of heterodimers by chemical cross-linking and subsequent immunoblotting. Extracts from mutants that met these criteria were found to bind a specific IHF site weakly if at all. These alleles therefore identify candidates for residues that may affect the DNA-binding surfaces of IHF. When projected onto the known tertiary structure of the closely related HU protein, these residues are found at the surface; however, with the exception of a single residue, different regions of the protein are implicated in each subunit. This suggests that, despite their homology, each subunit of IHF directs DNA recognition and binding in a distinct manner. To confirm the significance of the differential location of these mutations, we introduced in each subunit alterations that had been isolated as loss-of-function mutations at the corresponding position in the other subunit. In general, the engineered mutants have phenotypes that are strikingly different from those of their hydroxylamine-induced counterparts. In particular, most of the site-directed mutant IHF proteins form or maintain IHF:DNA complexes more readily than mutants that have the same change in the other subunit and were isolated as loss-of-function mutants. We discuss the positions of the mutant amino acid residues as they relate to a proposed molecular model of an IHF:DNA complex. JF - Journal of molecular biology AU - Granston, A E AU - Nash, H A AD - Laboratory of Molecular Biology, National Institute of Mental Health, Bethesda, MD 20892. Y1 - 1993/11/05/ PY - 1993 DA - 1993 Nov 05 SP - 45 EP - 59 VL - 234 IS - 1 SN - 0022-2836, 0022-2836 KW - Bacterial Proteins KW - 0 KW - DNA Primers KW - DNA-Binding Proteins KW - Integration Host Factors KW - Macromolecular Substances KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Molecular Sequence Data KW - Genetic Complementation Test KW - Amino Acid Sequence KW - Protein Binding KW - Structure-Activity Relationship KW - Protein Conformation KW - DNA Primers -- chemistry KW - Bacterial Proteins -- genetics KW - DNA-Binding Proteins -- chemistry KW - Bacterial Proteins -- chemistry KW - Bacterial Proteins -- metabolism KW - DNA-Binding Proteins -- genetics KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76057652?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Characterization+of+a+set+of+integration+host+factor+mutants+deficient+for+DNA+binding.&rft.au=Granston%2C+A+E%3BNash%2C+H+A&rft.aulast=Granston&rft.aufirst=A&rft.date=1993-11-05&rft.volume=234&rft.issue=1&rft.spage=45&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 - 1993-12-09 N1 - Date created - 1993-12-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - An AP-1-like factor and the pituitary-specific factor Pit-1 are both necessary to mediate hormonal induction of human thyrotropin beta gene expression. AN - 76036137; 8226861 AB - The human thyrotropin beta (hTSH beta) gene is inducible by various agents including thyrotropin-releasing hormone, phorbol esters, or the adenylyl cyclase activator forskolin. In this study, we have characterized the functional properties of the TGGGTCA motif at -1/+6 of the hTSH beta gene that is similar to the consensus phorbol ester response element (TRE) or the consensus cyclic AMP response element (CRE). We suggest that both protein kinases C and A as well as TRH share a common mediator which recognizes the TGGGTCA element in activating the hTSH beta promoter. Following stimulation by phorbol esters, forskolin, or TRH, the TGGGTCA-specific factor acts together with the pituitary-specific transcription factor Pit-1 (or GHF-1) bound to upstream sequences at -128 to -61 to mediate the induction of the hTSH beta promoter. The induction requires that both factors bind to their own binding sites, but Pit-1 neither increases the binding of the TGGGTCA-specific factor to its target sequences nor associates with this factor to form a heterodimer. The TGGGTCA-specific factor is present in three cell lines tested and is composed of protein(s) immunologically related to c-Jun and c-Fos but not to the CRE-binding protein, CREB. By using the hTSH beta reporter plasmids in which the TGGGTCA element is converted to consensus TRE or CRE motifs, we found that, within the context of the hTSH beta promoter, the TGGGTCA element is a more potent TRE or CRE than the consensus TRE or CRE sequences. Based upon the results of this study, we propose a model in which the TGGGTCA-specific AP-1-like factor functionally cooperates with the tissue-specific factor Pit-1 to activate the hTSH beta gene. JF - The Journal of biological chemistry AU - Kim, M K AU - McClaskey, J H AU - Bodenner, D L AU - Weintraub, B D AD - Molecular and Cellular Endocrinology Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/11/05/ PY - 1993 DA - 1993 Nov 05 SP - 23366 EP - 23375 VL - 268 IS - 31 SN - 0021-9258, 0021-9258 KW - DNA-Binding Proteins KW - 0 KW - Oligodeoxyribonucleotides KW - POU1F1 protein, human KW - Proto-Oncogene Proteins c-jun KW - RNA, Messenger KW - Transcription Factor Pit-1 KW - Transcription Factors KW - Colforsin KW - 1F7A44V6OU KW - Thyrotropin-Releasing Hormone KW - 5Y5F15120W KW - Thyrotropin KW - 9002-71-5 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Thyrotropin-Releasing Hormone -- pharmacology KW - Promoter Regions, Genetic KW - Colforsin -- pharmacology KW - Base Sequence KW - HeLa Cells KW - Oligodeoxyribonucleotides -- chemistry KW - Humans KW - Molecular Sequence Data KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Gene Expression Regulation KW - RNA, Messenger -- genetics KW - Transcription Factors -- physiology KW - Thyrotropin -- genetics KW - Proto-Oncogene Proteins c-jun -- physiology KW - DNA-Binding Proteins -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76036137?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=An+AP-1-like+factor+and+the+pituitary-specific+factor+Pit-1+are+both+necessary+to+mediate+hormonal+induction+of+human+thyrotropin+beta+gene+expression.&rft.au=Kim%2C+M+K%3BMcClaskey%2C+J+H%3BBodenner%2C+D+L%3BWeintraub%2C+B+D&rft.aulast=Kim&rft.aufirst=M&rft.date=1993-11-05&rft.volume=268&rft.issue=31&rft.spage=23366&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 - 1993-11-29 N1 - Date created - 1993-11-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dose-intensive therapy for breast cancer. AN - 76004057; 8411576 JF - JAMA AU - O'Shaughnessy, J A AU - Cowan, K H AD - Medical Breast Cancer Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/11/03/ PY - 1993 DA - 1993 Nov 03 SP - 2089 EP - 2092 VL - 270 IS - 17 SN - 0098-7484, 0098-7484 KW - Receptors, Estrogen KW - 0 KW - Tamoxifen KW - 094ZI81Y45 KW - Doxorubicin KW - 80168379AG KW - Granulocyte-Macrophage Colony-Stimulating Factor KW - 83869-56-1 KW - Cyclophosphamide KW - 8N3DW7272P KW - Leucovorin KW - Q573I9DVLP KW - Fluorouracil KW - U3P01618RT KW - Abridged Index Medicus KW - Index Medicus KW - Cyclophosphamide -- administration & dosage KW - Bone Marrow Transplantation -- methods KW - Fatal Outcome KW - Gene Transfer Techniques KW - Humans KW - Leucovorin -- administration & dosage KW - Receptors, Estrogen -- analysis KW - Doxorubicin -- administration & dosage KW - Tamoxifen -- administration & dosage KW - Fluorouracil -- administration & dosage KW - Neoplasm Recurrence, Local -- drug therapy KW - Adult KW - Chemotherapy, Adjuvant KW - Female KW - Breast Neoplasms -- drug therapy KW - Bone Marrow -- pathology KW - Carcinoma, Ductal, Breast -- pathology KW - Salvage Therapy KW - Breast Neoplasms -- therapy KW - Antineoplastic Combined Chemotherapy Protocols -- administration & dosage KW - Liver Neoplasms -- secondary KW - Granulocyte-Macrophage Colony-Stimulating Factor -- therapeutic use KW - Carcinoma, Ductal, Breast -- therapy KW - Brain Neoplasms -- secondary KW - Carcinoma, Ductal, Breast -- secondary KW - Carcinoma, Ductal, Breast -- drug therapy KW - Brain Neoplasms -- drug therapy KW - Breast Neoplasms -- pathology KW - Liver Neoplasms -- drug therapy KW - Brain Neoplasms -- radiotherapy KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76004057?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=proceeding&rft.jtitle=JAMA&rft.atitle=Dose-intensive+therapy+for+breast+cancer.&rft.au=O%27Shaughnessy%2C+J+A%3BCowan%2C+K+H&rft.aulast=O%27Shaughnessy&rft.aufirst=J&rft.date=1993-11-03&rft.volume=270&rft.issue=17&rft.spage=2089&rft.isbn=&rft.btitle=&rft.title=JAMA&rft.issn=00987484&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-11-19 N1 - Date created - 1993-11-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Desulfuration of 6-mercaptopurine. The basis for the paradoxical cytotoxicity of thiopurines in cultured human leukemic cells. AN - 76067615; 8240420 AB - The thiopurines have a wide array of effects on purine metabolism, but the primary mechanism of cytotoxicity for both 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG) appears to be incorporation of drug into DNA following conversion to the thioguanylate form. In murine leukemic cell lines exposed to a range of thiopurine concentrations in vitro, cell survival curves have displayed a phenomenon termed paradoxical cytotoxicity, defined as a decrease in cytotoxicity with increasing drug concentration. The paradoxical cytotoxicity of thiopurines has usually been attributed to concentration-dependent perturbations in the cell cycle. The present study assessed whether the paradoxical cytotoxicity of 6-MP occurred in cultured human leukemic cells, and investigated the biochemical and cell-cycle alterations occurring in these lines at thiopurine concentrations associated with the reverse of cytotoxicity. Paradoxical cytotoxicity was observed in the two human leukemic cell lines examined, but only when 6-MP concentrations exceeded 100 microM. The extent of incorporation of 6-MP metabolites into DNA as thiol-versus non-thiol-containing metabolites was analyzed by performing parallel experiments with 14C- and 35S-radiolabeled drug. With 5 microM 6-MP, approximately 50% of drug was incorporated into DNA as a thionucleotide; however, with increasing drug concentrations, the degree of thionucleotide incorporation remained unchanged or decreased, and the amount incorporated as the desulfurated metabolite (presumably adenylate or guanylate) increased. With 500 microM 6-MP, less than 10% of the drug was incorporated as the thionucleotide. Perturbations in cell cycle reflected the relative amounts of thiol- and non-thiol-containing nucleotide formed at various concentrations of 6-MP. These results suggest that thiopurines may be vulnerable to a unique mechanism of detoxification, in which a human cell can metabolize a cytotoxic drug to a comparatively potent "self-rescue" agent. JF - Biochemical pharmacology AU - Adamson, P C AU - Balis, F M AU - Hawkins, M E AU - Murphy, R F AU - Poplack, D G AD - Pharmacology and Experimental Therapeutics Section, National Cancer Institute, Bethesda, MD 20892. Y1 - 1993/11/02/ PY - 1993 DA - 1993 Nov 02 SP - 1627 EP - 1636 VL - 46 IS - 9 SN - 0006-2952, 0006-2952 KW - Carbon Radioisotopes KW - 0 KW - Hypoxanthines KW - Sulfur Radioisotopes KW - Thionucleotides KW - Hypoxanthine KW - 2TN51YD919 KW - DNA KW - 9007-49-2 KW - 6-Mercaptopurine KW - E7WED276I5 KW - Hypoxanthine Phosphoribosyltransferase KW - EC 2.4.2.8 KW - Thioguanine KW - FTK8U1GZNX KW - Index Medicus KW - Tumor Cells, Cultured -- drug effects KW - Dose-Response Relationship, Drug KW - Humans KW - Thionucleotides -- metabolism KW - Hypoxanthine Phosphoribosyltransferase -- metabolism KW - Thioguanine -- pharmacology KW - Inactivation, Metabolic KW - Cell Survival -- drug effects KW - Hypoxanthines -- pharmacology KW - Cell Cycle -- drug effects KW - DNA -- metabolism KW - 6-Mercaptopurine -- metabolism KW - 6-Mercaptopurine -- pharmacology KW - 6-Mercaptopurine -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76067615?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+pharmacology&rft.atitle=Desulfuration+of+6-mercaptopurine.+The+basis+for+the+paradoxical+cytotoxicity+of+thiopurines+in+cultured+human+leukemic+cells.&rft.au=Adamson%2C+P+C%3BBalis%2C+F+M%3BHawkins%2C+M+E%3BMurphy%2C+R+F%3BPoplack%2C+D+G&rft.aulast=Adamson&rft.aufirst=P&rft.date=1993-11-02&rft.volume=46&rft.issue=9&rft.spage=1627&rft.isbn=&rft.btitle=&rft.title=Biochemical+pharmacology&rft.issn=00062952&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-12-16 N1 - Date created - 1993-12-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Glycosylation-dependent activity of baculovirus-expressed human liver carboxylesterases: cDNA cloning and characterization of two highly similar enzyme forms. AN - 76026391; 8218228 AB - A cDNA, designated hCE, encoding the entire sequence of a carboxylesterase, was isolated from a human liver lambda gt11 library. The hCE-deduced protein sequence contained 568 amino acids, including an 18 amino acid signal peptide sequence, and had a calculated molecular mass of the mature protein of 60,609 Da. A second cDNA, designated hCEv, was isolated from the same lambda gt11 library and contained a 3-bp deletion resulting in the loss of the final amino acid in the signal peptide sequence (Ala-1) and a second 3-bp deletion leading to an in-frame loss of Gln345. Expression of mRNA corresponding to both hCE and hCEv was detected in eight adult human liver samples, with individual levels varying 5-fold (hCE) and 12-fold (hCEv). A single immunoreactive protein was detected in 13 adult human liver samples when probed with antibody directed against a rat carboxylesterase. Based on allele-specific oligonucleotide hybridizations, we believe that the hCE and hCEv cDNAs represent two distinct members of the carboxylesterase family. The carboxylesterase genes were localized to human chromosome 16 using a somatic cell hybrid mapping strategy. Baculovirus expression of hCE in Sf9 cells produced a protein with an estimated molecular mass of 59,000 Da. This enzyme was able to hydrolyze aromatic and aliphatic esters but possessed no catalytic activity toward amides or a fatty acyl CoA ester. Baculovirus-mediated expression of the hCEv cDNA yielded a second protein of 56,000 Da resulting from inefficient N-glycosylation of the hCEv protein. Although the substrate specificity for the hCEv protein was identical to that of expressed hCE for any given substrate, the specific activity for the hCE protein was always higher than that for the hCEv protein. Tunicamycin inhibition studies provided the first evidence that N-glycosylation of these luminal enzymes is essential for maximal catalytic activity. JF - Biochemistry AU - Kroetz, D L AU - McBride, O W AU - Gonzalez, F J AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/11/02/ PY - 1993 DA - 1993 Nov 02 SP - 11606 EP - 11617 VL - 32 IS - 43 SN - 0006-2960, 0006-2960 KW - DNA, Complementary KW - 0 KW - Isoenzymes KW - RNA, Messenger KW - Recombinant Proteins KW - Carboxylic Ester Hydrolases KW - EC 3.1.1.- KW - Index Medicus KW - Animals KW - Chromosomes, Human, Pair 16 KW - Humans KW - RNA, Messenger -- analysis KW - DNA, Complementary -- isolation & purification KW - Amino Acid Sequence KW - Glycosylation KW - Moths KW - Chromosome Mapping KW - Cloning, Molecular KW - Baculoviridae KW - Alleles KW - Base Sequence KW - Recombinant Proteins -- metabolism KW - Genetic Vectors KW - Molecular Sequence Data KW - Substrate Specificity KW - Carboxylic Ester Hydrolases -- metabolism KW - Liver -- enzymology KW - Carboxylic Ester Hydrolases -- genetics KW - Isoenzymes -- genetics KW - Isoenzymes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76026391?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Glycosylation-dependent+activity+of+baculovirus-expressed+human+liver+carboxylesterases%3A+cDNA+cloning+and+characterization+of+two+highly+similar+enzyme+forms.&rft.au=Kroetz%2C+D+L%3BMcBride%2C+O+W%3BGonzalez%2C+F+J&rft.aulast=Kroetz&rft.aufirst=D&rft.date=1993-11-02&rft.volume=32&rft.issue=43&rft.spage=11606&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-11-29 N1 - Date created - 1993-11-29 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - L07765; GENBANK; X71481; L07764; D17642; D17801; X71774; D17800; D17802; D17799; X74555 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Relative probability of mutagenic translesion synthesis on the leading and lagging strands during replication of UV-irradiated DNA in a human cell extract. AN - 75973953; 8218213 AB - We have previously demonstrated mutagenic bypass of pyrimidine dimers during SV40 origin-dependent replication of UV-irradiated DNA in human cell extracts [Thomas, D. C., & Kunkel, T. A. (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 7744-7748]. Here we use two vectors having the origin of replication on opposite sides of a lacZ alpha reporter gene to examine the relative probability of mutagenic translesion synthesis on the leading and lagging strands. Although replication of both vectors is inhibited by UVB irradiation in a dose-dependent manner, the covalently closed DNA products of replication contain T4 endonuclease sensitive sites, indicating that bypass of cyclobutane pyrimidine dimers occurred. At fluences of 70 and 100 J/m2, the mutant frequencies obtained with both vectors are substantially higher than with control DNAs. Sequence analysis of mutants obtained with both vectors reveal three types of mutations at frequencies significantly above those obtained from replication of undamaged DNA. These are C-->T transitions, accounting for about two-thirds of the mutants, a small number of CC-->TT substitutions, and complex mutations. Comparing the distribution of C-->T substitutions in the two spectra permits an estimation of the probability of mutagenic translesion replication of the same sequence when replicated as the leading or lagging strand. The data suggest that the overall average UV-independent C-->T substitution probability per phenotypically detectable dipyrimidine site is the same during leading and lagging strand replication. However, statistically significant differences are observed when the distribution of C-->T substitutions is considered.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Biochemistry AU - Thomas, D C AU - Nguyen, D C AU - Piegorsch, W W AU - Kunkel, T A AD - Laboratory of Molecular Genetics and Statistics and Biomathematics Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1993/11/02/ PY - 1993 DA - 1993 Nov 02 SP - 11476 EP - 11482 VL - 32 IS - 43 SN - 0006-2960, 0006-2960 KW - Pyrimidine Dimers KW - 0 KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Probability KW - Ultraviolet Rays KW - Base Sequence KW - HeLa Cells KW - Humans KW - Simian virus 40 KW - Molecular Sequence Data KW - DNA -- radiation effects KW - DNA Replication -- genetics KW - DNA Damage -- genetics KW - Mutagenesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75973953?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Relative+probability+of+mutagenic+translesion+synthesis+on+the+leading+and+lagging+strands+during+replication+of+UV-irradiated+DNA+in+a+human+cell+extract.&rft.au=Thomas%2C+D+C%3BNguyen%2C+D+C%3BPiegorsch%2C+W+W%3BKunkel%2C+T+A&rft.aulast=Thomas&rft.aufirst=D&rft.date=1993-11-02&rft.volume=32&rft.issue=43&rft.spage=11476&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-11-29 N1 - Date created - 1993-11-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A randomized, controlled trial of recombinant alpha-interferon therapy for chronic hepatitis B. AN - 85223582; pmid-8237937 AB - OBJECTIVES: To evaluate the effect of recombinant alpha-interferon in chronic hepatitis B. METHODS: Patients were stratified at entry according to their serum aspartate aminotransferase (AST) values, randomized to receive alpha-interferon (alfa-2b, 10 million units three times weekly) or to be untreated controls for 16 wk. Effect of therapy on levels of hepatitis B viral (HBV) DNA and aminotransferase activities in serum and hepatitis B e antigen (HBeAg) status was monitored. RESULTS: Forty-seven patients entered the trial; 11 of 25 (44%) patients receiving interferon responded by clearing HBeAg and HBV DNA within 6 months, compared to one of 22 (5%) controls (p 100 U/L, 60% responded. Within the 6-month study period, 36% of treated patients had normal serum alanine aminotransferase (ALT) values, and 16% had cleared hepatitis B surface antigen (HBsAg) from serum, whereas none of the controls had normal ALT values or had lost HBsAg. Interferon was stopped early in three patients (6.5%), and dosage was reduced in a further 16 patients (35%) because of adverse effects. Predictive factors for a response were the pretreatment serum ALT and AST activities. CONCLUSIONS: alpha-Interferon therapy (three times weekly) is relatively well tolerated and is effective in clearing HBeAg and HBV DNA in approximately one-third of treated patients. JF - The American Journal of Gastroenterology AU - Di Bisceglie A M AU - Fong, T L AU - Fried, M W AU - Swain, M G AU - Baker, B AU - Korenman, J AU - Bergasa, N V AU - Waggoner, J G AU - Park, Y AU - Hoofnagle, J H AD - Liver Diseases Section, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland. PY - 1993 SP - 1887 EP - 1892 VL - 88 IS - 11 SN - 0002-9270, 0002-9270 KW - Hepatitis B Surface Antigens KW - Hepatitis, Chronic KW - Human KW - Aspartate Aminotransferases KW - Hepatitis B Virus KW - Hepatitis B e Antigens KW - Alanine Transaminase KW - DNA, Viral KW - Comparative Study KW - Adult KW - Hepatitis B KW - Enzyme-Linked Immunosorbent Assay KW - Interferon Alfa-2b KW - Female KW - Male UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85223582?accountid=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+American+Journal+of+Gastroenterology&rft.atitle=A+randomized%2C+controlled+trial+of+recombinant+alpha-interferon+therapy+for+chronic+hepatitis+B.&rft.au=Di+Bisceglie+A+M%3BFong%2C+T+L%3BFried%2C+M+W%3BSwain%2C+M+G%3BBaker%2C+B%3BKorenman%2C+J%3BBergasa%2C+N+V%3BWaggoner%2C+J+G%3BPark%2C+Y%3BHoofnagle%2C+J+H&rft.aulast=Di+Bisceglie+A+M&rft.aufirst=&rft.date=1993-11-01&rft.volume=88&rft.issue=11&rft.spage=1887&rft.isbn=&rft.btitle=&rft.title=The+American+Journal+of+Gastroenterology&rft.issn=00029270&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - The regulatory subunit of cAMP-dependent protein kinase as a target for chemotherapy of cancer and other cellular dysfunctional-related diseases. AN - 76286073; 8022860 AB - Three separate experimental approaches, using site-selective cAMP analogs, antisense strategy and retroviral vector-mediated gene transfer, have provided evidence that two isoforms, the RI- and RII-regulatory subunits of cAMP-dependent protein kinase, have opposite roles in cell growth and differentiation; RI being growth stimulatory while RII is a growth-inhibitory and differentiation-inducing protein. As RI expression is enhanced during chemical or viral carcinogenesis, in human cancer cell lines and in primary human tumors, it is a target for cancer diagnosis and therapy. 8-Cl-cAMP and RI antisense oligodeoxynucleotide, those that effectively down-regulate RI alpha and up-regulate RII beta, provide new approaches toward the treatment of cancer. This approach to modulation of RI vs RII cAMP transducers may also be beneficial toward therapy of endocrine or cellular dysfunction-related diseases where abnormal signal transduction of cAMP is critically involved. JF - Pharmacology & therapeutics AU - Cho-Chung, Y S AU - Clair, T AD - Cellular Biochemistry Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/11// PY - 1993 DA - November 1993 SP - 265 EP - 288 VL - 60 IS - 2 SN - 0163-7258, 0163-7258 KW - Biomarkers KW - 0 KW - Cyclic AMP Receptor Protein KW - Cyclic AMP-Dependent Protein Kinase RIIbeta Subunit KW - Cyclic AMP-Dependent Protein Kinase RIalpha Subunit KW - Enzyme Inhibitors KW - Isoenzymes KW - Oligonucleotides, Antisense KW - PRKAR1A protein, human KW - PRKAR2B protein, human KW - Cyclic AMP-Dependent Protein Kinases KW - EC 2.7.11.11 KW - Index Medicus KW - Animals KW - Diabetes Mellitus -- metabolism KW - Humans KW - Cyclic AMP Receptor Protein -- physiology KW - Cell Transformation, Neoplastic -- drug effects KW - Amino Acid Sequence KW - Hypertension -- drug therapy KW - Oligonucleotides, Antisense -- therapeutic use KW - Gene Expression Regulation, Enzymologic KW - Isoenzymes -- physiology KW - Signal Transduction -- drug effects KW - Molecular Sequence Data KW - Psoriasis -- drug therapy KW - Psoriasis -- metabolism KW - Hypertension -- metabolism KW - Diabetes Mellitus -- drug therapy KW - Neoplasms -- drug therapy KW - Cyclic AMP-Dependent Protein Kinases -- physiology KW - Enzyme Inhibitors -- chemistry KW - Cyclic AMP-Dependent Protein Kinases -- therapeutic use KW - Enzyme Inhibitors -- pharmacology KW - Cyclic AMP-Dependent Protein Kinases -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76286073?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+therapeutics&rft.atitle=The+regulatory+subunit+of+cAMP-dependent+protein+kinase+as+a+target+for+chemotherapy+of+cancer+and+other+cellular+dysfunctional-related+diseases.&rft.au=Cho-Chung%2C+Y+S%3BClair%2C+T&rft.aulast=Cho-Chung&rft.aufirst=Y&rft.date=1993-11-01&rft.volume=60&rft.issue=2&rft.spage=265&rft.isbn=&rft.btitle=&rft.title=Pharmacology+%26+therapeutics&rft.issn=01637258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-08-04 N1 - Date created - 1994-08-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Prognosis of single unprovoked seizure. AN - 76285402; 8005923 AB - 201 patients (131 males and 70 females) with mean age of 18 years (range 5-55 years) who presented at median of 6 days after the onset of first unprovoked seizure were studied. They were followed for a mean period of 60 months (range 12-84 months). One hundred and fifty four (76%) patients were treated with anticonvulsant medication (group A) on a non-randomized basis and the remaining 47 patients (24%) were not treated (group B). Both the groups were comparable for age, sex, type of seizure and interval between onset of seizure and consultation. The cumulative risk of recurrence for entire study group was 24% at 1 month, 32% at 6 months, 34% at 12 months, 35% at 24 months and 36% at 36 months. The cumulative risk of recurrence in group A was 23%, 30%, 32%, 33% and 33% as compared to 28%, 36%, 40%, 43% and 45% at 1, 6, 12, 24 and 36 months respectively (p > 0.05). Maximum number of recurrences (67%) occurred within 1 month. No recurrence occurred after 36 months after the onset of first seizure. Age at onset, sex, seizure type, family history of seizure, EEG abnormalities and nature of antiepileptic drugs did not influence the risk of recurrence. JF - The Journal of the Association of Physicians of India AU - Gupta, S K AU - Satishchandra, P AU - Venkatesh, A AU - Subbakrishna, D K AD - Department of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India. Y1 - 1993/11// PY - 1993 DA - November 1993 SP - 709 EP - 710 VL - 41 IS - 11 SN - 0004-5772, 0004-5772 KW - Anticonvulsants KW - 0 KW - Index Medicus KW - Humans KW - Prognosis KW - Electroencephalography -- drug effects KW - Child KW - Recurrence KW - Child, Preschool KW - Prospective Studies KW - Adult KW - Follow-Up Studies KW - Middle Aged KW - Adolescent KW - Female KW - Male KW - Anticonvulsants -- adverse effects KW - Epilepsy -- drug therapy KW - Anticonvulsants -- therapeutic use KW - Epilepsy -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76285402?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+the+Association+of+Physicians+of+India&rft.atitle=Prognosis+of+single+unprovoked+seizure.&rft.au=Gupta%2C+S+K%3BSatishchandra%2C+P%3BVenkatesh%2C+A%3BSubbakrishna%2C+D+K&rft.aulast=Gupta&rft.aufirst=S&rft.date=1993-11-01&rft.volume=41&rft.issue=11&rft.spage=709&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+the+Association+of+Physicians+of+India&rft.issn=00045772&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-07-19 N1 - Date created - 1994-07-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Retroviruses and inflammatory myopathies in humans and primates. AN - 76279827; 8156147 AB - The human immunodeficiency virus (HIV), the human T cell lymphotropic virus (HTLV-1), the human foamy retrovirus and the simian immunodeficiency viruses have been associated with the development of an inflammatory myopathy in humans and primates. The myopathy caused by HIV and HTLV-1 is not due to direct infection of the muscle by these viruses, but rather due to an immunopathologic process triggered by the viruses, mediated by autoaggressive CD8+ cells in the context of MHC-class I antigen expression. This has been based on a series of studies utilizing immunocytochemistry, in situ hybridization, polymerase chain reaction, and co-cultivation of human myotubes with the viruses or with HIV-1 and HTLV-1-infected homologous lymphoid cells. Because the clinical, histological and immunological picture of patients with retroviral-associated inflammatory myopathies is identical to that of patients with retroviral-negative inflammatory myopathy, there is a reasonable possibility that retroviruses may be candidate viruses in triggering inflammatory myopathies. In recent years, the antiretroviral drug AZT (Zidovudine), commonly used for the treatment of AIDS, has been shown to cause a distinct mitochondrial myopathy characterized by depletion of the muscle mitochondrial DNA due to AZT's ability to inhibit the gamma-DNA polymerase of the mitochondrial matrix. Distinction of the AZT-myopathy is clinically important because it responds to discontinuation of AZT and to administration of another antiretroviral agent such as ddI or ddC. JF - Bailliere's clinical neurology AU - Dalakas, M C AD - Neuromuscular Diseases Section, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/11// PY - 1993 DA - November 1993 SP - 659 EP - 691 VL - 2 IS - 3 SN - 0961-0421, 0961-0421 KW - Zidovudine KW - 4B9XT59T7S KW - Index Medicus KW - AIDS/HIV KW - Zidovudine -- therapeutic use KW - Zidovudine -- adverse effects KW - HTLV-I Infections -- microbiology KW - Humans KW - Retroviridae KW - HIV Infections -- drug therapy KW - HIV Infections -- microbiology KW - HTLV-I Infections -- pathology KW - HIV Infections -- pathology KW - Myositis -- microbiology KW - Myositis -- drug therapy KW - Retroviridae Infections -- drug therapy KW - Myositis -- pathology KW - Retroviridae Infections -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76279827?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Bailliere%27s+clinical+neurology&rft.atitle=Retroviruses+and+inflammatory+myopathies+in+humans+and+primates.&rft.au=Dalakas%2C+M+C&rft.aulast=Dalakas&rft.aufirst=M&rft.date=1993-11-01&rft.volume=2&rft.issue=3&rft.spage=659&rft.isbn=&rft.btitle=&rft.title=Bailliere%27s+clinical+neurology&rft.issn=09610421&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-05-16 N1 - Date created - 1994-05-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Discovery and rediscovery. AN - 76274945; 8157166 JF - Allergy proceedings : the official journal of regional and state allergy societies AU - Cohen, S G AD - National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland. PY - 1993 SP - 427 EP - 428 VL - 14 IS - 6 SN - 1046-9354, 1046-9354 KW - Aspirin KW - R16CO5Y76E KW - Index Medicus KW - History of medicine KW - Nasal Mucosa -- secretion KW - Nasal Mucosa -- pathology KW - Asthma -- etiology KW - History, 20th Century KW - Drug Eruptions -- etiology KW - Aspirin -- adverse effects KW - Humans KW - Anaphylaxis -- etiology KW - Desensitization, Immunologic KW - Drug Eruptions -- therapy KW - Eosinophilia -- history KW - Eosinophilia -- diagnosis KW - Nose Diseases -- history KW - Rhinitis -- history KW - Rhinitis -- diagnosis KW - Nose Diseases -- diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76274945?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Allergy+proceedings+%3A+the+official+journal+of+regional+and+state+allergy+societies&rft.atitle=Discovery+and+rediscovery.&rft.au=Cohen%2C+S+G&rft.aulast=Cohen&rft.aufirst=S&rft.date=1993-11-01&rft.volume=14&rft.issue=6&rft.spage=427&rft.isbn=&rft.btitle=&rft.title=Allergy+proceedings+%3A+the+official+journal+of+regional+and+state+allergy+societies&rft.issn=10469354&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-05-19 N1 - Date created - 1994-05-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mortality in the coke oven plant of Carrara, Italy. AN - 76274567; 8177128 AB - A mortality study was undertaken on a cohort of 538 male workers employed at a coke plant in Carrara in the period 1960-1985. The follow-up period ranged from January 1 1960 to December 31 1990, with 10,665 person-years accumulated. A significant excess in mortality for lung cancer was observed: 19 observed deaths vs 10.02 expected deaths using national rates, SMR 190 (C.I. 95% = 114-296), and vs 11.19 expected deaths using regional rates, SMR 170 (C.I. 95% = 102-265). The results suggest the possible influence of this occupation on mortality from lung cancer, as was observed in previous studies performed on larger cohorts of coke oven workers. JF - La Medicina del lavoro AU - Franco, F AU - Chellini, E AU - Seniori Costantini, A AU - Gioia, A AU - Carra, G AU - Paolinelli, F AU - Martelli, C AU - Vigotti, M AD - Servizio di Prevenzione Igiene e Sicurezza nei Luoghi di Lavoro, USL 2, Massa Carrara. PY - 1993 SP - 443 EP - 447 VL - 84 IS - 6 SN - 0025-7818, 0025-7818 KW - Coke KW - 0 KW - Index Medicus KW - Occupational Exposure KW - Lung Neoplasms -- etiology KW - Humans KW - Adult KW - Lung Neoplasms -- mortality KW - Follow-Up Studies KW - Male KW - Italy KW - Occupational Diseases -- etiology KW - Coke -- adverse effects KW - Occupational Diseases -- mortality UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76274567?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=La+Medicina+del+lavoro&rft.atitle=Mortality+in+the+coke+oven+plant+of+Carrara%2C+Italy.&rft.au=Franco%2C+F%3BChellini%2C+E%3BSeniori+Costantini%2C+A%3BGioia%2C+A%3BCarra%2C+G%3BPaolinelli%2C+F%3BMartelli%2C+C%3BVigotti%2C+M&rft.aulast=Franco&rft.aufirst=F&rft.date=1993-11-01&rft.volume=84&rft.issue=6&rft.spage=443&rft.isbn=&rft.btitle=&rft.title=La+Medicina+del+lavoro&rft.issn=00257818&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-06-07 N1 - Date created - 1994-06-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pharmacokinetics, cerebrospinal fluid penetration, and metabolism of piroxantrone in the rhesus monkey. AN - 76257089; 8157468 AB - Piroxantrone is an anthrapyrazole derivative with broad anti-tumor activity in vitro and less cardiac toxicity than the anthracyclines. The metabolic pathways and central nervous system penetration of piroxantrone have not been determined. In this study we examined the pharmacokinetic behavior of piroxantrone in plasma and cerebrospinal fluid in a non-human primate model. In addition, a urinary metabolite of piroxantrone was isolated and its cytotoxicity evaluated in vitro. The disappearance of piroxantrone from plasma after an intravenous dose of 150 mg/m2 given over 60 minutes was biexponential with mean t1/2 alpha of 1.0 minutes and a mean t1/2 beta of 180 minutes. The mean area under the curve was 220 microM.min and the clearance was 1420 ml/min/m2. Piroxantrone was not detectable in the cerebrospinal fluid. Piroxantrone and three other compounds not present in pre-treatment samples were detected in urine. The major urinary metabolite was isolated. Its cytotoxicity against MOLT-4 cells in vitro was at least one log less than that of piroxantrone. In addition, one of the other compounds detected in urine was determined to be a glucuronide conjugation product of the major metabolite. The results of this study may be useful in the interpretation of the activity and toxicity of piroxantrone in clinical trials. JF - Investigational new drugs AU - Berg, S L AU - Balis, F M AU - Godwin, K S AU - Poplack, D G AD - Pediatric Branch, National Cancer Institute, Bethesda, MD 20892. Y1 - 1993/11// PY - 1993 DA - November 1993 SP - 255 EP - 261 VL - 11 IS - 4 SN - 0167-6997, 0167-6997 KW - Anthraquinones KW - 0 KW - Antineoplastic Agents KW - Glucuronates KW - Pyrazoles KW - piroxantrone KW - YL4TY9WH22 KW - Index Medicus KW - Drug Stability KW - Drug Screening Assays, Antitumor KW - Animals KW - Tumor Cells, Cultured KW - Glucuronates -- urine KW - Glucuronates -- pharmacology KW - Macaca mulatta KW - Male KW - Pyrazoles -- metabolism KW - Pyrazoles -- pharmacology KW - Antineoplastic Agents -- cerebrospinal fluid KW - Antineoplastic Agents -- pharmacokinetics KW - Antineoplastic Agents -- metabolism KW - Anthraquinones -- pharmacokinetics KW - Anthraquinones -- pharmacology KW - Anthraquinones -- metabolism KW - Antineoplastic Agents -- pharmacology KW - Anthraquinones -- cerebrospinal fluid KW - Pyrazoles -- pharmacokinetics KW - Pyrazoles -- cerebrospinal fluid UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76257089?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Investigational+new+drugs&rft.atitle=Pharmacokinetics%2C+cerebrospinal+fluid+penetration%2C+and+metabolism+of+piroxantrone+in+the+rhesus+monkey.&rft.au=Berg%2C+S+L%3BBalis%2C+F+M%3BGodwin%2C+K+S%3BPoplack%2C+D+G&rft.aulast=Berg&rft.aufirst=S&rft.date=1993-11-01&rft.volume=11&rft.issue=4&rft.spage=255&rft.isbn=&rft.btitle=&rft.title=Investigational+new+drugs&rft.issn=01676997&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-05-17 N1 - Date created - 1994-05-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Are binge drinkers more at risk of developing brain damage? AN - 76251260; 8123218 AB - Alcoholism is often associated with brain damage and cognitive deficits. Because drinking patterns can include periods of alcohol consumption followed by abstinence, binge drinking may enhance the possibility of brain damage. Chronic administration of ethanol leads to upregulation of N-methyl-D-aspartate (NMDA) and calcium receptors and increased release of glucocorticoids. NMDA-mediated mechanisms and glucocorticoid actions on the hippocampus are associated with brain damage. Thus, ethanol withdrawal may make the brain more vulnerable to damage from these mechanisms, especially with binge drinking. Therapeutic adjuncts for treating ethanol withdrawal, including NMDA, calcium, and glucocorticoid antagonists, may eventually prove useful in preventing further brain damage in alcoholism. JF - Alcohol (Fayetteville, N.Y.) AU - Hunt, W A AD - Neurosciences and Behavioral Research Branch, National Institute on Alcohol Abuse and Alcoholism, Rockville, MD 20857-0001. PY - 1993 SP - 559 EP - 561 VL - 10 IS - 6 SN - 0741-8329, 0741-8329 KW - Glucocorticoids KW - 0 KW - Neurotoxins KW - Receptors, N-Methyl-D-Aspartate KW - Ethanol KW - 3K9958V90M KW - Index Medicus KW - Glucocorticoids -- metabolism KW - Ethanol -- adverse effects KW - Animals KW - Substance Withdrawal Syndrome -- complications KW - Receptors, N-Methyl-D-Aspartate -- physiology KW - Substance Withdrawal Syndrome -- metabolism KW - Ethanol -- pharmacology KW - Risk Factors KW - Humans KW - Neurotoxins -- pharmacology KW - Drinking Behavior KW - Alcohol Drinking -- adverse effects KW - Brain Damage, Chronic -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76251260?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Alcohol+%28Fayetteville%2C+N.Y.%29&rft.atitle=Are+binge+drinkers+more+at+risk+of+developing+brain+damage%3F&rft.au=Hunt%2C+W+A&rft.aulast=Hunt&rft.aufirst=W&rft.date=1993-11-01&rft.volume=10&rft.issue=6&rft.spage=559&rft.isbn=&rft.btitle=&rft.title=Alcohol+%28Fayetteville%2C+N.Y.%29&rft.issn=07418329&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-04-14 N1 - Date created - 1994-04-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Implicit memory in patients with schizophrenia and normal controls: effects of task demands on susceptibility to priming. AN - 76246460; 8120123 AB - Two experiments employing a stem-completion priming paradigm are reported. The first of these compared patients with schizophrenia (SC) to normal controls and demonstrated impaired implicit memory in the SC patients under task conditions identical to those used previously with other patient groups. The second experiment was designed to examine the effects of implicit task demands and stimulus selection upon susceptibility to priming, with a second group of SC patients and normal controls. Results indicated that the ability to carry out the task demands of the implicit condition (i.e., generate completions for word-stems) was inversely related to susceptibility to priming in both the SC patients and controls. In addition, the baseline probability of specific completions was found to be correlated with the ease of priming those completions, suggesting a possible mechanism for producing statistical dissociations between implicit and explicit retrieval conditions with this paradigm. These findings suggest that certain implicit tasks may be susceptible to nonmemory psychological influences that have not been adequately investigated to date; these may be responsible for "normalizing" the performance of amnesic patients as well as producing statistical dissociations from explicit memory tasks. JF - Journal of clinical and experimental neuropsychology AU - Randolph, C AU - Gold, J M AU - Carpenter, C J AU - Goldberg, T E AU - Weinberger, D R AD - Clinical Brain Disorders Branch, IRP, NIMH, Bethesda, MD 20892. Y1 - 1993/11// PY - 1993 DA - November 1993 SP - 853 EP - 866 VL - 15 IS - 6 SN - 1380-3395, 1380-3395 KW - Index Medicus KW - Psychiatric Status Rating Scales KW - Humans KW - Alzheimer Disease -- psychology KW - Adult KW - Cues KW - Alcohol Amnestic Disorder -- psychology KW - Mental Recall KW - Huntington Disease -- psychology KW - Male KW - Female KW - Memory Disorders -- psychology KW - Schizophrenic Psychology KW - Memory -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76246460?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+and+experimental+neuropsychology&rft.atitle=Implicit+memory+in+patients+with+schizophrenia+and+normal+controls%3A+effects+of+task+demands+on+susceptibility+to+priming.&rft.au=Randolph%2C+C%3BGold%2C+J+M%3BCarpenter%2C+C+J%3BGoldberg%2C+T+E%3BWeinberger%2C+D+R&rft.aulast=Randolph&rft.aufirst=C&rft.date=1993-11-01&rft.volume=15&rft.issue=6&rft.spage=853&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+and+experimental+neuropsychology&rft.issn=13803395&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-04-01 N1 - Date created - 1994-04-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - An immunochemical approach of identifying and characterizing protein targets of toxic reactive metabolites. AN - 76240150; 8117916 JF - Chemical research in toxicology AU - Pohl, L R AD - Laboratory of Chemical Pharmacology, National Heart, Lung, and Blood Institute, Bethesda, Maryland 20892. PY - 1993 SP - 786 EP - 793 VL - 6 IS - 6 SN - 0893-228X, 0893-228X KW - Proteins KW - 0 KW - Index Medicus KW - Animals KW - Humans KW - Immunochemistry KW - Proteins -- drug effects KW - Proteins -- chemistry KW - Proteins -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76240150?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemical+research+in+toxicology&rft.atitle=An+immunochemical+approach+of+identifying+and+characterizing+protein+targets+of+toxic+reactive+metabolites.&rft.au=Pohl%2C+L+R&rft.aulast=Pohl&rft.aufirst=L&rft.date=1993-11-01&rft.volume=6&rft.issue=6&rft.spage=786&rft.isbn=&rft.btitle=&rft.title=Chemical+research+in+toxicology&rft.issn=0893228X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-04-04 N1 - Date created - 1994-04-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Applications of computers to toxicological research. AN - 76237474; 8117912 AB - Computers are used in toxicology in two ways. They are able to manage and manipulate large amounts of data, and it is because of this that they are used quite commonly to search toxicity databases. The mechanical ability of computers has led a number of organizations to pursue their use in regulatory compliance. The cost-benefit aspect of this issue being what it is, much more effort can be expected in this area. The other major use of computers has been to support efforts to predict or estimate toxicity properties. This task has proven to be very difficult, as was expected, and progress has been mixed. Developers of systems, testing their own development, report impressive accuracy, as has been seen. The "real world" view is less felicitous. In a highly publicized, head-to-head test of some of the computer methods against human experts, accurate prediction of carcinogenicity by computer was achieved for 49-59% of the compounds, depending upon the method used. The humans, on the other hand, scored between 65% and 84%. A conclusion that could be drawn from this experiment is that with compounds which "obviously" are or are not carcinogenic, both computers and humans score well. Once obviousness recedes however, both are at a disadvantage, but humans can improvise more effectively. As research continues, the computer methods will develop better learning sets, and so there will be incremental improvements in their performance.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Chemical research in toxicology AU - Wang, S AU - Milne, G W AD - Laboratory of Medicinal Chemistry, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. PY - 1993 SP - 748 EP - 753 VL - 6 IS - 6 SN - 0893-228X, 0893-228X KW - Index Medicus KW - Computers KW - Databases, Factual KW - Toxicology -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76237474?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemical+research+in+toxicology&rft.atitle=Applications+of+computers+to+toxicological+research.&rft.au=Wang%2C+S%3BMilne%2C+G+W&rft.aulast=Wang&rft.aufirst=S&rft.date=1993-11-01&rft.volume=6&rft.issue=6&rft.spage=748&rft.isbn=&rft.btitle=&rft.title=Chemical+research+in+toxicology&rft.issn=0893228X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-04-04 N1 - Date created - 1994-04-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phoenix mutagenesis: one-step reassembly of multiply cleaved plasmids with mixtures of mutant and wild-type fragments. AN - 76230541; 7906495 AB - A method for site-specific mutagenesis which can be used with any gene in any vector has been devised. This method has been named "phoenix mutagenesis." Upon selection of the mutation site, the plasmid bearing the gene in question is cleaved with one or two restriction enzymes that generate fragments with random staggered ends. The enzymes are chosen to maximize the protrusions while minimizing the size of the fragment to be mutated. Ligation of the fragments reconstitutes the original plasmid. Mutations are obtained by allowing mutant fragments, added in 10-fold molar excess, to compete with their wild-type counterparts for a place in the reassembled vector. In a test system with the restriction enzyme PflMI, which cleaves an 8-kb vector bearing the prothymosin alpha gene into four fragments, the efficiency of reassembly exceeded that of sealing linearized molecules. The recovery of mutated molecules was 20-50%. With Bsa1, which also cleaves the plasmid into four fragments, both the efficiency of reassembly and the production of mutants were reduced. To expedite the use of phoenix mutagenesis, a simple technique for generating mutant fragments in tandem polymerase chain reactions is presented. In the first step, a mutated subfragment is synthesized from the region of the mutation to one terminus; in the second step, the complete fragment is made with the aid of an oligomer targeted to the other terminus and one strand of the product of the first reaction. The complementary strand is present, but does not interfere with the amplification process. JF - Analytical biochemistry AU - Berger, S L AU - Manrow, R E AU - Lee, H Y AD - Section on Genes and Gene Products, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/11/01/ PY - 1993 DA - 1993 Nov 01 SP - 571 EP - 579 VL - 214 IS - 2 SN - 0003-2697, 0003-2697 KW - Protein Precursors KW - 0 KW - prothymosin alpha KW - Thymosin KW - 61512-21-8 KW - Index Medicus KW - Polymerase Chain Reaction KW - Reference Values KW - Base Sequence KW - Polymorphism, Restriction Fragment Length KW - Protein Precursors -- genetics KW - Molecular Sequence Data KW - Thymosin -- genetics KW - Thymosin -- analogs & derivatives KW - Mutagenesis, Site-Directed -- physiology KW - Plasmids KW - Mutation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76230541?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Analytical+biochemistry&rft.atitle=Phoenix+mutagenesis%3A+one-step+reassembly+of+multiply+cleaved+plasmids+with+mixtures+of+mutant+and+wild-type+fragments.&rft.au=Berger%2C+S+L%3BManrow%2C+R+E%3BLee%2C+H+Y&rft.aulast=Berger&rft.aufirst=S&rft.date=1993-11-01&rft.volume=214&rft.issue=2&rft.spage=571&rft.isbn=&rft.btitle=&rft.title=Analytical+biochemistry&rft.issn=00032697&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-03-21 N1 - Date created - 1994-03-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Anaphylactoid reaction with suramin. AN - 76219047; 8302692 AB - Suramin, a drug used to treat parasitic diseases, is currently being investigated as a treatment for metastatic prostate cancer. A 73-year-old man had an anaphylactoid reaction following the first dose of suramin. It was treated successfully with epinephrine, diphenhydramine, and hydrocortisone. Investigators should be aware of the possibility of such a reaction with parenteral administration of this drug. JF - Pharmacotherapy AU - Thibault, A AU - Figg, W D AU - Cooper, M R AU - Prindiville, S A AU - Sartor, A O AU - Headlee, D J AU - Myers, C E AD - Clinical Pharmacology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. PY - 1993 SP - 656 EP - 657 VL - 13 IS - 6 SN - 0277-0008, 0277-0008 KW - Suramin KW - 6032D45BEM KW - Index Medicus KW - Humans KW - Aged KW - Prostatic Neoplasms -- drug therapy KW - Infusions, Parenteral KW - Male KW - Suramin -- adverse effects KW - Anaphylaxis -- chemically induced KW - Suramin -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76219047?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pharmacotherapy&rft.atitle=Anaphylactoid+reaction+with+suramin.&rft.au=Thibault%2C+A%3BFigg%2C+W+D%3BCooper%2C+M+R%3BPrindiville%2C+S+A%3BSartor%2C+A+O%3BHeadlee%2C+D+J%3BMyers%2C+C+E&rft.aulast=Thibault&rft.aufirst=A&rft.date=1993-11-01&rft.volume=13&rft.issue=6&rft.spage=656&rft.isbn=&rft.btitle=&rft.title=Pharmacotherapy&rft.issn=02770008&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-03-08 N1 - Date created - 1994-03-08 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Pharmacotherapy 1994 Jan-Feb;14(1):following 125 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In vitro predictors of clinical response in patients receiving interleukin-2-based immunotherapy. AN - 76209335; 8305539 AB - Treatment of cancer patients with interleukin-2 has resulted in clinical regression of metastatic disease. The ability to predict which patients will respond to therapy could result in more efficacious and possibly less toxic treatments. Hence, attempts have been made to correlate patient parameters or in vitro characteristics with clinical response to immunotherapy. Some patient factors have been identified as prognostically favorable. However, parameters modulated by interleukin-2 have not been predictive of clinical outcome. Exciting new evidence does exist regarding in vitro characteristics of tumor-infiltrating lymphocytes. Measurement of the cytolytic ability of melanoma tumor-infiltrating lymphocytes may enhance our understanding of the immune-mediated antitumor response and lead to a new generation of selective immunotherapies. JF - Current opinion in oncology AU - Schwartzentruber, D J AD - National Cancer Institute, Bethesda, Maryland. Y1 - 1993/11// PY - 1993 DA - November 1993 SP - 1055 EP - 1058 VL - 5 IS - 6 SN - 1040-8746, 1040-8746 KW - Interleukin-2 KW - 0 KW - Index Medicus KW - Humans KW - Clinical Trials as Topic KW - Predictive Value of Tests KW - Kidney Neoplasms -- therapy KW - Carcinoma, Renal Cell -- therapy KW - Interleukin-2 -- therapeutic use KW - Immunotherapy KW - Melanoma -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76209335?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+oncology&rft.atitle=In+vitro+predictors+of+clinical+response+in+patients+receiving+interleukin-2-based+immunotherapy.&rft.au=Schwartzentruber%2C+D+J&rft.aulast=Schwartzentruber&rft.aufirst=D&rft.date=1993-11-01&rft.volume=5&rft.issue=6&rft.spage=1055&rft.isbn=&rft.btitle=&rft.title=Current+opinion+in+oncology&rft.issn=10408746&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-03-16 N1 - Date created - 1994-03-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - 2',5'-Oligoadenylate:antisense chimeras--synthesis and properties. AN - 76208988; 8305516 AB - We have synthesized a novel bioconjugate which joins an antisense oligonucleotide to a unique and potent inhibitor of translation,pn5'A2'(p5'A2')mp5'A(2-5A). Two residues of 4-hydroxybutyl phosphate were employed as linkers to attach the 2',5'-oligoadenylate moiety through its 2'-terminus to the 5'-terminus of the chosen antisense sequence, (dT)20. The syntheses were carried on a solid support according to the phosphite triester method of DNA synthesis (Letsinger, R.L., Lunsford, W.B. (1976) J. Am. Chem. Soc. 98, 3655-3661; Beaucage, S.L., and Caruthers, M.H. (1981) Tetrahedron Lett. 22, 1859-1862). The generated 2-5A antisense chimeras retained both the ability of the 2-5A molecule to activate the 2-5A-dependent RNase as well as the ability of the oligo(dT) moiety to hybridize to the complementary poly(A). Moreover, the chimera, when annealed to its target nucleic acid sequence, was still effectively bound to the 2-5A-dependent nuclease. The methodology described represents a new approach to the selective modulation of mRNA expression. JF - Bioconjugate chemistry AU - Lesiak, K AU - Khamnei, S AU - Torrence, P F AD - Section on Biomedical Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892. PY - 1993 SP - 467 EP - 472 VL - 4 IS - 6 SN - 1043-1802, 1043-1802 KW - Adenine Nucleotides KW - 0 KW - Cross-Linking Reagents KW - Immunotoxins KW - Oligonucleotides, Antisense KW - Oligoribonucleotides KW - 2',5'-oligoadenylate KW - 61172-40-5 KW - Index Medicus KW - Cross-Linking Reagents -- chemistry KW - Base Sequence KW - Nucleic Acid Conformation KW - Immunotoxins -- chemistry KW - Oligoribonucleotides -- chemical synthesis KW - Adenine Nucleotides -- chemistry KW - Oligonucleotides, Antisense -- chemistry KW - Oligoribonucleotides -- chemistry KW - Adenine Nucleotides -- chemical synthesis KW - Oligonucleotides, Antisense -- chemical synthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76208988?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Bioconjugate+chemistry&rft.atitle=2%27%2C5%27-Oligoadenylate%3Aantisense+chimeras--synthesis+and+properties.&rft.au=Lesiak%2C+K%3BKhamnei%2C+S%3BTorrence%2C+P+F&rft.aulast=Lesiak&rft.aufirst=K&rft.date=1993-11-01&rft.volume=4&rft.issue=6&rft.spage=467&rft.isbn=&rft.btitle=&rft.title=Bioconjugate+chemistry&rft.issn=10431802&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-03-15 N1 - Date created - 1994-03-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Purification and characterization of IL6-PE4E, a recombinant fusion of interleukin 6 with Pseudomonas exotoxin. AN - 76206738; 8305530 AB - We have developed a procedure to purify the recombinant fusion toxin IL6-PE4E from Escherichia coli which results in a high yield of fully active monomeric protein of high purity and very low endotoxin content. The chimeric toxin is composed of human interleukin 6 (IL6) fused to a derivative of Pseudomonas exotoxin (PE) containing mutations in the binding domain which prevent binding to the PE receptor. In a typical preparation, 20 g of E. coli cells expressing the plasmid encoding IL6-PE4E were treated with lysozyme and washed repeatedly with detergent (Triton X-100), to obtain 500 mg of inclusion bodies. The recombinant protein was denatured and reduced in guanidine hydrochloride solution containing dithioerythritol and refolded in a redox buffer containing oxidized glutathione and L-arginine. After purification of the dialyzed protein by anion-exchange, polymyxin B, and sizing chromatography, we obtained 100 mg (20% of recombinant protein) of purified monomer with 0.6-2.5 endotoxin units/mg of protein. Amino terminal sequencing confirmed the first 20 amino acids. IL6-PE4E purified in this manner was fully cytotoxic toward human multiple myeloma, hepatoma, epidermoid carcinoma, and prostate carcinoma cell lines. After intravenous injection into mice, we found the dose-limiting toxicity to be to the liver, by measurement of serum transaminases and histologic evaluation of the liver. The LD50 was 450 micrograms/kg. We conclude that IL6-PE4E can be purified efficiently for preclinical testing. JF - Bioconjugate chemistry AU - Kreitman, R J AU - Pastan, I AD - Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. PY - 1993 SP - 581 EP - 585 VL - 4 IS - 6 SN - 1043-1802, 1043-1802 KW - Exotoxins KW - 0 KW - IL-6-PE40 protein, chimeric KW - Interleukin-6 KW - Recombinant Fusion Proteins KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - Index Medicus KW - Animals KW - Dose-Response Relationship, Drug KW - Cells, Cultured KW - Humans KW - Lethal Dose 50 KW - Escherichia coli -- chemistry KW - Mice, Nude KW - Mice KW - Mutation KW - Female KW - Recombinant Fusion Proteins -- isolation & purification KW - Recombinant Fusion Proteins -- genetics KW - Exotoxins -- toxicity KW - Recombinant Fusion Proteins -- toxicity KW - Interleukin-6 -- toxicity KW - Interleukin-6 -- isolation & purification KW - Exotoxins -- isolation & purification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76206738?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Bioconjugate+chemistry&rft.atitle=Purification+and+characterization+of+IL6-PE4E%2C+a+recombinant+fusion+of+interleukin+6+with+Pseudomonas+exotoxin.&rft.au=Kreitman%2C+R+J%3BPastan%2C+I&rft.aulast=Kreitman&rft.aufirst=R&rft.date=1993-11-01&rft.volume=4&rft.issue=6&rft.spage=581&rft.isbn=&rft.btitle=&rft.title=Bioconjugate+chemistry&rft.issn=10431802&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-03-15 N1 - Date created - 1994-03-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evaluation of a new DTPA-derivative chelator: comparative biodistribution and imaging studies of 111In-labeled B3 monoclonal antibody in athymic mice bearing human epidermoid carcinoma xenografts. AN - 76201256; 8298575 AB - Biodistribution and imaging characteristics of monoclonal antibody (MAb) B3 conjugated to either the 2-(p-isothiocyanatobenzyl)-cyclohexyl-DTPA (CHX-B) or 2-(p-isothiocyanatobenzyl)-6-methyl-DTPA (1B4M) and labeled with 111In, were evaluated in nude mice bearing A431 human epidermoid carcinoma xenografts. MAb B3, is a murine IgG1k reacting with a carbohydrate antigen abundantly expressed by most carcinomas. Both 111In-(CHX-B)-B3 and 111In-(1B4M)-B3 showed good tumor targeting with peak values observed at 72 h with 27.6 +/- 7.6 and 25.4 +/- 1.7% ID/g, respectively (P > 0.05). High tumor-to-organ ratios were also observed and, confirmed by the imaging results. In particular, tumor-to-liver ratios increased from 5.0 +/- 0.9 at 24 h to 9.2 +/- 2.0 at 168 h for 111In-(CHX-B)-B3 and from 4.5 +/- 0.6 to 8.9 +/- 3.5 for 111In-(1B4M)-B3. This was mainly the result of low liver accumulation of both 111In-(CHX-B)-B3 and 111In-(1B4M)-B3, with only 2.48 +/- 0.46 and 2.5 +/- 0.9% ID/g at 168 h, respectively (P > 0.05). Our findings indicate that either CHX-B or 1B4M can be successfully used for 111In-labeling of MAbs and that 111In-B3 may represent a promising radioimmunoimaging agent. JF - Nuclear medicine and biology AU - Camera, L AU - Kinuya, S AU - Garmestani, K AU - Pai, L H AU - Brechbiel, M W AU - Gansow, O A AU - Paik, C H AU - Pastan, I AU - Carrasquillo, J A AD - Department of Nuclear Medicine, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/11// PY - 1993 DA - November 1993 SP - 955 EP - 962 VL - 20 IS - 8 SN - 0969-8051, 0969-8051 KW - Antibodies, Monoclonal KW - 0 KW - Chelating Agents KW - Immunotoxins KW - Indium Radioisotopes KW - Isothiocyanates KW - 2-(4-isothiocyanatobenzyl)-6-methyldiethylenetriaminepentaacetic acid KW - 141849-44-7 KW - N-(2-amino-3-(4-isothiocyanatophenyl)propyl)cyclohexane-1,2-diamine-N,N',N',N'',N''-pentaacetic acid KW - 142434-84-2 KW - Pentetic Acid KW - 7A314HQM0I KW - Index Medicus KW - Neoplasm Transplantation KW - Drug Stability KW - Animals KW - Antibodies, Monoclonal -- metabolism KW - Humans KW - Transplantation, Heterologous KW - Mice, Nude KW - Mice KW - Tissue Distribution KW - Female KW - Radionuclide Imaging KW - Isothiocyanates -- pharmacokinetics KW - Chelating Agents -- pharmacokinetics KW - Pentetic Acid -- analogs & derivatives KW - Carcinoma, Squamous Cell -- diagnostic imaging KW - Carcinoma, Squamous Cell -- metabolism KW - Immunotoxins -- metabolism KW - Pentetic Acid -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76201256?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nuclear+medicine+and+biology&rft.atitle=Evaluation+of+a+new+DTPA-derivative+chelator%3A+comparative+biodistribution+and+imaging+studies+of+111In-labeled+B3+monoclonal+antibody+in+athymic+mice+bearing+human+epidermoid+carcinoma+xenografts.&rft.au=Camera%2C+L%3BKinuya%2C+S%3BGarmestani%2C+K%3BPai%2C+L+H%3BBrechbiel%2C+M+W%3BGansow%2C+O+A%3BPaik%2C+C+H%3BPastan%2C+I%3BCarrasquillo%2C+J+A&rft.aulast=Camera&rft.aufirst=L&rft.date=1993-11-01&rft.volume=20&rft.issue=8&rft.spage=955&rft.isbn=&rft.btitle=&rft.title=Nuclear+medicine+and+biology&rft.issn=09698051&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-03-08 N1 - Date created - 1994-03-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Atrial natriuretic factor activates cyclic adenosine 3',5'-monophosphate phosphodiesterase in Xenopus laevis oocytes and potentiates progesterone-induced maturation via cyclic guanosine 5'-monophosphate accumulation. AN - 76170002; 8286573 AB - Xenopus oocytes were found to express atrial natriuretic factor (ANF) receptors that activate guanylate cyclase and stimulate cyclic guanosine 5'-monophosphate (cGMP) production in a dose- and time-dependent manner. A truncated fragment of ANF, known to bind to mammalian ANF receptors without stimulating cGMP accumulation, did not elicit a cGMP response in oocytes. In addition, preincubation with ANF increased the number of oocytes that underwent progesterone-induced maturation. The maximally effective dose of ANF (1 microM) elevated intracellular and extracellular cGMP accumulation from 50 to 200 and 5 to 800 fmol/oocyte, respectively, and increased the number of maturing oocytes by up to 3-fold. ANF's effects on progesterone-induced maturation were mimicked by nonhydrolyzable analogues of cGMP. ANF and 8-Br-cGMP had no effect on maturation in the absence of progesterone, indicating that elevation of cGMP alone is not sufficient to induce maturation. Dibutyryl-cGMP was as effective as 8-Br-cGMP, whereas 8-Br-guanosine monophosphate, 8-Br-guanosine, and 8-Br-cyclic inosine monophosphate did not potentiate ovum maturation. In Xenopus oocytes, an initial step in progesterone-induced maturation is the reduction of intracellular cAMP levels; both ANF and 8-Br-cGMP lowered cAMP levels and enhanced progesterone's ability to do so. This decrease in cAMP levels was attributable to increased cAMP-phosphodiesterase activity, which was enhanced by both ANF and 8-Br-cGMP. These findings, and the presence of functional ANF receptors on Xenopus oocytes, demonstrate that ANF can participate in ovum development by stimulation of cGMP accumulation and activation of cAMP phosphodiesterase, thereby potentiating progesterone's ability to decrease cAMP levels and promote ovum maturation. JF - Biology of reproduction AU - Sandberg, K AU - Bor, M AU - Ji, H AU - Carvallo, P M AU - Catt, K J AD - Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/11// PY - 1993 DA - November 1993 SP - 1074 EP - 1082 VL - 49 IS - 5 SN - 0006-3363, 0006-3363 KW - Progesterone KW - 4G7DS2Q64Y KW - Atrial Natriuretic Factor KW - 85637-73-6 KW - Cyclic AMP KW - E0399OZS9N KW - 3',5'-Cyclic-AMP Phosphodiesterases KW - EC 3.1.4.17 KW - 3',5'-Cyclic-GMP Phosphodiesterases KW - EC 3.1.4.35 KW - Receptors, Atrial Natriuretic Factor KW - EC 4.6.1.2 KW - Cyclic GMP KW - H2D2X058MU KW - Index Medicus KW - Xenopus laevis KW - Animals KW - Progesterone -- pharmacology KW - Receptors, Atrial Natriuretic Factor -- metabolism KW - 3',5'-Cyclic-GMP Phosphodiesterases -- antagonists & inhibitors KW - Progesterone -- administration & dosage KW - Cyclic GMP -- biosynthesis KW - Cell Membrane -- metabolism KW - Drug Synergism KW - 3',5'-Cyclic-AMP Phosphodiesterases -- antagonists & inhibitors KW - Receptors, Atrial Natriuretic Factor -- drug effects KW - Female KW - Oocytes -- growth & development KW - Oocytes -- metabolism KW - Oocytes -- drug effects KW - Cyclic AMP -- metabolism KW - Atrial Natriuretic Factor -- pharmacology KW - Atrial Natriuretic Factor -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76170002?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biology+of+reproduction&rft.atitle=Atrial+natriuretic+factor+activates+cyclic+adenosine+3%27%2C5%27-monophosphate+phosphodiesterase+in+Xenopus+laevis+oocytes+and+potentiates+progesterone-induced+maturation+via+cyclic+guanosine+5%27-monophosphate+accumulation.&rft.au=Sandberg%2C+K%3BBor%2C+M%3BJi%2C+H%3BCarvallo%2C+P+M%3BCatt%2C+K+J&rft.aulast=Sandberg&rft.aufirst=K&rft.date=1993-11-01&rft.volume=49&rft.issue=5&rft.spage=1074&rft.isbn=&rft.btitle=&rft.title=Biology+of+reproduction&rft.issn=00063363&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-02-18 N1 - Date created - 1994-02-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Sequence and localization of a novel FK506-binding protein to mouse chromosome 11. AN - 76166776; 7507077 AB - We have isolated a unique gene from a mouse JB6 epidermal cell cDNA expression library, termed FKBPRP, that codes for a protein having domains that share between 37 and 44% amino acid sequence identity and 60% similarity with members of the family of FK506-binding proteins. The FKBPRP protein has three repeats contained within its sequence that share between 48 and 58% identity to each other. We have localized the FKBPRP gene to mouse Chromosome 11, and crosses of different murine strains provided the gene order centromere--FKBPRP-Int-4-Pkca-Es-3. JF - Genomics AU - Simek, S L AU - Kozak, C A AU - Winterstein, D AU - Hegamyer, G AU - Colburn, N H AD - Biological Carcinogenesis and Development Program, NCI-Frederick Cancer Research and Development Center, Frederick, Maryland. Y1 - 1993/11// PY - 1993 DA - November 1993 SP - 407 EP - 409 VL - 18 IS - 2 SN - 0888-7543, 0888-7543 KW - FKBPRP KW - Carrier Proteins KW - 0 KW - Heat-Shock Proteins KW - Tacrolimus Binding Proteins KW - EC 5.2.1.- KW - Tacrolimus KW - WM0HAQ4WNM KW - Index Medicus KW - Animals KW - Humans KW - Molecular Sequence Data KW - Mice KW - Amino Acid Sequence KW - Sequence Homology, Amino Acid KW - Heat-Shock Proteins -- metabolism KW - Carrier Proteins -- metabolism KW - Tacrolimus -- metabolism KW - Carrier Proteins -- genetics KW - Chromosome Mapping KW - Heat-Shock Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76166776?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genomics&rft.atitle=Sequence+and+localization+of+a+novel+FK506-binding+protein+to+mouse+chromosome+11.&rft.au=Simek%2C+S+L%3BKozak%2C+C+A%3BWinterstein%2C+D%3BHegamyer%2C+G%3BColburn%2C+N+H&rft.aulast=Simek&rft.aufirst=S&rft.date=1993-11-01&rft.volume=18&rft.issue=2&rft.spage=407&rft.isbn=&rft.btitle=&rft.title=Genomics&rft.issn=08887543&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-02-22 N1 - Date created - 1994-02-22 N1 - Date revised - 2017-01-13 N1 - Gene symbol - FKBPRP N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A case of hyperdynamic shock caused by trimethoprim-sulfamethoxazole in which no tumor necrosis factor or features of anaphylaxis were detected. AN - 76164016; 8286631 AB - An unusual acute hypotensive syndrome has been observed in association with administration of trimethoprim-sulfamethoxazole (TMP-SMZ) to patients with human immunodeficiency virus (HIV) infection. In the 11 cases that have been reported, the syndrome differs from classic anaphylaxis and resembles septic shock. Mediation by tumor necrosis factor (TNF) has been hypothesized, but the mechanism has not been characterized with cytokine assays, and no invasive hemodynamic measurements have been reported. We describe a case of recurrent hyperdynamic shock--without classic features of anaphylaxis, without detectable IgE antibodies against TMP or SMZ, and without detectable levels of TNF--involving an HIV-infected patient rechallenged with TMP-SMZ. JF - Clinical infectious diseases : an official publication of the Infectious Diseases Society of America AU - Nguyen, B Y AU - Landucci, D L AU - Cunnion, R E AU - Yarchoan, R AU - Walker, R E AD - Medicine Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/11// PY - 1993 DA - November 1993 SP - 885 EP - 887 VL - 17 IS - 5 SN - 1058-4838, 1058-4838 KW - Interleukin-6 KW - 0 KW - Tumor Necrosis Factor-alpha KW - Trimethoprim, Sulfamethoxazole Drug Combination KW - 8064-90-2 KW - Complement System Proteins KW - 9007-36-7 KW - Index Medicus KW - AIDS/HIV KW - Hypotension -- chemically induced KW - Hemodynamics -- drug effects KW - Fever -- chemically induced KW - Pneumonia, Pneumocystis -- prevention & control KW - Interleukin-6 -- blood KW - Complement System Proteins -- metabolism KW - Humans KW - Adult KW - Anaphylaxis -- etiology KW - AIDS-Related Opportunistic Infections -- prevention & control KW - Tumor Necrosis Factor-alpha -- metabolism KW - Male KW - Shock -- chemically induced KW - Shock -- physiopathology KW - Trimethoprim, Sulfamethoxazole Drug Combination -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76164016?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+infectious+diseases+%3A+an+official+publication+of+the+Infectious+Diseases+Society+of+America&rft.atitle=A+case+of+hyperdynamic+shock+caused+by+trimethoprim-sulfamethoxazole+in+which+no+tumor+necrosis+factor+or+features+of+anaphylaxis+were+detected.&rft.au=Nguyen%2C+B+Y%3BLanducci%2C+D+L%3BCunnion%2C+R+E%3BYarchoan%2C+R%3BWalker%2C+R+E&rft.aulast=Nguyen&rft.aufirst=B&rft.date=1993-11-01&rft.volume=17&rft.issue=5&rft.spage=885&rft.isbn=&rft.btitle=&rft.title=Clinical+infectious+diseases+%3A+an+official+publication+of+the+Infectious+Diseases+Society+of+America&rft.issn=10584838&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-02-22 N1 - Date created - 1994-02-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Relative frequency of heavy drinking and the risk of alcohol dependence. AN - 76163107; 8286996 AB - Data from a national representative sample of US adults were analyzed to determine the association between the relative frequency of heavy drinking (the proportion of drinking occasions on which 5+ drinks were consumed) and past-year alcohol dependence, adjusting for the influences of average ethanol intake and sociodemographic factors. Fifty-seven percent of current drinkers reported never drinking 5+ drinks, and 21% drank 5+ drinks at least once but on less than 10% of all drinking occasions. Nine percent reported drinking 5+ drinks on at least half of all drinking occasions. Average daily intake was positively correlated with the relative frequency of heavy drinking, and both consumption measures were positively associated with the risk of alcohol dependence. Increases in either relative frequency of heavy drinking or average ethanol intake reduced, but did not eliminate, the effect of the other on the risk of dependence. The excess risk of dependence associated with frequent heavy drinking varied among population subgroups and was increased by age, education, and female gender. JF - Addiction (Abingdon, England) AU - Dawson, D A AU - Archer, L D AD - Division of Biometry and Epidemiology, National Institute on Alcohol Abuse and Alcoholism, Rockville, MD 20857. Y1 - 1993/11// PY - 1993 DA - November 1993 SP - 1509 EP - 1518 VL - 88 IS - 11 SN - 0965-2140, 0965-2140 KW - Ethanol KW - 3K9958V90M KW - Index Medicus KW - Educational Status KW - Age Factors KW - Sex Factors KW - Risk Factors KW - Humans KW - Adult KW - Substance-Related Disorders KW - African Americans KW - Adolescent KW - United States -- epidemiology KW - Male KW - Female KW - Alcohol Drinking -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76163107?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Relative+frequency+of+heavy+drinking+and+the+risk+of+alcohol+dependence.&rft.au=Dawson%2C+D+A%3BArcher%2C+L+D&rft.aulast=Dawson&rft.aufirst=D&rft.date=1993-11-01&rft.volume=88&rft.issue=11&rft.spage=1509&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 - 1994-02-22 N1 - Date created - 1994-02-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Swallowing disorders. AN - 76162710; 8292086 JF - ASHA AU - Sonies, B C AD - W. G. Magnuson Clinical Center, Department of Rehabilitation Medicine, National Institutes of Health, Bethesda, Maryland. Y1 - 1993/11// PY - 1993 DA - November 1993 SP - 59 EP - 60 VL - 35 IS - 11 SN - 0001-2475, 0001-2475 KW - Index Medicus KW - Humans KW - Drug-Related Side Effects and Adverse Reactions KW - Male KW - Female KW - Deglutition Disorders -- prevention & control KW - Deglutition Disorders -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76162710?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=ASHA&rft.atitle=Swallowing+disorders.&rft.au=Sonies%2C+B+C&rft.aulast=Sonies&rft.aufirst=B&rft.date=1993-11-01&rft.volume=35&rft.issue=11&rft.spage=59&rft.isbn=&rft.btitle=&rft.title=ASHA&rft.issn=00012475&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-02-22 N1 - Date created - 1994-02-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Structure and correlates of alcohol dependence in clinical samples in the United States and Russia. AN - 76162371; 8286999 AB - Using items from the Composite International Diagnostic Interview, dimensionality of the alcohol dependence syndrome was assessed in clinical samples in the United States and Russia. In both groups, a single-factor model provided a high degree of goodness of fit thus demonstrating cross-cultural coherence of the construct. The item dealing with narrowing of the drinking repertoire is most disparate in each sample. Severity of alcohol consequences was moderately related to alcohol dependence in both samples. Demographic variables, however, correlated less with severity of consequences. After the effects of severity of dependence and demographics were removed, quantity/frequency of recent alcohol consumption did not contribute to severity of consequences. Country, however, remained a significant, but small, predictor of severity of alcohol consequences. JF - Addiction (Abingdon, England) AU - Allen, J P AU - Fertig, J B AU - Towle, L H AU - Bryant, K AU - Altshuler, V B AU - Vrublevsky, A G AU - Valentik, Y V AD - National Institute on Alcohol Abuse and Alcoholism, Division of Clinical and Prevention Research, Rockville, MD 20857. Y1 - 1993/11// PY - 1993 DA - November 1993 SP - 1535 EP - 1543 VL - 88 IS - 11 SN - 0965-2140, 0965-2140 KW - Ethanol KW - 3K9958V90M KW - Index Medicus KW - Severity of Illness Index KW - Psychiatric Status Rating Scales KW - Humans KW - Cross-Cultural Comparison KW - Adult KW - Alcohol Drinking -- adverse effects KW - United States -- epidemiology KW - Male KW - Female KW - Russia -- epidemiology KW - Alcoholism -- epidemiology KW - Alcoholism -- diagnosis KW - Substance-Related Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76162371?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Structure+and+correlates+of+alcohol+dependence+in+clinical+samples+in+the+United+States+and+Russia.&rft.au=Allen%2C+J+P%3BFertig%2C+J+B%3BTowle%2C+L+H%3BBryant%2C+K%3BAltshuler%2C+V+B%3BVrublevsky%2C+A+G%3BValentik%2C+Y+V&rft.aulast=Allen&rft.aufirst=J&rft.date=1993-11-01&rft.volume=88&rft.issue=11&rft.spage=1535&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 - 1994-02-22 N1 - Date created - 1994-02-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Synapse elimination from the mouse neuromuscular junction in vitro: a non-Hebbian activity-dependent process. AN - 76158400; 8283186 AB - The effect of action potentials on elimination of mouse neuromuscular junctions (NMJ) was studied in a three-compartment cell culture preparation. Axons from superior cervical ganglion or ventral spinal cord neurons in two lateral compartments formed multiple neuromuscular junctions with muscle cells in a central compartment. The loss of synapses over a 2-7-day period was determined by serial electrophysiological recording and a functional assay. Electrical stimulation of axons from one side compartment during this period, using 30-Hz bursts of 2-s duration, repeated at 10-s intervals, caused a significant increase in synapse elimination compared to unstimulated cultures (p < 0.001). The extent of homosynaptic and heterosynaptic elimination was comparable, i.e., of the 226 functional synapses of each type studied, 111 (49%) of the synapses that had been stimulated were eliminated, and 87 (39%) of unstimulated synapses on the same muscle cells were eliminated. Also, simultaneous bilateral stimulation caused significantly greater elimination of synapses than unilateral stimulation (p < 0.005). These observations are contrary to the Hebbian hypothesis of synaptic plasticity. A spatial effect of stimulus-induced synapse elimination was also evident following simultaneous bilateral stimulation. Prior to stimulation, most muscle cells were innervated by axons from both side compartments, but after bilateral stimulation, muscle cells were predominantly unilaterally innervated by axons from the closer compartment. These experiments suggest that synapse elimination at the NMJ is an activity-dependent process, but it does not follow Hebbian or anti-Hebbian rules of synaptic plasticity. Rather, elimination is a consequence of postsynaptic activation and a function of location of the muscle cell relative to the neuron. An interaction between spatial and activity-dependent effects on synapse elimination could help produce optimal refinement of synaptic connections during postnatal development. JF - Journal of neurobiology AU - Nelson, P G AU - Fields, R D AU - Yu, C AU - Liu, Y AD - National Institutes of Health, NICHD, Laboratory of Developmental Neurobiology, Bethesda, Maryland 20892. Y1 - 1993/11// PY - 1993 DA - November 1993 SP - 1517 EP - 1530 VL - 24 IS - 11 SN - 0022-3034, 0022-3034 KW - Tetrodotoxin KW - 4368-28-9 KW - Index Medicus KW - Superior Cervical Ganglion -- physiology KW - Action Potentials -- physiology KW - Animals KW - Superior Cervical Ganglion -- ultrastructure KW - Motor Endplate -- physiology KW - Neuronal Plasticity -- physiology KW - Mice KW - Electric Stimulation KW - Nerve Degeneration -- physiology KW - Axons -- physiology KW - Parasympathetic Nervous System -- physiology KW - Cells, Cultured KW - Muscles -- innervation KW - Tetrodotoxin -- pharmacology KW - Parasympathetic Nervous System -- ultrastructure KW - Muscles -- ultrastructure KW - Synapses -- physiology KW - Synapses -- ultrastructure KW - Neuromuscular Junction -- ultrastructure KW - Neuromuscular Junction -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76158400?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+neurobiology&rft.atitle=Synapse+elimination+from+the+mouse+neuromuscular+junction+in+vitro%3A+a+non-Hebbian+activity-dependent+process.&rft.au=Nelson%2C+P+G%3BFields%2C+R+D%3BYu%2C+C%3BLiu%2C+Y&rft.aulast=Nelson&rft.aufirst=P&rft.date=1993-11-01&rft.volume=24&rft.issue=11&rft.spage=1517&rft.isbn=&rft.btitle=&rft.title=Journal+of+neurobiology&rft.issn=00223034&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-02-17 N1 - Date created - 1994-02-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Incapacitating autonomic neuropathy precipitated by taxol. AN - 76150377; 7903950 AB - Taxol is one of the more significant advances in cancer chemotherapy in the last 10-15 years with a 30-50% response rate in both breast and ovarian cancers. The toxicity profile of taxol is still evolving as changes in the dosing and scheduling of the drug are instituted. We herein present the first evidence of taxol-induced quantifiable, objective autonomic neuropathy in two patients, one with and one without diabetes. The patients did not have symptoms of autonomic dysfunction prior to taxol therapy. Both developed severe orthostatic hypotension following completion of 24-hr infusional taxol at 170-250 mg/m2 and both improved markedly on fludrocortisone. Other possible etiologies of orthostatic hypotension were ruled out. Noninvasive autonomic tests performed on the first patient included tilt test, Valsalva ratio, heart rate variation with respiration, and change in diastolic blood pressure with hand grip; all were markedly abnormal. Noninvasive autonomic tests should be considered as part of the evaluation of patients on taxol who develop generalized weakness and orthostasis. JF - Gynecologic oncology AU - Jerian, S M AU - Sarosy, G A AU - Link, C J AU - Fingert, H J AU - Reed, E AU - Kohn, E C AD - Medicine Branch, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1993/11// PY - 1993 DA - November 1993 SP - 277 EP - 280 VL - 51 IS - 2 SN - 0090-8258, 0090-8258 KW - Paclitaxel KW - P88XT4IS4D KW - Fludrocortisone KW - U0476M545B KW - Index Medicus KW - Humans KW - Hypotension, Orthostatic -- chemically induced KW - Fludrocortisone -- therapeutic use KW - Aged KW - Middle Aged KW - Ovarian Neoplasms -- drug therapy KW - Female KW - Diabetes Complications KW - Paclitaxel -- administration & dosage KW - Paclitaxel -- adverse effects KW - Autonomic Nervous System Diseases -- drug therapy KW - Autonomic Nervous System Diseases -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76150377?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Gynecologic+oncology&rft.atitle=Incapacitating+autonomic+neuropathy+precipitated+by+taxol.&rft.au=Jerian%2C+S+M%3BSarosy%2C+G+A%3BLink%2C+C+J%3BFingert%2C+H+J%3BReed%2C+E%3BKohn%2C+E+C&rft.aulast=Jerian&rft.aufirst=S&rft.date=1993-11-01&rft.volume=51&rft.issue=2&rft.spage=277&rft.isbn=&rft.btitle=&rft.title=Gynecologic+oncology&rft.issn=00908258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-02-09 N1 - Date created - 1994-02-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Lightweight aprons for protection against scattered radiation during fluoroscopy. AN - 76138991; 8273614 JF - AJR. American journal of roentgenology AU - Hubbert, T E AU - Vucich, J J AU - Armstrong, M R AD - Department of Radiology (Henry M. Jackson Foundation), Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/11// PY - 1993 DA - November 1993 SP - 1079 EP - 1081 VL - 161 IS - 5 SN - 0361-803X, 0361-803X KW - Abridged Index Medicus KW - Index Medicus KW - Scattering, Radiation KW - Humans KW - Fluoroscopy KW - Radiation Protection -- instrumentation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76138991?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=AJR.+American+journal+of+roentgenology&rft.atitle=Lightweight+aprons+for+protection+against+scattered+radiation+during+fluoroscopy.&rft.au=Hubbert%2C+T+E%3BVucich%2C+J+J%3BArmstrong%2C+M+R&rft.aulast=Hubbert&rft.aufirst=T&rft.date=1993-11-01&rft.volume=161&rft.issue=5&rft.spage=1079&rft.isbn=&rft.btitle=&rft.title=AJR.+American+journal+of+roentgenology&rft.issn=0361803X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-02-03 N1 - Date created - 1994-02-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Moderate alcohol consumption and the risk of endometrial cancer. AN - 76116664; 8268282 AB - In a multicenter case-control study that included 400 cases and 297 controls, we examined the relation of moderate alcohol consumption to risk of endometrial cancer. We estimated average weekly intake of alcohol during adulthood from the reported frequency of intake of beer, wine, and liquor. The relative risk of endometrial cancer was 0.82 (95% confidence interval = 0.6-1.2) among women who drank, compared with lifelong abstainers. The weak protective effect of alcohol was due to a stronger inverse association among young women ( 4 drinks per week), from lowest to highest, were 0.78, 0.64, and 0.41 compared with nondrinkers. The risk estimates were not materially altered after adjustment for a variety of factors related to alcohol intake and to low risk of the disease (for example, smoking, oral contraceptive use, low body mass index, increased physical activity). The protective effect of alcohol could not be attributed to one particular type of alcohol-containing beverage, but beer appeared to have the most pronounced effect. These results suggest an inverse association between moderate alcohol consumption and endometrial cancer risk among young women, but support for a causal association is qualified and requires confirmation. JF - Epidemiology (Cambridge, Mass.) AU - Swanson, C A AU - Wilbanks, G D AU - Twiggs, L B AU - Mortel, R AU - Berman, M L AU - Barrett, R J AU - Brinton, L A AD - Environmental Epidemiology Branch, National Cancer Institute, Bethesda, MD 20852. Y1 - 1993/11// PY - 1993 DA - November 1993 SP - 530 EP - 536 VL - 4 IS - 6 SN - 1044-3983, 1044-3983 KW - Contraceptives, Oral KW - 0 KW - Dietary Fats KW - Index Medicus KW - Contraceptives, Oral -- adverse effects KW - Humans KW - Aged KW - Body Mass Index KW - Exercise KW - Smoking -- epidemiology KW - Risk Factors KW - Adult KW - Case-Control Studies KW - Middle Aged KW - United States -- epidemiology KW - Female KW - Endometrial Neoplasms -- epidemiology KW - Alcohol Drinking -- epidemiology KW - Endometrial Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76116664?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Moderate+alcohol+consumption+and+the+risk+of+endometrial+cancer.&rft.au=Swanson%2C+C+A%3BWilbanks%2C+G+D%3BTwiggs%2C+L+B%3BMortel%2C+R%3BBerman%2C+M+L%3BBarrett%2C+R+J%3BBrinton%2C+L+A&rft.aulast=Swanson&rft.aufirst=C&rft.date=1993-11-01&rft.volume=4&rft.issue=6&rft.spage=530&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 - 1994-02-01 N1 - Date created - 1994-02-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Comparative carcinogenicity of polybrominated biphenyls with or without perinatal exposure in rats and mice. AN - 76105669; 8253298 AB - Chronic toxicity and carcinogenicity studies of a polybrominated biphenyl mixture (PBB) were conducted in F344/N rats and B6C3F1 mice of each sex. The major objective of the study was to determine if exposure to PBB during the perinatal period, in addition to conventional exposure of animals for 2 years, enhances the sensitivity of the bioassay to identify the carcinogenic potential of this chemical. The studies were designed to determine the toxic and carcinogenic effects of dietary PBB in rats and mice receiving (i) perinatal exposure up to 8 weeks of age followed by control diet for 2 years, (ii) exposure for 2 years beginning at the age of 8 weeks, and (iii) combined perinatal/adult exposure to PBB (perinatal exposure to 8 weeks of age followed by adult exposure for 2 years). During the perinatal period, rats were exposed to PBB at dose levels ranging from 1 to 10 ppm and adult exposure concentrations ranged from 3 to 30 ppm in the diet. In the mice, the dose levels ranged from 3 to 30 ppm in both perinatal and adult exposure portions of the chronic studies. A total of eight dose groups (including controls) were used with 60 animals in each group. Liver was the major target organ of PBB toxicity. Perinatal exposure alone (through dietary administration of 10 ppm PBB to the dams) had no effect on the incidences of neoplasms in female F344/N rats, but in male rats, perinatal exposure was associated with a marginally increased incidence of hepatocellular adenomas that may have been related to chemical administration. In male and female B6C3F1 mice, perinatal exposure to 30 ppm PBB resulted in significantly increased incidences of hepatocellular neoplasms. In adult-only dietary exposure studies, PBB was carcinogenic in male and female F344/N rats and male and female B6C3F1 mice based on increased incidences of hepatocellular neoplasms. Combined perinatal and adult dietary exposure to PBB confirmed the findings of the adult-only exposures for the increased incidences of hepatocellular neoplasms in rats and mice. In male rats, there were no enhancing effects of combined perinatal and adult exposure. However, perinatal exposure enhanced the susceptibility of female rats receiving adult exposure of 10 or 30 ppm to the induction of liver neoplasms. For male and female rats, a combined analysis of the incidences of leukemia in the adult-only, perinatal-only, and combined perinatal and adult exposure groups revealed an apparent association between increasing incidences of mononuclear cell leukemia and exposure to PBB.(ABSTRACT TRUNCATED AT 400 WORDS) JF - Fundamental and applied toxicology : official journal of the Society of Toxicology AU - Chhabra, R S AU - Bucher, J R AU - Haseman, J K AU - Elwell, M R AU - Kurtz, P J AU - Carlton, B D AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1993/11// PY - 1993 DA - November 1993 SP - 451 EP - 460 VL - 21 IS - 4 SN - 0272-0590, 0272-0590 KW - Carcinogens KW - 0 KW - Polybrominated Biphenyls KW - Index Medicus KW - Rats KW - Animals, Newborn KW - Animals KW - Rats, Inbred F344 KW - Age Factors KW - Mice, Inbred C57BL KW - Mice, Inbred C3H KW - Mice KW - Male KW - Female KW - Prenatal Exposure Delayed Effects KW - Pregnancy KW - Liver Neoplasms -- chemically induced KW - Carcinogens -- toxicity KW - Carcinogenicity Tests KW - Polybrominated Biphenyls -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76105669?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.atitle=Comparative+carcinogenicity+of+polybrominated+biphenyls+with+or+without+perinatal+exposure+in+rats+and+mice.&rft.au=Chhabra%2C+R+S%3BBucher%2C+J+R%3BHaseman%2C+J+K%3BElwell%2C+M+R%3BKurtz%2C+P+J%3BCarlton%2C+B+D&rft.aulast=Chhabra&rft.aufirst=R&rft.date=1993-11-01&rft.volume=21&rft.issue=4&rft.spage=451&rft.isbn=&rft.btitle=&rft.title=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.issn=02720590&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-01-13 N1 - Date created - 1994-01-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Preventing bacterial colonization associated with two types of implant abutments. AN - 76104726; 8254555 JF - The Journal of prosthetic dentistry AU - McCarthy, G R AU - Guckes, A D AD - Patient Care and Clinical Studies Section, National Institutes of Health, National Institute of Dental Research, Bethesda, Md. Y1 - 1993/11// PY - 1993 DA - November 1993 SP - 479 VL - 70 IS - 5 SN - 0022-3913, 0022-3913 KW - Dental Cements KW - 0 KW - Dental Implants KW - Eugenol KW - 3T8H1794QW KW - Opotow KW - 55126-37-9 KW - Zinc Oxide KW - SOI2LOH54Z KW - Dentistry KW - Index Medicus KW - Taste Disorders -- microbiology KW - Dental Abutments KW - Humans KW - Taste Disorders -- prevention & control KW - Dental Plaque -- prevention & control KW - Dental Plaque -- etiology KW - Dental Restoration, Temporary KW - Dental Implants -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76104726?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+prosthetic+dentistry&rft.atitle=Preventing+bacterial+colonization+associated+with+two+types+of+implant+abutments.&rft.au=McCarthy%2C+G+R%3BGuckes%2C+A+D&rft.aulast=McCarthy&rft.aufirst=G&rft.date=1993-11-01&rft.volume=70&rft.issue=5&rft.spage=479&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+prosthetic+dentistry&rft.issn=00223913&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-01-12 N1 - Date created - 1994-01-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Selective prothymocyte targeting by prenatal diethylstilbesterol exposure. AN - 76102872; 8242756 AB - Estrogens have been reported to modulate immunologic responses at both physiologic and pharmacologic concentrations. Treatment of experimental animals with the synthetic estrogen, diethylstilbesterol (DES), markedly decreases thymic cellularity, manifested histologically as a progressive loss of cortical thymic lymphocytes. In the present report thymic atrophy after prenatal DES exposure was found to be more severe than has been reported following adult exposure, indicating a possible greater sensitivity of the developing immune system to estrogenic hormones. DES exposure resulted in a limited alteration of cell maturation within the fetal thymus as evidenced by only slight alterations in the expression of CD4 and CD8 cell-surface antigens. To examine the possibility that DES targets hematopoietic stem cells in the fetal liver, cytometric analysis was conducted using a panel of fluorescent antibodies to quantitate the hematopoietic subpopulations present in control and DES-exposed Gestational Day (gd) 18 fetal mouse liver. There were no significant DES-induced alterations in the number of hematopoietic stem cells, or in fetal liver cells expressing CD44 (hematopoietic precursors), Mac-1 (granulocyte-macrophage lineage precursors), or CD45R (B-lineage lymphocytes) surface antigens. However, DES selectively reduced the number of fetal liver precursors containing the lymphocyte stem cell-specific DNA polymerase, terminal deoxynucleotidyl transferase, which suggested that DES may specifically target the fetal liver prothymocyte. Reconstitution of irradiated hosts with gd 18 fetal liver from vehicle and DES-exposed syngeneic donors demonstrated an impaired ability of the DES-treated fetal liver to repopulate the thymus of irradiated hosts. In addition, fetal liver cells enriched for prelymphoid cells contained potentially significant levels of estrogen specific receptors. Taken together these data, in conjunction with the lack of direct thymocyte injury (necrosis, apoptosis, and/or inhibition of cell proliferation) by DES treatment, suggest that estrogen-mediated thymic atrophy may result, at least in part, from a specific alteration in the lymphocyte stem cell population responsible for colonizing the thymus. JF - Cellular immunology AU - Holladay, S D AU - Blaylock, B L AU - Comment, C E AU - Heindel, J J AU - Fox, W M AU - Korach, K S AU - Luster, M I AD - Developmental and Reproductive Toxicology Group, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1993/11// PY - 1993 DA - November 1993 SP - 131 EP - 142 VL - 152 IS - 1 SN - 0008-8749, 0008-8749 KW - Antigens, CD4 KW - 0 KW - Antigens, CD8 KW - Diethylstilbestrol KW - 731DCA35BT KW - DNA Nucleotidylexotransferase KW - EC 2.7.7.31 KW - Index Medicus KW - Animals KW - Fetus -- drug effects KW - Liver -- immunology KW - Antigens, CD8 -- analysis KW - Mice KW - Liver -- embryology KW - Antigens, CD4 -- analysis KW - Liver -- drug effects KW - Mice, Inbred C57BL KW - Mice, Inbred C3H KW - DNA Nucleotidylexotransferase -- analysis KW - Cell Differentiation -- drug effects KW - Lymphocytes -- drug effects KW - Thymus Gland -- immunology KW - Hematopoietic Stem Cells -- immunology KW - Diethylstilbestrol -- toxicity KW - Thymus Gland -- embryology KW - Thymus Gland -- drug effects KW - Hematopoietic Stem Cells -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76102872?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cellular+immunology&rft.atitle=Selective+prothymocyte+targeting+by+prenatal+diethylstilbesterol+exposure.&rft.au=Holladay%2C+S+D%3BBlaylock%2C+B+L%3BComment%2C+C+E%3BHeindel%2C+J+J%3BFox%2C+W+M%3BKorach%2C+K+S%3BLuster%2C+M+I&rft.aulast=Holladay&rft.aufirst=S&rft.date=1993-11-01&rft.volume=152&rft.issue=1&rft.spage=131&rft.isbn=&rft.btitle=&rft.title=Cellular+immunology&rft.issn=00088749&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-01-06 N1 - Date created - 1994-01-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Subchronic toxicity of cupric sulfate administered in drinking water and feed to rats and mice. AN - 76101884; 8253299 AB - The effects of acute poisoning by cupric sulfate in a number of species are well known; however, the effects of chronic low-level ingestion of cupric sulfate are less well characterized. Because exposure of humans to cupric sulfate may occur through drinking water, food, soil, or ambient air, subchronic toxicity studies were conducted in male and female F344/N rats and B6C3F1 mice by the drinking water (2-week exposure) and dosed feed (2- and 13-week exposure) routes. Animals were evaluated for histopathology, clinical pathology, reproductive toxicity, and tissue metal accumulation, and target organs were examined by a variety of special stains and by electron microscopy to characterize the observed lesions. In drinking water, cupric sulfate concentrations of 300 to 100 ppm produced no ill effects, whereas concentrations of 3000 to 30,000 ppm were lethal to rats and mice within 2 weeks. In feed, cupric sulfate concentrations of 4000 to 16,000 ppm caused significant reductions in body weight gain in both species in the 2- and 13-week studies. Hyperplasia and hyperkeratosis of the limiting ridge of the forestomach were present in both species in the 2- and 13-week studies. Rats in the dosed feed studies had a dose-related increase in inflammation in the liver and changes in clinical chemistry parameters which were indicative of hepatocellular damage and cholestasis. Histologic changes in the kidneys of rats consisted of a dose-related increase in the number and size of eosinophilic protein droplets in the epithelial cytoplasm and the lumina of the proximal convoluted tubules. Droplets were larger and more numerous in males than in females. Urinalysis results were suggestive of renal tubular epithelial damage. Iron staining of spleens from treated animals indicated a marked depletion of iron stores in both male and female rats, but not in mice, while hematologic and clinical chemistry alterations in rats in the 13-week study, along with histologic changes in bone in the 2-week dosed feed study, were indicative of a microcytic anemia. Cupric sulfate produced no adverse effects on any of the reproductive parameters measured in rats or mice of either sex. These results indicate that cupric sulfate at high exposure levels is a hepatic and renal toxicant, as well as an inducer of anemia in rodents, with rats more sensitive than mice following subchronic exposure. JF - Fundamental and applied toxicology : official journal of the Society of Toxicology AU - Hébert, C D AU - Elwell, M R AU - Travlos, G S AU - Fitz, C J AU - Bucher, J R AD - Toxicology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1993/11// PY - 1993 DA - November 1993 SP - 461 EP - 475 VL - 21 IS - 4 SN - 0272-0590, 0272-0590 KW - Metals KW - 0 KW - Copper KW - 789U1901C5 KW - Copper Sulfate KW - LRX7AJ16DT KW - Index Medicus KW - Vagina -- drug effects KW - Animals KW - Liver -- pathology KW - Kidney -- pathology KW - Vagina -- pathology KW - Spermatozoa -- pathology KW - Kidney -- drug effects KW - Mice KW - Tissue Distribution KW - Metals -- pharmacokinetics KW - Rats KW - Mice, Inbred Strains KW - Rats, Inbred F344 KW - Liver -- drug effects KW - Spermatozoa -- drug effects KW - Blood Cell Count -- drug effects KW - Female KW - Male KW - Copper -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76101884?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.atitle=Subchronic+toxicity+of+cupric+sulfate+administered+in+drinking+water+and+feed+to+rats+and+mice.&rft.au=H%C3%A9bert%2C+C+D%3BElwell%2C+M+R%3BTravlos%2C+G+S%3BFitz%2C+C+J%3BBucher%2C+J+R&rft.aulast=H%C3%A9bert&rft.aufirst=C&rft.date=1993-11-01&rft.volume=21&rft.issue=4&rft.spage=461&rft.isbn=&rft.btitle=&rft.title=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.issn=02720590&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-01-13 N1 - Date created - 1994-01-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Residual myelotoxicity of lindane in mice. AN - 76097468; 7504641 AB - Lindane (gamma-1,2,3,4,5,6-hexachlorocyclohexane), a widely used insecticide, may be found at low concentrations in the human diet. Male B6C3F1 mice given lindane daily at doses of 20 and 40 mg/kg body wt by gavage in corn oil for 3 days had suppressed bone marrow cellularity, erythrocyte precursors, granulocyte-macrophage progenitor cells (CFU-GM), and residual progenitor cell damage, which could be demonstrated by two whole-body irradiations (WBI) at 200 rads. Lindane exposure for 10 consecutive days at doses of 0, 10, or 20 mg/kg did not cause clinical abnormality or changes in body weights, but there were dose-dependent decreases in marrow cellularity, in more pluripotent stem cells and in committed CFU-GMs, which returned to control values by 4 weeks. These mice were then subjected to two 100-rad exposures of WBI at 4 and 9 weeks following cessation of lindane treatment. This level of irradiation caused only a transient drop in number of marrow progenitor cells. Control and lindane-exposed mice were examined at 1 and 6 weeks following the last irradiation, which was 10 and 15 weeks following the final lindane exposure. The lindane-exposed mice had lower progenitor cell numbers and slower recovery from the irradiation. These results indicate that lindane has significant myelotoxicity in mice and short-term lindane exposure can induce residual progenitor cell damage that can be demonstrated by subsequent irradiation. JF - Fundamental and applied toxicology : official journal of the Society of Toxicology AU - Hong, H L AU - Boorman, G A AD - Pathology Branch, National Institute of Environmental Health Sciences, National Toxicology Program, Research Triangle Park, North Carolina 27709. Y1 - 1993/11// PY - 1993 DA - November 1993 SP - 500 EP - 507 VL - 21 IS - 4 SN - 0272-0590, 0272-0590 KW - Lindane KW - 59NEE7PCAB KW - Index Medicus KW - Erythroid Precursor Cells -- drug effects KW - Animals KW - Whole-Body Irradiation KW - Mice, Inbred C57BL KW - Mice, Inbred C3H KW - Mice KW - Erythroid Precursor Cells -- cytology KW - Male KW - Bone Marrow Transplantation KW - Lindane -- toxicity KW - Hematopoietic Stem Cells -- cytology KW - Hematopoietic Stem Cells -- radiation effects KW - Hematopoietic Stem Cells -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76097468?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.atitle=Residual+myelotoxicity+of+lindane+in+mice.&rft.au=Hong%2C+H+L%3BBoorman%2C+G+A&rft.aulast=Hong&rft.aufirst=H&rft.date=1993-11-01&rft.volume=21&rft.issue=4&rft.spage=500&rft.isbn=&rft.btitle=&rft.title=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.issn=02720590&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-01-13 N1 - Date created - 1994-01-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of CYP2C23 expressed in rat kidney as an arachidonic acid epoxygenase. AN - 76082878; 8246128 AB - A cDNA was isolated from a rat kidney cDNA library using mixed probes of CYP (cytochrome P450) 2C6, 2C7, 2C8, 2C9 and 2C18 cDNAs. The 3'-terminal and 5'-terminal regions of the cDNA were sequenced and were identical with those of cytochrome P450 2C23 (CYP2C23) except for a one-base deletion and a one-base addition in coding region. These changes caused a frame shift and changed the deduced amino acid sequence relative to the previously published sequence. This cDNA was expressed using a baculovirus expression system, and the resultant P450 had a lambda max of 450 nm when reduced and complexed with carbon monoxide. Specific content of the expressed P450 ranged from 0.27 to 0.43 nmol/mg of cell lysate protein. Arachidonic acid metabolism catalyzed by expressed CYP2C23 indicated that CYP2C23 efficiently produced epoxyeicosatrienoic acids (EETs). These EETs were characterized further by gas-liquid chromatography/negative ion chemical ionization mass spectrometry (GC/NCIMS) and were found to include 8,9-EET, 11,12-EET and 14,15-EET in a ratio of 1:2:1. No 5,6-EET was detected. A low rate of lauric acid hydroxylation at the (omega-1)-position was found, but the enzyme was unable to metabolize prostaglandin E1. These studies suggest that CYP2C23 is responsible, in part, for the production of EETs in rat kidney. JF - The Journal of pharmacology and experimental therapeutics AU - Imaoka, S AU - Wedlund, P J AU - Ogawa, H AU - Kimura, S AU - Gonzalez, F J AU - Kim, H Y AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland. Y1 - 1993/11// PY - 1993 DA - November 1993 SP - 1012 EP - 1016 VL - 267 IS - 2 SN - 0022-3565, 0022-3565 KW - CYP2C23 KW - DNA Probes KW - 0 KW - DNA, Complementary KW - Lauric Acids KW - lauric acid KW - 1160N9NU9U KW - Arachidonic Acid KW - 27YG812J1I KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Oxygenases KW - EC 1.13.- KW - arachidonate epoxygenase KW - EC 1.14.14.1 KW - Alprostadil KW - F5TD010360 KW - Index Medicus KW - Lauric Acids -- metabolism KW - Animals KW - DNA, Complementary -- genetics KW - DNA, Complementary -- isolation & purification KW - Amino Acid Sequence KW - Alprostadil -- metabolism KW - Arachidonic Acid -- metabolism KW - Cloning, Molecular KW - Rats KW - Base Sequence KW - Gene Expression -- genetics KW - Molecular Sequence Data KW - Spectrophotometry KW - Oxygenases -- metabolism KW - Cytochrome P-450 Enzyme System -- genetics KW - Kidney -- physiology KW - Kidney -- enzymology KW - Cytochrome P-450 Enzyme System -- metabolism KW - Oxygenases -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76082878?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Identification+of+CYP2C23+expressed+in+rat+kidney+as+an+arachidonic+acid+epoxygenase.&rft.au=Imaoka%2C+S%3BWedlund%2C+P+J%3BOgawa%2C+H%3BKimura%2C+S%3BGonzalez%2C+F+J%3BKim%2C+H+Y&rft.aulast=Imaoka&rft.aufirst=S&rft.date=1993-11-01&rft.volume=267&rft.issue=2&rft.spage=1012&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 - 1994-01-06 N1 - Date created - 1994-01-06 N1 - Date revised - 2017-01-13 N1 - Gene symbol - CYP2C23 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Excretion of food-derived heterocyclic amine carcinogens into breast milk of lactating rats and formation of DNA adducts in the newborn. AN - 76082428; 8242844 AB - The distribution, DNA adduction and excretion into breast milk of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) were examined in lactating female F344 rats with 5 day old pups. Six hours after a single dose (10 mg/kg, p.o.) of radiolabeled IQ, MeIQx or PhIP to lactating dams, radioactivity in the dams was highest in the liver and kidney followed, in descending order, by the mammary gland, omental fat and brain. By 24 h after carcinogen administration, all tissues of the dams showed significantly reduced levels of radioactivity except for omental fat which changed only marginally from 6 to 24 h. 32P-Postlabeling analysis showed that the level of DNA adducts in mammary gland 6 h after dosing was 2.2, 0.7 and 0.2 adducts/10(7) nucleotides for PhIP, IQ and MeIQx respectively. In contrast, in hepatic DNA, the levels of IQ-DNA adducts (5.5 adducts/10(7) nucleotides) were 11-fold higher than those of PhIP or MeIQx. The stomach contents, liver, kidney and urine of pups nursed by dams given radiolabeled IQ, MeIQx or PhIP were radioactive, indicating that these carcinogens (and/or metabolites) were excreted into breast milk and absorbed by the pups. After a 6 h suckling period, the amount of PhIP-derived radioactivity in the stomach contents of the pups was approximately 10-fold higher than that seen with IQ or MeIQx. Urine from pups from the three groups was mutagenic in the Ames assay with Salmonella TA98 in the presence of an S9 activating system. IQ-, MeIQx- and PhIP-DNA adducts, at levels in the range of 0.25-0.46 adducts per 10(8) nucleotides, were detected in the livers of pups using the 32P-postlabeling method under intensification conditions. The results from this study indicate that breast milk is a route of exposure of the newborn to heterocyclic amines. The presence of DNA adducts in the tissues of pups further suggests that this route of exposure may have a carcinogenic consequence to the newborn. JF - Carcinogenesis AU - Ghoshal, A AU - Snyderwine, E G AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-0037. Y1 - 1993/11// PY - 1993 DA - November 1993 SP - 2199 EP - 2203 VL - 14 IS - 11 SN - 0143-3334, 0143-3334 KW - Carcinogens KW - 0 KW - Imidazoles KW - Quinolines KW - Quinoxalines KW - 2-amino-3-methylimidazo(4,5-f)quinoline KW - 30GL3D3T0G KW - 2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline KW - 77500-04-0 KW - DNA KW - 9007-49-2 KW - 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine KW - 909C6UN66T KW - Index Medicus KW - Quinolines -- toxicity KW - Animals KW - Imidazoles -- toxicity KW - Kidney -- metabolism KW - Quinolines -- metabolism KW - Imidazoles -- metabolism KW - Quinoxalines -- metabolism KW - Liver -- metabolism KW - Salmonella typhimurium -- drug effects KW - Lactation KW - Rats KW - Animals, Newborn KW - Imidazoles -- pharmacokinetics KW - Rats, Inbred F344 KW - Mutagenicity Tests KW - Mammary Glands, Animal -- metabolism KW - Quinoxalines -- toxicity KW - Quinoxalines -- pharmacokinetics KW - Quinolines -- pharmacokinetics KW - Female KW - Animal Feed KW - Milk -- metabolism KW - Carcinogens -- metabolism KW - DNA -- metabolism KW - Milk -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76082428?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Excretion+of+food-derived+heterocyclic+amine+carcinogens+into+breast+milk+of+lactating+rats+and+formation+of+DNA+adducts+in+the+newborn.&rft.au=Ghoshal%2C+A%3BSnyderwine%2C+E+G&rft.aulast=Ghoshal&rft.aufirst=A&rft.date=1993-11-01&rft.volume=14&rft.issue=11&rft.spage=2199&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-12-29 N1 - Date created - 1993-12-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - FVB/N mice: an inbred strain sensitive to the chemical induction of squamous cell carcinomas in the skin. AN - 76078122; 8242866 AB - The widespread use of FVB/N mice for the establishment of transgenic lines containing active oncogenes suggested the importance of testing the parent FVB/N mice for sensitivity to experimental carcinogenesis. After initiation of mouse skin by a single treatment with 7,12-dimethylbenz[a]anthracene (DMBA) and promotion by 20 weekly applications of 12-O-tetradecanoylphorbol-13-acetate (TPA), the skin tumor incidence was compared in FVB/N mice, TPA-sensitive (SENCAR and CD-1) and TPA-resistant mice (BALB/c and C57BL/6). Initiation by 25 micrograms DMBA followed by promotion with a low dose of TPA (2 micrograms/week) induced one or more papillomas in only 25% of FVB/N mice, compared with 100% in SENCAR, 53% in CD-1, 17% in BALB/c and 0% in C57BL/6 mice. At a more effective dose of TPA (5 micrograms/week), FVB/N mice initiated by 5, 25 or 100 micrograms DMBA developed 3.4, 6.9 and 11.8 papillomas per mouse. In contrast, the incidence of squamous cell carcinomas (SCCs) (17-18/30 mice) did not increase with DMBA dose. TPA promotion of non-initiated mice induced only six papillomas, but three progressed to SCCs, a high rate of malignant conversion. Skin tumor induction by 20 weekly treatments with 10 micrograms DMBA produced few papillomas, but 50.0% of the papillomas progressed to carcinomas in FVB/N mice, compared with 9.15% in SENCAR, 37.5% in CD-1, 23.1% in BALB/c and 15.0% in C57CL/6 mice. The first carcinomas appeared after 14 weeks in FVB/N, 24 weeks in SENCAR, 26 weeks in CD-1 and C57BL/6 and 34 weeks in BALB/c mice. Thus, FVB/N mice develop an unusually high incidence of SCCs after treatment with repeated DMBA, DMBA initiation-TPA promotion and even TPA alone. JF - Carcinogenesis AU - Hennings, H AU - Glick, A B AU - Lowry, D T AU - Krsmanovic, L S AU - Sly, L M AU - Yuspa, S H AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, MD. Y1 - 1993/11// PY - 1993 DA - November 1993 SP - 2353 EP - 2358 VL - 14 IS - 11 SN - 0143-3334, 0143-3334 KW - Acetone KW - 1364PS73AF KW - 9,10-Dimethyl-1,2-benzanthracene KW - 57-97-6 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Mice, Inbred Strains KW - Animals KW - Drug Resistance -- genetics KW - Papilloma -- pathology KW - Mice, Inbred C57BL KW - Mice KW - Genetic Predisposition to Disease KW - Mice, Inbred BALB C KW - Species Specificity KW - Papilloma -- chemically induced KW - Female KW - Acetone -- toxicity KW - Tetradecanoylphorbol Acetate -- toxicity KW - Carcinoma, Squamous Cell -- pathology KW - 9,10-Dimethyl-1,2-benzanthracene -- toxicity KW - Skin Neoplasms -- chemically induced KW - Skin Neoplasms -- pathology KW - Carcinoma, Squamous Cell -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76078122?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=FVB%2FN+mice%3A+an+inbred+strain+sensitive+to+the+chemical+induction+of+squamous+cell+carcinomas+in+the+skin.&rft.au=Hennings%2C+H%3BGlick%2C+A+B%3BLowry%2C+D+T%3BKrsmanovic%2C+L+S%3BSly%2C+L+M%3BYuspa%2C+S+H&rft.aulast=Hennings&rft.aufirst=H&rft.date=1993-11-01&rft.volume=14&rft.issue=11&rft.spage=2353&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-12-29 N1 - Date created - 1993-12-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Comparative effects of immunotoxic chemicals on in vitro proliferative responses of human and rodent lymphocytes. AN - 76074961; 8253306 AB - In order to determine the comparability of human and rodent in vitro systems, the direct effects of various therapeutic or environmental chemicals on proliferative responses of lymphocytes of mouse, rat, and human origins were examined and analyzed by a detailed statistical approach. Four compounds of diverse structure and mechanism of action which are known to impair lymphocyte transformation, such as hydroquinone, T-2 toxin, lead nitrate, as well as the widely used immunosuppressive drug cyclosporin A, were chosen as model test substances. T cells were stimulated by phytohaemagglutinin as well as monoclonal antibodies directed at the T cell receptor/CD3 complex, while B cells were activated by the T-independent mitogens, including Staphylococcus aureus cells, Escherichia coli lipopolysaccharide, and Salmonella typhimurium mitogen with specificity for human, mouse, and rat lymphocytes, respectively. In almost all cases the chemicals altered lymphoproliferative responses in a concentration-related manner in all three species. In general, overall similarities in the relative sensitivity of lymphoblastogenesis were obtained when the human dose-response curves were compared to the rodent response curves. Frequent, statistically significant species-dependent discrepancies of the overall response curves between mice and rats were observed. Large, statistically significant differences were observed for inorganic lead, revealing obvious divergences of the effect patterns in all cases, across all species. In this case, rodent species, especially the rat, were very sensitive to immunomodulation by lead, whereas human cells were relatively resistant. It is suggested that direct interspecies comparisons of immunological effects due to chemical treatment in vitro can provide a greater understanding of the relationship between animal and human data, which will improve the confidence of extrapolation from findings in laboratory animals to human health risk. JF - Fundamental and applied toxicology : official journal of the Society of Toxicology AU - Lang, D S AU - Meier, K L AU - Luster, M I AD - Environmental Immunity Section, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1993/11// PY - 1993 DA - November 1993 SP - 535 EP - 545 VL - 21 IS - 4 SN - 0272-0590, 0272-0590 KW - Hydroquinones KW - 0 KW - Immunosuppressive Agents KW - Lipopolysaccharides KW - Nitrates KW - Lead KW - 2P299V784P KW - lead nitrate KW - 6E5P1699FI KW - Cyclosporine KW - 83HN0GTJ6D KW - T-2 Toxin KW - I3FL5NM3MO KW - hydroquinone KW - XV74C1N1AE KW - Index Medicus KW - Animals KW - Humans KW - Cyclosporine -- toxicity KW - Mice KW - Hydroquinones -- toxicity KW - Rats KW - Rats, Inbred F344 KW - Cells, Cultured KW - Lead -- toxicity KW - Nitrates -- toxicity KW - Escherichia coli KW - Mice, Inbred C3H KW - Mice, Inbred C57BL KW - T-2 Toxin -- toxicity KW - Species Specificity KW - Female KW - Lymphocyte Activation -- drug effects KW - Immunosuppressive Agents -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76074961?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.atitle=Comparative+effects+of+immunotoxic+chemicals+on+in+vitro+proliferative+responses+of+human+and+rodent+lymphocytes.&rft.au=Lang%2C+D+S%3BMeier%2C+K+L%3BLuster%2C+M+I&rft.aulast=Lang&rft.aufirst=D&rft.date=1993-11-01&rft.volume=21&rft.issue=4&rft.spage=535&rft.isbn=&rft.btitle=&rft.title=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.issn=02720590&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-01-13 N1 - Date created - 1994-01-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chemotherapy for patients with pulmonary Kaposi's sarcoma: benefit of filgrastim (G-CSF) in supporting dose administration. AN - 76059836; 7694375 AB - Kaposi's sarcoma (KS) is common in individuals infected with the human immunodeficiency virus (HIV-1). Although KS is frequently indolent, it can also be aggressive and life-threatening, especially in patients with pulmonary involvement (PKS), who have poor survival rates when untreated. In an effort to develop treatment regimens for PKS that would prolong life or reduce clinical symptoms, we used combination chemotherapy to treat 18 patients who had AIDS and PKS; 13 (72%) of them had a history of previous opportunistic infections. Doxorubicin, bleomycin, vinblastine, vincristine, actinomycin D, and dacarbazine were used in 3-week cycles with concomitant zidovudine, zalcitabine (dideoxycytidine), or didanocine (dideoxyinosine). Antiviral therapy was continued with chemotherapy. A partial or complete response to chemotherapy was obtained in 15 of the 18 patients (83%), as characterized by clearing of infiltrates on chest films and resolution of dyspnea and cough. Only 2 patients had opportunistic infections during treatment. Median survival was 9 months; patients who received dose reductions in less than three cycles of chemotherapy survived more than 1 year. Most deaths were related to unresponsive PKS. These results indicate that patients with symptomatic PKS can be safely and effectively treated with combination chemotherapy while receiving myelosuppressive drugs such as zidovudine. Such patients receive substantial relief from dyspnea and cough. Survival for treated patients exceeds survival for untreated historical controls. JF - Southern medical journal AU - Sloand, E AU - Kumar, P N AU - Pierce, P F AD - National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md. 20892. Y1 - 1993/11// PY - 1993 DA - November 1993 SP - 1219 EP - 1224 VL - 86 IS - 11 SN - 0038-4348, 0038-4348 KW - Recombinant Proteins KW - 0 KW - Granulocyte Colony-Stimulating Factor KW - 143011-72-7 KW - Filgrastim KW - PVI5M0M1GW KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Humans KW - Treatment Outcome KW - Recombinant Proteins -- therapeutic use KW - Survival Analysis KW - Sarcoma, Kaposi -- drug therapy KW - Granulocyte Colony-Stimulating Factor -- therapeutic use KW - Lung Neoplasms -- drug therapy KW - Neutropenia -- prevention & control KW - Neutropenia -- chemically induced KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Neutropenia -- drug therapy KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76059836?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Southern+medical+journal&rft.atitle=Chemotherapy+for+patients+with+pulmonary+Kaposi%27s+sarcoma%3A+benefit+of+filgrastim+%28G-CSF%29+in+supporting+dose+administration.&rft.au=Sloand%2C+E%3BKumar%2C+P+N%3BPierce%2C+P+F&rft.aulast=Sloand&rft.aufirst=E&rft.date=1993-11-01&rft.volume=86&rft.issue=11&rft.spage=1219&rft.isbn=&rft.btitle=&rft.title=Southern+medical+journal&rft.issn=00384348&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-12-20 N1 - Date created - 1993-12-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Prostaglandin E2 and other cyclic AMP elevating agents inhibit interleukin 2 gene transcription by counteracting calcineurin-dependent pathways. AN - 76055440; 7693857 AB - We have previously shown that prostaglandin E2 and other cAMP elevating agents inhibit the nuclear transcription of the human IL-2 gene by interfering with a Ca(2+)-sensitive T cell signal transduction pathway. Calcineurin, a Ca2+/calmodulin-dependent 2B protein phosphatase, is an essential component of the T cell receptor signal transduction pathway leading to IL-2 gene expression. We have therefore tested the hypothesis that this phosphatase may be a target for the inhibitory effects of cAMP on IL-2 gene transcription. We report here that PGE2 markedly reduces the IL-2 promoter activity that is induced by a constitutively active form of calcineurin. In contrast to the complete inhibition of promoter activity produced by the immunosuppressants cyclosporin A and FK-506, this partial block suggests that PGE2 modulates downstream events needed for lymphokine gene activation. Overexpression of calcineurin in Jurkat cells decreases their apparent sensitivity to the inhibitory effects of PGE2 consistent with the fact that this enzyme plays a physiological role in dephosphorylating substrates of cAMP-dependent kinases in several tissues. These results provide evidence that cAMP-dependent pathways may antagonize calcineurin-regulated cascades for T cell activation in vivo, and suggest crosstalk between the Ca2+ and the cAMP signaling pathways during T cell activation. JF - The Journal of experimental medicine AU - Paliogianni, F AU - Kincaid, R L AU - Boumpas, D T AD - Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/11/01/ PY - 1993 DA - 1993 Nov 01 SP - 1813 EP - 1817 VL - 178 IS - 5 SN - 0022-1007, 0022-1007 KW - Calmodulin-Binding Proteins KW - 0 KW - Interleukin-2 KW - Colforsin KW - 1F7A44V6OU KW - 8-Bromo Cyclic Adenosine Monophosphate KW - 23583-48-4 KW - Ionomycin KW - 56092-81-0 KW - Cyclic AMP KW - E0399OZS9N KW - Chloramphenicol O-Acetyltransferase KW - EC 2.3.1.28 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Calcineurin KW - EC 3.1.3.16 KW - Phosphoprotein Phosphatases KW - Dinoprostone KW - K7Q1JQR04M KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - 1-Methyl-3-isobutylxanthine KW - TBT296U68M KW - Index Medicus KW - Animals KW - Chloramphenicol O-Acetyltransferase -- biosynthesis KW - Humans KW - Ionomycin -- pharmacology KW - Mice KW - Chloramphenicol O-Acetyltransferase -- metabolism KW - Plasmids KW - Gene Deletion KW - Protein Kinase C -- metabolism KW - Polymerase Chain Reaction KW - Tumor Cells, Cultured KW - Promoter Regions, Genetic -- drug effects KW - Transfection KW - Kinetics KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Cell Line KW - Gene Expression -- drug effects KW - Dinoprostone -- pharmacology KW - Transcription, Genetic -- drug effects KW - Interleukin-2 -- biosynthesis KW - Calmodulin-Binding Proteins -- metabolism KW - Interleukin-2 -- genetics KW - 8-Bromo Cyclic Adenosine Monophosphate -- pharmacology KW - Calmodulin-Binding Proteins -- biosynthesis KW - T-Lymphocytes -- metabolism KW - Colforsin -- pharmacology KW - Cyclic AMP -- metabolism KW - Phosphoprotein Phosphatases -- biosynthesis KW - Phosphoprotein Phosphatases -- metabolism KW - 1-Methyl-3-isobutylxanthine -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76055440?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+experimental+medicine&rft.atitle=Prostaglandin+E2+and+other+cyclic+AMP+elevating+agents+inhibit+interleukin+2+gene+transcription+by+counteracting+calcineurin-dependent+pathways.&rft.au=Paliogianni%2C+F%3BKincaid%2C+R+L%3BBoumpas%2C+D+T&rft.aulast=Paliogianni&rft.aufirst=F&rft.date=1993-11-01&rft.volume=178&rft.issue=5&rft.spage=1813&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+experimental+medicine&rft.issn=00221007&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-11-29 N1 - Date created - 1993-11-29 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Exp Med. 1982 Mar 1;155(3):943-8 [6977613] J Clin Invest. 1993 Apr;91(4):1481-9 [8473495] J Biol Chem. 1984 Jul 10;259(13):8080-3 [6330098] J Biol Chem. 1986 Jun 25;261(18):8140-5 [3013843] Cell. 1986 Aug 1;46(3):401-5 [3015413] J Immunol. 1986 Nov 15;137(10):3299-305 [3021852] J Exp Med. 1977 Dec 1;146(6):1719-34 [411876] Eur J Biochem. 1978 Jun 15;87(2):341-51 [208844] Prostaglandins. 1979 Oct;18(4):605-16 [531227] Biochem Biophys Res Commun. 1986 Oct 15;140(1):320-8 [3022718] J Exp Med. 1987 Feb 1;165(2):395-407 [3102668] Prog Allergy. 1986;39:24-100 [3550817] Eur J Immunol. 1988 Nov;18(11):1791-6 [2849551] Biochemistry. 1989 Feb 21;28(4):1868-74 [2541767] Annu Rev Biochem. 1989;58:453-508 [2549856] N Engl J Med. 1990 Apr 26;322(17):1183-8 [2109195] J Biol Chem. 1990 Oct 15;265(29):17657-64 [2170390] J Immunol. 1990 Oct 15;145(8):2616-25 [1976699] J Immunol. 1991 Jul 1;147(1):14-21 [1711070] J Immunol. 1992 May 1;148(9):2845-52 [1374102] Nature. 1992 Jun 25;357(6380):692-4 [1377361] Nature. 1992 Jun 25;357(6380):695-7 [1377362] Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7394-7 [1380157] Eur J Biochem. 1983 May 2;132(2):297-307 [6301829] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Carbamazepine withdrawal: effects of taper rate on seizure frequency. AN - 76053387; 8232943 AB - We prospectively investigated the effects of rate of carbamazepine (CBZ) withdrawal and CBZ level on seizure type and frequency in 12 epilepsy patients withdrawn completely from antiepileptic drugs prior to entering an investigational monotherapy trial. Patients withdrawn from CBZ rapidly (over 4 days) experienced significantly more generalized tonic-clonic seizures (GTCSs) and GTCS clusters than did those withdrawn slowly (over 10 days). Complex partial seizure (CPS) frequency did not differ between the two groups. CPSs preceded GTCSs, with GTCSs occurring in the majority of patients after CBZ had been discontinued, at subtherapeutic or absent CBZ levels. Two of six patients who had been tapered rapidly and all six patients who had been tapered slowly were able to enter the investigational monotherapy trial. JF - Neurology AU - Malow, B A AU - Blaxton, T A AU - Stertz, B AU - Theodore, W H AD - Epilepsy Research Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, 20892. Y1 - 1993/11// PY - 1993 DA - November 1993 SP - 2280 EP - 2284 VL - 43 IS - 11 SN - 0028-3878, 0028-3878 KW - Carbamazepine KW - 33CM23913M KW - Abridged Index Medicus KW - Index Medicus KW - Analysis of Variance KW - Humans KW - Electroencephalography KW - Adult KW - Middle Aged KW - Male KW - Female KW - Epilepsy -- physiopathology KW - Epilepsy -- chemically induced KW - Carbamazepine -- adverse effects KW - Substance Withdrawal Syndrome -- physiopathology KW - Carbamazepine -- administration & dosage KW - Carbamazepine -- therapeutic use KW - Epilepsy -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76053387?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurology&rft.atitle=Carbamazepine+withdrawal%3A+effects+of+taper+rate+on+seizure+frequency.&rft.au=Malow%2C+B+A%3BBlaxton%2C+T+A%3BStertz%2C+B%3BTheodore%2C+W+H&rft.aulast=Malow&rft.aufirst=B&rft.date=1993-11-01&rft.volume=43&rft.issue=11&rft.spage=2280&rft.isbn=&rft.btitle=&rft.title=Neurology&rft.issn=00283878&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-12-20 N1 - Date created - 1993-12-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - High-dose carboplatin and recombinant granulocyte-macrophage colony-stimulating factor in advanced-stage recurrent ovarian cancer. AN - 76049909; 8229126 AB - We investigated whether carboplatin myelosuppression could be favorably modulated by the administration of recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF) in patients with advanced-stage ovarian cancer. Thirty-four patients with advanced-stage recurrent ovarian cancer were treated with high-dose carboplatin (800 mg/m2 per 35-day cycle) and rGM-CSF. rGM-CSF was administered as a daily subcutaneous injection starting 72 hours after the carboplatin dose and continuing until 7 days beyond the WBC nadir. rGM-CSF was administered in a phase I fashion. Seven patients were treated at an rGM-CSF dose of 3 micrograms/kg, 11 at 5 micrograms/kg, 10 at 10 micrograms/kg, and six at 20 micrograms/kg. rGM-CSF-related toxicities that were not dose-related included nonneutropenic fever, rib pain, acute hypersensitivity reaction, and pericarditis. At the rGM-CSF dose of 20 micrograms/kg, debilitating malaise was seen in four of six patients and this was the dose-limiting toxicity. Patient tolerance of the 3-micrograms/kg and 5-micrograms/kg doses was good, but tolerance was limited for the 10-micrograms/kg dose. Febrile neutropenia was seen in four of seven patients at 3 micrograms/kg, two of 11 at 5 micrograms/kg, two of 10 at 10 micrograms/kg, and one of six at 20 micrograms/kg. Cumulative carboplatin myelotoxicity was blunted only in respect to WBC count, and not for platelets or RBCs. Gastrointestinal bleeding was seen in seven patients. The administered dose-intensity of carboplatin averaged 134 mg/m2/wk for the cohort, or 670 mg/m2 per 35-day cycle. There were two clinical complete responses and eleven partial responses, for a response rate of 38%. rGM-CSF appears to be effective and tolerable at 5 micrograms/kg/d administered subcutaneously, if given with carboplatin doses up to approximately 600 mg/m2 over 35 days. The use of rGM-CSF with high-dose carboplatin is associated with a substantial response rate in poor-prognosis ovarian cancer patients. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Reed, E AU - Janik, J AU - Bookman, M A AU - Rothenberg, M AU - Smith, J AU - Young, R C AU - Ozols, R F AU - VanderMolen, L AU - Kohn, E AU - Jacob, J L AD - Medicine Branch, National Cancer Institute, Bethesda, MD 20892. Y1 - 1993/11// PY - 1993 DA - November 1993 SP - 2118 EP - 2126 VL - 11 IS - 11 SN - 0732-183X, 0732-183X KW - Recombinant Proteins KW - 0 KW - Granulocyte-Macrophage Colony-Stimulating Factor KW - 83869-56-1 KW - Carboplatin KW - BG3F62OND5 KW - Index Medicus KW - Leukocyte Count -- drug effects KW - Neoplasm Staging KW - Humans KW - Adult KW - Recombinant Proteins -- adverse effects KW - Injections, Subcutaneous KW - Blood Transfusion KW - Aged KW - Middle Aged KW - Recurrence KW - Recombinant Proteins -- therapeutic use KW - Female KW - Bone Marrow Diseases -- prevention & control KW - Bone Marrow Diseases -- chemically induced KW - Ovarian Neoplasms -- pathology KW - Bone Marrow Diseases -- therapy KW - Granulocyte-Macrophage Colony-Stimulating Factor -- therapeutic use KW - Granulocyte-Macrophage Colony-Stimulating Factor -- adverse effects KW - Carboplatin -- adverse effects KW - Carboplatin -- administration & dosage KW - Ovarian Neoplasms -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76049909?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=High-dose+carboplatin+and+recombinant+granulocyte-macrophage+colony-stimulating+factor+in+advanced-stage+recurrent+ovarian+cancer.&rft.au=Reed%2C+E%3BJanik%2C+J%3BBookman%2C+M+A%3BRothenberg%2C+M%3BSmith%2C+J%3BYoung%2C+R+C%3BOzols%2C+R+F%3BVanderMolen%2C+L%3BKohn%2C+E%3BJacob%2C+J+L&rft.aulast=Reed&rft.aufirst=E&rft.date=1993-11-01&rft.volume=11&rft.issue=11&rft.spage=2118&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 - 1993-12-01 N1 - Date created - 1993-12-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutagenicity of chemicals added to foods. AN - 76049413; 7694099 AB - Much attention has recently been brought to the fact that many natural components of the diet are mutagenic and/or carcinogenic. Approximately 2700 distinct chemical entities, chemical mixtures, and plant extracts are allowed as direct food additives by the US F.D.A. These include chemicals found in the body, natural components of foods, and synthetic chemicals. In addition to the chemicals among these additives that are mutagenic, there are a number of mutagens that are normally present in the plant products that are consumed as part of the normal diets. The mutagenicity in Salmonella of these food additives was identified using the National Toxicology Program and US E.P.A. Gene-Tox databases. Relatively few of the chemicals deliberately added to foods have been tested for mutagenicity. Among the chemicals tested, approximately 15% were mutagenic in Salmonella. The mutagens include both organic and inorganic substances. Many of the natural plant components, such as flavonoids, hydrazides, and tannins also have been shown to be mutagenic. However, these natural components are not considered as food additives. A large proportion of the mutagenic food additives appear to act through the generation of oxygen- or free radicals. Although the relationships between mutagenicity and carcinogenicity of electrophilic chemicals has been well studied, the potential hazard of low-level increases in free-radical generating substances on tumor incidences is unknown. JF - Mutation research AU - Zeiger, E AD - Environmental Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1993/11// PY - 1993 DA - November 1993 SP - 53 EP - 61 VL - 290 IS - 1 SN - 0027-5107, 0027-5107 KW - Food Additives KW - 0 KW - Free Radicals KW - Mutagens KW - Oxygen KW - S88TT14065 KW - Index Medicus KW - Animals KW - Oxygen -- metabolism KW - Humans KW - Molecular Sequence Data KW - Carbohydrate Sequence KW - Mutagens -- toxicity KW - Food Additives -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76049413?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mutagenicity+of+chemicals+added+to+foods.&rft.au=Zeiger%2C+E&rft.aulast=Zeiger&rft.aufirst=E&rft.date=1993-11-01&rft.volume=290&rft.issue=1&rft.spage=53&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 - 1993-12-10 N1 - Date created - 1993-12-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Differential regulation of actin polymerization following activation of resting T lymphocytes from young and aged mice. AN - 76047018; 8227168 AB - Actin polymerization accompanies receptor-mediated responses and is correlated with motility-related events. In T lymphocytes, there is a lateral redistribution of surface receptors into caps and aggregation of actin-myosin in cytoplasmic subcaps, and these are impaired in T cells from aged individuals. This study documents marked changes in age-related cytoskeletal actin filament function which may account for the reduced motility. Basal levels of filamentous actin (F-actin) are significantly higher in purified G(o) T cells from aged C57BL/6 mice, due to a preferential increase in the CD8+ subpopulation. Following activation of the resting T cells with Concanavalin A (Con A), F-actin depolymerized in cells from young mice for 2 min, followed by rapid polymerization, reaching a plateau 200% above resting levels. In cells from 15-17-month-old mice, an attenuated depolymerization phase was seen for 45 sec, followed by little polymerization. No depolymerization or polymerization phases occurred in cells from aged mice. Phorbol 12 myristate 13-acetate (PMA), which activates protein kinase C (PKC), bypassing receptor mediated signals, induced actin polymerization to 57% of the levels of that after Con A stimulation in cells from both young and old animals and partially eliminated the differences in actin filament assembly due to age. Perturbation of the cytoskeleton with cytochalasin E (CE) potentiated proliferation of Con A-stimulated T cells from aged mice but did not completely restore the deficit attributed to immunosenescence. The results show an age-related impairment of cytoskeletal functions and suggest that differences in early signal transduction events contribute to the decrements in surface receptor motility and subsequent proliferation of T lymphocytes from older individuals. JF - Journal of cellular physiology AU - Brock, M A AU - Chrest, F AD - Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224. Y1 - 1993/11// PY - 1993 DA - November 1993 SP - 367 EP - 378 VL - 157 IS - 2 SN - 0021-9541, 0021-9541 KW - Actins KW - 0 KW - Cytochalasins KW - Polymers KW - Receptors, Interleukin-2 KW - Concanavalin A KW - 11028-71-0 KW - cytochalasin E KW - 36011-19-5 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - Receptors, Interleukin-2 -- analysis KW - Cell Cycle -- physiology KW - Cell Division -- physiology KW - Cytoskeleton -- physiology KW - Cell Membrane -- physiology KW - Cytochalasins -- pharmacology KW - Receptors, Interleukin-2 -- metabolism KW - Actin Cytoskeleton -- metabolism KW - Cell Movement -- drug effects KW - Cell Membrane -- chemistry KW - Male KW - Cytoskeleton -- metabolism KW - Cell Division -- drug effects KW - Resting Phase, Cell Cycle KW - Mice KW - Signal Transduction -- physiology KW - Actin Cytoskeleton -- physiology KW - Cells, Cultured KW - Cell Movement -- physiology KW - Mice, Inbred C57BL KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Cell Membrane -- metabolism KW - Concanavalin A -- pharmacology KW - Aging -- physiology KW - Aging -- metabolism KW - Actins -- physiology KW - T-Lymphocytes -- metabolism KW - T-Lymphocytes -- cytology KW - Actins -- metabolism KW - T-Lymphocytes -- physiology KW - Actins -- analysis KW - Lymphocyte Activation -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76047018?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+cellular+physiology&rft.atitle=Differential+regulation+of+actin+polymerization+following+activation+of+resting+T+lymphocytes+from+young+and+aged+mice.&rft.au=Brock%2C+M+A%3BChrest%2C+F&rft.aulast=Brock&rft.aufirst=M&rft.date=1993-11-01&rft.volume=157&rft.issue=2&rft.spage=367&rft.isbn=&rft.btitle=&rft.title=Journal+of+cellular+physiology&rft.issn=00219541&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-12-01 N1 - Date created - 1993-12-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ultraviolet hypermutability of a shuttle vector propagated in xeroderma pigmentosum variant cells. AN - 76046367; 8228338 AB - Patients with the variant form of xeroderma pigmentosum (XP) have clinical XP including a high frequency of skin cancer but, in contrast to the other forms of XP, have normal post-ultraviolet (UV) DNA excision repair and nearly normal post-UV survival. However, like excision repair-deficient XP cells, the XP variant cells are UV hypermutable. We used a UV-treated plasmid shuttle vector, pZ189, to examine the DNA repair defect in lymphoblastoid cells from an XP variant patient, XPPHBE, and a normal control. Plasmid repair, mutagenesis, and replication occur within transfected cells in a process dependent on the cells' repair capacity. With the XP variant cells post-UV, plasmid survival was normal with but there was an abnormally increased post-UV plasmid mutation frequency. Sequence analysis of the mutated plasmids revealed an increased frequency of plasmids with single base substitution mutations with the XP variant cells. As in earlier studies with UV mutagenesis, there was a predominance of G:C-->A:T base substitution mutations with plasmids recovered from both cell lines. The frequency of G:C-->C:G transversions was significantly higher with plasmids recovered from the XP variant cells than from normal cells. The location of mutations in the marker gene was non-random with different mutagenic hotspots found in plasmids recovered from the XP variant cells and from the normal cells. This study suggests that plasmid UV hypermutability in the presence of normal UV survival may be related to the increased UV skin cancer susceptibility of XP variant patients. JF - The Journal of investigative dermatology AU - Waters, H L AU - Seetharam, S AU - Seidman, M M AU - Kraemer, K H AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1993/11// PY - 1993 DA - November 1993 SP - 744 EP - 748 VL - 101 IS - 5 SN - 0022-202X, 0022-202X KW - Index Medicus KW - Ultraviolet Rays KW - Base Sequence KW - DNA Repair KW - Humans KW - Genetic Vectors KW - Adult KW - Molecular Sequence Data KW - Plasmids KW - Male KW - Female KW - Cell Line KW - Xeroderma Pigmentosum -- genetics KW - Mutation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76046367?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+investigative+dermatology&rft.atitle=Ultraviolet+hypermutability+of+a+shuttle+vector+propagated+in+xeroderma+pigmentosum+variant+cells.&rft.au=Waters%2C+H+L%3BSeetharam%2C+S%3BSeidman%2C+M+M%3BKraemer%2C+K+H&rft.aulast=Waters&rft.aufirst=H&rft.date=1993-11-01&rft.volume=101&rft.issue=5&rft.spage=744&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+investigative+dermatology&rft.issn=0022202X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-11-26 N1 - Date created - 1993-11-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Keratinocyte differentiation is associated with changes in the expression and regulation of phospholipase C isoenzymes. AN - 76046306; 8228334 AB - In murine keratinocytes, Ca(++)-induced terminal differentiation is accompanied by a rapid and sustained increase of inositol phosphates and diacylglycerol. Based on Western blotting analysis, basal keratinocytes cultured in 0.05 mM Ca++ medium express phospholipase C (PLC)-gamma 1 predominantly and no detectable PLC-beta 1. Differentiating keratinocytes cultured in 1.4 mM Ca++ express two- to threefold more PLC-gamma 1 protein and PLC-delta 1, but no detectable PLC-beta 1. Although the amount of PLC-gamma 1 and -delta 1 protein increased, PLC-gamma 1 and -delta 1 mRNA decreased in differentiating cells. Thus the sustained rise of PLC activity induced by Ca++ in differentiating keratinocytes may be associated with higher amounts of both PLC-gamma 1 and -delta 1 in maturing cells, determined by a posttranscriptional mechanism. Tyrosine phosphate content in PLC-gamma 1 was low in basal cells and did not change in cells exposed to 1.4 mM Ca++. However, genistein inhibited the increase in PLC activity induced by 1.4 mM Ca++. In contrast, transforming growth factor (TGF)alpha, which stimulates both PLC activity and growth in basal keratinocytes, increased tyrosine phosphorylation of PLC-gamma 1. These results suggest that tyrosine phosphorylation of PLC-gamma 1 by the epidermal growth factor (EGF) receptor is linked to stimulated proliferation, whereas stimulation of PLC activity by Ca++ is linked to keratinocyte differentiation and involves the action of a tyrosine kinase but not tyrosine phosphorylation of PLC-gamma 1. Based on studies using the intracellular free Ca++ chelator BAPTA, a rise in intracellular free Ca++ was not required for stimulation of PLC activity by raising extracellular Ca++. Phorbol esters inhibited PLC stimulation by 1.4 mM Ca++ medium and increased serine phosphorylation of PLC-gamma 1. Exogenous phosphatidylinositol-specific and phosphatidylcholine-specific bacterial PLC also inhibited endogenous inositol phosphate formation and increased endogenous diacylglycerol (DAG). Thus, direct serine phosphorylation of PLC-gamma 1 by protein kinase C is associated with the inhibition of Ca(++)-mediated PLC stimulation. These results show that keratinocytes have multiple mechanisms to regulate PLC activity in response to a specific signal. JF - The Journal of investigative dermatology AU - Punnonen, K AU - Denning, M AU - Lee, E AU - Li, L AU - Rhee, S G AU - Yuspa, S H AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda 20892. Y1 - 1993/11// PY - 1993 DA - November 1993 SP - 719 EP - 726 VL - 101 IS - 5 SN - 0022-202X, 0022-202X KW - Isoenzymes KW - 0 KW - Tyrosine KW - 42HK56048U KW - Type C Phospholipases KW - EC 3.1.4.- KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Animals KW - Phosphorylation KW - Enzyme Activation KW - Cells, Cultured KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Cell Differentiation KW - Mice KW - Calcium -- pharmacology KW - Tyrosine -- metabolism KW - Mice, Inbred BALB C KW - Keratinocytes -- enzymology KW - Keratinocytes -- cytology KW - Isoenzymes -- metabolism KW - Type C Phospholipases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76046306?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+investigative+dermatology&rft.atitle=Keratinocyte+differentiation+is+associated+with+changes+in+the+expression+and+regulation+of+phospholipase+C+isoenzymes.&rft.au=Punnonen%2C+K%3BDenning%2C+M%3BLee%2C+E%3BLi%2C+L%3BRhee%2C+S+G%3BYuspa%2C+S+H&rft.aulast=Punnonen&rft.aufirst=K&rft.date=1993-11-01&rft.volume=101&rft.issue=5&rft.spage=719&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+investigative+dermatology&rft.issn=0022202X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-11-26 N1 - Date created - 1993-11-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regressive and non-regressive thyroid lesions of the rat induced by single injection of N-bis(2-hydroxypropyl)nitrosamine and iodine deficient diet. AN - 76044338; 7902219 AB - Six-week-old male F344 rats were divided into 4 groups. Rats in Groups 1 (n = 16) and 3 (n = 14) received a s.c. injection of N-bis(2-hydroxypropyl)nitrosamine (DHPN) (2800 mg/kg) in experimental week 1 while rats in Groups 2 (n = 5) and 4 (n = 5) received saline. From weeks 2-20, all rats were given an iodine deficient (I-def) diet and tap water. Groups 1 and 2 were killed for the measurements of thyroid-stimulating hormone (TSH), thyroxine (T4), the maximum thyroid width (MTW), thyroid weight, morphology, morphometrics and proliferating cell nuclear antigen (PCNA) labeling index (LI). The thyroids of the rats in Group 3 and 4 were surgically exposed and the MTWs were measured. These latter rats were given basal diet for 6 weeks to recover from iodine deficiency, and then killed for the same measurements. Thyroid nodular lesions in Group 1 rats were classified into five categories (NL0, NL1, NL2, NL3 and NL4) based upon incremental cellular and structural atypia. Two types of regressive nodules (NL'0 and NL'1+2) were identified in the recovered rats as the regressed form of NL0, NL1 and NL2 lesions. NL3 and NL4 nodules were seen in Groups 1 and 3. The mean number of combined NL0, NL1 or NL2 lesions was 28.44 +/- 6.12 nodules per rat (NPR) in Group 1 rats and the mean number of NL'0 and NL'1+2 lesions was 28.07 +/- 13.05 NPR in Group 3 rats. The mean number of NL3 or NL4 lesions was 1.70 NPR in Group 1 rats and 3.42 NPR in Group 3 rats. The LIs were NL0 (6.4 +/- 2.5%), NL1 (7.7 +/- 4.4%), NL2 (0.7 +/- 0.3%), NL3 (7.5 +/- 1.3%) and NL4 (14.4 +/- 5.3%) in Group 1 rats and NL'0 (< 0.001%), NL'1 + 2 (< 0.01%), NL3 (9.0 +/- 4.4%) and NL4 (23.3 +/- 17.8%) in Group 3 rats. The thyroid weights of Group 4 rats were 41% of Group 2 rats. The volume fraction (VF) of the non-NL3, non-NL4 areas in Group 3 rats was 40% of that in Group 1 rats. However, the VF of NL3 or NL4 lesions in Group 3 rats was 520% of that of Group 1 rats. In summary, the growth of the NL0, NL1 and NL2 lesions was TSH-dependent, whereas NL3 and NL4 lesions were TSH-independent.(ABSTRACT TRUNCATED AT 400 WORDS) JF - Carcinogenesis AU - Kanno, J AU - Maronpot, R R AU - Takahashi, M AU - Kasuga, T AU - Hayashi, Y AD - Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1993/11// PY - 1993 DA - November 1993 SP - 2389 EP - 2396 VL - 14 IS - 11 SN - 0143-3334, 0143-3334 KW - Carcinogens KW - 0 KW - Nitrosamines KW - Nuclear Proteins KW - Proliferating Cell Nuclear Antigen KW - diisopropanolnitrosamine KW - 4J072HB2ND KW - Thyrotropin KW - 9002-71-5 KW - Iodine KW - 9679TC07X4 KW - Thyroxine KW - Q51BO43MG4 KW - Index Medicus KW - Rats KW - Nuclear Proteins -- analysis KW - Animals KW - Rats, Inbred F344 KW - Thyrotropin -- blood KW - Cell Division -- drug effects KW - Thyroxine -- blood KW - Diet KW - Male KW - Organ Size -- drug effects KW - Thyroid Neoplasms -- chemically induced KW - Nitrosamines -- toxicity KW - Thyroid Gland -- drug effects KW - Iodine -- deficiency KW - Thyroid Gland -- pathology KW - Carcinogens -- toxicity KW - Thyroid Neoplasms -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76044338?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Regressive+and+non-regressive+thyroid+lesions+of+the+rat+induced+by+single+injection+of+N-bis%282-hydroxypropyl%29nitrosamine+and+iodine+deficient+diet.&rft.au=Kanno%2C+J%3BMaronpot%2C+R+R%3BTakahashi%2C+M%3BKasuga%2C+T%3BHayashi%2C+Y&rft.aulast=Kanno&rft.aufirst=J&rft.date=1993-11-01&rft.volume=14&rft.issue=11&rft.spage=2389&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-12-29 N1 - Date created - 1993-12-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Life-span and cancer: the induction time of tumors in diverse animal species treated with nitrosodiethylamine. AN - 76044294; 8242869 AB - To ascertain the possible relationship between animal lifespan and the rate of tumor development, the results of carcinogenesis studies in various species treated with similar doses of a carcinogenic nitrosamine have been compiled from the literature. Comparable experiments in 20 species of mammals, reptiles, birds, amphibians and fish were analyzed. The animals received approximately 1000 mg/kg body wt (400-2500 mg/kg) lifetime total dose of nitrosodiethylamine (NDEA). Animals with lifespans varying from 3 years (mouse) to > 50 years (snake) developed tumors with latent periods of roughly 1 year (range 0.5-1.9 year), showing no relationship to lifespan. The evidence suggests that the time dependence of tumor development is more likely related to the cumulative dose of carcinogen than to lifespan and the rate of aging. JF - Carcinogenesis AU - Lijinsky, W AD - National Institute of Environmental Health Sciences, DBRA, Research Triangle Park, NC 27709. Y1 - 1993/11// PY - 1993 DA - November 1993 SP - 2373 EP - 2375 VL - 14 IS - 11 SN - 0143-3334, 0143-3334 KW - Diethylnitrosamine KW - 3IQ78TTX1A KW - Index Medicus KW - Animals KW - Liver Neoplasms -- pathology KW - Liver Neoplasms -- chemically induced KW - Life Expectancy KW - Liver Neoplasms -- physiopathology KW - Species Specificity KW - Diethylnitrosamine -- toxicity KW - Aging -- physiology KW - Neoplasms, Experimental -- chemically induced KW - Aging -- drug effects KW - Neoplasms, Experimental -- pathology KW - Neoplasms, Experimental -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76044294?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Life-span+and+cancer%3A+the+induction+time+of+tumors+in+diverse+animal+species+treated+with+nitrosodiethylamine.&rft.au=Lijinsky%2C+W&rft.aulast=Lijinsky&rft.aufirst=W&rft.date=1993-11-01&rft.volume=14&rft.issue=11&rft.spage=2373&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-12-29 N1 - Date created - 1993-12-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Using triazolam to reduce dental anxiety. AN - 76042249; 8227774 AB - Triazolam, commonly prescribed to treat insomnia, also can be used to reduce dental anxiety. Despite controversial reports in the lay press, triazolam can be used safely at low doses for short periods. The authors review research concerning the drug's safety and discuss its use in dentistry. JF - Journal of the American Dental Association (1939) AU - Berthold, C W AU - Schneider, A AU - Dionne, R A AD - Clinical Pharmacology Unit, National Institutes of Health, Bethesda, Md. Y1 - 1993/11// PY - 1993 DA - November 1993 SP - 58 EP - 64 VL - 124 IS - 11 SN - 0002-8177, 0002-8177 KW - Triazolam KW - 1HM943223R KW - Dentistry KW - Index Medicus KW - Delirium -- chemically induced KW - Psychomotor Performance -- drug effects KW - Cognition -- drug effects KW - Memory -- drug effects KW - Humans KW - Preanesthetic Medication KW - Clinical Trials as Topic KW - Central Nervous System -- drug effects KW - Triazolam -- therapeutic use KW - Triazolam -- administration & dosage KW - Anesthesia, Dental -- methods KW - Triazolam -- adverse effects KW - Dental Anxiety -- prevention & control KW - Dental Anxiety -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76042249?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+American+Dental+Association+%281939%29&rft.atitle=Using+triazolam+to+reduce+dental+anxiety.&rft.au=Berthold%2C+C+W%3BSchneider%2C+A%3BDionne%2C+R+A&rft.aulast=Berthold&rft.aufirst=C&rft.date=1993-11-01&rft.volume=124&rft.issue=11&rft.spage=58&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+American+Dental+Association+%281939%29&rft.issn=00028177&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-12-22 N1 - Date created - 1993-12-22 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Am Dent Assoc. 1994 Apr;125(4):358, 360 [8031376] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Monitoring of 35S in ash of incinerated waste. AN - 76031309; 8225997 AB - The National Institute of Environmental Health Sciences incinerates low-level radioactive waste containing 3H, 14C, and 35S as a means of volume reduction. The primary isotope remaining in the ash is 35S. Some effects of the chemical and physical form of the waste on sulfur retention in ash and several methods for determining the activity remaining in the ash have been explored. It was found that the sulfur in sodium sulfate has a higher retention in ash than the sulfur in methionine and that the presence of glass appears to enhance the retention. Liquid scintillation and proportional counting methods were compared. A sulfur extraction procedure using liquid scintillation counting was found to give the lowest minimum detectable activity. However, it was determined that a more practical method for routine monitoring is to suspend a small quantity of ash in a liquid scintillation gel. JF - Health physics AU - Hamrick, P E AU - Davidson, W E AU - Velazquez, K W AU - Watson, J E AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1993/11// PY - 1993 DA - November 1993 SP - 556 EP - 559 VL - 65 IS - 5 SN - 0017-9078, 0017-9078 KW - Radioactive Waste KW - 0 KW - Sulfur Radioisotopes KW - Index Medicus KW - Environmental Monitoring KW - Incineration KW - Radioactive Waste -- analysis KW - Radiation Monitoring KW - Sulfur Radioisotopes -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76031309?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Health+physics&rft.atitle=Monitoring+of+35S+in+ash+of+incinerated+waste.&rft.au=Hamrick%2C+P+E%3BDavidson%2C+W+E%3BVelazquez%2C+K+W%3BWatson%2C+J+E&rft.aulast=Hamrick&rft.aufirst=P&rft.date=1993-11-01&rft.volume=65&rft.issue=5&rft.spage=556&rft.isbn=&rft.btitle=&rft.title=Health+physics&rft.issn=00179078&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-12-02 N1 - Date created - 1993-12-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Associations of postmenopausal estrogen use with cardiovascular disease and its risk factors in older women. The CHS Collaborative Research Group. AN - 76028398; 8222111 AB - Postmenopausal estrogen replacement therapy has been associated with favorable levels of cardiovascular disease risk factors, but these associations and the relations between estrogen use and subclinical disease have not been examined in large samples of older women. Present and past estrogen use was ascertained in 2955 women > or = 65 years old in the Cardiovascular Health Study, a study of risk factors for coronary heart disease and stroke in the elderly. Present estrogen use was reported by 12% of these women and past use by an additional 26.5%. Estrogen use (past or present) was strongly associated with lower low-density lipoprotein cholesterol, fibrinogen, glucose, insulin, obesity, and age and higher high-density lipoprotein cholesterol and socioeconomic status (all P or = 75 years) and smokers and nonsmokers and were unchanged after women with poor medication compliance were excluded. After adjustment for other factors, estrogen use was associated with decreased carotid wall thickness, although this association was of borderline significance after further adjustment for lipids. Postmenopausal estrogen use in this sample of older women was associated with favorable cardiovascular disease risk factor profiles and with lower measures of subclinical disease. These findings suggest that postmenopausal estrogen use may be associated with lower risk of cardiovascular disease in women well into the eighth decade of life. JF - Circulation AU - Manolio, T A AU - Furberg, C D AU - Shemanski, L AU - Psaty, B M AU - O'Leary, D H AU - Tracy, R P AU - Bush, T L AD - Division of Epidemiology and Clinical Applications, National Heart, Lung, and Blood Institute, Bethesda, Md. 20892. Y1 - 1993/11// PY - 1993 DA - November 1993 SP - 2163 EP - 2171 VL - 88 IS - 5 Pt 1 SN - 0009-7322, 0009-7322 KW - Abridged Index Medicus KW - Index Medicus KW - Smoking KW - Patient Compliance KW - Risk Factors KW - Humans KW - Electrocardiography KW - Carotid Stenosis -- diagnostic imaging KW - Aged KW - Ultrasonography KW - Heart Ventricles KW - Heart -- physiopathology KW - Female KW - Carotid Arteries -- diagnostic imaging KW - Aging -- physiology KW - Cardiovascular Diseases -- etiology KW - Estrogen Replacement Therapy -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76028398?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Associations+of+postmenopausal+estrogen+use+with+cardiovascular+disease+and+its+risk+factors+in+older+women.+The+CHS+Collaborative+Research+Group.&rft.au=Manolio%2C+T+A%3BFurberg%2C+C+D%3BShemanski%2C+L%3BPsaty%2C+B+M%3BO%27Leary%2C+D+H%3BTracy%2C+R+P%3BBush%2C+T+L&rft.aulast=Manolio&rft.aufirst=T&rft.date=1993-11-01&rft.volume=88&rft.issue=5+Pt+1&rft.spage=2163&rft.isbn=&rft.btitle=&rft.title=Circulation&rft.issn=00097322&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-12-03 N1 - Date created - 1993-12-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Individualized chemotherapy for patients with non-small cell lung cancer determined by prospective identification of neuroendocrine markers and in vitro drug sensitivity testing. AN - 76025318; 8221655 AB - We attempted to prospectively select individualized chemotherapy for 165 non-small cell lung cancer patients based on in vitro analysis of neuroendocrine (NE) markers and drug sensitivity testing (DST) using fresh tumor. The chemotherapy used for small cell lung cancer (SCLC) was selected when NE marker expression determined by L-dopa decarboxylase assay was documented. Selection of chemotherapy for other patients was guided by DST results using a modified dye exclusion assay when available; otherwise etoposide and cisplatin was administered. A total of 112 of 165 (68%) specimens were assayed for L-dopa decarboxylase and 36 patients (22%) had DST. In vitro data directed management for 27 of 96 (28%) patients given chemotherapy: 6 with NE markers were treated with the SCLC regimen; and 21 (58% of those with DST) received their DST-selected chemotherapy regimen. There were no significant differences in response rate among all 3 treatment arms (P = 0.076). However, response to chemotherapy for the patients treated prospectively with a SCLC regimen was 3 of 6 (50%), marginally better than patients given their DST-selected chemotherapy regimen (2 of 21; 9%; P = 0.056) or those treated with etoposide and cisplatin (10 of 69; 14%; P = 0.061). When patients whose NE markers were identified retrospectively are included, 4 of 9 (44%) responded to administered chemotherapy, compared to 7 of 55 (13%) with no NE markers present (P = 0.04). There were no differences in survival among the three treatment groups. Cisplatin and etoposide comprised the most active regimen in vitro for tumors from 16 of 36 (44%) patients, potentially limiting the benefit of DST since this is often the empiric therapy for non-SCLC. Furthermore, the correlation between in vitro and clinical response is nonsignificant for all drugs tested, highlighting the overall relative resistance of non-SCLC tumors to currently available chemotherapy. JF - Cancer research AU - Shaw, G L AU - Gazdar, A F AU - Phelps, R AU - Linnoila, R I AU - Ihde, D C AU - Johnson, B E AU - Oie, H K AU - Pass, H I AU - Steinberg, S M AU - Ghosh, B C AD - National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1993/11/01/ PY - 1993 DA - 1993 Nov 01 SP - 5181 EP - 5187 VL - 53 IS - 21 SN - 0008-5472, 0008-5472 KW - Antineoplastic Agents KW - 0 KW - Biomarkers, Tumor KW - Etoposide KW - 6PLQ3CP4P3 KW - Dopa Decarboxylase KW - EC 4.1.1.- KW - Cisplatin KW - Q20Q21Q62J KW - Index Medicus KW - Prospective Studies KW - Dopa Decarboxylase -- analysis KW - Tumor Cells, Cultured KW - Neoplasm Staging KW - Etoposide -- administration & dosage KW - Cell Survival -- drug effects KW - Humans KW - Middle Aged KW - Male KW - Female KW - Survival Analysis KW - Cisplatin -- administration & dosage KW - Carcinoma, Non-Small-Cell Lung -- surgery KW - Lung Neoplasms -- drug therapy KW - Biomarkers, Tumor -- analysis KW - Antineoplastic Agents -- toxicity KW - Neurosecretory Systems -- pathology KW - Drug Screening Assays, Antitumor -- methods KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Lung Neoplasms -- surgery KW - Carcinoma, Non-Small-Cell Lung -- drug therapy KW - Lung Neoplasms -- pathology KW - Carcinoma, Non-Small-Cell Lung -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76025318?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Individualized+chemotherapy+for+patients+with+non-small+cell+lung+cancer+determined+by+prospective+identification+of+neuroendocrine+markers+and+in+vitro+drug+sensitivity+testing.&rft.au=Shaw%2C+G+L%3BGazdar%2C+A+F%3BPhelps%2C+R%3BLinnoila%2C+R+I%3BIhde%2C+D+C%3BJohnson%2C+B+E%3BOie%2C+H+K%3BPass%2C+H+I%3BSteinberg%2C+S+M%3BGhosh%2C+B+C&rft.aulast=Shaw&rft.aufirst=G&rft.date=1993-11-01&rft.volume=53&rft.issue=21&rft.spage=5181&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 - 1993-11-29 N1 - Date created - 1993-11-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Multiple effects of morphine on facial scratching in monkeys. AN - 76023263; 8214729 AB - The medullary dorsal horn (MDH), the medullary homolog of the spinal dorsal horn, is a site where opioid-receptor agonists can act at opioid receptors to produce pronounced facial scratching, the behavioral correlate of pruritus. In the present study, after a 10-min baseline period, morphine (5.0 micrograms) was micro-injected into the MDH of monkeys. Behavior was videotaped and facial scratches were counted by two independent raters. Morphine greatly increased facial scratching behavior, which is consistent with previous findings where mu-opioid receptor agonists microinjected into the MDH have been to induce dose-dependent, naloxone-reversible facial scratching in monkeys. In the current research, intramuscular (IM) administration of the opioid-receptor antagonist, naloxone (0.5 mg/kg), reversed this MDH morphine-induced scratching. Additionally, IM morphine (1.0 mg/kg) produced a substantial reduction in facial scratching behavior. Scratching behavior continued at a high rate after injection of saline (0.1 mL/kg, IM). These findings support the hypothesis that morphine has both pruragenic and antipruragenic activity, depending on the site of action. JF - Anesthesia and analgesia AU - Thomas, D A AU - Williams, G M AU - Iwata, K AU - Kenshalo, D R AU - Dubner, R AD - Neurobiology and Anesthesiology Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/11// PY - 1993 DA - November 1993 SP - 933 EP - 935 VL - 77 IS - 5 SN - 0003-2999, 0003-2999 KW - Morphine KW - 76I7G6D29C KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Spinal Cord KW - Macaca fascicularis KW - Injections, Spinal KW - Male KW - Facial Dermatoses -- chemically induced KW - Behavior, Animal -- physiology KW - Pruritus -- chemically induced KW - Morphine -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76023263?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Anesthesia+and+analgesia&rft.atitle=Multiple+effects+of+morphine+on+facial+scratching+in+monkeys.&rft.au=Thomas%2C+D+A%3BWilliams%2C+G+M%3BIwata%2C+K%3BKenshalo%2C+D+R%3BDubner%2C+R&rft.aulast=Thomas&rft.aufirst=D&rft.date=1993-11-01&rft.volume=77&rft.issue=5&rft.spage=933&rft.isbn=&rft.btitle=&rft.title=Anesthesia+and+analgesia&rft.issn=00032999&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-11-18 N1 - Date created - 1993-11-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Protein interactions with DNA elements in variant equine infectious anemia virus enhancers and their impact on transcriptional activity. AN - 76018730; 8411361 AB - The long terminal repeats (LTRs) from various cloned equine infectious anemia virus (EIAV) proviruses differ significantly, but all contain cis-acting DNA elements identical to MDBP-, PEA2-, AP-1-, and PU.1 (ets)-binding sites. A prototype EIAV LTR would contain one of each of these conserved elements. The LTR variations originate from the insertion of novel sequences between the PEA2 and AP-1 elements in the transcriptional enhancer unit. Viewed in this way, the LTR from provirus clone lambda 12 has an 11-bp insertion containing a PEA2 site and the LTR of the lambda 6 provirus has a 31-bp insertion/duplication containing PEA2, AP-1, and PU.1 sites. Two other LTRs were cloned by amplification of cDNAs from the persistently infected cell line, EIAV-FEA. A third LTR was generated by site-directed mutagenesis of one of the LTRs from EIAV-FEA cells. The latter three had a single base change in the element next to the TATA box that abolished PU.1 binding; however, the variable regions of these LTRs were shown by gel mobility shift assays to contain one or two PU.1 sites. One variable region was shown to have an octamer site overlapping its tandem PU.1 elements. Basal, PMA-activated, and Tat trans-activated transcriptional activities of the LTRs were compared in several different cell lines by transient transfection. The various promoters displayed different relative levels of activity depending on the cell line used and the condition of activation. This natural set of variant promoters may help define how changes in the components of the transcription complex influence transactivation by Tat. The diverse LTRs could endow their respective proviruses with a unique pattern of expression and activation in vivo. JF - Journal of virology AU - Carvalho, M AU - Kirkland, M AU - Derse, D AD - Laboratory of Viral Carcinogenesis, National Cancer Institute, Frederick, Maryland 21702-1201. Y1 - 1993/11// PY - 1993 DA - November 1993 SP - 6586 EP - 6595 VL - 67 IS - 11 SN - 0022-538X, 0022-538X KW - DNA-Binding Proteins KW - 0 KW - Nuclear Proteins KW - Oligodeoxyribonucleotides KW - Index Medicus KW - Promoter Regions, Genetic KW - Base Sequence KW - Oligodeoxyribonucleotides -- chemistry KW - Binding, Competitive KW - Molecular Sequence Data KW - Transcription, Genetic KW - Oligodeoxyribonucleotides -- metabolism KW - Repetitive Sequences, Nucleic Acid KW - Nuclear Proteins -- metabolism KW - DNA-Binding Proteins -- metabolism KW - Gene Expression Regulation, Viral KW - Enhancer Elements, Genetic KW - Infectious Anemia Virus, Equine -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76018730?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Protein+interactions+with+DNA+elements+in+variant+equine+infectious+anemia+virus+enhancers+and+their+impact+on+transcriptional+activity.&rft.au=Carvalho%2C+M%3BKirkland%2C+M%3BDerse%2C+D&rft.aulast=Carvalho&rft.aufirst=M&rft.date=1993-11-01&rft.volume=67&rft.issue=11&rft.spage=6586&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 - 1993-11-24 N1 - Date created - 1993-11-24 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Am J Pathol. 1971 Feb;62(2):283-94 [4322275] Oncogene. 1990 May;5(5):663-8 [1693183] Intervirology. 1981;16(4):225-32 [6177659] Mol Cell Biol. 1982 Sep;2(9):1044-51 [6960240] Nucleic Acids Res. 1983 Mar 11;11(5):1475-89 [6828386] J Biol Chem. 1984 Aug 25;259(16):10539-44 [6206055] Nature. 1984 Nov 8-14;312(5990):159-62 [6095084] Nature. 1990 Jun 14;345(6276):636-40 [1971917] J Virol. 1990 Aug;64(8):3716-25 [2164593] Cell. 1990 Nov 16;63(4):655-7 [2225069] J Virol. 1991 Mar;65(3):1605-10 [1847479] J Virol. 1991 Jul;65(7):3468-74 [1645778] EMBO J. 1991 Dec;10(13):4189-96 [1756726] Mol Cell Biol. 1992 Jan;12(1):368-78 [1729611] J Virol. 1992 Apr;66(4):2000-7 [1312617] Genes Dev. 1992 Apr;6(4):655-66 [1559613] J Virol. 1992 Oct;66(10):5906-13 [1382143] Virology. 1992 Dec;191(2):968-72 [1448931] J Virol. 1993 Apr;67(4):2064-74 [8383228] J Virol. 1993 Jul;67(7):3885-90 [8389910] Rev Infect Dis. 1985 Jan-Feb;7(1):83-8 [2984759] J Virol. 1986 Jan;57(1):71-80 [3001367] J Virol. 1987 Mar;61(3):743-7 [3027401] J Virol. 1987 Apr;61(4):1067-72 [3029400] Nature. 1987 Dec 3-9;330(6147):489-93 [2825027] Virology. 1987 Dec;161(2):321-31 [2825406] J Virol. 1988 Sep;62(9):3522-6 [2841502] J Virol. 1989 Mar;63(3):1284-92 [2536834] Virology. 1989 Oct;172(2):609-15 [2552661] Cell. 1990 Apr 6;61(1):113-24 [2180582] J Virol. 1990 Apr;64(4):1616-24 [2157047] Genes Dev. 1990 Feb;4(2):233-42 [2338244] Arch Gesamte Virusforsch. 1973;41(1):1-10 [4123810] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Alternative splicing of human immunodeficiency virus type 1 mRNA modulates viral protein expression, replication, and infectivity. AN - 76014789; 8411338 AB - Multiple RNA splicing sites exist within human immunodeficiency virus type 1 (HIV-1) genomic RNA, and these sites enable the synthesis of many mRNAs for each of several viral proteins. We evaluated the biological significance of the alternatively spliced mRNA species during productive HIV-1 infections of peripheral blood lymphocytes and human T-cell lines to determine the potential role of alternative RNA splicing in the regulation of HIV-1 replication and infection. First, we used a semiquantitative polymerase chain reaction of cDNAs that were radiolabeled for gel analysis to determine the relative abundance of the diverse array of alternatively spliced HIV-1 mRNAs. The predominant rev, tat, vpr, and env RNAs contained a minimum of noncoding sequence, but the predominant nef mRNAs were incompletely spliced and invariably included noncoding exons. Second, the effect of altered RNA processing was measured following mutagenesis of the major 5' splice donor and several cryptic, constitutive, and competing 3' splice acceptor motifs of HIV-1NL4-3. Mutations that ablated constitutive splice sites led to the activation of new cryptic sites; some of these preserved biological function. Mutations that ablated competing splice acceptor sites caused marked alterations in the pool of virus-derived mRNAs and, in some instances, in virus infectivity and/or the profile of virus proteins. The redundant RNA splicing signals in the HIV-1 genome and alternatively spliced mRNAs provides a mechanism for regulating the relative proportions of HIV-1 proteins and, in some cases, viral infectivity. JF - Journal of virology AU - Purcell, D F AU - Martin, M A AD - Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892. Y1 - 1993/11// PY - 1993 DA - November 1993 SP - 6365 EP - 6378 VL - 67 IS - 11 SN - 0022-538X, 0022-538X KW - env KW - nef KW - rev KW - tat KW - tat1 KW - tat2 KW - vif KW - vpr KW - vpu KW - HIV Envelope Protein gp120 KW - 0 KW - Oligodeoxyribonucleotides KW - RNA, Messenger KW - RNA, Viral KW - Retroviridae Proteins KW - Index Medicus KW - AIDS/HIV KW - Virus Replication KW - Protein Biosynthesis KW - Polymerase Chain Reaction KW - Base Sequence KW - Oligodeoxyribonucleotides -- chemistry KW - Molecular Sequence Data KW - HIV Envelope Protein gp120 -- genetics KW - RNA, Viral -- genetics KW - RNA, Messenger -- genetics KW - HIV-1 -- genetics KW - Retroviridae Proteins -- genetics KW - Alternative Splicing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76014789?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Alternative+splicing+of+human+immunodeficiency+virus+type+1+mRNA+modulates+viral+protein+expression%2C+replication%2C+and+infectivity.&rft.au=Purcell%2C+D+F%3BMartin%2C+M+A&rft.aulast=Purcell&rft.aufirst=D&rft.date=1993-11-01&rft.volume=67&rft.issue=11&rft.spage=6365&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 - 1993-11-24 N1 - Date created - 1993-11-24 N1 - Date revised - 2017-01-13 N1 - Gene symbol - env; nef; rev; tat; tat1; tat2; vif; vpr; vpu N1 - SuppNotes - Cited By: J Virol. 1990 Dec;64(12):5966-75 [2243382] Proc Natl Acad Sci U S A. 1990 Oct;87(19):7787-91 [2217212] Nucleic Acids Res. 1981 Aug 11;9(15):3719-30 [6269091] Nature. 1985 Feb 7-13;313(6002):450-8 [2982104] Science. 1985 Jul 5;229(4708):74-7 [2990041] Cell. 1986 Mar 28;44(6):941-7 [2420471] J Virol. 1986 Aug;59(2):284-91 [3016298] Cell. 1986 Sep 12;46(6):807-17 [3638988] Proc Natl Acad Sci U S A. 1986 Dec;83(24):9734-8 [3025848] Cell. 1987 Feb 27;48(4):691-701 [3643816] Nature. 1987 Aug 20-26;328(6132):728-30 [2441266] J Exp Med. 1987 Nov 1;166(5):1548-66 [2824653] J Virol. 1988 Jan;62(1):139-47 [3257102] Science. 1988 Sep 2;241(4870):1221-3 [3261888] Proc Natl Acad Sci U S A. 1988 Dec;85(23):9224-8 [3194421] J Virol. 1989 Mar;63(3):1265-74 [2783738] Nature. 1989 Mar 16;338(6212):254-7 [2784194] Proc Natl Acad Sci U S A. 1989 Mar;86(5):1495-9 [2784208] J Virol. 1989 May;63(5):1959-66 [2704072] EMBO J. 1989 Mar;8(3):787-96 [2524382] Cell. 1989 Jun 30;57(7):1155-65 [2736624] J Virol. 1989 Sep;63(9):3708-13 [2760980] Cell. 1989 Dec 1;59(5):789-95 [2686839] Proc Natl Acad Sci U S A. 1989 Dec;86(23):9549-53 [2687884] Science. 1989 Dec 22;246(4937):1625-9 [2688093] Mol Cell Biol. 1990 Feb;10(2):696-704 [2153921] Gene. 1990 Nov 30;96(1):125-8 [2265750] Genes Dev. 1991 May;5(5):808-19 [1827422] Cell. 1991 May 17;65(4):651-62 [2032289] Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):5011-5 [1711215] Virology. 1991 Sep;184(1):319-29 [1871974] Cell. 1991 Oct 4;67(1):169-78 [1913815] Virology. 1991 Nov;185(1):258-70 [1926777] Mol Cell Biol. 1992 Jan;12(1):207-19 [1729599] Mol Cell Biol. 1992 Mar;12(3):1375-86 [1545819] Annu Rev Cell Biol. 1991;7:559-99 [1839712] Eur J Immunol. 1992 Jun;22(6):1513-8 [1601037] J Gen Virol. 1992 Jul;73 ( Pt 7):1825-8 [1629704] Virology. 1992 Aug;189(2):618-28 [1641982] Science. 1992 Sep 25;257(5078):1918-25 [1411506] J Virol. 1992 Dec;66(12):7328-35 [1433521] Annu Rev Cell Biol. 1992;8:133-55 [1335742] J Virol. 1993 Feb;67(2):902-12 [8380472] Nature. 1993 Mar 25;362(6418):355-8 [8455722] Nature. 1993 Mar 25;362(6418):359-62 [8096068] Science. 1993 Mar 19;259(5102):1749-54 [8096089] Cell. 1990 Feb 23;60(4):685-93 [1689218] Science. 1990 Feb 16;247(4944):845-8 [2406903] EMBO J. 1990 Mar;9(3):965-70 [2178928] J Virol. 1990 Jun;64(6):2505-18 [2186172] J Virol. 1990 Jun;64(6):2519-29 [2335812] J Virol. 1990 Jul;64(7):3391-8 [2191150] J Virol. 1990 Sep;64(9):4093-8 [2384914] J Virol. 1990 Sep;64(9):4585-8 [2384924] J Virol. 1990 Nov;64(11):5448-56 [2214021] Cell. 1978 Jul;14(3):725-31 [210957] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Sensitivity to subjective effects of cocaine in drug abusers: relationship to cerebral ventricle size. AN - 76010506; 8214181 AB - The purpose of this study was to assess the functional significance of ventricle-brain ratio (VBR) in terms of how it might affect sensitivity to cocaine, an indirect dopamine agonist. Relationships between VBR and subjective responses to acute intravenous cocaine hydrochloride were examined in 20 male polydrug abusers. Tests were performed in conjunction with positron emission tomography scans to measure cerebral glucose metabolism. Subjective measures of effects of cocaine, including self-report ratings of intensity of the drug effect, scores on the morphine-benzedrine scale of the Addiction Research Center Inventory, and several items on visual analogue scales, correlated negatively with VBR. VBR also differed significantly among subjects who were grouped according to scores on items ("rush" and "crash") of the Cocaine-Sensitive Scale (larger VBR in subjects with weaker responses). VBR was not correlated with cocaine-induced changes in cerebral metabolic rates for glucose. Relative insensitivity to the subjective effects of cocaine in polydrug abusers with ventricle enlargement suggests that ventriculomegaly may reflect changes in periventricular brain regions that mediate these effects of cocaine. JF - The American journal of psychiatry AU - Morgan, M J AU - Cascella, N G AU - Stapleton, J M AU - Phillips, R L AU - Yung, B C AU - Wong, D F AU - Shaya, E K AU - London, E D AD - Addiction Research Center, National Institute on Drug Abuse, Baltimore, MD 21224. Y1 - 1993/11// PY - 1993 DA - November 1993 SP - 1712 EP - 1717 VL - 150 IS - 11 SN - 0002-953X, 0002-953X KW - Cocaine KW - I5Y540LHVR KW - Glucose KW - IY9XDZ35W2 KW - Abridged Index Medicus KW - Index Medicus KW - Euphoria -- drug effects KW - Injections, Intravenous KW - Glucose -- metabolism KW - Humans KW - Tomography, X-Ray Computed KW - Personality Inventory KW - Psychiatric Status Rating Scales KW - Adult KW - Surveys and Questionnaires KW - Tomography, Emission-Computed KW - Cerebral Ventriculography KW - Individuality KW - Male KW - Substance-Related Disorders -- diagnosis KW - Cerebral Ventricles -- metabolism KW - Brain -- anatomy & histology KW - Cerebral Ventricles -- anatomy & histology KW - Brain -- metabolism KW - Substance-Related Disorders -- psychology KW - Cocaine -- pharmacology KW - Cerebral Ventricles -- diagnostic imaging KW - Brain -- diagnostic imaging KW - Emotions -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76010506?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+of+psychiatry&rft.atitle=Sensitivity+to+subjective+effects+of+cocaine+in+drug+abusers%3A+relationship+to+cerebral+ventricle+size.&rft.au=Morgan%2C+M+J%3BCascella%2C+N+G%3BStapleton%2C+J+M%3BPhillips%2C+R+L%3BYung%2C+B+C%3BWong%2C+D+F%3BShaya%2C+E+K%3BLondon%2C+E+D&rft.aulast=Morgan&rft.aufirst=M&rft.date=1993-11-01&rft.volume=150&rft.issue=11&rft.spage=1712&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+psychiatry&rft.issn=0002953X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-11-16 N1 - Date created - 1993-11-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetic determinants of dengue type 4 virus neurovirulence for mice. AN - 76009389; 8411360 AB - Mouse-adapted dengue type 4 virus (DEN4) strain H241 is highly neurovirulent for mice, whereas its non-mouse-adapted parent is rarely neurovirulent. The genetic basis for the neurovirulence of the mouse-adapted mutant was studied by comparing intratypic chimeric viruses that contained the three structural protein genes from the parental virus or the neurovirulent mutant in the background sequence of nonneurovirulent DEN4 strain 814669. The chimera that contained the three structural protein genes from mouse neurovirulent DEN4 strain H241 proved to be highly neurovirulent in mice, whereas the chimera that contained the corresponding genes from its non-mouse-adapted parent was not neurovirulent. This finding indicates that most of the genetic loci for the neurovirulence of the DEN4 mutant lie within the structural protein genes. A comparison of the amino acid sequences of the parent and its mouse neurovirulent mutant proteins revealed that there were only five amino acid differences in the structural protein region, and three of these were located in the envelope (E) glycoprotein. Analysis of chimeras which contained one or two of the variant amino acids of the mutant E sequence substituting for the corresponding sequence of the parental virus identified two of these amino acid changes as important determinants of mouse neurovirulence. First, the single substitution of Ile for Thr-155 which ablated one of the two conserved glycosylation sites in parental E yielded a virus that was almost as neurovirulent as the mouse-adapted mutant. Thus, the loss of an E glycosylation site appears to play a role in DEN4 neurovirulence. Second, the substitution of Leu for Phe-401 also yielded a neurovirulent virus, but it was less neurovirulent than the glycosylation mutant. These findings indicate that at least two of the genetic loci responsible for DEN4 mouse neurovirulence map within the structural protein genes. JF - Journal of virology AU - Kawano, H AU - Rostapshov, V AU - Rosen, L AU - Lai, C J AD - Molecular Viral Biology Section, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892. Y1 - 1993/11// PY - 1993 DA - November 1993 SP - 6567 EP - 6575 VL - 67 IS - 11 SN - 0022-538X, 0022-538X KW - Membrane Glycoproteins KW - 0 KW - Viral Envelope Proteins KW - Viral Structural Proteins KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Animals KW - Base Sequence KW - DNA Mutational Analysis KW - Capsid -- genetics KW - Molecular Sequence Data KW - Mice KW - Genes, Viral KW - Amino Acid Sequence KW - Viral Structural Proteins -- genetics KW - Viral Envelope Proteins -- genetics KW - Membrane Glycoproteins -- genetics KW - Nervous System Diseases -- microbiology KW - Dengue Virus -- pathogenicity KW - Dengue Virus -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76009389?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Genetic+determinants+of+dengue+type+4+virus+neurovirulence+for+mice.&rft.au=Kawano%2C+H%3BRostapshov%2C+V%3BRosen%2C+L%3BLai%2C+C+J&rft.aulast=Kawano&rft.aufirst=H&rft.date=1993-11-01&rft.volume=67&rft.issue=11&rft.spage=6567&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 - 1993-11-24 N1 - Date created - 1993-11-24 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Virology. 1985 Dec;147(2):264-74 [3855247] Virology. 1992 May;188(1):160-7 [1566570] J Mol Biol. 1986 Feb 5;187(3):309-23 [3009829] Virology. 1986 Nov;155(1):77-88 [3022479] Virology. 1986 Dec;155(2):365-77 [3024394] Arch Virol. 1987;94(3-4):331-8 [2437890] Virology. 1987 Nov;161(1):262-7 [3672932] Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10532-6 [1438242] J Infect Dis. 1952 Jan-Feb;90(1):1-9 [14888958] Am J Trop Med Hyg. 1952 Jan;1(1):30-50 [14903434] Am J Trop Med Hyg. 1952 Jan;1(1):66-77 [14903437] Science. 1954 Aug 27;120(3113):357 [13186860] Am J Trop Med Hyg. 1955 Mar;4(2):198-207 [14361897] Trans Assoc Am Physicians. 1960;73:140-55 [13711073] Science. 1960 Apr 15;131(3407):1102-3 [14399343] J Gen Virol. 1988 Jan;69 ( Pt 1):1-21 [2826659] Virology. 1988 Jan;162(1):167-80 [2827375] Science. 1988 Jan 29;239(4839):476-81 [3277268] J Gen Virol. 1988 Jun;69 ( Pt 6):1391-8 [3385407] J Virol. 1988 Aug;62(8):3027-31 [2969058] Gene. 1989 Feb 20;75(2):197-211 [2714651] Arch Virol. 1989;105(1-2):39-53 [2719554] J Virol. 1989 Jun;63(6):2853-6 [2724416] Virology. 1990 Jun;176(2):643-7 [2345967] J Virol. 1991 Mar;65(3):1400-7 [1995950] Proc Natl Acad Sci U S A. 1991 Jun 15;88(12):5139-43 [2052593] Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):10342-6 [1682924] Am J Trop Med Hyg. 1986 Mar;35(2):393-400 [3513650] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The murine alpha B-crystallin/small heat shock protein enhancer: identification of alpha BE-1, alpha BE-2, alpha BE-3, and MRF control elements. AN - 76002884; 8413303 AB - The murine alpha B-crystallin gene (a member of the small heat shock protein family) is expressed constitutively at high levels in the lens and at lower levels in many other tissues, including skeletal muscle. We have previously used the herpes simplex virus thymidine kinase promoter fused to the human growth hormone gene to identify an alpha B-crystallin enhancer at positions -427 to -259 that has high activity in muscle and low activity in lens cell lines. In the study reported here, we performed DNase I footprinting, transfection, mutagenesis, and electrophoretic mobility shift experiments using the murine C2C12 muscle and alpha TN4-1 lens cell lines and the rabbit N/N1003A lens cell line to identify sequences responsible for activity of this enhancer. Enhancer activity in both the muscle and lens cells was dependent on novel elements called alpha BE-1 (-407 to -397), alpha BE-2 (-360 to -327), and alpha BE-3 (-317 to -306). These elements were also weakly occupied by nuclear proteins in L929 cells, which appear to express the alpha B-crystallin gene at a very low level (detectable only by the polymerase chain reaction). A fourth element containing a consensus muscle regulatory factor-binding site called MRF (-300 to -288) was occupied and used only by the C2C12 muscle cells. Cotransfection in NIH 3T3 cells and antibody-gel shift experiments using C2C12 nuclear extracts indicated that MyoD, myogen, or a similar member of this family can activate the alpha B-crystallin enhancer by interaction with the MRF site. Taken together, we conclude that the alpha BE-1, alpha BE-2, and alpha BE-3 elements are shared by both lens and muscle cells, but the MRF element is used only in muscle cells, providing the first example of a muscle-specific control element in a crystallin gene. JF - Molecular and cellular biology AU - Gopal-Srivastava, R AU - Piatigorsky, J AD - Laboratory of Molecular and Developmental Biology, National Eye Institute, Bethesda, Maryland 20892. Y1 - 1993/11// PY - 1993 DA - November 1993 SP - 7144 EP - 7152 VL - 13 IS - 11 SN - 0270-7306, 0270-7306 KW - Crystallins KW - 0 KW - Heat-Shock Proteins KW - Recombinant Fusion Proteins KW - Growth Hormone KW - 9002-72-6 KW - DNA KW - 9007-49-2 KW - Thymidine Kinase KW - EC 2.7.1.21 KW - Deoxyribonuclease I KW - EC 3.1.21.1 KW - Index Medicus KW - Recombinant Fusion Proteins -- biosynthesis KW - Animals KW - Humans KW - Muscles -- metabolism KW - Amino Acid Sequence KW - Mice KW - Binding Sites KW - Mutagenesis, Site-Directed KW - Promoter Regions, Genetic KW - Base Sequence KW - Growth Hormone -- genetics KW - Transfection KW - Growth Hormone -- biosynthesis KW - Restriction Mapping KW - DNA -- genetics KW - Molecular Sequence Data KW - DNA -- chemistry KW - Thymidine Kinase -- biosynthesis KW - Cell Line KW - Thymidine Kinase -- genetics KW - Lens, Crystalline -- metabolism KW - Multigene Family KW - Enhancer Elements, Genetic KW - Crystallins -- genetics KW - Heat-Shock Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76002884?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+murine+alpha+B-crystallin%2Fsmall+heat+shock+protein+enhancer%3A+identification+of+alpha+BE-1%2C+alpha+BE-2%2C+alpha+BE-3%2C+and+MRF+control+elements.&rft.au=Gopal-Srivastava%2C+R%3BPiatigorsky%2C+J&rft.aulast=Gopal-Srivastava&rft.aufirst=R&rft.date=1993-11-01&rft.volume=13&rft.issue=11&rft.spage=7144&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 - 1993-11-18 N1 - Date created - 1993-11-18 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1988 Aug;85(15):5738-42 [2456582] J Biol Chem. 1992 Mar 5;267(7):4277-80 [1537817] Annu Rev Biochem. 1988;57:479-504 [3052280] Biochem Biophys Res Commun. 1989 Jan 16;158(1):319-25 [2912453] Cell. 1989 Feb 24;56(4):607-17 [2537150] Cell. 1989 Apr 7;57(1):71-8 [2539261] Cell. 1989 Apr 21;57(2):197-9 [2649248] EMBO J. 1989 Mar;8(3):701-9 [2721498] Mol Cell Biol. 1989 Mar;9(3):1083-91 [2725488] Oncogene. 1989 Jun;4(6):799-803 [2525241] Science. 1989 Jul 28;245(4916):371-8 [2667136] Eur J Biochem. 1974 Nov 1;49(1):157-68 [4477528] Science. 1977 May 27;196(4293):995-8 [193191] Proc Natl Acad Sci U S A. 1982 Apr;79(7):2360-4 [6285380] Nucleic Acids Res. 1983 Mar 11;11(5):1475-89 [6828386] Cell. 1983 Apr;32(4):1171-80 [6839359] Science. 1985 Jan 11;227(4683):134-40 [3917574] Nature. 1985 Feb 28-Mar 6;313(6005):798-801 [3919308] Proc Natl Acad Sci U S A. 1985 Dec;82(23):7815-9 [3865198] Differentiation. 1986;33(2):168-74 [3569698] Cell. 1987 Oct 23;51(2):251-60 [2822255] Cell. 1989 Aug 11;58(3):537-44 [2503252] Cell. 1989 Sep 8;58(5):823-31 [2550138] Trends Biochem Sci. 1989 Sep;14(9):365-8 [2688200] J Histochem Cytochem. 1990 Jan;38(1):31-9 [2294148] Dev Biol. 1990 Jan;137(1):68-76 [2295367] Cell. 1990 Mar 9;60(5):733-46 [2155707] Curr Eye Res. 1990 Jan;9(1):31-7 [2178867] J Cell Biol. 1990 Apr;110(4):929-37 [1691195] Genes Dev. 1990 Apr;4(4):582-95 [2163343] Mol Cell Biol. 1990 Aug;10(8):3934-44 [1695319] Proc Natl Acad Sci U S A. 1990 Aug;87(15):5623-7 [2377600] Lancet. 1990 Aug 25;336(8713):515-6 [1975030] Nucleic Acids Res. 1990 Nov 11;18(21):6239-46 [2243772] Mol Cell Biol. 1991 Jan;11(1):267-80 [1846022] Mol Cell Biol. 1991 Feb;11(2):803-12 [1846673] Proc Natl Acad Sci U S A. 1991 May 1;88(9):3652-6 [2023914] Acta Neuropathol. 1992;83(3):324-7 [1373027] Exp Eye Res. 1992 Mar;54(3):461-70 [1381680] J Biol Chem. 1992 Nov 15;267(32):23337-41 [1429679] Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10449-53 [1438232] Mol Biol Evol. 1993 Jan;10(1):103-26 [8450753] J Mol Biol. 1993 Mar 20;230(2):425-35 [8464058] Mol Cell Biol. 1991 Aug;11(8):3905-14 [1712899] Mol Cell Biol. 1991 Sep;11(9):4340-9 [1875925] Prog Nucleic Acid Res Mol Biol. 1991;41:259-81 [1882078] Biochim Biophys Acta. 1991 Oct 25;1080(2):173-80 [1932094] Biochem Cell Biol. 1988 Jun;66(6):584-93 [3048332] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Differential expression of gamma-aminobutyric acid receptors in immortalized luteinizing hormone-releasing hormone neurons. AN - 75998859; 8404645 AB - gamma-Aminobutyric acid (GABA) has been shown both to stimulate and inhibit LH secretion in vivo. GABA apparently exerts these effects at the hypothalamic level by regulating the release of LHRH. In this study, we have investigated the effect of GABAergic agents on LHRH secretion from an immortalized hypothalamic neuronal cell line (GT1-7). LHRH secretion was stimulated in a dose-dependent manner with increasing concentrations of GABA. This effect was mimicked by the GABAA receptor agonist, muscimol, and was blocked by the selective antagonist, bicuculline. The stimulatory effect of muscimol on LHRH secretion was synergistic with low concentrations of [K+]. By comparison, neither activation of the GABAB receptors with baclofen nor blockade with phaclofen influenced basal LHRH secretion. Baclofen, however, did depress [K+]-induced LHRH release. Binding studies confirmed the presence of GABAA and GABAB receptors on GT1-7 cells. In addition, Northern blots with probes to the GABAA receptor alpha 1, beta 3, and gamma 2L subunits revealed that only the beta 3 messenger RNA (mRNA) was expressed in the GT1-7 cells. These data provide the first demonstration that immortalized LHRH neurons are directly responsive to GABAergic agents. To the extent that these immortalized neurons may resemble those in vivo, our results suggest that GABAergic agents may play a dual role in reproductive physiology by exerting both stimulatory and inhibitory control over LHRH release. JF - Endocrinology AU - Favit, A AU - Wetsel, W C AU - Negro-Vilar, A AD - Reproductive Neuroendocrinology Section, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1993/11// PY - 1993 DA - November 1993 SP - 1983 EP - 1989 VL - 133 IS - 5 SN - 0013-7227, 0013-7227 KW - DNA Probes KW - 0 KW - RNA, Messenger KW - Receptors, GABA KW - Muscimol KW - 2763-96-4 KW - Gonadotropin-Releasing Hormone KW - 33515-09-2 KW - gamma-Aminobutyric Acid KW - 56-12-2 KW - Potassium KW - RWP5GA015D KW - Bicuculline KW - Y37615DVKC KW - Abridged Index Medicus KW - Index Medicus KW - Rats KW - Bicuculline -- pharmacology KW - Animals KW - Rats, Sprague-Dawley KW - Blotting, Northern KW - RNA, Messenger -- analysis KW - Potassium -- pharmacology KW - Drug Synergism KW - Muscimol -- pharmacology KW - Male KW - Cell Line KW - Hypothalamus -- secretion KW - Neurons -- metabolism KW - Hypothalamus -- drug effects KW - gamma-Aminobutyric Acid -- pharmacology KW - Gene Expression KW - Receptors, GABA -- physiology KW - Gonadotropin-Releasing Hormone -- secretion KW - gamma-Aminobutyric Acid -- administration & dosage KW - Receptors, GABA -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75998859?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Differential+expression+of+gamma-aminobutyric+acid+receptors+in+immortalized+luteinizing+hormone-releasing+hormone+neurons.&rft.au=Favit%2C+A%3BWetsel%2C+W+C%3BNegro-Vilar%2C+A&rft.aulast=Favit&rft.aufirst=A&rft.date=1993-11-01&rft.volume=133&rft.issue=5&rft.spage=1983&rft.isbn=&rft.btitle=&rft.title=Endocrinology&rft.issn=00137227&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-11-19 N1 - Date created - 1993-11-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Critical tyrosine residues regulate the enzymatic and biological activity of Raf-1 kinase. AN - 75996074; 7692235 AB - The serine/threonine kinase activity of the Raf-1 proto-oncogene product is stimulated by the activation of many tyrosine kinases, including growth factor receptors and pp60v-src. Recent studies of growth factor signal transduction pathways demonstrate that Raf-1 functions downstream of activated tyrosine kinases and p21ras and upstream of mitogen-activated protein kinase. However, coexpression of both activated tyrosine kinases and p21ras is required for maximal activation of Raf-1 in the baculovirus-Sf9 expression system. In this study, we investigated the role of tyrosine kinases and tyrosine phosphorylation in the regulation of Raf-1 activity. Using the baculovirus-Sf9 expression system, we identified Tyr-340 and Tyr-341 as the major tyrosine phosphorylation sites of Raf-1 when coexpressed with activated tyrosine kinases. Introduction of a negatively charged residue that may mimic the effect of phosphorylation at these sites activated the catalytic activity of Raf-1 and generated proteins that could transform BALB/3T3 cells and induce the meiotic maturation of Xenopus oocytes. In contrast, substitution of noncharged residues that were unable to be phosphorylated produced a protein that could not be enzymatically activated by tyrosine kinases and that could block the meiotic maturation of oocytes induced by components of the receptor tyrosine kinase pathway. These findings demonstrate that maturation of the tyrosine phosphorylation sites can dramatically alter the function of Raf-1. In addition, this is the first report that a transforming Raf-1 protein can be generated by a single amino acid substitution. JF - Molecular and cellular biology AU - Fabian, J R AU - Daar, I O AU - Morrison, D K AD - Molecular Mechanisms of Carcinogenesis Laboratory, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland 21702-1201. Y1 - 1993/11// PY - 1993 DA - November 1993 SP - 7170 EP - 7179 VL - 13 IS - 11 SN - 0270-7306, 0270-7306 KW - Proto-Oncogene Proteins KW - 0 KW - Phosphotyrosine KW - 21820-51-9 KW - Tyrosine KW - 42HK56048U KW - Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - Proto-Oncogene Proteins c-raf KW - Phosphoprotein Phosphatases KW - EC 3.1.3.16 KW - Index Medicus KW - 3T3 Cells KW - Animals KW - Gene Expression KW - Amino Acid Sequence KW - Mice KW - Protein-Tyrosine Kinases -- metabolism KW - Moths KW - Xenopus laevis KW - Oocytes -- metabolism KW - Phosphorylation KW - Transfection KW - Molecular Sequence Data KW - Phosphoprotein Phosphatases -- metabolism KW - Cell Line KW - Female KW - Protein-Serine-Threonine Kinases -- metabolism KW - Proto-Oncogene Proteins -- metabolism KW - Tyrosine -- analogs & derivatives KW - Proto-Oncogene Proteins -- genetics KW - Tyrosine -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75996074?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Critical+tyrosine+residues+regulate+the+enzymatic+and+biological+activity+of+Raf-1+kinase.&rft.au=Fabian%2C+J+R%3BDaar%2C+I+O%3BMorrison%2C+D+K&rft.aulast=Fabian&rft.aufirst=J&rft.date=1993-11-01&rft.volume=13&rft.issue=11&rft.spage=7170&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 - 1993-11-18 N1 - Date created - 1993-11-18 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1983 Jul;80(14):4218-22 [6308607] Science. 1992 Sep 4;257(5075):1404-7 [1326789] Nucleic Acids Res. 1987 Jan 26;15(2):595-609 [3029685] EMBO J. 1988 Mar;7(3):775-81 [3135183] Mol Cell Biol. 1988 Jun;8(6):2651-4 [3043188] Proc Natl Acad Sci U S A. 1988 Dec;85(23):8855-9 [3057494] Mol Cell Biol. 1989 Feb;9(2):639-47 [2710120] Mol Cell Biol. 1989 May;9(5):2247-50 [2501665] Cold Spring Harb Symp Quant Biol. 1988;53 Pt 1:173-84 [2978288] Cell. 1989 Aug 25;58(4):649-57 [2475255] Oncogene. 1990 Mar;5(3):345-51 [1690378] Mol Cell Biol. 1990 Jun;10(6):2503-12 [2188091] Blood. 1991 Jan 15;77(2):243-8 [1845931] Cell. 1991 Feb 8;64(3):479-82 [1846778] Nature. 1991 Jan 31;349(6308):426-8 [1992343] Proc Natl Acad Sci U S A. 1991 Feb 15;88(4):1227-31 [1996324] Cancer Cells. 1990 Dec;2(12):377-82 [2150916] Oncogene. 1991 Apr;6(4):495-500 [2030909] Methods Enzymol. 1991;201:110-49 [1943760] Methods Enzymol. 1991;200:3-37 [1835513] Methods Enzymol. 1991;200:62-81 [1956339] Biol Cell. 1991;72(1-2):39-45 [1721855] Adv Cancer Res. 1992;58:53-73 [1312290] Cell. 1992 Mar 20;68(6):1041-50 [1312393] Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):2922-6 [1372995] Genes Dev. 1992 Apr;6(4):545-56 [1313769] Science. 1992 Oct 16;258(5081):478-80 [1411546] Cell. 1992 Oct 16;71(2):335-42 [1330321] Nature. 1992 Dec 10;360(6404):534-5 [1334231] Nature. 1992 Dec 10;360(6404):600-3 [1461284] Proc Natl Acad Sci U S A. 1993 Jan 1;90(1):173-7 [8380494] Cell. 1993 Feb 12;72(3):407-14 [8381718] J Cell Biol. 1993 Mar;120(5):1197-202 [8436591] Science. 1993 Apr 16;260(5106):315-9 [8385802] Nature. 1993 May 13;363(6425):133-40 [8483497] Trends Biochem Sci. 1993 Apr;18(4):128-31 [8388132] Science. 1993 Jun 11;260(5114):1658-61 [8503013] Proc Natl Acad Sci U S A. 1993 Jun 15;90(12):5544-8 [7685905] Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6213-7 [8327501] Nature. 1993 Jul 22;364(6435):308-13 [8332187] Cell. 1993 Jul 16;74(1):205-14 [8334704] J Cell Biol. 1993 Aug;122(3):645-52 [8335690] J Biol Chem. 1993 Jul 25;268(21):16009-19 [8340422] J Biol Chem. 1993 Aug 15;268(23):17309-16 [8349614] Cell Growth Differ. 1991 Dec;2(12):609-17 [1687313] Nature. 1992 Jul 30;358(6385):417-21 [1322500] Oncogene. 1992 Sep;7(9):1867-73 [1386920] Mol Cell Biol. 1992 Sep;12(9):3733-42 [1508179] Virology. 1985 Oct 15;146(1):78-89 [2994296] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transcriptional control of the chicken cardiac myosin light-chain gene is mediated by two AT-rich cis-acting DNA elements and binding of serum response factor. AN - 75994481; 8413283 AB - Transcriptional control of the cardiac/slow skeletal alkali myosin light-chain (MLC1c/1s) gene is mediated, in part, by two highly conserved AT-rich cis-acting elements present in the immediate 5' flanking region. These elements cooperate to form an enhancer that can impart tissue specificity to heterologous promoters that are themselves not tissue specific in their pattern of expression. In the chicken, one of these elements matches the binding site for myocyte-specific enhancer-binding factor 2, while the other is a cis-acting element present in the transcriptional control regions of all striated alkali MLC genes (except MLC3f) and is referred to as the MLC box. The central decanucleotide core region of the MLC box closely resembles the CArG (CC[A/T]6GG) box of the serum response element, and the binding of muscle nuclear protein complexes to this element can be competed for with a synthetic serum response element. On the basis of their competition profiles and requirements for nonspecific competitor, two nuclear protein complexes, which compete for binding to the CArG-like region of the MLC box, have been identified. One of the complexes binds to a mutation of the CArG-like region that inactivates transcription of a linked reporter gene, while binding of the other complex is inhibited by this mutation. This latter complex reacts with an antibody to serum response factor (SRF) and exhibits the same binding characteristics as purified SRF. These results demonstrate that transcriptional control of the chicken MLC1c/1s gene resides in an upstream enhancer that is composed of two separate AT-rich elements, both of which are required to drive expression of a linked reporter gene. The binding of a nuclear protein complex containing SRF to one of these elements, the MLC box, is required for gene activation and apparently inhibited by other nuclear factors whose binding overlaps that of the SRF complex. JF - Molecular and cellular biology AU - Papadopoulos, N AU - Crow, M T AD - Laboratory of Cardiovascular Science, National Institute on Aging, Baltimore, Maryland 21224. Y1 - 1993/11// PY - 1993 DA - November 1993 SP - 6907 EP - 6918 VL - 13 IS - 11 SN - 0270-7306, 0270-7306 KW - Oligodeoxyribonucleotides KW - 0 KW - Oligonucleotide Probes KW - Recombinant Proteins KW - DNA KW - 9007-49-2 KW - Chloramphenicol O-Acetyltransferase KW - EC 2.3.1.28 KW - Myosin-Light-Chain Kinase KW - EC 2.7.11.18 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Animals KW - Chickens KW - Base Sequence KW - Recombinant Proteins -- biosynthesis KW - Chloramphenicol O-Acetyltransferase -- biosynthesis KW - Transfection KW - Molecular Sequence Data KW - Chloramphenicol O-Acetyltransferase -- metabolism KW - Transcriptional Activation KW - Cloning, Molecular KW - Binding Sites KW - Regulatory Sequences, Nucleic Acid KW - Myosin-Light-Chain Kinase -- genetics KW - Myosin-Light-Chain Kinase -- biosynthesis KW - Enhancer Elements, Genetic KW - DNA -- metabolism KW - Muscles -- metabolism KW - Liver -- metabolism KW - Transcription, Genetic KW - Gene Expression Regulation KW - Myocardium -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75994481?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+control+of+the+chicken+cardiac+myosin+light-chain+gene+is+mediated+by+two+AT-rich+cis-acting+DNA+elements+and+binding+of+serum+response+factor.&rft.au=Papadopoulos%2C+N%3BCrow%2C+M+T&rft.aulast=Papadopoulos&rft.aufirst=N&rft.date=1993-11-01&rft.volume=13&rft.issue=11&rft.spage=6907&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 - 1993-11-18 N1 - Date created - 1993-11-18 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Mol Cell Biol. 1989 May;9(5):2191-201 [2501661] Trends Biochem Sci. 1992 Oct;17(10):423-6 [1455511] Mol Cell Biol. 1990 Feb;10(2):528-38 [2300053] Development. 1989 May;106(1):67-78 [2627887] Genes Dev. 1990 Feb;4(2):255-68 [2110922] Mol Cell Biol. 1990 Jun;10(6):2562-9 [2342458] Biotechniques. 1990 May;8(5):503 [2357369] J Mol Biol. 1990 Jun 20;213(4):677-86 [2162966] Genes Dev. 1990 Jun;4(6):955-67 [2200737] Genes Dev. 1990 Oct;4(10):1811-22 [2123467] EMBO J. 1990 Dec;9(13):4477-84 [2176154] Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7 [271968] Dev Biol. 1978 Feb;62(2):473-85 [146629] Cell. 1978 Jul;14(3):725-31 [210957] Nucleic Acids Res. 1981 Dec 11;9(23):6505-25 [6275366] J Cell Biol. 1982 Feb;92(2):471-84 [6174531] Nucleic Acids Res. 1983 Mar 11;11(5):1475-89 [6828386] J Cell Biol. 1983 Mar;96(3):736-44 [6339522] Gene. 1984 Jun;28(3):351-9 [6235151] Biochem J. 1985 Oct 15;231(2):249-61 [3904738] Cell. 1986 Aug 15;46(4):567-74 [3524858] J Mol Biol. 1986 May 5;189(1):113-30 [3537305] Mol Cell Biol. 1986 Jun;6(6):2125-36 [3785189] Mol Cell Biol. 1986 Jul;6(7):2462-75 [3785201] Mol Cell Biol. 1986 Dec;6(12):4305-16 [3025651] Mol Cell Biol. 1987 Mar;7(3):1217-25 [3561415] J Biol Chem. 1987 Jul 15;262(20):9429-32 [3036859] EMBO J. 1987 Sep;6(9):2711-7 [3119326] Mol Cell Biol. 1987 Oct;7(10):3482-9 [3316979] Mol Cell Biol. 1988 Apr;8(4):1800-2 [3380098] J Biol Chem. 1988 Sep 5;263(25):12669-76 [2842339] Gene. 1988 Jul 30;67(2):271-7 [3169576] Nucleic Acids Res. 1988 Nov 11;16(21):10037-52 [3194193] Cell. 1988 Dec 23;55(6):989-1003 [3203386] J Biol Chem. 1989 Feb 5;264(4):2143-9 [2789520] Nucleic Acids Res. 1989 Feb 11;17(3):1177-95 [2493627] Cell. 1989 Mar 10;56(5):777-83 [2493990] Mol Cell Biol. 1989 Feb;9(2):515-22 [2710114] Nature. 1989 Jul 6;340(6228):68-70 [2786995] J Cell Biol. 1991 Nov;115(3):745-54 [1717491] Mol Cell Biol. 1991 Oct;11(10):4854-62 [1656214] Mol Cell Biol. 1991 Oct;11(10):5090-100 [1922033] Nucleic Acids Res. 1992 Jan 11;20(1):140 [1738593] Mol Cell Biol. 1992 Sep;12(9):4209-14 [1508214] Genes Dev. 1992 Sep;6(9):1783-98 [1516833] Proc Natl Acad Sci U S A. 1992 Oct 15;89(20):9814-8 [1409704] Mol Biol Cell. 1992 Oct;3(10):1073-83 [1421567] Development. 1992 Aug;115(4):1087-101 [1360403] EMBO J. 1989 Jun;8(6):1785-92 [2504586] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Expression of multidrug resistance genes in rat liver during regeneration and after carbon tetrachloride intoxication. AN - 75990238; 7693574 AB - We analyzed expression of multidrug resistance (mdr) genes in rat liver during regeneration after partial hepatectomy or carbon tetrachloride-induced necrosis. In situ hybridization revealed that in the normal liver the cellular distribution of mdr transcripts and protein is restricted to hepatocytes and that a gradient, highest in zone 1 and lowest in zone 3, exists in the level of the mdr transcripts in the liver acinus. Increased levels of mdr1a and mdr1b transcripts were observed 3 hr after administration of carbon tetrachloride and remained increased for the next 5 days. In contrast, increased expression of mdr1a and mdr1b was first observed 24 hr after partial hepatectomy. Use of gene-specific probes to compare the time courses of mdr1b and mdr2 expression after carbon tetrachloride administration showed distinctly different patterns of expression; mdr1b reached a maximum level of expression at 12 hr, whereas increased mdr2 expression was first observed 48 hr after administration. Nuclear run-on analysis at 12 and 24 hr after carbon tetrachloride administration demonstrated 10-fold and eightfold increases in mdr transcription, respectively. However, 72 hr after carbon tetrachloride treatment the rate of mdr transcription was back to the control level. The cellular patterns of mdr expression after partial hepatectomy and carbon tetrachloride administration were similar; the increase was first observed in zone 1 and gradually extended into zone 3. These data strongly suggest that the physiological roles of mdr1b and mdr2 are different and that liver regeneration is an appropriate model for elucidating these differences. JF - Hepatology (Baltimore, Md.) AU - Nakatsukasa, H AU - Silverman, J A AU - Gant, T W AU - Evarts, R P AU - Thorgeirsson, S S AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-0037. Y1 - 1993/11// PY - 1993 DA - November 1993 SP - 1202 EP - 1207 VL - 18 IS - 5 SN - 0270-9139, 0270-9139 KW - Carrier Proteins KW - 0 KW - Membrane Glycoproteins KW - P-Glycoprotein KW - RNA KW - 63231-63-0 KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Animals KW - Carrier Proteins -- metabolism KW - Carrier Proteins -- genetics KW - Hepatectomy -- methods KW - Transcription, Genetic KW - DNA -- biosynthesis KW - Rats KW - Rats, Inbred F344 KW - In Situ Hybridization KW - Necrosis KW - RNA -- metabolism KW - Male KW - Membrane Glycoproteins -- genetics KW - Membrane Glycoproteins -- metabolism KW - Gene Expression -- drug effects KW - Liver Regeneration -- drug effects KW - Carbon Tetrachloride Poisoning -- genetics KW - Liver -- pathology KW - Drug Resistance -- genetics KW - Carbon Tetrachloride Poisoning -- metabolism KW - Liver -- drug effects KW - Carbon Tetrachloride Poisoning -- pathology KW - Liver -- metabolism KW - Liver Regeneration -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75990238?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Expression+of+multidrug+resistance+genes+in+rat+liver+during+regeneration+and+after+carbon+tetrachloride+intoxication.&rft.au=Nakatsukasa%2C+H%3BSilverman%2C+J+A%3BGant%2C+T+W%3BEvarts%2C+R+P%3BThorgeirsson%2C+S+S&rft.aulast=Nakatsukasa&rft.aufirst=H&rft.date=1993-11-01&rft.volume=18&rft.issue=5&rft.spage=1202&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 - 1993-11-29 N1 - Date created - 1993-11-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Taxol in combination with doxorubicin or etoposide. Possible antagonism in vitro. AN - 75990237; 8104682 AB - Taxol is a novel chemotherapeutic agent that promotes microtubule assembly and stabilizes tubulin polymer formation. Clinical evaluation of its antineoplastic activity as a single agent and in combination with other chemotherapeutic drugs is in progress. To evaluate the effect of combining taxol with other commonly used antineoplastic agents, clonogenic survival of human breast cancer MCF7 cells, human lung adenocarcinoma A549 cells, and human ovarian cancer OVG1 cells were assayed after an initial exposure to taxol for 24 hours (approximately LD90 for taxol), followed by a 1-hour incubation with varying concentrations of doxorubicin or etoposide (total taxol incubation time, 25 hours). When corrected for taxol-induced cytotoxicity, doxorubicin and etoposide caused less cell killing in the presence of taxol compared with control incubations of doxorubicin and etoposide alone. To determine if a different schedule of drug application resulted in a similar finding, MCF7, A549, and OVG1 cells were exposed to doxorubicin for 1 hour, followed by incubation with varying concentrations of taxol for 24 hours. Less-than-additive cytotoxicity for the combination of taxol and doxorubicin was found. Flow cytometry studies in MCF7 cells showed that taxol caused a G2/M cell cycle block. Fewer cells were found to be in S-phase, which is the most doxorubicin-sensitive phase of the cell cycle. The application of doxorubicin or etoposide to MCF7 cells for 1 hour resulted in partial G1 and G2/M cell cycle blocks. Fewer cells were found to be moving through the cell cycle, which is likely required for taxol cytotoxicity. Although direct antagonism of the cytotoxicity of doxorubicin or etoposide by taxol has not been proven, there is less-than-additive in vitro cytotoxicity when taxol is combined with these chemotherapeutic agents. The clinical implications of these findings are unknown; however, these findings generate concern about the combination of these agents in clinical trials and suggest that additional studies to determine optimal scheduling are needed. JF - Cancer AU - Hahn, S M AU - Liebmann, J E AU - Cook, J AU - Fisher, J AU - Goldspiel, B AU - Venzon, D AU - Mitchell, J B AU - Kaufman, D AD - Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/11/01/ PY - 1993 DA - 1993 Nov 01 SP - 2705 EP - 2711 VL - 72 IS - 9 SN - 0008-543X, 0008-543X KW - DNA, Neoplasm KW - 0 KW - Etoposide KW - 6PLQ3CP4P3 KW - Doxorubicin KW - 80168379AG KW - Paclitaxel KW - P88XT4IS4D KW - Abridged Index Medicus KW - Index Medicus KW - DNA, Neoplasm -- drug effects KW - Breast Neoplasms -- drug therapy KW - Drug Screening Assays, Antitumor KW - Drug Interactions KW - Tumor Cells, Cultured -- drug effects KW - Humans KW - Lung Neoplasms -- drug therapy KW - Flow Cytometry KW - Ovarian Neoplasms -- drug therapy KW - Female KW - Paclitaxel -- administration & dosage KW - Etoposide -- pharmacology KW - Etoposide -- antagonists & inhibitors KW - Etoposide -- administration & dosage KW - Doxorubicin -- pharmacology KW - Doxorubicin -- antagonists & inhibitors KW - Paclitaxel -- pharmacology KW - Doxorubicin -- administration & dosage KW - Antineoplastic Combined Chemotherapy Protocols -- pharmacology KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75990237?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Taxol+in+combination+with+doxorubicin+or+etoposide.+Possible+antagonism+in+vitro.&rft.au=Hahn%2C+S+M%3BLiebmann%2C+J+E%3BCook%2C+J%3BFisher%2C+J%3BGoldspiel%2C+B%3BVenzon%2C+D%3BMitchell%2C+J+B%3BKaufman%2C+D&rft.aulast=Hahn&rft.aufirst=S&rft.date=1993-11-01&rft.volume=72&rft.issue=9&rft.spage=2705&rft.isbn=&rft.btitle=&rft.title=Cancer&rft.issn=0008543X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-11-10 N1 - Date created - 1993-11-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - 6-[18F]fluoro-L-dihydroxyphenylalanine metabolism and positron emission tomography after catechol-O-methyltransferase inhibition in normal and hemiparkinsonian monkeys. AN - 76171162; 8281420 AB - Increased and sustained central delivery of L-dihydroxyphenylalanine (L-DOPA) is a desirable therapeutic strategy in Parkinson's disease. We investigated the effects of peripheral catechol-O-methyltransferase (COMT) inhibition, by the non-toxic drug nitecapone on the metabolism of 6-[18F]fluoro-L-dihydroxyphenylalanine (6FD) and on its positron emission tomography (PET) imaging in non-human primates. Nitecapone produced a dose-dependent inhibition in the formation of 3-O-methyl-6-[18F]fluorodihydroxyphenylalanine (OMFD). This inhibition of OMFD formation was attended by increased production of other metabolites, in particular 6-[18F]fluorodopamine (6FDA), 6-[18F]fluorodihydroxyphenylacetic acid (FDOPAC), 6-[18F]fluorohomovanillic acid (FHVA) and [18F]-sulfated conjugates (FSC). Although nitecapone had no effect on plasma 6FD pharmacokinetics, high-dose nitecapone increased contrast of cerebral 18F uptake and retention between regions with high (striatum) versus sparse (parieto-occipital lobes) dopaminergic innervation. 18F uptake contrast was also improved between structures known to possess an intermediate dopaminergic innervation, including the upper brainstem, frontal and temporal lobes, versus sparsely innervated regions. This increased contrast was secondary to decreased activity in sparsely innervated structures and not to increased activity in highly innervated structures. Contrast was correlated inversely with the plasma OMFD/6FD concentration ratio, OMFD being the main 6FD metabolite which can cross the blood brain barrier. We conclude that nitecapone is an effective inhibitor of COMT in non-human primates. This inhibition results in increased 6FD flux through other catabolic pathways. Because of decreased OMFD formation, however, COMT inhibition improves the specificity of 6FD-PET and facilitates in-vivo detection of a wide range of dopaminergic innervation densities in cerebral structures. JF - Brain research AU - Miletich, R S AU - Comi, G AU - Bankiewicz, K AU - Plunkett, R AU - Adams, R AU - Di Chiro, G AU - Kopin, I J AD - Neuroimaging Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/10/29/ PY - 1993 DA - 1993 Oct 29 SP - 1 EP - 13 VL - 626 IS - 1-2 SN - 0006-8993, 0006-8993 KW - Catechol O-Methyltransferase Inhibitors KW - 0 KW - Catechols KW - Fluorine Radioisotopes KW - Pentanones KW - fluorodopa F 18 KW - 2C598205QX KW - Dihydroxyphenylalanine KW - 63-84-3 KW - nitecapone KW - 98BS722498 KW - Index Medicus KW - Animals KW - Reference Values KW - Macaca mulatta KW - Radioligand Assay KW - Catechols -- pharmacology KW - Parkinson Disease, Secondary -- metabolism KW - Parkinson Disease, Secondary -- chemically induced KW - Dihydroxyphenylalanine -- metabolism KW - Tomography, Emission-Computed KW - Dihydroxyphenylalanine -- blood KW - Parkinson Disease, Secondary -- diagnostic imaging KW - Pentanones -- pharmacology KW - Dihydroxyphenylalanine -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76171162?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=6-%5B18F%5Dfluoro-L-dihydroxyphenylalanine+metabolism+and+positron+emission+tomography+after+catechol-O-methyltransferase+inhibition+in+normal+and+hemiparkinsonian+monkeys.&rft.au=Miletich%2C+R+S%3BComi%2C+G%3BBankiewicz%2C+K%3BPlunkett%2C+R%3BAdams%2C+R%3BDi+Chiro%2C+G%3BKopin%2C+I+J&rft.aulast=Miletich&rft.aufirst=R&rft.date=1993-10-29&rft.volume=626&rft.issue=1-2&rft.spage=1&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 - 1994-02-14 N1 - Date created - 1994-02-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Maternal drug use in perinatal HIV studies. The Women and Infants Transmission Study. AN - 76125425; 8267268 JF - Annals of the New York Academy of Sciences AU - Rodriguez, E M AU - Mendez, H AU - Rich, K AU - Sheon, A AU - Fox, H AU - Green, K AU - Diaz, C AU - Brambilla, D AU - Mofenson, L AD - Division of AIDS, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/10/29/ PY - 1993 DA - 1993 Oct 29 SP - 245 EP - 248 VL - 693 SN - 0077-8923, 0077-8923 KW - Index Medicus KW - AIDS/HIV KW - Infant KW - Perinatology KW - Pregnancy Complications KW - Mothers KW - Humans KW - Cohort Studies KW - United States -- epidemiology KW - Female KW - Prevalence KW - Pregnancy KW - HIV Infections -- transmission KW - HIV Infections -- complications KW - Substance-Related Disorders -- complications KW - HIV Infections -- epidemiology KW - Substance-Related Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76125425?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Maternal+drug+use+in+perinatal+HIV+studies.+The+Women+and+Infants+Transmission+Study.&rft.au=Rodriguez%2C+E+M%3BMendez%2C+H%3BRich%2C+K%3BSheon%2C+A%3BFox%2C+H%3BGreen%2C+K%3BDiaz%2C+C%3BBrambilla%2C+D%3BMofenson%2C+L&rft.aulast=Rodriguez&rft.aufirst=E&rft.date=1993-10-29&rft.volume=693&rft.issue=&rft.spage=245&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 - 1994-01-26 N1 - Date created - 1994-01-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Clinical implications of the p53 tumor-suppressor gene. AN - 76007368; 8413413 JF - The New England journal of medicine AU - Harris, C C AU - Hollstein, M AD - National Cancer Institute, Laboratory of Human Carcinogenesis, Bethesda, Md. 20892. Y1 - 1993/10/28/ PY - 1993 DA - 1993 Oct 28 SP - 1318 EP - 1327 VL - 329 IS - 18 SN - 0028-4793, 0028-4793 KW - Tumor Suppressor Protein p53 KW - 0 KW - Abridged Index Medicus KW - Index Medicus KW - Humans KW - Transcription, Genetic KW - Mutation KW - Gene Deletion KW - Neoplasms -- diagnosis KW - Genes, Tumor Suppressor KW - Tumor Suppressor Protein p53 -- genetics KW - Neoplasms -- therapy KW - Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76007368?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Clinical+implications+of+the+p53+tumor-suppressor+gene.&rft.au=Harris%2C+C+C%3BHollstein%2C+M&rft.aulast=Harris&rft.aufirst=C&rft.date=1993-10-28&rft.volume=329&rft.issue=18&rft.spage=1318&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 - 1993-11-01 N1 - Date created - 1993-11-01 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: N Engl J Med. 1994 Mar 24;330(12):864-5 [8114848] N Engl J Med. 1994 Mar 24;330(12):865 [8166834] N Engl J Med. 1994 Mar 24;330(12):865 [8114849] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tyrosine kinase(s) regulate apoptosis and bcl-2 expression in a growth factor-dependent cell line. AN - 76051503; 8226783 AB - Apoptosis (programmed cell death) plays a critical role in many physiological processes, but the mechanism(s) which regulate apoptosis are poorly understood. We demonstrate that in a hematopoietic cell line, which can grow in either interleukin (IL)-2 or IL-3, both of these growth factors can increase bcl-2 mRNA levels and prevent apoptosis normally seen following growth factor withdrawal. Herbimycin A, a protein tyrosine kinase inhibitor, blocks the ability of IL-2 and IL-3 to up-regulate bcl-2 mRNA levels and induces apoptosis. Transfection of a bcl-2 expression vector not only prolongs survival following growth factor withdrawal but also confers resistance to the effect of herbimycin A. We conclude that herbimycin A-sensitive protein tyrosine kinases are involved in the regulation of apoptosis and bcl-2 expression, but these protein tyrosine kinases appear not to be required for the action of Bcl-2 since Bcl-2 can exert its growth survival effect even in the presence of herbimycin A. JF - The Journal of biological chemistry AU - Otani, H AU - Erdos, M AU - Leonard, W J AD - Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/10/25/ PY - 1993 DA - 1993 Oct 25 SP - 22733 EP - 22736 VL - 268 IS - 30 SN - 0021-9258, 0021-9258 KW - bcl-2 KW - Benzoquinones KW - 0 KW - Culture Media, Conditioned KW - Growth Substances KW - Interleukin-2 KW - Interleukin-3 KW - Lactams, Macrocyclic KW - Proto-Oncogene Proteins KW - Proto-Oncogene Proteins c-bcl-2 KW - Quinones KW - RNA, Messenger KW - Recombinant Proteins KW - Rifabutin KW - 1W306TDA6S KW - herbimycin KW - 70563-58-5 KW - Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - Index Medicus KW - Animals KW - Interleukin-2 -- pharmacology KW - Rifabutin -- analogs & derivatives KW - Recombinant Proteins -- pharmacology KW - Electroporation KW - Humans KW - Interleukin-3 -- pharmacology KW - Cell Division -- drug effects KW - Mice KW - RNA, Messenger -- biosynthesis KW - Quinones -- toxicity KW - RNA, Messenger -- metabolism KW - Cell Survival -- drug effects KW - Kinetics KW - Cell Line KW - Protein-Tyrosine Kinases -- antagonists & inhibitors KW - Proto-Oncogene Proteins -- biosynthesis KW - Gene Expression Regulation, Enzymologic KW - Growth Substances -- pharmacology KW - Apoptosis -- physiology KW - Apoptosis -- drug effects KW - Protein-Tyrosine Kinases -- biosynthesis KW - Protein-Tyrosine Kinases -- metabolism KW - Proto-Oncogenes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76051503?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Tyrosine+kinase%28s%29+regulate+apoptosis+and+bcl-2+expression+in+a+growth+factor-dependent+cell+line.&rft.au=Otani%2C+H%3BErdos%2C+M%3BLeonard%2C+W+J&rft.aulast=Otani&rft.aufirst=H&rft.date=1993-10-25&rft.volume=268&rft.issue=30&rft.spage=22733&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 - 1993-12-01 N1 - Date created - 1993-12-01 N1 - Date revised - 2017-01-13 N1 - Gene symbol - bcl-2 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A novel intersubunit repair mechanism in the tryptophan synthase alpha 2 beta 2 complex. Critical role of the beta subunit lysine 167 in intersubunit communication. AN - 76045002; 8226734 AB - This study explores intersubunit communication in the tryptophan synthase alpha 2 beta 2 complex from Salmonella typhimurium. We find that an engineered mutation in the contact region between the alpha and beta subunits remarkably alters the catalytic and spectroscopic properties of the beta subunit in the alpha 2 beta 2 complex. Ligands that bind to the alpha subunit largely repair the deleterious effects of the beta subunit mutation in the alpha 2 beta 2 complex. The conserved residue chosen for mutation, beta subunit lysine 167, appears to form an ion pair with alpha subunit aspartate 56 in the crystal structure of the wild type alpha 2 beta 2 complex. Although replacement of beta subunit lysine 167 by threonine does not prevent formation of the alpha 2 beta 2 complex, this mutation reduces the rate of synthesis of L-tryptophan from L-serine and indole (beta reaction) 25-fold. Ligands that bind to the alpha subunit (indole-3-glycerol phosphate, indole-3-propanol phosphate, alpha-glycerol 3-phosphate, or potassium phosphate) largely restore the activity of the mutant alpha 2 beta 2 complex in the beta reaction. We conclude that beta subunit lysine 167 plays an important role in intersubunit communication in the alpha 2 beta 2 complex. The striking allosteric effects of alpha subunit ligands on the mutant beta subunit in the alpha 2 beta 2 complex may result from ligand-induced conformational changes in the alpha subunit that are transmitted to the beta subunit and repair the mutational defect in the beta subunit. JF - The Journal of biological chemistry AU - Yang, X J AU - Miles, E W AD - Laboratory of Biochemical Pharmacology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/10/25/ PY - 1993 DA - 1993 Oct 25 SP - 22269 EP - 22272 VL - 268 IS - 30 SN - 0021-9258, 0021-9258 KW - trp KW - DNA Primers KW - 0 KW - Macromolecular Substances KW - Recombinant Proteins KW - Tryptophan Synthase KW - EC 4.2.1.20 KW - Lysine KW - K3Z4F929H6 KW - Index Medicus KW - Amino Acid Sequence KW - Binding Sites KW - Cloning, Molecular KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Recombinant Proteins -- metabolism KW - Kinetics KW - Escherichia coli KW - Molecular Sequence Data KW - Spectrophotometry KW - Substrate Specificity KW - Recombinant Proteins -- chemistry KW - Tryptophan Synthase -- metabolism KW - Tryptophan Synthase -- chemistry KW - Salmonella typhimurium -- genetics KW - Salmonella typhimurium -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76045002?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+novel+intersubunit+repair+mechanism+in+the+tryptophan+synthase+alpha+2+beta+2+complex.+Critical+role+of+the+beta+subunit+lysine+167+in+intersubunit+communication.&rft.au=Yang%2C+X+J%3BMiles%2C+E+W&rft.aulast=Yang&rft.aufirst=X&rft.date=1993-10-25&rft.volume=268&rft.issue=30&rft.spage=22269&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 - 1993-12-01 N1 - Date created - 1993-12-01 N1 - Date revised - 2017-01-13 N1 - Gene symbol - trp N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - ClpX, an alternative subunit for the ATP-dependent Clp protease of Escherichia coli. Sequence and in vivo activities. AN - 76035352; 8226770 AB - The ATP-dependent Clp protease of Escherichia coli consists of two subunits, the ClpP subunit, which has the proteolytic active site, and ClpA, which possesses ATPase activity and activates the proteolytic activity of ClpP in vitro. Recently, Zylicz and co-workers (Wojtkowiak, D., Georgopoulos, C., and Zylicz, M. (1993) J. Biol. Chem. 268, 22609-22617) identified another E. coli protein that activated ATP-dependent degradation of lambda O protein in the presence of ClpP. The amino-terminal sequence of this protein corresponds to the translated amino-terminal sequence of a gene that we have named clpX. clpX encodes a protein with M(r) 46,300, similar to that observed for the protein purified by Wojtkowiak et al. clpX is an operon with clpP; both genes are cotranscribed in a single heat-inducible 2200-base mRNA, with clpP the promoter proximal gene. The sequence of ClpX includes a single consensus ATP-binding site motif and has limited homology to regions of ClpA and other members of the ClpA/B/C family. A third group of proteins, ClpY, closely related to ClpX, has been identified by sequence homology. Mutations in either clpX or clpP abolish degradation of the highly unstable lambda O protein in vivo. clpX mutants are not defective in degradation of previously identified ClpA/ClpP substrates such as a ClpA-beta-galactosidase fusion protein. It appears that selectivity of degradation by ClpP in vivo is determined by interaction of ClpP with different regulatory ATPase subunits. JF - The Journal of biological chemistry AU - Gottesman, S AU - Clark, W P AU - de Crecy-Lagard, V AU - Maurizi, M R AD - Laboratory of Molecular Biology, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1993/10/25/ PY - 1993 DA - 1993 Oct 25 SP - 22618 EP - 22626 VL - 268 IS - 30 SN - 0021-9258, 0021-9258 KW - bolA KW - clpP KW - clpX KW - hupB KW - lon KW - tlg KW - ClpYQ protease, E coli KW - 0 KW - Escherichia coli Proteins KW - Heat-Shock Proteins KW - Macromolecular Substances KW - O protein, Bacteriophage lambda KW - Viral Proteins KW - ATP-Dependent Proteases KW - EC 3.4.21.- KW - Serine Endopeptidases KW - Endopeptidase Clp KW - EC 3.4.21.92 KW - Adenosine Triphosphatases KW - EC 3.6.1.- KW - Index Medicus KW - Genes, Bacterial KW - Amino Acid Sequence KW - Chromosome Mapping KW - Mutagenesis, Site-Directed KW - Genotype KW - Promoter Regions, Genetic KW - Base Sequence KW - Kinetics KW - Chromosomes, Bacterial KW - Bacteriophage lambda -- metabolism KW - Molecular Sequence Data KW - Viral Proteins -- metabolism KW - Sequence Homology, Amino Acid KW - DNA Replication KW - Heat-Shock Proteins -- metabolism KW - Serine Endopeptidases -- metabolism KW - Serine Endopeptidases -- genetics KW - Adenosine Triphosphatases -- metabolism KW - Escherichia coli -- genetics KW - Serine Endopeptidases -- isolation & purification KW - Escherichia coli -- enzymology KW - Consensus Sequence KW - Heat-Shock Proteins -- isolation & purification KW - Heat-Shock Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76035352?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=ClpX%2C+an+alternative+subunit+for+the+ATP-dependent+Clp+protease+of+Escherichia+coli.+Sequence+and+in+vivo+activities.&rft.au=Gottesman%2C+S%3BClark%2C+W+P%3Bde+Crecy-Lagard%2C+V%3BMaurizi%2C+M+R&rft.aulast=Gottesman&rft.aufirst=S&rft.date=1993-10-25&rft.volume=268&rft.issue=30&rft.spage=22618&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 - 1993-12-01 N1 - Date created - 1993-12-01 N1 - Date revised - 2017-01-13 N1 - Gene symbol - bolA; clpP; clpX; hupB; lon; tlg N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Primary soft tissue sarcomas of the breast: local-regional control with post-operative radiotherapy. AN - 76043955; 8226163 AB - A retrospective analysis was undertaken to determine the efficacy of postoperative radiotherapy in patients with primary sarcoma of the breast. Ten patients with high-grade nonmetastatic primary sarcoma of the breast were treated at the National Cancer Institute, NIH, between 1979 and 1989 with mastectomy and adjuvant radiotherapy. Chemotherapy was given to three patients as part of a randomized trial. With a median potential followup of 99 months postoperatively, seven patients remain alive and without evidence of disease 142, 119, 82, 48, 45, 28, and 19 months postoperatively. Three patients died of metastatic disease 7, 25, and 29 months, postoperatively. There were no local or regional failures. Actuarial 5-year disease free and overall survival were 68% and 66%, respectively. Sarcomas of the breast have a prognosis similar to that of extremity sarcomas. When adjuvant radiotherapy is used, excellent local control may be achieved. JF - International journal of radiation oncology, biology, physics AU - Johnstone, P A AU - Pierce, L J AU - Merino, M J AU - Yang, J C AU - Epstein, A H AU - DeLaney, T F AD - Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/10/20/ PY - 1993 DA - 1993 Oct 20 SP - 671 EP - 675 VL - 27 IS - 3 SN - 0360-3016, 0360-3016 KW - Index Medicus KW - Mastectomy, Simple KW - Mastectomy, Radical KW - Mastectomy, Modified Radical KW - Combined Modality Therapy KW - Humans KW - Adult KW - Retrospective Studies KW - Middle Aged KW - Adolescent KW - Female KW - Radiotherapy -- adverse effects KW - Sarcoma -- radiotherapy KW - Sarcoma -- surgery KW - Mastectomy KW - Breast Neoplasms -- surgery KW - Breast Neoplasms -- radiotherapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76043955?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+radiation+oncology%2C+biology%2C+physics&rft.atitle=Primary+soft+tissue+sarcomas+of+the+breast%3A+local-regional+control+with+post-operative+radiotherapy.&rft.au=Johnstone%2C+P+A%3BPierce%2C+L+J%3BMerino%2C+M+J%3BYang%2C+J+C%3BEpstein%2C+A+H%3BDeLaney%2C+T+F&rft.aulast=Johnstone&rft.aufirst=P&rft.date=1993-10-20&rft.volume=27&rft.issue=3&rft.spage=671&rft.isbn=&rft.btitle=&rft.title=International+journal+of+radiation+oncology%2C+biology%2C+physics&rft.issn=03603016&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-12-14 N1 - Date created - 1993-12-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Carcinogenic effects in rats of nitrosopiperazines administered intravesically: possible implications for the use of piperazine. AN - 76177702; 8287362 AB - Two nitrosamines derived from nitrosation of piperazine, 1-nitrosopiperazine (NO-PIP) and 1,4-dinitrosopiperazine (DNP), were administered to groups of twelve female F344 rats intravesically. The doses were, respectively, 40 mg and 5.2 mg twice a week for 48 and 36 weeks in aqueous solution. Ten DNP-treated animals survived the treatment; six had tumors related to the treatment, nasal mucosa adenocarcinomas or neuroblastomas in five and a transitional cell carcinoma of the bladder in one. Rats treated with NO-PIP received a ten times greater dose, and all died by week 59, two with transitional cell neoplasms of the bladder and four with carcinomas of the nasal mucosa. NO-PIP was probably in part converted by transnitrosation to DNP. Piperazine, widely used as an oral anti-helminthic, could interact with nitrosating agents in vivo to form the two nitrosamines here shown to pose a possible carcinogenic risk if present in the bladder, by absorption through the bladder wall. JF - Cancer letters AU - Lijinsky, W AU - Kovatch, R M AD - ABL Basic Research Program, NCI Frederick Cancer Research and Development Center, MD 21702. Y1 - 1993/10/15/ PY - 1993 DA - 1993 Oct 15 SP - 101 EP - 103 VL - 74 IS - 1-2 SN - 0304-3835, 0304-3835 KW - Anthelmintics KW - 0 KW - Carcinogens KW - Nitrosamines KW - Piperazines KW - 1-nitrosopiperazine KW - 5632-47-3 KW - N,N'-dinitrosopiperazine KW - GU48C6581I KW - Index Medicus KW - Urinary Bladder -- metabolism KW - Animals KW - Adenocarcinoma -- chemically induced KW - Anthelmintics -- toxicity KW - Carcinoma, Transitional Cell -- chemically induced KW - Nasal Mucosa -- drug effects KW - Administration, Intravesical KW - Urinary Bladder -- drug effects KW - Rats KW - Rats, Inbred F344 KW - Biotransformation KW - Nose Neoplasms -- chemically induced KW - Neuroblastoma -- chemically induced KW - Nitrosation KW - Female KW - Piperazines -- pharmacokinetics KW - Nitrosamines -- toxicity KW - Carcinogens -- administration & dosage KW - Carcinogens -- toxicity KW - Piperazines -- toxicity KW - Urinary Bladder Neoplasms -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76177702?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+letters&rft.atitle=Carcinogenic+effects+in+rats+of+nitrosopiperazines+administered+intravesically%3A+possible+implications+for+the+use+of+piperazine.&rft.au=Lijinsky%2C+W%3BKovatch%2C+R+M&rft.aulast=Lijinsky&rft.aufirst=W&rft.date=1993-10-15&rft.volume=74&rft.issue=1-2&rft.spage=101&rft.isbn=&rft.btitle=&rft.title=Cancer+letters&rft.issn=03043835&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-02-24 N1 - Date created - 1994-02-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Delayed effects of neonatal hippocampal damage on haloperidol-induced catalepsy and apomorphine-induced stereotypic behaviors in the rat. AN - 76140098; 7903225 AB - The developmental effects of neonatal excitotoxic ventral hippocampal (VH) damage on behaviors related to dopaminergic (DA) transmission in the basal ganglia were investigated in the rat. Ibotenic acid (in Lesion) or artificial cerebrospinal fluid (in Sham) was infused into the VH of 7-day-old (PD7) rat pups. Haloperidol-induced (1 mg/kg, i.p.) catalepsy and apomorphine-induced (0.75 mg/kg, s.c.) stereotypic behaviors as well as locomotion were assessed in Sham and Lesion rats prior to (PD35) and after puberty (PD56). On PD35, Lesion and Sham animals did not differ in induced catalepsy or stereotypy. On PD56, however, Lesion animals were less cataleptic following haloperidol injection and manifested supersensitivity to apomorphine as compared to Sham rats. At both, PD35 and PD56, locomotor activity after apomorphine was significantly increased in Lesion animals as compared with controls. These results indicate that the neonatal excitotoxic VH lesion results in a unique time-dependent pattern of behavioral changes related to striatal DA transmission. Moreover, the response to apomorphine differs qualitatively from that previously reported after the analogous lesion induced in adult animals in which stereotypy was reduced. These findings suggest that early hippocampal deafferentation affects the development of other brain regions, such as the medial prefrontal cortex, that are also involved in the regulation of striatal DA function. JF - Brain research. Developmental brain research AU - Lipska, B K AU - Weinberger, D R AD - Clinical Brain Disorders Branch, National Institute of Mental Health, NIH, Neuroscience Center, St. Elizabeths, Washington, DC 20032. Y1 - 1993/10/15/ PY - 1993 DA - 1993 Oct 15 SP - 213 EP - 222 VL - 75 IS - 2 SN - 0165-3806, 0165-3806 KW - Dopamine Agents KW - 0 KW - Receptors, Dopamine D1 KW - Receptors, Dopamine D2 KW - Haloperidol KW - J6292F8L3D KW - Apomorphine KW - N21FAR7B4S KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Animals KW - Dopamine Agents -- pharmacology KW - Dopamine -- physiology KW - Receptors, Dopamine D1 -- drug effects KW - Basal Ganglia -- physiology KW - Neurons, Afferent -- physiology KW - Pregnancy KW - Rats KW - Rats, Sprague-Dawley KW - Corpus Striatum -- physiology KW - Corpus Striatum -- growth & development KW - Receptors, Dopamine D2 -- drug effects KW - Neurons, Afferent -- drug effects KW - Motor Activity -- drug effects KW - Basal Ganglia -- drug effects KW - Female KW - Catalepsy -- chemically induced KW - Hippocampus -- physiology KW - Hippocampus -- growth & development KW - Apomorphine -- pharmacology KW - Hippocampus -- injuries KW - Stereotyped Behavior -- drug effects KW - Animals, Newborn -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76140098?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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.+Developmental+brain+research&rft.atitle=Delayed+effects+of+neonatal+hippocampal+damage+on+haloperidol-induced+catalepsy+and+apomorphine-induced+stereotypic+behaviors+in+the+rat.&rft.au=Lipska%2C+B+K%3BWeinberger%2C+D+R&rft.aulast=Lipska&rft.aufirst=B&rft.date=1993-10-15&rft.volume=75&rft.issue=2&rft.spage=213&rft.isbn=&rft.btitle=&rft.title=Brain+research.+Developmental+brain+research&rft.issn=01653806&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-01-26 N1 - Date created - 1994-01-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Withdrawal from chronic cocaine enhances behavioral sensitivity to the 5-HT2/1C agonist DOI. AN - 76135738; 8274588 JF - Biological psychiatry AU - Baumann, M H AU - Brockington, A M AU - Rothman, R B AD - Clinical Psychopharmacology Section, National Institute on Drug Abuse/Addiction Research Center, National Institutes of Health, Baltimore, MD 21224. Y1 - 1993/10/15/ PY - 1993 DA - 1993 Oct 15 SP - 576 EP - 577 VL - 34 IS - 8 SN - 0006-3223, 0006-3223 KW - Amphetamines KW - 0 KW - Receptors, Serotonin KW - Serotonin Receptor Agonists KW - Cocaine KW - I5Y540LHVR KW - 4-iodo-2,5-dimethoxyphenylisopropylamine KW - OOM10GW9UE KW - Index Medicus KW - Rats KW - Brain -- physiopathology KW - Animals KW - Rats, Sprague-Dawley KW - Stereotyped Behavior -- physiology KW - Humans KW - Brain -- drug effects KW - Stereotyped Behavior -- drug effects KW - Motor Activity -- physiology KW - Motor Activity -- drug effects KW - Serotonin Receptor Agonists -- pharmacology KW - Receptors, Serotonin -- physiology KW - Receptors, Serotonin -- drug effects KW - Behavior, Animal -- drug effects KW - Substance Withdrawal Syndrome -- physiopathology KW - Amphetamines -- pharmacology KW - Cocaine -- toxicity KW - Behavior, Animal -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76135738?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biological+psychiatry&rft.atitle=Withdrawal+from+chronic+cocaine+enhances+behavioral+sensitivity+to+the+5-HT2%2F1C+agonist+DOI.&rft.au=Baumann%2C+M+H%3BBrockington%2C+A+M%3BRothman%2C+R+B&rft.aulast=Baumann&rft.aufirst=M&rft.date=1993-10-15&rft.volume=34&rft.issue=8&rft.spage=576&rft.isbn=&rft.btitle=&rft.title=Biological+psychiatry&rft.issn=00063223&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-02-08 N1 - Date created - 1994-02-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - MK-801, but not drugs acting at strychnine-insensitive glycine receptors, attenuate methamphetamine nigrostriatal toxicity. AN - 76106760; 8242398 AB - Repeated administration of methamphetamine (METH) results in damage to nigrostriatal dopaminergic neurons. Both competitive N-methyl-D-aspartate (NMDA) receptor antagonists and use-dependent cation channel blockers attenuate METH-induced damage. The objectives of the present study were to examine whether comparable reductions in METH-induced damage could be obtained by compounds acting at strychnine-insensitive glycine receptors on the NMDA receptor complex. Four injections of METH (5 mg/kg i.p.) resulted in a approximately 70.9% depletion of striatal dopamine (DA) and approximately 62.7% depletion of dihydroxyphenylacetic acid (DOPAC) content, respectively. A significant protection against METH-induced DA and DOPAC depletion was afforded by the use-dependent channel blocker, MK-801. The competitive glycine antagonist 7-chlorokynurenic acid (7-Cl-KA), the low efficacy glycine partial agonist (+)-3-amino-1-hydroxy-2-pyrrolidone ((+)-HA-966), and the high efficacy partial glycine agonist 1-aminocyclopropane-carboxylic acid (ACPC) were ineffective against METH-induced toxicity despite their abilities to attenuate glutamate-induced neurotoxicity under both in vivo and in vitro conditions. These results indicate that glycinergic ligands do not possess the same broad neuroprotective spectrum as other classes of NMDA antagonists. JF - Brain research AU - Layer, R T AU - Bland, L R AU - Skolnick, P AD - Laboratory of Neuroscience, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/10/15/ PY - 1993 DA - 1993 Oct 15 SP - 38 EP - 44 VL - 625 IS - 1 SN - 0006-8993, 0006-8993 KW - Amino Acids KW - 0 KW - Amino Acids, Cyclic KW - Receptors, Glycine KW - 3,4-Dihydroxyphenylacetic Acid KW - 102-32-9 KW - 1-aminocyclopropane-1-carboxylic acid KW - 3K9EJ633GL KW - Methamphetamine KW - 44RAL3456C KW - Dizocilpine Maleate KW - 6LR8C1B66Q KW - Kynurenic Acid KW - H030S2S85J KW - Strychnine KW - H9Y79VD43J KW - 7-chlorokynurenic acid KW - S7936QON2K KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Mice, Inbred Strains KW - Animals KW - 3,4-Dihydroxyphenylacetic Acid -- metabolism KW - Strychnine -- pharmacology KW - Dopamine -- metabolism KW - Mice KW - Kynurenic Acid -- analogs & derivatives KW - Receptors, Glycine -- drug effects KW - Amino Acids -- pharmacology KW - Kynurenic Acid -- pharmacology KW - Male KW - Substantia Nigra -- metabolism KW - Corpus Striatum -- metabolism KW - Substantia Nigra -- drug effects KW - Corpus Striatum -- drug effects KW - Methamphetamine -- antagonists & inhibitors KW - Methamphetamine -- toxicity KW - Dizocilpine Maleate -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76106760?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=MK-801%2C+but+not+drugs+acting+at+strychnine-insensitive+glycine+receptors%2C+attenuate+methamphetamine+nigrostriatal+toxicity.&rft.au=Layer%2C+R+T%3BBland%2C+L+R%3BSkolnick%2C+P&rft.aulast=Layer&rft.aufirst=R&rft.date=1993-10-15&rft.volume=625&rft.issue=1&rft.spage=38&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 - 1993-12-29 N1 - Date created - 1993-12-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mechanism of action of Pseudomonas exotoxin. Identification of a rate-limiting step. AN - 75997094; 8408034 AB - Pseudomonas exotoxin (PE) enters cells by receptor-mediated endocytosis and is cleaved by a cellular protease between Arg279 and Gly280 to produce an NH2-terminal fragment of 28 kDa which contains the toxin's binding domain and a COOH-terminal fragment of 37 kDa which has translocating and ADP-ribosylating activity. After proteolysis, the COOH-terminal fragment reaches the endoplasmic reticulum by retrograde transport where it translocates to the cytosol and inhibits protein synthesis by ADP-ribosylating elongation factor 2. To understand how the 37-kDa fragment functions, we focused on the role of specific amino acids located near its NH2 terminus. We found that there was a 4-250-fold loss in toxic activity when tryptophan 281, leucine 284, or tyrosine 289 were changed to other residues. Mutations at these three positions did not interfere with the receptor binding, cell-mediated proteolytic cleavage, or ADP-ribosylating activity. To determine the role of these amino acids, a competition assay was devised in which the addition of excess PE delta 553, a mutant form of PE that lacks ADP-ribosylation activity, competed efficiently for the toxicity of PE. Excess PE with mutations near the NH2 terminus of the 37-kDa fragment competed poorly. This competition occurred after proteolysis since PEGly276, a mutant form of PE that is not cleaved, did not complete. We conclude that specific amino acids at the NH2 terminus of the 37-kDa fragment interact in a saturable manner with an unknown intracellular component. JF - The Journal of biological chemistry AU - Zdanovsky, A G AU - Chiron, M AU - Pastan, I AU - FitzGerald, D J AD - Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/10/15/ PY - 1993 DA - 1993 Oct 15 SP - 21791 EP - 21799 VL - 268 IS - 29 SN - 0021-9258, 0021-9258 KW - Amino Acids KW - 0 KW - Bacterial Toxins KW - Exotoxins KW - Oligodeoxyribonucleotides KW - Virulence Factors KW - Adenosine Diphosphate Ribose KW - 20762-30-5 KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - toxA protein, Pseudomonas aeruginosa KW - EC 2.4.2.31 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Animals KW - Base Sequence KW - Cells, Cultured KW - Kinetics KW - Humans KW - Binding, Competitive KW - Amino Acids -- analysis KW - Molecular Sequence Data KW - Mice KW - Adenosine Diphosphate Ribose -- metabolism KW - Hydrolysis KW - Exotoxins -- pharmacology KW - Exotoxins -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75997094?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mechanism+of+action+of+Pseudomonas+exotoxin.+Identification+of+a+rate-limiting+step.&rft.au=Zdanovsky%2C+A+G%3BChiron%2C+M%3BPastan%2C+I%3BFitzGerald%2C+D+J&rft.aulast=Zdanovsky&rft.aufirst=A&rft.date=1993-10-15&rft.volume=268&rft.issue=29&rft.spage=21791&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 - 1993-11-18 N1 - Date created - 1993-11-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The carboxyl-terminal domain of the human pregnancy-specific glycoprotein specifies intracellular retention and stability. AN - 75996658; 8408064 AB - The pregnancy-specific glycoproteins (PSGs), which are members of the immunoglobulin superfamily, are the major pregnancy-associated proteins synthesized by the human placenta. Thirty or more PSG members have been identified which are encoded by at least 11 linked genes. The PSG proteins share 85-95% sequence homology in the coding region, but show variability at the carboxyl-terminal (COOH) domains. In the present study, we examined the effects of PSG COOH domains on protein secretion and stability. Using PSGs containing short (11-12 residues) hydrophilic (PSG1e, PSG11s, and PSG16a), short (22 residues) hydrophobic (PSG6r), and long (81 residues) hydrophobic (PSG11w) COOH domains, we showed that most PSG members were secretory proteins except PSG11w which was largely retained in cells. When the PSG11w COOH domain was replaced with a short COOH domain of PSG1e, the resulting PSG-N11w/C1e chimera became secreted into the medium. On the other hand, chimeras that harbored the PSG11w COOH domain, PSG-N1e/C11w and PSG-N16a/C11w, remained in cells, demonstrating that the COOH domain of PSG11w confers intracellular retention. Deletion analysis showed that mutant (PSG11w-C2) that contained the first 21 amino acids of PSG11w COOH domain or mutant (PSG11w-C3) that contained a deletion of hydrophobic residues 372-392 in the PSG11w COOH domain remained largely in cells. In contrast, the PSG11w-C1 mutant which contained the first 12 residues of the PSG11w COOH domain became a secretory protein. Studies of PSG synthesis and processing in the presence of Brefeldin A, a drug that impedes protein transport from endoplasmic reticulum to the Golgi system, showed that PSG11w resided and degraded in the endoplasmic reticulum. The endoplasmic reticulum localization of PSG11w and the cell-associated mutant PSGs was further demonstrated by their sensitivity to endoglycosidase H and indirect immunofluorescence analysis. JF - The Journal of biological chemistry AU - Chen, H AU - Chan, W Y AU - Chen, C L AU - Mansfield, B C AU - Chou, J Y AD - Human Genetics Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/10/15/ PY - 1993 DA - 1993 Oct 15 SP - 22066 EP - 22075 VL - 268 IS - 29 SN - 0021-9258, 0021-9258 KW - DNA, Single-Stranded KW - 0 KW - Glycoproteins KW - Pregnancy Proteins KW - Recombinant Proteins KW - Index Medicus KW - Animals KW - Recombinant Proteins -- secretion KW - Humans KW - Protein Processing, Post-Translational KW - Amino Acid Sequence KW - Pregnancy KW - Cloning, Molecular KW - Endoplasmic Reticulum -- chemistry KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Recombinant Proteins -- metabolism KW - Kinetics KW - Molecular Sequence Data KW - Recombinant Proteins -- chemistry KW - Cell Line KW - Female KW - Pregnancy Proteins -- secretion KW - Glycoproteins -- metabolism KW - Glycoproteins -- chemistry KW - Pregnancy Proteins -- metabolism KW - Pregnancy Proteins -- chemistry KW - Glycoproteins -- secretion UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75996658?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+carboxyl-terminal+domain+of+the+human+pregnancy-specific+glycoprotein+specifies+intracellular+retention+and+stability.&rft.au=Chen%2C+H%3BChan%2C+W+Y%3BChen%2C+C+L%3BMansfield%2C+B+C%3BChou%2C+J+Y&rft.aulast=Chen&rft.aufirst=H&rft.date=1993-10-15&rft.volume=268&rft.issue=29&rft.spage=22066&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 - 1993-11-18 N1 - Date created - 1993-11-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A phase I study of continuous infusion 5-fluorouracil plus calcium leucovorin in combination with N-(phosphonacetyl)-L-aspartate in metastatic gastrointestinal adenocarcinoma. AN - 75995573; 8402669 AB - Preclinical studies suggest that the biochemical effects of N-(phosphonacetyl)-L-aspartate (PALA), an inhibitor of aspartate carbamoyltransferase (ACTase), may increase the metabolic activation of 5-fluorouracil (5-FU) and enhance its cytotoxicity through both RNA- and DNA-directed mechanisms. In this Phase I trial, 22 evaluable patients with adenocarcinoma of the gastrointestinal tract were entered at escalating doses of 5-FU starting at 1150 mg/m2/day given as a concurrent 72-h i.v. infusion with a fixed dose of leucovorin (LCV), 500 mg/m2/day. The dose of 5-FU was escalated within patients according to individual tolerance, and then PALA at 250 mg/m2 was added 24 h prior to the initiation of the 5-FU/LCV infusion of the subsequent cycle. Dose-limiting mucositis and myelosuppression occurred during the initial cycle in 3 of 5 patients treated with 2300 mg/m2/day 5-FU; therefore, the recommended dose of 5-FU with concurrent LCV is 2000 mg/m2/day. Twenty-seven additional patients were then treated with escalating doses of PALA ranging from 375 to 2848 mg/m2, i.v., followed 24 h later by 2000 mg/m2/day 5-FU with high-dose LCV. Dose-limiting mucositis and myelosuppression occurred during the initial cycle in 2 of 3 patients entered at 2848 mg/m2 PALA. Dose-limiting mucositis and skin rash ultimately required both PALA and 5-FU dose reductions in 4 of 6 patients treated with 1899 mg/m2 PALA. Toxicity was similar, however, in patients receiving PALA at doses ranging from 375 to 1266 mg/m2. The mean steady-state plasma concentration of 5-FU at 2000 mg/m2/day was 6.5 +/- 0.9 microM; patients with 5-FU levels > 9 microM had a significantly higher incidence of serious gastrointestinal and hematological toxicity. Compared to each patient's own baseline, a significant trend for decreasing ACTase activity with increasing PALA dose was evident using cytosol isolated from peripheral blood mononuclear cells 24 h after PALA treatment (P2 = 0.01). PALA 50% from baseline was seen in only 29% of cycles. More consistent inhibition of ACTase activity was seen with PALA > or = 1266 mg/m2. Even with the highest PALA doses, however, ACTase activity returned to baseline by 96 h in most patients.(ABSTRACT TRUNCATED AT 400 WORDS) JF - Cancer research AU - Grem, J L AU - McAtee, N AU - Steinberg, S M AU - Hamilton, J M AU - Murphy, R F AU - Drake, J AU - Chisena, T AU - Balis, F AU - Cysyk, R AU - Arbuck, S G AD - Clinical Oncology Program, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/10/15/ PY - 1993 DA - 1993 Oct 15 SP - 4828 EP - 4836 VL - 53 IS - 20 SN - 0008-5472, 0008-5472 KW - Antineoplastic Agents KW - 0 KW - Aspartic Acid KW - 30KYC7MIAI KW - sparfosic acid KW - 78QVZ7RG8L KW - Aspartate Carbamoyltransferase KW - EC 2.1.3.2 KW - Phosphonoacetic Acid KW - N919E46723 KW - Leucovorin KW - Q573I9DVLP KW - Fluorouracil KW - U3P01618RT KW - Index Medicus KW - Infusions, Intravenous KW - Aspartate Carbamoyltransferase -- blood KW - Humans KW - Leucovorin -- administration & dosage KW - Monocytes -- enzymology KW - Aged KW - Adult KW - Neoplasm Metastasis KW - Aspartate Carbamoyltransferase -- antagonists & inhibitors KW - Monocytes -- drug effects KW - Middle Aged KW - Female KW - Male KW - Aspartic Acid -- toxicity KW - Phosphonoacetic Acid -- toxicity KW - Antineoplastic Agents -- administration & dosage KW - Phosphonoacetic Acid -- analogs & derivatives KW - Gastrointestinal Neoplasms -- drug therapy KW - Antineoplastic Combined Chemotherapy Protocols -- toxicity KW - Adenocarcinoma -- pathology KW - Fluorouracil -- administration & dosage KW - Aspartic Acid -- administration & dosage KW - Aspartic Acid -- analogs & derivatives KW - Fluorouracil -- toxicity KW - Phosphonoacetic Acid -- administration & dosage KW - Antineoplastic Agents -- toxicity KW - Gastrointestinal Neoplasms -- pathology KW - Adenocarcinoma -- drug therapy KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Fluorouracil -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75995573?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+phase+I+study+of+continuous+infusion+5-fluorouracil+plus+calcium+leucovorin+in+combination+with+N-%28phosphonacetyl%29-L-aspartate+in+metastatic+gastrointestinal+adenocarcinoma.&rft.au=Grem%2C+J+L%3BMcAtee%2C+N%3BSteinberg%2C+S+M%3BHamilton%2C+J+M%3BMurphy%2C+R+F%3BDrake%2C+J%3BChisena%2C+T%3BBalis%2C+F%3BCysyk%2C+R%3BArbuck%2C+S+G&rft.aulast=Grem&rft.aufirst=J&rft.date=1993-10-15&rft.volume=53&rft.issue=20&rft.spage=4828&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 - 1993-11-09 N1 - Date created - 1993-11-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phase I evaluation and pharmacokinetic study of pyrazine-2-diazohydroxide administered as a single bolus intravenous injection in patients with advanced solid tumors. AN - 75991863; 8402671 AB - The sodium salt of pyrazine-2-diazohydroxide (PZDH; NSC 361456) was identified as an active congener of the antitumor lead pyridine-2-diazotate with enhanced chemical stability under physiological conditions. In a phase I trial of PZDH administered as a single i.v. bolus injection, 19 patients with refractory solid tumors received 44 courses of therapy at dose levels ranging from 50 to 350 mg/m2. No objective responses to PZDH were noted. Myelosuppression characterized by prolonged, delayed onset leukopenia and thrombocytopenia was the dose limiting toxicity. A maximum tolerated dose of 350 mg/m2 was identified for this treatment schedule. Nonhematological toxicity was limited to severe nausea and vomiting, experienced by all patients treated at the lower doses, although reasonably well controlled when antiemetics were given prior to chemotherapy. The plasma pharmacokinetics of PZDH was evaluated following a single course of therapy in 16 patients. Drug levels were monitored using a specific capillary gas chromatographic assay with a 1-ng/ml lower limit of quantitation. In patients treated with doses greater than 50 mg/m2, the concentration of PZDH in plasma declined in a distinctly triexponential manner and remained above 1.5 ng/ml for at least 8 h. However, the initial decay phase, characterized by a harmonic mean half-life of 3.9 +/- 3.5 (SD) min (range, 2.2-6.3 min), was the primary determinant of drug disposition, as indicated by its 85.5-93.1% contribution to the area under the plasma concentration-time profiles from time zero to infinity. The harmonic mean terminal half-life increased with escalations in dose from 2.7 +/- 0.8 h (n = 2) at 100 mg/m2 to 8.5 +/- 3.0 h at 350 mg/m2 (n = 6). Total plasma drug clearance was very similar in patients treated with doses of 50-250 mg/m2, exhibiting a mean value of 42.5 +/- 7.8 liters/h/m2 (n = 10); however, it was significantly lower at the 350 mg/m2 dose level, 27.2 +/- 6.6 liters/h/m2 (n = 6; P < 0.002), denoting a departure from linear pharmacokinetic behavior. The rather low steady state apparent volume of distribution, which ranged from 6.0 +/- 1.5 (50 mg/m2, n = 2) to 12.7 +/- 8.0 (350 mg/m2, n = 6) liters/m2, was indicative of limited distribution of the drug into body tissue. The absence of objective antitumor effects should not discourage continued evaluation of PZDH against solid tumors selected for probable sensitivity as indicated by preclinical testing. A dose of 250 mg/m2 on a single i.v. bolus schedule is recommended for these phase II trials. JF - Cancer research AU - Supko, J G AU - Balcerzak, S P AU - Kraut, E H AD - Developmental Therapeutics Program, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1993/10/15/ PY - 1993 DA - 1993 Oct 15 SP - 4843 EP - 4849 VL - 53 IS - 20 SN - 0008-5472, 0008-5472 KW - Antineoplastic Agents KW - 0 KW - Pyrazines KW - pyrazine-2-diazohydroxide KW - 103829-56-7 KW - Index Medicus KW - Neoplasm Staging KW - Injections, Intravenous KW - Dose-Response Relationship, Drug KW - Humans KW - Adult KW - Metabolic Clearance Rate KW - Aged KW - Middle Aged KW - Male KW - Female KW - Pyrazines -- toxicity KW - Neoplasms -- drug therapy KW - Pyrazines -- administration & dosage KW - Neoplasms -- pathology KW - Antineoplastic Agents -- pharmacokinetics KW - Antineoplastic Agents -- toxicity KW - Pyrazines -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75991863?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Phase+I+evaluation+and+pharmacokinetic+study+of+pyrazine-2-diazohydroxide+administered+as+a+single+bolus+intravenous+injection+in+patients+with+advanced+solid+tumors.&rft.au=Supko%2C+J+G%3BBalcerzak%2C+S+P%3BKraut%2C+E+H&rft.aulast=Supko&rft.aufirst=J&rft.date=1993-10-15&rft.volume=53&rft.issue=20&rft.spage=4843&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 - 1993-11-09 N1 - Date created - 1993-11-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The suprabasal expression of alpha 6 beta 4 integrin is associated with a high risk for malignant progression in mouse skin carcinogenesis. AN - 75991427; 8402665 AB - Enhanced expression of the alpha 6 beta 4 integrin complex has been linked to malignant progression in mouse skin carcinogenesis. To determine if alpha 6 beta 4 expression can predict risk for malignant conversion among populations of benign skin tumors, we analyzed the distribution of alpha 6 beta 4 and other markers of progression in papillomas at high and low risk for malignant progression. After initiation with 7,12-dimethylbenz[a]anthracene, mice were promoted with 12-O-tetradecanoylphorbol-13-acetate to induce predominantly low risk tumors or promoted with mezerein to produce predominantly high risk tumors. When tumors first appeared at 8 weeks after promotion, high risk papillomas demonstrated basal and suprabasal alpha 6 beta 4 expression, loss of keratin 1, and aberrant expression of keratin 13. In these tumors alpha 6 beta 4 expression coincided with an expansion of the proliferating compartment as indicated by suprabasal bromodeoxyuridine labeling. In contrast, alpha 6 beta 4 immunostaining was confined to basal cells in low risk tumors, keratin 1 was abundant, and keratin 13 was absent in the majority of this group, while proliferating cells were largely in the basal compartment. By 33 weeks, alpha 6 beta 4 suprabasal expression continued to distinguish groups at higher risk for malignant conversion, but keratin 13 was expressed in all groups. At this time, high risk tumors displayed focal expression of keratin 8 and gamma-glutamyltranspeptidase, markers also found in chemically induced carcinomas. Keratin 8 and gamma-glutamyltranspeptidase were expressed only in alpha 6 beta 4 positive cells. These results indicate that expression of alpha 6 beta 4 integrin in suprabasal strata serves as an early predictive marker to identify benign squamous tumors at high risk for malignant progression. JF - Cancer research AU - Tennenbaum, T AU - Weiner, A K AU - Belanger, A J AU - Glick, A B AU - Hennings, H AU - Yuspa, S H AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1993/10/15/ PY - 1993 DA - 1993 Oct 15 SP - 4803 EP - 4810 VL - 53 IS - 20 SN - 0008-5472, 0008-5472 KW - Antigens, Surface KW - 0 KW - Biomarkers, Tumor KW - Diterpenes KW - Integrin alpha6beta4 KW - Terpenes KW - mezerein KW - 34807-41-5 KW - 9,10-Dimethyl-1,2-benzanthracene KW - 57-97-6 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Mice, Inbred Strains KW - Animals KW - Risk Factors KW - Kinetics KW - Mice KW - Time Factors KW - Immunohistochemistry KW - Female KW - Skin -- drug effects KW - Papilloma -- pathology KW - Skin Neoplasms -- chemically induced KW - Skin -- pathology KW - Biomarkers, Tumor -- analysis KW - Skin Neoplasms -- pathology KW - Antigens, Surface -- biosynthesis KW - Skin Neoplasms -- metabolism KW - Papilloma -- chemically induced KW - Papilloma -- metabolism KW - Antigens, Surface -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75991427?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+suprabasal+expression+of+alpha+6+beta+4+integrin+is+associated+with+a+high+risk+for+malignant+progression+in+mouse+skin+carcinogenesis.&rft.au=Tennenbaum%2C+T%3BWeiner%2C+A+K%3BBelanger%2C+A+J%3BGlick%2C+A+B%3BHennings%2C+H%3BYuspa%2C+S+H&rft.aulast=Tennenbaum&rft.aufirst=T&rft.date=1993-10-15&rft.volume=53&rft.issue=20&rft.spage=4803&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 - 1993-11-09 N1 - Date created - 1993-11-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - p53 protein accumulates frequently in early bronchial neoplasia. AN - 75977951; 8402667 AB - p53 mutations are common in human lung cancer and frequently generate levels of p53 protein that are detectable by immunohistochemistry. For this reason, p53 protein accumulation is a candidate biomarker, but little is known about its timing or frequency in multistage bronchial carcinogenesis. We studied human lung tissues containing preinvasive squamous neoplasms from 34 donors with and without lung cancer. Nuclear p53 protein was present in 0% of normal mucosas, 6.7% of squamous metaplasias, 29.5% of mild dysplasias, 26.9% of moderate dysplasias, 59.7% of severe dysplasias, 58.5% of carcinomas in situ, 67.5% of microinvasive carcinomas, and 79.5% of invasive tumors. These data indicate that (a) p53 protein accumulates in about 30% of the earliest recognized neoplastic lesions (i.e., mild dysplasia), (b) there is an increasing frequency of p53 protein accumulation starting with mild dysplasia, and (c) p53 protein accumulates infrequently in normal or metaplastic mucosa. In a subset of six patients whose most advanced lesion was carcinoma in situ without evidence of invasive cancer, p53 protein was detected in 0% of normal mucosas, 8.3% of squamous metaplasias, 37.5% of mild dysplasias, 12.5% of moderate dysplasias, 93.8% of severe dysplasias, and 55% of carcinoma in situ lesions. These data show clearly that p53 alterations can occur before invasion and suggest that the frequency is similar to that observed in the full series. Since two-thirds or more of lung cancers have p53 alterations, the timing and frequency of p53 protein accumulation make the p53 tumor suppressor gene an attractive marker for early diagnosis and evaluation of chemoprevention agents. JF - Cancer research AU - Bennett, W P AU - Colby, T V AU - Travis, W D AU - Borkowski, A AU - Jones, R T AU - Lane, D P AU - Metcalf, R A AU - Samet, J M AU - Takeshima, Y AU - Gu, J R AD - Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1993/10/15/ PY - 1993 DA - 1993 Oct 15 SP - 4817 EP - 4822 VL - 53 IS - 20 SN - 0008-5472, 0008-5472 KW - Biomarkers, Tumor KW - 0 KW - Tumor Suppressor Protein p53 KW - Index Medicus KW - Neoplasm Invasiveness KW - Cell Nucleus -- ultrastructure KW - Humans KW - Mucous Membrane -- pathology KW - Immunohistochemistry KW - Carcinoma in Situ -- pathology KW - Carcinoma in Situ -- classification KW - Carcinoma, Squamous Cell -- metabolism KW - Precancerous Conditions -- metabolism KW - Lung Neoplasms -- classification KW - Tumor Suppressor Protein p53 -- metabolism KW - Precancerous Conditions -- pathology KW - Tumor Suppressor Protein p53 -- analysis KW - Precancerous Conditions -- classification KW - Carcinoma, Squamous Cell -- pathology KW - Biomarkers, Tumor -- analysis KW - Carcinoma in Situ -- metabolism KW - Carcinoma, Squamous Cell -- classification KW - Lung Neoplasms -- metabolism KW - Lung Neoplasms -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75977951?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=p53+protein+accumulates+frequently+in+early+bronchial+neoplasia.&rft.au=Bennett%2C+W+P%3BColby%2C+T+V%3BTravis%2C+W+D%3BBorkowski%2C+A%3BJones%2C+R+T%3BLane%2C+D+P%3BMetcalf%2C+R+A%3BSamet%2C+J+M%3BTakeshima%2C+Y%3BGu%2C+J+R&rft.aulast=Bennett&rft.aufirst=W&rft.date=1993-10-15&rft.volume=53&rft.issue=20&rft.spage=4817&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 - 1993-11-09 N1 - Date created - 1993-11-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Data torturing. AN - 75924847; 8166792 JF - The New England journal of medicine AU - Mills, J L AD - National Institute of Child Health and Human Development, Bethesda, MD 20892. Y1 - 1993/10/14/ PY - 1993 DA - 1993 Oct 14 SP - 1196 EP - 1199 VL - 329 IS - 16 SN - 0028-4793, 0028-4793 KW - Abridged Index Medicus KW - Index Medicus KW - Probability KW - Research Design -- statistics & numerical data KW - Environmental Exposure -- statistics & numerical data KW - Humans KW - Confidence Intervals KW - Data Interpretation, Statistical UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75924847?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Data+torturing.&rft.au=Mills%2C+J+L&rft.aulast=Mills&rft.aufirst=J&rft.date=1993-10-14&rft.volume=329&rft.issue=16&rft.spage=1196&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 - 1993-10-21 N1 - Date created - 1993-10-21 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: N Engl J Med. 1994 Mar 24;330(12):862 [8114844] N Engl J Med. 1994 Mar 24;330(12):861-2 [8114843] N Engl J Med. 1994 Mar 24;330(12):861 [8114842] N Engl J Med. 1994 Mar 24;330(12):861; author reply 862 [8166833] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Drosophila Rrp1 complements E. coli xth nfo mutants: protection against both oxidative and alkylation-induced DNA damage. AN - 19795583; 8731039 AB - Drosophila Rrp1 protein has four tightly associated enzymatic activities: DNA strand transfer, ssDNA renaturation, dsDNA 3'-exonuclease and apurinic/apyrimidinic (AP) endonuclease. The carboxy-terminal region of Rrp1 is homologous to Escherichia coli exonuclease III and several eukaryotic AP endonucleases. All members of this protein family cleave abasic sites. Rrp1 protein was expressed under the control of the E. coli RNA polymerase tac promoter (pRrp1-tac) in two repair deficient E. coli strains (BW528 and LG101) lacking both exonuclease III (xth) and endonuclease IV (nfo). Rrp1 confers resistance to killing by oxidative, antitumor and alkylating agents that damage DNA (hydrogen peroxide, t-butylhydroperoxide, bleomycin, methyl methanesulfonate, and mitomycin C). Complementation of the repair deficiency by Rrp1 provides up to a two log increase in survival and requires the C-terminal nuclease region of Rrp1, but not its N-terminal region. The AP endonuclease activity in extracts from the repair deficient strain LG101 is increased up to 12-fold when the strain contains pRrp1-tac. These results indicate that pRrp1-tac directs the synthesis of active enzyme, and that the nuclease activities of Rrp1 are likely to be the cause of the increased resistance to DNA damage of the mutant cells. Images JF - Nucleic Acids Research AU - Gu, L AU - Huang, S M AU - Sander, M AD - Laboratory of Genetics D3-04, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1993/10/11/ PY - 1993 DA - 1993 Oct 11 SP - 4788 EP - 4795 PB - Oxford University Press, Oxford Journals, Great Clarendon Street VL - 21 IS - 20 SN - 0305-1048, 0305-1048 KW - Microbiology Abstracts B: Bacteriology; Entomology Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - Alkylating agents KW - Methyl methanesulfonate KW - Renaturation KW - t-Butylhydroperoxide KW - Survival KW - Nuclease KW - protein families KW - Mitomycin C KW - Bleomycin KW - Promoters KW - DNA damage KW - DNA-directed RNA polymerase KW - Hydrogen peroxide KW - Escherichia coli KW - exonuclease KW - AP endonuclease KW - Enzymatic activity KW - Endonuclease KW - Drosophila KW - J 02310:Genetics & Taxonomy KW - N 14820:DNA Metabolism & Structure KW - Z 05360:Genetics and Evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19795583?accountid=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=Nucleic+Acids+Research&rft.atitle=Drosophila+Rrp1+complements+E.+coli+xth+nfo+mutants%3A+protection+against+both+oxidative+and+alkylation-induced+DNA+damage.&rft.au=Gu%2C+L%3BHuang%2C+S+M%3BSander%2C+M&rft.aulast=Gu&rft.aufirst=L&rft.date=1993-10-11&rft.volume=21&rft.issue=20&rft.spage=4788&rft.isbn=&rft.btitle=&rft.title=Nucleic+Acids+Research&rft.issn=03051048&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2008-12-01 N1 - Last updated - 2015-03-27 N1 - SubjectsTermNotLitGenreText - Methyl methanesulfonate; Alkylating agents; Renaturation; protein families; Nuclease; Survival; t-Butylhydroperoxide; Mitomycin C; Bleomycin; DNA damage; Promoters; DNA-directed RNA polymerase; Hydrogen peroxide; exonuclease; AP endonuclease; Enzymatic activity; Endonuclease; Escherichia coli; Drosophila ER - TY - JOUR T1 - Administration of pentosan polysulfate to patients with human immunodeficiency virus-associated Kaposi's sarcoma. AN - 76002946; 7692072 AB - Neovascularization induced by basic fibroblast growth factor (basic FGF) or FGF-like cytokines is thought to play a substantial role in the pathogenesis of human immunodeficiency virus (HIV)-associated Kaposi's sarcoma. Pentosan polysulfate has been shown to inhibit basic FGF and FGF-like dependent tumor growth both in vitro and in vivo. Moreover, it has been found to inhibit the growth of Kaposi's sarcoma-derived spindle cells in vitro. These observations suggested that pentosan polysulfate might be worth exploring as a potential agent for the treatment of Kaposi's sarcoma. The purpose of this phase 1 clinical trial was to determine the maximum tolerated dose of pentosan polysulfate in patients with HIV-associated Kaposi's sarcoma and whether or not this compound had activity against this neoplasm. Sixteen HIV-seropositive patients with Kaposi's sarcoma received pentosan polysulfate via continuous venous infusion for 3-6 weeks and then received a subcutaneous dose three times per week. Three different doses of pentosan polysulfate were administered: 2 mg/kg per day by infusion followed by 2 mg/kg per dose given subcutaneously (six patients), 3 mg/kg per day by infusion followed by 3 mg/kg per dose given subcutaneously (five patients), and 4 mg/kg per day by infusion followed by 4 mg/kg per dose given subcutaneously (five patients). Five of the 16 patients in the study also received injections of 1 mg of pentosan polysulfate into two different lesions two times a week for 3 weeks, followed by intralesional therapy once weekly. After receiving pentosan polysulfate for 6 weeks, patients were administered 100 mg zidovudine (AZT) orally every 4 hours in conjunction with pentosan polysulfate. The maximally tolerated dose of pentosan polysulfate given by continuous venous infusion was found to be 3 mg/kg per day. No patient had an objective clinical antitumor response to either systemic or intralesional pentosan polysulfate administration; however, three patients had stable Kaposi's sarcoma for 3-27 weeks. No statistically significant effect on CD4 cells or serum HIV p24 antigen was noted during pentosan polysulfate administration. Dose-limiting toxic effects were characterized by anticoagulation and thrombocytopenia and were reversible. Pentosan polysulfate was well tolerated in this patient population. However, no objective tumor response or evidence of anti-HIV activity was noted; therefore, no claim of activity can be made in this trial. Continued investigation into the use of angiogenesis inhibitors with improved activity and toxicity profiles or different mechanisms of action is warranted. JF - Journal of the National Cancer Institute AU - Pluda, J M AU - Shay, L E AU - Foli, A AU - Tannenbaum, S AU - Cohen, P J AU - Goldspiel, B R AU - Adamo, D AU - Cooper, M R AU - Broder, S AU - Yarchoan, R AD - Medicine Branch, National Cancer Institute, National Institutes of Health, Bethesda, Md. Y1 - 1993/10/06/ PY - 1993 DA - 1993 Oct 06 SP - 1585 EP - 1592 VL - 85 IS - 19 SN - 0027-8874, 0027-8874 KW - Pentosan Sulfuric Polyester KW - 37300-21-3 KW - Index Medicus KW - AIDS/HIV KW - HIV -- drug effects KW - Humans KW - Adult KW - CD4-Positive T-Lymphocytes -- drug effects KW - Sarcoma, Kaposi -- drug therapy KW - Pentosan Sulfuric Polyester -- therapeutic use KW - Pentosan Sulfuric Polyester -- pharmacokinetics KW - Pentosan Sulfuric Polyester -- adverse effects KW - HIV Seropositivity -- complications KW - Sarcoma, Kaposi -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76002946?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+National+Cancer+Institute&rft.atitle=Administration+of+pentosan+polysulfate+to+patients+with+human+immunodeficiency+virus-associated+Kaposi%27s+sarcoma.&rft.au=Pluda%2C+J+M%3BShay%2C+L+E%3BFoli%2C+A%3BTannenbaum%2C+S%3BCohen%2C+P+J%3BGoldspiel%2C+B+R%3BAdamo%2C+D%3BCooper%2C+M+R%3BBroder%2C+S%3BYarchoan%2C+R&rft.aulast=Pluda&rft.aufirst=J&rft.date=1993-10-06&rft.volume=85&rft.issue=19&rft.spage=1585&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+National+Cancer+Institute&rft.issn=00278874&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-11-10 N1 - Date created - 1993-11-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular biology of human xenobiotic-metabolizing cytochromes P450: role of vaccinia virus cDNA expression in evaluating catalytic function. AN - 76062102; 8236283 AB - Mammalian xenobiotic-metabolizing cytochromes P450s are membrane-bound enzymes that use O2 and electrons from NADPH to oxidize their substrates. For most chemical substrates, stable metabolites are produced that are destined for further metabolism and elimination from the cell. These enzymes are also capable of metabolically-converting promutagens and procarcinogens to their active proximate metabolites that can kill and transform cells. The xenobiotic-metabolizing P450s reside with three distinct families of the large P450 super-family. To study the catalytic activities of P450s, particularly human P450s that cannot be easily purified, a cDNA expression system was developed using vaccinia virus. P450 cDNAs incorporated into this lytic virus are efficiently expressed into catalytically-active enzymes that can be used to determine substrate specificities of specific human P450s forms. Activation of the hepatocarcinogen aflatoxin B1 was determined using a series of vaccinia virus-expressed P450s establishing that it is metabolically-activated to a DnA-binding derivative by several human P450 forms, albeit to differing extents. JF - Toxicology AU - Gonzalez, F J AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institute of Health, Bethesda, MD 20892. Y1 - 1993/10/05/ PY - 1993 DA - 1993 Oct 05 SP - 77 EP - 88 VL - 82 IS - 1-3 SN - 0300-483X, 0300-483X KW - DNA, Complementary KW - 0 KW - Recombinant Proteins KW - Xenobiotics KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Index Medicus KW - Animals KW - Recombinant Proteins -- metabolism KW - Humans KW - Recombinant Proteins -- genetics KW - Cloning, Molecular KW - Vaccinia virus -- genetics KW - Cytochrome P-450 Enzyme System -- genetics KW - Xenobiotics -- metabolism KW - Cytochrome P-450 Enzyme System -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76062102?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Molecular+biology+of+human+xenobiotic-metabolizing+cytochromes+P450%3A+role+of+vaccinia+virus+cDNA+expression+in+evaluating+catalytic+function.&rft.au=Gonzalez%2C+F+J&rft.aulast=Gonzalez&rft.aufirst=F&rft.date=1993-10-05&rft.volume=82&rft.issue=1-3&rft.spage=77&rft.isbn=&rft.btitle=&rft.title=Toxicology&rft.issn=0300483X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-12-09 N1 - Date created - 1993-12-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Association of anti-58 kDa endoplasmic reticulum antibodies with halothane hepatitis. AN - 76010398; 8216376 AB - We recently showed that when rats were administered the inhalation anesthetic halothane, a 58 kDa liver endoplasmic reticulum protein became covalently trifluoroacetylated by the trifluoroacetyl chloride metabolite of halothane. Although the 58 kDa protein showed 99% identity to that of the deduced amino acid sequence of a cDNA reported to correspond to phosphatidylinositol-specific phospholipase C-alpha, it did not have phosphatidylinositol-specific phospholipase C activity. It was concluded that the reported cDNA of phosphatidylinositol-specific phospholipase C-alpha actually encoded for the 58 kDa endoplasmic reticulum protein of unknown function. Other researchers have come to the same conclusion and have shown that the 58 kDa protein has protein disulfide-isomerase and protease activities. We now report that patients with halothane hepatitis have serum antibodies that react with both purified trifluoroacetylated and native rat liver 58 kDa proteins. These results suggest that when patients are exposed to halothane a human liver orthologue of the rat liver trifluoroacetylated-58 kDa protein is formed. In certain patients, this protein may become immunogenic and lead to the formation of specific antibodies and or specific T-cells, which may react with both trifluoroacetylated and native 58 kDa proteins, and ultimately be responsible, at least in part, for the hepatitis caused by halothane. JF - Biochemical pharmacology AU - Martin, J L AU - Reed, G F AU - Pohl, L R AD - Laboratory of Chemical Pharmacology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/10/05/ PY - 1993 DA - 1993 Oct 05 SP - 1247 EP - 1250 VL - 46 IS - 7 SN - 0006-2952, 0006-2952 KW - Antibodies KW - 0 KW - Fluoroacetates KW - Proteins KW - Halothane KW - UQT9G45D1P KW - Index Medicus KW - Rats KW - Antigen-Antibody Reactions KW - Animals KW - Proteins -- isolation & purification KW - Humans KW - Microsomes, Liver -- immunology KW - Proteins -- immunology KW - Antibodies -- immunology KW - Halothane -- adverse effects KW - Antibodies -- analysis KW - Endoplasmic Reticulum -- immunology KW - Chemical and Drug Induced Liver Injury -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76010398?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+pharmacology&rft.atitle=Association+of+anti-58+kDa+endoplasmic+reticulum+antibodies+with+halothane+hepatitis.&rft.au=Martin%2C+J+L%3BReed%2C+G+F%3BPohl%2C+L+R&rft.aulast=Martin&rft.aufirst=J&rft.date=1993-10-05&rft.volume=46&rft.issue=7&rft.spage=1247&rft.isbn=&rft.btitle=&rft.title=Biochemical+pharmacology&rft.issn=00062952&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-11-23 N1 - Date created - 1993-11-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Plasmid addiction genes of bacteriophage P1: doc, which causes cell death on curing of prophage, and phd, which prevents host death when prophage is retained. AN - 76000620; 8411153 AB - P1 lysogens of Escherichia coli carry the prophage as a stable low copy number plasmid. The frequency with which viable cells cured of prophage are produced is about 10(-5) per cell per generation. Here we show that a significant part of this remarkable stability can be attributed to a plasmid-encoded mechanism that causes death of cells that have lost P1. In other words, the lysogenic cells appear to be addicted to the presence of the prophage. The plasmid withdrawal response depends on a gene named doc (death on curing), encoding a 126 amino acid protein. Expression of doc is not SOS-inducing and killing by Doc is recA-independent. In cells that retain P1 the killing is prevented by the product of a gene named phd (prevent host death), encoding a 73 amino acid protein. The genes phd and doc have been cloned and expressed from a 0.7 kb segment of P1 DNA. The two genes constitute an operon and the synthesis of Doc appears to be translationally coupled to that of Phd. Homologs of the P1 addiction genes are found elsewhere, but phd and doc are unrelated to previously described genes of other plasmids that also cause an apparent increase in plasmid stability by post-segregational killing. JF - Journal of molecular biology AU - Lehnherr, H AU - Maguin, E AU - Jafri, S AU - Yarmolinsky, M B AD - Laboratory of Biochemistry, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/10/05/ PY - 1993 DA - 1993 Oct 05 SP - 414 EP - 428 VL - 233 IS - 3 SN - 0022-2836, 0022-2836 KW - doc KW - phd KW - DNA, Viral KW - 0 KW - Doc protein, Enterobacteria phage P1 KW - Phd protein, Enterobacteria phage P1 KW - Viral Proteins KW - Index Medicus KW - Base Sequence KW - SOS Response (Genetics) KW - Sequence Homology, Nucleic Acid KW - Restriction Mapping KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Sequence Analysis, DNA KW - Virus Integration -- genetics KW - DNA, Viral -- genetics KW - Mutagenesis, Insertional KW - Sequence Deletion KW - Cloning, Molecular KW - Viral Proteins -- genetics KW - Plasmids -- genetics KW - Genes, Viral -- genetics KW - Proviruses -- genetics KW - Bacteriophage P1 -- genetics KW - Escherichia coli -- growth & development UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76000620?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Plasmid+addiction+genes+of+bacteriophage+P1%3A+doc%2C+which+causes+cell+death+on+curing+of+prophage%2C+and+phd%2C+which+prevents+host+death+when+prophage+is+retained.&rft.au=Lehnherr%2C+H%3BMaguin%2C+E%3BJafri%2C+S%3BYarmolinsky%2C+M+B&rft.aulast=Lehnherr&rft.aufirst=H&rft.date=1993-10-05&rft.volume=233&rft.issue=3&rft.spage=414&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 - 1993-11-12 N1 - Date created - 1993-11-12 N1 - Date revised - 2017-01-13 N1 - Gene symbol - doc; phd N1 - Genetic sequence - M95666; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Auditory spatial tuning of cortical neurons is sharpened in cats with early blindness. AN - 85237794; pmid-8283227 AB - 1. The specificity for the location of a sound source in azimuth was measured in single neurons of the anterior ectosylvian (AE) region of the cat's cortex, which includes the anterior auditory field (AAF) and the anterior ectosylvian auditory field (AEA). 2. The influence of visual experience on auditory spatial tuning of these neurons was determined by comparing responses in cats with binocular deprivation from birth with those in normal control cats. 3. Spatial tuning was measured under near free-field conditions by presenting broadband sounds through a speaker in seven different azimuthal locations, from -60 to +60 degree at 20 degree intervals. Elevation was constant at the cats' ears. 4. In normal cats, a little over one-half of the neurons in the AE region (82/146 = 56%) showed some degree of azimuthal spatial tuning, as defined by at least a 2:1 ratio of responses between best and worst location. The rest (44%) were omnidirectional. 5. In binocularly deprived cats, a significantly higher proportion (70/82 = 86%) of the neurons in the AE region were spatially tuned. Only 14% were omnidirectional. Median spatial tuning width was significantly sharper than in normal cats. 6. We conclude that visual deprivation from birth induces intermodal changes that enhance the response specificity of neurons in the auditory cortex. These modifications may constitute the neural basis of behavioral compensation for early blindness. JF - Journal of Neurophysiology AU - Korte, M AU - Rauschecker, J P AD - Laboratory of Neurophysiology, National Institute of Mental Health, Poolesville, Maryland 20837. PY - 1993 SP - 1717 EP - 1721 VL - 70 IS - 4 SN - 0022-3077, 0022-3077 KW - Auditory Cortex KW - Sound Localization KW - Neurons KW - Cats KW - Animal KW - Space Perception KW - Blindness KW - Electrophysiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85237794?accountid=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+Neurophysiology&rft.atitle=Auditory+spatial+tuning+of+cortical+neurons+is+sharpened+in+cats+with+early+blindness.&rft.au=Korte%2C+M%3BRauschecker%2C+J+P&rft.aulast=Korte&rft.aufirst=M&rft.date=1993-10-01&rft.volume=70&rft.issue=4&rft.spage=1717&rft.isbn=&rft.btitle=&rft.title=Journal+of+Neurophysiology&rft.issn=00223077&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - A perspective on nonmutagenic mechanisms in carcinogenesis. AN - 76262512; 8143623 AB - Although there is compelling evidence for multiple mutagenic events in the induction of cancers, there is also substantial evidence in support of nonmutagenic mechanisms. It is proposed that the genetic basis of noninduced or spontaneous tumors, as well as cancers induced by nonmutagens, involves heritable changes in the regulation of gene expression. JF - Environmental health perspectives AU - Tennant, R W AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1993/10// PY - 1993 DA - October 1993 SP - 231 EP - 236 VL - 101 Suppl 3 SN - 0091-6765, 0091-6765 KW - Index Medicus KW - Animals KW - Male KW - Female KW - Mutagenesis KW - Neoplasms -- genetics KW - Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76262512?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+perspective+on+nonmutagenic+mechanisms+in+carcinogenesis.&rft.au=Tennant%2C+R+W&rft.aulast=Tennant&rft.aufirst=R&rft.date=1993-10-01&rft.volume=101+Suppl+3&rft.issue=&rft.spage=231&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 - 1994-05-05 N1 - Date created - 1994-05-05 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1980 Apr;77(4):1763-7 [6929519] Toxicol Pathol. 1992;20(1):52-60 [1411131] J Natl Cancer Inst. 1985 Nov;75(5):975-84 [3863995] Carcinogenesis. 1986 Oct;7(10):1701-7 [3757172] Science. 1987 Sep 11;237(4820):1309-16 [3629242] Nature. 1989 Jun 22;339(6226):593-7 [2733791] Cancer Res. 1989 Oct 15;49(20):5489-96 [2676144] Cell. 1990 Jun 1;61(5):759-67 [2188735] Science. 1990 Aug 31;249(4972):970-1 [2136249] Nature. 1990 Oct 18;347(6294):645-50 [2129546] Cell. 1991 Jan 25;64(2):235-48 [1988146] Mutat Res. 1991 May;257(3):229-306 [1707500] Cancer Res. 1991 Jun 1;51(11):2751-61 [2032214] Science. 1991 Nov 22;254(5035):1131-8 [1957166] Science. 1991 Nov 22;254(5035):1138-46 [1659741] Science. 1991 Nov 22;254(5035):1153-60 [1957167] Cancer Res. 1991 Dec 15;51(24):6493-505 [1742722] Mol Carcinog. 1991;4(6):420-40 [1793481] Nature. 1981 Jan 29;289(5796):353-7 [6258076] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Functional toxicology: a new approach to detect biologically active xenobiotics. AN - 76239144; 8119246 AB - The pervasiveness of chemicals in the environment with estrogenic activity and other biological functions recommends the development of new approaches to monitor and study them. Chemicals can be screened for activity in vitro using a panel of human or animal cells that have been transfected with a specific receptor and reporter gene; for example, the estrogen receptor. By using a variety of different receptors, the screening of xenobiotics for biological functions can be broad. Chemicals could then be classified by their function in vitro which, in some cases, may be a useful guide for toxicological studies. JF - Environmental health perspectives AU - McLachlan, J A AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1993/10// PY - 1993 DA - October 1993 SP - 386 EP - 387 VL - 101 IS - 5 SN - 0091-6765, 0091-6765 KW - Estrogens KW - 0 KW - Xenobiotics KW - Diethylstilbestrol KW - 731DCA35BT KW - Index Medicus KW - Molecular Structure KW - Animals KW - Diethylstilbestrol -- adverse effects KW - Humans KW - Estrogens -- adverse effects KW - Drug Evaluation, Preclinical KW - Male KW - Female KW - Animals, Wild KW - Environmental Health KW - Xenobiotics -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76239144?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Functional+toxicology%3A+a+new+approach+to+detect+biologically+active+xenobiotics.&rft.au=McLachlan%2C+J+A&rft.aulast=McLachlan&rft.aufirst=J&rft.date=1993-10-01&rft.volume=101&rft.issue=5&rft.spage=386&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 - 1994-04-07 N1 - Date created - 1994-04-07 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Teratog Carcinog Mutagen. 1987;7(4):377-89 [2888216] Mol Pharmacol. 1988 Jan;33(1):120-6 [3122017] Environ Health Perspect. 1991 May;92:167-73 [1935846] Endocrinology. 1993 Jun;132(6):2279-86 [8504731] J Natl Cancer Inst. 1993 Apr 21;85(8):648-52 [8468722] Lancet. 1993 May 29;341(8857):1392-5 [8098802] BMJ. 1992 Sep 12;305(6854):609-13 [1393072] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Directed migration of transplanted glial cells toward a spinal cord demyelinating lesion. AN - 76238613; 8116474 AB - To investigate the migration of transplanted glial cells in normal adult mice with a focal demyelinating lesion, we have used A2G mice which have the autosomal dominant Mx-1 allele as donor. Mx-1 protein expression is inducible by interferon and is detected in a dotted pattern in the nucleus of A2G cells. A/J mice were used as recipient animals as they express the same major histocompatibility antigens as A2G but cannot express the Mx-1 protein. An acute demyelinating lesion was produced in the A/J spinal cord by intraspinal injection of lysolecithin. Mixed glial cultures derived from newborn A2G brain were treated with alpha/beta interferon for 24 hr. These Mx-1 expressing glial cells were then transplanted two intervertebral spaces away from the demyelinating lesion. The fate of the grafted cells was followed over the next 13 days, during which the induced Mx-1 protein can still be detected by immunocytochemistry. Grafted cells were found between the transplantation site and the lesion at 24 hr and some of the Mx-1+ cells reached the lesion at 4 days. The majority of the Mx-1+ migrating cells expressed GFAP and were located in the myelinated white matter and around the blood vessels. Scattered MBP+, Mx-1+ cells were detected in the lesion indicating that some of the transplanted cells may participate in the repair process. The Mx-1 is a useful marker to follow the migration events in the days after grafting and to determined what factors may attract transplanted cells toward a demyelinating lesion. JF - International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience AU - Gout, O AU - Dubois-Dalcq, M AD - Laboratory of Viral and Molecular Pathogenesis, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892. Y1 - 1993/10// PY - 1993 DA - October 1993 SP - 613 EP - 623 VL - 11 IS - 5 SN - 0736-5748, 0736-5748 KW - Glial Fibrillary Acidic Protein KW - 0 KW - Lysophosphatidylcholines KW - Mx1 protein, mouse KW - Myxovirus Resistance Proteins KW - Proteins KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - Index Medicus KW - Protein Biosynthesis KW - Mice, Inbred Strains KW - Animals KW - Glial Fibrillary Acidic Protein -- immunology KW - Cell Movement -- physiology KW - Glial Fibrillary Acidic Protein -- metabolism KW - Mice KW - Immunohistochemistry KW - Animals, Newborn -- physiology KW - Proteins -- immunology KW - Spinal Cord -- physiology KW - Brain Tissue Transplantation -- physiology KW - Neuroglia -- physiology KW - Demyelinating Diseases -- chemically induced KW - Spinal Cord -- cytology KW - Demyelinating Diseases -- physiopathology KW - Cell Transplantation -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76238613?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+developmental+neuroscience+%3A+the+official+journal+of+the+International+Society+for+Developmental+Neuroscience&rft.atitle=Directed+migration+of+transplanted+glial+cells+toward+a+spinal+cord+demyelinating+lesion.&rft.au=Gout%2C+O%3BDubois-Dalcq%2C+M&rft.aulast=Gout&rft.aufirst=O&rft.date=1993-10-01&rft.volume=11&rft.issue=5&rft.spage=613&rft.isbn=&rft.btitle=&rft.title=International+journal+of+developmental+neuroscience+%3A+the+official+journal+of+the+International+Society+for+Developmental+Neuroscience&rft.issn=07365748&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-03-31 N1 - Date created - 1994-03-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Predicting chemical carcinogenesis in rodents. AN - 76238233; 8119256 JF - Environmental health perspectives AU - Wachsman, J T AU - Bristol, D W AU - Spalding, J AU - Shelby, M AU - Tennant, R W AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1993/10// PY - 1993 DA - October 1993 SP - 444 EP - 445 VL - 101 IS - 5 SN - 0091-6765, 0091-6765 KW - Index Medicus KW - Animals KW - Humans KW - Biological Assay KW - Predictive Value of Tests KW - Carcinogenicity Tests -- methods KW - Rodentia UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76238233?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Predicting+chemical+carcinogenesis+in+rodents.&rft.au=Wachsman%2C+J+T%3BBristol%2C+D+W%3BSpalding%2C+J%3BShelby%2C+M%3BTennant%2C+R+W&rft.aulast=Wachsman&rft.aufirst=J&rft.date=1993-10-01&rft.volume=101&rft.issue=5&rft.spage=444&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 - 1994-04-07 N1 - Date created - 1994-04-07 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Mutagenesis. 1992 Mar;7(2):91-4 [1579072] Mutagenesis. 1991 Sep;6(5):423-5 [1795649] Hum Exp Toxicol. 1991 Jul;10(4):261-73 [1679649] Mutagenesis. 1990 Sep;5(5):433-5 [2263201] Mutagenesis. 1990 Sep;5(5):425-32 [2263200] Mutagenesis. 1990 Jul;5(4):305-6 [2398815] Mutagenesis. 1990 Jan;5(1):3-14 [2184307] Mutagenesis. 1991 Nov;6(6):507-14 [1800899] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - 3-Nitropropionic acid is an indirect excitotoxin to cultured cerebellar granule neurons. AN - 76170975; 7904944 AB - The ability of N-methyl-D-aspartate (NMDA) receptor agonists and antagonists to modify 3-nitropropionic acid toxicity was studied in cultured rat cerebellar granule neurons. Exposure of these neurons to 3-nitropropionic acid resulted in a concentration and time-dependent neurotoxicity. In contrast to glutamate toxicity, 3-nitropropionic acid toxicity was potentiated by preexposure to subtoxic concentrations of NMDA. Presumably, the 3-nitropropionic acid-induced energy depletion relieved the voltage-dependent Mg2+ block of the NMDA receptor and induced vulnerability to subtoxic concentrations of NMDA receptor agonists. MK-801 and 2-amino-5-phosphonovaleric acid (APV) delayed but did not prevent 3-nitropropionic acid toxicity, indicating that prolonged exposure to 3-nitropropionic acid ultimately resulted in histotoxic neuronal death. We conclude that there are at least two distinct mechanisms of 3-nitropropionic acid toxicity of cerebellar granule neurons, one indirectly involving NMDA receptor-mediated excitotoxicity and one that is NMDA receptor-independent. JF - European journal of pharmacology AU - Weller, M AU - Paul, S M AD - Section on Molecular Pharmacology, National Institute of Mental Health, Bethesda, MD 20892. Y1 - 1993/10/01/ PY - 1993 DA - 1993 Oct 01 SP - 223 EP - 228 VL - 248 IS - 3 SN - 0014-2999, 0014-2999 KW - Glutamates KW - 0 KW - Neurotoxins KW - Nitro Compounds KW - Propionates KW - Receptors, N-Methyl-D-Aspartate KW - Glutamic Acid KW - 3KX376GY7L KW - Dizocilpine Maleate KW - 6LR8C1B66Q KW - 2-Amino-5-phosphonovalerate KW - 76726-92-6 KW - 3-nitropropionic acid KW - QY4L0FOX0D KW - Index Medicus KW - Animals KW - Electrophysiology KW - Dizocilpine Maleate -- pharmacology KW - Rats KW - Rats, Sprague-Dawley KW - 2-Amino-5-phosphonovalerate -- pharmacology KW - Receptors, N-Methyl-D-Aspartate -- drug effects KW - Cells, Cultured KW - Receptors, N-Methyl-D-Aspartate -- antagonists & inhibitors KW - Cytoplasmic Granules -- drug effects KW - Glutamates -- toxicity KW - Cerebellum -- cytology KW - Propionates -- toxicity KW - Neurons -- drug effects KW - Cerebellum -- drug effects KW - Neurotoxins -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76170975?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+pharmacology&rft.atitle=3-Nitropropionic+acid+is+an+indirect+excitotoxin+to+cultured+cerebellar+granule+neurons.&rft.au=Weller%2C+M%3BPaul%2C+S+M&rft.aulast=Weller&rft.aufirst=M&rft.date=1993-10-01&rft.volume=248&rft.issue=3&rft.spage=223&rft.isbn=&rft.btitle=&rft.title=European+journal+of+pharmacology&rft.issn=00142999&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-03-02 N1 - Date created - 1994-03-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Measurement of aspartate carbamoyltransferase activity by high performance liquid chromatography. AN - 76167114; 8292811 AB - We developed an assay which permits measurement of aspartate carbamoyltransferase (ACTase) activity. Cytosol from human peripheral blood mononuclear cells was used as the enzyme source. Using [14C]carbamoyl phosphate as the radiolabeled substrate, the formation of [14C]carbamoyl aspartate was quantitated by high performance liquid chromatography (HPLC) using an anion-exchange column with UV detection at 200-280 nm and an on-line liquid scintillation detector. A gradient method from an initially low concentration of ammonium phosphate, 1 mM (pH 3.0), to a higher concentration, 38 mM (pH 4.5), was used. The apparent Km values of carbamoyl phosphate and aspartate were 58 microM and 1.9 mM, respectively. ACTase inhibition by N-(phosphonacetyl)-l-aspartate (PALA) was consistent with a competitive model with respect to carbamoyl phosphate. The assay conditions were optimized to permit measurement of ACTase activity prior to and following therapy with PALA; ACTase was inhibited in a dose-dependent manner. This HPLC method permits direct quantitation of both the product of the reaction and the initial integrity of the substrate, [14C]carbamoyl phosphate, which is unstable in aqueous solutions. JF - Anti-cancer drugs AU - Grem, J L AU - Drake, J C AU - Allegra, C J AD - NCI-Navy Medical Oncology Program, National Naval Medical Center, Bethesda, MD 20889-5105. Y1 - 1993/10// PY - 1993 DA - October 1993 SP - 545 EP - 554 VL - 4 IS - 5 SN - 0959-4973, 0959-4973 KW - Antimetabolites, Antineoplastic KW - 0 KW - Aspartic Acid KW - 30KYC7MIAI KW - sparfosic acid KW - 78QVZ7RG8L KW - Aspartate Carbamoyltransferase KW - EC 2.1.3.2 KW - Phosphonoacetic Acid KW - N919E46723 KW - Index Medicus KW - Leukocytes, Mononuclear -- enzymology KW - Aspartic Acid -- pharmacology KW - Erythrocytes -- enzymology KW - Aspartic Acid -- analogs & derivatives KW - Enzyme Activation KW - Humans KW - Cytosol -- enzymology KW - Phosphonoacetic Acid -- analogs & derivatives KW - Phosphonoacetic Acid -- pharmacology KW - Hydrolysis KW - Chromatography, High Pressure Liquid KW - Antimetabolites, Antineoplastic -- pharmacology KW - Aspartate Carbamoyltransferase -- blood KW - Aspartate Carbamoyltransferase -- antagonists & inhibitors KW - Aspartate Carbamoyltransferase -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76167114?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Measurement+of+aspartate+carbamoyltransferase+activity+by+high+performance+liquid+chromatography.&rft.au=Grem%2C+J+L%3BDrake%2C+J+C%3BAllegra%2C+C+J&rft.aulast=Grem&rft.aufirst=J&rft.date=1993-10-01&rft.volume=4&rft.issue=5&rft.spage=545&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 - 1994-03-01 N1 - Date created - 1994-03-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evidence for a new variant CYP2D6 allele CYP2D6J in a Japanese population associated with lower in vivo rates of sparteine metabolism. AN - 76163106; 8287064 AB - A group of Japanese subjects were phenotyped for CYP2D6 activity by administration of sparteine and determination of urine metabolic ratios (MR). The CYP2D6 alleles from two subjects having a high MR, characteristic of slower rates of sparteine metabolism, were cloned in lambda EMBL3 and subjected to sequence analysis. One individual possessed a CYP2D6B allele, typically found in Caucasians, that is inactive due to an altered 3' splice recognition site and other potentially disruptive mutations. The second allele from this individual was identical to the wild type normal Caucasian CYP2D6 allele except for C188T and G4268C base differences in exons 1 and 9, respectively, that result in P34S and S486T amino acid substitutions. This allele was designated CYP2D6J. The second individual possessed two CYP2D6J alleles. PCR assays were performed to detect this allele and other alleles from a group of subjects exhibiting low rates of sparteine metabolism, i.e. with MRs > 1.5. Eleven CYP2D6J alleles were detected in 14 subjects exhibiting low rates of metabolism and including four individuals who were homozygous for this variant and had very low rates of sparteine metabolism (MRs > 2.5). In contrast, only two CYP2D6J alleles were found in 14 subjects having MRs of < 1.0. These data suggest that CYP2D6J encodes an enzyme having lower rates of sparteine metabolism. JF - Pharmacogenetics AU - Yokota, H AU - Tamura, S AU - Furuya, H AU - Kimura, S AU - Watanabe, M AU - Kanazawa, I AU - Kondo, I AU - Gonzalez, F J AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/10// PY - 1993 DA - October 1993 SP - 256 EP - 263 VL - 3 IS - 5 SN - 0960-314X, 0960-314X KW - CYP2D6 KW - CYP2D6J KW - DNA Primers KW - 0 KW - Sparteine KW - 298897D62S KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Mixed Function Oxygenases KW - EC 1.- KW - Cytochrome P-450 CYP2D6 KW - EC 1.14.14.1 KW - Index Medicus KW - Genetic Variation KW - DNA Primers -- genetics KW - Exons KW - Humans KW - Asian Continental Ancestry Group -- genetics KW - Genotype KW - Phenotype KW - Sparteine -- metabolism KW - Base Sequence KW - Molecular Sequence Data KW - Mutation KW - Japan KW - Alleles KW - Mixed Function Oxygenases -- metabolism KW - Cytochrome P-450 Enzyme System -- genetics KW - Cytochrome P-450 Enzyme System -- metabolism KW - Mixed Function Oxygenases -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76163106?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pharmacogenetics&rft.atitle=Evidence+for+a+new+variant+CYP2D6+allele+CYP2D6J+in+a+Japanese+population+associated+with+lower+in+vivo+rates+of+sparteine+metabolism.&rft.au=Yokota%2C+H%3BTamura%2C+S%3BFuruya%2C+H%3BKimura%2C+S%3BWatanabe%2C+M%3BKanazawa%2C+I%3BKondo%2C+I%3BGonzalez%2C+F+J&rft.aulast=Yokota&rft.aufirst=H&rft.date=1993-10-01&rft.volume=3&rft.issue=5&rft.spage=256&rft.isbn=&rft.btitle=&rft.title=Pharmacogenetics&rft.issn=0960314X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-02-22 N1 - Date created - 1994-02-22 N1 - Date revised - 2017-01-13 N1 - Gene symbol - CYP2D6; CYP2D6J N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - ICD-10 and proposed DSM-IV harmful use of alcohol/alcohol abuse and dependence, United States 1988: a nosological comparison. AN - 76160031; 8279672 AB - The purpose of this study was to compare ICD-10 and the proposed DSM-IV (options 1 and 2) diagnostic criteria for harmful use/abuse and dependence in a representative sample of the United States general population. Harmful use/abuse and dependence categories were contrasted in terms of prevalence and overlap. The prevalences of DSM-IV diagnoses of alcohol abuse and dependence combined were much greater than those for the corresponding ICD-10 diagnoses. Disaggregation of the harmful use/abuse and dependence diagnoses showed that the major discrepancy between the classification systems resided between harmful use and abuse categories. The prevalence of the harmful use of alcohol was nearly nonexistent in this general population sample. Reasons for this and other discrepancies are discussed in terms of the hypothesized severity of the harmful use criteria, differences in the number of diagnostic criteria and the content of the ICD-10 and DSM-IV dependence categories, the relationship between the harmful use/abuse and dependence categories, and the impact of the duration criterion. JF - Alcoholism, clinical and experimental research AU - Grant, B F AD - Division of Biometry and Epidemiology, National Institute on Alcohol Abuse and Alcoholism, Rockville, Maryland 20857. Y1 - 1993/10// PY - 1993 DA - October 1993 SP - 1093 EP - 1101 VL - 17 IS - 5 SN - 0145-6008, 0145-6008 KW - Index Medicus KW - Cross-Sectional Studies KW - Humans KW - Adult KW - Sampling Studies KW - Incidence KW - Aged KW - Middle Aged KW - Adolescent KW - United States -- epidemiology KW - Psychometrics KW - Male KW - Female KW - Alcoholism -- epidemiology KW - Alcoholism -- diagnosis KW - Alcoholism -- classification KW - Psychiatric Status Rating Scales -- statistics & numerical data KW - Alcoholism -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76160031?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=ICD-10+and+proposed+DSM-IV+harmful+use+of+alcohol%2Falcohol+abuse+and+dependence%2C+United+States+1988%3A+a+nosological+comparison.&rft.au=Grant%2C+B+F&rft.aulast=Grant&rft.aufirst=B&rft.date=1993-10-01&rft.volume=17&rft.issue=5&rft.spage=1093&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 - 1994-02-08 N1 - Date created - 1994-02-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Critique does not validate assumptions in the model on alpha 2u-globulin and renal carcinogenesis. AN - 76157754; 7506437 JF - Regulatory toxicology and pharmacology : RTP AU - Melnick, R L AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1993/10// PY - 1993 DA - October 1993 SP - 365 EP - 368 VL - 18 IS - 2 SN - 0273-2300, 0273-2300 KW - Alpha-Globulins KW - 0 KW - alpha 2u globulin KW - Index Medicus KW - Rats KW - Animals KW - Humans KW - Disease Models, Animal KW - Kidney Neoplasms -- pathology KW - Kidney Diseases -- pathology KW - Kidney Neoplasms -- chemically induced KW - Kidney Diseases -- chemically induced KW - Alpha-Globulins -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76157754?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Regulatory+toxicology+and+pharmacology+%3A+RTP&rft.atitle=Critique+does+not+validate+assumptions+in+the+model+on+alpha+2u-globulin+and+renal+carcinogenesis.&rft.au=Melnick%2C+R+L&rft.aulast=Melnick&rft.aufirst=R&rft.date=1993-10-01&rft.volume=18&rft.issue=2&rft.spage=365&rft.isbn=&rft.btitle=&rft.title=Regulatory+toxicology+and+pharmacology+%3A+RTP&rft.issn=02732300&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-02-08 N1 - Date created - 1994-02-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Alterations in large gut associated lymphatic tissues (LGALT) during experimental colorectal carcinogenesis. AN - 76156149; 8276429 AB - Alterations in large gut associated lymphatic tissues (LGALT) were studied histologically during 20-methylcholanthrene (MCA) induced colorectal carcinogenesis. Precancerous changes in LGALT included hyperplasia, hyperchromasia of lymphocytes and enlargement of lymphoid follicles. In addition, follicular invasion in muscular layer and cellular disorganization of diffuse lymphatic tissues were observed in neoplasia. Since, LGALT showed remarkable changes during carcinogenesis, this aspect may be considered during assessment of preneoplastic lesions, along with other histologic features of early neoplasia. JF - Indian journal of experimental biology AU - Baral, R AU - Chakraborty, A AU - Maity, P AD - Department of Cell Biology, Chittaranjan National Cancer Institute, Calcutta, India. Y1 - 1993/10// PY - 1993 DA - October 1993 SP - 793 EP - 796 VL - 31 IS - 10 SN - 0019-5189, 0019-5189 KW - Methylcholanthrene KW - 56-49-5 KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Methylcholanthrene -- toxicity KW - Precancerous Conditions -- pathology KW - Male KW - Intestine, Large -- pathology KW - Lymphoid Tissue -- pathology KW - Colorectal Neoplasms -- pathology KW - Colorectal Neoplasms -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76156149?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Indian+journal+of+experimental+biology&rft.atitle=Alterations+in+large+gut+associated+lymphatic+tissues+%28LGALT%29+during+experimental+colorectal+carcinogenesis.&rft.au=Baral%2C+R%3BChakraborty%2C+A%3BMaity%2C+P&rft.aulast=Baral&rft.aufirst=R&rft.date=1993-10-01&rft.volume=31&rft.issue=10&rft.spage=793&rft.isbn=&rft.btitle=&rft.title=Indian+journal+of+experimental+biology&rft.issn=00195189&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-02-07 N1 - Date created - 1994-02-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Neuroscience research: how has it contributed to our understanding of alcohol abuse and alcoholism? A review. AN - 76144001; 7506499 AB - Alcohol abuse and alcoholism are the greatest substance abuse problems in the United States today and contribute to numerous medical and social problems. To deal with many of these problems, an understanding of how alcohol acts on the brain is extremely important. Advances in neuroscience research have provided significant clues about where and how alcohol works on the brain. Alcohol clearly acts on membrane function, altering such processes as ion movements and neurotransmitter interactions with their receptors. Although these alcohol-induced alterations are presumed to relate to changes in behavior, this has not been clearly established. However, alcohol research is on the threshold of making a giant leap forward in our understanding the etiology of alcoholism. JF - Alcoholism, clinical and experimental research AU - Hunt, W A AD - Neurosciences and Behavioral Research Branch, National Institute on Alcohol Abuse and Alcoholism, Rockville, Maryland 20857-0001. Y1 - 1993/10// PY - 1993 DA - October 1993 SP - 1055 EP - 1065 VL - 17 IS - 5 SN - 0145-6008, 0145-6008 KW - Ion Channels KW - 0 KW - Neurotransmitter Agents KW - Index Medicus KW - Animals KW - Second Messenger Systems -- physiology KW - Neurotransmitter Agents -- physiology KW - Humans KW - Second Messenger Systems -- drug effects KW - Ion Channels -- drug effects KW - Research KW - Ion Channels -- physiology KW - Synaptic Membranes -- physiology KW - Synaptic Membranes -- drug effects KW - Brain -- physiopathology KW - Synaptic Transmission -- drug effects KW - Brain -- drug effects KW - Alcohol Drinking -- adverse effects KW - Synaptic Transmission -- physiology KW - Alcoholism -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76144001?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Neuroscience+research%3A+how+has+it+contributed+to+our+understanding+of+alcohol+abuse+and+alcoholism%3F+A+review.&rft.au=Hunt%2C+W+A&rft.aulast=Hunt&rft.aufirst=W&rft.date=1993-10-01&rft.volume=17&rft.issue=5&rft.spage=1055&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 - 1994-02-08 N1 - Date created - 1994-02-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of haloperidol, lithium, and valproate on phosphoinositide turnover in rat brain. AN - 76122246; 8265687 AB - The effects of acute, subacute, and chronic treatment with haloperidol, lithium, and valproate on inositol phosphate (IP) formation were examined. Acute treatment with haloperidol or the combination of haloperidol and lithium significantly reduced IP basal cortical levels. Subacute (three days) treatment with lithium decreased the IP basal level in the frontal cortex. Chronic treatment with haloperidol (14 and 28 days) caused a significant attenuation of carbachol-sensitive IP accumulation in the frontal cortex and striatum and a significant decrease in norepinephrine (NE)-induced IP formation in the frontal cortex (14 and 28 days) and striatum (28 days). Lithium treatment for 14 days produced a significant reduction in the IP basal cortical value, and a significant reduction in cortical carbachol- and NE-induced IP formation was found after 28 days of lithium treatment. The combination of haloperidol and lithium for 28 days decreased the striatal carbachol- and cortical NE-induced IP accumulation and caused a significant increase in NE-sensitive IP formation in the striatum at 14 days. Valproate treatment for 28 days was associated with a significant attenuation in striatal agonist-stimulated IP formation. Therefore, three drugs with different specificities for primary neurotransmitters may have common effects on second-messenger systems. JF - Pharmacology, biochemistry, and behavior AU - Li, R AU - Wing, L L AU - Wyatt, R J AU - Kirch, D G AD - Neuropsychiatry Branch, National Institute of Mental Health, Neuroscience Center at St. Elizabeth's, Washington, DC 20032. Y1 - 1993/10// PY - 1993 DA - October 1993 SP - 323 EP - 329 VL - 46 IS - 2 SN - 0091-3057, 0091-3057 KW - Phosphatidylinositols KW - 0 KW - Valproic Acid KW - 614OI1Z5WI KW - Carbachol KW - 8Y164V895Y KW - Lithium KW - 9FN79X2M3F KW - Haloperidol KW - J6292F8L3D KW - Norepinephrine KW - X4W3ENH1CV KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Drug Interactions KW - Prefrontal Cortex -- metabolism KW - Norepinephrine -- metabolism KW - Corpus Striatum -- metabolism KW - Corpus Striatum -- drug effects KW - Carbachol -- pharmacology KW - Male KW - Valproic Acid -- pharmacology KW - Phosphatidylinositols -- metabolism KW - Brain Chemistry -- drug effects KW - Haloperidol -- pharmacology KW - Lithium -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76122246?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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%2C+biochemistry%2C+and+behavior&rft.atitle=Effects+of+haloperidol%2C+lithium%2C+and+valproate+on+phosphoinositide+turnover+in+rat+brain.&rft.au=Li%2C+R%3BWing%2C+L+L%3BWyatt%2C+R+J%3BKirch%2C+D+G&rft.aulast=Li&rft.aufirst=R&rft.date=1993-10-01&rft.volume=46&rft.issue=2&rft.spage=323&rft.isbn=&rft.btitle=&rft.title=Pharmacology%2C+biochemistry%2C+and+behavior&rft.issn=00913057&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-01-27 N1 - Date created - 1994-01-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Management of acute radiodermatitis. Pharmacological or nonpharmacological remedies? AN - 76117047; 8261385 AB - The medical and nursing literature suggests a wide variety of pharmacological and nonpharmacological approaches to treatment of acute radiation skin damages (erythema, dry and moist desquamation, ulceration), but no specific and standardized therapy. The incidence of radiodermatitis has decreased with mega-voltage instruments, but it can nevertheless influence the therapeutic program and impair quality of life of patients. A study has been conducted to evaluate the tolerability and effectiveness of a nonpharmacological remedy, a mixture of hydrophobic (stearic acid) and hydrophilic (propylene glycol, glycerol, and polyunsaturated alcohols) components in a foam emulsion for the treatment of acute skin injuries following radiotherapy. Thirty-eight of 42 initial patients were evaluable: we observed a complete response in 22 (57.9%), improvement in 14 (36.8%), and failure in only two (5.3%). JF - Cancer nursing AU - Dini, D AU - Macchia, R AU - Gozza, A AU - Bertelli, G AU - Forno, G G AU - Guenzi, M AU - Bacigalupo, A AU - Scolaro, T AU - Vitale, V AD - Cancer Rehabilitation Department, National Cancer Institute, Genoa, Italy. Y1 - 1993/10// PY - 1993 DA - October 1993 SP - 366 EP - 370 VL - 16 IS - 5 SN - 0162-220X, 0162-220X KW - Bioshield KW - 0 KW - Drug Combinations KW - Emulsions KW - Radiation-Protective Agents KW - Stearates KW - Glycerol KW - PDC6A3C0OX KW - Index Medicus KW - Nursing KW - Acute Disease KW - Humans KW - Aged KW - Radiotherapy -- adverse effects KW - Glycerol -- administration & dosage KW - Radiation-Protective Agents -- administration & dosage KW - Aged, 80 and over KW - Stearates -- administration & dosage KW - Adult KW - Middle Aged KW - Female KW - Male KW - Remission Induction KW - Radiodermatitis -- etiology KW - Radiodermatitis -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76117047?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+nursing&rft.atitle=Management+of+acute+radiodermatitis.+Pharmacological+or+nonpharmacological+remedies%3F&rft.au=Dini%2C+D%3BMacchia%2C+R%3BGozza%2C+A%3BBertelli%2C+G%3BForno%2C+G+G%3BGuenzi%2C+M%3BBacigalupo%2C+A%3BScolaro%2C+T%3BVitale%2C+V&rft.aulast=Dini&rft.aufirst=D&rft.date=1993-10-01&rft.volume=16&rft.issue=5&rft.spage=366&rft.isbn=&rft.btitle=&rft.title=Cancer+nursing&rft.issn=0162220X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-01-21 N1 - Date created - 1994-01-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Concurrent strong tyrosine phosphorylation of a 42,000 MW ERK and a 100,000 MW protein is associated with IL-2 production in human Jurkat T cells. AN - 76114166; 7903276 AB - The tyrosine phosphorylated protein(s) responsible for the signalling for interleukin-2 (IL-2) production has not been clearly defined. In this study, the relationship between IL-2 production and the protein tyrosine phosphorylation pattern of human Jurkat T cells was investigated using phosphotyrosine immunoblotting analysis. With anti-CD3 or anti-CD2 activation the cells showed only a low (anti-CD3) or a moderate (anti-CD2) level of tyrosine phosphorylation of a 42,000 MW external signal-regulated kinase (ERK), which was accompanied by undetectable (anti-CD3) or low level (anti-CD2) IL-2 production. In the presence of phorbol myristate acetate (PMA), large amounts of IL-2 were induced by both anti-CD3 and anti-CD2 stimulation, which was accompanied by strong concurrent tyrosine phosphorylation of the 42,000 MW ERK and a 100,000 MW protein. PMA alone, which induced high levels of tyrosine phosphorylation of the ERK protein, neither induced any detectable IL-2 nor increased the level of tyrosine phosphorylation of the 100,000 MW protein. These observations suggest that concurrent tyrosine phosphorylation of the 42,000 MW ERK and a 100,000 MW protein may be required for IL-2 production. JF - Immunology AU - Song, L AU - Adler, W H AU - Chung, S AU - Kim, Y H AU - TenBrook, J AU - Collins, G D AU - Nagel, J E AD - Clinical Immunology Section, National Institute on Aging, NIH, Baltimore, MD 21224. Y1 - 1993/10// PY - 1993 DA - October 1993 SP - 222 EP - 228 VL - 80 IS - 2 SN - 0019-2805, 0019-2805 KW - Antigens, CD KW - 0 KW - Antigens, CD2 KW - Antigens, CD3 KW - Antigens, Differentiation, T-Lymphocyte KW - Interleukin-2 KW - Receptors, Immunologic KW - Tyrosine KW - 42HK56048U KW - Protein Kinases KW - EC 2.7.- KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Antigens, CD3 -- immunology KW - Receptors, Immunologic -- immunology KW - Phosphorylation KW - Lymphocyte Activation -- immunology KW - Electrophoresis, Polyacrylamide Gel KW - Cells, Cultured KW - Humans KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Antigens, Differentiation, T-Lymphocyte -- immunology KW - Molecular Weight KW - Antigens, CD -- immunology KW - Protein Kinases -- metabolism KW - Tyrosine -- physiology KW - Interleukin-2 -- biosynthesis KW - T-Lymphocytes -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76114166?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Immunology&rft.atitle=Concurrent+strong+tyrosine+phosphorylation+of+a+42%2C000+MW+ERK+and+a+100%2C000+MW+protein+is+associated+with+IL-2+production+in+human+Jurkat+T+cells.&rft.au=Song%2C+L%3BAdler%2C+W+H%3BChung%2C+S%3BKim%2C+Y+H%3BTenBrook%2C+J%3BCollins%2C+G+D%3BNagel%2C+J+E&rft.aulast=Song&rft.aufirst=L&rft.date=1993-10-01&rft.volume=80&rft.issue=2&rft.spage=222&rft.isbn=&rft.btitle=&rft.title=Immunology&rft.issn=00192805&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-01-24 N1 - Date created - 1994-01-24 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Immunol. 1980 Jun;124(6):2708-13 [6966296] J Immunol. 1992 May 15;148(10):3230-7 [1533654] J Immunol. 1984 Jul;133(1):123-8 [6327821] J Immunol. 1986 Sep 1;137(5):1420-8 [2427570] Adv Exp Med Biol. 1987;213:45-9 [2957896] J Immunol Methods. 1988 May 9;109(2):277-85 [2452204] J Immunol. 1988 Jul 15;141(2):404-9 [3260251] J Biol Chem. 1988 Sep 5;263(25):12721-7 [2842341] EMBO J. 1988 Jul;7(7):1973-7 [2901344] J Immunol. 1990 Jan 15;144(2):647-52 [1688582] Nature. 1990 Feb 15;343(6259):651-3 [2154696] FEBS Lett. 1990 Feb 26;261(2):331-4 [1690148] J Immunol. 1990 Apr 1;144(7):2683-9 [2156931] J Immunol. 1990 Aug 1;145(3):971-9 [2165097] J Immunol. 1990 Oct 1;145(7):2189-98 [1697878] J Immunol. 1990 Oct 15;145(8):2448-54 [1976695] J Biol Chem. 1990 Nov 15;265(32):19728-35 [1700979] Cell. 1991 May 17;65(4):663-75 [2032290] Biochim Biophys Acta. 1991 May 17;1092(3):350-7 [1646641] Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):6142-6 [1712480] Immunology. 1991 Jun;73(2):129-33 [1676984] Biochem J. 1991 Jul 15;277 ( Pt 2):573-6 [1650188] J Immunol. 1991 Aug 1;147(3):788-94 [1677669] J Biol Chem. 1991 Aug 15;266(23):15277-85 [1651323] Eur J Immunol. 1991 Sep;21(9):2203-9 [1679714] Cell. 1984 Apr;36(4):897-906 [6231105] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Styrene inhalation toxicity studies in mice. III. Strain differences in susceptibility. AN - 76104936; 8258386 AB - Inhalation toxicity studies were conducted to evaluate mouse strain differences in the susceptibility to styrene vapors. Male and female B6C3F1, C57BL/6, Swiss, and DBA/2 mice (8 weeks old) were exposed to 0, 125, 250, or 500 ppm styrene 6 hr/day, for 4 days (20/sex/dose). Histopathological changes and changes in liver weights were evaluated as a measure of hepatotoxicity. Styrene uptake and styrene-7,8-oxide (SO) formation were estimated by measuring levels of styrene and SO in blood. An estimate of SO detoxification by conjugation with GSH was obtained by measuring hepatic GSH depletion. In general, mortality, increased liver weights, and hepatocellular necrosis were observed in the 250 and 500 ppm dose groups for all strains and both sexes. Considerable sex and strain differences were observed. Mortality, increased liver weights, and hepatocellular necrosis were greatest in B6C3F1 and C57BL/6 mice in the 250 ppm dose group and in males; hepatotoxicity was similar in both strains. Swiss mice exhibited dose-dependent increases in mortality, liver weights, and in hepatocellular necrosis, with only slight sex differences at early time points. Hepatotoxicity in DBA/2, B6C3F1, and C57BL/6 strains was greater at 250 than 500 ppm; however, toxicity was less severe in DBA/2 than in other strains based on absence of mortality in either sex and less extensive liver necrosis at both 250 and 500 ppm. Blood styrene and SO levels did not correlate well with strain differences in toxicity.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Fundamental and applied toxicology : official journal of the Society of Toxicology AU - Morgan, D L AU - Mahler, J F AU - Dill, J A AU - Price, H C AU - O'Connor, R W AU - Adkins, B AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1993/10// PY - 1993 DA - October 1993 SP - 326 EP - 333 VL - 21 IS - 3 SN - 0272-0590, 0272-0590 KW - Epoxy Compounds KW - 0 KW - Styrenes KW - styrene oxide KW - 9QH06NGT6O KW - Glutathione KW - GAN16C9B8O KW - Index Medicus KW - Animals KW - Liver -- pathology KW - Random Allocation KW - Liver -- metabolism KW - Mice KW - Mice, Inbred DBA KW - Necrosis KW - Epoxy Compounds -- blood KW - Liver -- drug effects KW - Body Weight -- drug effects KW - Mice, Inbred C57BL KW - Administration, Inhalation KW - Female KW - Male KW - Organ Size -- drug effects KW - Mice, Inbred Strains -- physiology KW - Styrenes -- blood KW - Styrenes -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76104936?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.atitle=Styrene+inhalation+toxicity+studies+in+mice.+III.+Strain+differences+in+susceptibility.&rft.au=Morgan%2C+D+L%3BMahler%2C+J+F%3BDill%2C+J+A%3BPrice%2C+H+C%3BO%27Connor%2C+R+W%3BAdkins%2C+B&rft.aulast=Morgan&rft.aufirst=D&rft.date=1993-10-01&rft.volume=21&rft.issue=3&rft.spage=326&rft.isbn=&rft.btitle=&rft.title=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.issn=02720590&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-01-19 N1 - Date created - 1994-01-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Adhesion molecules and inhibitors of glycosylation in cancer. AN - 76104658; 8257778 AB - Expression of aberrant oligosaccharide moieties of glycoproteins and glycolipids is a typical characteristic of essentially all animal and human tumors, irrespective of the carcinogenic mechanism. Evidence is presented to document that transformation-associated alternations in the oligosaccharide moieties of surface and adhesive glycoproteins are responsible, at least in part, for expression of the malignant phenotype. However, the contribution of carbohydrates to tumor progression and metastasis cannot be fully assessed until more information is available concerning the multiple mechanisms that regulate cell adhesion and carbohydrate biosynthesis. Nevertheless, our rudimentary understanding of the carbohydrate-dependent events involved in cell adhesion and metastasis has resulted in animal studies to develop novel and exciting approaches to cancer therapy. JF - Seminars in cancer biology AU - Olden, K AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709-2233. Y1 - 1993/10// PY - 1993 DA - October 1993 SP - 269 EP - 276 VL - 4 IS - 5 SN - 1044-579X, 1044-579X KW - Oligosaccharides KW - 0 KW - Index Medicus KW - Animals KW - Humans KW - Glycosylation KW - Neoplasms -- therapy KW - Cell Transformation, Neoplastic KW - Neoplasms -- metabolism KW - Oligosaccharides -- metabolism KW - Neoplasm Metastasis KW - Oligosaccharides -- chemistry KW - Cell Adhesion UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76104658?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+cancer+biology&rft.atitle=Adhesion+molecules+and+inhibitors+of+glycosylation+in+cancer.&rft.au=Olden%2C+K&rft.aulast=Olden&rft.aufirst=K&rft.date=1993-10-01&rft.volume=4&rft.issue=5&rft.spage=20&rft.isbn=&rft.btitle=&rft.title=Alternatives+Journal&rft.issn=12057398&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-01-14 N1 - Date created - 1994-01-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of the mechanism of receptor-mediated gene expression on the shape of the dose-response curve. AN - 76104165; 8259447 AB - A mathematical model of receptor-mediated gene expression that includes receptor binding of natural and xenobiotic ligands, protein synthesis and degradation, and metabolism of the xenobiotic ligand was created to identify the determinants of the shape of the dose-response profile. Values of the model's parameters were varied to reflect alternative mechanisms of expression of the protein. These assumptions had dramatic effects on the computed response to a bolus dose of the xenobiotic ligand. If all processes in the model exhibit hyperbolic kinetics, the dose-response curves can appear sigmoidal but actually be linear with a positive slope at low doses. The slope of the curve only approached zero at low dose, indicative of a threshold for response, if binding of the xenobiotic ligand to the receptor exhibited positive cooperativity (ligand binding at one site increases the affinity for ligand at another binding site on the receptor). Positive cooperativity in the rate-limiting step of protein synthesis produced dose-response curves which were "U-shaped" at low doses, also indicative of a threshold. Positive cooperativity in the metabolism of the xenobiotic ligand produced dose-response curves that increased more rapidly than linearly with increasing dose. The model illustrates the fact that response cannot be predicted from qualitative mechanistic arguments alone; any assessment of risk to health from xenobiotic chemicals must be based on a detailed quantitative examination of the kinetic behavior of each chemical species individually. JF - Risk analysis : an official publication of the Society for Risk Analysis AU - Kohn, M C AU - Portier, C J AD - Statistics and Biomathematics Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1993/10// PY - 1993 DA - October 1993 SP - 565 EP - 572 VL - 13 IS - 5 SN - 0272-4332, 0272-4332 KW - Ligands KW - 0 KW - Polychlorinated Dibenzodioxins KW - Xenobiotics KW - Index Medicus KW - Risk Factors KW - Polychlorinated Dibenzodioxins -- adverse effects KW - Gene Expression Regulation -- physiology KW - Dose-Response Relationship, Drug KW - Environmental Exposure KW - Xenobiotics -- adverse effects KW - Models, Biological UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76104165?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Risk+analysis+%3A+an+official+publication+of+the+Society+for+Risk+Analysis&rft.atitle=Effects+of+the+mechanism+of+receptor-mediated+gene+expression+on+the+shape+of+the+dose-response+curve.&rft.au=Kohn%2C+M+C%3BPortier%2C+C+J&rft.aulast=Kohn&rft.aufirst=M&rft.date=1993-10-01&rft.volume=13&rft.issue=5&rft.spage=565&rft.isbn=&rft.btitle=&rft.title=Risk+analysis+%3A+an+official+publication+of+the+Society+for+Risk+Analysis&rft.issn=02724332&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-01-19 N1 - Date created - 1994-01-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A rapid method for site-specific mutagenesis using larger plasmids as templates. AN - 76104112; 8251172 AB - To facilitate the introduction of specific point mutations in plasmids that are too large to be amplified efficiently by a single PCR, we have developed a method for site-directed mutagenesis by generating partial plasmid fragments, which introduces changes as simply as conventional techniques. Plasmids containing a fragment of the human immunodeficiency virus type-1 (HIV-1) envelope gene were subjected to PCR with four pairs of PCR primers for each desired point mutation. One primer in each of two of these four pairs contained the desired mutation. The four pairs of primers were designed so that four overlapping fragments were amplified from the plasmid template, two of which contained the mutation. These fragments were then reannealed and electroporated directly into Escherichia coli. The desired mutation was typically found in 66% to 83% of the resulting colonies. The technique is almost as simple as previous techniques, shows similar efficiency and is applicable to plasmids that would normally be too large for efficient site-specific mutagenesis. The entire procedure, from PCR amplification to transfection into E. coli, can be completed in one day. JF - BioTechniques AU - Watkins, B A AU - Davis, A E AU - Cocchi, F AU - Reitz, M S AD - National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/10// PY - 1993 DA - October 1993 SP - 700 EP - 704 VL - 15 IS - 4 SN - 0736-6205, 0736-6205 KW - Viral Envelope Proteins KW - 0 KW - Index Medicus KW - AIDS/HIV KW - Polymerase Chain Reaction KW - Hot Temperature KW - Base Sequence KW - Transfection KW - Molecular Sequence Data KW - Escherichia coli -- genetics KW - Cloning, Molecular KW - Mutagenesis, Site-Directed KW - HIV-1 -- genetics KW - Templates, Genetic KW - Plasmids KW - Viral Envelope Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76104112?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=BioTechniques&rft.atitle=A+rapid+method+for+site-specific+mutagenesis+using+larger+plasmids+as+templates.&rft.au=Watkins%2C+B+A%3BDavis%2C+A+E%3BCocchi%2C+F%3BReitz%2C+M+S&rft.aulast=Watkins&rft.aufirst=B&rft.date=1993-10-01&rft.volume=15&rft.issue=4&rft.spage=700&rft.isbn=&rft.btitle=&rft.title=BioTechniques&rft.issn=07366205&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-01-07 N1 - Date created - 1994-01-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Styrene inhalation toxicity studies in mice. II. Sex differences in susceptibility of B6C3F1 mice. AN - 76095717; 8258385 AB - Styrene is a commercially important chemical used in the production of plastics and resins. In initial short-term styrene inhalation studies, toxicity was significantly greater in male B6C3F1 mice than in females, suggesting that males may metabolize styrene more extensively and/or may be less able to detoxify reactive metabolites. In addition, a nonlinear dose-response was observed where toxicity and mortality were greater in mice exposed to 250 ppm than in those exposed to 500 ppm. These studies were conducted to investigate potential mechanism(s) for sex differences and the nonlinear dose-response in styrene toxicity by evaluating the effects of repeated styrene exposure on styrene oxide production, hepatic GSH availability, and hepatotoxicity in male and female B6C3F1 mice. Mice (36/sex/dose) were exposed to 0, 125, 250, or 500 ppm styrene 6 hr/day for up to 3 days. Styrene exposure caused increased mortality and hepatotoxicity (centrilobular necrosis, increased serum liver enzymes) in males and females after one or two exposures to 250 and 500 ppm. Hepatic GSH levels were decreased in a dose-dependent manner in males and females. After one exposure, GSH levels in males rebounded above controls in all dose groups. After three exposures to 125 or 250 ppm males appeared to maintain GSH levels; GSH was still decreased in the 500 ppm group. GSH levels in females were decreased after each exposure in all dose groups to lower levels than in males, and did not rebound above controls.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Fundamental and applied toxicology : official journal of the Society of Toxicology AU - Morgan, D L AU - Mahler, J F AU - Dill, J A AU - Price, H C AU - O'Connor, R W AU - Adkins, B AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1993/10// PY - 1993 DA - October 1993 SP - 317 EP - 325 VL - 21 IS - 3 SN - 0272-0590, 0272-0590 KW - Epoxy Compounds KW - 0 KW - Styrenes KW - styrene oxide KW - 9QH06NGT6O KW - Glutathione KW - GAN16C9B8O KW - Index Medicus KW - Animals KW - Liver -- pathology KW - Sex Characteristics KW - Dose-Response Relationship, Drug KW - Chemical and Drug Induced Liver Injury KW - Glutathione -- metabolism KW - Epoxy Compounds -- metabolism KW - Liver -- metabolism KW - Mice KW - Body Weight KW - Mice, Inbred Strains KW - Necrosis KW - Epoxy Compounds -- blood KW - Liver -- drug effects KW - Liver Diseases -- pathology KW - Administration, Inhalation KW - Male KW - Female KW - Organ Size -- drug effects KW - Styrenes -- blood KW - Styrenes -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76095717?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.atitle=Styrene+inhalation+toxicity+studies+in+mice.+II.+Sex+differences+in+susceptibility+of+B6C3F1+mice.&rft.au=Morgan%2C+D+L%3BMahler%2C+J+F%3BDill%2C+J+A%3BPrice%2C+H+C%3BO%27Connor%2C+R+W%3BAdkins%2C+B&rft.aulast=Morgan&rft.aufirst=D&rft.date=1993-10-01&rft.volume=21&rft.issue=3&rft.spage=317&rft.isbn=&rft.btitle=&rft.title=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.issn=02720590&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-01-19 N1 - Date created - 1994-01-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mechanisms of drug-induced immunologically mediated cytopenias. AN - 76088223; 8241611 JF - Transfusion medicine reviews AU - Shulman, N R AU - Reid, D M AD - Clinical Hematology Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/10// PY - 1993 DA - October 1993 SP - 215 EP - 229 VL - 7 IS - 4 SN - 0887-7963, 0887-7963 KW - Haptens KW - 0 KW - Methyldopa KW - 56LH93261Y KW - Gold KW - 7440-57-5 KW - Index Medicus KW - Humans KW - Methyldopa -- adverse effects KW - Gold -- adverse effects KW - Hematologic Diseases -- chemically induced KW - Hematologic Diseases -- immunology KW - Blood Cells -- immunology KW - Autoimmune Diseases -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76088223?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+medicine+reviews&rft.atitle=Mechanisms+of+drug-induced+immunologically+mediated+cytopenias.&rft.au=Shulman%2C+N+R%3BReid%2C+D+M&rft.aulast=Shulman&rft.aufirst=N&rft.date=1993-10-01&rft.volume=7&rft.issue=4&rft.spage=215&rft.isbn=&rft.btitle=&rft.title=Transfusion+medicine+reviews&rft.issn=08877963&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-12-23 N1 - Date created - 1993-12-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nicotine delivery kinetics and abuse liability. AN - 76076880; 8245272 AB - It is well established that nicotine meets all criteria of a highly addictive drug. However, as recognized by the U.S. surgeon general, the nicotine delivery system itself is an important determinant of the toxic and addictive effects engendered by nicotine use. Therefore, altering the form of nicotine dosing may allow for selective therapeutic action in efforts to develop safer and less addictive nicotine replacement therapies. While it is the case that initial tobacco use often escalates to compulsive use accompanied by tolerance and physical dependence, this is not usually observed with nicotine replacement therapies. These observations are consistent with laboratory data indicating that (a) nicotine polacrilex and transdermal systems deliver nicotine more slowly and at lower dose levels than tobacco-based forms, and (b) human data suggesting that the abuse liability of these systems is substantially lower than that of the tobacco-based nicotine delivery systems. Because the drug dosage form can be systematically manipulated and evaluated, further research in developing alternative nicotine delivery forms may hold substantial promise in the treatment of tobacco dependence. Psychological research methods can play an important part in their evaluation. JF - Journal of consulting and clinical psychology AU - Henningfield, J E AU - Keenan, R M AD - National Institute on Drug Abuse, Addiction Research Center, Baltimore, Maryland 21224. Y1 - 1993/10// PY - 1993 DA - October 1993 SP - 743 EP - 750 VL - 61 IS - 5 SN - 0022-006X, 0022-006X KW - Nicotine KW - 6M3C89ZY6R KW - Index Medicus KW - Administration, Oral KW - Administration, Cutaneous KW - Dose-Response Relationship, Drug KW - Humans KW - Substance Withdrawal Syndrome -- blood KW - Administration, Inhalation KW - Smoking -- blood KW - Nicotine -- pharmacokinetics KW - Nicotine -- adverse effects KW - Smoking -- adverse effects KW - Nicotine -- administration & dosage KW - Smoking -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76076880?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Nicotine+delivery+kinetics+and+abuse+liability.&rft.au=Henningfield%2C+J+E%3BKeenan%2C+R+M&rft.aulast=Henningfield&rft.aufirst=J&rft.date=1993-10-01&rft.volume=61&rft.issue=5&rft.spage=743&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 - 1994-01-06 N1 - Date created - 1994-01-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of human cytochrome P-450s in risk assessment and susceptibility to environmentally based disease. AN - 76061740; 8230303 AB - Cytochromes P-450 (P-450s) are a large group of heme-containing proteins that carry out oxidation of numerous chemicals. In mammals, a limited number of P-450s are involved in metabolic pathways of steroid synthesis, while most of these enzymes are involved in metabolism of foreign compounds. The principal beneficial function of P-450s is to convert chemicals into derivatives that can be easily eliminated from the body. This generally occurs through P-450-mediated oxidations of hydrophobic substances followed by conjugation reactions. For many foreign compounds, P-450 metabolism results in production of "activated" metabolites that can cause cell death and gene mutations. During the past several years, it has become widely recognized that marked species differences occur among the foreign compound-metabolizing P-450s. In addition to this interspecies variability in metabolism, marked intraspecies variability, frequently referred to as drug oxidation polymorphisms, occurs in virtually all mammals examined to date. Based on these observations, it is necessary to develop new human P-450-based systems that can be used to study foreign compound metabolism in order to predict human risk. This is being accomplished by use of cDNA-directed expression in B lymphoblastoid cells. These cells can be used to predict how humans will metabolize a chemical and whether it will be metabolically activated to a toxic or mutagenic metabolite. To study human P-450 polymorphisms, polymerase chain reaction (PCR) assays have been developed for diagnosis of known mutant P-450 genes. Molecular probes are also being used to screen populations for levels of expression of carcinogen-activating P-450s in an effort to determine whether expression of certain P-450 forms is associated with increased risk for development of environmentally based disease. JF - Journal of toxicology and environmental health AU - Gonzalez, F J AU - Gelboin, H V AD - National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. PY - 1993 SP - 289 EP - 308 VL - 40 IS - 2-3 SN - 0098-4108, 0098-4108 KW - Environmental Pollutants KW - 0 KW - Genetic Markers KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Index Medicus KW - Animals KW - Polymorphism, Genetic KW - Risk Factors KW - Humans KW - Gene Expression KW - Species Specificity KW - Liver -- enzymology KW - Environmental Pollutants -- metabolism KW - Liver -- drug effects KW - Cytochrome P-450 Enzyme System -- genetics KW - Liver -- metabolism KW - Cytochrome P-450 Enzyme System -- metabolism KW - Environmental Pollutants -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76061740?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+toxicology+and+environmental+health&rft.atitle=Role+of+human+cytochrome+P-450s+in+risk+assessment+and+susceptibility+to+environmentally+based+disease.&rft.au=Gonzalez%2C+F+J%3BGelboin%2C+H+V&rft.aulast=Gonzalez&rft.aufirst=F&rft.date=1993-10-01&rft.volume=40&rft.issue=2-3&rft.spage=289&rft.isbn=&rft.btitle=&rft.title=Journal+of+toxicology+and+environmental+health&rft.issn=00984108&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-12-13 N1 - Date created - 1993-12-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dual topoisomerase I and II inhibition by intoplicine (RP-60475), a new antitumor agent in early clinical trials. AN - 76059726; 8232227 AB - The mechanisms of action of intoplicine (RP-60475), a 7H-benzo[e]pyrido[4,3-b]indole derivative that is presently in early clinical trials, have been investigated. Intoplicine induced both topoisomerase I- and II-mediated DNA strand breaks, using purified topoisomerases. The topoisomerase cleavage site patterns induced by intoplicine were unique, relative to those of camptothecin, 4'-(9-acridinylamino)methanesulfon-m-anisidide (m-AMSA), and other known topoisomerase inhibitors. Both topoisomerase I- and II-induced DNA breaks decreased at drug concentrations higher than 1 microM, which is consistent with the DNA-intercalating activity of intoplicine. DNA damage was investigated in KB cells in culture by using alkaline elution. Intoplicine induced single-strand breaks (SSB) in a bell-shaped manner with respect to drug concentration (maximum frequency at 1 microM approximately 220 rad-equivalents). SSB formation was fast, whereas reversal after drug removal was slow. Similar bell-shaped curves were obtained for DNA double-strand breaks (DSB) and DNA-protein cross-links. SSB and DNA-protein cross-link frequencies were approximately equal, and no protein-free breaks were detectable, indicating the protein concealment of the breaks, as expected for topoisomerase inhibition. Comparison of SSB and DSB frequencies indicated that intoplicine produced a significant amount of SSB not related to DSB, which is consistent with concomitant inhibition of both DNA topoisomerases I and II in cells. Data derived from resistant cell lines indicated that multidrug-resistant cells were cross-resistant to intoplicine but that m-AMSA- and camptothecin-resistant cells were sensitive to intoplicine. Hence, intoplicine might circumvent topoisomerase I-mediated and topoisomerase II-mediated resistance by poisoning both enzymes simultaneously. JF - Molecular pharmacology AU - Poddevin, B AU - Riou, J F AU - Lavelle, F AU - Pommier, Y AD - Laboratory of Molecular Pharmacology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/10// PY - 1993 DA - October 1993 SP - 767 EP - 774 VL - 44 IS - 4 SN - 0026-895X, 0026-895X KW - Antineoplastic Agents KW - 0 KW - DNA, Neoplasm KW - Indoles KW - Pyridines KW - Topoisomerase I Inhibitors KW - Topoisomerase II Inhibitors KW - intoplicine KW - FB2CIN6HMI KW - Index Medicus KW - DNA, Neoplasm -- drug effects KW - KB Cells KW - Animals KW - Tumor Cells, Cultured KW - Leukemia P388 -- drug therapy KW - DNA Damage KW - Kinetics KW - Humans KW - Mice KW - DNA, Neoplasm -- metabolism KW - Indoles -- toxicity KW - Pyridines -- toxicity KW - Antineoplastic Agents -- toxicity KW - Indoles -- pharmacology KW - Pyridines -- pharmacology KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76059726?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Dual+topoisomerase+I+and+II+inhibition+by+intoplicine+%28RP-60475%29%2C+a+new+antitumor+agent+in+early+clinical+trials.&rft.au=Poddevin%2C+B%3BRiou%2C+J+F%3BLavelle%2C+F%3BPommier%2C+Y&rft.aulast=Poddevin&rft.aufirst=B&rft.date=1993-10-01&rft.volume=44&rft.issue=4&rft.spage=767&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 - 1993-11-29 N1 - Date created - 1993-11-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of dopamine D1 receptors in the lethal effects of cocaine and a quaternary methiodide analog. AN - 76055004; 7901394 AB - Acute cocaine overdose can result in convulsions and death although the mechanisms associated with this toxicity are poorly understood. The role of D1 receptors in the central and peripheral actions in cocaine were investigated by comparisons of cocaine with the stable charged cocaine analog, cocaine methiodide. Both cocaine and cocaine methiodide produced dose-related increases in lethality in male, Swiss Webster mice, with cocaine methiodide being slightly more potent than cocaine; however, only cocaine produced convulsions. Several dopamine D1 antagonists ([R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3- benzazepine] (SCH 23390), [(-)-trans-6,7,7a,8, 9,13b-hexahydro-3-chloro-2-hydroxy-N-methyl-5H-benzo[d]naptho++ +-(2-1-b)azepin e (SCH 39166), 1-(2-bromo-4,5-dimethoxybenzyl)-7-hydroxy-6-methoxy-2-methyl- 1,2,3,4-tetrahydroisoquinoline HBr (A-69024), [R-(+)-7-bromo-8-hydroxy-3- methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine] (SK F83566)) produced dose-dependent protection against the lethal effects of both compounds. Protection against cocaine methiodide-induced lethality was conferred by lower doses of the D1 antagonists than those effective against cocaine. Stereoselectivity of this effect was demonstrated by the lack of activity of the inactive enantiomer of SCH 23390. The D2 antagonist haloperidol was ineffective against either cocaine- or cocaine methiodide-induced lethality. Lethal effects of the nondopaminergic local anesthetic, lidocaine, were not influenced by prior treatment with D1 antagonists. Lethal effects of cocaine were enhanced by both centrally and peripherally acting D1 agonists but not by the D2 agonist quinpirole. Cocaine methiodide-induced lethality was also enhanced by the peripherally active DA1 agonist, fenoldopam.(ABSTRACT TRUNCATED AT 250 WORDS) JF - The Journal of pharmacology and experimental therapeutics AU - Witkin, J M AU - Newman, A H AU - Nowak, G AU - Katz, J L AD - Drug Development Group, National Institute on Drug Abuse, Baltimore, Maryland. Y1 - 1993/10// PY - 1993 DA - October 1993 SP - 266 EP - 274 VL - 267 IS - 1 SN - 0022-3565, 0022-3565 KW - Benzazepines KW - 0 KW - Dopamine D2 Receptor Antagonists KW - Receptors, Dopamine D1 KW - Receptors, Dopamine D2 KW - cocaine methiodide KW - 5937-29-1 KW - 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine KW - 67287-49-4 KW - Lidocaine KW - 98PI200987 KW - 1H-3-benzazepin-7-ol, 8-bromo-2,3,4,5-tetrahydro-3-methyl-5-phenyl- KW - D203LR7XUS KW - Cocaine KW - I5Y540LHVR KW - Fenoldopam KW - INU8H2KAWG KW - Index Medicus KW - Seizures -- chemically induced KW - Animals KW - Benzazepines -- pharmacology KW - Mice KW - 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine -- pharmacology KW - Structure-Activity Relationship KW - Rats KW - Rats, Inbred F344 KW - Receptors, Dopamine D2 -- drug effects KW - 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine -- analogs & derivatives KW - Lidocaine -- pharmacology KW - Motor Activity -- drug effects KW - Male KW - Cocaine -- analogs & derivatives KW - Receptors, Dopamine D1 -- antagonists & inhibitors KW - Cocaine -- toxicity KW - Receptors, Dopamine D1 -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76055004?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Role+of+dopamine+D1+receptors+in+the+lethal+effects+of+cocaine+and+a+quaternary+methiodide+analog.&rft.au=Witkin%2C+J+M%3BNewman%2C+A+H%3BNowak%2C+G%3BKatz%2C+J+L&rft.aulast=Witkin&rft.aufirst=J&rft.date=1993-10-01&rft.volume=267&rft.issue=1&rft.spage=266&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 - 1993-11-29 N1 - Date created - 1993-11-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Spongistatin 1, a highly cytotoxic, sponge-derived, marine natural product that inhibits mitosis, microtubule assembly, and the binding of vinblastine to tubulin. AN - 76054032; 8232226 AB - A highly cytotoxic macrocyclic lactone polyether has been isolated from a Spongia species and named spongistatin 1. With L1210 murine leukemia cells an IC50 value for cell proliferation of 20 pM was obtained, and an increase in the mitotic index concordant with the decrease in cell number was observed. Kangaroo rat kidney PtK1 cells were examined by indirect immunofluorescence with a spongistatin 1 concentration that caused 50% reduction in cellular protein (0.3 nM) and with a 10-fold higher concentration. These cells displayed mitotic and nuclear aberrations at both concentrations, and intracellular microtubules were reduced in number at the lower concentration and disappeared at the higher. Similar changes in PtK1 cells were observed after treatment with equivalent toxic concentrations of the antimitotic agents colchicine, vinblastine, halichondrin B, and dolastatin 10. Spongistatin 1 inhibited the glutamate-induced polymerization of purified tubulin (IC50 value of 3.6 microM versus 2.1 microM for dolastatin 10 and vinblastine and 5.2 microM for halichondrin B). Spongistatin 1 had no effect on the binding of colchicine to tubulin, but it was a potent inhibitor of the binding of vinblastine and GTP to tubulin. In initial experiments with 5 microM tubulin and 5 microM vinblastine, spongistatin 1 and dolastatin 10 both had IC50 values of 2 microM, whereas halichondrin B had an IC50 value of 5 microM. Spongistatin 1 thus represents a new member of the group of complex natural products that inhibit mitosis by binding in the Vinca alkaloid domain of tubulin. JF - Molecular pharmacology AU - Bai, R AU - Cichacz, Z A AU - Herald, C L AU - Pettit, G R AU - Hamel, E AD - Laboratory of Molecular Pharmacology, National Cancer Institute, Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/10// PY - 1993 DA - October 1993 SP - 757 EP - 766 VL - 44 IS - 4 SN - 0026-895X, 0026-895X KW - Antineoplastic Agents KW - 0 KW - Depsipeptides KW - Ethers, Cyclic KW - Lactones KW - Macrolides KW - Marine Toxins KW - Oligopeptides KW - Tubulin KW - halichondrin B KW - 103614-76-2 KW - dolastatin 10 KW - 110417-88-4 KW - spongistatin 1 KW - 148179-94-6 KW - Vinblastine KW - 5V9KLZ54CY KW - Guanosine Triphosphate KW - 86-01-1 KW - Index Medicus KW - Animals KW - Leukemia L1210 -- pathology KW - Porifera KW - Cell Division -- drug effects KW - Oligopeptides -- pharmacology KW - Mice KW - Leukemia L1210 -- drug therapy KW - Guanosine Triphosphate -- metabolism KW - Marine Toxins -- pharmacology KW - Vinblastine -- metabolism KW - Ethers, Cyclic -- toxicity KW - Microtubules -- metabolism KW - Tubulin -- metabolism KW - Ethers, Cyclic -- pharmacology KW - Microtubules -- drug effects KW - Lactones -- toxicity KW - Lactones -- pharmacology KW - Antineoplastic Agents -- toxicity KW - Mitosis -- drug effects KW - Antineoplastic Agents -- pharmacology KW - Marine Toxins -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76054032?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Spongistatin+1%2C+a+highly+cytotoxic%2C+sponge-derived%2C+marine+natural+product+that+inhibits+mitosis%2C+microtubule+assembly%2C+and+the+binding+of+vinblastine+to+tubulin.&rft.au=Bai%2C+R%3BCichacz%2C+Z+A%3BHerald%2C+C+L%3BPettit%2C+G+R%3BHamel%2C+E&rft.aulast=Bai&rft.aufirst=R&rft.date=1993-10-01&rft.volume=44&rft.issue=4&rft.spage=757&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 - 1993-11-29 N1 - Date created - 1993-11-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Substance P increases release of acetylcholine in the dorsal striatum of freely moving rats. AN - 76037966; 7693302 AB - Little is known about the role that neuropeptides such as substance P play in cell-to-cell interactions in the striatum. The effect of locally perfused substance P on extracellular acetylcholine (ACh) in the dorsal striatum of awake, freely moving rats was examined using microdialysis. Neostigmine (1 microM) was included in the perfusate to improve recovery of ACh. Basal extracellular ACh was sensitive to Na(+)-channel blockade with tetrodotoxin (0.3 microM) and Ca(2+)-channel blockade with MgCl2 (10 mM) and therefore largely neuronal in origin. Local perfusion with 10 and 25 microM substance P for 20 min elevated extracellular ACh by 30% and 51%, respectively. The NK1 receptor antagonist, CP 96,345 (10 microM), which by itself had no effect on extracellular ACh, prevented the substance P-induced increase in extracellular ACh. These results suggest that stimulation of NK1 receptors by substance P enhances ACh release in the dorsal striatum and is consistent with anatomical evidence of a substance P-cholinergic circuit in this region. JF - Brain research AU - Anderson, J J AU - Chase, T N AU - Engber, T M AD - Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/10/01/ PY - 1993 DA - 1993 Oct 01 SP - 189 EP - 194 VL - 623 IS - 2 SN - 0006-8993, 0006-8993 KW - Substance P KW - 33507-63-0 KW - Tetrodotoxin KW - 4368-28-9 KW - Magnesium KW - I38ZP9992A KW - Acetylcholine KW - N9YNS0M02X KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Dialysis KW - Extracellular Space -- metabolism KW - Motor Activity KW - Magnesium -- pharmacology KW - Tetrodotoxin -- pharmacology KW - Male KW - Acetylcholine -- metabolism KW - Substance P -- pharmacology KW - Corpus Striatum -- metabolism KW - Substance P -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76037966?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Substance+P+increases+release+of+acetylcholine+in+the+dorsal+striatum+of+freely+moving+rats.&rft.au=Anderson%2C+J+J%3BChase%2C+T+N%3BEngber%2C+T+M&rft.aulast=Anderson&rft.aufirst=J&rft.date=1993-10-01&rft.volume=623&rft.issue=2&rft.spage=189&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 - 1993-12-13 N1 - Date created - 1993-12-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Profile of prostaglandins induced by endothelin-1 in human brain capillary endothelium. AN - 76031710; 8220180 AB - The vasoactive peptide, endothelin-1 (ET-1) has been implicated in the pathophysiology of various diseases. Recently, we have shown that human brain endothelial cells both secrete and express immunoreactive ET-1 high-affinity ETA receptors coupled to activation of phospholipase C (PLC). The present study demonstrates concentration-dependent stimulation of prostanoids [thromboxane B2 (TxB2), prostaglandin F2 alpha (PGF2 alpha), 6-keto prostaglandin F1 alpha (6-keto PGF1 alpha) prostaglandin E2 (PGE2), and prostaglandin D2 (PGD2)] production by ET-1 in capillary endothelial cells derived from human brain (HBCEC). The increase in the vasoconstrictive prostanoids TxA2 and PGF2 alpha temporally preceded that of the vasodilatory PGI2, PGE2 and PGD2, and was seen after 15 min of incubation with ET-1 (10 nM). Increased production of vasodilatory prostanoids was observed between 4-8 h of incubation, whereas normalization of both vasoconstrictive and vasodilatory prostaglandins occurred 24 h after addition of ET-1. Both ET-1-stimulated prostanoid and IP3 production were inhibited by BQ123, a specific antagonist of ETA receptors. ET-1-induced prostanoid secretion by HBCEC was also inhibited by dexamethasone (50 microM) and diminished by neomycin (50 microM) and verapamil (10 microM) but not by nifedipine. Phorbol myristate ester potentiated ET-1-stimulated prostanoid secretion, whereas it inhibited IP3 production. Data indicate that ET-1 activates phospholipase A2 (PLA2) and PLC in HBCEC by different intracellular mechanisms. The subsequently induced secretion of vasoactive prostanoids by HBCEC may contribute both qualitatively and temporally to the vasoactive actions of ET-1. JF - Neurochemistry international AU - Stanimirovic, D B AU - Bacic, F AU - Uematsu, S AU - Spatz, M AD - Stroke Branch, NINDS, NIH, Bethesda, MD 20892. Y1 - 1993/10// PY - 1993 DA - October 1993 SP - 385 EP - 393 VL - 23 IS - 4 SN - 0197-0186, 0197-0186 KW - Endothelin Receptor Antagonists KW - 0 KW - Endothelins KW - Peptides, Cyclic KW - Prostaglandins KW - Neomycin KW - 1404-04-2 KW - Inositol KW - 4L6452S749 KW - Dexamethasone KW - 7S5I7G3JQL KW - Verapamil KW - CJ0O37KU29 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - cyclo(Trp-Asp-Pro-Val-Leu) KW - S2A8YZM151 KW - Index Medicus KW - Analysis of Variance KW - Dexamethasone -- pharmacology KW - Humans KW - Epilepsy -- metabolism KW - Verapamil -- pharmacology KW - Inositol -- metabolism KW - Capillaries KW - Neomycin -- pharmacology KW - Epilepsy -- surgery KW - Kinetics KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Peptides, Cyclic -- pharmacology KW - Cell Line KW - Endothelins -- pharmacology KW - Endothelium, Vascular -- metabolism KW - Endothelium, Vascular -- drug effects KW - Temporal Lobe -- surgery KW - Prostaglandins -- biosynthesis KW - Temporal Lobe -- blood supply KW - Prostaglandins -- isolation & purification KW - Prostaglandins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76031710?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurochemistry+international&rft.atitle=Profile+of+prostaglandins+induced+by+endothelin-1+in+human+brain+capillary+endothelium.&rft.au=Stanimirovic%2C+D+B%3BBacic%2C+F%3BUematsu%2C+S%3BSpatz%2C+M&rft.aulast=Stanimirovic&rft.aufirst=D&rft.date=1993-10-01&rft.volume=23&rft.issue=4&rft.spage=385&rft.isbn=&rft.btitle=&rft.title=Neurochemistry+international&rft.issn=01970186&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-12-14 N1 - Date created - 1993-12-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cisplatin sensitivity/resistance in UV repair-deficient Chinese hamster ovary cells of complementation groups 1 and 3. AN - 76027777; 8222071 AB - We assessed the possible role of the human repair genes, ERCC1 and ERCC3, in resistance to cisplatin-induced cytotoxicity. The UV repair-deficient Chinese hamster ovary (CHO) 43:3B [designated ERCC1(-)] cell line and its paired subline 83-J5, which is stably transfected with the human DNA excision repair gene ERCC1 [designated ERCC1(+)], were used in this study. UV repair-deficient CHO 27-1 cells [designated ERCC3(-)] and its paired subline designated 'ERCC3(+)', which is stably transfected with the human DNA excision repair gene ERCC3, were also used. In each pair of cell lines, we assessed cisplatin cytotoxicity, cellular drug accumulation and platinum-DNA adduct repair after 1 h drug exposures. Drug accumulation and DNA repair were assessed by atomic absorption spectrometry with Zeeman background correction. ERCC1(+) cells (IC50 = 4.0 microM) were 5-fold more resistant to cisplatin than ERCC1(-) cells (IC50 = 0.75 microM). ERCC1(+) cells repaired 25% of DNA lesions in cellular DNA within a 6 h time period following an IC50 drug exposure and repaired 48% over 24 h. No DNA repair was observed in ERCC1(-) cells during the same time periods. Both cell lines showed similar patterns of drug accumulation. For ERCC3(-) cells (IC50 = 54 microM) and ERCC3(+) cells (IC50 = 49 microM), the profiles of cisplatin sensitivity and cellular drug accumulation were similar. When treated with 50 microM cisplatin, these cells showed similar patterns of drug accumulation, and were equally efficient at forming and repairing lesions in cellular DNA. These data show that in UV repair-deficient CHO cells, ERCC1 confers resistance to cisplatin and confers the ability to remove platinum from cellular DNA. In contrast, ERCC3 does not influence cisplatin drug sensitivity or adduct repair capability. This suggests that ERCC1 may be a determinant of cisplatin resistance, whereas ERCC3 is probably not. JF - Carcinogenesis AU - Lee, K B AU - Parker, R J AU - Bohr, V AU - Cornelison, T AU - Reed, E AD - Medical Ovarian Cancer Section, National Cancer Institute, Bethesda, MD 20892. Y1 - 1993/10// PY - 1993 DA - October 1993 SP - 2177 EP - 2180 VL - 14 IS - 10 SN - 0143-3334, 0143-3334 KW - ERCC1 KW - ERCC3 KW - DNA Adducts KW - 0 KW - cisplatin-DNA adduct KW - DNA KW - 9007-49-2 KW - Cisplatin KW - Q20Q21Q62J KW - Index Medicus KW - Animals KW - Drug Resistance -- genetics KW - CHO Cells -- metabolism KW - DNA Damage KW - CHO Cells -- drug effects KW - Cell Death KW - DNA -- analysis KW - Time Factors KW - Cricetinae KW - DNA Repair -- genetics KW - Cisplatin -- pharmacokinetics KW - Cisplatin -- pharmacology KW - Cisplatin -- analysis KW - Genes -- physiology KW - Gene Expression Regulation -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76027777?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Cisplatin+sensitivity%2Fresistance+in+UV+repair-deficient+Chinese+hamster+ovary+cells+of+complementation+groups+1+and+3.&rft.au=Lee%2C+K+B%3BParker%2C+R+J%3BBohr%2C+V%3BCornelison%2C+T%3BReed%2C+E&rft.aulast=Lee&rft.aufirst=K&rft.date=1993-10-01&rft.volume=14&rft.issue=10&rft.spage=2177&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-12-01 N1 - Date created - 1993-12-01 N1 - Date revised - 2017-01-13 N1 - Gene symbol - ERCC1; ERCC3 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dynorphin agonist therapy of Parkinson's disease. AN - 76023589; 8106151 AB - Striatal dynorphin system function may be altered in Parkinson's disease. To evaluate whether treatment with a selective dynorphin agonist improves motor symptoms, four parkinsonian patients received single daily injections of spiradoline under controlled conditions. Doses ranging from 1 to 4 micrograms/kg had no discernible effect on motor performance when given alone or in combination with levodopa-carbidopa. Three patients developed dose-limiting adverse effects, especially behavioral alterations. These results suggest that dynorphin replacement strategies, using spiradoline-like kappa-1 agonists, may have limited value in the therapy of patients with Parkinson's disease. JF - Clinical neuropharmacology AU - Giuffra, M AU - Mouradian, M M AU - Davis, T L AU - Ownby, J AU - Chase, T N AD - Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892. Y1 - 1993/10// PY - 1993 DA - October 1993 SP - 444 EP - 447 VL - 16 IS - 5 SN - 0362-5664, 0362-5664 KW - Pyrrolidines KW - 0 KW - Levodopa KW - 46627O600J KW - Dynorphins KW - 74913-18-1 KW - spiradoline KW - N18ZH0M4NP KW - Index Medicus KW - Drug Therapy, Combination KW - Double-Blind Method KW - Dose-Response Relationship, Drug KW - Humans KW - Adult KW - Levodopa -- therapeutic use KW - Motor Activity -- drug effects KW - Middle Aged KW - Pyrrolidines -- therapeutic use KW - Pyrrolidines -- adverse effects KW - Parkinson Disease -- physiopathology KW - Dynorphins -- physiology KW - Parkinson Disease -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76023589?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+neuropharmacology&rft.atitle=Dynorphin+agonist+therapy+of+Parkinson%27s+disease.&rft.au=Giuffra%2C+M%3BMouradian%2C+M+M%3BDavis%2C+T+L%3BOwnby%2C+J%3BChase%2C+T+N&rft.aulast=Giuffra&rft.aufirst=M&rft.date=1993-10-01&rft.volume=16&rft.issue=5&rft.spage=444&rft.isbn=&rft.btitle=&rft.title=Clinical+neuropharmacology&rft.issn=03625664&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-12-22 N1 - Date created - 1993-12-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Enzymatic phase II activation of the N-hydroxylamines of IQ, MeIQx and PhIP by various organs of monkeys and rats. AN - 76022825; 8222059 AB - 2-Amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) are mutagenic and carcinogenic heterocyclic amines produced during the ordinary cooking of meat. These compounds undergo metabolic activation via both cytochrome P450-mediated N-oxidation and phase II esterification in order to exert their genotoxicity. In the current study, we examined the in vitro phase II activation of N-hydroxy-IQ, N-hydroxy-PhIP and N-hydroxy-MeIQx by cytosolic acetyltransferase, sulfotransferase, aminoacyl-tRNA synthetase and phosphatase from a number of tissues including liver, kidney, colon and heart. These tissues were chosen for study because each is either a target organ for carcinogenicity or has displayed high levels of DNA adducts in in vivo studies with the heterocyclic amines. Cytosol from various tissues of both monkeys and rats was incubated with and without the respective cofactors, and carcinogen binding to calf thymus DNA was measured by 32P-postlabeling analysis. Our results show that all four phase II enzymes may participate in the activation of the N-hydroxylamines. However, the degree of activation depends on the substrate, tissue and animal species. For example, in both monkeys and rats, the highest acetyl CoA-enhanced binding was observed with N-hydroxy-IQ and the lowest acetyl CoA-enhanced binding was observed with N-hydroxy-MeIQx. In contrast, no significant adenosine 3'-phosphate 5'-phosphosulfate-dependent activation of N-hydroxy-IQ was observed with monkey cytosol from liver, kidney, heart or colon but the sulfotransferase-mediated activation of N-hydroxy-PhIP was at least 10 times higher in all four tissues of monkeys than in rats. Prolylation appears important in the activation of all three N-hydroxylamines by rat liver and heart cytosol, whereas in monkeys, prolylation appears important in kidney cytosol. The differences observed in the phase II activation of heterocyclic amines may have implications for DNA adduct formation, toxicity and carcinogenicity. JF - Carcinogenesis AU - Davis, C D AU - Schut, H A AU - Snyderwine, E G AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, Bethesda, MD 20892. Y1 - 1993/10// PY - 1993 DA - October 1993 SP - 2091 EP - 2096 VL - 14 IS - 10 SN - 0143-3334, 0143-3334 KW - Imidazoles KW - 0 KW - Quinolines KW - Quinoxalines KW - 2-amino-3-methylimidazo(4,5-f)quinoline KW - 30GL3D3T0G KW - 2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline KW - 77500-04-0 KW - DNA KW - 9007-49-2 KW - 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine KW - 909C6UN66T KW - Acetyltransferases KW - EC 2.3.1.- KW - Sulfotransferases KW - EC 2.8.2.- KW - Phosphoric Monoester Hydrolases KW - EC 3.1.3.2 KW - Amino Acyl-tRNA Synthetases KW - EC 6.1.1.- KW - Index Medicus KW - Rats KW - Cytosol -- metabolism KW - Animals KW - Sulfotransferases -- metabolism KW - Rats, Inbred F344 KW - Macaca fascicularis KW - Acetyltransferases -- metabolism KW - Amino Acyl-tRNA Synthetases -- metabolism KW - Species Specificity KW - Phosphoric Monoester Hydrolases -- metabolism KW - Male KW - Quinolines -- metabolism KW - Kidney -- metabolism KW - Imidazoles -- metabolism KW - DNA -- metabolism KW - Colon -- metabolism KW - Quinoxalines -- metabolism KW - Liver -- metabolism KW - Myocardium -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76022825?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Enzymatic+phase+II+activation+of+the+N-hydroxylamines+of+IQ%2C+MeIQx+and+PhIP+by+various+organs+of+monkeys+and+rats.&rft.au=Davis%2C+C+D%3BSchut%2C+H+A%3BSnyderwine%2C+E+G&rft.aulast=Davis&rft.aufirst=C&rft.date=1993-10-01&rft.volume=14&rft.issue=10&rft.spage=2091&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-12-01 N1 - Date created - 1993-12-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - New chemotherapeutic agents for the treatment of low-grade non-Hodgkin's lymphomas. AN - 76019650; 8105539 JF - Seminars in oncology AU - Cheson, B D AD - Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD 20892. Y1 - 1993/10// PY - 1993 DA - October 1993 SP - 96 EP - 110 VL - 20 IS - 5 Suppl 5 SN - 0093-7754, 0093-7754 KW - Alkylating Agents KW - 0 KW - Antibiotics, Antineoplastic KW - Antineoplastic Agents KW - Depsipeptides KW - Peptides, Cyclic KW - Suramin KW - 6032D45BEM KW - didemnins KW - 77327-04-9 KW - Gallium KW - CH46OC8YV4 KW - Mitoguazone KW - OD5Q0L447W KW - Paclitaxel KW - P88XT4IS4D KW - gallium nitrate KW - VRA0C6810N KW - Index Medicus KW - Alkylating Agents -- therapeutic use KW - Animals KW - Peptides, Cyclic -- therapeutic use KW - Humans KW - Mitoguazone -- therapeutic use KW - Paclitaxel -- therapeutic use KW - Gallium -- therapeutic use KW - Suramin -- therapeutic use KW - Antibiotics, Antineoplastic -- therapeutic use KW - Lymphoma, Non-Hodgkin -- drug therapy KW - Antineoplastic Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76019650?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=New+chemotherapeutic+agents+for+the+treatment+of+low-grade+non-Hodgkin%27s+lymphomas.&rft.au=Cheson%2C+B+D&rft.aulast=Cheson&rft.aufirst=B&rft.date=1993-10-01&rft.volume=20&rft.issue=5+Suppl+5&rft.spage=96&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 - 1993-11-12 N1 - Date created - 1993-11-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The Escherichia coli galK2 papillation assay: its specificity and application to seven newly isolated mutator strains. AN - 76016302; 7692254 AB - The Escherichia coli dnaE and dnaQ genes encode, respectively, the alpha (polymerase) and epsilon (proofreading) subunits of DNA polymerase III. Mutations in these genes resulting in mutator or antimutator phenotypes provide important tools to understand the mechanisms by which mutations occur. One way to isolate such strains is the use of papillation assays. We used one such assay based on the reversion of the galK2 allele in cells grown on MacConkey-Gal plates. Here, we describe the identification of the galK2 mutation and its possible reversion pathways, and the characterization of 7 mutators isolated using this system. 1 mutator resided in dnaE and 6 in dnaQ. Sequencing of the galK2 allele revealed a G.C-->T.A transversion at base pair 571 that changed a glu codon (GAA) to a stop codon (TAA). The analysis of 319 revertants showed that a Gal+ phenotype can be achieved by A.T-->G.C transition, A.T-->T.A transversion and A.T-->C.G transversion. We characterized the mutator phenotypes of the newly isolated mutators by determining (i) their mutation frequencies to resistance to rifampicin and nalidixic acid in both wild-type and mutL backgrounds, (ii) their temperature sensitivity and medium dependence and (iii) their mutational specificity (by analyzing the nature of galK revertants). Based on the genomic locations of their mutations, specificity of reversion pathways and magnitude of mutator effects, the mutators can be grouped into 3 classes. These classes may represent different mutational mechanisms that include defective base insertion, defective proofreading and interference with the postreplicative mismatch-repair system. JF - Mutation research AU - Oller, A R AU - Fijalkowska, I J AU - Schaaper, R M AD - Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1993/10// PY - 1993 DA - October 1993 SP - 175 EP - 185 VL - 292 IS - 2 SN - 0027-5107, 0027-5107 KW - dnaE KW - dnaQ KW - galK2 KW - DNA Polymerase III KW - EC 2.7.7.- KW - DNA polymerase III, alpha subunit KW - Rifampin KW - VJT6J7R4TR KW - Index Medicus KW - Phenotype KW - Drug Resistance -- genetics KW - DNA Mutational Analysis KW - DNA Polymerase III -- genetics KW - Rifampin -- pharmacology KW - Mutagenesis KW - Genes, Bacterial KW - Escherichia coli -- genetics KW - Mutation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76016302?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+Escherichia+coli+galK2+papillation+assay%3A+its+specificity+and+application+to+seven+newly+isolated+mutator+strains.&rft.au=Oller%2C+A+R%3BFijalkowska%2C+I+J%3BSchaaper%2C+R+M&rft.aulast=Oller&rft.aufirst=A&rft.date=1993-10-01&rft.volume=292&rft.issue=2&rft.spage=175&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 - 1993-11-02 N1 - Date created - 1993-11-02 N1 - Date revised - 2017-01-13 N1 - Gene symbol - dnaE; dnaQ; galK2 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Specificity determinants of the P1 and P7 plasmid centromere analogs. AN - 76016018; 8415682 AB - The cis-acting parS sites of P1 and P7 are similar in sequence and promote active partition of their respective plasmid prophages to daughter cells when the cognate Par proteins are supplied. Forty of the 94 relevant bases differ between the P1 and P7 parS sites, and the protein-site interactions show complete species specificity. A method was developed to predict which subset of the differing parS bases is responsible. When the four P1 bases thus identified were substituted into the P7 parS site, a complete switch to P1 specificity was observed. The P1-specific bases constitute two CG dinucleotide elements situated 66 bp apart. They lie within repeats of the TCGCCA sequence implicated in secondary contacts with the P1 ParB protein. The equivalent TC dinucleotides in the P7 site were found to be involved in P7 specificity. However, three other P7 bases can also contribute, including two in the heptamer repeats primarily responsible for ParB binding, and the P7-specific information shows some redundancy. The motifs containing the specificity dinucleotides and the primary ParB binding (heptamer) sites bear no obvious relationship of spacing or orientation to each other. For the ParB protein to contact both types of motif at the same time, the topology of the interaction must be complex. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Hayes, F AU - Austin, S J AD - Laboratory of Chromosome Biology, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702. Y1 - 1993/10/01/ PY - 1993 DA - 1993 Oct 01 SP - 9228 EP - 9232 VL - 90 IS - 19 SN - 0027-8424, 0027-8424 KW - parA KW - parB KW - parS KW - Bacterial Proteins KW - 0 KW - chromosome partition proteins, bacterial KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Bacterial Proteins -- genetics KW - Molecular Sequence Data KW - Repetitive Sequences, Nucleic Acid KW - Structure-Activity Relationship KW - Centromere -- physiology KW - Genes, Bacterial KW - Plasmids -- physiology KW - Escherichia coli -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76016018?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Specificity+determinants+of+the+P1+and+P7+plasmid+centromere+analogs.&rft.au=Hayes%2C+F%3BAustin%2C+S+J&rft.aulast=Hayes&rft.aufirst=F&rft.date=1993-10-01&rft.volume=90&rft.issue=19&rft.spage=9228&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 - 1993-11-10 N1 - Date created - 1993-11-10 N1 - Date revised - 2017-01-13 N1 - Gene symbol - parA; parB; parS N1 - SuppNotes - Cited By: Mol Gen Genet. 1977 Mar 28;152(1):71-6 [325389] J Mol Biol. 1969 May 14;41(3):459-72 [4896022] Gene. 1982 Jun;18(3):335-41 [6290337] J Mol Biol. 1983 Sep 15;169(2):353-72 [6312056] Gene. 1984 Nov;31(1-3):165-71 [6098521] J Mol Biol. 1985 Sep 20;185(2):261-72 [3903163] Proc Natl Acad Sci U S A. 1987 Dec;84(23):8544-7 [3317415] J Mol Biol. 1989 Oct 5;209(3):393-406 [2585492] Annu Rev Genet. 1989;23:37-69 [2694936] EMBO J. 1990 Apr;9(4):991-8 [2182325] Nucleic Acids Res. 1990 Sep 11;18(17):4993-5000 [2205834] J Bacteriol. 1991 Jun;173(12):3630-4 [2050624] Mol Microbiol. 1992 May;6(9):1141-7 [1534133] J Biol Chem. 1993 Feb 15;268(5):3616-24 [8429038] J Bacteriol. 1993 Jun;175(11):3443-51 [8501048] J Mol Biol. 1968 Apr 14;33(1):327-9 [4869227] J Bacteriol. 1982 Oct;152(1):63-71 [6749822] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - End-of-dose dystonia in Parkinson's disease. AN - 76013969; 8413978 AB - To evaluate the pathogenesis of end-of-dose dystonia in levodopa-treated patients with Parkinson's disease, we discontinued a steady-state optimal-dose levodopa infusion either abruptly or slowly. Although dystonic signs appeared sooner after sudden levodopa termination, in both situations dystonia emerged only when circulating drug levels had fallen to the same concentration and parkinsonian scores had declined by the same amount. Dystonia onset thus appears to reflect the degree, rather than the rate, of reduction in dopaminergic stimulation, and may involve the preferential interaction of dopamine with a receptor subpopulation that does not mediate its antiparkinsonian efficacy. JF - Neurology AU - Bravi, D AU - Mouradian, M M AU - Roberts, J W AU - Davis, T L AU - Chase, T N AD - Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/10// PY - 1993 DA - October 1993 SP - 2130 EP - 2131 VL - 43 IS - 10 SN - 0028-3878, 0028-3878 KW - Selegiline KW - 2K1V7GP655 KW - Levodopa KW - 46627O600J KW - Carbidopa KW - MNX7R8C5VO KW - Abridged Index Medicus KW - Index Medicus KW - Substance Withdrawal Syndrome -- physiopathology KW - Infusions, Intravenous KW - Selegiline -- therapeutic use KW - Humans KW - Adult KW - Middle Aged KW - Carbidopa -- therapeutic use KW - Levodopa -- administration & dosage KW - Parkinson Disease -- blood KW - Dystonia -- chemically induced KW - Parkinson Disease -- physiopathology KW - Levodopa -- adverse effects KW - Parkinson Disease -- drug therapy KW - Levodopa -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76013969?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurology&rft.atitle=End-of-dose+dystonia+in+Parkinson%27s+disease.&rft.au=Bravi%2C+D%3BMouradian%2C+M+M%3BRoberts%2C+J+W%3BDavis%2C+T+L%3BChase%2C+T+N&rft.aulast=Bravi&rft.aufirst=D&rft.date=1993-10-01&rft.volume=43&rft.issue=10&rft.spage=2130&rft.isbn=&rft.btitle=&rft.title=Neurology&rft.issn=00283878&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-11-12 N1 - Date created - 1993-11-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Biologic therapies for low-grade lymphomas. AN - 76007538; 8211201 JF - Seminars in oncology AU - Parkinson, D R AU - Sznol, M AU - Cheson, B D AD - Investigational Drug Branch, National Cancer Institute, Bethesda, MD 20892. Y1 - 1993/10// PY - 1993 DA - October 1993 SP - 111 EP - 117 VL - 20 IS - 5 Suppl 5 SN - 0093-7754, 0093-7754 KW - Alkylating Agents KW - 0 KW - Antibodies, Monoclonal KW - Interferon-alpha KW - Interleukin-2 KW - Interleukin-4 KW - 207137-56-2 KW - Index Medicus KW - Alkylating Agents -- therapeutic use KW - Animals KW - Interferon-alpha -- therapeutic use KW - Interleukin-2 -- therapeutic use KW - Humans KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Interleukin-4 -- therapeutic use KW - Antibodies, Monoclonal -- therapeutic use KW - Lymphoma, Non-Hodgkin -- therapy KW - Immunotherapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76007538?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Biologic+therapies+for+low-grade+lymphomas.&rft.au=Parkinson%2C+D+R%3BSznol%2C+M%3BCheson%2C+B+D&rft.aulast=Parkinson&rft.aufirst=D&rft.date=1993-10-01&rft.volume=20&rft.issue=5+Suppl+5&rft.spage=111&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 - 1993-11-12 N1 - Date created - 1993-11-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - An evaluation of human recombinant alpha interferon in patients with metastatic gastrinoma. AN - 76003268; 8405864 AB - Metastatic gastrinoma is becoming increasingly recognized in patients with Zollinger-Ellison Syndrome. The mean 5-year survival of these patients is < 20%. Chemotherapeutic regimens are of limited benefit. The aim of this study was to evaluate the use of interferon in these patients because a preliminary report suggested it might be effective. The efficacy and toxicity of interferon was assessed in 13 consecutive Zollinger-Ellison syndrome patients with liver metastases. Patients were treated with human recombinant alpha interferon (5 million IU, subcutaneously [SC]) daily and followed up at 3-month intervals with multiple imaging studies. At each follow-up, toxicity of therapy was assessed and fasting serum gastrin concentrations were obtained. No patient showed a reduction in tumor size at any follow-up. One patient died after 2 months. At 6 months, six patients (46%) had stable tumor size in the liver, although new bone metastases developed in one patient. Three patients showed stable disease for up to 21 months. Changes in serum gastrin correlated with tumor response at 6 months. All patients developed some side effects of therapy. Thirty-one percent required dose reduction, and one patient (8%) had to have interferon therapy interrupted briefly. These results fail to define a therapeutic role for interferon in the treatment of metastatic gastrinoma. JF - Gastroenterology AU - Pisegna, J R AU - Slimak, G G AU - Doppman, J L AU - Strader, D B AU - Metz, D C AU - Benya, R V AU - Orbuch, M AU - Fishbeyn, V A AU - Fraker, D L AU - Norton, J A AD - Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health, Bethesda, Maryland. Y1 - 1993/10// PY - 1993 DA - October 1993 SP - 1179 EP - 1183 VL - 105 IS - 4 SN - 0016-5085, 0016-5085 KW - Gastrins KW - 0 KW - Interferon-alpha KW - Recombinant Proteins KW - Abridged Index Medicus KW - Index Medicus KW - Prospective Studies KW - Humans KW - Gastrins -- blood KW - Adult KW - Recombinant Proteins -- adverse effects KW - Middle Aged KW - Follow-Up Studies KW - Zollinger-Ellison Syndrome -- pathology KW - Recombinant Proteins -- therapeutic use KW - Male KW - Female KW - Interferon-alpha -- therapeutic use KW - Interferon-alpha -- adverse effects KW - Liver Neoplasms -- therapy KW - Gastrinoma -- therapy KW - Liver Neoplasms -- epidemiology KW - Gastrinoma -- epidemiology KW - Liver Neoplasms -- secondary KW - Gastrinoma -- secondary UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76003268?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Gastroenterology&rft.atitle=An+evaluation+of+human+recombinant+alpha+interferon+in+patients+with+metastatic+gastrinoma.&rft.au=Pisegna%2C+J+R%3BSlimak%2C+G+G%3BDoppman%2C+J+L%3BStrader%2C+D+B%3BMetz%2C+D+C%3BBenya%2C+R+V%3BOrbuch%2C+M%3BFishbeyn%2C+V+A%3BFraker%2C+D+L%3BNorton%2C+J+A&rft.aulast=Pisegna&rft.aufirst=J&rft.date=1993-10-01&rft.volume=105&rft.issue=4&rft.spage=1179&rft.isbn=&rft.btitle=&rft.title=Gastroenterology&rft.issn=00165085&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-10-28 N1 - Date created - 1993-10-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characterization of the human interleukin-2 receptor beta-chain gene promoter: regulation of promoter activity by ets gene products. AN - 76002071; 8413220 AB - The interleukin-2 receptor (IL-2R) beta chain (IL-2R beta) is an essential signaling component of high- and intermediate-affinity IL-2Rs. Our laboratory previously reported that a DNA fragment containing 857 bp of 5'-flanking sequence of the human IL-2R beta gene exhibited promoter activity. We have now further characterized the promoter and delineated cis-acting regulatory regions. The region downstream of -363 is critical for basal and phorbol myristate acetate-inducible IL-2R beta promoter activity and contains at least three enhancer-like regions. Among them, the -56 to -34 enhancer was the most potent and had high-level activity in two T-cell lines but not in nonlymphoid HeLaS3 and MG63 cells. This enhancer contains a GGAA Ets binding site which bound two Ets family proteins, Ets-1 and GA-binding protein in vitro. Mutation of the Ets motif strongly diminished both promoter and enhancer activities. We conclude that this Ets binding site plays a key role in regulating basal and phorbol myristate acetate-inducible IL-2R beta promoter activity and may also contribute to tissue-specific expression of the IL-2R beta gene. JF - Molecular and cellular biology AU - Lin, J X AU - Bhat, N K AU - John, S AU - Queale, W S AU - Leonard, W J AD - Section on Pulmonary and Molecular Immunology, National Heart, Lung, and Blood Institute, Bethesda, Maryland 20892. Y1 - 1993/10// PY - 1993 DA - October 1993 SP - 6201 EP - 6210 VL - 13 IS - 10 SN - 0270-7306, 0270-7306 KW - ets KW - ETS1 protein, human KW - 0 KW - Proto-Oncogene Protein c-ets-1 KW - Proto-Oncogene Proteins KW - Proto-Oncogene Proteins c-ets KW - Receptors, Interleukin-2 KW - Transcription Factors KW - DNA KW - 9007-49-2 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Transcription Factors -- metabolism KW - HeLa Cells KW - Humans KW - Amino Acid Sequence KW - Organ Specificity KW - Binding Sites KW - Mutagenesis KW - Base Sequence KW - Enhancer Elements, Genetic KW - Molecular Sequence Data KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Promoter Regions, Genetic KW - Gene Expression Regulation KW - Receptors, Interleukin-2 -- genetics KW - Proto-Oncogene Proteins -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76002071?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Characterization+of+the+human+interleukin-2+receptor+beta-chain+gene+promoter%3A+regulation+of+promoter+activity+by+ets+gene+products.&rft.au=Lin%2C+J+X%3BBhat%2C+N+K%3BJohn%2C+S%3BQueale%2C+W+S%3BLeonard%2C+W+J&rft.aulast=Lin&rft.aufirst=J&rft.date=1993-10-01&rft.volume=13&rft.issue=10&rft.spage=6201&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 - 1993-10-26 N1 - Date created - 1993-10-26 N1 - Date revised - 2017-01-13 N1 - Gene symbol - ets N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1990 May;87(10):3723-7 [2187191] Genes Dev. 1992 Dec;6(12B):2502-12 [1340465] Nature. 1990 Jul 12;346(6280):191-3 [2114554] Nucleic Acids Res. 1990 Jul 11;18(13):3697-703 [1973832] EMBO J. 1990 Oct;9(10):3137-44 [2209540] Science. 1990 Nov 9;250(4982):814-8 [2237431] Genes Dev. 1990 Sep;4(9):1451-3 [2253872] Science. 1991 Aug 16;253(5021):762-8 [1876833] Mol Cell Biol. 1982 Sep;2(9):1044-51 [6960240] Nucleic Acids Res. 1983 Mar 11;11(5):1475-89 [6828386] Nature. 1984 Oct 18-24;311(5987):626-31 [6090948] Nature. 1984 Oct 18-24;311(5987):631-5 [6090949] J Exp Med. 1987 Jan 1;165(1):223-38 [3098894] Proc Natl Acad Sci U S A. 1986 Dec;83(24):9694-8 [3099289] Cell. 1987 Apr 10;49(1):47-56 [3030566] Nature. 1987 Jun 11-17;327(6122):518-22 [3108674] Nucleic Acids Res. 1987 Jul 10;15(13):5490 [3037497] Proc Natl Acad Sci U S A. 1987 Aug;84(15):5394-8 [3110786] Blood. 1987 Oct;70(4):1069-72 [3115332] Science. 1987 Oct 2;238(4823):75-8 [3116668] J Exp Med. 1988 Mar 1;167(3):1265-70 [2832509] Genes Dev. 1988 Jun;2(6):730-42 [2843426] Science. 1989 May 5;244(4904):551-6 [2785715] Annu Rev Biochem. 1989;58:875-911 [2673025] Immunol Today. 1989 Aug;10(8):272-8 [2679647] Annu Rev Cell Biol. 1989;5:397-425 [2688708] Genes Dev. 1989 Sep;3(9):1372-83 [2558055] J Exp Med. 1990 May 1;171(5):1509-26 [1692080] Proc Natl Acad Sci U S A. 1990 May;87(9):3440-4 [2333293] Science. 1991 Aug 16;253(5021):789-92 [1876836] J Virol. 1991 Oct;65(10):5513-23 [1895400] Oncogene. 1991 Dec;6(12):2249-54 [1766672] Nucleic Acids Res. 1992 Feb 25;20(4):699-704 [1542566] J Immunol. 1992 Apr 1;148(7):2154-8 [1545122] Mol Cell Biol. 1992 Mar;12(3):1043-53 [1545787] Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3551-5 [1373502] Genes Dev. 1992 Jun;6(6):975-90 [1592264] Science. 1992 Jul 17;257(5068):379-82 [1631559] Cell Growth Differ. 1992 May;3(5):327-34 [1633115] Trends Biochem Sci. 1992 Jul;17(7):251-6 [1502727] J Biol Chem. 1992 Sep 5;267(25):17957-65 [1517230] J Virol. 1992 Oct;66(10):5890-7 [1527846] J Exp Med. 1992 Nov 1;176(5):1265-72 [1402672] Proc Natl Acad Sci U S A. 1992 Oct 15;89(20):9934-8 [1409722] J Immunol. 1993 Feb 1;150(3):960-70 [8380826] J Immunol. 1993 Mar 1;150(5):1979-87 [8436829] Genes Dev. 1990 Apr;4(4):667-79 [2163347] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cytotoxicity and antitumor effects of growth factor-toxin fusion proteins on human glioblastoma multiforme cells. AN - 75999734; 7692018 AB - The prognosis of glioblastoma multiforme remains poor despite advances in treatment by surgery, irradiation, and chemotherapy. Many malignant gliomas overexpress growth factor receptors. The possibility of targeting these receptors with selective cytotoxic molecules constructed by fusing deoxyribonucleic acid (DNA)-encoding mutant forms of Pseudomonas exotoxin A (PE) with complementary DNA-encoding growth factors was investigated. Several recombinant toxins have been produced, including those in which transforming growth factor (TGF)-alpha, insulin-like growth factor (IGF)-I, and acidic fibroblast growth factor (FGF) were fused to mutant forms of PE lacking the native cell-binding domain. These recombinant proteins are cytotoxic to cells that express specific cell-surface receptors. The cytotoxic activity of TGF-alpha, IGF-I, and acidic FGF chimeric toxins was tested in vitro against human glioblastoma cell lines. Each recombinant toxin exhibited potent and specific killing of cells. The TGF-alpha-PE40 construct was cytotoxic to seven of the eight cell lines and was active at concentrations as low as 0.5 ng/ml (1.1 x 10(-11) M). The acidic FGF-PE40 toxin was also active on seven of the eight cell lines but was 50-fold less active than the TGF-alpha-PE40. The IGF-I-PE40 construct was active on only two cell lines. To determine the possible therapeutic effect in animals, TGF-alpha-PE40 was administered to nude mice bearing subcutaneous human glioblastoma xenografts. The animals were treated for 7 days via a continuous infusion pump placed in the peritoneal cavity. A constant serum level of TGF-alpha-PE40 was achieved that was nontoxic to the mice yet caused a reduction in tumor volume and retarded growth beyond the treatment period. The overexpression of the epidermal growth factor receptor in glioblastomas multiforme and the potency and specificity of the TGF-alpha-PE40 construct designed to target this receptor suggests that TGF-alpha-PE40 has the potential to be an effective antitumor agent for the adjuvant therapy of these carcinomas. JF - Journal of neurosurgery AU - Kunwar, S AU - Pai, L H AU - Pastan, I AD - Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland. Y1 - 1993/10// PY - 1993 DA - October 1993 SP - 569 EP - 576 VL - 79 IS - 4 SN - 0022-3085, 0022-3085 KW - Antineoplastic Agents KW - 0 KW - Bacterial Toxins KW - Exotoxins KW - Growth Substances KW - Recombinant Fusion Proteins KW - Transforming Growth Factor alpha KW - Virulence Factors KW - acidic fibroblast growth factor-Pseudomonas exotoxin A KW - insulin-like growth factor I-Pseudomonas exotoxin A (40) KW - transforming growth factor alpha-Pseudomonas exotoxin A (40) KW - Fibroblast Growth Factor 1 KW - 104781-85-3 KW - Insulin-Like Growth Factor I KW - 67763-96-6 KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - toxA protein, Pseudomonas aeruginosa KW - EC 2.4.2.31 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Drug Stability KW - Humans KW - Mice KW - Mice, Nude KW - Mice, Inbred BALB C KW - Insulin-Like Growth Factor I -- pharmacology KW - Neoplasm Transplantation KW - Fibroblast Growth Factor 1 -- pharmacology KW - Tumor Cells, Cultured KW - Lethal Dose 50 KW - Transplantation, Heterologous KW - Transforming Growth Factor alpha -- pharmacology KW - Pseudomonas aeruginosa KW - Female KW - Exotoxins -- pharmacology KW - Glioblastoma -- pathology KW - Growth Substances -- pharmacology KW - Recombinant Fusion Proteins -- pharmacology KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75999734?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+neurosurgery&rft.atitle=Cytotoxicity+and+antitumor+effects+of+growth+factor-toxin+fusion+proteins+on+human+glioblastoma+multiforme+cells.&rft.au=Kunwar%2C+S%3BPai%2C+L+H%3BPastan%2C+I&rft.aulast=Kunwar&rft.aufirst=S&rft.date=1993-10-01&rft.volume=79&rft.issue=4&rft.spage=569&rft.isbn=&rft.btitle=&rft.title=Journal+of+neurosurgery&rft.issn=00223085&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-11-02 N1 - Date created - 1993-11-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interaction of human beta 1 thyroid hormone receptor and its mutants with DNA and retinoid X receptor beta. T3 response element-dependent dominant negative potency. AN - 75996359; 8408652 AB - Mutations in the human beta thyroid hormone receptor (h-TR beta) gene are associated with the syndrome of generalized resistance to thyroid hormone. We investigated the interaction of three h-TR beta 1 mutants representing different types of functional impairment (kindreds ED, OK, and PV) with different response elements for 3,3',5-triiodothyronine (T3) and with retinoid X receptor beta (RXR beta). The mutant receptors showed an increased tendency to form homodimers on a palindromic T3-response element (TREpal), a direct repeat (DR + 4), and an inverted palindrome (TRElap). On TRElap, wild type TR binding was decreased by T3, while the mutant receptors showed a variably decreased degree of dissociation from TRElap in response to T3. The extent of dissociation was proportional to their T3 binding affinities. RXR beta induced the formation of h-TR beta 1:RXR beta heterodimers equally well for mutants and the wild type h-TR beta 1 on these T3 response elements. However, the T3-dependent increase in heterodimerization with RXR beta was absent or reduced for the mutant TRs. Transient transfection studies indicated that the dominant negative potency was several-fold more pronounced on the TRElap as compared to TREpal or DR + 4. In CV-1 and HeLa cells, transfection of RXR beta could not reverse the dominant negative action. These results demonstrate that the binding of mutant h-TRs to DNA, as well as their dominant negative potency, are TRE dependent. In addition, competition for DNA binding, rather than for limiting amounts of RXR beta, is likely to mediate the dominant negative action. JF - The Journal of clinical investigation AU - Meier, C A AU - Parkison, C AU - Chen, A AU - Ashizawa, K AU - Meier-Heusler, S C AU - Muchmore, P AU - Cheng, S Y AU - Weintraub, B D AD - Molecular and Cellular Endocrinology Branch, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/10// PY - 1993 DA - October 1993 SP - 1986 EP - 1993 VL - 92 IS - 4 SN - 0021-9738, 0021-9738 KW - Oligodeoxyribonucleotides KW - 0 KW - Receptors, Cytoplasmic and Nuclear KW - Receptors, Retinoic Acid KW - Receptors, Thyroid Hormone KW - Recombinant Proteins KW - Retinoid X Receptors KW - Retinoids KW - Transcription Factors KW - Triiodothyronine KW - 06LU7C9H1V KW - Chloramphenicol O-Acetyltransferase KW - EC 2.3.1.28 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Protein Biosynthesis KW - Retinoids -- metabolism KW - Triiodothyronine -- pharmacology KW - Chloramphenicol O-Acetyltransferase -- biosynthesis KW - Humans KW - Transcription, Genetic KW - Chloramphenicol O-Acetyltransferase -- metabolism KW - Cloning, Molecular KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Transfection KW - Recombinant Proteins -- metabolism KW - Genetic Vectors KW - Kinetics KW - Molecular Sequence Data KW - Receptors, Thyroid Hormone -- drug effects KW - Receptors, Cytoplasmic and Nuclear -- metabolism KW - Receptors, Cytoplasmic and Nuclear -- drug effects KW - Receptors, Thyroid Hormone -- metabolism KW - Receptors, Thyroid Hormone -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75996359?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Interaction+of+human+beta+1+thyroid+hormone+receptor+and+its+mutants+with+DNA+and+retinoid+X+receptor+beta.+T3+response+element-dependent+dominant+negative+potency.&rft.au=Meier%2C+C+A%3BParkison%2C+C%3BChen%2C+A%3BAshizawa%2C+K%3BMeier-Heusler%2C+S+C%3BMuchmore%2C+P%3BCheng%2C+S+Y%3BWeintraub%2C+B+D&rft.aulast=Meier&rft.aufirst=C&rft.date=1993-10-01&rft.volume=92&rft.issue=4&rft.spage=1986&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 - 1993-11-12 N1 - Date created - 1993-11-12 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1989 Nov;86(22):8977-81 [2510172] Mol Endocrinol. 1988 Dec;2(12):1217-20 [2905763] Cell. 1990 May 4;61(3):505-14 [2159385] Cell. 1990 Jun 15;61(6):1035-49 [1972036] Mol Endocrinol. 1990 Sep;4(9):1293-301 [2172797] Proc Natl Acad Sci U S A. 1990 Oct;87(20):8160-4 [2236029] Mol Endocrinol. 1990 Oct;4(10):1522-31 [2284000] Mol Endocrinol. 1990 Dec;4(12):1988-94 [2082193] Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3130-4 [1901656] Mol Endocrinol. 1991 Jan;5(1):94-9 [1850112] J Clin Invest. 1991 Jun;87(6):1977-84 [2040690] J Clin Endocrinol Metab. 1992 Jan;74(1):49-55 [1727829] J Clin Invest. 1991 Dec;88(6):2123-30 [1661299] Cell. 1991 Dec 20;67(6):1251-66 [1662118] Nature. 1992 Jan 23;355(6358):359-61 [1309942] Cell. 1992 Jan 24;68(2):377-95 [1310259] Cell. 1992 Jan 24;68(2):397-406 [1310260] Nature. 1992 Jan 30;355(6359):441-6 [1310350] J Biol Chem. 1992 Feb 25;267(6):3565-8 [1740410] Genes Dev. 1992 Mar;6(3):329-44 [1312497] EMBO J. 1992 Apr;11(4):1419-35 [1314168] Mol Endocrinol. 1992 Feb;6(2):248-58 [1569968] Mol Endocrinol. 1992 Mar;6(3):429-42 [1316541] Proc Natl Acad Sci U S A. 1992 Jun 15;89(12):5572-6 [1608968] J Biol Chem. 1992 Jun 25;267(18):13014-9 [1618799] J Biol Chem. 1992 Aug 5;267(22):15784-8 [1379237] Nature. 1992 Aug 13;358(6387):587-91 [1323763] J Biol Chem. 1992 Nov 15;267(32):23248-52 [1331079] J Clin Invest. 1992 Nov;90(5):1825-31 [1430208] J Biol Chem. 1993 Feb 25;268(6):3825-8 [7680034] Nucleic Acids Res. 1983 Mar 11;11(5):1475-89 [6828386] Nature. 1986 Dec 18-31;324(6098):641-6 [2879243] J Biol Chem. 1987 May 5;262(13):6373-82 [3471759] J Endocrinol Invest. 1986 Dec;9(6):459-70 [3571851] Cell. 1988 Jul 29;54(3):313-23 [3396073] J Clin Invest. 1990 Jan;85(1):93-100 [2153155] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Parenteral control of gastric acid hypersecretion in patients with Zollinger-Ellison syndrome. AN - 75994337; 8104773 AB - Parenteral control of gastric acid hypersecretion in patients with Zollinger-Ellison syndrome is increasingly required; however, existing methods of determining the required dose are cumbersome and not applicable in all centers. A previous study suggested that the required parenteral dose of histamine H2-receptor antagonists correlated with the previous oral dose. In the present study, in 31 patients with Zollinger-Ellison syndrome we evaluated the hypothesis that an effective parenteral histamine H2-receptor antagonist dose could be predicted from the previous oral dose. Twenty-three patients were taking oral ranitidine (mean 1.3 g/day), six patients famotidine (152 mg/day), and two patients cimetidine (1.8 g/day). Each patient was treated with a continuous intravenous infusion of the equivalent dose of ranitidine (mean dose 1 mg/kg/hr with 35% requiring 0.5 mg/kg/hr, 49% 1 mg/kg/hr, 3% 1.5 mg/kg/hr, 10% 2 mg/kg/hr, and 3% 2.5 mg/kg/hr. This dose of ranitidine acutely controlled acid secretion ( 10 days. The predicted dose continued to control acid secretion in 95% of patients with one patient requiring one dose adjustment. No biochemical, clinical, or hematological toxicity was seen, although ranitidine was stopped in one patient because of skin rash. These results demonstrate that the parenteral dose of ranitidine required to control acid secretion in patients with Zollinger-Ellison syndrome can be predicted from the oral dose.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Digestive diseases and sciences AU - Vinayek, R AU - Hahne, W F AU - Euler, A R AU - Norton, J A AU - Jensen, R T AD - Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892. Y1 - 1993/10// PY - 1993 DA - October 1993 SP - 1857 EP - 1865 VL - 38 IS - 10 SN - 0163-2116, 0163-2116 KW - Histamine H2 Antagonists KW - 0 KW - Famotidine KW - 5QZO15J2Z8 KW - Cimetidine KW - 80061L1WGD KW - Ranitidine KW - 884KT10YB7 KW - Abridged Index Medicus KW - Index Medicus KW - Administration, Oral KW - Prospective Studies KW - Infusions, Intravenous KW - Famotidine -- administration & dosage KW - Dose-Response Relationship, Drug KW - Humans KW - Cimetidine -- administration & dosage KW - Middle Aged KW - Time Factors KW - Male KW - Female KW - Zollinger-Ellison Syndrome -- surgery KW - Ranitidine -- administration & dosage KW - Zollinger-Ellison Syndrome -- drug therapy KW - Ranitidine -- therapeutic use KW - Zollinger-Ellison Syndrome -- physiopathology KW - Histamine H2 Antagonists -- therapeutic use KW - Histamine H2 Antagonists -- administration & dosage KW - Gastric Acid -- secretion UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75994337?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Digestive+diseases+and+sciences&rft.atitle=Parenteral+control+of+gastric+acid+hypersecretion+in+patients+with+Zollinger-Ellison+syndrome.&rft.au=Vinayek%2C+R%3BHahne%2C+W+F%3BEuler%2C+A+R%3BNorton%2C+J+A%3BJensen%2C+R+T&rft.aulast=Vinayek&rft.aufirst=R&rft.date=1993-10-01&rft.volume=38&rft.issue=10&rft.spage=1857&rft.isbn=&rft.btitle=&rft.title=Digestive+diseases+and+sciences&rft.issn=01632116&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-11-10 N1 - Date created - 1993-11-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Deposition of chromosomal protein HMG-17 during replication affects the nucleosomal ladder and transcriptional potential of nascent chromatin. AN - 75993487; 8404854 AB - A cell-free system from Xenopus eggs was used to study the role of chromosomal protein HMG-17 in the generation of the chromatin structure of transcriptionally active genes. Addition of HMG-17 protein to the extracts, which do not contain structural homologs of the HMG-14/-17 protein family, indicates the protein is incorporated into the nascent template during replication, prior to completion of chromatin assembly. The protein binds to and stabilizes the structure of the nucleosomal core thereby improving the apparent periodicity of the nucleosomal spacing of nascent chromatin. Assembly of HMG-17 into the nascent chromatin structure significantly increased the transcription potential of the 5S RNA gene and satellite I chromatin. Kinetic studies indicate that the increase in transcriptional potential is observed only when HMG-17 is incorporated into nucleosomes during chromatin assembly. JF - The EMBO journal AU - Crippa, M P AU - Trieschmann, L AU - Alfonso, P J AU - Wolffe, A P AU - Bustin, M AD - Laboratory of Molecular Carcinogenesis, NCI, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/10// PY - 1993 DA - October 1993 SP - 3855 EP - 3864 VL - 12 IS - 10 SN - 0261-4189, 0261-4189 KW - Chromatin KW - 0 KW - High Mobility Group Proteins KW - Nucleosomes KW - Index Medicus KW - Xenopus laevis KW - Animals KW - Blotting, Western KW - Oocytes KW - Periodicity KW - Cell-Free System KW - Chromatin -- metabolism KW - Nucleosomes -- metabolism KW - Transcription, Genetic KW - High Mobility Group Proteins -- metabolism KW - DNA Replication UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75993487?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Deposition+of+chromosomal+protein+HMG-17+during+replication+affects+the+nucleosomal+ladder+and+transcriptional+potential+of+nascent+chromatin.&rft.au=Crippa%2C+M+P%3BTrieschmann%2C+L%3BAlfonso%2C+P+J%3BWolffe%2C+A+P%3BBustin%2C+M&rft.aulast=Crippa&rft.aufirst=M&rft.date=1993-10-01&rft.volume=12&rft.issue=10&rft.spage=3855&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 - 1993-10-27 N1 - Date created - 1993-10-27 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nature. 1970 Aug 15;227(5259):680-5 [5432063] Mol Cell Biol. 1991 Feb;11(2):655-65 [1990277] Prog Nucleic Acid Res Mol Biol. 1991;40:143-84 [2031082] Nucleic Acids Res. 1991 Jun 11;19(11):3115-21 [2057367] Proc Natl Acad Sci U S A. 1991 Aug 1;88(15):6829-33 [1650485] Mol Cell Biol. 1991 Sep;11(9):4483-9 [1908554] J Cell Sci. 1991 Jun;99 ( Pt 2):201-6 [1885667] EMBO J. 1991 Oct;10(10):3043-50 [1915279] Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10596-600 [1961726] Biochemistry. 1992 Jan 21;31(2):364-70 [1731893] J Biol Chem. 1992 Feb 15;267(5):2837-40 [1310672] Methods Cell Biol. 1991;36:541-59 [1811151] Arch Biochem Biophys. 1992 May 15;295(1):115-9 [1575506] J Biol Chem. 1992 Jul 25;267(21):15041-8 [1634540] Science. 1976 Sep 3;193(4256):848-56 [948749] Cell. 1976 Jul;8(3):333-47 [986252] Proc Natl Acad Sci U S A. 1976 Nov;73(11):3966-70 [1069279] Proc Natl Acad Sci U S A. 1979 Feb;76(2):630-4 [284387] Cell. 1980 Jan;19(1):289-301 [6244103] J Biol Chem. 1980 Apr 25;255(8):3673-84 [7364765] Cell. 1980 May;20(1):131-41 [6248230] Nucleic Acids Res. 1980 Jun 25;8(12):2787-805 [6448987] Science. 1980 Sep 26;209(4464):1534-6 [7433974] Nucleic Acids Res. 1980 Sep 11;8(17):3757-78 [6449690] Nucleic Acids Res. 1982 Mar 25;10(6):2007-16 [6210881] J Mol Biol. 1983 Apr 25;165(4):567-85 [6189999] J Cell Biol. 1983 Sep;97(3):838-48 [6224801] Proc Natl Acad Sci U S A. 1983 Nov;80(22):6735-9 [6196774] J Biol Chem. 1984 Jan 25;259(2):699-702 [6229533] Cell. 1984 May;37(1):33-41 [6327057] Cell. 1984 Jun;37(2):645-52 [6722885] Chromosoma. 1984;90(5):355-65 [6439496] Exp Cell Res. 1985 Feb;156(2):295-310 [3881264] Exp Cell Res. 1986 Mar;163(1):95-102 [3510889] Exp Cell Res. 1986 Oct;166(2):486-96 [3743668] Nucleic Acids Res. 1987 Apr 24;15(8):3549-61 [3575100] Cell. 1987 Dec 24;51(6):1009-18 [3690659] EMBO J. 1988 Apr;7(4):1071-9 [3402432] EMBO J. 1988 May;7(5):1395-402 [3409869] EMBO J. 1988 Dec 20;7(13):4355-65 [2854062] EMBO J. 1989 Feb;8(2):527-37 [2721490] EMBO J. 1990 Feb;9(2):573-82 [2303043] J Biol Chem. 1990 Mar 15;265(8):4592-9 [2307678] Biochemistry. 1990 Jan 23;29(3):719-31 [1692479] Mol Cell Biol. 1990 Jun;10(6):2863-73 [2160586] Biochim Biophys Acta. 1990 Jul 30;1049(3):231-43 [2200521] Nucleic Acids Res. 1990 Oct 11;18(19):5767-74 [2216769] J Biol Chem. 1990 Nov 25;265(33):20077-80 [2243079] EMBO J. 1990 Dec;9(12):3997-4006 [2249661] Biochemistry. 1992 Sep 1;31(34):7977-88 [1510985] Cell. 1992 Oct 2;71(1):11-22 [1394427] J Mol Biol. 1992 Nov 20;228(2):442-9 [1453455] Exp Cell Res. 1993 Mar;205(1):1-15 [8453983] J Mol Biol. 1993 Apr 5;230(3):824-36 [8478937] J Biol Chem. 1993 May 25;268(15):11389-93 [8496189] Bioessays. 1992 Sep;14(9):597-603 [1365915] Trends Genet. 1990 Dec;6(12):395-400 [2087781] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Halothane hepatitis patients have serum antibodies that react with protein disulfide isomerase. AN - 75990681; 8406360 AB - Clinical and laboratory evidence suggests that the fulminant liver failure sometimes associated with the inhalation anesthetic halothane may be an immune-mediated toxicity. Most importantly, the vast majority of patients with a clinical diagnosis of halothane hepatitis have serum antibodies, which react with one or more specific liver microsomal proteins that have been covalently altered by the trifluoroacetyl chloride metabolite of halothane. The serum antibodies are specific to halothane hepatitis patients and are not seen in sera of patients with other types of liver pathology. In this study, a 57-kD trifluoroacetylated liver microsomal neoantigen associated with halothane hepatitis and native 57-kD protein were purified from liver microsomes of halothane-treated and -untreated rats, respectively. When the purified trifluoroacetylated 57-kD and native 57-kD proteins were used as test antigens in an enzyme-linked immunosorbent assay, serum antibodies from halothane hepatitis patients (n = 40) reacted with both of these proteins to a significantly greater extent than did serum antibodies from control patients (n = 32). On the basis of its apparent monomeric molecular mass, isoelectric point and NH2-terminal amino acid and tryptic peptide sequences, the 57-kD protein has been identified as rat liver protein disulfide isomerase. Antibodies raised against rat liver protein disulfide isomerase also reacted with a protein of approximately 58-kD in human liver microsomes. The results of this investigation suggest that trifluoroacetylated protein disulfide isomerase is one of the immunogens associated with halothane hepatitis. In certain patients it might lead either to specific antibodies or, possibly, to specific T cells, which could be responsible for halothane hepatitis. JF - Hepatology (Baltimore, Md.) AU - Martin, J L AU - Kenna, J G AU - Martin, B M AU - Thomassen, D AU - Reed, G F AU - Pohl, L R AD - Laboratory of Chemical Pharmacology, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/10// PY - 1993 DA - October 1993 SP - 858 EP - 863 VL - 18 IS - 4 SN - 0270-9139, 0270-9139 KW - Antibodies KW - 0 KW - Antigens KW - Trifluoroacetic Acid KW - E5R8Z4G708 KW - Isomerases KW - EC 5.- KW - Protein Disulfide-Isomerases KW - EC 5.3.4.1 KW - Halothane KW - UQT9G45D1P KW - Index Medicus KW - Trifluoroacetic Acid -- immunology KW - Humans KW - Microsomes, Liver -- immunology KW - Antigens -- immunology KW - Trifluoroacetic Acid -- chemistry KW - Molecular Weight KW - Halothane -- metabolism KW - Chemical and Drug Induced Liver Injury -- etiology KW - Antibodies -- blood KW - Isomerases -- immunology KW - Halothane -- adverse effects KW - Chemical and Drug Induced Liver Injury -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75990681?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Halothane+hepatitis+patients+have+serum+antibodies+that+react+with+protein+disulfide+isomerase.&rft.au=Martin%2C+J+L%3BKenna%2C+J+G%3BMartin%2C+B+M%3BThomassen%2C+D%3BReed%2C+G+F%3BPohl%2C+L+R&rft.aulast=Martin&rft.aufirst=J&rft.date=1993-10-01&rft.volume=18&rft.issue=4&rft.spage=858&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 - 1993-10-22 N1 - Date created - 1993-10-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Polyethylene glycol-modified chimeric toxin composed of transforming growth factor alpha and Pseudomonas exotoxin. AN - 75986444; 8402632 AB - Modification of proteins with monomethoxy-polyethylene glycol (mPEG) has been shown to prolong circulation time and to reduce immunogenicity. To make a mPEG-modified recombinant toxin that retained cytotoxic activity but had a longer residence time in circulation, we have constructed an altered form of TGF alpha-PE40, a recombinant toxin composed of human transforming growth factor alpha (TGF alpha) fused to a fragment of Pseudomonas exotoxin (PE38) devoid of its cell-binding domain. In the newly designed protein, termed TGF alpha R29-L2-CH2-PE38QQ delta (TCP), there are no lysine residues in the TGF alpha and PE38 portions. Human IgG4 constant region CH2 and a tetradecapeptide linker; L2, are inserted between TGF alpha and PE38. Together, L2 and CH2 contain 13 lysine residues as potential modification sites for mPEG. mPEG conjugates of TCP (PEG-TCP) were generated and the products were resolved by ion exchange chromatography. Two PEG-TCP species termed B4 and B6 retained 15 and 4% of cytotoxicity, respectively, and 26% of their receptor binding activity compared with the unmodified TCP. Both B4 and B6 had prolonged circulation times in the blood and reduced toxicity in animals. The mean residence times of B4 and B6 were 37 and 68 min, respectively, compared to 7 min for TCP. When administered i.v. to tumor bearing mice, both B4 and B6 produced marked antitumor effects whereas the unmodified TCP had none. Also, the immunogenicity of PEG-TCP was 5-10 times less than that of TCP. We suggest that the prolonged circulating time and reduced toxicity of PEG-TCP compensate for a diminished cytotoxic activity and enlarge significantly the therapeutic window of this chimeric toxin. JF - Cancer research AU - Wang, Q C AU - Pai, L H AU - Debinski, W AU - FitzGerald, D J AU - Pastan, I AD - Laboratory of Molecular Biology, National Cancer Institute, NIH, Bethesda, Maryland 20892. Y1 - 1993/10/01/ PY - 1993 DA - 1993 Oct 01 SP - 4588 EP - 4594 VL - 53 IS - 19 SN - 0008-5472, 0008-5472 KW - Antibodies KW - 0 KW - Bacterial Toxins KW - Exotoxins KW - Immunoglobulin Constant Regions KW - Immunoglobulin G KW - Immunotoxins KW - Recombinant Fusion Proteins KW - Transforming Growth Factor alpha KW - Virulence Factors KW - Polyethylene Glycols KW - 30IQX730WE KW - monomethoxypolyethylene glycol KW - 9004-74-4 KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - toxA protein, Pseudomonas aeruginosa KW - EC 2.4.2.31 KW - Index Medicus KW - Animals KW - Humans KW - Amino Acid Sequence KW - Mice KW - Mice, Nude KW - Mice, Inbred BALB C KW - Cloning, Molecular KW - Immunoglobulin G -- classification KW - Tumor Cells, Cultured KW - Escherichia coli KW - Molecular Sequence Data KW - Transplantation, Heterologous KW - Pseudomonas aeruginosa KW - Antibodies -- analysis KW - Transforming Growth Factor alpha -- therapeutic use KW - Recombinant Fusion Proteins -- pharmacokinetics KW - Polyethylene Glycols -- therapeutic use KW - Transforming Growth Factor alpha -- pharmacokinetics KW - Polyethylene Glycols -- pharmacokinetics KW - Immunotoxins -- metabolism KW - Exotoxins -- pharmacokinetics KW - Immunotoxins -- therapeutic use KW - Exotoxins -- therapeutic use KW - Carcinoma, Squamous Cell -- drug therapy KW - Recombinant Fusion Proteins -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75986444?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Polyethylene+glycol-modified+chimeric+toxin+composed+of+transforming+growth+factor+alpha+and+Pseudomonas+exotoxin.&rft.au=Wang%2C+Q+C%3BPai%2C+L+H%3BDebinski%2C+W%3BFitzGerald%2C+D+J%3BPastan%2C+I&rft.aulast=Wang&rft.aufirst=Q&rft.date=1993-10-01&rft.volume=53&rft.issue=19&rft.spage=4588&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 - 1993-11-02 N1 - Date created - 1993-11-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Modulation of the pulmonary cytochrome P450 system as a factor in pulmonary-selective toxic responses: fact and fiction. AN - 75983848; 8398173 JF - American journal of respiratory cell and molecular biology AU - Philpot, R M AD - Molecular Pharmacology Section, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1993/10// PY - 1993 DA - October 1993 SP - 347 EP - 349 VL - 9 IS - 4 SN - 1044-1549, 1044-1549 KW - Xenobiotics KW - 0 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Index Medicus KW - Animals KW - Humans KW - Xenobiotics -- pharmacology KW - Lung -- drug effects KW - Cytochrome P-450 Enzyme System -- metabolism KW - Lung -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75983848?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+respiratory+cell+and+molecular+biology&rft.atitle=Modulation+of+the+pulmonary+cytochrome+P450+system+as+a+factor+in+pulmonary-selective+toxic+responses%3A+fact+and+fiction.&rft.au=Philpot%2C+R+M&rft.aulast=Philpot&rft.aufirst=R&rft.date=1993-10-01&rft.volume=9&rft.issue=4&rft.spage=347&rft.isbn=&rft.btitle=&rft.title=American+journal+of+respiratory+cell+and+molecular+biology&rft.issn=10441549&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-11-05 N1 - Date created - 1993-11-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of a recombinant CD4-IgG on in vitro T helper cell function: data from a phase I/II study of patients with AIDS. AN - 75975087; 8376811 AB - Ten patients with AIDS were enrolled in a phase I/II protocol of recombinant CD4-IgG (rCD4-IgG) treatment. Patients' peripheral blood leukocytes (PBL) were tested before, during, and after therapy with rCD4-IgG for T helper (TH) cell function assessed by antigen- and mitogen-stimulated proliferation and interleukin-2 production in response to influenza A virus, allogeneic PBL (alloantigens), and phytohemagglutinin. Although clinical benefit was not evident, rCD4-IgG treatment was associated with rapid and potent improved TH cell function for two of three stimuli tested in 90% of the patients. These data are complemented by an in vitro experimental model that demonstrates the opposing immunologic effects of rgp120 and rCD4-IgG on TH cell function of PBL from uninfected individuals. Thus, restoration of TH cell function by rCD4-IgG in the absence of increased CD4 cell counts could be due to removal of an immunosuppressive factor, possibly gp120. These findings suggest that rCD4-IgG can induce partial restoration of immune function in AIDS patients, even in the absence of apparent short-term clinical benefit. JF - The Journal of infectious diseases AU - Clerici, M AU - Yarchoan, R AU - Blatt, S AU - Hendrix, C W AU - Ammann, A J AU - Broder, S AU - Shearer, G M AD - Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/10// PY - 1993 DA - October 1993 SP - 1012 EP - 1016 VL - 168 IS - 4 SN - 0022-1899, 0022-1899 KW - Antigens, CD4 KW - 0 KW - Immunoglobulin G KW - Interleukin-2 KW - Recombinant Proteins KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Leukocytes -- immunology KW - Humans KW - In Vitro Techniques KW - Interleukin-2 -- biosynthesis KW - Leukocytes -- drug effects KW - Recombinant Proteins -- toxicity KW - Acquired Immunodeficiency Syndrome -- therapy KW - Acquired Immunodeficiency Syndrome -- blood KW - Acquired Immunodeficiency Syndrome -- immunology KW - T-Lymphocytes, Helper-Inducer -- drug effects KW - Antigens, CD4 -- toxicity KW - Immunoglobulin G -- toxicity KW - T-Lymphocytes, Helper-Inducer -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75975087?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Effect+of+a+recombinant+CD4-IgG+on+in+vitro+T+helper+cell+function%3A+data+from+a+phase+I%2FII+study+of+patients+with+AIDS.&rft.au=Clerici%2C+M%3BYarchoan%2C+R%3BBlatt%2C+S%3BHendrix%2C+C+W%3BAmmann%2C+A+J%3BBroder%2C+S%3BShearer%2C+G+M&rft.aulast=Clerici&rft.aufirst=M&rft.date=1993-10-01&rft.volume=168&rft.issue=4&rft.spage=1012&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 - 1993-10-21 N1 - Date created - 1993-10-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The special deterrent effects of a jail sanction on first-time drunk drivers: a quasi-experimental study. AN - 75973769; 8397659 AB - This study examines the special deterrent effects of alternative sanctions on first-time offenders convicted of driving while intoxicated (DWI). It uses a quasi-experimental design based on the fact that in Hennepin County, Minnesota, some judges did not comply with the judicial policy that mandated a two-day jail sentence for all first-time DWI offenders. Data were collected on all drunk driving cases adjudicated by two judges during an 11-month period. One judge was known to sentence few first offenders to jail; the other was reputed to sentence virtually all first offenders to jail. Of the 383 offenders sentenced by the two judges, 60 were, reconvicted within the 23-month follow-up period. Using judge as an indirect measure of the jail sanction, we found no statistically significant difference in the recidivism rates of persons sentenced by the "jail" and "no jail" judges. Nor did the sanction have a direct effect. After statistically controlling for offender characteristics and prior traffic record, there was no significant difference between those sentenced to a fine (large or small) with no jail and those who were given a two-day jail sentence plus a small fine. Thus, a two-day jail stay is found to be no more effective in deterring subsequent drunk driving by convicted first offenders than an alternative monetary sanction. JF - Accident; analysis and prevention AU - Martin, S E AU - Annan, S AU - Forst, B AD - Prevention Research Branch, National Institute on Alcohol Abuse and Alcoholism, Rockville, MD 20857. Y1 - 1993/10// PY - 1993 DA - October 1993 SP - 561 EP - 568 VL - 25 IS - 5 SN - 0001-4575, 0001-4575 KW - Index Medicus KW - Regression Analysis KW - Humans KW - Adult KW - Middle Aged KW - Recurrence KW - Male KW - Female KW - Prisons KW - Automobile Driving -- psychology KW - Alcoholic Intoxication KW - Automobile Driving -- legislation & jurisprudence UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75973769?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Accident%3B+analysis+and+prevention&rft.atitle=The+special+deterrent+effects+of+a+jail+sanction+on+first-time+drunk+drivers%3A+a+quasi-experimental+study.&rft.au=Martin%2C+S+E%3BAnnan%2C+S%3BForst%2C+B&rft.aulast=Martin&rft.aufirst=S&rft.date=1993-10-01&rft.volume=25&rft.issue=5&rft.spage=561&rft.isbn=&rft.btitle=&rft.title=Accident%3B+analysis+and+prevention&rft.issn=00014575&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-10-27 N1 - Date created - 1993-10-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Congo red inhibition of scrapie agent replication. AN - 75965540; 8103804 AB - Congo red inhibits the accumulation of protease-resistant PrP in scrapie-infected mouse neuroblastoma cells. Here we show that Congo red also inhibits the replication of scrapie infectivity in these cells. This observation is consistent with the idea that protease-resistant PrP is a vital component of the scrapie agent or that agent replication depends on the presence of protease-resistant PrP in the cell. JF - Journal of virology AU - Caughey, B AU - Ernst, D AU - Race, R E AD - Laboratory of Persistent Viral Diseases, National Institute of Allergy and Infectious Diseases, Rocky Mountain Laboratories, Hamilton, Montana 59840. Y1 - 1993/10// PY - 1993 DA - October 1993 SP - 6270 EP - 6272 VL - 67 IS - 10 SN - 0022-538X, 0022-538X KW - Membrane Glycoproteins KW - 0 KW - PrPSc Proteins KW - Prions KW - Congo Red KW - 3U05FHG59S KW - Index Medicus KW - Animals KW - Membrane Glycoproteins -- biosynthesis KW - Tumor Cells, Cultured KW - Mice KW - Neuroblastoma KW - Prions -- biosynthesis KW - Prions -- drug effects KW - Virus Replication -- drug effects KW - Prions -- isolation & purification KW - Congo Red -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75965540?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Congo+red+inhibition+of+scrapie+agent+replication.&rft.au=Caughey%2C+B%3BErnst%2C+D%3BRace%2C+R+E&rft.aulast=Caughey&rft.aufirst=B&rft.date=1993-10-01&rft.volume=67&rft.issue=10&rft.spage=6270&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 - 1993-10-12 N1 - Date created - 1993-10-12 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: N Engl J Med. 1980 Jun 12;302(24):1333-43 [6990257] J Gen Virol. 1992 Dec;73 ( Pt 12):3319-23 [1361522] Science. 1982 Dec 24;218(4579):1309-11 [6815801] Cell. 1983 Nov;35(1):57-62 [6414721] Nature. 1983 Dec 1-7;306(5942):476-8 [6685822] Cell. 1983 Dec;35(2 Pt 1):349-58 [6418385] J Gen Virol. 1984 Feb;65 ( Pt 2):423-8 [6198455] J Gen Virol. 1984 Aug;65 ( Pt 8):1325-30 [6205119] Nature. 1984 Aug 2-8;310(5976):418-21 [6431296] Cell. 1985 Apr;40(4):735-46 [2859120] Nature. 1985 May 23-29;315(6017):331-3 [3923361] J Gen Virol. 1986 Mar;67 ( Pt 3):463-73 [2419489] Antimicrob Agents Chemother. 1986 Sep;30(3):409-13 [2430521] J Virol. 1987 Jan;61(1):42-9 [2878092] J Virol. 1988 Aug;62(8):2845-9 [2899175] J Virol. 1991 Feb;65(2):1031-4 [1846182] J Gen Virol. 1991 Feb;72 ( Pt 2):457-60 [1704414] J Gen Virol. 1992 Mar;73 ( Pt 3):661-5 [1372039] Nature. 1992 Apr 16;356(6370):598-601 [1348570] Curr Top Microbiol Immunol. 1991;172:195-232 [1687381] J Neurochem. 1992 Aug;59(2):768-71 [1352803] J Virol. 1993 Feb;67(2):643-50 [7678300] Acta Neuropathol. 1981;54(1):63-74 [7195134] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Human immunodeficiency virus infection of the human thymus and disruption of the thymic microenvironment in the SCID-hu mouse. AN - 75964730; 8376927 AB - Infection with the human immunodeficiency virus (HIV) results in immunosuppression and depletion of circulating CD4+ T cells. Since the thymus is the primary organ in which T cells mature it is of interest to examine the effects of HIV infection in this tissue. HIV infection has been demonstrated in the thymuses of infected individuals and thymocytes have been previously demonstrated to be susceptible to HIV infection both in vivo, using the SCID-hu mouse, and in vitro. The present study sought to determine which subsets of thymocytes were infected in the SCID-hu mouse model and to evaluate HIV-related alterations in the thymic microenvironment. Using two different primary HIV isolates, infection was found in CD4+/CD8+ double positive thymocytes as well as in both the CD4+ and CD8+ single positive subsets of thymocytes. The kinetics of infection and resulting viral burden differed among the three thymocyte subsets and depended on which HIV isolate was used for infection. Thymic epithelial (TE) cells were also shown to endocytose virus and to often contain copious amounts of viral RNA in the cytoplasm by in situ hybridization, although productive infection of these cells could not be definitively shown. Furthermore, degenerating TE cells were observed even without detection of HIV in the degenerating cells. Two striking morphologic patterns of infection were seen, involving either predominantly thymocyte infection and depletion, or TE cell involvement with detectable cytoplasmic viral RNA and/or TE cell toxicity. Thus, a variety of cells in the human thymus is susceptible to HIV infection, and infection with HIV results in a marked disruption of the thymic microenvironment leading to depletion of thymocytes and degeneration of TE cells. JF - The Journal of experimental medicine AU - Stanley, S K AU - McCune, J M AU - Kaneshima, H AU - Justement, J S AU - Sullivan, M AU - Boone, E AU - Baseler, M AU - Adelsberger, J AU - Bonyhadi, M AU - Orenstein, J AD - Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/10/01/ PY - 1993 DA - 1993 Oct 01 SP - 1151 EP - 1163 VL - 178 IS - 4 SN - 0022-1007, 0022-1007 KW - gag KW - rev KW - tat KW - Antigens, CD4 KW - 0 KW - Antigens, CD8 KW - DNA, Viral KW - RNA, Viral KW - Index Medicus KW - AIDS/HIV KW - Animals KW - Humans KW - Antigens, CD8 -- analysis KW - Mice KW - Polymerase Chain Reaction KW - Antigens, CD4 -- analysis KW - Chimera KW - DNA, Viral -- analysis KW - T-Lymphocyte Subsets -- microbiology KW - Microscopy, Electron KW - Mice, SCID KW - Fluorescent Antibody Technique KW - RNA, Viral -- analysis KW - Thymus Gland -- immunology KW - Thymus Gland -- ultrastructure KW - HIV Infections -- immunology KW - HIV -- isolation & purification KW - HIV Infections -- microbiology KW - Thymus Gland -- microbiology KW - HIV Infections -- pathology KW - HIV -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75964730?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+experimental+medicine&rft.atitle=Human+immunodeficiency+virus+infection+of+the+human+thymus+and+disruption+of+the+thymic+microenvironment+in+the+SCID-hu+mouse.&rft.au=Stanley%2C+S+K%3BMcCune%2C+J+M%3BKaneshima%2C+H%3BJustement%2C+J+S%3BSullivan%2C+M%3BBoone%2C+E%3BBaseler%2C+M%3BAdelsberger%2C+J%3BBonyhadi%2C+M%3BOrenstein%2C+J&rft.aulast=Stanley&rft.aufirst=S&rft.date=1993-10-01&rft.volume=178&rft.issue=4&rft.spage=1151&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+experimental+medicine&rft.issn=00221007&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-10-15 N1 - Date created - 1993-10-15 N1 - Date revised - 2017-01-13 N1 - Gene symbol - gag; rev; tat N1 - SuppNotes - Cited By: Science. 1987 May 15;236(4803):819-22 [3646751] Nature. 1993 Jun 24;363(6431):732-6 [8515816] Science. 1988 Feb 5;239(4840):617-22 [3277274] Hum Pathol. 1988 Mar;19(3):350-61 [3346011] J Exp Med. 1988 Mar 1;167(3):914-23 [3127528] AIDS. 1988 Jun;2(3):171-7 [2456086] Science. 1988 Sep 23;241(4873):1632-9 [2971269] Science. 1988 Nov 11;242(4880):919-22 [2460922] Science. 1988 Dec 23;242(4886):1684-6 [3201256] J Immunol. 1989 Jan 15;142(2):431-8 [2463307] J Clin Immunol. 1988 Nov;8(6):453-8 [2975670] Clin Immunol Immunopathol. 1989 May;51(2):185-95 [2467778] Science. 1989 Jul 21;245(4915):305-8 [2665081] Am J Pathol. 1989 Jun;134(6):1329-38 [2474255] J Immunol. 1990 Jan 1;144(1):94-102 [2404066] AIDS Res Hum Retroviruses. 1990 Mar;6(3):287-98 [1692721] J Virol. 1990 Aug;64(8):4016-20 [2370688] Ann Intern Med. 1990 Sep 15;113(6):438-43 [1974752] J Exp Med. 1990 Oct 1;172(4):1055-63 [2212942] Proc Natl Acad Sci U S A. 1990 Oct;87(19):7727-31 [2217206] J Immunol. 1991 Apr 1;146(7):2220-6 [1706390] J Immunol. 1991 Jun 1;146(11):3751-6 [1827814] J Immunol. 1991 Jun 15;146(12):4173-9 [1674954] Annu Rev Immunol. 1991;9:399-429 [1910684] J Infect Dis. 1991 Dec;164(6):1051-7 [1955708] Am J Pathol. 1992 Jan;140(1):15-22 [1530997] J Exp Med. 1992 Feb 1;175(2):331-40 [1346269] Pediatrics. 1992 Feb;89(2):297-301 [1734399] J Exp Med. 1984 Apr 1;159(4):1149-68 [6200562] Hum Pathol. 1984 May;15(5):469-74 [6609873] Cell Tissue Res. 1984;237(2):227-37 [6478491] Arch Pathol Lab Med. 1985 Feb;109(2):142-6 [3838438] Am J Clin Pathol. 1985 Jul;84(1):85-95 [4014079] J Exp Med. 1986 Jul 1;164(1):280-90 [3014036] J Immunol. 1987 Feb 1;138(3):680-6 [3492529] Med Hypotheses. 1992 Jan;37(1):16-9 [1349151] J Immunol. 1992 Jul 15;149(2):689-97 [1378076] Nature. 1993 Mar 25;362(6418):355-8 [8455722] Proc Natl Acad Sci U S A. 1987 Jul;84(13):4601-5 [3037522] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A pilot study of sequential therapy with zidovudine plus acyclovir, dideoxyinosine, and dideoxycytidine in patients with severe human immunodeficiency virus infection. AN - 75958272; 8397267 AB - A pilot study was initiated to explore a sequential combination antiretroviral regimen in 21 patients with AIDS or advanced human immunodeficiency virus (HIV) infection, who had received little or no prior anti-HIV therapy. The mean entry CD4 cell count was 184/mm3. Patients received 3-week cycles consisting of zidovudine plus acyclovir, dideoxyinosine, and dideoxycytidine for 1 week each. Overall, the regimen was well tolerated for up to 3 years. The principal toxicities were anemia, nausea, and vomiting; 1 patient developed retinal lesions. The mean CD4 cell count reached a peak of 64 cells/mm3 above baseline at week 8 (P = .005 compared to baseline) and remained above baseline for > 40 weeks. Patients also gained weight and had decreases in serum HIV p24 antigen. Eight patients developed opportunistic infections or tumors. Only 4 patients died during 3 years of follow-up. This regimen appears to be generally tolerable and to have anti-HIV activity. Additional studies will be needed, however, to learn how to best combine the available agents in patients with HIV infection. JF - The Journal of infectious diseases AU - Nguyen, B Y AU - Shay, L E AU - Wyvill, K M AU - Pluda, J M AU - Brawley, O AU - Cohen, R B AU - Whitcup, S M AU - Venzon, D J AU - Broder, S AU - Yarchoan, R AD - Medicine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/10// PY - 1993 DA - October 1993 SP - 810 EP - 817 VL - 168 IS - 4 SN - 0022-1899, 0022-1899 KW - Antigens, CD KW - 0 KW - Antigens, CD4 KW - Biomarkers KW - HIV Core Protein p24 KW - Zidovudine KW - 4B9XT59T7S KW - Zalcitabine KW - 6L3XT8CB3I KW - Didanosine KW - K3GDH6OH08 KW - Acyclovir KW - X4HES1O11F KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Drug Administration Schedule KW - HIV Core Protein p24 -- blood KW - Humans KW - Pilot Projects KW - Antigens, CD -- blood KW - Body Weight KW - Drug Therapy, Combination KW - Antigens, CD4 -- blood KW - T-Lymphocyte Subsets -- immunology KW - Adult KW - Middle Aged KW - Time Factors KW - Biomarkers -- blood KW - Male KW - Zidovudine -- therapeutic use KW - AIDS-Related Complex -- immunology KW - Acyclovir -- therapeutic use KW - Acyclovir -- administration & dosage KW - Acquired Immunodeficiency Syndrome -- drug therapy KW - Zidovudine -- administration & dosage KW - Didanosine -- therapeutic use KW - Zalcitabine -- administration & dosage KW - Acquired Immunodeficiency Syndrome -- blood KW - AIDS-Related Complex -- drug therapy KW - Acquired Immunodeficiency Syndrome -- immunology KW - Didanosine -- administration & dosage KW - AIDS-Related Complex -- blood KW - Zalcitabine -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75958272?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+infectious+diseases&rft.atitle=A+pilot+study+of+sequential+therapy+with+zidovudine+plus+acyclovir%2C+dideoxyinosine%2C+and+dideoxycytidine+in+patients+with+severe+human+immunodeficiency+virus+infection.&rft.au=Nguyen%2C+B+Y%3BShay%2C+L+E%3BWyvill%2C+K+M%3BPluda%2C+J+M%3BBrawley%2C+O%3BCohen%2C+R+B%3BWhitcup%2C+S+M%3BVenzon%2C+D+J%3BBroder%2C+S%3BYarchoan%2C+R&rft.aulast=Nguyen&rft.aufirst=B&rft.date=1993-10-01&rft.volume=168&rft.issue=4&rft.spage=810&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 - 1993-10-21 N1 - Date created - 1993-10-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Moloney murine leukemia virus protease: bacterial expression and characterization of the purified enzyme. AN - 75949569; 8372434 AB - The Moloney murine leukemia virus (Mo-MuLV) protease has been cloned into the prokaryotic expression vector pGEX-2T, expressed in fusion with the glutathione S-transferase from Schistosoma japonicum, and purified to apparent homogeneity after thrombin cleavage of the chimeric protein. The purified protease showed maximum activity at pH 6.0 and was inhibited by several aspartyl protease inhibitors, found to be active toward the human immunodeficiency virus-1 (HIV-1) protease. Peptides representing maturation cleavage sites in Gag and Gag-Pol polyproteins were accurately cleaved by the recombinant protease, and kinetic parameters have been determined. In addition, oligopeptides mimicking the cleavage site found in the transmembrane protein and leading to the formation of p15E and p2E were also hydrolyzed at the expected position. The Mo-MuLV protease appears to be more closely related to the HIV-1 protease than to the mouse mammary tumor virus enzyme, based on its substrate specificity and sensitivity to aspartyl protease inhibitors. JF - Virology AU - Menéndez-Arias, L AU - Gotte, D AU - Oroszlan, S AD - Laboratory of Molecular Virology and Carcinogenesis, NCI-Frederick Cancer Research and Development Center, Maryland 21702-1201. Y1 - 1993/10// PY - 1993 DA - October 1993 SP - 557 EP - 563 VL - 196 IS - 2 SN - 0042-6822, 0042-6822 KW - Fusion Proteins, gag-pol KW - 0 KW - Gene Products, env KW - Gene Products, gag KW - Peptide Fragments KW - Recombinant Fusion Proteins KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Aspartic Acid Endopeptidases KW - EC 3.4.23.- KW - protease, Moloney murine leukemia virus KW - Index Medicus KW - AIDS/HIV KW - Recombinant Fusion Proteins -- metabolism KW - Peptide Fragments -- metabolism KW - Gene Products, env -- metabolism KW - Fusion Proteins, gag-pol -- metabolism KW - Base Sequence KW - Glutathione Transferase -- biosynthesis KW - Molecular Sequence Data KW - Escherichia coli -- genetics KW - Glutathione Transferase -- genetics KW - Amino Acid Sequence KW - Substrate Specificity KW - Gene Products, gag -- metabolism KW - Moloney murine leukemia virus -- enzymology KW - Aspartic Acid Endopeptidases -- genetics KW - Aspartic Acid Endopeptidases -- metabolism KW - Moloney murine leukemia virus -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75949569?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Virology&rft.atitle=Moloney+murine+leukemia+virus+protease%3A+bacterial+expression+and+characterization+of+the+purified+enzyme.&rft.au=Men%C3%A9ndez-Arias%2C+L%3BGotte%2C+D%3BOroszlan%2C+S&rft.aulast=Men%C3%A9ndez-Arias&rft.aufirst=L&rft.date=1993-10-01&rft.volume=196&rft.issue=2&rft.spage=557&rft.isbn=&rft.btitle=&rft.title=Virology&rft.issn=00426822&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-10-14 N1 - Date created - 1993-10-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Work, Self, and Life Satisfaction for Persons with Severe and Persistent Mental Disorders AN - 61635335; 199500157 AB - Interviews with 88 psychiatrically disabled clients of a large mental health center in SC are used to evaluate changes in vocational & residential status, & community tenure in relation to subjective client outcomes. Data regarding self-efficacy, self-esteem, & life satisfaction reveal that only 6-month change in vocational status was positively & significantly related to these subjective outcomes. Findings support a model wherein improvement in vocational status results in higher self-efficacy, which then affects life satisfaction through its impact on self-esteem. 3 Tables, 2 Figures, 30 References. Adapted from the source document. JF - Psychosocial Rehabilitation Journal AU - Arns, Paul G AU - Linney, Jean Ann AD - NIMH Clinical Services Research Program U California, San Francisco 94143 Y1 - 1993/10// PY - 1993 DA - October 1993 SP - 63 EP - 79 VL - 17 IS - 2 SN - 0147-5622, 0147-5622 KW - satisfaction level, vocational/residential factors, psychiatrically disabled clients KW - interviews KW - South Carolina KW - Mental Patients KW - Life Satisfaction KW - Vocational Education KW - Mental Illness KW - Job Training KW - article KW - 6144: social welfare UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/61635335?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Asocialservices&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psychosocial+Rehabilitation+Journal&rft.atitle=Work%2C+Self%2C+and+Life+Satisfaction+for+Persons+with+Severe+and+Persistent+Mental+Disorders&rft.au=Arns%2C+Paul+G%3BLinney%2C+Jean+Ann&rft.aulast=Arns&rft.aufirst=Paul&rft.date=1993-10-01&rft.volume=17&rft.issue=2&rft.spage=63&rft.isbn=&rft.btitle=&rft.title=Psychosocial+Rehabilitation+Journal&rft.issn=01475622&rft_id=info:doi/ LA - English DB - Social Services Abstracts N1 - Date revised - 2007-05-01 N1 - Last updated - 2016-09-28 N1 - SubjectsTermNotLitGenreText - South Carolina; Life Satisfaction; Mental Patients; Mental Illness; Vocational Education; Job Training ER - TY - JOUR T1 - Antimutagenic and mutagenic potentials of Chinese radish. AN - 21253254; 11701536 AB - The edible part of fresh Chinese radish was chopped into small pieces, lyophilized, and then extracted sequentially with hexane, chloroform, and methanol. The solvent in each fraction was removed by evaporation under reduced pressure at 50-55 degrees C, and the residue was dissolved in dimethylsufoxide just before being tested for antimutagenicity as well as mutagenicity using the Salmonella/mammalian microsome mutagenicity test. We found that none of the three fractions exhibited any mutagenicity toward S. typhimurium strains TA98 and TA100 when tested either in the presence or absence of S-9 mix. Interestingly, however, hexane and chloroform extracts could strongly inhibit the mutagenicities of both direct mutagens (e.g., 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide and sodium azide) and indirect mutagens (e.g., aflatoxin B1). In contrast, however, these two fractions did not inhibit the mutagenicity of benzo[a]pyrene, which is also an indirect mutagen. Both hexane and chloroform extracts could also markedly inhibit the activities of rat liver aniline hydroxylase and aminopyrine demethylase. The methanol fraction could inhibit neither the mutagenicities of direct or indirect mutagens tested nor the activities of those two rat liver enzymes. Results of the present study demonstrate that Chinese radish may not contain any mutagenic compound but does contain some nonpolar compounds with antimutagenic activity toward both direct and indirect mutagens. In addition, the antimutagenic activity toward aflatoxin B1 may be partly due to the inhibition of enzymes necessary for activation of this mutagen. JF - Environmental Health Perspectives AU - Rojanapo, W AU - Tepsuwan, A AD - Biochemistry and Chemical Carcinogenesis Section, National Cancer Institute, Bangkok, Thailand. Y1 - 1993/10// PY - 1993 DA - Oct 1993 SP - 247 EP - 252 PB - US Government Printing Office, Superintendent of Documents, P.O. Box 371954 Pittsburgh PA 15250-7954 USA VL - 101 IS - Suppl 3 SN - 0091-6765, 0091-6765 KW - Microbiology Abstracts B: Bacteriology; Environment Abstracts KW - Mutagens KW - Sodium azide KW - Evaporation KW - Methanol KW - Chloroform KW - Hydroxylase KW - Pressure KW - Aflatoxin B1 KW - Microsomes KW - Mutagenicity KW - Aflatoxins KW - Solvents KW - Enzymes KW - Salmonella typhimurium KW - Sodium KW - Liver KW - Benzo(a)pyrene KW - n-Hexane KW - Aniline KW - J 02420:Plant Diseases KW - ENA 02:Toxicology & Environmental Safety UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/21253254?accountid=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=Environmental+Health+Perspectives&rft.atitle=Antimutagenic+and+mutagenic+potentials+of+Chinese+radish.&rft.au=Rojanapo%2C+W%3BTepsuwan%2C+A&rft.aulast=Rojanapo&rft.aufirst=W&rft.date=1993-10-01&rft.volume=101&rft.issue=Suppl+3&rft.spage=247&rft.isbn=&rft.btitle=&rft.title=Environmental+Health+Perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-01-01 N1 - Last updated - 2015-03-31 N1 - SubjectsTermNotLitGenreText - Aflatoxin B1; Mutagens; Mutagenicity; Sodium azide; Microsomes; Evaporation; Methanol; Solvents; Enzymes; Chloroform; Liver; Benzo(a)pyrene; Pressure; Hydroxylase; n-Hexane; Aniline; Sodium; Aflatoxins; Salmonella typhimurium ER - TY - JOUR T1 - Cocaine and Metabolite Excretion in Saliva under Stimulated and Nonstimulated Conditions AN - 1093466376; 17185455 AB - The accessibility of saliva for rapid, noninvasive sampling makes it an attractive biological fluid for detecting drug use. However, little is known about salivary excretion patterns of the major cocaine metabolites, benzoylecgonine (BE) and ecgonine methyl ester (EME). Additionally, there is a general lack of information on the effects of salivary collection conditions on cocaine excretion in saliva. This study documents the profile of cocaine and metabolites in human saliva under stimulated and nonstimulated saliva flow conditions. Saliva samples were obtained periodically from six healthy volunteers who were administered three, equally spaced, single intravenous doses of 25 mg of cocaine during a 6-h test session. On different days, whole saliva was obtained either under nonstimulated or stimulated (sour candy) conditions. The samples were analyzed for cocaine and metabolites by GC/MS. Cocaine, BE, and EME were detected and quantitated in the saliva of all subjects. Cocaine was the predominant analyte identified in all samples. Nonstimulated saliva contained substantially more drug than stimulated samples. The ratio of the area under the curve (AUC) of cocaine in nonstimulated saliva to that of stimulated saliva was variable and ranged from 3.0 to 9.5. The AUC ratios of BE and EME were similar to those observed for cocaine. The lowering of cocaine concentration in saliva in the stimulated flow condition was likely due to an increase in saliva pH associated with increased saliva flow rate; it is known that an increase in saliva pH retards cocaine partitioning into this biological fluid. Generally, the results of this study indicated that cocaine is the predominant analyte in saliva and that concentrations of cocaine and metabolites can be influenced substantially by the method of collection. These factors should be taken into account in the design of saliva tests for detection of cocaine exposure. JF - Journal of Analytical Toxicology AU - Kato, Kenichi AU - Hillsgrove, Mary AU - Weinhold, Linda AU - Gorelick, David A AU - Darwin, William D AU - Cone, Edward J AD - Addiction Research Center, National Institute on Drug Abuse, Baltimore, MD 21224 Y1 - 1993/10// PY - 1993 DA - Oct 1993 SP - 338 EP - 341 PB - Preston Publications, Inc., 6600 W. Touhy Ave. Niles IL 60714 United States VL - 17 IS - 6 SN - 0146-4760, 0146-4760 KW - Toxicology Abstracts KW - Cocaine KW - Drug abuse KW - Excretion KW - Guanylate cyclase KW - Intravenous administration KW - Metabolites KW - Saliva KW - Sampling KW - Sour taste KW - pH effects KW - X 24380:Social Poisons & Drug Abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1093466376?accountid=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+Analytical+Toxicology&rft.atitle=Cocaine+and+Metabolite+Excretion+in+Saliva+under+Stimulated+and+Nonstimulated+Conditions&rft.au=Kato%2C+Kenichi%3BHillsgrove%2C+Mary%3BWeinhold%2C+Linda%3BGorelick%2C+David+A%3BDarwin%2C+William+D%3BCone%2C+Edward+J&rft.aulast=Kato&rft.aufirst=Kenichi&rft.date=1993-10-01&rft.volume=17&rft.issue=6&rft.spage=338&rft.isbn=&rft.btitle=&rft.title=Journal+of+Analytical+Toxicology&rft.issn=01464760&rft_id=info:doi/ L2 - http://www.ingentaconnect.com/content/oup/jat/1993/00000017/00000006/art00003 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2012-10-01 N1 - Last updated - 2012-10-19 N1 - SubjectsTermNotLitGenreText - Guanylate cyclase; Sour taste; Intravenous administration; Excretion; Metabolites; Sampling; Saliva; Drug abuse; Cocaine; pH effects ER - TY - JOUR T1 - Influence of culture medium and protein supplementation on in vitro oocyte maturation and fertilization in the domestic cat. AN - 1037244591; 16727364 AB - Domestic cat oocytes were cultured either in Waymouth MB 753/1 Medium (WAY) or in Eagle's Minimum Essential Medium (MEM) containing FSH, LH and estradiol-17beta and supplememted with one of the following: 5% fetal calf serum (FCS); 4 mg/ml bovine serum albumin (BSA); or 3 mg/ml polyvinylalcohol (PVA, a non-protein control). The oocytes were evaluated for: nuclear maturation after 48 hours of culture (in vitro maturation, IVM); fertilization and cleavage 24 to 30 hours postinsemination (in vitro fertilization, IVF); and early embryo development 48 hours postinsemination. Maturation rates were similar (P>0.05) for WAY + BSA (29.4%), MEM + BSA (46.7%) and MEM + PVA (43.3%), but were different (P0.05) for WAY + BSA (51.4%, 30.5%), MEM + BSA (45.8%, 40.1%) and MEM + PVA (56.1%, 37.4%) and were greater (P<0.05) than all other treatments. These IVM/IVF oocytes were capable of culturing beyond 2-cells, with the highest proportion of 4- and 8- cell embryos forming in WAY and MEM media in the presence of BSA or in MEM medium containing PVA. In the domestic cat IVM/IVF system: both the type of culture medium and protein supplement influence the proportion of oocytes reaching Metaphase II; the type of protein supplement has a more significant (P<0.05) impact than medium on fertilization, cleavage and early embryo development; and nuclear maturation and fertilization in vitro can proceed in this species in the absence of supplementary protein. JF - Theriogenology AU - Johnston, L A AU - Donoghue, A M AU - O'brien, S J AU - Wildt, D E AD - National Zoological Park, Smithsonian Institution Washington, DC 20008 USA; Henry Doorly Zoo, 3701 South 10th Street Omaha, NE 68107 USA; Laboratory of Viral Carcinogenesis, National Cancer Institute Frederick Cancer Research and Development Center Frederick, MD 21701 USA. Y1 - 1993/10// PY - 1993 DA - October 1993 SP - 829 EP - 839 VL - 40 IS - 4 SN - 0093-691X, 0093-691X UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1037244591?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Theriogenology&rft.atitle=Influence+of+culture+medium+and+protein+supplementation+on+in+vitro+oocyte+maturation+and+fertilization+in+the+domestic+cat.&rft.au=Johnston%2C+L+A%3BDonoghue%2C+A+M%3BO%27brien%2C+S+J%3BWildt%2C+D+E&rft.aulast=Johnston&rft.aufirst=L&rft.date=1993-10-01&rft.volume=40&rft.issue=4&rft.spage=829&rft.isbn=&rft.btitle=&rft.title=Theriogenology&rft.issn=0093691X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2012-10-02 N1 - Date created - 2006-05-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Studies on the mutagenic activation of heterocyclic amines by cynomolgus monkey, rat and human microsomes show that cynomolgus monkeys have a low capacity to N-oxidize the quinoxaline-type heterocyclic amines. AN - 76025056; 8221635 AB - A number of mutagens and carcinogens have been isolated from cooked meats. In the current study we investigated the ability of hepatic microsomes from cynomolgus monkeys, Fischer-344 rats and humans to metabolically activate these compounds. Monkeys had almost no capacity to activate the quinoxaline-type compounds to mutagens in the Ames test relative to rats and humans but were able to activate the quinoline, pyridoindole and pyridoimidazole compounds. Differences in the mutagenicity of the quinoline and quinoxaline compounds by monkeys and rats was related to differences in cytochrome P-450-mediated N-oxidation between the species. This suggests that monkeys and rats may have different hepatic cytochrome P-450 isozymes, which are important for the metabolic activation of quinolines and quinoxalines, or that the orthologous monkey cytochromes show a select substrate specificity for the quinolines over the quinoxalines. JF - Cancer letters AU - Davis, C D AU - Adamson, R H AU - Snyderwine, E G AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-0037. Y1 - 1993/09/30/ PY - 1993 DA - 1993 Sep 30 SP - 95 EP - 104 VL - 73 IS - 2-3 SN - 0304-3835, 0304-3835 KW - Imidazoles KW - 0 KW - Indoles KW - Mutagens KW - Quinolines KW - Quinoxalines KW - 2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline KW - 77500-04-0 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Index Medicus KW - Rats KW - Oxidation-Reduction KW - Imidazoles -- pharmacokinetics KW - Animals KW - Rats, Inbred F344 KW - Mutagenicity Tests KW - Imidazoles -- toxicity KW - Macaca fascicularis KW - Biotransformation KW - Humans KW - Cytochrome P-450 Enzyme System -- metabolism KW - Male KW - Indoles -- pharmacokinetics KW - Microsomes, Liver -- metabolism KW - Quinoxalines -- toxicity KW - Quinoxalines -- pharmacokinetics KW - Mutagens -- pharmacokinetics KW - Quinolines -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76025056?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+letters&rft.atitle=Studies+on+the+mutagenic+activation+of+heterocyclic+amines+by+cynomolgus+monkey%2C+rat+and+human+microsomes+show+that+cynomolgus+monkeys+have+a+low+capacity+to+N-oxidize+the+quinoxaline-type+heterocyclic+amines.&rft.au=Davis%2C+C+D%3BAdamson%2C+R+H%3BSnyderwine%2C+E+G&rft.aulast=Davis&rft.aufirst=C&rft.date=1993-09-30&rft.volume=73&rft.issue=2-3&rft.spage=95&rft.isbn=&rft.btitle=&rft.title=Cancer+letters&rft.issn=03043835&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-11-26 N1 - Date created - 1993-11-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - An improved method for generating single-chain antibodies from hybridomas. AN - 75999073; 8409471 AB - Cloning the correct VL kappa gene from hybridomas derived from MOPC-21 can be problematic because such cell lines variably express a transcript which is aberrantly rearranged at the VJ recombination site. Cellular levels of the aberrant transcript can exceed that of productive light chain RNA, so a large proportion of the VL gene-derived products obtained on PCR amplification of hybridoma cDNA may not encode a functional protein. We have developed a method in which antibody variable region genes are recovered from hybridoma cDNA using a unique set of V gene family-specific primers; the V region genes are then spliced by PCR, in the form 5'-VL-LINKER-VH-3' (where the linker encodes [GlyGlyGlyGlySer]3), and cloned into an expression vector under control of T7 RNA polymerase. Plasmid DNA is isolated from colonies, and the insert is expressed in an in vitro rabbit reticulocyte lysate-based coupled transcription/translation system, in a microtiter plate format. Since aberrantly rearranged VL kappa genes contain a translation termination codon at amino acid position 105, only constructs containing the correctly rearranged gene produce a protein of the predicted size. We demonstrate the method by producing the single-chain form of OKT9, a murine IgG1 which binds to the human transferrin receptor, and extend the results to show that the protein generated by the in vitro expression system retains the antigen binding properties of the parent antibody. Our method will be generally useful for screening single-chain antibodies for function prior to large scale production in vivo. JF - Journal of immunological methods AU - Nicholls, P J AU - Johnson, V G AU - Blanford, M D AU - Andrew, S M AD - Biochemistry Section, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/09/27/ PY - 1993 DA - 1993 Sep 27 SP - 81 EP - 91 VL - 165 IS - 1 SN - 0022-1759, 0022-1759 KW - Immunoglobulin Fragments KW - 0 KW - Immunoglobulin Variable Region KW - Receptors, Transferrin KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Animals KW - Humans KW - Amino Acid Sequence KW - Plasmids KW - Polymerase Chain Reaction KW - Base Sequence KW - Tumor Cells, Cultured KW - Receptors, Transferrin -- genetics KW - DNA -- genetics KW - Molecular Sequence Data KW - Vero Cells KW - Receptors, Transferrin -- immunology KW - Mutagenesis, Insertional KW - Immunoglobulin Variable Region -- genetics KW - Immunoglobulin Fragments -- biosynthesis KW - Immunoglobulin Fragments -- genetics KW - Hybridomas -- immunology KW - Immunoglobulin Variable Region -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75999073?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+immunological+methods&rft.atitle=An+improved+method+for+generating+single-chain+antibodies+from+hybridomas.&rft.au=Nicholls%2C+P+J%3BJohnson%2C+V+G%3BBlanford%2C+M+D%3BAndrew%2C+S+M&rft.aulast=Nicholls&rft.aufirst=P&rft.date=1993-09-27&rft.volume=165&rft.issue=1&rft.spage=81&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunological+methods&rft.issn=00221759&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-11-09 N1 - Date created - 1993-11-09 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - L10422; GENBANK; L10423 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Serines and threonines in the gastrin-releasing peptide receptor carboxyl terminus mediate internalization. AN - 75975093; 8397203 AB - Most seven-transmembrane G-protein-coupled receptors are rapidly internalized after binding agonist, but the general amino acid recognition sequences mediating this phenomenon have not been identified. In this study, components of the gastrin-releasing peptide receptor (GRP-R) regulating internalization were identified. Four GRP-R mutants with stop codons placed at variable distances distal to the putative palmitoylation sites Cys340-341 were transiently expressed in CHOP fibroblasts. A construct with a minimal carboxyl tail deletion, T375, bound and internalized agonist similarly to wild type receptor. Progressively larger truncations of the carboxyl terminus, however, increasingly impaired GRP-R-mediated internalization without altering receptor-agonist affinity. Three additional constructs were created: one with the putative palmitoylation sites replaced with Ala (CC340-341AA), one with the carboxyl-terminal protein kinase C-consensus sequence converted to Ala (TS360-361AA), and one with all Ser and Thr distal to Cys341 converted to Ala, Asn, or Gly (JF1). All constructs bound agonist similarly to wild type receptor. CC340-341AA internalized similarly to native receptor (93 +/- 3% of wild type by 60 min), whereas internalization of TS360-361AA was partially attenuated (64 +/- 2% of wild type by 60 min). JF1, however, internalized as poorly as T346, with only 16 +/- 2% of the wild type receptors internalized by 60 min. To assess G-protein coupling, selected receptor constructs were stably transfected into Balb fibroblasts, and phosphoinositol hydrolysis was determined. The largest GRP-R truncation, T346, increased total inositol phosphates (EC50 = 2.9 +/- 0.9 nM) similarly to wild type receptor (EC50 = 5.1 +/- 2.2 nM), as did CC340-341AA (EC50 = 5.4 +/- 1.5 nM) and TS360-361AA (EC50 = 3.1 +/- 1.2 nM). These data demonstrate that the multiple Ser and Thr located within the GRP-R carboxyl terminus distal to Cys341, including but not limited to those within the protein kinase C-consensus sequence, specifically regulate GRP-R internalization rates independent of receptor-G-protein coupling. JF - The Journal of biological chemistry AU - Benya, R V AU - Fathi, Z AU - Battey, J F AU - Jensen, R T AD - Digestive Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/09/25/ PY - 1993 DA - 1993 Sep 25 SP - 20285 EP - 20290 VL - 268 IS - 27 SN - 0021-9258, 0021-9258 KW - Receptors, Bombesin KW - 0 KW - Receptors, Neurotransmitter KW - Recombinant Proteins KW - Threonine KW - 2ZD004190S KW - Serine KW - 452VLY9402 KW - Inositol 1,4,5-Trisphosphate KW - 85166-31-0 KW - DNA KW - 9007-49-2 KW - Bombesin KW - PX9AZU7QPK KW - Index Medicus KW - Animals KW - Recombinant Proteins -- biosynthesis KW - DNA -- metabolism KW - Amino Acid Sequence KW - Mice KW - Fibroblasts -- metabolism KW - Cloning, Molecular KW - Inositol 1,4,5-Trisphosphate -- metabolism KW - Mutagenesis, Site-Directed KW - Transfection KW - Recombinant Proteins -- metabolism KW - Kinetics KW - Binding, Competitive KW - DNA -- genetics KW - Molecular Sequence Data KW - CHO Cells KW - Sequence Deletion KW - Cricetinae KW - Receptors, Neurotransmitter -- metabolism KW - Bombesin -- metabolism KW - Receptors, Neurotransmitter -- genetics KW - Bombesin -- pharmacology KW - Receptors, Neurotransmitter -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75975093?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Serines+and+threonines+in+the+gastrin-releasing+peptide+receptor+carboxyl+terminus+mediate+internalization.&rft.au=Benya%2C+R+V%3BFathi%2C+Z%3BBattey%2C+J+F%3BJensen%2C+R+T&rft.aulast=Benya&rft.aufirst=R&rft.date=1993-09-25&rft.volume=268&rft.issue=27&rft.spage=20285&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 - 1993-10-20 N1 - Date created - 1993-10-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phorbol ester-induced myeloid differentiation is mediated by protein kinase C-alpha and -delta and not by protein kinase C-beta II, -epsilon, -zeta, and -eta. AN - 75974916; 8376369 AB - It is generally accepted that the multiple, similar protein kinase C (PKC) isozymes are responsible for different specialized physiological processes, but evidence that directly assigns specific functions to specific isozymes is scarce. To test whether specific PKC isozymes are involved in myeloid differentiation, we have studied the effect of overexpression of PKC-alpha, -beta II, -delta, -epsilon, -zeta and -eta in 32D, a mouse myeloid progenitor cell line that does not differentiate in response to 12-O-tetradecanoylphorbol-13-acetate (TPA). No significant morphological or phenotypic changes could be observed in unstimulated cells that overexpress any of these isozymes. However, the cell lines that overexpressed PKC-alpha or -delta had acquired the ability to become mature macrophages 2-6 h after TPA stimulation. The overexpression of PKC-beta II, -epsilon, -zeta, or -eta, in contrast, did not permit TPA-induced differentiation. These results indicate that only these two members of the PKC gene family can participate in TPA-induced myeloid differentiation. JF - The Journal of biological chemistry AU - Mischak, H AU - Pierce, J H AU - Goodnight, J AU - Kazanietz, M G AU - Blumberg, P M AU - Mushinski, J F AD - Laboratory of Genetics, National Cancer Institute, Bethesda, Maryland 20892-0037. Y1 - 1993/09/25/ PY - 1993 DA - 1993 Sep 25 SP - 20110 EP - 20115 VL - 268 IS - 27 SN - 0021-9258, 0021-9258 KW - Isoenzymes KW - 0 KW - Recombinant Proteins KW - Protein Kinase C KW - EC 2.7.11.13 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - Recombinant Proteins -- biosynthesis KW - Electrophoresis, Polyacrylamide Gel KW - Mice KW - Phenotype KW - Recombinant Proteins -- isolation & purification KW - Blotting, Western KW - Transfection KW - Recombinant Proteins -- metabolism KW - Kinetics KW - Stem Cells KW - Time Factors KW - Cell Line KW - Protein Kinase C -- metabolism KW - Macrophages -- enzymology KW - Macrophages -- cytology KW - Isoenzymes -- isolation & purification KW - Isoenzymes -- biosynthesis KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Protein Kinase C -- isolation & purification KW - Protein Kinase C -- biosynthesis KW - Macrophages -- drug effects KW - Cell Differentiation -- drug effects KW - Isoenzymes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75974916?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Phorbol+ester-induced+myeloid+differentiation+is+mediated+by+protein+kinase+C-alpha+and+-delta+and+not+by+protein+kinase+C-beta+II%2C+-epsilon%2C+-zeta%2C+and+-eta.&rft.au=Mischak%2C+H%3BPierce%2C+J+H%3BGoodnight%2C+J%3BKazanietz%2C+M+G%3BBlumberg%2C+P+M%3BMushinski%2C+J+F&rft.aulast=Mischak&rft.aufirst=H&rft.date=1993-09-25&rft.volume=268&rft.issue=27&rft.spage=20110&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 - 1993-10-20 N1 - Date created - 1993-10-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The risk of childhood cancer after neonatal exposure to vitamin K. AN - 75923364; 8361503 AB - Two recent studies have found that infants who received intramuscular vitamin K were at twice the expected risk for cancer during childhood. Since nearly all newborns in the United States receive this drug, the public health implications of this association, if confirmed, would be substantial. We examined the relation between vitamin K and cancer in a nested case-control study that used data from the Collaborative Perinatal Project, a multi-center, prospective study of pregnancy, delivery, and childhood. Among 54,795 children born from 1959 through 1966, 48 cases of cancer were diagnosed after the first day of life and before the eighth birthday. Each case child was matched with five randomly selected controls whose last study visit occurred at or after the age when the case child's cancer was diagnosed. Exposure to vitamin K was determined from study forms and medical records. Vitamin K had been administered to 68 percent of the 44 case children and 71 percent of the 226 controls for whom data were available (matched odds ratio, 0.84; 95 percent confidence interval, 0.41 to 1.71). The odds ratio was 0.47 (95 percent confidence interval, 0.14 to 1.55) for leukemia and 1.08 (95 percent confidence interval, 0.45 to 2.61) for other cancers. Sequential adjustment for potential confounding factors did not change the results substantially. We found no association between exposure to vitamin K and an increased risk of any childhood cancer or of all childhood cancers combined, although a slightly increased risk could not be ruled out. The benefits of neonatal vitamin K prophylaxis against hemorrhagic disease have been well described. Unless other evidence supporting an association between vitamin K and cancer appears, there is no reason to abandon the routine administration of vitamin K to newborns. JF - The New England journal of medicine AU - Klebanoff, M A AU - Read, J S AU - Mills, J L AU - Shiono, P H AD - Division of Epidemiology, Statistics, and Prevention Research, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda 20892. Y1 - 1993/09/23/ PY - 1993 DA - 1993 Sep 23 SP - 905 EP - 908 VL - 329 IS - 13 SN - 0028-4793, 0028-4793 KW - Vitamin K KW - 12001-79-5 KW - Abridged Index Medicus KW - Index Medicus KW - Vitamin K Deficiency Bleeding -- prevention & control KW - Odds Ratio KW - Prospective Studies KW - Risk Factors KW - Humans KW - Injections, Intramuscular KW - Confounding Factors (Epidemiology) KW - Infant, Newborn KW - Case-Control Studies KW - Confidence Intervals KW - Child KW - Male KW - Female KW - Vitamin K -- adverse effects KW - Vitamin K -- administration & dosage KW - Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75923364?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+risk+of+childhood+cancer+after+neonatal+exposure+to+vitamin+K.&rft.au=Klebanoff%2C+M+A%3BRead%2C+J+S%3BMills%2C+J+L%3BShiono%2C+P+H&rft.aulast=Klebanoff&rft.aufirst=M&rft.date=1993-09-23&rft.volume=329&rft.issue=13&rft.spage=905&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 - 1993-09-29 N1 - Date created - 1993-09-29 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: N Engl J Med. 1993 Sep 23;329(13):957-8 [8361511] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Saliva testing for drugs of abuse. AN - 76018386; 8215090 AB - Saliva testing for drugs of abuse can provide both qualitative and quantitative information on the drug status of an individual undergoing testing. Self-administration by the oral, intranasal, and smoking routes often produces "shallow depots" of drug that contaminate the oral cavity. This depot produces elevated drug concentrations that can be detected for several hours. Thereafter, saliva drug concentrations generally reflect the free fraction of drug in blood. Also, many drugs are weak bases and saliva concentrations may be highly dependent upon pH conditions. These factors lead to highly variable S/P ratios for many of the drugs of abuse. Table 3 provides a compilation of experimental and theoretical S/P (total) ratios determined for drugs of abuse. Estimations of the theoretical S/P (total) ratios for acidic and basic drugs were based on the Henderson-Hasselbalch equation. Saliva pH was assumed to be 6.8 unless reported otherwise by the investigators. Generally, there was a high correlation of saliva drug concentrations with plasma, especially when oral contamination was eliminated. Assay methodology varied considerably, indicating that saliva assays could be readily developed from existing methodology. There are many potential applications for saliva testing for drugs of abuse. Table 4 lists several general areas in which information from saliva testing would be useful. Clearly, saliva drug tests can reveal the presence of a pharmacologically active drug in an individual at the time of testing. Significant correlations have been found between saliva concentrations of drugs of abuse and behavioral and physiological effects. Results indicate that saliva testing can provide valuable information in diagnostics, treatment, and forensic investigations of individuals suspected of drug abuse. It is expected that saliva testing for drugs of abuse will develop over the next decade into a mature science with substantial new applications. JF - Annals of the New York Academy of Sciences AU - Cone, E J AD - Addiction Research Center, National Institute on Drug Abuse, Baltimore, Maryland 21224. Y1 - 1993/09/20/ PY - 1993 DA - 1993 Sep 20 SP - 91 EP - 127 VL - 694 SN - 0077-8923, 0077-8923 KW - Pharmaceutical Preparations KW - 0 KW - Index Medicus KW - Substance-Related Disorders -- diagnosis KW - Humans KW - Pharmaceutical Preparations -- analysis KW - Saliva -- chemistry KW - Substance Abuse Detection -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76018386?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Saliva+testing+for+drugs+of+abuse.&rft.au=Cone%2C+E+J&rft.aulast=Cone&rft.aufirst=E&rft.date=1993-09-20&rft.volume=694&rft.issue=&rft.spage=91&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 - 1993-11-04 N1 - Date created - 1993-11-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Information analysis of sequences that bind the replication initiator RepA. AN - 75979685; 8377199 AB - The replication initiator protein RepA of plasmid P1 can bind to 14 sites on the plasmid. These sites are variously used to autoregulate RepA synthesis and for initiation and control of DNA replication. Analysis of information (degree of conservation) at the sites revealed three sequence patches of high conservation. By saturation mutagenesis, the conservation at the outer two patches was found to contribute to RepA binding more critically. The guanine bases that are likely to contact RepA through the major groove were identified by methylation interference and methylation protection experiments. These bases mapped to the outer two patches and were separated by one turn of the helix. Therefore, they belong to major grooves on the same face of DNA. All backbone contacts of the protein, determined by hydroxyl radical footprinting, also mapped to the same face. We conclude from this that RepA binds to its site on one face of the DNA. Information analysis of binding sites for several prokaryotic repressors and activators, where the nature of DNA-protein contacts are known, revealed a correlation between the positions of high conservation and the positions of major grooves that faced the protein. The middle patch of high conservation in the RepA binding sites is an exception since in this region a minor groove is likely to face the protein. The simplest model for minor groove contacts suggests that in B-form DNA a T.A base-pair cannot easily be distinguished from an A.T pair by inspection of the minor groove. Yet in the RepA site, a T-->A mutation in the middle patch significantly affects binding. Therefore, the simplest models for both minor and major groove contacts are unlikely. It is possible that the patch determines the proper conformation of the site and thereby contributes to recognition indirectly. JF - Journal of molecular biology AU - Papp, P P AU - Chattoraj, D K AU - Schneider, T D AD - Laboratory of Biochemistry, National Cancer Institute, NIH, Bethesda, MD 20892. Y1 - 1993/09/20/ PY - 1993 DA - 1993 Sep 20 SP - 219 EP - 230 VL - 233 IS - 2 SN - 0022-2836, 0022-2836 KW - Bacterial Proteins KW - 0 KW - DNA, Bacterial KW - DNA-Binding Proteins KW - Oligodeoxyribonucleotides KW - Proteins KW - Recombinant Proteins KW - Repressor Proteins KW - Trans-Activators KW - replication initiator protein KW - DNA Helicases KW - EC 3.6.4.- KW - Index Medicus KW - Recombinant Proteins -- biosynthesis KW - Models, Molecular KW - Repressor Proteins -- metabolism KW - Plasmids KW - Nucleic Acid Conformation KW - Binding Sites KW - Cloning, Molecular KW - Mathematics KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Conserved Sequence KW - Recombinant Proteins -- metabolism KW - Kinetics KW - Molecular Sequence Data KW - Templates, Genetic KW - Oligodeoxyribonucleotides -- metabolism KW - Models, Theoretical KW - Escherichia coli -- metabolism KW - Bacterial Proteins -- biosynthesis KW - DNA, Bacterial -- chemistry KW - Bacterial Proteins -- metabolism KW - DNA, Bacterial -- metabolism KW - DNA Replication KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75979685?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Information+analysis+of+sequences+that+bind+the+replication+initiator+RepA.&rft.au=Papp%2C+P+P%3BChattoraj%2C+D+K%3BSchneider%2C+T+D&rft.aulast=Papp&rft.aufirst=P&rft.date=1993-09-20&rft.volume=233&rft.issue=2&rft.spage=219&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 - 1993-10-20 N1 - Date created - 1993-10-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Neutrophil attractant protein-1 and monocyte chemoattractant protein-1 in human serum. Effects of intravenous lipopolysaccharide on free attractants, specific IgG autoantibodies and immune complexes. AN - 75965798; 8376779 AB - We recently found that normal human sera contain IgG antibodies against two chemoattractants, neutrophil attractant protein-1 (NAP-1/IL-8) and monocyte chemoattractant protein-1 (MCP-1), as well as immune complexes of these proteins. Intravenously administered LPS was reported to cause a sharp rise in serum NAP-1 concentration. Our study was designed to determine if LPS also caused an increase in MCP-1 and to measure associated changes in concentrations of antibody and immune complex. LPS caused a rise to peak within 2 to 3 h in serum concentrations of free NAP-1 and MCP-1, followed by an almost equally rapid fall toward base-line levels by about 5 h postinjection. MCP-1 concentration in sera from the 11 subjects rose to a peak of 330 +/- 52 pM. The peak value for NAP-1 was 80 +/- 11 pM. In 10 of the 11 subjects, free IgG autoantibody to MCP-1 decreased from a mean pre-LPS value of 1820 +/- 660 pM to a mean low of 53% of the respective initial values. Corresponding data for IgG anti-NAP-1 were a pre-LPS concentration of 216 +/- 7 pM, which decreased to a mean low of 44% of the respective initial values. The finding in some subjects of a rapid rise in free antibody after the nadir suggests the possibility of acute regulation of autoantibody secretion rates. Although the results suggested that LPS-induced chemoattractant combined with free antibody, serum concentrations of MCP-1-IgG or NAP-1-IgG did not increase, which points to an as yet unknown mechanism for trapping and elimination of the immune complexes. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Sylvester, I AU - Suffredini, A F AU - Boujoukos, A J AU - Martich, G D AU - Danner, R L AU - Yoshimura, T AU - Leonard, E J AD - Biological Carcinogenesis and Development Program, Program Resources, Inc./DynCorp, National Cancer Institute-Frederick Cancer Research and Development Center, MD. Y1 - 1993/09/15/ PY - 1993 DA - 1993 Sep 15 SP - 3292 EP - 3298 VL - 151 IS - 6 SN - 0022-1767, 0022-1767 KW - Antigen-Antibody Complex KW - 0 KW - Autoantibodies KW - Chemokine CCL2 KW - Chemotactic Factors KW - Immunoglobulin G KW - Interleukin-8 KW - Lipopolysaccharides KW - Abridged Index Medicus KW - Index Medicus KW - Humans KW - Adult KW - Homeostasis KW - Immunoglobulin G -- metabolism KW - Male KW - Female KW - Lipopolysaccharides -- pharmacology KW - Autoantibodies -- blood KW - Chemotactic Factors -- metabolism KW - Antigen-Antibody Complex -- metabolism KW - Interleukin-8 -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75965798?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Neutrophil+attractant+protein-1+and+monocyte+chemoattractant+protein-1+in+human+serum.+Effects+of+intravenous+lipopolysaccharide+on+free+attractants%2C+specific+IgG+autoantibodies+and+immune+complexes.&rft.au=Sylvester%2C+I%3BSuffredini%2C+A+F%3BBoujoukos%2C+A+J%3BMartich%2C+G+D%3BDanner%2C+R+L%3BYoshimura%2C+T%3BLeonard%2C+E+J&rft.aulast=Sylvester&rft.aufirst=I&rft.date=1993-09-15&rft.volume=151&rft.issue=6&rft.spage=3292&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 - 1993-10-20 N1 - Date created - 1993-10-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Amyloid precursor protein in the cerebral cortex is rapidly and persistently induced by loss of subcortical innervation. AN - 75960028; 8378353 AB - Lesions of the cholinergic nucleus basalis of Meynert elevate the ex vivo synthesis of beta amyloid precursor protein (beta-APP) in the cerebral cortex, a major projection region. We have found that this elevation is reflected by increased levels of beta-APP mRNA. The induction is rapid (occurring 60 min after placement of the lesion) and persistent (remaining for at least 45 days after lesioning). Two other subcortical lesions, which result in reductions of cortical adrenergic and serotonergic innervation, similarly induced cortical beta-APP. The beta-APP induction is reversible and does not require loss of the subcortical neurons. Infusion of lidocaine, a calcium antagonist that disrupts neurotransmitter release, into the nucleus basalis of Meynert leads to the temporary reduction of released acetylcholine in the cortex. In this model, beta-APP mRNA levels are elevated shortly after the infusion of lidocaine (90 min) but return to preinfusion levels 7 days after the lidocaine treatment. However, metabolic stresses of the brain, including chronic physostigmine, glucocorticoid, and diabetogenic treatments, fail to induce the beta-APP response. These results suggest that the induction of beta-APP is a specific response to the loss of functional innervation in the cortex. Importantly, these studies show that cortical beta-APP is induced by lesions that mimic the neurochemical deficits most frequently observed in Alzheimer disease. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Wallace, W AU - Ahlers, S T AU - Gotlib, J AU - Bragin, V AU - Sugar, J AU - Gluck, R AU - Shea, P A AU - Davis, K L AU - Haroutunian, V AD - National Institute of Mental Health Neuroscience Center at St. Elizabeths Hospital, Washington, DC 20032. Y1 - 1993/09/15/ PY - 1993 DA - 1993 Sep 15 SP - 8712 EP - 8716 VL - 90 IS - 18 SN - 0027-8424, 0027-8424 KW - Actins KW - 0 KW - Amyloid beta-Protein Precursor KW - Glucocorticoids KW - RNA, Messenger KW - 5,7-Dihydroxytryptamine KW - 31363-74-3 KW - N-Methylaspartate KW - 6384-92-5 KW - Oxidopamine KW - 8HW4YBZ748 KW - Lidocaine KW - 98PI200987 KW - Physostigmine KW - 9U1VM840SP KW - Choline O-Acetyltransferase KW - EC 2.3.1.6 KW - Acetylcholine KW - N9YNS0M02X KW - Norepinephrine KW - X4W3ENH1CV KW - Index Medicus KW - Animals KW - Afferent Pathways -- pathology KW - Physostigmine -- pharmacology KW - RNA, Messenger -- analysis KW - Afferent Pathways -- physiology KW - Diabetes Mellitus, Experimental -- metabolism KW - Polyribosomes -- metabolism KW - Choline O-Acetyltransferase -- metabolism KW - Glucocorticoids -- pharmacology KW - Rats KW - Norepinephrine -- physiology KW - Acetylcholine -- metabolism KW - Rats, Sprague-Dawley KW - RNA, Messenger -- metabolism KW - Afferent Pathways -- drug effects KW - Oxidopamine -- toxicity KW - Kinetics KW - N-Methylaspartate -- toxicity KW - Lidocaine -- pharmacology KW - 5,7-Dihydroxytryptamine -- toxicity KW - Actins -- biosynthesis KW - Time Factors KW - Male KW - Functional Laterality KW - Raphe Nuclei -- physiology KW - Cerebral Cortex -- drug effects KW - Cerebral Cortex -- metabolism KW - Raphe Nuclei -- pathology KW - Amyloid beta-Protein Precursor -- biosynthesis KW - Substantia Innominata -- drug effects KW - Raphe Nuclei -- drug effects KW - Substantia Innominata -- pathology KW - Substantia Innominata -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75960028?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Amyloid+precursor+protein+in+the+cerebral+cortex+is+rapidly+and+persistently+induced+by+loss+of+subcortical+innervation.&rft.au=Wallace%2C+W%3BAhlers%2C+S+T%3BGotlib%2C+J%3BBragin%2C+V%3BSugar%2C+J%3BGluck%2C+R%3BShea%2C+P+A%3BDavis%2C+K+L%3BHaroutunian%2C+V&rft.aulast=Wallace&rft.aufirst=W&rft.date=1993-09-15&rft.volume=90&rft.issue=18&rft.spage=8712&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 - 1993-10-20 N1 - Date created - 1993-10-20 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Neurochem. 1975 Feb;24(2):407-9 [1113118] Exp Brain Res. 1981;43(2):159-72 [6265265] Science. 1982 Mar 5;215(4537):1237-9 [7058341] Brain Res. 1985 Dec 30;361(1-2):212-6 [2935223] Exp Neurol. 1986 Mar;91(3):628-33 [2936617] Nature. 1987 Feb 19-25;325(6106):733-6 [2881207] Neuropharmacology. 1987 Jul;26(7B):903-9 [2821432] EMBO J. 1989 Dec 1;8(12):3627-32 [2583112] Brain Res. 1990 Jan 22;507(2):261-6 [2110845] Aging (Milano). 1990 Sep;2(3):245-58 [1982730] Brain Res Mol Brain Res. 1991 May;10(2):173-8 [1649369] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Glucose transporter recycling in rat adipose cells. Effects of potassium depletion. AN - 75954943; 7690030 AB - Depletion of intracellular potassium (K+) induced a 4-fold increase in basal and 1 microM phorbol-12-myristate-13-acetate (PMA)-stimulated 3-O-methylglucose transport in rat adipose cells. K+ depletion had no effect on the maximum insulin (0.7 microM)-stimulated transport rate but enhanced the sensitivity to insulin 3-fold (EC50 = 0.05 versus 0.15 nM) by a mechanism that did not result from changes in the insulin receptor binding, autophosphorylation, or tyrosine kinase activity. Western blotting analysis revealed that K+ depletion induced a 2.2-fold increase in GLUT4 in plasma membranes from basal cells, enhanced the PMA-stimulated GLUT4 translocation by 4-fold, and increased the 5-fold insulin-stimulated GLUT4 translocation by 15%, indicating the presence of an inactive GLUT4 intermediate. The time course for insulin's stimulation of transport activity was accelerated by K+ depletion (t1/2 = 3 versus 1.5 min). Conversely, the reversal of transport activity, on removal of insulin, was delayed (t1/2 = 11 versus 22 min). The corresponding t1/2 values for the loss of GLUT4 were 22 min in control cells and 40 min in K(+)-depleted cells, again indicating the existence of an inactive intermediate. Photolabeling intact cells with the impermeant, exofacial photolabel 2-N-4-(1-azi-2,2,2-trifluoroethyl)benzoyl-1,3-bis(D-mannos-4 - yloxy)-2-propylamine in the continuous presence of insulin revealed that K+ depletion had no effect on the GLUT4 externalization rate but halved the rate of internalization. K+ depletion elicited entirely analogous effects on the recycling of insulin-like growth factor II/mannose 6-phosphate receptor, strongly supporting the involvement of a coated pit mechanism in the recycling of GLUT4 transporters. An inactive conformation of GLUT4 has been detected in plasma membranes from insulin-stimulated cells, which is enhanced by K+ depletion, suggesting a limitation in the adipose cells' capacity to express active GLUT4 transporters. JF - The Journal of biological chemistry AU - Nishimura, H AU - Zarnowski, M J AU - Simpson, I A AD - Experimental Diabetes, Metabolism and Nutrition Section, National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/09/15/ PY - 1993 DA - 1993 Sep 15 SP - 19246 EP - 19253 VL - 268 IS - 26 SN - 0021-9258, 0021-9258 KW - Insulin KW - 0 KW - Methylglucosides KW - Monosaccharide Transport Proteins KW - Phosphoproteins KW - Receptor, IGF Type 2 KW - 3-O-Methylglucose KW - 146-72-5 KW - Phosphotyrosine KW - 21820-51-9 KW - Tyrosine KW - 42HK56048U KW - Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - Receptor, Insulin KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Potassium KW - RWP5GA015D KW - Index Medicus KW - Animals KW - Receptor, IGF Type 2 -- metabolism KW - Insulin -- pharmacology KW - Protein-Tyrosine Kinases -- metabolism KW - Tyrosine -- analysis KW - Biological Transport -- drug effects KW - Rats KW - Blotting, Western KW - Phosphorylation KW - Kinetics KW - In Vitro Techniques KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Receptor, IGF Type 2 -- isolation & purification KW - Tyrosine -- analogs & derivatives KW - Cell Membrane -- metabolism KW - Intracellular Membranes -- metabolism KW - Phosphoproteins -- isolation & purification KW - Male KW - Receptor, Insulin -- metabolism KW - Phosphoproteins -- metabolism KW - Monosaccharide Transport Proteins -- metabolism KW - Adipose Tissue -- metabolism KW - Methylglucosides -- metabolism KW - Adipose Tissue -- drug effects KW - Potassium -- pharmacology KW - Monosaccharide Transport Proteins -- isolation & purification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75954943?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Glucose+transporter+recycling+in+rat+adipose+cells.+Effects+of+potassium+depletion.&rft.au=Nishimura%2C+H%3BZarnowski%2C+M+J%3BSimpson%2C+I+A&rft.aulast=Nishimura&rft.aufirst=H&rft.date=1993-09-15&rft.volume=268&rft.issue=26&rft.spage=19246&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 - 1993-10-07 N1 - Date created - 1993-10-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Somatic mutations in c-myc intron I cluster in discrete domains that define protein binding sequences. AN - 75954139; 8366102 AB - The activated c-myc allele in Burkitt's lymphoma tumor cells is associated with a clustering of somatic mutations within intron I near the exon I boundary. We have identified several discrete protein binding sites within this region of c-myc intron I designated as myc intron factor-1 (MIF-1), MIF-2, and MIF-3. In addition to our previous characterization of a 20-nucleotide binding site for MIF-1, we now have identified adjacent 20-nucleotide and 34-nucleotide binding sites for MIF-2 and MIF-3, respectively. All three elements are protected from exonuclease digestion by nuclear protein extracts, and each gives rise to a distinct migration pattern on mobility shift assays. In addition, MIF-1, 2, and 3 share a 5-nucleotide (TTATG) internal sequence, which may account for cross-competition of these binding sites in the exonuclease protection experiment. Deletion mutant analyses showed that selective removal of the MIF-3 binding site alone was sufficient to enhance chloramphenicol acetyltransferase reporter activity similar to that observed with larger deletions of myc intron I. We have demonstrated that somatic mutations in activated c-myc alleles are frequently clustered in discrete domains that define protein recognition sequences. JF - The Journal of biological chemistry AU - Yu, B W AU - Ichinose, I AU - Bonham, M A AU - Zajac-Kaye, M AD - Medicine Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/09/15/ PY - 1993 DA - 1993 Sep 15 SP - 19586 EP - 19592 VL - 268 IS - 26 SN - 0021-9258, 0021-9258 KW - c-myc KW - Oligodeoxyribonucleotides KW - 0 KW - Recombinant Proteins KW - Luciferases KW - EC 1.13.12.- KW - Chloramphenicol O-Acetyltransferase KW - EC 2.3.1.28 KW - Index Medicus KW - Base Composition KW - Sequence Homology, Nucleic Acid KW - Exons KW - HeLa Cells KW - Humans KW - Luciferases -- metabolism KW - Chloramphenicol O-Acetyltransferase -- metabolism KW - Binding Sites KW - Mutagenesis KW - Chloramphenicol O-Acetyltransferase -- genetics KW - Promoter Regions, Genetic KW - Base Sequence KW - Tumor Cells, Cultured KW - Transfection KW - Recombinant Proteins -- metabolism KW - Molecular Sequence Data KW - Oligodeoxyribonucleotides -- metabolism KW - Luciferases -- genetics KW - Sequence Deletion KW - Genes, myc KW - Cell Nucleus -- metabolism KW - Introns UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75954139?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Somatic+mutations+in+c-myc+intron+I+cluster+in+discrete+domains+that+define+protein+binding+sequences.&rft.au=Yu%2C+B+W%3BIchinose%2C+I%3BBonham%2C+M+A%3BZajac-Kaye%2C+M&rft.aulast=Yu&rft.aufirst=B&rft.date=1993-09-15&rft.volume=268&rft.issue=26&rft.spage=19586&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 - 1993-10-07 N1 - Date created - 1993-10-07 N1 - Date revised - 2017-01-13 N1 - Gene symbol - c-myc N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - N-methyl-D-aspartate receptor agonists decrease protooncogene bcl-2 mRNA expression in cultured rat cerebellar granule neurons. AN - 75942966; 8103985 AB - The protooncogene bcl-2 was studied as a candidate gene for N-methyl-D-aspartate-(NMDA)-induced excitoprotection of cerebellar granule neurons. Exposure of these neurons to excitoprotective concentrations of NMDA and to excitotoxic concentrations of glutamate decreased bcl-2 mRNA levels. Preexposure to NMDA failed to modify the glutamate-evoked decrease in bcl-2 mRNA but increased neuronal survival from 20% to 100%. Neither the intracellular mechanisms underlying the cascade of excitoprotection induced by NMDA nor those underlying the cascade of glutamate toxicity of cerebellar granule neurons seem to specifically involve changes in bcl-2 mRNA levels. Glutamate did not induce nucleosomal DNA fragmentation but glutamate toxicity was inhibited by aurintricarboxylic acid. Glutamate toxicity of cerebellar granule neurons differs considerably from classical programmed cell death. JF - Biochemical and biophysical research communications AU - Montpied, P AU - Weller, M AU - Paul, S M AD - Section on Molecular Pharmacology, National Institute of Mental Health, Bethesda, Maryland. Y1 - 1993/09/15/ PY - 1993 DA - 1993 Sep 15 SP - 623 EP - 629 VL - 195 IS - 2 SN - 0006-291X, 0006-291X KW - bcl-2 KW - Actins KW - 0 KW - Glutamates KW - Proto-Oncogene Proteins KW - Proto-Oncogene Proteins c-bcl-2 KW - RNA, Messenger KW - Receptors, N-Methyl-D-Aspartate KW - Glutamic Acid KW - 3KX376GY7L KW - Aurintricarboxylic Acid KW - 4431-00-9 KW - N-Methylaspartate KW - 6384-92-5 KW - Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - Index Medicus KW - Rats KW - Animals KW - Dose-Response Relationship, Drug KW - Cells, Cultured KW - Kinetics KW - Protein-Tyrosine Kinases -- biosynthesis KW - Aurintricarboxylic Acid -- pharmacology KW - Actins -- biosynthesis KW - Time Factors KW - Neurons -- metabolism KW - Neurons -- drug effects KW - RNA, Messenger -- biosynthesis KW - Cerebellum -- metabolism KW - Proto-Oncogene Proteins -- biosynthesis KW - Receptors, N-Methyl-D-Aspartate -- physiology KW - Cerebellum -- cytology KW - Glutamates -- pharmacology KW - N-Methylaspartate -- pharmacology KW - Receptors, N-Methyl-D-Aspartate -- drug effects KW - Cerebellum -- drug effects KW - Neurons -- cytology KW - Proto-Oncogenes -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75942966?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+and+biophysical+research+communications&rft.atitle=N-methyl-D-aspartate+receptor+agonists+decrease+protooncogene+bcl-2+mRNA+expression+in+cultured+rat+cerebellar+granule+neurons.&rft.au=Montpied%2C+P%3BWeller%2C+M%3BPaul%2C+S+M&rft.aulast=Montpied&rft.aufirst=P&rft.date=1993-09-15&rft.volume=195&rft.issue=2&rft.spage=623&rft.isbn=&rft.btitle=&rft.title=Biochemical+and+biophysical+research+communications&rft.issn=0006291X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-10-12 N1 - Date created - 1993-10-12 N1 - Date revised - 2017-01-13 N1 - Gene symbol - bcl-2 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Single-copy transduction and expression of human gamma-globin in K562 erythroleukemia cells using recombinant adeno-associated virus vectors: the effect of mutations in NF-E2 and GATA-1 binding motifs within the hypersensitivity site 2 enhancer. AN - 75934821; 8400240 AB - The use of recombinant adeno-associated virus (rAAV) vectors provides a new strategy to investigate the role of specific regulatory elements and trans-acting factors in globin gene expression. We linked hypersensitivity site 2 (HS2) from the locus control region (LCR) to a A gamma-globin gene (A gamma*) mutationally marked to allow its transcript to be distinguished from endogenous gamma-globin mRNA. The vector also contains the phosphotransferase gene that confers resistance to neomycin (NeoR). HS2 region mutations within the NF-E2 motifs prevented NF-E2 binding while preserving AP-1 binding. Another set in the GATA-1 motif prevented binding of the factor. Several NeoR K562 clones containing a single unrearranged RAAV genome with the A gamma* gene linked to the native HS2 core fragment (WT), mutant NF-E2 HS2 (mut-NFE2), mutant GATA-1 HS2 (mut-GATA1), or no HS [(-)HS] were identified. In uninduced K562 cells, mut-NFE2 clones expressed A gamma* mRNA at the same level as the WT clones, compared with a lack of A gamma* signal in the (-)HS2 clones. However, hemin induction of mut-NFE2 clones did not result in an increase in the A gamma* signal above the level seen in uninduced cells. Mut-GATA1 clones expressed the A gamma* mRNA at the same level as WT clones in both uninduced and induced cells. Thus, GATA-1 binding to this site does not appear to be required for the enhancing function of HS2 in this context. This single-copy rAAV transduction model is useful for evaluating the effects of specific mutations in regulatory elements on the transcription of linked genes. JF - Blood AU - Miller, J L AU - Walsh, C E AU - Ney, P A AU - Samulski, R J AU - Nienhuis, A W AD - Clinical Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/09/15/ PY - 1993 DA - 1993 Sep 15 SP - 1900 EP - 1906 VL - 82 IS - 6 SN - 0006-4971, 0006-4971 KW - DNA-Binding Proteins KW - 0 KW - Erythroid-Specific DNA-Binding Factors KW - GATA1 Transcription Factor KW - GATA1 protein, human KW - NF-E2 Transcription Factor KW - NF-E2 Transcription Factor, p45 Subunit KW - NFE2 protein, human KW - RNA, Messenger KW - Transcription Factors KW - Globins KW - 9004-22-2 KW - Abridged Index Medicus KW - Index Medicus KW - Electrophoresis, Polyacrylamide Gel KW - Humans KW - Dependovirus -- genetics KW - Gene Expression KW - Gene Rearrangement KW - RNA, Messenger -- biosynthesis KW - Binding Sites KW - Mutagenesis, Site-Directed KW - Polymerase Chain Reaction KW - Leukemia, Erythroblastic, Acute KW - Tumor Cells, Cultured KW - Genetic Vectors KW - Recombination, Genetic KW - Zinc Fingers -- physiology KW - Globins -- isolation & purification KW - Transcription Factors -- metabolism KW - Zinc Fingers -- genetics KW - Enhancer Elements, Genetic KW - Transcription Factors -- isolation & purification KW - Globins -- genetics KW - DNA-Binding Proteins -- genetics KW - DNA-Binding Proteins -- isolation & purification KW - Transcription Factors -- genetics KW - Globins -- biosynthesis KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75934821?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Single-copy+transduction+and+expression+of+human+gamma-globin+in+K562+erythroleukemia+cells+using+recombinant+adeno-associated+virus+vectors%3A+the+effect+of+mutations+in+NF-E2+and+GATA-1+binding+motifs+within+the+hypersensitivity+site+2+enhancer.&rft.au=Miller%2C+J+L%3BWalsh%2C+C+E%3BNey%2C+P+A%3BSamulski%2C+R+J%3BNienhuis%2C+A+W&rft.aulast=Miller&rft.aufirst=J&rft.date=1993-09-15&rft.volume=82&rft.issue=6&rft.spage=1900&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-10-25 N1 - Date created - 1993-10-25 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Blood 1995 Feb 1;85(3):862 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Collaboration between growth factors and diverse chemical carcinogens in hepatocarcinogenesis of transforming growth factor alpha transgenic mice. AN - 75924565; 8364928 AB - Transforming growth factor alpha (TGF-alpha) has been shown to induce liver tumors within 1 year in transgenic male mice in which this potent mitogen is overexpressed. To determine more precisely how TGF-alpha participates in multistep tumorigenesis of the liver, genotoxic (diethylnitrosamine or dimethylnitrosamine) and nongenotoxic (phenobarbital) chemical carcinogens were administered independently to TGF-alpha transgenic mice [line MT42 on a Crl:CD-1(ICR)BR background]. TGF-alpha overexpression dramatically accelerated carcinogen-induced hepatocarcinogenesis in MT42 males but not females. Interestingly, all three chemical agents were found to enhance strongly both hepatic tumor formation and progression in TGF-alpha transgenic male mice. In this study 100%, 90%, and 78% of transgenic males exposed to diethylnitrosamine, dimethylnitrosamine or phenobarbital, respectively, developed tumors between 24 and 32 weeks of age. Moreover, approximately 70% of tumor-bearing transgenic mice from each treatment group had hepatocellular carcinomas; no malignant lesions were found in any carcinogen-treated or untreated nontransgenic mice or in untreated MT42 mice at this age. These results demonstrate that chemical agents as diverse as nitrosamines and phenobarbital act as cocarcinogens with TGF-alpha in the livers of these transgenic mice, indicating that TGF-alpha possesses the unique ability to complement both initiation and promotion in hepatocarcinogenesis. Furthermore, because carcinogen-induced malignant conversion was restricted to transgenic mice, constitutive TGF-alpha overexpression may promote liver tumor progression as well. JF - Cancer research AU - Takagi, H AU - Sharp, R AU - Takayama, H AU - Anver, M R AU - Ward, J M AU - Merlino, G AD - Laboratory of Molecular Biology, National Cancer Institute, NIH, Bethesda, Maryland 20892. Y1 - 1993/09/15/ PY - 1993 DA - 1993 Sep 15 SP - 4329 EP - 4336 VL - 53 IS - 18 SN - 0008-5472, 0008-5472 KW - Transforming Growth Factor alpha KW - 0 KW - Diethylnitrosamine KW - 3IQ78TTX1A KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - Dimethylnitrosamine KW - M43H21IO8R KW - Index Medicus KW - Diethylnitrosamine -- toxicity KW - Animals KW - Dimethylnitrosamine -- toxicity KW - Mice KW - Receptor, Epidermal Growth Factor -- analysis KW - Mice, Transgenic KW - Male KW - Female KW - Transforming Growth Factor alpha -- genetics KW - Transforming Growth Factor alpha -- physiology KW - Liver Neoplasms, Experimental -- chemically induced KW - Transforming Growth Factor alpha -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75924565?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Collaboration+between+growth+factors+and+diverse+chemical+carcinogens+in+hepatocarcinogenesis+of+transforming+growth+factor+alpha+transgenic+mice.&rft.au=Takagi%2C+H%3BSharp%2C+R%3BTakayama%2C+H%3BAnver%2C+M+R%3BWard%2C+J+M%3BMerlino%2C+G&rft.aulast=Takagi&rft.aufirst=H&rft.date=1993-09-15&rft.volume=53&rft.issue=18&rft.spage=4329&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 - 1993-10-01 N1 - Date created - 1993-10-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - L-BOAA induces selective inhibition of brain mitochondrial enzyme, NADH-dehydrogenase. AN - 76094237; 8242335 AB - Lathyrism, a human neurological disorder has been linked to the excessive consumption of a plant toxin, beta-oxalylamino-L-alanine (L-BOAA) present in Lathyrus sativus. The present study was carried out to elucidate the biochemical mechanisms underlying L-BOAA-induced toxic insult. Incubation of sagittal slices of mouse brain with L-BOAA resulted in dose and time-dependent inhibition of mitochondrial NADH-dehydrogenase (NADH-DH). Significant inhibition of NADH-DH was seen following incubation of brain slices with very low concentration of L-BOAA (0.1 pM). L-BOAA also induced lactate dehydrogenase (LDH) leakage from the slice into the medium in dose-dependent manner. The inhibition of NADH-DH preceded LDH leakage from the slices into the medium. L-BOAA had no effect on other mitochondrial enzymes, namely, isocitrate dehydrogenase or cytochrome c oxidase. Incubation of isolated mouse brain mitochondria with L-BOAA also resulted in inhibition of NADH-DH. L-BOAA-induced inhibition of NADH-DH was prevented by non-N-methyl-D-aspartate (non-NMDA) glutamate receptor antagonists in general and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor antagonist (NBQX) in particular. Other glutamate agonists examined namely, N-methyl-D-aspartate, beta-N-methylamino-L-alanine (L-BMAA), L-glutamic acid, N-acetylaspartylglutamate (NAAG), quisqualic acid, kainic acid or AMPA did not have any effect on NADH-DH activity in slices although they induced LDH leakage from the slice into the medium. Incubation of brain slices with L-BOAA did not induce lipid peroxidation or changes in glutathione levels.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Brain research AU - Pai, K S AU - Ravindranath, V AD - Department of Neurochemistry, National Institute of Mental Health and Neuro Sciences, Bangalore, India. Y1 - 1993/09/10/ PY - 1993 DA - 1993 Sep 10 SP - 215 EP - 221 VL - 621 IS - 2 SN - 0006-8993, 0006-8993 KW - Amino Acids, Diamino KW - 0 KW - Receptors, Glutamate KW - beta-Alanine KW - 11P2JDE17B KW - oxalyldiaminopropionic acid KW - 7554-90-7 KW - L-Lactate Dehydrogenase KW - EC 1.1.1.27 KW - NADH Dehydrogenase KW - EC 1.6.99.3 KW - Index Medicus KW - Animals KW - Dose-Response Relationship, Drug KW - Receptors, Glutamate -- drug effects KW - In Vitro Techniques KW - Mice KW - L-Lactate Dehydrogenase -- metabolism KW - Brain -- enzymology KW - beta-Alanine -- analogs & derivatives KW - Mitochondria -- enzymology KW - Brain -- drug effects KW - Mitochondria -- drug effects KW - NADH Dehydrogenase -- antagonists & inhibitors KW - beta-Alanine -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76094237?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=L-BOAA+induces+selective+inhibition+of+brain+mitochondrial+enzyme%2C+NADH-dehydrogenase.&rft.au=Pai%2C+K+S%3BRavindranath%2C+V&rft.aulast=Pai&rft.aufirst=K&rft.date=1993-09-10&rft.volume=621&rft.issue=2&rft.spage=215&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 - 1993-12-23 N1 - Date created - 1993-12-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Differential modulation of P-glycoprotein transport by protein kinase inhibition. AN - 75940018; 7690250 AB - Previous studies of P-glycoprotein have demonstrated that its function can be modulated by phosphorylation. In the present study, inhibition of protein kinase C with calphostin C or stauroporine or prolonged treatment with the phorbol ester TPA decreased phosphorylation of P-glycoprotein, and impaired transport of vinblastine. Calphostin C also inhibited transport of actinomycin D, vincristine, rhodamine, and azidopine in SW620 Ad300 multidrug-resistant human colon carcinoma cells. Photoaffinity labeling of P-glycoprotein with azidopine was decreased by calphostin C, suggesting that dephosphorylation alters the affinity of P-glycoprotein for its substrates. Impaired transport of rhodamine in normal T lymphocytes treated with staurosporine demonstrates that modulation of P-glycoprotein function is not limited to cells selected for drug resistance in vitro. Transport of P-glycoprotein antagonists in SW620 Ad300 cells was also affected by calphostin C. Cyclosporin A transport decreased, while verapamil transport increased. Cyclosporin A in calphostin C-treated cells resulted in additive P-glycoprotein antagonism, while no additive effect could be demonstrated with verapamil, suggesting that the increase in verapamil transport makes it a poorer P-glycoprotein antagonist. These studies suggest that transport by P-glycoprotein is a dynamic process which can be modulated by phosphorylation, and that antagonists may block P-glycoprotein differently in different phosphorylation states. JF - Biochemistry AU - Bates, S E AU - Lee, J S AU - Dickstein, B AU - Spolyar, M AU - Fojo, A T AD - Medicine Branch, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1993/09/07/ PY - 1993 DA - 1993 Sep 07 SP - 9156 EP - 9164 VL - 32 IS - 35 SN - 0006-2960, 0006-2960 KW - Affinity Labels KW - 0 KW - Alkaloids KW - Azides KW - Carrier Proteins KW - Dihydropyridines KW - Isoenzymes KW - Membrane Glycoproteins KW - Naphthalenes KW - P-Glycoprotein KW - Polycyclic Compounds KW - Rhodamines KW - calphostin complex KW - Dactinomycin KW - 1CC1JFE158 KW - Rhodamine 123 KW - 1N3CZ14C5O KW - Vincristine KW - 5J49Q6B70F KW - Vinblastine KW - 5V9KLZ54CY KW - azidopine KW - 63XR70204A KW - Cyclosporine KW - 83HN0GTJ6D KW - Verapamil KW - CJ0O37KU29 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Staurosporine KW - H88EPA0A3N KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Vinblastine -- pharmacology KW - Drug Resistance -- physiology KW - Dihydropyridines -- pharmacology KW - Rhodamines -- pharmacology KW - Humans KW - Vincristine -- pharmacology KW - Polycyclic Compounds -- pharmacology KW - Verapamil -- pharmacology KW - Isoenzymes -- metabolism KW - Biological Transport -- drug effects KW - Dactinomycin -- pharmacology KW - T-Lymphocytes -- metabolism KW - Affinity Labels -- pharmacology KW - Tumor Cells, Cultured KW - Cyclosporine -- pharmacology KW - Azides -- pharmacology KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Alkaloids -- pharmacology KW - Protein Kinase C -- antagonists & inhibitors KW - Carrier Proteins -- metabolism KW - Membrane Glycoproteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75940018?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Differential+modulation+of+P-glycoprotein+transport+by+protein+kinase+inhibition.&rft.au=Bates%2C+S+E%3BLee%2C+J+S%3BDickstein%2C+B%3BSpolyar%2C+M%3BFojo%2C+A+T&rft.aulast=Bates&rft.aufirst=S&rft.date=1993-09-07&rft.volume=32&rft.issue=35&rft.spage=9156&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-10-08 N1 - Date created - 1993-10-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evidence that the transcription factor USF is a component of the human beta-globin locus control region heteromeric protein complex. AN - 75923292; 8360172 AB - The human locus control region (LCR) consists of four DNase I hypersensitive sites upstream of the epsilon-globin gene and is intimately involved in globin gene transcription. We have used DNase I footprinting with K562 erythroleukemia cell extracts to identify protein components of the minimal LCR element, hypersensitive site 2. Six major regions of protection were observed, and the occupation of two regions (sites II and V) was strongly temperature-dependent. Fractionation of K562 nuclear proteins revealed a single major protein that bound tightly to site II. An E-box was necessary for high affinity binding to DNA. We used antibodies and recombinant USF protein to prove that the helix-loop-helix transcription factor USF is the only detectable component in K562 cells that binds to this site. Despite significant differences between site II and a canonical USF-binding site, the USF binding affinity was comparable for the two sites. In both cases the interaction with the E-box of either wild-type USF or a approximately 15-kDa minimal USF DNA binding polypeptide displays an unusual positive temperature dependence, consistent with the observed footprinting behavior. The results show that a relatively ubiquitous factor, not confined to erythroid cells, is an important part of the complex of proteins bound at hypersensitive site 2 of the LCR in K562 cells. JF - The Journal of biological chemistry AU - Bresnick, E H AU - Felsenfeld, G AD - Laboratory of Molecular Biology, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892. Y1 - 1993/09/05/ PY - 1993 DA - 1993 Sep 05 SP - 18824 EP - 18834 VL - 268 IS - 25 SN - 0021-9258, 0021-9258 KW - DNA Probes KW - 0 KW - DNA-Binding Proteins KW - Nuclear Proteins KW - Recombinant Proteins KW - Transcription Factors KW - USF1 protein, human KW - Upstream Stimulatory Factors KW - Globins KW - 9004-22-2 KW - DNA KW - 9007-49-2 KW - Deoxyribonuclease I KW - EC 3.1.21.1 KW - Index Medicus KW - Electrophoresis, Polyacrylamide Gel KW - Humans KW - Cell Nucleus -- chemistry KW - Temperature KW - Binding Sites KW - Mutagenesis, Site-Directed KW - Promoter Regions, Genetic KW - Base Sequence KW - Leukemia, Erythroblastic, Acute KW - Tumor Cells, Cultured KW - Recombinant Proteins -- metabolism KW - Enhancer Elements, Genetic KW - Molecular Sequence Data KW - Nuclear Proteins -- metabolism KW - Transcription Factors -- metabolism KW - DNA -- metabolism KW - Globins -- genetics KW - DNA -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75923292?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Evidence+that+the+transcription+factor+USF+is+a+component+of+the+human+beta-globin+locus+control+region+heteromeric+protein+complex.&rft.au=Bresnick%2C+E+H%3BFelsenfeld%2C+G&rft.aulast=Bresnick&rft.aufirst=E&rft.date=1993-09-05&rft.volume=268&rft.issue=25&rft.spage=18824&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 - 1993-09-30 N1 - Date created - 1993-09-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Influence of age on the secretory rates of the human minor salivary glands and whole saliva. AN - 85257663; pmid-8240083 AB - This investigation comprised two studies of healthy, unmedicated individuals. The first measured the effect of collection time on the volume of secretions of the minor salivary glands at four specified areas of the lower lip of 13 individuals before and after a mild gustatory stimulus. The second (n = 51) monitored the influence of age and gender on the secretory rates of unstimulated labial, buccal and palatal salivary glands. Also, unstimulated and stimulated flow rates of whole saliva were monitored to provide a point of reference. Volumes of minor gland secretions were measured with a Periotron unit. Results of the first study indicated a linear increase in volumes with collection time (15, 30, 45 and 60 s). Flow rates were similar among the four labial sites, approx. 1 microliter/cm2/min, and were not influenced by mild citric acid stimulation. Results of the second study indicated that flow rates differed significantly (p = 0.0001) among the anatomical sites, with similar rates on the right- and left-hand sides. Gender exerted no influence on flow from the minor salivary glands. Similarly, age exerted no influence on flow from the buccal or labial glands. However, the secretory rate for the palatal glands decreased significantly with age (r = -0.44; p < 0.005). As for unstimulated whole saliva, secretory rates were not influenced by age nor gender; rates for stimulated whole saliva increased with age (r = 0.31; p < 0.05). No association was detected between the flow rates of the whole saliva and that of the minor salivary glands. JF - Archives of Oral Biology AU - Shern, R J AU - Fox, P C AU - Li, S H AD - Clinical Investigations and Patient Care Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892. PY - 1993 SP - 755 EP - 761 VL - 38 IS - 9 SN - 0003-9969, 0003-9969 KW - Regression Analysis KW - Age Factors KW - Salivation KW - Sex Factors KW - Human KW - Aging KW - Citric Acid KW - Specimen Handling KW - Aged KW - Secretory Rate KW - Citrates KW - Multivariate Analysis KW - Stimulation, Chemical KW - Salivary Glands, Minor KW - Aged, 80 and over KW - Adult KW - Middle Age KW - Saliva KW - Time Factors KW - Male KW - Female UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85257663?accountid=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+Oral+Biology&rft.atitle=Influence+of+age+on+the+secretory+rates+of+the+human+minor+salivary+glands+and+whole+saliva.&rft.au=Shern%2C+R+J%3BFox%2C+P+C%3BLi%2C+S+H&rft.aulast=Shern&rft.aufirst=R&rft.date=1993-09-01&rft.volume=38&rft.issue=9&rft.spage=755&rft.isbn=&rft.btitle=&rft.title=Archives+of+Oral+Biology&rft.issn=00039969&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Sodium- and chloride-dependent transporters in brain, kidney, and gut: lessons from complementary DNA cloning and structure-function studies. AN - 76307857; 7922216 AB - The family of Na(+)- and Cl(-)-dependent, 12 transmembrane domain transporter proteins now includes transporters for neurotransmitter molecules in the brain and for substances important in extraneuronal tissues, including adrenal, kidney, and gut. Transported substrates include monoamine and amino acid neurotransmitters and nonperturbing osmolytes. A common protein topology is predicted and features intracellular N- and C-termini possessing phosphorylation sites and at least one large extramembranous loop with N-linked glycosylation. Using the rat dopamine transporter as a template, molecular modeling of putative transmembrane domains coupled with amino acid sequence conservation analysis indicates amino acid residues potentially involved in substrate and/or ion recognition. Targeting such residues with site-directed mutagenesis will help clarify substrate and ion binding sites and should facilitate rational design of therapeutics to combat depression, locomotor disorders, and substance abuse. JF - Current opinion in nephrology and hypertension AU - Surratt, C K AU - Wang, J B AU - Yuhasz, S AU - Amzel, M AU - Kwon, H M AU - Handler, J S AU - Uhl, G R AD - National Institute on Drug Abuse, National Institutes of Health, Bethesda, Maryland. Y1 - 1993/09// PY - 1993 DA - September 1993 SP - 744 EP - 760 VL - 2 IS - 5 SN - 1062-4821, 1062-4821 KW - Carrier Proteins KW - 0 KW - Chlorides KW - Dopamine Plasma Membrane Transport Proteins KW - Membrane Glycoproteins KW - Membrane Transport Proteins KW - Nerve Tissue Proteins KW - DNA KW - 9007-49-2 KW - Sodium KW - 9NEZ333N27 KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Animals KW - Kidney -- metabolism KW - Models, Molecular KW - Humans KW - Digestive System -- metabolism KW - Dopamine -- metabolism KW - Amino Acid Sequence KW - Brain -- metabolism KW - Structure-Activity Relationship KW - Cloning, Molecular KW - DNA -- genetics KW - Molecular Sequence Data KW - Carrier Proteins -- metabolism KW - Carrier Proteins -- chemistry KW - Carrier Proteins -- genetics KW - Chlorides -- metabolism KW - Sodium -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76307857?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+nephrology+and+hypertension&rft.atitle=Sodium-+and+chloride-dependent+transporters+in+brain%2C+kidney%2C+and+gut%3A+lessons+from+complementary+DNA+cloning+and+structure-function+studies.&rft.au=Surratt%2C+C+K%3BWang%2C+J+B%3BYuhasz%2C+S%3BAmzel%2C+M%3BKwon%2C+H+M%3BHandler%2C+J+S%3BUhl%2C+G+R&rft.aulast=Surratt&rft.aufirst=C&rft.date=1993-09-01&rft.volume=2&rft.issue=5&rft.spage=744&rft.isbn=&rft.btitle=&rft.title=Current+opinion+in+nephrology+and+hypertension&rft.issn=10624821&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-10-28 N1 - Date created - 1994-10-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - [Back pain in health care workers]. TT - Il mal di schiena nel personale sanitario. AN - 76234448; 8114654 AB - Back pain is a major health and economic problem for preventive medicine. It has been found to be significantly associated with nursing. The present paper reviews a number of epidemiological studies on back pain in nurses and examines the main confounding factors. The different approaches to back pain prevention are briefly discussed. JF - La Medicina del lavoro AU - Tartaglia, R AU - Baldasseroni, A AU - Occhipinti, E AU - Colombini, D AU - Carnevale, F AU - Giuliano, G AD - Servizio di Prevenzione, Igiene e Sicurezza nei Luoghi di Lavoro USL, Firenze. PY - 1993 SP - 403 EP - 415 VL - 84 IS - 5 SN - 0025-7818, 0025-7818 KW - Index Medicus KW - Humans KW - Back Pain -- epidemiology KW - Occupational Diseases -- prevention & control KW - Health Personnel KW - Occupational Diseases -- epidemiology KW - Back Pain -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76234448?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=La+Medicina+del+lavoro&rft.atitle=%5BBack+pain+in+health+care+workers%5D.&rft.au=Tartaglia%2C+R%3BBaldasseroni%2C+A%3BOcchipinti%2C+E%3BColombini%2C+D%3BCarnevale%2C+F%3BGiuliano%2C+G&rft.aulast=Tartaglia&rft.aufirst=R&rft.date=1993-09-01&rft.volume=84&rft.issue=5&rft.spage=403&rft.isbn=&rft.btitle=&rft.title=La+Medicina+del+lavoro&rft.issn=00257818&rft_id=info:doi/ LA - Italian DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-03-31 N1 - Date created - 1994-03-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dopamine transporter mutants selectively enhance MPP+ transport. AN - 76225101; 8310426 AB - MPP+ (1-methyl-4-phenylpyridinium), a dopaminergic neurotoxin that provides the best available experimental model of Parkinson's disease, is selectively concentrated in dopamine neurons by the dopamine transporter (DAT). DAT also serves as a primary recognition site for cocaine. To help define selective molecular mechanisms by which MPP+ uptake occurs, we have tested dopamine transporters mutated in several residues for their abilities to accumulate dopamine and MPP+, and to bind a cocaine analog. Mutants in DAT 7th and 11th hydrophobic putative transmembrane domains increase MPP+ uptake velocity and affinity (1/KD), respectively. These mutations exert much more modest effects on dopamine uptake and have little impact on cocaine analog binding. These findings provide the first example of mutations that enhance transport and identify specific DAT amino acids selectively involved in neurotoxin uptake. They may also have implications for the feasibility of developing drugs that could specifically block accumulation of Parkinsonism-inducing neurotoxins. JF - Synapse (New York, N.Y.) AU - Kitayama, S AU - Wang, J B AU - Uhl, G R AD - Molecular Neurobiology Branch, National Institute on Drug Abuse, Baltimore, Maryland 21224. Y1 - 1993/09// PY - 1993 DA - September 1993 SP - 58 EP - 62 VL - 15 IS - 1 SN - 0887-4476, 0887-4476 KW - Carrier Proteins KW - 0 KW - Dopamine Plasma Membrane Transport Proteins KW - Membrane Glycoproteins KW - Membrane Transport Proteins KW - Nerve Tissue Proteins KW - Recombinant Proteins KW - 1-Methyl-4-phenylpyridinium KW - R865A5OY8J KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Animals KW - Protein Structure, Secondary KW - Biological Transport KW - Amino Acid Sequence KW - Structure-Activity Relationship KW - Mutagenesis, Site-Directed KW - Transfection KW - Recombinant Proteins -- metabolism KW - Kinetics KW - Binding, Competitive KW - Recombinant Proteins -- chemistry KW - Cell Line KW - Carrier Proteins -- metabolism KW - Carrier Proteins -- chemistry KW - Dopamine -- metabolism KW - 1-Methyl-4-phenylpyridinium -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76225101?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Dopamine+transporter+mutants+selectively+enhance+MPP%2B+transport.&rft.au=Kitayama%2C+S%3BWang%2C+J+B%3BUhl%2C+G+R&rft.aulast=Kitayama&rft.aufirst=S&rft.date=1993-09-01&rft.volume=15&rft.issue=1&rft.spage=58&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 - 1994-03-17 N1 - Date created - 1994-03-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Serum antibodies from halothane hepatitis patients react with the rat endoplasmic reticulum protein ERp72. AN - 76169743; 8292737 AB - Immunoblotting studies have previously shown that serum antibodies from halothane hepatitis patients react with several liver microsomal proteins that have been modified by the trifluoroacetyl halide metabolite of halothane. In this study, an 80-kDa protein recognized by the patients' antibodies has been purified from rat liver microsomes and characterized. When the purified trifluoroacetylated 80-kDa and native 80-kDa proteins were employed as test antigens in an enzyme-linked immunosorbent assay, serum antibodies from halothane hepatitis patients reacted with both of these proteins to a significantly greater extent than did serum antibodies from control patients. Amino acid sequence analyses of several hydrolytic peptide fragments of the 80-kDa protein showed that the protein was 99% identical to the deduced amino acid sequence of a murine cDNA of the luminal endoplasmic reticulum protein ERp72. These results indicate that trifluoroacetylated ERp72 in the liver of halothane hepatitis patients may induce immune responses against epitopes present on the covalently altered protein and those present on the native protein and may have a role in halothane hepatitis. In addition, immunoblot and immunohistochemical studies revealed that the 80-kDa protein was present in all tissues studied, but was in highest concentration in liver, adipose tissue, ovaries, and testes and was enriched in specific cells of some organs. In the future, these findings should help define the physiological function of ERp72. JF - Chemical research in toxicology AU - Pumford, N R AU - Martin, B M AU - Thomassen, D AU - Burris, J A AU - Kenna, J G AU - Martin, J L AU - Pohl, L R AD - Laboratory of Chemical Pharmacology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892. PY - 1993 SP - 609 EP - 615 VL - 6 IS - 5 SN - 0893-228X, 0893-228X KW - Antibodies KW - 0 KW - Membrane Glycoproteins KW - endoplasmic reticulum glycoprotein p72 KW - Trifluoroacetic Acid KW - E5R8Z4G708 KW - Halothane KW - UQT9G45D1P KW - Index Medicus KW - Animals KW - Immunoblotting KW - Microsomes, Liver -- chemistry KW - Humans KW - Amino Acid Sequence KW - Rats KW - Rats, Sprague-Dawley KW - Molecular Sequence Data KW - Enzyme-Linked Immunosorbent Assay KW - Microsomes, Liver -- immunology KW - Immunohistochemistry KW - Trifluoroacetic Acid -- chemistry KW - Male KW - Endoplasmic Reticulum -- metabolism KW - Antibodies -- immunology KW - Halothane -- toxicity KW - Membrane Glycoproteins -- immunology KW - Chemical and Drug Induced Liver Injury -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76169743?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemical+research+in+toxicology&rft.atitle=Serum+antibodies+from+halothane+hepatitis+patients+react+with+the+rat+endoplasmic+reticulum+protein+ERp72.&rft.au=Pumford%2C+N+R%3BMartin%2C+B+M%3BThomassen%2C+D%3BBurris%2C+J+A%3BKenna%2C+J+G%3BMartin%2C+J+L%3BPohl%2C+L+R&rft.aulast=Pumford&rft.aufirst=N&rft.date=1993-09-01&rft.volume=6&rft.issue=5&rft.spage=609&rft.isbn=&rft.btitle=&rft.title=Chemical+research+in+toxicology&rft.issn=0893228X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-03-01 N1 - Date created - 1994-03-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of metallothionein in zinc(II) and chromium(III) mediated tolerance to carbon tetrachloride hepatotoxicity: evidence against a trichloromethyl radical-scavenging mechanism. AN - 76168553; 8292750 AB - The .CCl3 radical generated during the metabolism of CCl4 is readily spin trapped in vivo and in vitro by phenyl N-tert-butylnitrone (PBN) to form the stable PBN/.CCl3 radical adduct, which can then be extracted into organic solvents and detected by ESR spectroscopy. We have used this technique to examine the proposed protective roles of Zn(II), Cr(III), and metallothionein (MT) against carbon tetrachloride toxicity in vivo. Hepatic MT, which is induced by Zn(II), has been proposed to protect against CCl4-induced cellular damage by scavenging the free radical metabolites formed. CCl4-induced hepatotoxicity was significantly suppressed in male Sprague-Dawley rats pretreated with a single dose of 5 mg/kg Zn(II) or Cr(III) according to standard serum assays for liver-specific enzymes, and hepatic MT was elevated after pretreatment with either Zn(II) or Cr(III). In vitro, no difference was detected in either the amount of CCl4-derived free radical metabolites formed or the rate at which they were formed by microsomes from rats pretreated 24 h in advance with 5 mg/kg Zn(II) or Cr(III). Extraction of rat liver with 2:1 chloroform/methanol 1 h after the administration of a 0.8 mL/kg intraperitoneal or intragastric dose of CCl4 also revealed no difference in the amount of trichloromethyl radical spin trapped in vivo following pretreatment with either Zn(II) or Cr(III). These results suggest that pretreatment with either Zn(II) or Cr(III) does not affect CCl4 metabolism nor does the MT significantly scavenge the trichloromethyl free radical metabolite. JF - Chemical research in toxicology AU - Hanna, P M AU - Kadiiska, M B AU - Jordan, S J AU - Mason, R P AD - Laboratory of Molecular Biophysics, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709. PY - 1993 SP - 711 EP - 717 VL - 6 IS - 5 SN - 0893-228X, 0893-228X KW - Free Radical Scavengers KW - 0 KW - Chromium KW - 0R0008Q3JB KW - Chloroform KW - 7V31YC746X KW - Metallothionein KW - 9038-94-2 KW - Zinc KW - J41CSQ7QDS KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Microsomes, Liver -- metabolism KW - Microsomes, Liver -- enzymology KW - In Vitro Techniques KW - Male KW - Chloroform -- metabolism KW - Chemical and Drug Induced Liver Injury -- prevention & control KW - Zinc -- pharmacology KW - Carbon Tetrachloride Poisoning -- prevention & control KW - Chromium -- pharmacology KW - Metallothionein -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76168553?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemical+research+in+toxicology&rft.atitle=Role+of+metallothionein+in+zinc%28II%29+and+chromium%28III%29+mediated+tolerance+to+carbon+tetrachloride+hepatotoxicity%3A+evidence+against+a+trichloromethyl+radical-scavenging+mechanism.&rft.au=Hanna%2C+P+M%3BKadiiska%2C+M+B%3BJordan%2C+S+J%3BMason%2C+R+P&rft.aulast=Hanna&rft.aufirst=P&rft.date=1993-09-01&rft.volume=6&rft.issue=5&rft.spage=711&rft.isbn=&rft.btitle=&rft.title=Chemical+research+in+toxicology&rft.issn=0893228X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-03-01 N1 - Date created - 1994-03-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cytotoxic effects of vascular smooth muscle cells of the chimeric toxin, heparin binding TGF alpha-Pseudomonas exotoxin. AN - 76163342; 8287449 AB - Smooth muscle cell proliferation appears to be very important in restenosis after angioplasty. A chimeric toxin created by genetically fusing the gene encoding TGF alpha (targets the EGF receptor) to the gene encoding Pseudomonas exotoxin (PE) preferentially kills rapidly proliferating smooth muscle cells. Recently, a heparin binding EGF-like growth factor (HB-EGF) has been identified. The HB domain enhances the mitogenic activity for smooth muscle cells. The purpose of this study was to design a new chimeric toxin, having both heparin binding and EGF receptor binding function, and to determine whether it is more cytotoxic to smooth muscle cells. By recombinant DNA techniques, a new chimeric toxin, HB-TGF alpha-PE4EKDEL, was synthesised. Cytotoxic assays were performed by assessing the capacity to inhibit protein synthesis of rat vascular smooth muscle cells. The toxin preferentially killed rapidly proliferating smooth muscle cells (p < 0.025). The HB domain increased the cytotoxicity of the molecule when compared to the other chimeric toxins tested against smooth muscle cells. The cytotoxic effect of the new molecule was significantly decreased by exogenously added heparin (p < 0.05). The presence of a heparin binding domain increases the smooth muscle cell cytotoxicity of the TGF alpha fusion toxin, perhaps because HB-TGF alpha-PE4EKDEL functions as a molecule with two ligands. It will be important to determine whether the greater smooth muscle cell cytotoxicity that exists in vitro will facilitate the specific targeting and killing of rapidly proliferating cells in vivo. JF - Cardiovascular research AU - Fu, Y M AU - Mesri, E A AU - Yu, Z X AU - Kreitman, R J AU - Pastan, I AU - Epstein, S E AD - National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/09// PY - 1993 DA - September 1993 SP - 1691 EP - 1697 VL - 27 IS - 9 SN - 0008-6363, 0008-6363 KW - Exotoxins KW - 0 KW - Immunotoxins KW - Recombinant Fusion Proteins KW - Transforming Growth Factor alpha KW - transforming growth factor(alpha)-Pseudomonas exotoxin A (35) KW - Heparin KW - 9005-49-6 KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - Leucine KW - GMW67QNF9C KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Receptor, Epidermal Growth Factor -- metabolism KW - Cells, Cultured KW - Leucine -- metabolism KW - Cell Division -- drug effects KW - Heparin -- metabolism KW - Protein Binding KW - Muscles -- cytology KW - Exotoxins -- pharmacology KW - Muscles -- metabolism KW - Transforming Growth Factor alpha -- pharmacology KW - Recombinant Fusion Proteins -- pharmacology KW - Immunotoxins -- pharmacology KW - Muscles -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76163342?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cardiovascular+research&rft.atitle=Cytotoxic+effects+of+vascular+smooth+muscle+cells+of+the+chimeric+toxin%2C+heparin+binding+TGF+alpha-Pseudomonas+exotoxin.&rft.au=Fu%2C+Y+M%3BMesri%2C+E+A%3BYu%2C+Z+X%3BKreitman%2C+R+J%3BPastan%2C+I%3BEpstein%2C+S+E&rft.aulast=Fu&rft.aufirst=Y&rft.date=1993-09-01&rft.volume=27&rft.issue=9&rft.spage=1691&rft.isbn=&rft.btitle=&rft.title=Cardiovascular+research&rft.issn=00086363&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-02-22 N1 - Date created - 1994-02-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Clinical pharmacological issues in treating psychiatric disorders of patients with mental retardation. AN - 76157819; 8281242 AB - The following practical issues in psychopharmacotherapy of patients with mental retardation (MR) or other developmental disability (DD) are discussed, with some theoretical speculations: Persons with MR/DD have high rates of psychiatric disorders/symptoms, many of which are drug-responsive and not satisfactorily treated with other modalities alone. However, diagnosis is often complicated by concurrent multiple disorders (both psychiatric and medical/surgical), masking or distortion of symptoms, and communication impairments. Comorbidity and associated treatments should be considered in medication choice. Compared to psychiatric patients of normal IQ, patients with MR may be more sensitive to side effects and toxicity as well as responsive to lower doses, possibly related to less neuronal substrate, qualitative brain differences, or developmental stage. Unexpected or disappointing drug responses may also be related to such statistical quirks as "end-of-curve" phenomena. Ripples, ratcheting, and other ecobehavioral considerations influence treatment outcome and drug management. Target symptoms and expected drug benefits should be defined in consultation with caregivers as well as, when possible, the patient. Because drug responses of patients with MR are especially unpredictable, unreliable, sensitive to dose, and fraught with side effects, each medication trial might ideally be approached as a single-subject experiment on a compassionate protocol: quantify the baseline with ratings, behavior counts or other objective measures; start low and titrate slowly; monitor progress with repeated objective measures. JF - Annals of clinical psychiatry : official journal of the American Academy of Clinical Psychiatrists AU - Arnold, L E AD - Child and Adolescent Disorders Research Branch, NIMH, Rockville, Md., 20857. Y1 - 1993/09// PY - 1993 DA - September 1993 SP - 189 EP - 197 VL - 5 IS - 3 SN - 1040-1237, 1040-1237 KW - Psychotropic Drugs KW - 0 KW - Index Medicus KW - Brain -- physiopathology KW - Brain -- abnormalities KW - Psychiatric Status Rating Scales KW - Humans KW - Brain -- drug effects KW - Psychotropic Drugs -- therapeutic use KW - Psychotropic Drugs -- adverse effects KW - Male KW - Female KW - Intellectual Disability -- complications KW - Mental Disorders -- drug therapy KW - Mental Disorders -- metabolism KW - Mental Disorders -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76157819?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+clinical+psychiatry+%3A+official+journal+of+the+American+Academy+of+Clinical+Psychiatrists&rft.atitle=Clinical+pharmacological+issues+in+treating+psychiatric+disorders+of+patients+with+mental+retardation.&rft.au=Arnold%2C+L+E&rft.aulast=Arnold&rft.aufirst=L&rft.date=1993-09-01&rft.volume=5&rft.issue=3&rft.spage=189&rft.isbn=&rft.btitle=&rft.title=Annals+of+clinical+psychiatry+%3A+official+journal+of+the+American+Academy+of+Clinical+Psychiatrists&rft.issn=10401237&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-02-14 N1 - Date created - 1994-02-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CONF T1 - Fate, transport, and interactions of metals. AN - 76139524; 7903938 JF - Environmental health perspectives AU - Dieter, M P Y1 - 1993/09// PY - 1993 DA - September 1993 SP - 344 EP - 345 VL - 101 IS - 4 KW - Hazardous Waste KW - 0 KW - Metals KW - Index Medicus KW - Risk Factors KW - Humans KW - Environmental Monitoring KW - Metals -- chemistry KW - Metals -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76139524?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&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=Environmental+health+perspectives&rft.atitle=Fate%2C+transport%2C+and+interactions+of+metals.&rft.au=Dieter%2C+M+P&rft.aulast=Dieter&rft.aufirst=M&rft.date=1993-09-01&rft.volume=101&rft.issue=4&rft.spage=344&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 - 1994-02-09 N1 - Date created - 1994-02-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tetanus toxin light chain expression in Sertoli cells of transgenic mice causes alterations of the actin cytoskeleton and disrupts spermatogenesis. AN - 76119333; 8253064 AB - Tetanus toxin is a powerful neurotoxin known to inhibit neurotransmitter release. The tetanus toxin light chain is a metalloprotease that cleaves some members of the synaptobrevin gene family with high specificity. Here, we report the expression of a synthetic gene encoding the tetanus toxin light chain in the seminiferous epithelium of transgenic mice. Spermatogenesis was severely impaired and mature spermatozoa were completely absent. Late spermatids exhibited pleomorphic shapes and acrosomal distortions. The number of Leydig cells was greatly increased. In situ hybridization analysis revealed that the toxin acts on Sertoli cells. Affected cells exhibited an aberrant distribution of actin filaments and many cells contained large vacuoles. Our results demonstrate that tetanus toxin is active in non-neuronal cells and suggest an important function for members of the synaptobrevin gene family during the late stages of spermatogenesis. JF - The EMBO journal AU - Eisel, U AU - Reynolds, K AU - Riddick, M AU - Zimmer, A AU - Niemann, H AD - Developmental Biology Unit, National Institute of Mental Health, Bethesda, MD 20892. Y1 - 1993/09// PY - 1993 DA - September 1993 SP - 3365 EP - 3372 VL - 12 IS - 9 SN - 0261-4189, 0261-4189 KW - tetLC KW - Actins KW - 0 KW - Macromolecular Substances KW - Tetanus Toxin KW - Index Medicus KW - Protein Biosynthesis KW - Animals KW - Gene Expression KW - Actins -- metabolism KW - Transcription, Genetic KW - Amino Acid Sequence KW - Genes, Synthetic KW - Mice KW - Plasmids KW - Mice, Transgenic KW - Base Sequence KW - In Situ Hybridization KW - Cells, Cultured KW - Restriction Mapping KW - Molecular Sequence Data KW - Female KW - Male KW - Sertoli Cells -- ultrastructure KW - Sertoli Cells -- metabolism KW - Tetanus Toxin -- biosynthesis KW - Tetanus Toxin -- genetics KW - Cytoskeleton -- ultrastructure KW - Spermatogenesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76119333?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Tetanus+toxin+light+chain+expression+in+Sertoli+cells+of+transgenic+mice+causes+alterations+of+the+actin+cytoskeleton+and+disrupts+spermatogenesis.&rft.au=Eisel%2C+U%3BReynolds%2C+K%3BRiddick%2C+M%3BZimmer%2C+A%3BNiemann%2C+H&rft.aulast=Eisel&rft.aufirst=U&rft.date=1993-09-01&rft.volume=12&rft.issue=9&rft.spage=3365&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 - 1994-01-10 N1 - Date created - 1994-01-10 N1 - Date revised - 2017-01-13 N1 - Gene symbol - tetLC N1 - Genetic sequence - L19522; GENBANK N1 - SuppNotes - Cited By: Arch Androl. 1984;13(1):37-57 [6534279] Adv Exp Med Biol. 1984;173:201-13 [6331111] Curr Top Microbiol Immunol. 1986;129:93-179 [3533452] Nucleic Acids Res. 1986 Oct 10;14(19):7809-12 [3774547] EMBO J. 1986 Oct;5(10):2495-502 [3536478] Proc Natl Acad Sci U S A. 1987 Mar;84(6):1600-4 [2436220] Cell. 1987 Jul 31;50(3):435-43 [3649277] Science. 1987 Dec 11;238(4833):1563-5 [3685993] Biochem J. 1987 Oct 15;247(2):249-58 [3322260] Genes Dev. 1988 Apr;2(4):453-61 [3286373] J Biol Chem. 1988 Oct 15;263(29):14956-63 [2844793] FEBS Lett. 1989 Jan 2;242(2):245-8 [2914606] EMBO J. 1989 Feb;8(2):379-84 [2498078] Endocrinology. 1989 Dec;125(6):3029-36 [2555135] Nucleic Acids Res. 1989 Dec 25;17(24):10191-202 [2690015] Int Rev Cytol. 1989;119:1-56 [2695482] Neuron. 1988 Jul;1(5):367-76 [2483097] Neuron. 1989 Aug;3(2):257-65 [2576215] Biotechniques. 1988 Jul-Aug;6(7):632-8 [3273409] Science. 1990 Apr 13;248(4952):223-6 [2109351] J Cell Biol. 1990 May;110(5):1779-89 [2335570] Proc Natl Acad Sci U S A. 1990 Oct;87(20):7844-8 [2236000] Mol Endocrinol. 1990 Nov;4(11):1689-97 [2177840] Nature. 1991 Mar 7;350(6313):74-7 [1848356] Annu Rev Neurosci. 1991;14:93-122 [1851609] Mol Cell Biol. 1991 Aug;11(8):4207-16 [1712906] Neuroreport. 1991 Jan;2(1):33-6 [1768846] J Biol Chem. 1992 Jul 5;267(19):13267-71 [1352294] Cell Tissue Res. 1992 Apr;268(1):179-89 [1323421] EMBO J. 1992 Oct;11(10):3577-83 [1396558] J Neurochem. 1992 Oct;59(4):1336-43 [1328520] Nature. 1992 Oct 29;359(6398):832-5 [1331807] Biochem Biophys Res Commun. 1992 Dec 15;189(2):1017-23 [1361727] Nature. 1993 Mar 25;362(6418):318-24 [8455717] Am J Anat. 1956 Nov;99(3):391-413 [13402725] Arch Pathol. 1973 Mar;95(3):151-9 [4405609] Virchows Arch A Pathol Anat Histol. 1975 Jul 17;367(2):93-112 [808897] Fertil Steril. 1976 Jun;27(6):609-20 [6340] Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387-95 [6546423] J Androl. 1986 Jan-Feb;7(1):32-41 [3003018] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of ibotenic acid lesion of the medial prefrontal cortex on dopamine agonist-related behaviors in the rat. AN - 76115857; 7902985 AB - Behavioral responses to apomorphine and to the selective D1 and D2 dopamine receptor agonists SK&F38393 and quinpirole were evaluated in rats following ibotenic acid (IA) or sham lesion of the medial prefrontal cortex (MPFC). IA-lesioned rats showed an increased responsiveness to the postsynaptic effects of all of the dopamine agonists. Patterns of the responses to the selective agonists administered alone and in combination suggest that these effects might be due to selective increases in the sensitivity of postsynaptic D1 receptor-associated mechanisms. In addition, IA-lesioned rats pretreated with saline were hyperactive in comparison to sham-lesioned rats when animals were exposed to a novel open field, but spontaneous motor activity did not differ between these two groups when animals were pretreated with low doses (0.03 mg/kg) of quinpirole. The fact that hyperreactivity observed in lesioned animals is inhibited by a dose of quinpirole that is felt to act presynaptically, selectively attenuating endogenous dopaminergic tone, suggests that effects of the MPFC lesion may be mediated presynaptically as well. JF - Pharmacology, biochemistry, and behavior AU - Braun, A R AU - Jaskiw, G E AU - Vladar, K AU - Sexton, R H AU - Kolachana, B S AU - Weinberger, D R AD - Voice, Speech and Language Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/09// PY - 1993 DA - September 1993 SP - 51 EP - 60 VL - 46 IS - 1 SN - 0091-3057, 0091-3057 KW - Dopamine Agents KW - 0 KW - Ergolines KW - Receptors, Dopamine KW - Receptors, Presynaptic KW - Quinpirole KW - 20OP60125T KW - Ibotenic Acid KW - 2552-55-8 KW - 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine KW - 67287-49-4 KW - Apomorphine KW - N21FAR7B4S KW - Index Medicus KW - Receptors, Dopamine -- drug effects KW - Animals KW - Apomorphine -- pharmacology KW - Ergolines -- administration & dosage KW - Ergolines -- pharmacology KW - Stereotyped Behavior -- drug effects KW - 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine -- pharmacology KW - Receptors, Presynaptic -- drug effects KW - Rats KW - Rats, Sprague-Dawley KW - Injections, Subcutaneous KW - Motor Activity -- drug effects KW - Male KW - Behavior, Animal -- drug effects KW - Prefrontal Cortex -- anatomy & histology KW - Dopamine Agents -- pharmacology KW - Prefrontal Cortex -- physiology KW - Ibotenic Acid -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76115857?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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%2C+biochemistry%2C+and+behavior&rft.atitle=Effects+of+ibotenic+acid+lesion+of+the+medial+prefrontal+cortex+on+dopamine+agonist-related+behaviors+in+the+rat.&rft.au=Braun%2C+A+R%3BJaskiw%2C+G+E%3BVladar%2C+K%3BSexton%2C+R+H%3BKolachana%2C+B+S%3BWeinberger%2C+D+R&rft.aulast=Braun&rft.aufirst=A&rft.date=1993-09-01&rft.volume=46&rft.issue=1&rft.spage=51&rft.isbn=&rft.btitle=&rft.title=Pharmacology%2C+biochemistry%2C+and+behavior&rft.issn=00913057&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-01-10 N1 - Date created - 1994-01-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Impulse control disorders. AN - 76102220; 7504705 JF - International clinical psychopharmacology AU - Linnoila, M AU - Virkkunen, M AU - George, T AU - Higley, D AD - Laboratory of Clinical Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD. Y1 - 1993/09// PY - 1993 DA - September 1993 SP - 53 EP - 56 VL - 8 Suppl 1 SN - 0268-1315, 0268-1315 KW - Serotonin KW - 333DO1RDJY KW - Hydroxyindoleacetic Acid KW - 54-16-0 KW - Index Medicus KW - Frontal Lobe -- physiopathology KW - Serotonin -- physiology KW - Alcoholism -- diagnosis KW - Risk Factors KW - Humans KW - Alcoholism -- physiopathology KW - Violence KW - Alcoholism -- psychology KW - Aggression -- physiology KW - Disruptive, Impulse Control, and Conduct Disorders -- diagnosis KW - Disruptive, Impulse Control, and Conduct Disorders -- physiopathology KW - Disruptive, Impulse Control, and Conduct Disorders -- psychology KW - Hydroxyindoleacetic Acid -- cerebrospinal fluid UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76102220?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+clinical+psychopharmacology&rft.atitle=Impulse+control+disorders.&rft.au=Linnoila%2C+M%3BVirkkunen%2C+M%3BGeorge%2C+T%3BHigley%2C+D&rft.aulast=Linnoila&rft.aufirst=M&rft.date=1993-09-01&rft.volume=8+Suppl+1&rft.issue=&rft.spage=53&rft.isbn=&rft.btitle=&rft.title=International+clinical+psychopharmacology&rft.issn=02681315&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-01-11 N1 - Date created - 1994-01-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A system for testing the development and reversal of anticonvulsant tolerance to benzodiazepines in mice. AN - 76100617; 7902275 AB - Tolerance to the anticonvulsant effects of benzodiazepines limits their use in epilepsy treatment. Animal models producing tolerance have been developed, but they require repetitive injections over several days or use silastic capsules which must be made for each drug and do not provide a constant infusion rate. Alzet 2001 osmotic pumps deliver at a constant rate (1 microliter/h) and dosage can be easily adjusted. Various solvents, PEG 400, propylene glycol, 2% Tween, 50% DMSO, saline, Molecusol, and 0.5% methyl cellulose, were tried and found unsuitable because benzodiazepines were not maintained in solution or proconvulsant activity was seen. Tetraglycol was chosen as it did not demonstrate these shortcomings. Anticonvulsant activity was evaluated by PTZ i.v. tail infusion using forelimb clonus as the endpoint. This study describes a simple method for testing the development of tolerance and its reversal with flumazenil or ZK 93426. At 72 h of pump infusion with diazepam or flunitrazepam, tolerance to anticonvulsant activity was evident. Acute treatment with flumazenil or ZK 93426 reversed this tolerance. When flumazenil or ZK 93426 was given to diazepam tolerant mice, this reversal was complete. In flunitrazepam tolerant mice reversal with flumazenil was partial, but significant. When flumazenil was chronically coinfused with diazepam or flunitrazepam, anticonvulsant activity was antagonized. Similarly, when ZK 93426 was coinfused with diazepam, anticonvulsant activity was antagonized. The method described is suitable for screening putative anticonvulsant drugs for development of tolerance and the reversal of tolerance by other compounds. JF - Epilepsy research AU - Torchin, C D AU - Kapetanovic, I M AU - Kupferberg, H J AD - Preclinical Pharmacology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/09// PY - 1993 DA - September 1993 SP - 27 EP - 35 VL - 16 IS - 1 SN - 0920-1211, 0920-1211 KW - Anti-Anxiety Agents KW - 0 KW - Anticonvulsants KW - Carbolines KW - Solvents KW - Flumazenil KW - 40P7XK9392 KW - Flunitrazepam KW - 620X0222FQ KW - ZK 93426 KW - 89592-45-0 KW - Diazepam KW - Q3JTX2Q7TU KW - Pentylenetetrazole KW - WM5Z385K7T KW - Index Medicus KW - Animals KW - Infusion Pumps, Implantable KW - Diazepam -- pharmacology KW - Mice KW - Infusions, Parenteral KW - Flumazenil -- pharmacology KW - Drug Tolerance KW - Mice, Inbred Strains KW - Pentylenetetrazole -- toxicity KW - Pentylenetetrazole -- administration & dosage KW - Carbolines -- pharmacology KW - Flunitrazepam -- pharmacology KW - Time Factors KW - Male KW - Seizures -- chemically induced KW - Anticonvulsants -- pharmacology KW - Anti-Anxiety Agents -- pharmacology KW - Anti-Anxiety Agents -- administration & dosage KW - Seizures -- physiopathology KW - Seizures -- drug therapy KW - Anticonvulsants -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76100617?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Epilepsy+research&rft.atitle=A+system+for+testing+the+development+and+reversal+of+anticonvulsant+tolerance+to+benzodiazepines+in+mice.&rft.au=Torchin%2C+C+D%3BKapetanovic%2C+I+M%3BKupferberg%2C+H+J&rft.aulast=Torchin&rft.aufirst=C&rft.date=1993-09-01&rft.volume=16&rft.issue=1&rft.spage=27&rft.isbn=&rft.btitle=&rft.title=Epilepsy+research&rft.issn=09201211&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-12-28 N1 - Date created - 1993-12-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Expression of deletion constructs of bovine beta-1,4-galactosyltransferase in Escherichia coli: importance of Cys134 for its activity. AN - 76096487; 8248102 AB - Bovine beta-1,4-galactosyltransferase (beta-1,4-GT; EC 2.4.1.90) belongs to the glycosyltransferase family and as such shares a general topology: an N-terminal cytoplasmic tail, a signal anchor followed by a stem region and a catalytic domain at the C-terminal end of the protein. cDNA constructs of the N-terminal deleted forms of beta-1,4-GT were prepared in pGEX-2T vector and expressed in E. coli as glutathione-S-transferase (GST) fusion proteins. Recombinant proteins accumulated within inclusion bodies as insoluble aggregates that were solubilized in 5 M guanidine HCl and required an 'oxido-shuffling' reagent for regeneration of the enzyme activity. The recombinant beta-1,4-GT, devoid of the GST domain, has 30-85% of the sp. act. of bovine milk beta-1,4-GT with apparent Kms for N-acetylglucosamine and UDP-galactose similar to those of milk enzyme. Deletion analyses show that both beta-1,4-GT and lactose synthetase activities remain intact even in the absence of the first 129 residues (pGT-d129). The activities are lost when either deletions extend up to residue 142 (pGT-d142) or Cys134 is mutated to Ser (pGT-d129C134S). These results suggest that the formation of a disulfide bond involving Cys134 holds the protein in a conformation that is required for enzymatic activity. JF - Protein engineering AU - Boeggeman, E E AU - Balaji, P V AU - Sethi, N AU - Masibay, A S AU - Qasba, P K AD - Laboratory of Mathematical Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/09// PY - 1993 DA - September 1993 SP - 779 EP - 785 VL - 6 IS - 7 SN - 0269-2139, 0269-2139 KW - Recombinant Fusion Proteins KW - 0 KW - N-Acetyllactosamine Synthase KW - EC 2.4.1.90 KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Glutathione KW - GAN16C9B8O KW - Cysteine KW - K848JZ4886 KW - Index Medicus KW - Animals KW - Glutathione -- metabolism KW - Recombinant Fusion Proteins -- isolation & purification KW - Protein Denaturation KW - Amino Acid Sequence KW - Glutathione Transferase -- genetics KW - Structure-Activity Relationship KW - Recombinant Fusion Proteins -- chemistry KW - Cloning, Molecular KW - Mutagenesis KW - Recombinant Fusion Proteins -- metabolism KW - Polymerase Chain Reaction KW - Base Sequence KW - Cattle KW - Kinetics KW - Molecular Sequence Data KW - N-Acetyllactosamine Synthase -- genetics KW - N-Acetyllactosamine Synthase -- chemistry KW - Gene Expression KW - Escherichia coli -- genetics KW - N-Acetyllactosamine Synthase -- metabolism KW - Gene Deletion UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76096487?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Child+Sexual+Abuse&rft.atitle=Differences+in+Perceptions+of+Child+Sexual+Abuse+Based+on+Perpetrator+Age+and+Respondent+Gender&rft.au=Giglio%2C+Jessie+J%3BWolfteich%2C+Paula+M%3BGabrenya%2C+William+K%3BSohn%2C+Mary+L&rft.aulast=Giglio&rft.aufirst=Jessie&rft.date=2011-07-01&rft.volume=20&rft.issue=4&rft.spage=396&rft.isbn=&rft.btitle=&rft.title=Journal+of+Child+Sexual+Abuse&rft.issn=10538712&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-01-06 N1 - Date created - 1994-01-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A measure of tumorigenic potency incorporating dose-response shape. AN - 76095824; 8241378 AB - Many researchers have considered the problem of ranking chemical agents based on their carcinogenic potency. Sawyer et al. (1984, Biometrics 40, 27-40) proposed a carcinogenic potency estimate that incorporates both intercurrent mortality and background tumor rates. Since then, many authors have either generalized the method outlined by Sawyer et al. or developed their own method based on a slightly different adjustment for treatment-related changes in survival. None of these methods, however, has estimated the shape of the dose-response curve and incorporated such an estimate in potency estimation. In this manuscript, a measure of tumorigenic potency is proposed that utilizes the estimated shape of the dose-response relationship, in addition to estimated dose effects, in order to rank chemicals on the basis of carcinogenic risk. Comparison of this new measure to that of Sawyer et al. is done using a large database of animal carcinogenicity experiments from the National Cancer Institute and the National Toxicology Program. JF - Biometrics AU - Meier, K L AU - Bailer, A J AU - Portier, C J AD - Risk Methodology Section, National Institute of Environmental Health Sciences Research Triangle Park, North Carolina 27709. Y1 - 1993/09// PY - 1993 DA - September 1993 SP - 917 EP - 926 VL - 49 IS - 3 SN - 0006-341X, 0006-341X KW - Carcinogens KW - 0 KW - Index Medicus KW - Rats KW - Evaluation Studies as Topic KW - Animals KW - Neoplasms, Experimental -- chemically induced KW - Dose-Response Relationship, Drug KW - Linear Models KW - Models, Statistical KW - Mice KW - Male KW - Female KW - Proportional Hazards Models KW - Carcinogens -- administration & dosage KW - Biometry -- methods KW - Carcinogens -- toxicity KW - Carcinogenicity Tests -- methods KW - Carcinogenicity Tests -- statistics & numerical data UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76095824?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biometrics&rft.atitle=A+measure+of+tumorigenic+potency+incorporating+dose-response+shape.&rft.au=Meier%2C+K+L%3BBailer%2C+A+J%3BPortier%2C+C+J&rft.aulast=Meier&rft.aufirst=K&rft.date=1993-09-01&rft.volume=49&rft.issue=3&rft.spage=917&rft.isbn=&rft.btitle=&rft.title=Biometrics&rft.issn=0006341X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-12-29 N1 - Date created - 1993-12-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Metabolism and elimination of oxazepam in B6C3F1 and Swiss-Webster mice. AN - 76094830; 7902256 AB - The National Toxicology Program has recently determined oxazepam to be hepatocarcinogenic in mice. To aid in the assessment of the risks associated with human use of this drug, the metabolism and elimination of oxazepam in mice were exhaustively examined in B6C3F1 and Swiss-Webster mice. In this study males were given 25, 250, and 500 mg/kg by gavage, a range that includes doses found to be carcinogenic and noncarcinogenic in the National Toxicology Program bioassay. Metabolism of oxazepam by female mice of both strains was studied following administration of 500 mg/kg. More than 90% of the recovered activity was identified. Few strain differences were detected. Females of both strains metabolize oxazepam to a slightly greater extent than do males. Dose-dependent differences were detected, but they were usually nonlinear over the range examined. The routes of elimination in mice given a single dose of oxazepam were by order of importance: fecal > urinary > expired air. Pretreatment with dosed feed for 14 days (to model autoinduction in bioassay animals) resulted in a significant shift from the fecal to the urinary route of elimination, an approximately 2-fold increase in elimination of oxazepam glucuronide, and a significant decrease in excretion of unchanged oxazepam. Results of this study indicate that following constant exposure to oxazepam, mice metabolize and eliminate oxazepam in a manner more similar to that by humans than that by naive mice. This observation enhances the significance of data obtained in the bioassay and the extrapolation of that data to predict risks to human health. JF - Drug metabolism and disposition: the biological fate of chemicals AU - Griffin, R J AU - Burka, L T AD - National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. PY - 1993 SP - 918 EP - 926 VL - 21 IS - 5 SN - 0090-9556, 0090-9556 KW - Oxazepam KW - 6GOW6DWN2A KW - Index Medicus KW - Animals KW - Sex Characteristics KW - Dose-Response Relationship, Drug KW - Humans KW - Liver -- metabolism KW - Male KW - Female KW - Chromatography, High Pressure Liquid KW - Oxazepam -- pharmacokinetics KW - Oxazepam -- metabolism KW - Mice, Inbred Strains -- metabolism KW - Mice -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76094830?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Drug+metabolism+and+disposition%3A+the+biological+fate+of+chemicals&rft.atitle=Metabolism+and+elimination+of+oxazepam+in+B6C3F1+and+Swiss-Webster+mice.&rft.au=Griffin%2C+R+J%3BBurka%2C+L+T&rft.aulast=Griffin&rft.aufirst=R&rft.date=1993-09-01&rft.volume=21&rft.issue=5&rft.spage=918&rft.isbn=&rft.btitle=&rft.title=Drug+metabolism+and+disposition%3A+the+biological+fate+of+chemicals&rft.issn=00909556&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-12-28 N1 - Date created - 1993-12-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Endogenous protein kinase-C activation in osteoblast-like cells modulates responsiveness to estrogen and estrogen receptor levels. AN - 76079972; 8247015 AB - The osteoblast-like osteosarcoma cell line ROS 17/2.8, which expresses very low levels of estrogen receptor (ER), was stably transfected with the mouse ER in order to more easily evaluate the physiological role of estrogens in bone cell homeostasis. These transfected ROS.SMER 14 cells are highly responsive to estrogenic stimulation at subconfluence, but become refractory to estrogenic stimulation when postconfluency is reached. The purpose of these studies was to determine the mechanisms underlying this loss of responsiveness in these ER stably transfected cells at postconfluence. When proliferative capacity was evaluated by bromodeoxyuridine immunocytochemistry, approximately 70% of the subconfluent cells were actively dividing, whereas none of the postconfluent cells underwent division. Subconfluent cells were found to contain 2500-3000 ER-binding sites/cell, whereas the ER in postconfluent cells was low and often undetectable. Steady state ER mRNA levels were not significantly modified by postconfluency. ER protein levels were also unaffected by confluency status. Since protein kinase-C (PKC) has been reported to influence cell proliferation and steroid hormone receptor binding, PKC activity was measured in sub- and postconfluent cells. Calcium-dependent PKC activity was approximately about 2-fold higher in postconfluent compared to subconfluent cells, whereas no differences were discerned in calcium-independent PKC activity. In an effort to examine the role of PKC in greater detail, postconfluent cells were treated with PKC inhibitors (H-7 or staurosporine) or with the tumor promoter TPA (12-O-tetradecanoylphorbol-13-acetate) to down-regulate PKC activity, and changes in ER were evaluated. Inhibition or down-regulation of the PKC activity in postconfluent cells enhanced ER-binding capacity in a dose-dependent manner and estrogen responsiveness of an exogenous reporter gene and of the endogenous alkaline phosphatase, representing an endogenous estrogen-stimulated gene. These data indicate that there is an interaction between the PKC and ER signaling systems in bone cells and that this interaction may be influenced by the proliferative and/or differentiative state of the cells, resulting in modulation of hormone responsiveness. JF - Molecular endocrinology (Baltimore, Md.) AU - Migliaccio, S AU - Wetsel, W C AU - Fox, W M AU - Washburn, T F AU - Korach, K S AD - Receptor Biology Section, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709. Y1 - 1993/09// PY - 1993 DA - September 1993 SP - 1133 EP - 1143 VL - 7 IS - 9 SN - 0888-8809, 0888-8809 KW - Alkaloids KW - 0 KW - Isoquinolines KW - Piperazines KW - RNA, Messenger KW - Receptors, Estrogen KW - Estradiol KW - 4TI98Z838E KW - 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine KW - 84477-87-2 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Alkaline Phosphatase KW - EC 3.1.3.1 KW - Staurosporine KW - H88EPA0A3N KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Animals KW - Blotting, Northern KW - Enzyme Activation KW - Cell Division -- drug effects KW - Osteosarcoma KW - Alkaline Phosphatase -- metabolism KW - Homeostasis KW - Piperazines -- pharmacology KW - Calcium -- metabolism KW - Isoquinolines -- pharmacology KW - Tumor Cells, Cultured KW - RNA, Messenger -- metabolism KW - Transfection KW - Kinetics KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Alkaloids -- pharmacology KW - Protein Kinase C -- metabolism KW - Osteoblasts -- metabolism KW - Osteoblasts -- drug effects KW - Receptors, Estrogen -- biosynthesis KW - Estradiol -- pharmacology KW - Protein Kinase C -- isolation & purification KW - Receptors, Estrogen -- metabolism KW - Osteoblasts -- cytology KW - Estradiol -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76079972?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Endogenous+protein+kinase-C+activation+in+osteoblast-like+cells+modulates+responsiveness+to+estrogen+and+estrogen+receptor+levels.&rft.au=Migliaccio%2C+S%3BWetsel%2C+W+C%3BFox%2C+W+M%3BWashburn%2C+T+F%3BKorach%2C+K+S&rft.aulast=Migliaccio&rft.aufirst=S&rft.date=1993-09-01&rft.volume=7&rft.issue=9&rft.spage=1133&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 - 1994-01-04 N1 - Date created - 1994-01-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hodgkin's disease in adults. Part II. AN - 76046645; 8225893 AB - The development of a secondary cancer is an often fatal and therefore devastating complication of the successful therapy of Hodgkin's disease. The risk of developing a secondary cancer is not the same for all patients, nor is it the same for all treatments. In 1993, treatment decisions are complicated because there are often a number of management approaches that can effectively eradicate Hodgkin's disease. Certain subgroups can be treated safely with more limited therapy. Patients with peripheral IA disease experience excellent survival following involved field radiotherapy alone without staging laparotomy. Early-stage patients with good prognostic factors can be treated with radiotherapy or chemotherapy alone after a discussion of the short and long-term risks of both approaches. If unfavorable prognostic factors are present or if the patient has IIIA disease, we favor chemotherapy alone while others may employ combined modality therapy, a treatment strategy we reserve for patients with massive mediastinal disease. For advanced-stage disease, full-dose combination chemotherapy with a regimen that is familiar to the oncologist should be given. The addition of radiotherapy in this setting has not been shown to be of benefit. Each treatment strategy has to consider the individual patient and their likelihood of developing one of the complications, fatal or otherwise, of treatment. Although secondary complications must be considered in the initial strategy, unfounded fears about toxicity should not detract from delivery of therapy that has the greatest chance of cure while at the same time minimizing the risk to the patient. JF - Investigative radiology AU - Urba, W J AU - Longo, D L AD - Clinical Services Program, National Cancer Institute, Frederick Cancer Research and Development Center, MD 21702-1201. Y1 - 1993/09// PY - 1993 DA - September 1993 SP - 848 EP - 859 VL - 28 IS - 9 SN - 0020-9996, 0020-9996 KW - Index Medicus KW - Neoplasms, Second Primary KW - Humans KW - Salvage Therapy KW - Hodgkin Disease -- therapy KW - Hodgkin Disease -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76046645?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Investigative+radiology&rft.atitle=Hodgkin%27s+disease+in+adults.+Part+II.&rft.au=Urba%2C+W+J%3BLongo%2C+D+L&rft.aulast=Urba&rft.aufirst=W&rft.date=1993-09-01&rft.volume=28&rft.issue=9&rft.spage=848&rft.isbn=&rft.btitle=&rft.title=Investigative+radiology&rft.issn=00209996&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-12-15 N1 - Date created - 1993-12-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Lung cancer, race, and a CYP1A1 genetic polymorphism. AN - 76042791; 8220094 AB - The assessment of human cancer risk using molecular epidemiological techniques involves determining the relative contributions of inherited and acquired genetic predispositions, in the context of environmental exposures. Recently described genetic polymorphisms for CYP1A1, a gene involved in the metabolic activation of polycyclic aromatic hydrocarbons, have been associated with lung cancer risk in a Japanese population. We report herein findings from a United States case-control study of lung cancer (56 cases; 48 controls). The polymerase chain reaction followed by an Msp1 restriction enzyme digestion was used to analyze constitutive DNA but no association between the restriction fragment length polymorphism and lung cancer risk was found (odds ratio, 0.7; 95% confidence interval, = 0.3-1.6). Analysis of genotype by cumulative smoking status did not reveal an elevated risk among lesser or greater smokers. The presence of the CYP1A1 Msp1 site-present allele, which was previously found to be associated with Japanese lung cancer risk, was statistically increased in African compared to Caucasian Americans (odds ratio, 2.9; 95% confidence interval, 1.2-2.7). When stratified by race, however, no association between case status and the polymorphism was observed, but the small number of study subjects within each racial group limited the statistical power. Larger studies are required to evaluate the risk of the CYP1A1 Msp1 polymorphism in African Americans. JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology AU - Shields, P G AU - Caporaso, N E AU - Falk, R T AU - Sugimura, H AU - Trivers, G E AU - Trump, B F AU - Hoover, R N AU - Weston, A AU - Harris, C C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, NIH, Bethesda, Maryland 20892. PY - 1993 SP - 481 EP - 485 VL - 2 IS - 5 SN - 1055-9965, 1055-9965 KW - CYP1A1 KW - DNA, Neoplasm KW - 0 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Index Medicus KW - Homozygote KW - Gene Frequency KW - Humans KW - Asthma -- genetics KW - DNA, Neoplasm -- analysis KW - Smoking -- genetics KW - Lung Diseases, Obstructive -- genetics KW - Neoplasms -- genetics KW - Genotype KW - Polymerase Chain Reaction KW - Blotting, Southern KW - Risk Factors KW - Heterozygote KW - Case-Control Studies KW - DNA, Neoplasm -- genetics KW - African Continental Ancestry Group -- genetics KW - Cytochrome P-450 Enzyme System -- genetics KW - Polymorphism, Genetic -- genetics KW - Lung Neoplasms -- genetics KW - European Continental Ancestry Group -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76042791?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+epidemiology%2C+biomarkers+%26+prevention+%3A+a+publication+of+the+American+Association+for+Cancer+Research%2C+cosponsored+by+the+American+Society+of+Preventive+Oncology&rft.atitle=Lung+cancer%2C+race%2C+and+a+CYP1A1+genetic+polymorphism.&rft.au=Shields%2C+P+G%3BCaporaso%2C+N+E%3BFalk%2C+R+T%3BSugimura%2C+H%3BTrivers%2C+G+E%3BTrump%2C+B+F%3BHoover%2C+R+N%3BWeston%2C+A%3BHarris%2C+C+C&rft.aulast=Shields&rft.aufirst=P&rft.date=1993-09-01&rft.volume=2&rft.issue=5&rft.spage=481&rft.isbn=&rft.btitle=&rft.title=Cancer+epidemiology%2C+biomarkers+%26+prevention+%3A+a+publication+of+the+American+Association+for+Cancer+Research%2C+cosponsored+by+the+American+Society+of+Preventive+Oncology&rft.issn=10559965&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-12-10 N1 - Date created - 1993-12-10 N1 - Date revised - 2017-01-13 N1 - Gene symbol - CYP1A1 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A cohort study of smoking, alcohol consumption, and dietary factors for pancreatic cancer (United States). AN - 76039279; 8218880 AB - Risk factors for pancreatic cancer were evaluated in a cohort study of 17,633 White men in the United States who responded to a mailed questionnaire in 1966 and were followed-up through 1986 for mortality. Cigarette smoking and alcohol consumption were found to be important risk factors for pancreatic cancer. Risks increased significantly with number of cigarettes smoked, reaching fourfold for smokers of 25 or more cigarettes per day relative to nonsmokers. Alcohol intake also was related significantly to risk, with consumers of 10 or more drinks per month having three times the risk of nondrinkers, but dose-response trends among drinkers were not smooth. Coffee consumption was unrelated to risk. Dietary analyses revealed a rising rate of pancreatic cancer mortality with increasing consumption of meat after adjustment for other risk factors. Men in the highest quartile of meat intake had about three times the risk of those in the lowest quartile. No consistent association, however, was observed for consumption of fruits, vegetables, or grains. This study confirms cigarette smoking as an important risk factor for pancreatic cancer, and provides evidence that elevated intake of alcohol and meat may increase the risk of this fatal malignancy. JF - Cancer causes & control : CCC AU - Zheng, W AU - McLaughlin, J K AU - Gridley, G AU - Bjelke, E AU - Schuman, L M AU - Silverman, D T AU - Wacholder, S AU - Co-Chien, H T AU - Blot, W J AU - Fraumeni, J F AD - Epidemiology and Biostatistics Program, National Cancer Institute, Bethesda, MD 20892. Y1 - 1993/09// PY - 1993 DA - September 1993 SP - 477 EP - 482 VL - 4 IS - 5 SN - 0957-5243, 0957-5243 KW - Coffee KW - 0 KW - Index Medicus KW - Animals KW - Humans KW - Alcoholic Beverages -- statistics & numerical data KW - Tobacco, Smokeless KW - Plants, Toxic KW - Meat KW - Risk Factors KW - European Continental Ancestry Group KW - Fishes KW - Adult KW - Cohort Studies KW - Follow-Up Studies KW - Beer -- statistics & numerical data KW - United States -- epidemiology KW - Male KW - Pancreatic Neoplasms -- mortality KW - Pancreatic Neoplasms -- epidemiology KW - Feeding Behavior KW - Alcohol Drinking -- epidemiology KW - Smoking -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76039279?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+causes+%26+control+%3A+CCC&rft.atitle=A+cohort+study+of+smoking%2C+alcohol+consumption%2C+and+dietary+factors+for+pancreatic+cancer+%28United+States%29.&rft.au=Zheng%2C+W%3BMcLaughlin%2C+J+K%3BGridley%2C+G%3BBjelke%2C+E%3BSchuman%2C+L+M%3BSilverman%2C+D+T%3BWacholder%2C+S%3BCo-Chien%2C+H+T%3BBlot%2C+W+J%3BFraumeni%2C+J+F&rft.aulast=Zheng&rft.aufirst=W&rft.date=1993-09-01&rft.volume=4&rft.issue=5&rft.spage=477&rft.isbn=&rft.btitle=&rft.title=Cancer+causes+%26+control+%3A+CCC&rft.issn=09575243&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-12-03 N1 - Date created - 1993-12-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Immunocompetence in the long sleep and short sleep mouse lines: baseline versus primed responses. AN - 76038435; 8219412 AB - Two lines of mice which were selectively bred for high (Long Sleep; LS) and low (Short Sleep; SS) reactivities to a sedative dose of ethanol, are also differentiated by agents that act at the GABAA-receptor complex. Since this supramolecular complex may also modulate immune function, measures of immunity have been examined in these lines. In the present study the immune responsiveness before and after an allogeneic priming stimulus was investigated. Lower mitogen-induced T-cell proliferation, mixed leukocyte reaction, and cytotoxic T lymphocyte activity were found in unprimed LS compared to unprimed SS mice. In contrast, the LS line exhibited a marked augmentation of these responses after priming, while the SS mice appeared unresponsive to this challenge. Addition of splenocytes or cell-free splenic cultures from primed mice to cultures from unprimed mice suggested that differences in priming-induced cell-to-cell interactions, rather than the release of a soluble helper factor(s) into the medium, are responsible for the marked augmentation of the secondary response in LS, compared to SS mice. Fewer T-helper and T-suppressor/cytotoxic cells were found in LS compared to SS mice, and this was unaffected by priming. These results extend previous findings demonstrating a higher natural killer cell activity and rate of tumor rejection in LS mice and suggest that these lines may be useful in studying the regulatory role of the GABAA complex in immune function. JF - Brain, behavior, and immunity AU - Fride, E AU - McIntyre, T AU - Skolnick, P AU - Arora, P K AD - Laboratory of Neuroscience, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/09// PY - 1993 DA - September 1993 SP - 231 EP - 242 VL - 7 IS - 3 SN - 0889-1591, 0889-1591 KW - Receptors, GABA KW - 0 KW - Receptors, GABA-A KW - Ethanol KW - 3K9958V90M KW - Index Medicus KW - Lymphocyte Activation -- drug effects KW - Animals KW - Receptors, GABA-A -- physiology KW - Lymphocyte Subsets -- drug effects KW - Cytotoxicity Tests, Immunologic KW - Crosses, Genetic KW - Mice KW - Selection, Genetic KW - Male KW - Immunocompetence -- genetics KW - Sleep -- genetics KW - Immunologic Memory -- drug effects KW - Ethanol -- pharmacology KW - Immunity, Cellular -- drug effects KW - Receptors, GABA -- physiology KW - Mice, Inbred Strains -- physiology KW - Neuroimmunomodulation -- drug effects KW - Immunocompetence -- physiology KW - Mice, Inbred Strains -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76038435?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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%2C+behavior%2C+and+immunity&rft.atitle=Immunocompetence+in+the+long+sleep+and+short+sleep+mouse+lines%3A+baseline+versus+primed+responses.&rft.au=Fride%2C+E%3BMcIntyre%2C+T%3BSkolnick%2C+P%3BArora%2C+P+K&rft.aulast=Fride&rft.aufirst=E&rft.date=1993-09-01&rft.volume=7&rft.issue=3&rft.spage=231&rft.isbn=&rft.btitle=&rft.title=Brain%2C+behavior%2C+and+immunity&rft.issn=08891591&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-12-10 N1 - Date created - 1993-12-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Glycine stimulates striatal dopamine release in conscious rats. AN - 76037190; 8220914 AB - 1. Glycine is an inhibitory neurotransmitter in the spinal cord and brainstem. The mechanism of this inhibition is via binding of glycine to specific receptors, increasing transmembrane Cl- conductance and hyperpolarizing neurones. Strychnine selectively antagonizes these effects. The role of glycinergic neurones in supraspinal regions is poorly understood. 2. Effects of glycine on release of catecholamines in the striatum were examined by microdialysis in freely-moving rats. Transcription of the genes encoding strychnine-sensitive glycine receptors was assessed in the striatum and substantia nigra, by use of reverse transcription followed by the polymerase chain reaction. 3. Glycine administered via the microdialysis probe dose-dependently increased concentrations of dopamine and its metabolites, dihydroxyphenylacetic acid and homovanillic acid, in the perfusate, indicating increased local release and metabolism of dopamine. Strychnine markedly attenuated these responses. Whereas striatal tissue did not contain mRNA for either the adult or neonatal form of strychnine-sensitive glycine receptor, nigral tissue contained a message for the adult form. 4. The results suggest that dopaminergic cells in the substantia nigra synthesize strychnine-sensitive glycine receptors and transport the receptors to terminals in the striatum. Occupation of the glycine receptors then exerts a net stimulatory effect on striatal dopamine release in vivo. JF - British journal of pharmacology AU - Yadid, G AU - Pacak, K AU - Golomb, E AU - Harvey-White, J D AU - Lieberman, D M AU - Kopin, I J AU - Goldstein, D S AD - Clinical Neuroscience Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/09// PY - 1993 DA - September 1993 SP - 50 EP - 53 VL - 110 IS - 1 SN - 0007-1188, 0007-1188 KW - DNA Primers KW - 0 KW - RNA, Messenger KW - Receptors, Glycine KW - Strychnine KW - H9Y79VD43J KW - Glycine KW - TE7660XO1C KW - Dopamine KW - VTD58H1Z2X KW - Homovanillic Acid KW - X77S6GMS36 KW - Index Medicus KW - Animals KW - Dialysis KW - Receptors, Glycine -- biosynthesis KW - Transcription, Genetic KW - Homovanillic Acid -- metabolism KW - Chromatography, High Pressure Liquid KW - RNA, Messenger -- biosynthesis KW - Substantia Nigra -- metabolism KW - Rats KW - Polymerase Chain Reaction KW - Base Sequence KW - Rats, Sprague-Dawley KW - Molecular Sequence Data KW - Strychnine -- pharmacology KW - Male KW - Receptors, Glycine -- genetics KW - Glycine -- pharmacology KW - Corpus Striatum -- metabolism KW - Dopamine -- metabolism KW - Corpus Striatum -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76037190?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+pharmacology&rft.atitle=Glycine+stimulates+striatal+dopamine+release+in+conscious+rats.&rft.au=Yadid%2C+G%3BPacak%2C+K%3BGolomb%2C+E%3BHarvey-White%2C+J+D%3BLieberman%2C+D+M%3BKopin%2C+I+J%3BGoldstein%2C+D+S&rft.aulast=Yadid&rft.aufirst=G&rft.date=1993-09-01&rft.volume=110&rft.issue=1&rft.spage=50&rft.isbn=&rft.btitle=&rft.title=British+journal+of+pharmacology&rft.issn=00071188&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-12-14 N1 - Date created - 1993-12-14 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Brain Res. 1984 Feb 27;294(1):127-32 [6697228] Br J Pharmacol. 1983 Jul;79(3):799-806 [6418249] Anal Biochem. 1987 Apr;162(1):156-9 [2440339] Naunyn Schmiedebergs Arch Pharmacol. 1988 May;337(5):552-5 [2842697] Eur J Pharmacol. 1990 Jan 17;175(3):365-6 [2157604] J Neurochem. 1990 Jun;54(6):2077-81 [2338557] Synapse. 1990;5(3):190-200 [2160740] Neuron. 1990 Dec;5(6):867-73 [2176511] Eur J Pharmacol. 1990 Aug 10;184(2-3):239-50 [2150375] EMBO J. 1991 Sep;10(9):2401-9 [1651228] Br J Pharmacol. 1991 Nov;104(3):760-4 [1797336] Brain Res. 1992 Aug 28;589(1):91-6 [1422825] Eur J Pharmacol. 1992 Oct 20;221(2-3):389-91 [1426016] Exp Brain Res. 1968;6(1):1-18 [5721755] Proc Natl Acad Sci U S A. 1973 Oct;70(10):2832-6 [4200724] Brain Res. 1978 Jan 6;139(1):115-30 [620345] J Neurochem. 1979 May;32(5):1539-45 [438822] Biochem Pharmacol. 1979 Jul 15;28(14):2193-7 [497000] J Neurochem. 1982 Feb;38(2):574-81 [7108557] Nature. 1987 Jul 16-22;328(6127):215-20 [3037383] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The role of agricultural pesticide use in the development of non-Hodgkin's lymphoma in women. AN - 76028162; 8215601 AB - Non-Hodgkin's lymphoma has been found to be associated with agricultural pesticide use in men, but little is known about the risk in women. In a recent population-based, case-control study conducted in eastern Nebraska, no increased risk of non-Hodgkin's lymphoma was found in women who had ever lived or worked on a farm (odds ratio [OR] = 1.0). Neither the use of insecticides (OR = 0.8) nor herbicides (OR = 0.7) on the farm was associated with non-Hodgkin's lymphoma; however, the number of women who mixed or applied pesticides was small, particularly in comparison to men on farms. Small nonsignificant associations were observed among the women who personally handled insecticides (OR = 1.3) or herbicides (OR = 1.2). Women who personally handled organophosphate insecticides had a significant 4.5-fold increased risk of non-Hodgkin's lymphoma. Use of chlorinated hydrocarbon insecticides was associated with an OR of 1.6; however, the use on dairy cattle was associated with a 3-fold increased risk. Pesticide-related risks were greater among women with a family history of cancer, particularly a history of lymphatic or hematopoietic cancer among first-degree relatives. JF - Archives of environmental health AU - Zahm, S H AU - Weisenburger, D D AU - Saal, R C AU - Vaught, J B AU - Babbitt, P A AU - Blair, A AD - Occupational Studies Section, National Cancer Institute, Rockville, Maryland. PY - 1993 SP - 353 EP - 358 VL - 48 IS - 5 SN - 0003-9896, 0003-9896 KW - Agrochemicals KW - 0 KW - Herbicides KW - Insecticides KW - Abridged Index Medicus KW - Index Medicus KW - Odds Ratio KW - Risk Factors KW - Humans KW - Adult KW - Case-Control Studies KW - Aged KW - Middle Aged KW - Female KW - Nebraska -- epidemiology KW - Lymphoma, Non-Hodgkin -- epidemiology KW - Insecticides -- adverse effects KW - Herbicides -- adverse effects KW - Agricultural Workers' Diseases -- epidemiology KW - Agricultural Workers' Diseases -- chemically induced KW - Occupational Exposure -- adverse effects KW - Lymphoma, Non-Hodgkin -- chemically induced KW - Occupational Exposure -- analysis KW - Agrochemicals -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76028162?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+environmental+health&rft.atitle=The+role+of+agricultural+pesticide+use+in+the+development+of+non-Hodgkin%27s+lymphoma+in+women.&rft.au=Zahm%2C+S+H%3BWeisenburger%2C+D+D%3BSaal%2C+R+C%3BVaught%2C+J+B%3BBabbitt%2C+P+A%3BBlair%2C+A&rft.aulast=Zahm&rft.aufirst=S&rft.date=1993-09-01&rft.volume=48&rft.issue=5&rft.spage=353&rft.isbn=&rft.btitle=&rft.title=Archives+of+environmental+health&rft.issn=00039896&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-11-04 N1 - Date created - 1993-11-04 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Enhanced single-strand conformation polymorphism (SSCP) detection of point mutations utilizing methylmercury hydroxide. AN - 76025578; 8217149 JF - BioTechniques AU - Weghorst, C M AU - Buzard, G S AD - Laboratory of Comparative Carcinogenesis National Cancer Institute, Frederick, MD 21702-1201. Y1 - 1993/09// PY - 1993 DA - September 1993 SP - 396 EP - 8, 400 VL - 15 IS - 3 SN - 0736-6205, 0736-6205 KW - DNA, Single-Stranded KW - 0 KW - Methylmercury Compounds KW - methylmercury hydroxide KW - EZ74BDI0HB KW - Index Medicus KW - Rats KW - Kidney Neoplasms -- genetics KW - Polymerase Chain Reaction KW - Animals KW - Base Sequence KW - Electrophoresis KW - Genes, p53 KW - Molecular Sequence Data KW - Kidney Neoplasms -- chemistry KW - Point Mutation KW - DNA, Single-Stranded -- chemistry KW - Nucleic Acid Conformation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76025578?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=BioTechniques&rft.atitle=Enhanced+single-strand+conformation+polymorphism+%28SSCP%29+detection+of+point+mutations+utilizing+methylmercury+hydroxide.&rft.au=Weghorst%2C+C+M%3BBuzard%2C+G+S&rft.aulast=Weghorst&rft.aufirst=C&rft.date=1993-09-01&rft.volume=15&rft.issue=3&rft.spage=396&rft.isbn=&rft.btitle=&rft.title=BioTechniques&rft.issn=07366205&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-11-26 N1 - Date created - 1993-11-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mortality among workers at a nuclear power plant in the United States. AN - 76024079; 8218874 AB - A second follow-up of 9,000 workers at the Calvert Cliffs Nuclear Power Plant (MD, USA) identified 346 deaths in the years 1969-88, 101 of which were attributed to malignant neoplasms. The original study had the primary purpose of assessing the feasibility of studies of workers based upon individual plant and Nuclear Regulatory Commission records. The average, cumulative, occupational dose through 1984 was low, only 21 mSv, but ranged up to 470 mSv, with 12 percent of the workers receiving more than 50 mSv. Mortality from most causes of death was low and there was a deficit of deaths from diseases of the circulatory system. Ionizing radiation exposures were not related to the probability of death from neoplasms generally or from any specific form of cancer. There were only two deaths from leukemia, whereas four were expected at population death rates. Larger numbers of workers, followed for longer periods of time, are needed to determine the mortality risk to workers in the nuclear power industry. The difficulties in obtaining dose information for transient workers were so great, and so time consuming, as to make questionable the practicability of studying the workers at a large number of power plants in this way. JF - Cancer causes & control : CCC AU - Jablon, S AU - Boice, J D AD - National Cancer Institute, Radiation Epidemiology Branch, Bethesda, MD 20892. Y1 - 1993/09// PY - 1993 DA - September 1993 SP - 427 EP - 430 VL - 4 IS - 5 SN - 0957-5243, 0957-5243 KW - Index Medicus KW - Healthy Worker Effect KW - Radiation Dosage KW - Humans KW - Aged KW - Film Dosimetry KW - Cardiovascular Diseases -- mortality KW - Respiratory Tract Neoplasms -- mortality KW - Risk Factors KW - Adult KW - Cohort Studies KW - Follow-Up Studies KW - Maryland -- epidemiology KW - Middle Aged KW - Male KW - Power Plants KW - Neoplasms -- mortality KW - Occupational Diseases -- mortality KW - Nuclear Energy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76024079?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+causes+%26+control+%3A+CCC&rft.atitle=Mortality+among+workers+at+a+nuclear+power+plant+in+the+United+States.&rft.au=Jablon%2C+S%3BBoice%2C+J+D&rft.aulast=Jablon&rft.aufirst=S&rft.date=1993-09-01&rft.volume=4&rft.issue=5&rft.spage=427&rft.isbn=&rft.btitle=&rft.title=Cancer+causes+%26+control+%3A+CCC&rft.issn=09575243&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-12-03 N1 - Date created - 1993-12-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Low frequency of H-ras activation in naturally occurring hepatocellular tumors of C3H/HeNCr mice. AN - 75999333; 8403222 AB - Previous reports from several laboratories have consistently shown that approximately 30% of spontaneous hepatocellular adenomas and 70-80% of spontaneous hepatocellular carcinomas found in aged B6C3F1 [C57BL/6 (liver tumor resistant) x C3H (liver tumor susceptible)] male mice contain one of three missense point mutations in codon 61 of the H-ras oncogene, CAA-->AAA, CGA or CTA. Irrespective of subline, the C3H mouse, the paternal parent strain of the B6C3F1 hybrid, is more susceptible to spontaneous liver tumorigenesis than the B6C3F1 mouse. However, the role of H-ras in the pathogenesis of hepatocellular tumors in C3H mice is less clear, as widely different frequencies of activation of this gene, but by the same point mutations in codon 61, have been reported by various laboratories. The present study was undertaken to characterize H-ras involvement in hepatocellular tumors of aged C3H/He mice from the NCI-Frederick Cancer Research and Development Center Colony (C3H/HeNCr). Oncogene activation was evaluated in 45 C3H/HeNCr hepatocellular tumors by the NIH 3T3 transfection assays, and point mutations in the H-ras oncogene were detected and characterized in DNA fragments amplified by PCR, using dot blot hybridization analysis with mutation-specific oligonucleotide probes and direct dideoxy sequencing of PCR products. The only transforming gene detected in these tumors by NIH 3T3 transfection was H-ras. Only 17% (1/6) of spontaneous carcinomas and 8% (3/39) of spontaneous adenomas contained transforming H-ras sequences, each with a point mutation in codon 61. In all four cases with H-ras mutations, mutated sequences comprised a minor fraction of total H-ras gene copies in DNA extracted from primary tumors. H-ras mutations thus appear to have arisen relatively late in the pathogenesis of the neoplasms. For comparison, sections of formalin-fixed, paraffin-embedded hepatocellular tumors that occurred in untreated B6C3F1 hybrid mice sired by C3H/HeNCr males were assayed for the same H-ras mutations by PCR and dot blot hybridization. Nine of 13 such tumors (4/6 carcinomas, 5/7 adenomas) were positive. The overall difference in frequency of H-ras codon 61 mutations in hepatocellular tumors in C3H/HeNCr (4/45) versus B6C3F1 (9/13) was highly significant (P = 0.000035, Fisher's exact test). These data indicate that point mutations in H-ras do not generally play a major or an initiating role in spontaneous hepatocarcinogenesis of inbred C3H/HeNCr mice and contrast with the high rate of ras mutations in liver tumors of the B6C3F1 hybrid. JF - Carcinogenesis AU - Enomoto, T AU - Weghorst, C M AU - Ward, J M AU - Anderson, L M AU - Perantoni, A O AU - Rice, J M AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick, MD 21702-1201. Y1 - 1993/09// PY - 1993 DA - September 1993 SP - 1939 EP - 1944 VL - 14 IS - 9 SN - 0143-3334, 0143-3334 KW - H-ras KW - Oligonucleotide Probes KW - 0 KW - Index Medicus KW - Polymerase Chain Reaction KW - Animals KW - 3T3 Cells KW - Base Sequence KW - Transfection KW - Molecular Sequence Data KW - Mice, Inbred C3H KW - Oligonucleotide Probes -- chemistry KW - Mice KW - Male KW - Female KW - Cell Transformation, Neoplastic -- genetics KW - Point Mutation -- genetics KW - Adenoma, Liver Cell -- genetics KW - Genes, ras -- genetics KW - Gene Amplification -- genetics KW - Carcinoma, Hepatocellular -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75999333?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Low+frequency+of+H-ras+activation+in+naturally+occurring+hepatocellular+tumors+of+C3H%2FHeNCr+mice.&rft.au=Enomoto%2C+T%3BWeghorst%2C+C+M%3BWard%2C+J+M%3BAnderson%2C+L+M%3BPerantoni%2C+A+O%3BRice%2C+J+M&rft.aulast=Enomoto&rft.aufirst=T&rft.date=1993-09-01&rft.volume=14&rft.issue=9&rft.spage=1939&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-11-05 N1 - Date created - 1993-11-05 N1 - Date revised - 2017-01-13 N1 - Gene symbol - H-ras N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - TCDD-mediated changes in hepatic epidermal growth factor receptor may be a critical event in the hepatocarcinogenic action of TCDD. AN - 75987740; 8403215 AB - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent liver tumor promoter in rats, with females being more sensitive than males. The epidermal growth factor receptor (EGFR) pathway has been implicated in altered cell growth patterns induced by tumor promoters. We investigated hepatic EGFR levels in a two-stage initiation promotion model. The TCDD doses were chosen to encompass the dose range administered in a previous chronic bioassay currently used to determine the cancer potency commonly used for human health risk assessments. TCDD was administered biweekly by oral gavage to female Sprague-Dawley rats for 30 weeks following initiation by a single dose of diethylnitrosamine (DEN). TCDD-mediated decreased EGF receptor levels were demonstrated in intact but not ovariectomized animals, consistent with previous tumor data. Likewise, previous studies have shown that TCDD induces cell proliferation in intact rats but not ovariectomized rats. We report a significant dose-dependent decrease in plasma membrane EGF receptor maximum binding capacity in both initiated and non-initiated intact rats at TCDD doses equivalent to 3.5, 10.7, 35.7 and 125 ng/kg/day. There was a significant correlation between EGF receptor effects and liver TCDD concentration. The decrease in plasma membrane EGFR determined by equilibrium binding was confirmed quantitatively by EGF stimulation of EGFR autophosphorylation as well as qualitatively by immunohistochemical detection in control and treated rats. These results demonstrate that the observed down modulation of the EGFR by TCDD is ovarian-dependent and is a sensitive effect induced at dose levels associated with TCDD hepatocarcinogenicity in rodent bioassays. JF - Carcinogenesis AU - Sewall, C H AU - Lucier, G W AU - Tritscher, A M AU - Clark, G C AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1993/09// PY - 1993 DA - September 1993 SP - 1885 EP - 1893 VL - 14 IS - 9 SN - 0143-3334, 0143-3334 KW - Polychlorinated Dibenzodioxins KW - 0 KW - Diethylnitrosamine KW - 3IQ78TTX1A KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - Index Medicus KW - Animals KW - Analysis of Variance KW - Dose-Response Relationship, Drug KW - Cell Division -- drug effects KW - Liver Neoplasms, Experimental -- chemically induced KW - Rats KW - Rats, Sprague-Dawley KW - Phosphorylation KW - Ovariectomy KW - Cell Membrane -- metabolism KW - Down-Regulation -- drug effects KW - Female KW - Receptor, Epidermal Growth Factor -- drug effects KW - Liver -- cytology KW - Receptor, Epidermal Growth Factor -- metabolism KW - Polychlorinated Dibenzodioxins -- pharmacology KW - Polychlorinated Dibenzodioxins -- toxicity KW - Liver -- metabolism KW - Receptor, Epidermal Growth Factor -- analysis KW - Liver -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75987740?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=TCDD-mediated+changes+in+hepatic+epidermal+growth+factor+receptor+may+be+a+critical+event+in+the+hepatocarcinogenic+action+of+TCDD.&rft.au=Sewall%2C+C+H%3BLucier%2C+G+W%3BTritscher%2C+A+M%3BClark%2C+G+C&rft.aulast=Sewall&rft.aufirst=C&rft.date=1993-09-01&rft.volume=14&rft.issue=9&rft.spage=1885&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-11-05 N1 - Date created - 1993-11-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Studies on the role of topoisomerases in general, gene- and strand-specific DNA repair. AN - 75983722; 8403208 AB - Using specific inhibitors we have assessed the role of topoisomerases I and II in DNA repair of the overall genome and in both strands of an essential gene, the dihydrofolate reductase (DHFR) gene in chinese hamster ovary (CHO) cells. In these studies we have: (1) used inhibitors of topoisomerases during the repair incubation and (2) studied the DNA repair in cells with altered levels of topoisomerase activity. When cells were allowed to repair after UV irradiation, the gene-specific DNA repair was not affected by either topoisomerase I or topoisomerase II inhibitors alone. However, when topoisomerase I and topoisomerase II inhibitors were added simultaneously the gene- and strand-specific DNA repair were markedly inhibited. In contrast, the overall genome DNA repair was only marginally affected. This suggests that topoisomerases are involved in gene-specific DNA repair and that one type may substitute for the other in the repair process. That concept is further supported by our findings using a mutant cell line with a decreased level of topoisomerase I: gene-specific DNA repair can be inhibited by a topoisomerase II inhibitor alone. By analyzing the steady-state expression of the DHFR gene we find that inhibition of repair in the DHFR gene is not ascribed to an obvious change in the messenger level. Furthermore, using agents other than UV, we observe that the inhibitors have no effect on gene-specific repair of DNA damage introduced by the chemotherapeutic agents cisplatin and nitrogen mustard. JF - Carcinogenesis AU - Stevnsner, T AU - Bohr, V A AD - Laboratory of Molecular Pharmacology, National Cancer Institute, NIH, Bethesda, MD 20892. Y1 - 1993/09// PY - 1993 DA - September 1993 SP - 1841 EP - 1850 VL - 14 IS - 9 SN - 0143-3334, 0143-3334 KW - DHFR KW - Pyrimidine Dimers KW - 0 KW - RNA, Messenger KW - Thiobarbiturates KW - Topoisomerase I Inhibitors KW - Topoisomerase II Inhibitors KW - Mechlorethamine KW - 50D9XSG0VR KW - merbarone KW - 97534-21-9 KW - Tetrahydrofolate Dehydrogenase KW - EC 1.5.1.3 KW - DNA Topoisomerases, Type I KW - EC 5.99.1.2 KW - DNA Topoisomerases, Type II KW - EC 5.99.1.3 KW - Cisplatin KW - Q20Q21Q62J KW - Camptothecin KW - XT3Z54Z28A KW - Index Medicus KW - Animals KW - RNA, Messenger -- metabolism KW - Dose-Response Relationship, Drug KW - CHO Cells -- enzymology KW - CHO Cells -- drug effects KW - Cisplatin -- pharmacology KW - Mechlorethamine -- pharmacology KW - CHO Cells -- radiation effects KW - Cricetinae KW - Pyrimidine Dimers -- genetics KW - DNA Replication -- radiation effects KW - Camptothecin -- pharmacology KW - DNA Topoisomerases, Type I -- physiology KW - Tetrahydrofolate Dehydrogenase -- metabolism KW - DNA Topoisomerases, Type II -- physiology KW - DNA Replication -- drug effects KW - DNA Repair -- drug effects KW - Thiobarbiturates -- pharmacology KW - Tetrahydrofolate Dehydrogenase -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75983722?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Studies+on+the+role+of+topoisomerases+in+general%2C+gene-+and+strand-specific+DNA+repair.&rft.au=Stevnsner%2C+T%3BBohr%2C+V+A&rft.aulast=Stevnsner&rft.aufirst=T&rft.date=1993-09-01&rft.volume=14&rft.issue=9&rft.spage=1841&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-11-05 N1 - Date created - 1993-11-05 N1 - Date revised - 2017-01-13 N1 - Gene symbol - DHFR N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hematopoietic cytokines: similarities and differences in the structures, with implications for receptor binding. AN - 75975971; 8401223 AB - Crystal and NMR structures of helical cytokines--interleukin-4 (IL-4), granulocyte-macrophage colony-stimulating factor (GM-CSF), and interleukin-2 (IL-2)--have been compared. Root mean square deviations in the C alpha coordinates for the conserved regions of the helices were 1-2 A between different cytokines, about twice the differences observed for independently determined crystal and solution structures of IL-4. Considerable similarity in amino acid sequence in the areas expected to interact with the receptors was detected, and the available mutagenesis data for these cytokines were correlated with structure conservation. Models of cytokine-receptor interactions were postulated for IL-4 based on its structure as well as on the published structure of human growth hormone interacting with its receptors (de Vos, A.M., Ultsch, M., & Kossiakoff, A.A., 1992, Science 255, 306-312). Patches of positively charged residues on the surfaces of helices C and D of IL-4 may be responsible for the interactions with the negatively charged residues found in the complementary parts of the IL-4 receptors. JF - Protein science : a publication of the Protein Society AU - Wlodawer, A AU - Pavlovsky, A AU - Gustchina, A AD - Macromolecular Structure Laboratory, NCI-Frederick Cancer Research and Development Center, Maryland 21702. Y1 - 1993/09// PY - 1993 DA - September 1993 SP - 1373 EP - 1382 VL - 2 IS - 9 SN - 0961-8368, 0961-8368 KW - Cytokines KW - 0 KW - Interleukin-2 KW - Receptors, Cytokine KW - Interleukin-4 KW - 207137-56-2 KW - Granulocyte-Macrophage Colony-Stimulating Factor KW - 83869-56-1 KW - Index Medicus KW - Molecular Structure KW - Granulocyte-Macrophage Colony-Stimulating Factor -- chemistry KW - Crystallization KW - Models, Molecular KW - Humans KW - Molecular Sequence Data KW - Crystallography, X-Ray KW - Amino Acid Sequence KW - Interleukin-4 -- chemistry KW - Magnetic Resonance Spectroscopy KW - Interleukin-2 -- chemistry KW - Cytokines -- metabolism KW - Cytokines -- chemistry KW - Receptors, Cytokine -- metabolism KW - Hematopoiesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75975971?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Social+Work&rft.atitle=Exploring+the+relationship+between+exposure+to+interparental+violence+and+child+physical+abuse+in+childhood+and+the+impacts+on+mental+health+problems+in+later+young+adulthood+among+South+Korean+college+students&rft.au=Han%2C+Meekyung%3BChoi%2C+Young%3BJung%2C+Soyon&rft.aulast=Han&rft.aufirst=Meekyung&rft.date=2016-11-01&rft.volume=59&rft.issue=6&rft.spage=821&rft.isbn=&rft.btitle=&rft.title=International+Social+Work&rft.issn=00208728&rft_id=info:doi/10.1177%2F0020872814562481 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-11-23 N1 - Date created - 1993-11-23 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: EMBO J. 1992 Sep;11(9):3193-201 [1505514] Science. 1992 Aug 14;257(5072):961-4 [1502561] Biochemistry. 1992 Aug 25;31(33):7741-4 [1510960] FEBS Lett. 1992 Aug 31;309(1):59-64 [1511746] Science. 1992 Nov 20;258(5086):1358-62 [1455231] J Biol Chem. 1992 Oct 5;267(28):20371-6 [1400355] EMBO J. 1992 Nov;11(11):3921-6 [1396586] Nature. 1993 May 13;363(6425):172-6 [8483502] Proc Natl Acad Sci U S A. 1993 Jun 1;90(11):5167-71 [7685117] Biochemistry. 1993 Jul 6;32(26):6744-62 [8329398] Sci Am. 1985 Oct;253(4):88-99 [4071032] Methods Enzymol. 1985;115:157-71 [3841179] Proc Natl Acad Sci U S A. 1986 Apr;83(8):2458-62 [3085095] J Mol Biol. 1986 Aug 20;190(4):593-604 [3097327] J Biol Chem. 1987 Apr 25;262(12):5723-31 [3106342] Proc Natl Acad Sci U S A. 1987 Sep;84(18):6434-7 [2819877] Science. 1987 Dec 18;238(4834):1707-9 [3500515] EMBO J. 1988 Apr;7(4):1061-9 [3261239] Annu Rev Biochem. 1989;58:45-77 [2549855] Proc Natl Acad Sci U S A. 1990 Sep;87(18):6934-8 [2169613] Proc Natl Acad Sci U S A. 1991 Jan 15;88(2):502-6 [1988949] Biochemistry. 1991 Feb 12;30(6):1515-23 [1993171] J Biol Chem. 1991 Mar 15;266(8):5333-41 [2002066] Science. 1991 May 3;252(5006):698-702 [1902591] Proc Natl Acad Sci U S A. 1991 May 15;88(10):4498-502 [2034689] J Clin Invest. 1991 Jun;87(6):2147-52 [2040697] Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):4636-40 [2052547] J Biol Chem. 1991 Jul 25;266(21):13804-10 [1856212] FEBS Lett. 1991 Jul 29;286(1-2):58-60 [1864379] J Biol Chem. 1991 Nov 15;266(32):21791-7 [1939201] Proteins. 1991;10(4):325-39 [1946342] Science. 1991 Dec 20;254(5039):1779-82 [1837174] EMBO J. 1992 Mar;11(3):909-16 [1532144] Science. 1992 Jan 17;255(5042):306-12 [1549776] J Mol Biol. 1992 Apr 20;224(4):1075-85 [1569568] EMBO J. 1992 Jun;11(6):2047-53 [1600937] Science. 1992 Jun 19;256(5064):1673-7 [1609277] Nature. 1992 Jul 2;358(6381):86-9 [1614539] Science. 1992 Jul 17;257(5068):410-3 [1631562] EMBO J. 1992 Sep;11(9):3237-44 [1387082] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Expression of Chinese hamster cAMP-dependent protein kinase in Escherichia coli results in growth inhibition of bacterial cells: a model system for the rapid screening of mutant type I regulatory subunits. AN - 75963024; 8396261 AB - The regulatory and catalytic subunits of cAMP-dependent protein kinase (PKA) were coexpressed within the same bacterial cell using a polycistronic bacterial T7 expression vector encoding Chinese hamster cDNAs for the type I regulatory (RI) and catalytic alpha (C alpha) subunits of PKA. Basal expression of active RI/C alpha holoenzyme in the BL21(DE3) strain of Escherichia coli caused severe growth inhibition resulting in extremely small colony size. Several lines of evidence demonstrate that this growth inhibition requires active PKA subunits and cAMP: (i) this phenotype is dependent on cAMP since it is not seen in a strain lacking adenylyl cyclase activity, but the growth rate of these transformants is slower when exogenous cAMP is added; (ii) normal growth occurs when wild-type RI cDNA is replaced by a mutant RI cDNA encoding a RI protein with reduced cAMP binding; and (iii) the growth-inhibited phenotype of the transformed BL21(DE3) cells requires soluble, active C alpha protein. Holoenzyme expressed in bacteria is activated by cAMP, which stimulates phosphorylation of an endogenous 50-kDa protein that is missing in four host mutants selected for normal growth after transformation with PKA holoenzyme. A mutant RI cDNA library was generated by PCR random mutagenesis and screened by polycistronic expression in BL21(DE3) cells. The RI cDNA sequence from one revertant has base-pair substitutions creating two amino acid substitutions within the cAMP binding sites. The coexpression of the RI/C alpha subunits in BL21(DE3) bacterial cells provides a system for rapidly selecting mutations in the RI subunits of PKA. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Gosse, M E AU - Padmanabhan, A AU - Fleischmann, R D AU - Gottesman, M M AD - Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/09/01/ PY - 1993 DA - 1993 Sep 01 SP - 8159 EP - 8163 VL - 90 IS - 17 SN - 0027-8424, 0027-8424 KW - Macromolecular Substances KW - 0 KW - Oligodeoxyribonucleotides KW - Recombinant Proteins KW - Cyclic AMP KW - E0399OZS9N KW - Protein Kinases KW - EC 2.7.- KW - Index Medicus KW - Animals KW - Recombinant Proteins -- biosynthesis KW - Cricetulus KW - Enzyme Activation KW - Cloning, Molecular KW - Polymerase Chain Reaction KW - Base Sequence KW - Phosphorylation KW - Recombinant Proteins -- metabolism KW - Kinetics KW - Restriction Mapping KW - Cyclic AMP -- pharmacology KW - Molecular Sequence Data KW - Substrate Specificity KW - Cricetinae KW - Mutagenesis, Site-Directed KW - Protein Kinases -- metabolism KW - Genes KW - Protein Kinases -- biosynthesis KW - Protein Kinases -- genetics KW - Escherichia coli -- genetics KW - Escherichia coli -- growth & development UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75963024?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Expression+of+Chinese+hamster+cAMP-dependent+protein+kinase+in+Escherichia+coli+results+in+growth+inhibition+of+bacterial+cells%3A+a+model+system+for+the+rapid+screening+of+mutant+type+I+regulatory+subunits.&rft.au=Gosse%2C+M+E%3BPadmanabhan%2C+A%3BFleischmann%2C+R+D%3BGottesman%2C+M+M&rft.aulast=Gosse&rft.aufirst=M&rft.date=1993-09-01&rft.volume=90&rft.issue=17&rft.spage=8159&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 - 1993-10-05 N1 - Date created - 1993-10-05 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cell. 1985 Jul;41(3):745-51 [2988785] Biochemistry. 1984 Aug 28;23(18):4193-9 [6487597] J Biol Chem. 1986 Aug 25;261(24):11091-6 [3525560] J Biol Chem. 1986 Dec 15;261(35):16288-91 [3023347] Annu Rev Biochem. 1987;56:567-613 [2956925] Science. 1987 Oct 16;238(4825):336-41 [2443975] Biochem Biophys Res Commun. 1987 Dec 31;149(3):939-45 [3426618] Proc Natl Acad Sci U S A. 1989 May;86(10):3489-93 [2542933] Eur J Biochem. 1989 May 15;181(3):563-70 [2659343] J Biol Chem. 1989 Dec 15;264(35):20940-6 [2687267] Gene. 1989 Dec 14;84(2):487-91 [2693217] Proc Natl Acad Sci U S A. 1990 Feb;87(3):1066-70 [2105495] Genes Dev. 1990 Apr;4(4):515-24 [2163340] J Biol Chem. 1990 Jul 15;265(20):11960-6 [2164022] J Biol Chem. 1990 Jul 15;265(20):11967-72 [2164023] Proc Natl Acad Sci U S A. 1990 Jul;87(14):5573-7 [2196572] Annu Rev Biochem. 1990;59:971-1005 [2165385] Methods Enzymol. 1990;185:60-89 [2199796] Gene. 1990 Sep 14;93(2):229-34 [2227436] J Mol Biol. 1991 May 5;219(1):37-44 [2023259] Virology. 1991 Jun;182(2):846-51 [1850930] J Biol Chem. 1991 Jun 5;266(16):10189-95 [1645343] Eur J Biochem. 1991 May 23;198(1):25-30 [2040287] Biochim Biophys Acta. 1991 Aug 27;1090(1):70-80 [1883844] J Biol Chem. 1991 Oct 5;266(28):18446-53 [1917968] FEBS Lett. 1992 Jan 20;296(2):179-83 [1733774] Biochemistry. 1992 Apr 14;31(14):3720-6 [1567825] Eur J Biochem. 1992 Apr 15;205(2):575-81 [1572358] Anal Biochem. 1976 May 7;72:248-54 [942051] Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7 [271968] Proc Natl Acad Sci U S A. 1983 Jun;80(12):3608-12 [6190178] Proc Natl Acad Sci U S A. 1986 Mar;83(5):1300-4 [3456589] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Further evidence of the tumor-suppressive effects of cadmium in the B6C3F1 mouse liver and lung: late stage vulnerability of tumors to cadmium and the role of metallothionein. AN - 75957017; 8371163 AB - Previously, we studied the ability of cadmium to initiate or promote tumors in B6C3F1 mice and, contrary to expectation, found that cadmium inhibited development of N-nitrosodiethylamine (NDEA)-initiated and sodium barbital-promoted liver tumors. In this study, the time course of cadmium inhibition of NDEA-initiated tumor formation was studied. A single dose of NDEA (90 mg/kg i.p.) was given at 5 weeks of age (time 0) followed by cadmium (1000 ppm) in drinking water from 2 to 48, 4 to 48, 8 to 48, 16 to 48 and 32 to 48 weeks. The study ended at 48 weeks. NDEA-induced elevations in liver tumor incidence (22 tumor-bearing mice/25 total) over control (5/25) were prevented by cadmium regardless of the period of administration (NDEA + cadmium: 2-48 weeks, 2/25; 4-48 weeks, 1/25; 8-48 weeks, 1/25; 16-48 weeks, 2/25; 32-48 weeks, 6/24). Cadmium alone (2-48 weeks) eliminated (0/25) spontaneously occurring liver tumors (5/25). NDEA-induced lung tumor incidence (25/25) and multiplicity (7.28 tumors/lung) were also reduced by cadmium (maximal decreases 28% and 80%, respectively). Some evidence of a specific deficiency of metallothionein in tumor cells was seen immunohistologically in NDEA-induced hepatic lesions and pulmonary lesions. These results indicate that cadmium prevents or reduces tumor formation in the B6C3F1 mouse liver and lung regardless of the exposure interval and apparently by cell-specific cytotoxicity. Auxiliary studies indicated that in mice bearing multiple liver foci resulting from NDEA treatment there was a marked reduction in basal metallothionein levels and in response to zinc induction.(ABSTRACT TRUNCATED AT 250 WORDS) JF - The Journal of pharmacology and experimental therapeutics AU - Waalkes, M P AU - Diwan, B A AU - Weghorst, C M AU - Ward, J M AU - Rice, J M AU - Cherian, M G AU - Goyer, R A AD - National Cancer Institute, PRI/DynCorp, Frederick Cancer Research and Development Center, Maryland. Y1 - 1993/09// PY - 1993 DA - September 1993 SP - 1656 EP - 1663 VL - 266 IS - 3 SN - 0022-3565, 0022-3565 KW - Anticarcinogenic Agents KW - 0 KW - Cadmium KW - 00BH33GNGH KW - Diethylnitrosamine KW - 3IQ78TTX1A KW - Metallothionein KW - 9038-94-2 KW - Index Medicus KW - Mice, Inbred Strains KW - Animals KW - Liver -- drug effects KW - Body Weight -- drug effects KW - Mice, Inbred C3H KW - Lung -- drug effects KW - Mice KW - Time Factors KW - Liver -- chemistry KW - Male KW - Lung Neoplasms -- prevention & control KW - Anticarcinogenic Agents -- therapeutic use KW - Metallothionein -- analysis KW - Metallothionein -- physiology KW - Liver Neoplasms, Experimental -- chemically induced KW - Lung Neoplasms -- chemically induced KW - Liver Neoplasms, Experimental -- prevention & control KW - Liver Neoplasms, Experimental -- chemistry KW - Cadmium -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75957017?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Further+evidence+of+the+tumor-suppressive+effects+of+cadmium+in+the+B6C3F1+mouse+liver+and+lung%3A+late+stage+vulnerability+of+tumors+to+cadmium+and+the+role+of+metallothionein.&rft.au=Waalkes%2C+M+P%3BDiwan%2C+B+A%3BWeghorst%2C+C+M%3BWard%2C+J+M%3BRice%2C+J+M%3BCherian%2C+M+G%3BGoyer%2C+R+A&rft.aulast=Waalkes&rft.aufirst=M&rft.date=1993-09-01&rft.volume=266&rft.issue=3&rft.spage=1656&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 - 1993-10-14 N1 - Date created - 1993-10-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Enhanced stimulation by ribavirin of the 5'-phosphorylation and anti-human immunodeficiency virus activity of purine 2'-beta-fluoro-2',3'-dideoxynucleosides. AN - 75956813; 8371712 AB - The purine dideoxynucleosides 2'-beta-fluoro-2',3'-dideoxyadenosine (2'-beta-F-ddAdo), 2'-beta-fluoro-2',3'-dideoxyinosine, and 2'-beta-fluoro-2',3'-dideoxyguanosine (2'-beta-F-ddGuo) are active inhibitors of the replication of the human immunodeficiency virus (HIV) in the ATH8 assay system, with 2'-beta-F-ddAdo and 2'-beta-fluoro-2',3'- dideoxyinosine showing activity and potency equivalent to those of their respective parent compounds, 2',3'-dideoxyadenosine (ddAdo) and 2',3'-dideoxyinosine. Because inhibitors of IMP dehydrogenase such as ribavirin and tiazofurin stimulate the 5'-phosphorylation and consequently the anti-HIV activity of the three nonfluorinated parent compounds (ddAdo, 2',3'-dideoxyinosine, and 2',3'-dideoxyguanosine), we have undertaken a study in MOLT-4 cells to determine whether a similar stimulatory effect is observed with their 2'-beta-fluorinated analogs. The 5'-phosphorylation of all the fluoro compounds was found to be greatly enhanced by low levels (10 microM) of either ribavirin or tiazofurin, with the greatest increase being seen with 2'-beta-F-ddAdo, where stimulation of the formation of the 5'-mono-, di-, and triphosphorylated nucleotides was approximately 20-fold, 6-fold, and 5-fold, respectively. These increases were approximately 3-fold greater than the increases seen with the nonfluorinated parent compound ddAdo. In the case of 2'-beta-F-ddGuo, the greatest stimulation (8-fold) was seen in the formation of the 5'-diphosphate. In parallel with the increased phosphorylation of 2'-beta-F-ddAdo and 2'-beta-F-ddGuo, the anti-HIV potency of these two compounds at the 5 microM level was approximately doubled in the presence of ribavirin (5 microM). JF - Molecular pharmacology AU - Johns, D G AU - Ahluwalia, G S AU - Cooney, D A AU - Mitsuya, H AU - Driscoll, J S AD - Laboratory of Medicinal Chemistry, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/09// PY - 1993 DA - September 1993 SP - 519 EP - 523 VL - 44 IS - 3 SN - 0026-895X, 0026-895X KW - Dideoxynucleosides KW - 0 KW - Purine Nucleosides KW - 2'-fluoro-2',3'-dideoxyguanosine KW - 125291-17-0 KW - 2'-fluoro-2',3'-dideoxyinosine KW - 134892-26-5 KW - lodenosine KW - 3WB2LGT4R1 KW - Ribavirin KW - 49717AWG6K KW - Dideoxyadenosine KW - 4Q86AH641A KW - Didanosine KW - K3GDH6OH08 KW - Index Medicus KW - AIDS/HIV KW - Dideoxyadenosine -- pharmacology KW - Drug Synergism KW - Dideoxyadenosine -- analogs & derivatives KW - Didanosine -- pharmacology KW - Structure-Activity Relationship KW - Phosphorylation -- drug effects KW - Didanosine -- analogs & derivatives KW - Dideoxynucleosides -- metabolism KW - Dideoxynucleosides -- pharmacology KW - Ribavirin -- pharmacology KW - Purine Nucleosides -- metabolism KW - HIV-1 -- drug effects KW - Purine Nucleosides -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75956813?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Child+Abuse+%26+Neglect&rft.atitle=Intervention+effects+on+negative+affect+of+CPS-referred+children%3A+Results+of+a+randomized+clinical+trial&rft.au=Lind%2C+Teresa%3BBernard%2C+Kristin%3BRoss%2C+Emily%3BDozier%2C+Mary&rft.aulast=Lind&rft.aufirst=Teresa&rft.date=2014-09-01&rft.volume=38&rft.issue=9&rft.spage=1459&rft.isbn=&rft.btitle=&rft.title=Child+Abuse+%26+Neglect&rft.issn=01452134&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-10-14 N1 - Date created - 1993-10-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Enkephalin gene transcription in bovine chromaffin cells is regulated by calcium and protein kinase A signal transduction pathways: identification of DNase I-hypersensitive sites. AN - 75949407; 8396715 AB - The bovine enkephalin gene is responsive to multiple signaling pathways in primary chromaffin cell cultures. We examined the effects of activation of the calcium and protein kinase A pathways on accumulation of enkephalin peptide and mRNA, gene transcription, and chromatin structure in the 5' region of the gene. We show here that the increase of enkephalin mRNA and peptide after depolarization of chromaffin cells with KCl or activation of adenylate cyclase with forskolin is preceded by an increase in enkephalin gene transcription. Both enkephalin peptide and mRNA were reduced by co-treatment of KCl- or forskolin-stimulated cultures with phorbol esters. Three enhancer sequences that were previously shown to be responsive to calcium, protein kinase A, and phorbol esters in the human gene in vitro were identified in the bovine enkephalin promoter, identifying a potential locus of control for these pathways in vivo. DNase I hypersensitivity mapping identified two tissue-specific sites that are associated with enkephalin gene expression in adrenal medulla and chromaffin cells; site 1 is in the promoter, which contains the three enhancer elements, and site 2 is in the first intron. These results suggest that regulation of the enkephalin gene in primary chromaffin cells by the calcium, protein kinase A, and protein kinase C signaling pathways occurs by modulation of transcription factor activity at several discrete loci on the enkephalin gene. JF - Molecular pharmacology AU - MacArthur, L AU - Koller, K J AU - Eiden, L E AD - Section on Molecular Neuroscience, National Institute of Mental Health, Bethesda, Maryland 20892. Y1 - 1993/09// PY - 1993 DA - September 1993 SP - 545 EP - 551 VL - 44 IS - 3 SN - 0026-895X, 0026-895X KW - Chromatin KW - 0 KW - Enkephalins KW - Cyclic AMP KW - E0399OZS9N KW - Protein Kinases KW - EC 2.7.- KW - Deoxyribonuclease I KW - EC 3.1.21.1 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Animals KW - Sequence Homology, Nucleic Acid KW - Membrane Potentials -- physiology KW - Cyclic AMP -- physiology KW - Signal Transduction -- physiology KW - Base Sequence KW - Cattle KW - Promoter Regions, Genetic KW - Chromatin -- chemistry KW - In Vitro Techniques KW - Molecular Sequence Data KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Transcription, Genetic -- physiology KW - Enkephalins -- genetics KW - Protein Kinases -- physiology KW - Gene Expression Regulation -- physiology KW - Calcium -- physiology KW - Adrenal Medulla -- cytology KW - Adrenal Medulla -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75949407?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Enkephalin+gene+transcription+in+bovine+chromaffin+cells+is+regulated+by+calcium+and+protein+kinase+A+signal+transduction+pathways%3A+identification+of+DNase+I-hypersensitive+sites.&rft.au=MacArthur%2C+L%3BKoller%2C+K+J%3BEiden%2C+L+E&rft.aulast=MacArthur&rft.aufirst=L&rft.date=1993-09-01&rft.volume=44&rft.issue=3&rft.spage=545&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 - 1993-10-14 N1 - Date created - 1993-10-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Long-term testolactone therapy for precocious puberty in girls with the McCune-Albright syndrome. AN - 75948186; 8370686 AB - We used the aromatase inhibitor testolactone (40 mg/kg.day) to treat 12 girls with precocious puberty due to the McCune-Albright syndrome for periods of 0.5-5 yr. In the 7 girls who received testolactone for at least 3 yr, the mean +/- SD serum estradiol level was 618 +/- 268 pmol/L at the start of therapy and fell to 156 +/- 84 pmol/L at 1 yr, 116 +/- 48 pmol/L at 2 yr, and 241 +/- 260 pmol/L at 3 yr (P < 0.05 compared to the start of therapy), with recurrent ovarian cysts at 3 yr in 2 patients. These 7 girls averaged 8 menses/yr before therapy. The average frequency of menses decreased to 2 episodes/yr during the first year of treatment, 3/yr during the second year, and 4/yr during the third year. The mean +/- SD testosterone levels were slightly above the normal prepubertal range (0.51 +/- 0.2 nmol/L) before treatment and did not change significantly during treatment. The mean +/- SD androstenedione levels rose from 1.1 +/- 0.6 nmol/L before treatment to 2.1 +/- 0.1 nmol/L at 2 yr and 2.8 +/- 0.1 nmol/L after 3 yr of treatment (P < 0.05 compared to before treatment) and were consistent with normal adrenarche. The mean predicted adult stature was 143.0 +/- 7.8 cm before treatment and 147.3 +/- 11.5 cm at 3 yr (P = NS). In 3 of 12 girls, all with bone age greater than 12 yr, the gonadotropin responses to LHRH indicated early central precocious puberty after 1-4 yr of treatment. The adverse effects of testolactone were transient abdominal pain, headache, and diarrhea in 3 girls and elevated hepatic enzymes in 1 girl who had abnormal liver function before treatment. Six families acknowledged difficulty in adhering to the daily dosing schedule. We conclude that testolactone can be effective in the treatment of LHRH-independent precocious puberty in girls with McCune-Albright syndrome, but that some patients exhibit an escape from the effects of treatment after 1-3 yr. JF - The Journal of clinical endocrinology and metabolism AU - Feuillan, P P AU - Jones, J AU - Cutler, G B AD - Developmental Endocrinology Branch, National Institute for Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/09// PY - 1993 DA - September 1993 SP - 647 EP - 651 VL - 77 IS - 3 SN - 0021-972X, 0021-972X KW - Gonadotropin-Releasing Hormone KW - 33515-09-2 KW - Testosterone KW - 3XMK78S47O KW - Androstenedione KW - 409J2J96VR KW - Estradiol KW - 4TI98Z838E KW - Testolactone KW - 6J9BLA949Q KW - Luteinizing Hormone KW - 9002-67-9 KW - Follicle Stimulating Hormone KW - 9002-68-0 KW - Abridged Index Medicus KW - Index Medicus KW - Body Height KW - Humans KW - Child KW - Androstenedione -- blood KW - Follicle Stimulating Hormone -- blood KW - Child, Preschool KW - Bone Development KW - Age Determination by Skeleton KW - Estradiol -- blood KW - Testosterone -- blood KW - Menstruation KW - Luteinizing Hormone -- blood KW - Female KW - Puberty KW - Testolactone -- adverse effects KW - Fibrous Dysplasia, Polyostotic -- blood KW - Fibrous Dysplasia, Polyostotic -- complications KW - Testolactone -- therapeutic use KW - Puberty, Precocious -- drug therapy KW - Puberty, Precocious -- etiology KW - Puberty, Precocious -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75948186?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Family+Therapy&rft.atitle=The+Complexity+of+Investigating+Possible+Sexual+Abuse+of+a+Child&rft.au=Lowenstein%2C+Ludwig+F&rft.aulast=Lowenstein&rft.aufirst=Ludwig&rft.date=2011-08-10&rft.volume=39&rft.issue=4&rft.spage=292&rft.isbn=&rft.btitle=&rft.title=The+American+Journal+of+Family+Therapy&rft.issn=01926187&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-10-14 N1 - Date created - 1993-10-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A rapid method for cloning mutagenic DNA repair genes: isolation of umu-complementing genes from multidrug resistance plasmids R391, R446b, and R471a. AN - 75943970; 8366028 AB - Genetic and physiological experiments have demonstrated that the products of the umu-like operon are directly required for mutagenic DNA repair in enterobacteria. To date, five such operons have been cloned and studied at the molecular level. Given the apparent wide occurrence of these mutagenic DNA repair genes in enterobacteria, it seems likely that related genes will be identified in other bacterial species and perhaps even in higher organisms. We are interested in identifying such genes. However, standard methods based on either DNA or protein cross-hybridization are laborious and, given the overall homology between previously identified members of this family (41 to 83% at the protein level), would probably have limited success. To facilitate the rapid identification of more diverse umu-like genes, we have constructed two Escherichia coli strains that allow us to identify umu-like genes after phenotypic complementation assays. With these two strains, we have cloned novel umu-like genes from three R plasmids, the IncJ plasmid R391 and two IncL/M plasmids, R446b and R471a. JF - Journal of bacteriology AU - Ho, C AU - Kulaeva, O I AU - Levine, A S AU - Woodgate, R AD - Section on DNA Replication, Repair and Mutagenesis, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/09// PY - 1993 DA - September 1993 SP - 5411 EP - 5419 VL - 175 IS - 17 SN - 0021-9193, 0021-9193 KW - umu KW - DNA, Bacterial KW - 0 KW - Index Medicus KW - Phenotype KW - Ultraviolet Rays KW - DNA, Bacterial -- genetics KW - Restriction Mapping KW - Drug Resistance, Microbial -- genetics KW - Genetic Complementation Test KW - Mutagenesis KW - Cloning, Molecular KW - DNA Repair -- genetics KW - Genes, Bacterial KW - R Factors -- radiation effects KW - Escherichia coli -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75943970?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+bacteriology&rft.atitle=A+rapid+method+for+cloning+mutagenic+DNA+repair+genes%3A+isolation+of+umu-complementing+genes+from+multidrug+resistance+plasmids+R391%2C+R446b%2C+and+R471a.&rft.au=Ho%2C+C%3BKulaeva%2C+O+I%3BLevine%2C+A+S%3BWoodgate%2C+R&rft.aulast=Ho&rft.aufirst=C&rft.date=1993-09-01&rft.volume=175&rft.issue=17&rft.spage=5411&rft.isbn=&rft.btitle=&rft.title=Journal+of+bacteriology&rft.issn=00219193&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-10-01 N1 - Date created - 1993-10-01 N1 - Date revised - 2017-01-13 N1 - Gene symbol - umu N1 - SuppNotes - Cited By: J Gen Microbiol. 1972 Oct;72(3):543-52 [4564689] J Bacteriol. 1989 May;171(5):2415-23 [2651400] J Gen Microbiol. 1973 Aug;77(2):249-59 [4584057] J Gen Microbiol. 1975 Jan;86(1):88-92 [1089756] Mol Gen Genet. 1977 Nov 14;156(2):121-31 [340898] Mol Gen Genet. 1978 Sep 20;165(1):87-93 [362169] Mutat Res. 1980 Aug;72(1):155-9 [6777687] J Gen Microbiol. 1981 Oct;126(2):305-10 [6279761] Nature. 1982 Nov 18;300(5889):278-81 [6755263] Gene. 1983 Aug;23(2):167-74 [6311684] Gene. 1984 Nov;31(1-3):165-71 [6098521] J Bacteriol. 1985 Apr;162(1):155-61 [2984171] Mol Gen Genet. 1985;199(1):133-40 [3889546] Mutat Res. 1985 Jun-Jul;150(1-2):147-58 [2987687] Proc Natl Acad Sci U S A. 1985 Jun;82(12):4193-7 [3889923] Proc Natl Acad Sci U S A. 1985 Jul;82(13):4331-5 [2989816] Proc Natl Acad Sci U S A. 1985 Jul;82(13):4336-40 [2989817] Mutat Res. 1986 Jul;166(1):29-37 [3014325] Plasmid. 1986 Jul;16(1):30-6 [3016779] Proc Natl Acad Sci U S A. 1987 Oct;84(19):6805-9 [3309946] Proc Natl Acad Sci U S A. 1988 Mar;85(6):1806-10 [3126496] Proc Natl Acad Sci U S A. 1988 Mar;85(6):1811-5 [3279417] Proc Natl Acad Sci U S A. 1988 Mar;85(6):1816-20 [3279418] Mutat Res. 1990 Sep-Nov;236(2-3):301-11 [2169028] Nucleic Acids Res. 1990 Sep 11;18(17):5045-50 [2129552] J Bacteriol. 1991 Feb;173(3):1051-63 [1991707] Crit Rev Biochem Mol Biol. 1990;25(6):415-56 [2292186] Mol Microbiol. 1991 Jan;5(1):149-55 [1707475] J Biol Chem. 1991 Aug 25;266(24):15710-5 [1874728] J Bacteriol. 1991 Sep;173(18):5604-11 [1885540] Mol Gen Genet. 1991 Sep;229(1):81-5 [1910151] Biochimie. 1991 Apr;73(4):479-84 [1911948] Proc Natl Acad Sci U S A. 1991 Oct 15;88(20):9127-31 [1924375] Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11450-4 [1722334] Mutat Res. 1992 Mar;281(3):221-5 [1371846] J Bacteriol. 1992 May;174(9):2809-15 [1569012] Cell. 1992 May 1;69(3):439-56 [1581960] Cell. 1992 May 1;69(3):457-70 [1581961] Proc Natl Acad Sci U S A. 1992 Sep 1;89(17):8068-72 [1518831] J Bacteriol. 1992 Nov;174(21):6844-51 [1400235] J Bacteriol. 1992 Nov;174(21):6948-55 [1400244] Mol Microbiol. 1992 Aug;6(16):2213-8 [1406263] Science. 1993 Mar 26;259(5103):1892-6 [8456313] Science. 1993 Mar 26;259(5103):1896-9 [8456314] Nucleic Acids Res. 1993 Apr 11;21(7):1577-80 [8479908] Nucleic Acids Res. 1993 Apr 11;21(7):1665 [8479919] Mol Gen Genet. 1972;119(2):93-102 [4565757] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ascorbic acid accumulation and transport in human fibroblasts. AN - 75943616; 8373364 AB - As the initial step in the use of fibroblasts as a model system for 'in situ kinetics', ascorbic acid (vitamin C) accumulation in normal human fibroblasts was investigated for the first time. Ascorbic acid was transported into fibroblasts and accumulated against a concentration gradient up to 20-fold, as measured by h.p.l.c. with coulometric electrochemical detection. Ascorbic acid accumulation was mediated by two concentration-dependent transport activities. The first was a high-affinity activity with an apparent Km of 6 microM and an apparent Vmax. of 203 microM/h, and the second was a low-affinity activity with an apparent Km of 5 mM and an apparent Vmax. of 1.8 mM/h. Both activities were inhibited by metabolic inhibitors and inhibitors of ascorbic acid transport in human neutrophils. The low-affinity transporter could not be accounted for by diffusion. Although the high-affinity transport activity was comparable with that described for human neutrophils, the low-affinity transporter was different. These data provide the first evidence that two-component ascorbic acid transport may be a generalized mechanism for accumulation of this vitamin in humans. JF - The Biochemical journal AU - Welch, R W AU - Bergsten, P AU - Butler, J D AU - Levine, M AD - Laboratory of Cell Biology and Genetics, National Institute of Diabetes, Digestive, and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/09/01/ PY - 1993 DA - 1993 Sep 01 SP - 505 EP - 510 VL - 294 ( Pt 2) SN - 0264-6021, 0264-6021 KW - Carrier Proteins KW - 0 KW - Dinitrophenols KW - Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone KW - 370-86-5 KW - Cytochalasin B KW - 3CHI920QS7 KW - Sodium KW - 9NEZ333N27 KW - Potassium Cyanide KW - MQD255M2ZO KW - Ascorbic Acid KW - PQ6CK8PD0R KW - 2,4-Dinitrophenol KW - Q13SKS21MN KW - Phloretin KW - S5J5OE47MK KW - Index Medicus KW - Carrier Proteins -- metabolism KW - Humans KW - Hydrogen-Ion Concentration KW - Biological Transport KW - Cytochalasin B -- pharmacology KW - Potassium Cyanide -- pharmacology KW - Phloretin -- pharmacology KW - Chromatography, High Pressure Liquid KW - Sodium -- pharmacology KW - Neutrophils -- metabolism KW - Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone -- pharmacology KW - Kinetics KW - Dinitrophenols -- pharmacology KW - Cell Line KW - Ascorbic Acid -- metabolism KW - Fibroblasts -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75943616?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Biochemical+journal&rft.atitle=Ascorbic+acid+accumulation+and+transport+in+human+fibroblasts.&rft.au=Welch%2C+R+W%3BBergsten%2C+P%3BButler%2C+J+D%3BLevine%2C+M&rft.aulast=Welch&rft.aufirst=R&rft.date=1993-09-01&rft.volume=294+%28+Pt+2%29&rft.issue=&rft.spage=505&rft.isbn=&rft.btitle=&rft.title=The+Biochemical+journal&rft.issn=02646021&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-10-13 N1 - Date created - 1993-10-13 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1968 Aug;60(4):1473-8 [5244754] J Biol Chem. 1972 May 10;247(9):2964-6 [4337109] J Biol Chem. 1973 Feb 25;248(4):1175-82 [4346946] Arch Biochem Biophys. 1975 Nov;171(1):259-67 [1238052] Eur J Biochem. 1977 Mar 1;73(2):485-92 [191255] Methods Enzymol. 1979;55:462-42 [156853] J Biol Chem. 1983 Nov 10;258(21):12886-94 [6630211] Anal Biochem. 1985 Oct;150(1):76-85 [3843705] N Engl J Med. 1986 Apr 3;314(14):892-902 [3513016] J Cell Physiol. 1986 Apr;127(1):95-105 [3958060] J Biol Chem. 1986 Jun 5;261(16):7347-56 [3711090] Biochim Biophys Acta. 1987 Jul 23;901(2):283-90 [3607050] Biochem J. 1988 Apr 1;251(1):63-72 [3390161] Vitam Horm. 1988;44:103-54 [3070929] J Biol Chem. 1989 Sep 15;264(26):15404-9 [2768269] J Biol Chem. 1989 Nov 15;264(32):18996-9002 [2681206] Anal Biochem. 1989 Sep;181(2):276-82 [2817392] J Biol Chem. 1990 Feb 15;265(5):2584-7 [2303417] J Biol Chem. 1991 Mar 25;266(9):5384-7 [1825997] Nutrition. 1989 Nov-Dec;5(6):428 [2520339] J Biol Chem. 1992 Nov 25;267(33):23568-74 [1429700] J Biol Chem. 1953 Apr;201(2):689-96 [13061407] Proc Natl Acad Sci U S A. 1965 Feb;53:335-42 [14294066] Biochem J. 1950 Apr;46(4):484-99 [15420177] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cross-reactivity of thirteen monoclonal antibodies with ten vaccinia cDNA expressed rat, mouse and human cytochrome P450s. AN - 75942749; 8373431 AB - Twelve monoclonal antibodies (MAbs) to rat cytochrome P450s and one MAb to a scup (fish) P450 have been isolated, characterized, and are currently in common use. Expression of cDNAs for different P450s from a vaccinia vector offers a rapid and simple way toward the production of individual P450s. The thirteen MAbs were examined for their cross-reactivity with ten cDNA expressed human, rat, and mouse P450s. Three MAbs to rat 1A1 and fish 1A1 cross-reacted with cDNA expressed mouse 1A1. One of the latter MAbs, 1-7-1 but none of the others cross-reacted with mouse 1A2. Surprisingly, the fish MAb to 1A1 also cross-reacted with human 2E1. Two MAbs to rat 2B1/2B2 cross-reacted with rat 2A1. An MAb to rat 2C11 cross-reacted with human 2C9. Two MAbs to rat 2E1 cross-reacted with human 2E1. Finally, two MAbs to rat 3A1 cross-reacted strongly with human 3A4. These studies open the door to constructing a library of MAbs with defined binding activity to the P450s of human and other species. JF - Biochemical pharmacology AU - Goldfarb, I AU - Korzekwa, K AU - Krausz, K W AU - Gonzalez, F AU - Gelboin, H V AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/09/01/ PY - 1993 DA - 1993 Sep 01 SP - 787 EP - 790 VL - 46 IS - 5 SN - 0006-2952, 0006-2952 KW - Antibodies, Monoclonal KW - 0 KW - DNA, Viral KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Index Medicus KW - Rats KW - Animals KW - Humans KW - Genetic Vectors KW - Fishes KW - Mice KW - Cross Reactions KW - Vaccinia virus -- genetics KW - Antibodies, Monoclonal -- isolation & purification KW - Cytochrome P-450 Enzyme System -- genetics KW - DNA, Viral -- immunology KW - Cytochrome P-450 Enzyme System -- immunology KW - Cytochrome P-450 Enzyme System -- biosynthesis KW - DNA, Viral -- metabolism KW - Antibodies, Monoclonal -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75942749?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+pharmacology&rft.atitle=Cross-reactivity+of+thirteen+monoclonal+antibodies+with+ten+vaccinia+cDNA+expressed+rat%2C+mouse+and+human+cytochrome+P450s.&rft.au=Goldfarb%2C+I%3BKorzekwa%2C+K%3BKrausz%2C+K+W%3BGonzalez%2C+F%3BGelboin%2C+H+V&rft.aulast=Goldfarb&rft.aufirst=I&rft.date=1993-09-01&rft.volume=46&rft.issue=5&rft.spage=787&rft.isbn=&rft.btitle=&rft.title=Biochemical+pharmacology&rft.issn=00062952&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-10-14 N1 - Date created - 1993-10-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Methoxyresorufin and benzyloxyresorufin: substrates preferentially metabolized by cytochromes P4501A2 and 2B, respectively, in the rat and mouse. AN - 75940321; 8373445 AB - The cytochrome P450 isozyme specificity for the O-dealkylation of methoxyresorufin (MTR) and benzyloxyresorufin (BZR) in the rat and mouse was investigated. The induction of various alkoxyresorufin O-dealkylation activities was measured in male F344/NCr rats exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin or 3,4,5,3',4',5'-hexachlorobiphenyl. MTR and ethoxyresorufin (ETR) O-dealkylation activities were induced 30- and 80-fold, respectively, in the liver. ETR O-dealkylation activity was induced > 250-fold in the kidney, whereas the metabolism of MTR was induced only 30-fold in this extrahepatic tissue. Phenacetin, a fairly specific CYP1A2 inhibitor, caused concentration-dependent competitive inhibition of MTR O-dealkylation (ki approximately 20 microM at 0.5 microM substrate) in hepatic microsomes from 3,4,5,3',4',5'-hexachlorobiphenyl-treated rats. The corresponding ki for inhibition of ETR O-dealkylation by phenacetin was > or = 333 microM at a 0.5 microM substrate concentration. A monoclonal antibody displaying inhibitory activity against rat CYP1A1 inhibited ETR O-dealkylation activity, whereas it failed to inhibit MTR O-dealkylation activity. In contrast, a monoclonal antibody reactive with both CYP1A1 and CYP1A2 inhibited both O-dealkylation activities to an equal extent. Similar experiments, employing phenacetin or specific monoclonal antibodies, yielded comparable results when performed with mouse microsomes. The maximal induction of MTR O-dealkylation activity in mice was > 100-fold. The P450 isozyme specificity of BZR O-dealkylation was also examined in both rats and mice. Pregnenolone-alpha-carbonitrile, a strong inducer of CYP3A, only weakly induced BZR O-dealkylation activity. In addition, a monoclonal antibody that specifically inhibits CYP2B caused inhibition of BZR metabolism in microsomes from phenobarbital- or dexamethasone-pretreated rats. In B6C3F1 mice exposed to dietary Aroclor 1254, significant induction of hepatic MTR O-dealkylation activity was observed at concentrations lower than those required for the induction of ETR or BZR O-dealkylation. In summary, it would appear that MTR is a relatively specific substrate for CYP1A2 activity in rodents, while BZR appears to be relatively specific for CYP2B. JF - Biochemical pharmacology AU - Nerurkar, P V AU - Park, S S AU - Thomas, P E AU - Nims, R W AU - Lubet, R A AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, MD 21702. Y1 - 1993/09/01/ PY - 1993 DA - 1993 Sep 01 SP - 933 EP - 943 VL - 46 IS - 5 SN - 0006-2952, 0006-2952 KW - Cytochrome P-450 Enzyme Inhibitors KW - 0 KW - Oxazines KW - Xenobiotics KW - 7-methoxyresorufin KW - 5725-89-3 KW - ethoxyresorufin KW - 5725-91-7 KW - benzyloxyresorufin KW - 87687-02-3 KW - pentoxyresorufin KW - 87687-03-4 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Oxidoreductases KW - EC 1.- KW - Cytochrome P-450 CYP2B1 KW - EC 1.14.14.1 KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Enzyme Induction KW - Microsomes -- enzymology KW - Mice KW - Male KW - Oxidoreductases -- metabolism KW - Cytochrome P-450 Enzyme System -- metabolism KW - Cytochrome P-450 Enzyme System -- biosynthesis KW - Oxidoreductases -- antagonists & inhibitors KW - Oxazines -- metabolism KW - Oxidoreductases -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75940321?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+pharmacology&rft.atitle=Methoxyresorufin+and+benzyloxyresorufin%3A+substrates+preferentially+metabolized+by+cytochromes+P4501A2+and+2B%2C+respectively%2C+in+the+rat+and+mouse.&rft.au=Nerurkar%2C+P+V%3BPark%2C+S+S%3BThomas%2C+P+E%3BNims%2C+R+W%3BLubet%2C+R+A&rft.aulast=Nerurkar&rft.aufirst=P&rft.date=1993-09-01&rft.volume=46&rft.issue=5&rft.spage=933&rft.isbn=&rft.btitle=&rft.title=Biochemical+pharmacology&rft.issn=00062952&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-10-14 N1 - Date created - 1993-10-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Targeting of the UmuD, UmuD', and MucA' mutagenesis proteins to DNA by RecA protein. AN - 75938209; 8367479 AB - In addition to its critical role in genetic recombination, the Escherichia coli RecA protein plays a pivotal role in SOS-induced mutagenesis. This role can be separated genetically into three steps: (i) depression of the SOS regulon by mediating the posttranslational cleavage of the LexA repressor, (ii) activation of UmuD'-like proteins by mediating cleavage of the UmuD-like proteins, and (iii) a direct step, possibly to interact with and to target the Umu-like mutagenesis proteins to lesions in DNA. We have analyzed RecA's third role biochemically using protein affinity chromatography and an agarose-based DNA mobility-shift assay. RecA730 protein from a crude cell extract was specifically retained on UmuD and UmuD' protein affinity columns, suggesting that these proteins physically interact. Normally, neither UmuD nor UmuD' shows any affinity for DNA. In the presence of RecA protein, however, UmuD and UmuD' were targeted to DNA. RecA1730 protein, which is defective for UmuD' but proficient for MucA'-promoted mutagenesis, showed a dramatically reduced capacity to target UmuD' to DNA but was able to target a significant portion of MucA' to DNA. These data support the suggestion that the direct role of RecA protein in SOS-induced mutagenesis is to interact with and target the Umu-like mutagenesis proteins to DNA. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Frank, E G AU - Hauser, J AU - Levine, A S AU - Woodgate, R AD - Section on DNA Replication, Repair, and Mutagenesis, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/09/01/ PY - 1993 DA - 1993 Sep 01 SP - 8169 EP - 8173 VL - 90 IS - 17 SN - 0027-8424, 0027-8424 KW - umuC KW - umuD KW - umuD' KW - Bacterial Proteins KW - 0 KW - DNA, Bacterial KW - Escherichia coli Proteins KW - MucA protein, Bacteria KW - Recombinant Proteins KW - Rec A Recombinases KW - EC 2.7.7.- KW - DNA-Directed DNA Polymerase KW - EC 2.7.7.7 KW - UmuD protein, E coli KW - Index Medicus KW - Chromatography, Affinity KW - Recombinant Proteins -- isolation & purification KW - Genes, Bacterial KW - Recombinant Proteins -- biosynthesis KW - Recombinant Proteins -- metabolism KW - Restriction Mapping KW - Rec A Recombinases -- isolation & purification KW - Escherichia coli -- metabolism KW - Bacterial Proteins -- biosynthesis KW - Bacterial Proteins -- metabolism KW - Escherichia coli -- genetics KW - Bacterial Proteins -- isolation & purification KW - Rec A Recombinases -- metabolism KW - DNA, Bacterial -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75938209?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Targeting+of+the+UmuD%2C+UmuD%27%2C+and+MucA%27+mutagenesis+proteins+to+DNA+by+RecA+protein.&rft.au=Frank%2C+E+G%3BHauser%2C+J%3BLevine%2C+A+S%3BWoodgate%2C+R&rft.aulast=Frank&rft.aufirst=E&rft.date=1993-09-01&rft.volume=90&rft.issue=17&rft.spage=8169&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 - 1993-10-05 N1 - Date created - 1993-10-05 N1 - Date revised - 2017-01-13 N1 - Gene symbol - umuC; umuD; umuD' N1 - SuppNotes - Cited By: Mol Gen Genet. 1976 Feb 27;144(1):53-8 [772414] Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10777-81 [1438275] Mol Gen Genet. 1977 Nov 14;156(2):121-31 [340898] Mol Gen Genet. 1978 Sep 20;165(1):87-93 [362169] Microbiol Rev. 1984 Mar;48(1):60-93 [6371470] Proc Natl Acad Sci U S A. 1985 May;82(10):3325-9 [3159017] Proc Natl Acad Sci U S A. 1985 Jun;82(12):4193-7 [3889923] Gene. 1985;38(1-3):31-8 [2998948] Mol Gen Genet. 1986 Nov;205(2):234-9 [3027502] Proc Natl Acad Sci U S A. 1987 Jun;84(12):4195-9 [3295877] Proc Natl Acad Sci U S A. 1987 Oct;84(19):6805-9 [3309946] J Mol Biol. 1987 Aug 5;196(3):497-504 [2960817] Proc Natl Acad Sci U S A. 1988 Mar;85(6):1806-10 [3126496] Proc Natl Acad Sci U S A. 1988 Mar;85(6):1811-5 [3279417] Proc Natl Acad Sci U S A. 1988 Mar;85(6):1816-20 [3279418] J Bacteriol. 1989 May;171(5):2415-23 [2651400] Proc Natl Acad Sci U S A. 1989 Oct;86(19):7301-5 [2552436] Proc Natl Acad Sci U S A. 1989 Nov;86(21):8363-7 [2554312] J Mol Biol. 1989 Dec 5;210(3):473-84 [2693735] J Bacteriol. 1990 Jun;172(6):3030-6 [2188949] Methods Enzymol. 1990;185:60-89 [2199796] Mutat Res. 1990 Sep-Nov;236(2-3):301-11 [2169028] Proc Natl Acad Sci U S A. 1990 Sep;87(18):7190-4 [2205854] J Biol Chem. 1990 Nov 25;265(33):20641-5 [2147025] Proc Natl Acad Sci U S A. 1991 Feb 15;88(4):1251-5 [1847514] Mol Gen Genet. 1991 Sep;229(1):10-6 [1654503] Biochimie. 1991 Apr;73(4):479-84 [1911948] Biochimie. 1991 Apr;73(4):485-9 [1911949] Nature. 1992 Jan 23;355(6358):318-25 [1731246] Mutat Res. 1992 Mar;281(3):221-5 [1371846] J Bacteriol. 1992 May;174(10):3133-9 [1349601] Mol Gen Genet. 1992 Apr;232(3):489-97 [1534140] Mol Gen Genet. 1992 Jun;233(3):443-8 [1320188] J Bacteriol. 1992 Nov;174(21):6844-51 [1400235] Mol Microbiol. 1992 Aug;6(16):2213-8 [1406263] Bacteriol Rev. 1976 Dec;40(4):869-907 [795416] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Toxicity studies of retroviral-mediated gene transfer for the treatment of brain tumors. AN - 75937873; 8395592 AB - Retroviral-mediated transfer of the herpes simplex virus thymidine kinase (HSVtk) gene into malignant tumors confers drug susceptibility to the antiviral drug ganciclovir. The authors have recently shown that in situ transduction of the rat 9L brain tumor following HSVtk-producer cell implantation led to tumor regression after ganciclovir administration in treated rats. A wide spectrum of potential adverse effects may, however, be associated with the application of this approach to treat brain tumors, including dissemination of the retroviral vector to nontumoral tissues within or outside the central nervous system, proliferation of the injected murine vector-producer cells at the injection site, immune-mediated responses to the implantation of xenogeneic cells, and damage to the brain from toxic by-products of the HSVtk-ganciclovir interaction. These possibilities were investigated using intracerebral and systemic injections of retroviral vector-producer cells carrying the HSVtk or the lacZ gene in mice, rats, and nonhuman primates. Using the lacZ gene as a reporter gene, no evidence of beta-galactosidase activity consistent with vector transduction was detected in any major body organ in the treated mice or rats. Similarly, the HSVtk gene transfer did not result in toxicity, with or without ganciclovir administration. In studies using rat and monkey models, no proliferation of the vector-producer cells occurred after intracerebral injection. Vector-producer cell survival was limited to 7 to 14 days. High-dose steroid therapy did not appear to extend the survival of these xenogeneic cells in rats. No significant inflammatory response was observed in the meninges or brain parenchyma. Endothelial cells were occasionally transduced in brain capillaries adjacent to the injected site of the vector-producer cells. Injection of producer cells into brain tissue elicited mild edema and reactive gliosis surrounding the injection site, which were probably the cause of a transient toxic response arising 4 to 5 days following injection of the producer cells; short-term administration of dexamethasone eliminated that response. No neurological deficits were observed in the rats or primates treated with the HSVtk vector-producer cells, with or without ganciclovir. In primates injected with producer cells, magnetic resonance imaging before, during, and after ganciclovir administration showed minimal and localized breakdown of the blood-brain barrier without significant edema or mass effect. Similarly, histological examination of the monkeys' brains showed no damage to neurons, astroglia, or myelin. Long-term clinical (> 9 months) and radiological (3 months) assessment of the primates has revealed no evidence of toxicity.(ABSTRACT TRUNCATED AT 400 WORDS) JF - Journal of neurosurgery AU - Ram, Z AU - Culver, K W AU - Walbridge, S AU - Frank, J A AU - Blaese, R M AU - Oldfield, E H AD - Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland. Y1 - 1993/09// PY - 1993 DA - September 1993 SP - 400 EP - 407 VL - 79 IS - 3 SN - 0022-3085, 0022-3085 KW - Thymidine Kinase KW - EC 2.7.1.21 KW - beta-Galactosidase KW - EC 3.2.1.23 KW - Ganciclovir KW - P9G3CKZ4P5 KW - Abridged Index Medicus KW - Index Medicus KW - Injections, Intraperitoneal KW - Magnetic Resonance Imaging KW - Animals KW - Injections, Intravenous KW - Simplexvirus -- enzymology KW - Mice KW - Rats KW - Rats, Inbred F344 KW - Cell Physiological Phenomena KW - Genetic Vectors KW - Simplexvirus -- genetics KW - Ganciclovir -- adverse effects KW - Mice, Inbred C57BL KW - Transplantation, Heterologous KW - beta-Galactosidase -- genetics KW - Macaca mulatta KW - Cell Transplantation KW - Thymidine Kinase -- genetics KW - Ganciclovir -- pharmacology KW - Brain Neoplasms -- pathology KW - Brain Neoplasms -- therapy KW - Transfection KW - Retroviridae -- physiology KW - Brain Neoplasms -- diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75937873?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+neurosurgery&rft.atitle=Toxicity+studies+of+retroviral-mediated+gene+transfer+for+the+treatment+of+brain+tumors.&rft.au=Ram%2C+Z%3BCulver%2C+K+W%3BWalbridge%2C+S%3BFrank%2C+J+A%3BBlaese%2C+R+M%3BOldfield%2C+E+H&rft.aulast=Ram&rft.aufirst=Z&rft.date=1993-09-01&rft.volume=79&rft.issue=3&rft.spage=400&rft.isbn=&rft.btitle=&rft.title=Journal+of+neurosurgery&rft.issn=00223085&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-09-28 N1 - Date created - 1993-09-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Zn2+ potentiates excitatory action of ATP on mammalian neurons. AN - 75936759; 7690146 AB - Despite the increasing recognition that ATP is an important extracellular excitatory mediator in the nervous system, the regulation of ATP receptors is poorly understood. Because the extracellular Zn2+ concentration is regulated in a variety of biological tissues, we studied modulation of the ATP-gated cation channel by Zn2+ in mammalian neurons using the whole-cell patch-clamp technique. In approximately 73% of cells tested, the amplitude of ATP-activated membrane ion current increased up to 5-fold in the presence of micromolar concentrations of Zn2+. The characteristics of this action suggest that Zn2+ increases the apparent affinity of the receptor for ATP. In addition, Zn2+ increased membrane depolarization and action potential firing elicited by ATP. These observations suggest that Zn2+ may play a physiological role in regulating the excitatory action of ATP on mammalian neurons. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Li, C AU - Peoples, R W AU - Li, Z AU - Weight, F F AD - Laboratory of Molecular and Cellular Neurobiology, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD 20852. Y1 - 1993/09/01/ PY - 1993 DA - 1993 Sep 01 SP - 8264 EP - 8267 VL - 90 IS - 17 SN - 0027-8424, 0027-8424 KW - Ion Channels KW - 0 KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - Zinc KW - J41CSQ7QDS KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Dose-Response Relationship, Drug KW - Ion Channels -- drug effects KW - In Vitro Techniques KW - Membrane Potentials -- drug effects KW - Ion Channels -- physiology KW - Drug Synergism KW - Male KW - Zinc -- pharmacology KW - Neurons -- drug effects KW - Ganglia, Sympathetic -- physiology KW - Neurons -- physiology KW - Adenosine Triphosphate -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75936759?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Zn2%2B+potentiates+excitatory+action+of+ATP+on+mammalian+neurons.&rft.au=Li%2C+C%3BPeoples%2C+R+W%3BLi%2C+Z%3BWeight%2C+F+F&rft.aulast=Li&rft.aufirst=C&rft.date=1993-09-01&rft.volume=90&rft.issue=17&rft.spage=8264&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 - 1993-10-05 N1 - Date created - 1993-10-05 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Lab Invest. 1967 Dec;17(6):588-98 [6074495] Int Arch Allergy Appl Immunol. 1963;22:112-23 [14032072] Annu Rev Med. 1970;21:67-74 [4192970] Biochem Biophys Res Commun. 1970 Oct 23;41(2):313-20 [5518163] Science. 1971 Sep 10;173(4001):1035-6 [4329180] Can J Biochem. 1973 Jan;51(1):87-92 [4689096] J Gen Physiol. 1973 Jun;61(6):687-708 [4541078] Acta Pharmacol Toxicol (Copenh). 1974 May;34(5):368-84 [4134219] FEBS Lett. 1974 Feb 1;39(1):73-4 [4853383] Eur J Pharmacol. 1978 May 15;49(2):145-9 [658131] Science. 1982 Nov 12;218(4573):693-5 [6291151] J Physiol. 1984 Sep;354:419-29 [6481640] Biochem J. 1986 Jan 15;233(2):309-19 [3006665] Adv Exp Med Biol. 1986;203:545-55 [2878572] Nature. 1987 Feb 5-11;325(6104):529-31 [2433595] Nature. 1987 Aug 13-19;328(6131):640-3 [3039375] J Physiol. 1988 Feb;396:515-33 [2900892] Int Rev Neurobiol. 1989;31:145-238 [2689380] Proc R Soc Lond B Biol Sci. 1990 Mar 22;239(1295):119-27 [1691854] Agents Actions. 1990 Apr;30(1-2):64-6 [1695463] Ann N Y Acad Sci. 1990;603:1-17; discussion 18 [1981306] Br J Pharmacol. 1991 Aug;103(4):1837-9 [1655141] Br Med Bull. 1991 Jul;47(3):534-48 [1724403] Trends Pharmacol Sci. 1992 Mar;13(3):87-90 [1374198] FASEB J. 1992 May;6(8):2514-23 [1375568] Nature. 1992 Jun 11;357(6378):503-5 [1351659] Nature. 1992 Sep 10;359(6391):144-7 [1381811] Nature. 1992 Sep 17;359(6392):241-4 [1388246] Br J Pharmacol. 1992 Aug;106(4):762-3 [1327385] Trends Pharmacol Sci. 1993 Feb;14(2):50-4 [8480374] J Physiol. 1954 Oct 28;126(1):124-40 [13212735] Aust J Exp Biol Med Sci. 1968 Feb;46(1):119-21 [5655433] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The medullary dorsal horn. A site of action of morphine in producing facial scratching in monkeys. AN - 75933769; 8363081 AB - Pruritus is a common side effect of epidural and intrathecal morphine administration in humans. This naloxone-reversible pruritus is typically present on the trunk, but is often severe around the eyes and nose, of the patients. The brain stem has been proposed as the site where opioids act to produce this effect. The authors studied the effect of morphine administered into the medullary dorsal horn (MDH), the brain stem homologue of the spinal dorsal horn, on facial-scratching behavior in monkeys. Morphine was unilaterally microinjected into the MDH of rhesus monkeys. Systemic injections of the opioid-receptor antagonist naloxone (0.5 mg/kg intramuscularly) were also made in combination with morphine microinjection. Systemic injections of the antihistamine chlorcyclizine (1.0 and 2.5 mg/kg intramuscularly) were also made to determine if facial scratching was mediated through histamine release. The monkeys were videotaped for 10-15 min before and 1-2 h after opioid microinjection, and the number and location of scratches were counted. A dose-response curve was established for the mu/delta-opioid-receptor agonist morphine (0.5, 1.0, 2.5, and 5.0 micrograms). Specificity of the site of action within the MDH was examined by systematically changing the microinjection site, and examining the area of the face that the monkeys scratched. Morphine produced large dose-dependent increases in facial scratching ipsilateral to the microinjection. Increases in facial scratching were also observed contralateral to the microinjections. These effects were reversed by naloxone. The facial area scratched after microinjection of morphine was directly related to the injection site, with 1-mm changes in the location of the microinjection resulting in pronounced changes in the area of the face that the monkeys scratched. Systemic injection of chlorcyclizine produced only a small, transient attenuation of morphine's effect. Data from this study demonstrate that the MDH is a site where morphine acts to produce facial scratching in monkeys by acting at opioid receptors. It is also likely that the MDH is a site where centrally administered opioids act in producing facial pruritus in humans. The effects of morphine on facial-scratching behavior were only modestly attenuated with chlorcyclizine, indicating a minor involvement of a histamine-dependent mechanism of action. JF - Anesthesiology AU - Thomas, D A AU - Williams, G M AU - Iwata, K AU - Kenshalo, D R AU - Dubner, R AD - Neurobiology and Anesthesiology Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/09// PY - 1993 DA - September 1993 SP - 548 EP - 554 VL - 79 IS - 3 SN - 0003-3022, 0003-3022 KW - Morphine KW - 76I7G6D29C KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Macaca fascicularis KW - Male KW - Facial Dermatoses -- chemically induced KW - Morphine -- adverse effects KW - Spinal Cord -- drug effects KW - Spinal Cord -- physiology KW - Pruritus -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75933769?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Anesthesiology&rft.atitle=The+medullary+dorsal+horn.+A+site+of+action+of+morphine+in+producing+facial+scratching+in+monkeys.&rft.au=Thomas%2C+D+A%3BWilliams%2C+G+M%3BIwata%2C+K%3BKenshalo%2C+D+R%3BDubner%2C+R&rft.aulast=Thomas&rft.aufirst=D&rft.date=1993-09-01&rft.volume=79&rft.issue=3&rft.spage=548&rft.isbn=&rft.btitle=&rft.title=Anesthesiology&rft.issn=00033022&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-09-30 N1 - Date created - 1993-09-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The paradoxical effect of tumor necrosis factor alpha (TNF-alpha) in endotoxin-induced uveitis. AN - 75924803; 8360023 AB - To investigate the role of TNF-alpha in endotoxin-induced uveitis (EIU) in mice. To neutralize TNF-alpha activity, mice were pretreated with either repeated injections of this cytokine or a single injection of antibody against it. The mice were then injected intraperitoneally with 500 micrograms endotoxin, to induce lethal septic shock, or into the footpad with 200 micrograms to induce EIU. Although both pretreatments conferred protection against the systemic toxic effects of LPS, TNF-resistant mice and mice treated with anti-TNF-alpha antibody demonstrated an exacerbation of EIU when compared to control animals. Unlike its apparent participation in the systemic effect of endotoxin, TNF-alpha is not directly involved in the pathogenesis of EIU and may even protect against the inflammatory processes of this disease. JF - Investigative ophthalmology & visual science AU - Kasner, L AU - Chan, C C AU - Whitcup, S M AU - Gery, I AD - Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/09// PY - 1993 DA - September 1993 SP - 2911 EP - 2917 VL - 34 IS - 10 SN - 0146-0404, 0146-0404 KW - Bacterial Toxins KW - 0 KW - Endotoxins KW - Recombinant Proteins KW - Tumor Necrosis Factor-alpha KW - salmonella toxin KW - Index Medicus KW - Acute Disease KW - Animals KW - Recombinant Proteins -- immunology KW - Mice, Inbred C3H KW - Disease Models, Animal KW - Mice KW - Salmonella typhimurium KW - Female KW - Uveitis, Anterior -- prevention & control KW - Uveitis, Anterior -- immunology KW - Uveitis, Anterior -- pathology KW - Tumor Necrosis Factor-alpha -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75924803?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Investigative+ophthalmology+%26+visual+science&rft.atitle=The+paradoxical+effect+of+tumor+necrosis+factor+alpha+%28TNF-alpha%29+in+endotoxin-induced+uveitis.&rft.au=Kasner%2C+L%3BChan%2C+C+C%3BWhitcup%2C+S+M%3BGery%2C+I&rft.aulast=Kasner&rft.aufirst=L&rft.date=1993-09-01&rft.volume=34&rft.issue=10&rft.spage=2911&rft.isbn=&rft.btitle=&rft.title=Investigative+ophthalmology+%26+visual+science&rft.issn=01460404&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-09-30 N1 - Date created - 1993-09-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of psychosine (galactosylsphingosine) on the survival and the fine structure of cultured Schwann cells. AN - 75919997; 8360702 AB - The cytotoxicity of psychosine (galactosylsphingosine) for cultured rat Schwann cells was studied by maintaining them in medium containing 1, 10, 50, 75 and 100 microM psychosine for 24, 48 and 72 hours (h). When incubated in 50-100 microM concentrations of psychosine for 24 h, 52-99% of cultured Schwann cells did not survive. Lower concentrations (1-10 microM) did not significantly reduce Schwann cell numbers for the first 24 h. However, only 43-69% of cultured Schwann cells survived in these low concentrations for 48 h, and substantially fewer remained after 72 h of incubation. During incubations in psychosine, bipolar processes of Schwann cells retracted; the resulting oval and rounded Schwann cells still were S-100 positive. When these Schwann cells were transferred into normal medium, their processes elongated quickly. When examined with the electron microscope, the cytoplasm of Schwann cells incubated in psychosine contained numerous membranous inclusions and fewer mitochondria, some of which were swollen. There also were fewer profiles of granular endoplasmic reticulum and some had widely dilated cisternae. These results suggest that 1) exogenous psychosine in concentrations of 1 microM and greater is cytotoxic for cultured rat Schwann cells; 2) psychosine has reversible toxic effects and its turnover is rapid; and 3) psychosine produces membranous inclusions and abnormalities in the mitochondria and granular endoplasmic reticulum of cultured Schwann cells. Our findings support the hypothesis that the accumulation of psychosine in human and murine globoid cell leukodystrophy is toxic for Schwann cells, produces changes in their capacity to maintain myelin, and leads to Schwann cell dysfunction. JF - Journal of neuropathology and experimental neurology AU - Tanaka, K AU - Webster, H D AD - Laboratory of Experimental Neuropathology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/09// PY - 1993 DA - September 1993 SP - 490 EP - 498 VL - 52 IS - 5 SN - 0022-3069, 0022-3069 KW - S100 Proteins KW - 0 KW - Psychosine KW - 2238-90-6 KW - Index Medicus KW - Animals KW - Dose-Response Relationship, Drug KW - S100 Proteins -- analysis KW - Rats KW - Animals, Newborn KW - Rats, Sprague-Dawley KW - Mitochondria -- ultrastructure KW - Cells, Cultured KW - Kinetics KW - Mitochondria -- drug effects KW - Microscopy, Electron KW - Time Factors KW - Immunohistochemistry KW - Immunoenzyme Techniques KW - Schwann Cells -- ultrastructure KW - Cell Survival -- drug effects KW - Sciatic Nerve -- cytology KW - Schwann Cells -- drug effects KW - Schwann Cells -- cytology KW - Psychosine -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75919997?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+neuropathology+and+experimental+neurology&rft.atitle=Effects+of+psychosine+%28galactosylsphingosine%29+on+the+survival+and+the+fine+structure+of+cultured+Schwann+cells.&rft.au=Tanaka%2C+K%3BWebster%2C+H+D&rft.aulast=Tanaka&rft.aufirst=K&rft.date=1993-09-01&rft.volume=52&rft.issue=5&rft.spage=490&rft.isbn=&rft.btitle=&rft.title=Journal+of+neuropathology+and+experimental+neurology&rft.issn=00223069&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-09-30 N1 - Date created - 1993-09-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Time-related loss of glutamine from hippocampal slices and concomitant changes in neurotransmitter amino acids. AN - 75918660; 8103084 AB - A dramatic, time-dependent loss of L-glutamine was observed in mouse and rat hippocampal slices equilibrated in normal artificial CSF under static (no-flow) and superfused (constant-flow) conditions. Concomitant with the decline in L-glutamine, there was a significant, but less pronounced, decrease in levels of the neurotransmitter amino acids, gamma-aminobutyric acid, L-aspartate, and L-glutamate. The disappearance of L-glutamine was a result of diffusion from the tissue to the artificial CSF rather than chemical or biochemical transformation. The loss of amino acids from the hippocampal slices was prevented to different degrees by the addition of 0.5 mM exogenous L-glutamine to the artificial CSF. The levels of newly synthesized amino acids were also determined, because they may be more indicative of the neuronal activity than the total tissue levels of amino acids. The effects of perturbations in glutamine (length of the equilibration time and addition of exogenous glutamine) on newly synthesized glutamate were more pronounced under 4-aminopyridine-stimulated than control (unstimulated) conditions. Therefore, a loss of L-glutamine from the hippocampal slices may have neurophysiological effects and warrants further investigation. JF - Journal of neurochemistry AU - Kapetanovic, I M AU - Yonekawa, W D AU - Kupferberg, H J AD - Preclinical Pharmacology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/09// PY - 1993 DA - September 1993 SP - 865 EP - 872 VL - 61 IS - 3 SN - 0022-3042, 0022-3042 KW - Amino Acids KW - 0 KW - Glutamates KW - Neurotransmitter Agents KW - Glutamine KW - 0RH81L854J KW - Glutamic Acid KW - 3KX376GY7L KW - Tetrodotoxin KW - 4368-28-9 KW - 4-Aminopyridine KW - BH3B64OKL9 KW - Index Medicus KW - Osmolar Concentration KW - Mice, Inbred Strains KW - Animals KW - 4-Aminopyridine -- pharmacology KW - Glutamates -- metabolism KW - In Vitro Techniques KW - Mice KW - Glutamates -- cerebrospinal fluid KW - Tetrodotoxin -- pharmacology KW - Time Factors KW - Male KW - Neurotransmitter Agents -- metabolism KW - Glutamine -- metabolism KW - Glutamine -- cerebrospinal fluid KW - Hippocampus -- metabolism KW - Amino Acids -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75918660?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Time-related+loss+of+glutamine+from+hippocampal+slices+and+concomitant+changes+in+neurotransmitter+amino+acids.&rft.au=Kapetanovic%2C+I+M%3BYonekawa%2C+W+D%3BKupferberg%2C+H+J&rft.aulast=Kapetanovic&rft.aufirst=I&rft.date=1993-09-01&rft.volume=61&rft.issue=3&rft.spage=865&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 - 1993-09-27 N1 - Date created - 1993-09-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transplacental carcinogenicity of cisplatin: initiation of skin tumors and induction of other preneoplastic and neoplastic lesions in SENCAR mice. AN - 75913939; 8358711 AB - cis-Dichlorodiammineplatinum (cis-DDP), an anticancer agent sometimes used in pregnant women for the treatment of malignant ovarian and uterine tumors, was tested for transplacental carcinogenic and/or tumor-initiating effects in SENCAR mice. Pregnant mice were given a single i.p. injection of either cis-DDP (7.5 mg/kg body weight) in 2.5% NaCl or the same weight-adjusted volume of NaCl (5 ml/kg body weight) on day 17 of gestation. Offspring were delivered and raised by their natural mothers until weaning at 3 weeks of age. Starting at week 4, offspring in experimental groups received topical applications of 2 micrograms 12-O-tetradecanoylphorbol-13-acetate (TPA) in acetone twice a week for 20 weeks while those in control groups received only acetone (0.2 ml/application) for the same duration. The experiment was terminated at 25 weeks of age. A high incidence (18 of 37; 48.7%) of papillomas was observed in offspring exposed transplacentally to cis-DDP and postnatally to TPA, while only 10% (4 of 40) of offspring exposed to TPA alone developed such tumors (P < 0.0002). Although no skin tumors were observed without TPA promotion, transplacental administration of cis-DDP resulted in development of thymic lymphomas, lung tumors, and proliferative kidney lesions in offspring. These results provide the first evidence that cis-DDP can initiate and/or induce preneoplastic and neoplastic lesions in multiple tissues transplacentally. JF - Cancer research AU - Diwan, B A AU - Anderson, L M AU - Rehm, S AU - Rice, J M AD - Biological Carcinogenesis and Development Program, PRI/DynCorp, NCI-Frederick Cancer Research and Development Center, Maryland 21702-1201. Y1 - 1993/09/01/ PY - 1993 DA - 1993 Sep 01 SP - 3874 EP - 3876 VL - 53 IS - 17 SN - 0008-5472, 0008-5472 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Cisplatin KW - Q20Q21Q62J KW - Index Medicus KW - Mice, Inbred Strains KW - Animals KW - Cocarcinogenesis KW - Kidney Neoplasms -- chemically induced KW - Precancerous Conditions -- chemically induced KW - Mice KW - Lung Neoplasms -- chemically induced KW - Male KW - Female KW - Pregnancy KW - Cisplatin -- pharmacokinetics KW - Maternal-Fetal Exchange KW - Skin Neoplasms -- chemically induced KW - Cisplatin -- toxicity KW - Papilloma -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75913939?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Transplacental+carcinogenicity+of+cisplatin%3A+initiation+of+skin+tumors+and+induction+of+other+preneoplastic+and+neoplastic+lesions+in+SENCAR+mice.&rft.au=Diwan%2C+B+A%3BAnderson%2C+L+M%3BRehm%2C+S%3BRice%2C+J+M&rft.aulast=Diwan&rft.aufirst=B&rft.date=1993-09-01&rft.volume=53&rft.issue=17&rft.spage=3874&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 - 1993-09-24 N1 - Date created - 1993-09-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Immunotoxins and recombinant toxins in the treatment of solid carcinomas. AN - 75910097; 8368439 AB - Cancer remains the second most common cause of death in our society, and advanced disease is often refractory to surgical, chemotherapeutic, and radiologic interventions. One novel approach to cancer treatment involves targeting a cytotoxic agent to a cancer cell. Immunotoxins have been developed that contain a potent toxin (either Pseudomonas exotoxin, ricin toxin, or diphtheria toxin) coupled to a targeting moiety that directs the molecule to cells expressing a certain antigen. Chemically coupled immunotoxins have been developed over the past 12 years. These bind to and kill cells expressing many tumor-associated antigens. Initial clinical results were disappointing, but recent results have been more promising. Furthermore, newer immunotoxins have been developed that will soon be in clinical trials. Some of these are recombinant toxins that have been developed using techniques of genetic engineering. Transforming growth factor-alpha, acidic fibroblast growth factor, insulin-like growth factor-1, interleukin-2, interleukin-4, interleukin-6, the binding portions of monoclonal antibodies, and CD4 have been used to direct toxins to cancer cells or cells infected with the human immunodeficiency virus type 1. Efforts are under way to circumvent problems such as immunogenicity that may limit the clinical usefulness of immunotoxins. JF - American journal of surgery AU - Theuer, C P AU - Pastan, I AD - Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/09// PY - 1993 DA - September 1993 SP - 284 EP - 288 VL - 166 IS - 3 SN - 0002-9610, 0002-9610 KW - Antibodies, Monoclonal KW - 0 KW - Bacterial Toxins KW - Exotoxins KW - Immunotoxins KW - Recombinant Proteins KW - Transforming Growth Factor alpha KW - Virulence Factors KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - toxA protein, Pseudomonas aeruginosa KW - EC 2.4.2.31 KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Transforming Growth Factor alpha -- therapeutic use KW - Humans KW - Forecasting KW - Exotoxins -- therapeutic use KW - Antibodies, Monoclonal -- therapeutic use KW - Recombinant Proteins -- metabolism KW - Bacterial Toxins -- therapeutic use KW - Immunotoxins -- therapeutic use KW - Immunotoxins -- metabolism KW - Neoplasms -- therapy KW - Recombinant Proteins -- therapeutic use KW - Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75910097?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+surgery&rft.atitle=Immunotoxins+and+recombinant+toxins+in+the+treatment+of+solid+carcinomas.&rft.au=Theuer%2C+C+P%3BPastan%2C+I&rft.aulast=Theuer&rft.aufirst=C&rft.date=1993-09-01&rft.volume=166&rft.issue=3&rft.spage=284&rft.isbn=&rft.btitle=&rft.title=American+journal+of+surgery&rft.issn=00029610&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-10-04 N1 - Date created - 1993-10-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Functional domains of wild-type and mutant p53 proteins involved in transcriptional regulation, transdominant inhibition, and transformation suppression. AN - 75906731; 8355677 AB - The wild-type (wt) p53 protein has transcriptional activation functions which may be linked to its tumor suppressor activity. Many mutant p53 proteins expressed in cancers have lost the ability to function as transcriptional activators and furthermore may inhibit wt p53 function. To study the mechanisms by which mutant forms of p53 have lost their transactivation function and can act in a dominant negative manner, a structure-function analysis of both mutant and engineered truncated forms of p53 was carried out. We show that different mutant p53 proteins found in cancers vary in the ability to inhibit the transcriptional transactivation and specific DNA binding activities of wt human p53. This transdominant effect was mediated through the carboxy-terminal oligomerization region. The role of the transactivation activity in transformation suppression by wt p53 was also examined by constructing an N-terminal deletion mutant lacking the transactivation domain. This mutant was unable to transactivate but could bind specifically to DNA. Although it was impaired in its ability to suppress transformation of primary rat embryo fibroblasts by adenovirus E1A plus activated ras, the N-terminal deletion mutant still had some suppression activity, suggesting that additional functions of p53 may contribute to transformation suppression. JF - Molecular and cellular biology AU - Unger, T AU - Mietz, J A AU - Scheffner, M AU - Yee, C L AU - Howley, P M AD - Laboratory of Tumor Virus Biology, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1993/09// PY - 1993 DA - September 1993 SP - 5186 EP - 5194 VL - 13 IS - 9 SN - 0270-7306, 0270-7306 KW - DNA-Binding Proteins KW - 0 KW - Oligodeoxyribonucleotides KW - Tumor Suppressor Protein p53 KW - Index Medicus KW - Rats KW - Mutagenesis, Site-Directed KW - Animals KW - Base Sequence KW - Genes, Dominant KW - DNA-Binding Proteins -- chemistry KW - Oligodeoxyribonucleotides -- chemistry KW - In Vitro Techniques KW - Molecular Sequence Data KW - Cell Line KW - Structure-Activity Relationship KW - Sequence Deletion KW - Tumor Suppressor Protein p53 -- physiology KW - Genes, p53 KW - Transcription, Genetic KW - Transcriptional Activation KW - Cell Transformation, Viral UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75906731?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Functional+domains+of+wild-type+and+mutant+p53+proteins+involved+in+transcriptional+regulation%2C+transdominant+inhibition%2C+and+transformation+suppression.&rft.au=Unger%2C+T%3BMietz%2C+J+A%3BScheffner%2C+M%3BYee%2C+C+L%3BHowley%2C+P+M&rft.aulast=Unger&rft.aufirst=T&rft.date=1993-09-01&rft.volume=13&rft.issue=9&rft.spage=5186&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 - 1993-09-23 N1 - Date created - 1993-09-23 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Oncogene. 1990 Dec;5(12):1829-32 [2284102] Science. 1990 Aug 31;249(4972):1049-51 [2144364] Cell Growth Differ. 1990 Dec;1(12):571-80 [2288874] Cell. 1991 May 31;65(5):765-74 [2040013] Nature. 1991 Jun 6;351(6326):453-6 [2046748] Science. 1991 Jun 21;252(5013):1708-11 [2047879] Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):4570-1 [1647009] Science. 1991 Jul 5;253(5015):49-53 [1905840] Nature. 1991 Jul 25;352(6333):345-7 [1852210] Proc Natl Acad Sci U S A. 1991 Sep 1;88(17):7605-9 [1652755] Nucleic Acids Res. 1991 Oct 11;19(19):5191-8 [1923804] Proc Natl Acad Sci U S A. 1991 Oct 15;88(20):8982-6 [1924360] Mol Cell Biol. 1991 Dec;11(12):6067-74 [1944276] Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):9979-83 [1946467] Nature. 1992 Jan 9;355(6356):176-9 [1530885] Oncogene. 1992 Jan;7(1):71-6 [1741167] Mol Carcinog. 1992;5(2):102-6 [1554407] EMBO J. 1992 Apr;11(4):1383-90 [1314165] Nature. 1992 May 7;357(6373):82-5 [1533443] Nucleic Acids Res. 1992 Apr 11;20(7):1539-45 [1579447] Proc Natl Acad Sci U S A. 1992 May 15;89(10):4495-9 [1584781] Mol Cell Biol. 1992 Jun;12(6):2866-71 [1588974] Science. 1992 May 8;256(5058):827-30 [1589764] Nature. 1992 Jul 2;358(6381):80-3 [1614537] Nature. 1992 Jul 2;358(6381):83-6 [1614538] Cell. 1992 Jun 26;69(7):1237-45 [1535557] Genes Dev. 1992 Jul;6(7):1143-52 [1628822] Oncogene. 1992 Aug;7(8):1513-23 [1321401] Proc Natl Acad Sci U S A. 1992 Jul 15;89(14):6413-7 [1631137] Cell. 1992 Aug 21;70(4):523-6 [1505019] J Virol. 1992 Oct;66(10):6164-70 [1356162] Genes Dev. 1992 Oct;6(10):1886-98 [1398068] Virology. 1973 Apr;52(2):456-67 [4705382] Nature. 1979 Mar 15;278(5701):261-3 [218111] Cell. 1979 May;17(1):43-52 [222475] Cell. 1982 Feb;28(2):387-94 [6277513] Nature. 1982 Jun 10;297(5866):474-8 [6283357] Mol Cell Biol. 1982 Sep;2(9):1044-51 [6960240] Cell. 1983 Nov;35(1):127-36 [6313219] J Virol. 1988 Dec;62(12):4737-44 [3054153] Science. 1989 Apr 14;244(4901):217-21 [2649981] Cell. 1989 Jun 30;57(7):1083-93 [2525423] Nucleic Acids Res. 1989 Aug 11;17(15):6419 [2771659] Proc Natl Acad Sci U S A. 1989 Nov;86(22):8763-7 [2530586] Science. 1989 Oct 27;246(4929):491-4 [2554494] Science. 1990 Apr 6;248(4951):76-9 [2157286] Oncogene. 1990 Jul;5(7):945-52 [2142762] Science. 1990 Aug 31;249(4972):1046-9 [2144363] Mol Cell Biol. 1990 Nov;10(11):5772-81 [2233717] Science. 1990 Nov 30;250(4985):1233-8 [1978757] Nature. 1990 Dec 20-27;348(6303):747-9 [2259385] Proc Natl Acad Sci U S A. 1992 Oct 1;89(19):9210-4 [1409626] Cell. 1992 Nov 13;71(4):587-97 [1423616] Cell. 1992 Nov 27;71(5):875-86 [1423635] Mol Cell Biol. 1992 Dec;12(12):5581-92 [1448088] EMBO J. 1992 Dec;11(13):5013-20 [1464323] Mol Cell Biol. 1993 Jan;13(1):301-6 [8417333] Science. 1993 Jan 1;259(5091):84-7 [8418500] Nat Genet. 1992 Apr;1(1):45-9 [1301998] Genes Dev. 1991 Feb;5(2):151-9 [1995413] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phase I study of high-dose piroxantrone with granulocyte colony-stimulating factor. AN - 75904489; 7689093 AB - We performed a phase I trial of piroxantrone with and without granulocyte colony-stimulating factor (G-CSF) to determine whether the use of this cytokine would enable us to increase the dose-intensity of piroxantrone. Thirty-eight patients received 121 courses of piroxantrone administered once every 21 days. Initial patient cohorts received piroxantrone alone starting at 150 mg/m2 and the dose was escalated in subsequent patients until dose-limiting toxicity (DLT) was reached. Patient cohorts then received escalating doses of piroxantrone starting at 185 mg/m2 administered with G-CSF beginning day 2. Dose-limiting neutropenia occurred in three of six patients treated with 185 mg/m2 piroxantrone; the maximum-tolerated dose (MTD) of piroxantrone alone was 150 mg/m2. Three of six patients treated with piroxantrone and G-CSF exhibited dose-limiting thrombocytopenia at 445 mg/m2; the MTD of piroxantrone with G-CSF was thus 355 mg/m2. Seven patients developed symptomatic congestive heart failure (CHF) at cumulative piroxantrone doses ranging from 855 to 2,475 mg/m2 and two have died of cardiotoxicity. Of these patients, six of seven had previously received doxorubicin. Other nonhematologic toxicity was mild. The use of G-CSF results in a more than twofold increase in the MTD of piroxantrone. However, symptomatic cardiotoxicity is prominent, especially in patients who have received prior treatment with anthracyclines. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Savarese, D M AU - Denicoff, A M AU - Berg, S L AU - Hillig, M AU - Baker, S P AU - O'Shaughnessy, J A AU - Chow, C AU - Otterson, G A AU - Balis, F M AU - Poplack, D G AD - Medicine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/09// PY - 1993 DA - September 1993 SP - 1795 EP - 1803 VL - 11 IS - 9 SN - 0732-183X, 0732-183X KW - Anthraquinones KW - 0 KW - Antineoplastic Agents KW - Pyrazoles KW - Granulocyte Colony-Stimulating Factor KW - 143011-72-7 KW - piroxantrone KW - YL4TY9WH22 KW - Index Medicus KW - Drug Administration Schedule KW - Bone Marrow Diseases -- prevention & control KW - Bone Marrow Diseases -- chemically induced KW - Logistic Models KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Male KW - Female KW - Multivariate Analysis KW - Pyrazoles -- administration & dosage KW - Neoplasms -- drug therapy KW - Anthraquinones -- adverse effects KW - Granulocyte Colony-Stimulating Factor -- therapeutic use KW - Antineoplastic Agents -- administration & dosage KW - Anthraquinones -- administration & dosage KW - Pyrazoles -- adverse effects KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75904489?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.atitle=Phase+I+study+of+high-dose+piroxantrone+with+granulocyte+colony-stimulating+factor.&rft.au=Savarese%2C+D+M%3BDenicoff%2C+A+M%3BBerg%2C+S+L%3BHillig%2C+M%3BBaker%2C+S+P%3BO%27Shaughnessy%2C+J+A%3BChow%2C+C%3BOtterson%2C+G+A%3BBalis%2C+F+M%3BPoplack%2C+D+G&rft.aulast=Savarese&rft.aufirst=D&rft.date=1993-09-01&rft.volume=11&rft.issue=9&rft.spage=1795&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 - 1993-09-23 N1 - Date created - 1993-09-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Maturation of dimeric viral RNA of Moloney murine leukemia virus. AN - 75895823; 8350405 AB - We have analyzed the dimeric RNA present in Moloney murine leukemia virus (MoMuLV) particles. We found that the RNA in newly released virions is in a conformation different from that in mature virions, since it has a different electrophoretic mobility in nondenaturing agarose gels and dissociates into monomers at a lower temperature. On the basis of these results, we suggest that the RNA initially packaged into nascent virions is already dimeric but that the dimer undergoes a maturation process after the virus is released from the cell. In further experiments, we tested the possibility that this maturation event is linked to the maturation cleavage of the virion proteins, which is catalyzed by the viral protease (PR). We found that the dimeric RNA isolated from PR- mutant virions resembles that from immature virions: it has a lower electrophoretic mobility and a lower sedimentation rate, and it also dissociates at a lower temperature than does RNA from mature wild-type virions. When Kirsten sarcoma virus is rescued by a PR- mutant or by a somewhat leaky cysteine array mutant of MoMuLV, its RNA also exhibits a electrophoretic mobility lower than that in the wild-type pseudotype. These results suggest that the maturation of dimeric RNA in released virus particles requires the cleavage of the Gag precursor and the presence of an intact cysteine array in the released nucleocapsid protein. JF - Journal of virology AU - Fu, W AU - Rein, A AD - Laboratory of Molecular Virology and Carcinogenesis, NCI-Frederick Cancer Research and Development Center, Maryland 21702. Y1 - 1993/09// PY - 1993 DA - September 1993 SP - 5443 EP - 5449 VL - 67 IS - 9 SN - 0022-538X, 0022-538X KW - DNA, Viral KW - 0 KW - Macromolecular Substances KW - RNA, Double-Stranded KW - Uridine KW - WHI7HQ7H85 KW - Index Medicus KW - Animals KW - 3T3 Cells KW - Nucleic Acid Denaturation KW - Thermodynamics KW - Virion -- genetics KW - Electrophoresis, Polyacrylamide Gel KW - Kinetics KW - CHO Cells KW - Uridine -- metabolism KW - Mice KW - Virion -- metabolism KW - Cricetinae KW - DNA, Viral -- biosynthesis KW - RNA, Double-Stranded -- isolation & purification KW - RNA, Double-Stranded -- biosynthesis KW - Moloney murine leukemia virus -- genetics KW - DNA, Viral -- isolation & purification KW - RNA, Double-Stranded -- metabolism KW - Moloney murine leukemia virus -- metabolism KW - DNA, Viral -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75895823?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Maturation+of+dimeric+viral+RNA+of+Moloney+murine+leukemia+virus.&rft.au=Fu%2C+W%3BRein%2C+A&rft.aulast=Fu&rft.aufirst=W&rft.date=1993-09-01&rft.volume=67&rft.issue=9&rft.spage=5443&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 - 1993-09-13 N1 - Date created - 1993-09-13 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Virol. 1981 Dec;40(3):683-90 [6172599] Intervirology. 1976;7(4-5):211-24 [188781] Mol Cell Biol. 1984 Aug;4(8):1577-82 [6092920] Virology. 1985 Sep;145(2):280-92 [2411050] J Virol. 1986 Nov;60(2):450-9 [2430109] Anal Biochem. 1986 Nov 15;159(1):227-32 [2433961] J Virol. 1988 Oct;62(10):3802-6 [3418786] Proc Natl Acad Sci U S A. 1988 Nov;85(22):8420-4 [3141927] J Virol. 1989 Apr;63(4):1558-68 [2926863] J Virol. 1989 May;63(5):2405-10 [2784837] J Virol. 1990 Feb;64(2):774-83 [2153242] Curr Top Microbiol Immunol. 1990;157:125-52 [2394131] J Virol. 1990 Oct;64(10):4978-87 [2168981] J Virol. 1990 Oct;64(10):5076-92 [1697912] J Virol. 1990 Dec;64(12):5757-63 [1700822] J Virol. 1993 Jan;67(1):178-88 [8380070] J Virol. 1993 Feb;67(2):623-31 [8380458] Proc Natl Acad Sci U S A. 1968 Aug;60(4):1511-8 [4299948] J Virol. 1969 Oct;4(4):454-9 [4309879] J Virol. 1972 Jul;10(1):23-31 [4339194] Virology. 1972 Dec;50(3):851-64 [4344944] Proc Natl Acad Sci U S A. 1973 Feb;70(2):401-5 [4119788] J Virol. 1974 Jul;14(1):152-61 [4134468] J Virol. 1975 Nov;16(5):1161-70 [171447] Cell. 1983 May;33(1):153-9 [6678608] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Functional studies of a germ-line polymorphism at codon 47 within the p53 gene. AN - 75895359; 8352280 AB - A rare germ-line polymorphism in codon 47 of the p53 gene replaces the wild-type proline (CCG) with a serine (TCG). Restriction analysis of 101 human samples revealed the frequency of the rare allele to be 0% (n = 69) in Caucasians and 4.7% (3/64, n = 32) among African-Americans. To investigate the consequence of this amino acid substitution, a cDNA construct (p53 mut47ser) containing the mutation was introduced into a lung adenocarcinoma cell line (Calu-6) that does not express p53. A growth suppression similar to that obtained after introduction of a wild-type p53 cDNA construct was observed, in contrast to the result obtained by introduction of p53 mut143ala. Furthermore, expression of neither p53 mut47ser nor wild-type p53 was tolerated by growing cells. In transient expression assays, both mut47ser and wild-type p53 activated the expression of a reporter gene linked to a p53 binding sequence (PG13-CAT) and inhibited the expression of the luciferase gene under the control of the Rous sarcoma virus promoter (RSVluc). In the same assay, mut143ala did not activate the expression of PG13-CAT and produced only a slight inhibitory effect on RSVluc. These findings indicate that the p53 variant with a serine at codon 47 should be considered as a rare germ-line polymorphism that does not alter the growth-suppression activity of p53. JF - American journal of human genetics AU - Felley-Bosco, E AU - Weston, A AU - Cawley, H M AU - Bennett, W P AU - Harris, C C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, MD 20892. Y1 - 1993/09// PY - 1993 DA - September 1993 SP - 752 EP - 759 VL - 53 IS - 3 SN - 0002-9297, 0002-9297 KW - Tumor Suppressor Protein p53 KW - 0 KW - Serine KW - 452VLY9402 KW - Proline KW - 9DLQ4CIU6V KW - Index Medicus KW - United States KW - Gene Frequency KW - Humans KW - European Continental Ancestry Group -- genetics KW - Structure-Activity Relationship KW - Serine -- genetics KW - Cloning, Molecular KW - Mutagenesis, Site-Directed KW - Proline -- genetics KW - Polymerase Chain Reaction KW - Alleles KW - Base Sequence KW - Tumor Cells, Cultured KW - African Continental Ancestry Group -- genetics KW - Transfection KW - Molecular Sequence Data KW - Immunohistochemistry KW - Tumor Suppressor Protein p53 -- physiology KW - Polymorphism, Genetic KW - Genes, p53 -- genetics KW - Point Mutation KW - Tumor Suppressor Protein p53 -- chemistry KW - Tumor Suppressor Protein p53 -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75895359?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+human+genetics&rft.atitle=Functional+studies+of+a+germ-line+polymorphism+at+codon+47+within+the+p53+gene.&rft.au=Felley-Bosco%2C+E%3BWeston%2C+A%3BCawley%2C+H+M%3BBennett%2C+W+P%3BHarris%2C+C+C&rft.aulast=Felley-Bosco&rft.aufirst=E&rft.date=1993-09-01&rft.volume=53&rft.issue=3&rft.spage=752&rft.isbn=&rft.btitle=&rft.title=American+journal+of+human+genetics&rft.issn=00029297&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-09-16 N1 - Date created - 1993-09-16 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1992 Jul 15;89(14):6413-7 [1631137] Cancer Epidemiol Biomarkers Prev. 1992 Sep-Oct;1(6):481-3 [1302561] Science. 1993 Jan 1;259(5091):84-7 [8418500] Nature. 1984 Dec 13-19;312(5995):646-9 [6095116] Nature. 1984 Dec 13-19;312(5995):649-51 [6390217] Nature. 1984 Dec 13-19;312(5995):651-4 [6095117] EMBO J. 1985 May;4(5):1251-5 [4006916] Mol Cell Biol. 1986 Dec;6(12):4650-6 [3025664] Mol Cell Biol. 1987 Feb;7(2):725-37 [3821727] Mol Cell Biol. 1987 Feb;7(2):961-3 [3547088] Anal Biochem. 1987 Apr;162(1):156-9 [2440339] Mol Cell Biol. 1988 Feb;8(2):531-9 [2832726] EMBO J. 1990 May;9(5):1595-602 [1691710] Science. 1990 Aug 24;249(4971):912-5 [2144057] Nucleic Acids Res. 1990 Aug 25;18(16):4963 [1697680] Oncogene. 1990 Sep;5(9):1409-10 [1977117] Science. 1990 Nov 30;250(4985):1233-8 [1978757] Mol Cell Biol. 1991 Jan;11(1):1-11 [1986214] Science. 1991 Jun 21;252(5013):1708-11 [2047879] Cancer Res. 1991 Aug 1;51(15):4090-6 [1855224] Proc Natl Acad Sci U S A. 1991 Sep 1;88(17):7605-9 [1652755] Oncogene. 1991 Sep;6(9):1691-2 [1923533] Am J Pathol. 1991 Oct;139(4):839-45 [1656762] Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):9979-83 [1946467] Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):2759-63 [1557382] Cancer Res. 1992 Apr 15;52(8):2340-3 [1559236] N Engl J Med. 1992 May 14;326(20):1301-8 [1565143] N Engl J Med. 1992 May 14;326(20):1309-15 [1565144] J Virol. 1992 Aug;66(8):4757-62 [1352831] Cancer Res. 1992 Dec 15;52(24):6976-8 [1458490] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transformation-specific interaction of the bovine papillomavirus E5 oncoprotein with the platelet-derived growth factor receptor transmembrane domain and the epidermal growth factor receptor cytoplasmic domain. AN - 75892619; 8394451 AB - The bovine papillomavirus E5 transforming protein appears to activate both the epidermal growth factor receptor (EGF-R) and the platelet-derived growth factor receptor (PDGF-R) by a ligand-independent mechanism. To further investigate the ability of E5 to activate receptors of different classes and to determine whether this stimulation occurs through the extracellular domain required for ligand activation, we constructed chimeric genes encoding PDGF-R and EGF-R by interchanging the extracellular, membrane, and cytoplasmic coding domains. Chimeras were transfected into NIH 3T3 and CHO(LR73) cells. All chimeras expressed stable protein which, upon addition of the appropriate ligand, could be activated as assayed by tyrosine autophosphorylation and biological transformation. Cotransfection of E5 with the wild-type and chimeric receptors resulted in the ligand-independent activation of receptors, provided that a receptor contained either the transmembrane domain of the PDGF-R or the cytoplasmic domain of the EGF-R. Chimeric receptors that contained both of these domains exhibited the highest level of E5-induced biochemical and biological stimulation. These results imply that E5 activates the PDGF-R and EGR-R by two distinct mechanisms, neither of which specifically involves the extracellular domain of the receptor. Consistent with the biochemical and biological activation data, coimmunoprecipitation studies demonstrated that E5 formed a complex with any chimera that contained a PDGF-R transmembrane domain or an EGF-R cytoplasmic domain, with those chimeras containing both domains demonstrating the greatest efficiency of complex formation. These results suggest that although different domains of the PDGF-R and EGF-R are required for E5 activation, both receptors are activated directly by formation of an E5-containing complex. JF - Journal of virology AU - Cohen, B D AU - Goldstein, D J AU - Rutledge, L AU - Vass, W C AU - Lowy, D R AU - Schlegel, R AU - Schiller, J T AD - Laboratory of Cellular Oncology, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1993/09// PY - 1993 DA - September 1993 SP - 5303 EP - 5311 VL - 67 IS - 9 SN - 0022-538X, 0022-538X KW - Macromolecular Substances KW - 0 KW - Oncogene Proteins, Viral KW - Recombinant Fusion Proteins KW - oncogene protein E5, Bovine papillomavirus type 1 KW - Cholera Toxin KW - 9012-63-9 KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - Receptors, Platelet-Derived Growth Factor KW - Index Medicus KW - 3T3 Cells KW - Animals KW - Models, Structural KW - Humans KW - Recombinant Fusion Proteins -- isolation & purification KW - Cell Division -- drug effects KW - Cholera Toxin -- pharmacology KW - Mice KW - Protein Binding KW - Cloning, Molecular KW - Recombinant Fusion Proteins -- metabolism KW - Transfection KW - CHO Cells KW - Cell Line KW - Cricetinae KW - Bovine papillomavirus 1 -- metabolism KW - Receptors, Platelet-Derived Growth Factor -- metabolism KW - Receptors, Platelet-Derived Growth Factor -- isolation & purification KW - Receptor, Epidermal Growth Factor -- metabolism KW - Receptor, Epidermal Growth Factor -- genetics KW - Receptor, Epidermal Growth Factor -- isolation & purification KW - Receptors, Platelet-Derived Growth Factor -- genetics KW - Oncogene Proteins, Viral -- metabolism KW - Cell Transformation, Neoplastic KW - Oncogene Proteins, Viral -- isolation & purification KW - Bovine papillomavirus 1 -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75892619?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Transformation-specific+interaction+of+the+bovine+papillomavirus+E5+oncoprotein+with+the+platelet-derived+growth+factor+receptor+transmembrane+domain+and+the+epidermal+growth+factor+receptor+cytoplasmic+domain.&rft.au=Cohen%2C+B+D%3BGoldstein%2C+D+J%3BRutledge%2C+L%3BVass%2C+W+C%3BLowy%2C+D+R%3BSchlegel%2C+R%3BSchiller%2C+J+T&rft.aulast=Cohen&rft.aufirst=B&rft.date=1993-09-01&rft.volume=67&rft.issue=9&rft.spage=5303&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 - 1993-09-13 N1 - Date created - 1993-09-13 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: New Biol. 1990 Nov;2(11):992-1003 [1983208] Nature. 1991 Jul 25;352(6333):347-9 [1649407] J Virol. 1992 Jan;66(1):405-13 [1370089] Oncogene. 1992 Jan;7(1):27-32 [1311063] Mol Cell Biol. 1992 Jul;12(7):2949-57 [1320192] J Cell Physiol. 1992 Aug;152(2):253-63 [1639860] Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):6736-40 [1323117] EMBO J. 1992 Dec;11(13):4851-9 [1334459] Virology. 1980 Jun;103(2):369-75 [6247821] J Cell Physiol. 1982 Apr;111(1):42-8 [6282904] Microbiol Rev. 1982 Jun;46(2):191-207 [6289064] Science. 1983 Jul 15;221(4607):275-7 [6304883] Nature. 1983 Jul 7-13;304(5921):35-9 [6306471] Nature. 1984 May 31-Jun 6;309(5967):418-25 [6328312] DNA. 1985 Oct;4(5):333-49 [3935400] J Virol. 1986 Jan;57(1):1-6 [3001335] Science. 1986 Jul 25;233(4762):464-7 [3014660] EMBO J. 1987 Aug;6(8):2381-5 [2822390] Virology. 1988 May;164(1):182-92 [3363864] Proc Natl Acad Sci U S A. 1988 Aug;85(15):5394-8 [2899890] Mol Cell Biol. 1988 Oct;8(10):4071-8 [2847028] J Cell Biochem. 1989 Feb;39(2):153-66 [2565908] Virology. 1989 May;170(1):334-9 [2541554] Nature. 1989 Jun 22;339(6226):587 [2567498] Cell. 1989 Oct 6;59(1):21-32 [2551505] J Virol. 1989 Nov;63(11):4515-9 [2552136] EMBO J. 1990 Jan;9(1):137-45 [1688529] J Infect Dis. 1990 Dec;162(6):1263-9 [1700026] EMBO J. 1991 Apr;10(4):845-55 [1849073] J Virol. 1991 Dec;65(12):7078-83 [1658398] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Passive immunization of mice against D factor blocks lethality and cytokine release during endotoxemia. AN - 75887881; 8350047 AB - D factor, also known as leukemia inhibitory factor, is a pleiotropic cytokine whose role during acute injury and inflammation is not known. Intraperitoneal administration of Escherichia coli endotoxin induced D factor gene expression in mice, and passive immunization against D factor protected them from the lethal effects of endotoxin and blocked endotoxin-induced increases in serum levels of interleukin 1 and 6. Peak levels of tumor necrosis factor and interferon gamma were not affected. These results indicate that D factor is an essential early mediator of the inflammatory cytokine response and therefore may be important in the pathogenesis of the many inflammatory conditions, such as sepsis, arthritis, allograft rejection, and cancer immunotherapy. JF - The Journal of experimental medicine AU - Block, M I AU - Berg, M AU - McNamara, M J AU - Norton, J A AU - Fraker, D L AU - Alexander, H R AD - Surgical Metabolism Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/09/01/ PY - 1993 DA - 1993 Sep 01 SP - 1085 EP - 1090 VL - 178 IS - 3 SN - 0022-1007, 0022-1007 KW - Cytokines KW - 0 KW - Growth Inhibitors KW - Interleukin-1 KW - Interleukin-6 KW - Leukemia Inhibitory Factor KW - Lif protein, mouse KW - Lipopolysaccharides KW - Lymphokines KW - Oligodeoxyribonucleotides KW - RNA, Messenger KW - Tumor Necrosis Factor-alpha KW - Interferon-gamma KW - 82115-62-6 KW - Index Medicus KW - Animals KW - Interleukin-6 -- metabolism KW - Gene Expression KW - Mice KW - RNA, Messenger -- genetics KW - Lymphocyte Activation KW - Base Sequence KW - Interleukin-1 -- metabolism KW - Oligodeoxyribonucleotides -- chemistry KW - Immunization, Passive KW - Molecular Sequence Data KW - Mice, Inbred C57BL KW - Escherichia coli KW - Interferon-gamma -- metabolism KW - Lipopolysaccharides -- toxicity KW - Tumor Necrosis Factor-alpha -- metabolism KW - Female KW - Growth Inhibitors -- genetics KW - Cytokines -- secretion KW - Lymphokines -- genetics KW - Shock, Septic -- physiopathology KW - Lymphokines -- physiology KW - Growth Inhibitors -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75887881?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+experimental+medicine&rft.atitle=Passive+immunization+of+mice+against+D+factor+blocks+lethality+and+cytokine+release+during+endotoxemia.&rft.au=Block%2C+M+I%3BBerg%2C+M%3BMcNamara%2C+M+J%3BNorton%2C+J+A%3BFraker%2C+D+L%3BAlexander%2C+H+R&rft.aulast=Block&rft.aufirst=M&rft.date=1993-09-01&rft.volume=178&rft.issue=3&rft.spage=1085&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+experimental+medicine&rft.issn=00221007&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-09-13 N1 - Date created - 1993-09-13 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Biol Chem. 1984 Sep 10;259(17):10978-82 [6469994] Infect Immun. 1991 Nov;59(11):3889-94 [1937748] Nature. 1987 Dec 17-23;330(6149):662-4 [3317066] EMBO J. 1987 Dec 20;6(13):3995-4002 [3127201] Anal Biochem. 1988 Sep;173(2):359-67 [3142300] Nature. 1988 Dec 15;336(6200):684-7 [3143916] Biochem Biophys Res Commun. 1989 May 15;160(3):1085-92 [2730639] J Immunol. 1989 Aug 15;143(4):1163-7 [2473120] J Exp Med. 1989 Nov 1;170(5):1627-33 [2809510] Science. 1989 Dec 15;246(4936):1412-6 [2512641] Endocrinology. 1990 Mar;126(3):1416-20 [2106430] Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11408-12 [1722331] Transplantation. 1992 Mar;53(3):655-8 [1549861] J Exp Med. 1992 Apr 1;175(4):1139-42 [1552284] Cytokine. 1992 Mar;4(2):101-5 [1633261] J Immunol. 1992 Sep 1;149(5):1666-70 [1506688] J Clin Invest. 1992 Sep;90(3):888-96 [1522240] Proc Natl Acad Sci U S A. 1992 Sep 15;89(18):8616-20 [1528870] J Clin Invest. 1992 Nov;90(5):2031-7 [1430224] Proc Natl Acad Sci U S A. 1989 Aug;86(15):5948-52 [2569739] Mol Cell Biol. 1990 Jul;10(7):3801-5 [2113178] Endocrinology. 1990 Jul;127(1):185-90 [2113864] Blood. 1990 Jul 1;76(1):50-6 [2114187] J Exp Med. 1991 Apr 1;173(4):1029-32 [1826127] Exp Hematol. 1991 Jun;19(5):347-51 [1709108] Int J Cell Cloning. 1991 Mar;9(2):95-108 [1645391] J Surg Res. 1991 May;50(5):421-4 [2038179] J Cell Biochem. 1991 May;46(1):21-6 [1908473] Science. 1985 Aug 30;229(4716):869-71 [3895437] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phase II study of fluorouracil, leucovorin, and interferon alfa-2a in metastatic colorectal carcinoma. AN - 75884729; 8355041 AB - To test the activity of a regimen of interferon alfa-2a (IFN alpha-2a) 5 x 10(6) U/m2 subcutaneously (SC) days 1 through 7 combined with leucovorin 500 mg/m2/d intravenously (IV) over 30 minutes and fluorouracil (5-FU) 370 mg/m2/d through IV push 1 hour after leucovorin days 2 through 6 in a phase II study. Forty-six patients with a good performance status (PS) with measurable colorectal cancer and no prior therapy for metastatic disease were entered. Cycles were repeated at 3-week intervals if toxicity had resolved. The 5-FU dose was increased by 15% if toxicity was mild, and decreased by 15% for grade 3 to 4 nonhematologic or grade 4 hematologic toxicity. Three complete responses (CRs) and 21 partial responses (PRs) were seen among 44 assessable patients (54%; 95% confidence interval, 39% to 70%). A moderately strong association was noted between PS and response: PS O (n = 26), two CRs and 15 PRs (65%); PS 1 (n = 13), one CR and six PRs (54%); PS 2 (n = 5), zero CRs and zero PRs (0%; two-tailed P = .026). With a median follow-up duration of 18.8 months, the median time to treatment failure (TTF) and survival were 7.8 months and 16.3 months, respectively. Doses were escalated to 425 mg/m2/d 5-FU in 10 patients, but only four tolerated the higher dose. When expressed as the most severe degree of toxicity experienced by each patient across all cycles, grade 3 to 4 toxicity of the following types was observed; mucositis, 37%; diarrhea, 40%; rash, 7%; fatigue, 14%; granulocytopenia, 13%. Dose-limiting toxicity at 370 mg/m2/d 5-FU eventually occurred in 28 patients (61%). Twelve patients (26%) required an IFN alpha-2a dose reduction for constitutional toxicity. This regimen has promising activity in advanced colorectal cancer, particularly in patients with an Eastern Cooperative Oncology Group (ECOG) PS of 0 to 1. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Grem, J L AU - Jordan, E AU - Robson, M E AU - Binder, R A AU - Hamilton, J M AU - Steinberg, S M AU - Arbuck, S G AU - Beveridge, R A AU - Kales, A N AU - Miller, J A AD - Clinical Oncology Program, National Cancer Institute, Bethesda, MD. Y1 - 1993/09// PY - 1993 DA - September 1993 SP - 1737 EP - 1745 VL - 11 IS - 9 SN - 0732-183X, 0732-183X KW - Interferon-alpha KW - 0 KW - Recombinant Proteins KW - interferon alfa-2a KW - 47RRR83SK7 KW - Leucovorin KW - Q573I9DVLP KW - Fluorouracil KW - U3P01618RT KW - Index Medicus KW - Fluorouracil -- administration & dosage KW - Drug Administration Schedule KW - Interferon-alpha -- administration & dosage KW - Leucovorin -- administration & dosage KW - Humans KW - Adult KW - Neoplasm Metastasis KW - Aged KW - Middle Aged KW - Male KW - Female KW - Survival Analysis KW - Colorectal Neoplasms -- pathology KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Colorectal Neoplasms -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75884729?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.atitle=Phase+II+study+of+fluorouracil%2C+leucovorin%2C+and+interferon+alfa-2a+in+metastatic+colorectal+carcinoma.&rft.au=Grem%2C+J+L%3BJordan%2C+E%3BRobson%2C+M+E%3BBinder%2C+R+A%3BHamilton%2C+J+M%3BSteinberg%2C+S+M%3BArbuck%2C+S+G%3BBeveridge%2C+R+A%3BKales%2C+A+N%3BMiller%2C+J+A&rft.aulast=Grem&rft.aufirst=J&rft.date=1993-09-01&rft.volume=11&rft.issue=9&rft.spage=1737&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 - 1993-09-23 N1 - Date created - 1993-09-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Risk for sustained amenorrhea in patients with systemic lupus erythematosus receiving intermittent pulse cyclophosphamide therapy. AN - 75859497; 8338289 AB - To determine the risk for secondary amenorrhea after pulse cyclophosphamide therapy in premenopausal women with systemic lupus erythematosus. Controlled, retrospective clinical study. Government referral-based research hospital. Thirty-nine women younger than 40 years treated with pulse cyclophosphamide therapy for active lupus nephritis or neuropsychiatric lupus. Sixteen women who received pulses of intravenous methylprednisolone were controls. Sixteen patients received pulse cyclophosphamide (0.5 to 1.0 g/m2 body surface area) monthly for a total of 7 doses (short-CY), and 23 patients received 15 or more doses (long-CY). Control patients were treated with monthly pulses of methylprednisolone (1.0 g/m2) for a total of nine doses. Rates of amenorrhea were evaluated according to duration of treatment (number of doses) and age at the initiation of pulse therapy. Two of 16 patients (12%) in the Short-CY group and 9 of 23 (39%) in the long-CY group developed sustained amenorrhea (P = 0.07). Rates of sustained amenorrhea (short- and long-CY) according to age at the start of pulse therapy were: or = 31 years, 5/8 (62%) (P = 0.04). The increased risk for sustained amenorrhea in patients treated with long-CY was most evident in patients older than 25 years (short-CY [2/12] compared with long-CY [7/11]; P = 0.03). Three other patients with short-CY had reversal of amenorrhea fewer than 12 months after cessation of therapy. Amenorrhea was not observed in any of the 16 control patients. Intermittent pulse cyclophosphamide therapy in patients with systemic lupus erythematosus is associated with sustained amenorrhea, which is related to both age and number of doses of cyclophosphamide. JF - Annals of internal medicine AU - Boumpas, D T AU - Austin, H A AU - Vaughan, E M AU - Yarboro, C H AU - Klippel, J H AU - Balow, J E AD - National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland. Y1 - 1993/09/01/ PY - 1993 DA - 1993 Sep 01 SP - 366 EP - 369 VL - 119 IS - 5 SN - 0003-4819, 0003-4819 KW - Cyclophosphamide KW - 8N3DW7272P KW - Abridged Index Medicus KW - Index Medicus KW - Drug Administration Schedule KW - Age Factors KW - Lupus Nephritis -- drug therapy KW - Risk Factors KW - Humans KW - Ovary -- drug effects KW - Adult KW - Retrospective Studies KW - Female KW - Fertility -- drug effects KW - Cyclophosphamide -- administration & dosage KW - Lupus Erythematosus, Systemic -- drug therapy KW - Amenorrhea -- chemically induced KW - Cyclophosphamide -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75859497?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+internal+medicine&rft.atitle=Risk+for+sustained+amenorrhea+in+patients+with+systemic+lupus+erythematosus+receiving+intermittent+pulse+cyclophosphamide+therapy.&rft.au=Boumpas%2C+D+T%3BAustin%2C+H+A%3BVaughan%2C+E+M%3BYarboro%2C+C+H%3BKlippel%2C+J+H%3BBalow%2C+J+E&rft.aulast=Boumpas&rft.aufirst=D&rft.date=1993-09-01&rft.volume=119&rft.issue=5&rft.spage=366&rft.isbn=&rft.btitle=&rft.title=Annals+of+internal+medicine&rft.issn=00034819&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-08-26 N1 - Date created - 1993-08-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Removal of dyes from aqueous solutions by low pressure batch ultrafiltration AN - 16832928; 3558724 AB - The use of a low pressure batch ultrafiltration method to separate dyes from aqueous solutions was investigated at 22 degree C. Several factors affecting the membrane performance, such as the hydraulic permeability and the rejection coefficient, were examined, including initial dye concentration, the operating pressure, as well as especially the membrane material and the ionic nature of dye molecules. JF - Separation Science and Technology AU - Juang, Ruey-Shin AU - Liang, Ji-Feng AU - Jiang, Jiann-Der AD - Dep. Chem. Eng., Yuan-Ze Inst. Technol., Nei-Li, Taoyuan, 32026, Taiwan Y1 - 1993/09// PY - 1993 DA - Sep 1993 SP - 2049 EP - 2059 VL - 28 IS - 11-12 SN - 0149-6395, 0149-6395 KW - Water Resources Abstracts KW - membranes KW - wastewater treatment KW - filtration KW - dye concentrations KW - separation techniques KW - dyes KW - SW 3040:Wastewater treatment processes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16832928?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Awaterresources&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Separation+Science+and+Technology&rft.atitle=Removal+of+dyes+from+aqueous+solutions+by+low+pressure+batch+ultrafiltration&rft.au=Juang%2C+Ruey-Shin%3BLiang%2C+Ji-Feng%3BJiang%2C+Jiann-Der&rft.aulast=Juang&rft.aufirst=Ruey-Shin&rft.date=1993-09-01&rft.volume=28&rft.issue=11-12&rft.spage=2049&rft.isbn=&rft.btitle=&rft.title=Separation+Science+and+Technology&rft.issn=01496395&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 - filtration; separation techniques; dyes; wastewater treatment; dye concentrations; membranes ER - TY - JOUR T1 - Inhibition of DNA repair and sensitization of cisplatin in human ovarian carcinoma cells by interleukin-1 alpha. AN - 75897029; 8363610 AB - Interleukin-1 alpha induced an increase in both the cellular accumulation of cis-diamminedichloroplatinum (II) (cisplatin) and DNA platination and significantly reduced the removal of platinum from DNA of human ovarian (NIH: OVCAR-3) carcinoma cells in culture. The combinations of IL-1 alpha and cisplatin were highly synergistic against these ovarian carcinoma cells and maximum levels of sensitization (15-20-fold) were observed during simultaneous exposure of cisplatin and IL-1 alpha. IL-1 alpha specific receptor antagonist decreased this synergy. These results strongly indicate that IL-1 alpha inhibits DNA repair, and this inhibition of DNA repair may explain, in part, a strong synergistic interaction between IL-1 alpha and cisplatin in NIH: OVCAR-3 cells. JF - Biochemical and biophysical research communications AU - Benchekroun, M N AU - Parker, R AU - Reed, E AU - Sinha, B K AD - Biochemical and Molecular Pharmacology Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/08/31/ PY - 1993 DA - 1993 Aug 31 SP - 294 EP - 300 VL - 195 IS - 1 SN - 0006-291X, 0006-291X KW - Interleukin-1 KW - 0 KW - Receptors, Interleukin-1 KW - Recombinant Proteins KW - Cisplatin KW - Q20Q21Q62J KW - Index Medicus KW - Recombinant Proteins -- toxicity KW - Ovarian Neoplasms KW - Tumor Cells, Cultured KW - Cell Survival -- drug effects KW - Dose-Response Relationship, Drug KW - Kinetics KW - Humans KW - Receptors, Interleukin-1 -- antagonists & inhibitors KW - Drug Synergism KW - Female KW - Cell Line KW - Cisplatin -- toxicity KW - Interleukin-1 -- toxicity KW - Cisplatin -- metabolism KW - DNA Repair -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75897029?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+and+biophysical+research+communications&rft.atitle=Inhibition+of+DNA+repair+and+sensitization+of+cisplatin+in+human+ovarian+carcinoma+cells+by+interleukin-1+alpha.&rft.au=Benchekroun%2C+M+N%3BParker%2C+R%3BReed%2C+E%3BSinha%2C+B+K&rft.aulast=Benchekroun&rft.aufirst=M&rft.date=1993-08-31&rft.volume=195&rft.issue=1&rft.spage=294&rft.isbn=&rft.btitle=&rft.title=Biochemical+and+biophysical+research+communications&rft.issn=0006291X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-09-28 N1 - Date created - 1993-09-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Requirement of phenylalanine 343 for the preferential delta 4-lyase versus delta 5-lyase activity of rat CYP17. AN - 75889081; 8349703 AB - Site-directed mutagenesis of a domain (amino acids 343-348) within the conserved region of rat CYP17 was performed to investigate species-specific differences between rat and human/bovine delta 4-versus delta 5-lyase activity. This domain displays substantial deviations between the rat and human/bovine/pig sequences and includes Arg346, which is known to be essential for delta 4-lyase (Kitamura, M., Buczko, E., and Dufau, M. L. (1991) Mol. Endocrinol. 5, 1373-1380) and delta 5-lyase activities. Analysis of the delta 4-lyase activity of mutant rat CYP17 cDNA expressed in nonsteroidogenic COS-1 cells revealed that substitution of Phe at position 343 in the rat with Ile of the human/bovine sequence resulted in a reduction in delta 4-lyase activity to levels in the range of the delta 5-supported reaction. This Phe343-->Ile mutant CYP17 did not exhibit changes either in delta 5-supported lyase activity or in delta 4- and delta 5-hydroxylase activities. Substitution of Asn344, Ser347, and His348 in rat CYP17 with the corresponding bovine amino acids Ser, Asn, and Arg did not enhance this effect. Thus, the reduced activity of the bovine CYP17 delta 4-lyase reaction can be mimicked in part in the rat polypeptide by the substitution of Phe343 with the bovine counterpart, Ile. Unlike the bovine CYP17-catalyzed reaction, the rat Phe343-->Ile mutant exhibited a low level lyase activity (kcat) that did not discriminate between delta 4- and delta 5-substrates. These results suggest that the presence of Phe343 enhances the delta 4-supported lyase activity possibly through stabilization of a delta 4-specific interaction. JF - The Journal of biological chemistry AU - Koh, Y AU - Buczko, E AU - Dufau, M L AD - Section on Molecular Endocrinology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/08/25/ PY - 1993 DA - 1993 Aug 25 SP - 18267 EP - 18271 VL - 268 IS - 24 SN - 0021-9258, 0021-9258 KW - CYP17 KW - Recombinant Proteins KW - 0 KW - Phenylalanine KW - 47E5O17Y3R KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Steroid 17-alpha-Hydroxylase KW - EC 1.14.14.19 KW - Aldehyde-Lyases KW - EC 4.1.2.- KW - Index Medicus KW - Animals KW - Recombinant Proteins -- biosynthesis KW - Models, Molecular KW - Humans KW - Amino Acid Sequence KW - Microsomes -- enzymology KW - Binding Sites KW - Cloning, Molecular KW - Rats KW - Mutagenesis, Site-Directed KW - Recombinant Proteins -- isolation & purification KW - Blotting, Western KW - Cattle KW - Transfection KW - Recombinant Proteins -- metabolism KW - Kinetics KW - Molecular Sequence Data KW - Substrate Specificity KW - Sequence Homology, Amino Acid KW - Cell Line KW - Protein Conformation KW - Steroid 17-alpha-Hydroxylase -- metabolism KW - Aldehyde-Lyases -- metabolism KW - Steroid 17-alpha-Hydroxylase -- isolation & purification KW - Cytochrome P-450 Enzyme System -- metabolism KW - Steroid 17-alpha-Hydroxylase -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75889081?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Requirement+of+phenylalanine+343+for+the+preferential+delta+4-lyase+versus+delta+5-lyase+activity+of+rat+CYP17.&rft.au=Koh%2C+Y%3BBuczko%2C+E%3BDufau%2C+M+L&rft.aulast=Koh&rft.aufirst=Y&rft.date=1993-08-25&rft.volume=268&rft.issue=24&rft.spage=18267&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 - 1993-09-16 N1 - Date created - 1993-09-16 N1 - Date revised - 2017-01-13 N1 - Gene symbol - CYP17 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cloning and site-directed mutagenesis of human ADP-ribosylarginine hydrolase. AN - 75889061; 8349667 AB - Mono-ADP-ribosylation of arginine is a reversible modification of proteins with NAD:arginine ADP-ribosyltransferases and ADP-ribosylarginine hydrolases catalyzing the opposing reactions in the cycle. ADP-ribosylarginine hydrolases differ in their dithiothreitol (DTT) requirements. Rat and mouse hydrolases require DTT for maximal activity, but calf, guinea pig, and human hydrolases are DTT-independent. To define the molecular basis for these differences, brain ADP-ribosylarginine hydrolases were cloned. Deduced amino acid sequences of mouse and rat hydrolases were 94% identical with 5 conserved cysteines. The human hydrolase sequence was 83% identical to that of rat but contained only 4 cysteines with cysteine 108 in rat corresponding to serine 103 in human. To investigate the role of rat cysteine 108, human and rat wild-type hydrolases and mutants, in which serine 103 in human was replaced by cysteine (S103C) and cysteine 108 in rat was replaced by serine (C108S), were expressed in Escherichia coli. Affinity-purified anti-rat brain hydrolase antibodies reacted with recombinant wild-type rat hydrolase, but only weakly with the C108S mutant. They did not react with human wild-type or the S103C mutant. Human hydrolase and rat C108S were DTT-independent; human S103C was, however, DTT-dependent. These data clearly show that cysteine 108 in rat hydrolase plays a critical role in DTT dependence and may be important in immunoreactivity. JF - The Journal of biological chemistry AU - Takada, T AU - Iida, K AU - Moss, J AD - Laboratory of Cellular Metabolism, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/08/25/ PY - 1993 DA - 1993 Aug 25 SP - 17837 EP - 17843 VL - 268 IS - 24 SN - 0021-9258, 0021-9258 KW - Oligodeoxyribonucleotides KW - 0 KW - Recombinant Proteins KW - DNA KW - 9007-49-2 KW - Hydrolases KW - EC 3.- KW - Glycoside Hydrolases KW - EC 3.2.1.- KW - N-Glycosyl Hydrolases KW - EC 3.2.2.- KW - ADP-ribosylarginine hydrolase KW - EC 3.2.2.19 KW - Dithiothreitol KW - T8ID5YZU6Y KW - Index Medicus KW - Animals KW - Recombinant Proteins -- biosynthesis KW - Guinea Pigs KW - Humans KW - Mice KW - Amino Acid Sequence KW - Cloning, Molecular KW - Rats KW - Recombinant Proteins -- isolation & purification KW - DNA -- isolation & purification KW - Base Sequence KW - Cattle KW - Chromatography, Gel KW - Recombinant Proteins -- metabolism KW - Kinetics KW - DNA -- genetics KW - Dithiothreitol -- pharmacology KW - Molecular Sequence Data KW - Sequence Homology, Amino Acid KW - Mutagenesis, Site-Directed KW - Hydrolases -- metabolism KW - Hydrolases -- isolation & purification KW - Hydrolases -- genetics KW - Lung -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75889061?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cloning+and+site-directed+mutagenesis+of+human+ADP-ribosylarginine+hydrolase.&rft.au=Takada%2C+T%3BIida%2C+K%3BMoss%2C+J&rft.aulast=Takada&rft.aufirst=T&rft.date=1993-08-25&rft.volume=268&rft.issue=24&rft.spage=17837&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 - 1993-09-16 N1 - Date created - 1993-09-16 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - L13290; GENBANK; L13291 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Sulfhydryl reagents and cAMP-dependent kinase increase the sensitivity of the inositol 1,4,5-trisphosphate receptor in hepatocytes. AN - 75888818; 8394353 AB - Sulfhydryl reagents such as tert-butyl hydroperoxide (TBHP) have been shown to increase cytosolic Ca2+ concentration ([Ca2+]i) in rat hepatocytes in a way that resembles responses to Ca(2+)-mobilizing hormones (Saikada, I., Thomas, A. P., and Farber, J. L. (1991) J. Biol. Chem. 266, 717-722; Rooney, T. A., Renard, D. C., Sass, E. J., and Thomas, A. P. (1991) J. Biol. Chem. 266, 12272-12282) and to increase the amount of Ca2+ released by inositol 1,4,5-trisphosphate ((1,4,5)IP3) from permeable rat liver cells (Rooney et al., 1991, op. cit.; Missiaen, L., Taylor, C. W., and Berridge, M. J. (1991) Nature 352, 241-244; Renard, D. C., Seitz, M. B., and Thomas, A. P. (1992) Biochem. J. 284, 507-512). The effects of sulfhydryl reagents were studied in fura-2-injected rat and guinea pig hepatocytes and compared with the actions of cAMP (Burgess, G. M., Bird, G. St. J., Obie, J. F., and Putney, J. W., Jr. (1991) J. Biol. Chem. 261, 4772-4781). In rat liver cells, the increases in [Ca2+]i induced by TBHP and thimerosal were prevented by microinjection of the cells with the (1,4,5)IP3 receptor antagonist heparin. In guinea pig hepatocytes, TBHP was not able to increase [Ca2+]i unless the cells were pretreated with angiotensin II to raise endogenous levels of (1,4,5)IP3 or were first injected with a sub-threshold concentration of inositol 2,4,5-trisphosphate ((2,4,5)IP3). The responses to TBHP in (2,4,5)IP3-injected guinea pig cells were also blocked by heparin. In many respects, the actions of TBHP appeared to be similar to those of cAMP, which has previously been shown to increase sensitivity to (1,4,5)IP3 in intact guinea pig hepatocytes (Burgess et al., 1991, op. cit.). TBHP also mimicked the effect of cAMP-dependent kinase (PKA) in permeabilized guinea pig hepatocytes by increasing the amount of Ca2+ released by (1,4,5)IP3. The responses to TBHP and cAMP in (2,4,5)IP3-injected guinea pig hepatocytes differed, however, in that the increase in [Ca2+]i evoked by elevating intracellular cAMP was greatly reduced by Wiptide, an inhibitor of PKA, while Wiptide had no effect on the Ca2+ transients induced by TBHP. This provides evidence that the sensitizing effect of TBHP is not mediated by PKA and is more likely to be a direct effect on the inositol trisphosphate receptor. It is possible, however, that the sulfhydryl reagents and PKA act on a common regulatory site on the receptor protein. JF - The Journal of biological chemistry AU - Bird, G S AU - Burgess, G M AU - Putney, J W AD - Calcium Regulation Section, National Institute of Environmental Health Sciences, Research Traingle Park, North Carolina 27709. Y1 - 1993/08/25/ PY - 1993 DA - 1993 Aug 25 SP - 17917 EP - 17923 VL - 268 IS - 24 SN - 0021-9258, 0021-9258 KW - Calcium Channels KW - 0 KW - Inositol 1,4,5-Trisphosphate Receptors KW - Inositol Phosphates KW - Oxidants KW - Peroxides KW - Receptors, Cell Surface KW - Receptors, Cytoplasmic and Nuclear KW - Sulfhydryl Reagents KW - Bucladesine KW - 63X7MBT2LQ KW - Inositol 1,4,5-Trisphosphate KW - 85166-31-0 KW - Heparin KW - 9005-49-6 KW - inositol 2,4,5-trisphosphate KW - 91840-07-2 KW - tert-Butylhydroperoxide KW - 955VYL842B KW - Protein Kinases KW - EC 2.7.- KW - Isoproterenol KW - L628TT009W KW - Calcium KW - SY7Q814VUP KW - Fura-2 KW - TSN3DL106G KW - Index Medicus KW - Rats KW - Animals KW - Oxidants -- pharmacology KW - Guinea Pigs KW - Cells, Cultured KW - Kinetics KW - Heparin -- pharmacology KW - Cell Membrane Permeability KW - Bucladesine -- pharmacology KW - Isoproterenol -- pharmacology KW - Inositol Phosphates -- pharmacology KW - Peroxides -- pharmacology KW - Liver -- metabolism KW - Inositol 1,4,5-Trisphosphate -- metabolism KW - Inositol 1,4,5-Trisphosphate -- pharmacology KW - Calcium -- metabolism KW - Protein Kinases -- pharmacology KW - Receptors, Cell Surface -- metabolism KW - Protein Kinases -- metabolism KW - Liver -- drug effects KW - Sulfhydryl Reagents -- pharmacology KW - Receptors, Cell Surface -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75888818?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Sulfhydryl+reagents+and+cAMP-dependent+kinase+increase+the+sensitivity+of+the+inositol+1%2C4%2C5-trisphosphate+receptor+in+hepatocytes.&rft.au=Bird%2C+G+S%3BBurgess%2C+G+M%3BPutney%2C+J+W&rft.aulast=Bird&rft.aufirst=G&rft.date=1993-08-25&rft.volume=268&rft.issue=24&rft.spage=17917&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 - 1993-09-16 N1 - Date created - 1993-09-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - L-deprenyl confers specific protection against MPTP-induced Parkinson's disease-like movement disorder in the goldfish. AN - 76093145; 8243537 AB - Administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to the goldfish causes a reversible, Parkinson's disease-like syndrome which includes loss of noradrenaline and dopamine from the brain, accumulation of the toxic metabolite 1-methyl-4-phenylpyridinium species (MPP+), and substantial reduction in movement. L-Deprenyl, a selective monoamine oxidase-B inhibitor, protects the goldfish from loss of movement, but clorgyline, a selective monoamine oxidase-A inhibitor, has no such protective action. L-Deprenyl and clorgyline primarily inhibit goldfish brain monoamine oxidase-B and monoamine oxidase-A, respectively. The mechanism by which MPTP causes reduced movement in goldfish is to cause an increase in resting time. Otherwise normal average velocity occurred during periods of movement. L-Deprenyl protection results in entirely 'normal' levels of resting time and average velocity during times of movement. Equivalent observations regarding l-deprenyl and clorgyline have been made in primate models of MPTP toxicity, and l-deprenyl is used for treatment of Parkinson's disease in humans. Therefore it is suggested that the evolutionarily equivalent subcortical circuitry and neural density of the goldfish brain may provide a useful model upon which to search for drugs relevant to human Parkinson's disease. JF - European journal of pharmacology AU - Adeyemo, O M AU - Youdim, M B AU - Markey, S P AU - Markey, C J AU - Pollard, H B AD - Laboratory of Cell Biology and Genetics, N.I.D.D.K., National Institute of Health, Bethesda, MD 20892. Y1 - 1993/08/24/ PY - 1993 DA - 1993 Aug 24 SP - 185 EP - 193 VL - 240 IS - 2-3 SN - 0014-2999, 0014-2999 KW - Selegiline KW - 2K1V7GP655 KW - Monoamine Oxidase KW - EC 1.4.3.4 KW - Clorgyline KW - LYJ16FZU9Q KW - Dopamine KW - VTD58H1Z2X KW - Norepinephrine KW - X4W3ENH1CV KW - Index Medicus KW - Brain -- enzymology KW - Animals KW - Norepinephrine -- metabolism KW - Brain -- drug effects KW - Dopamine -- metabolism KW - Monoamine Oxidase -- metabolism KW - Parkinson Disease, Secondary -- chemically induced KW - Selegiline -- pharmacology KW - MPTP Poisoning KW - Goldfish KW - Disease Models, Animal KW - Motor Activity -- drug effects KW - Clorgyline -- pharmacology KW - Parkinson Disease, Secondary -- prevention & control KW - Parkinson Disease, Secondary -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76093145?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+pharmacology&rft.atitle=L-deprenyl+confers+specific+protection+against+MPTP-induced+Parkinson%27s+disease-like+movement+disorder+in+the+goldfish.&rft.au=Adeyemo%2C+O+M%3BYoudim%2C+M+B%3BMarkey%2C+S+P%3BMarkey%2C+C+J%3BPollard%2C+H+B&rft.aulast=Adeyemo&rft.aufirst=O&rft.date=1993-08-24&rft.volume=240&rft.issue=2-3&rft.spage=185&rft.isbn=&rft.btitle=&rft.title=European+journal+of+pharmacology&rft.issn=00142999&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-01-03 N1 - Date created - 1994-01-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The G protein alpha s subunit incorporates [3H]palmitic acid and mutation of cysteine-3 prevents this modification. AN - 75879862; 8347607 AB - We investigated whether alpha s could be acylated by palmitate by transfecting COS cells with the cDNA for the wild-type, long form of alpha s and metabolically labeling with [3H]palmitate or [35S]methionine. Cells were separated into particulate and soluble fractions and immunoprecipitated with a specific peptide antibody. [3H]Palmitate was incorporated into both endogenous and transfected alpha s. Inhibition of protein synthesis with cycloheximide did not block the radiolabeling of alpha s with [3H]palmitate. Hydroxylamine treatment caused a release of the tritium radiolabel, demonstrating that the incorporation was through a thioester bond. The tritium radiolabel was base-labile and comigrated with [3H]palmitate on thin-layer chromatography. The third residue of the wild-type alpha s was mutated from a cysteine to an alanine by site-directed mutagenesis. This mutant was expressed in COS cells and localized to the particulate fraction as determined by immunoprecipitation of the [35S]methionine-labeled cells. The cysteine-3 mutant did not undergo radiolabeling with [3H]palmitate, indicating that this residue is crucial for the modification. JF - Biochemistry AU - Degtyarev, M Y AU - Spiegel, A M AU - Jones, T L AD - Molecular Pathophysiology Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/08/17/ PY - 1993 DA - 1993 Aug 17 SP - 8057 EP - 8061 VL - 32 IS - 32 SN - 0006-2960, 0006-2960 KW - Palmitic Acids KW - 0 KW - Tritium KW - 10028-17-8 KW - Palmitic Acid KW - 2V16EO95H1 KW - Cycloheximide KW - 98600C0908 KW - Methionine KW - AE28F7PNPL KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - Cysteine KW - K848JZ4886 KW - Index Medicus KW - Animals KW - Immunoblotting KW - Gene Expression KW - Methionine -- metabolism KW - Rats KW - Base Sequence KW - Transfection KW - Cycloheximide -- pharmacology KW - Molecular Sequence Data KW - Immunosorbent Techniques KW - Cell Line KW - Mutagenesis, Site-Directed KW - Palmitic Acids -- metabolism KW - GTP-Binding Proteins -- metabolism KW - Cysteine -- genetics KW - GTP-Binding Proteins -- chemistry KW - GTP-Binding Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75879862?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+G+protein+alpha+s+subunit+incorporates+%5B3H%5Dpalmitic+acid+and+mutation+of+cysteine-3+prevents+this+modification.&rft.au=Degtyarev%2C+M+Y%3BSpiegel%2C+A+M%3BJones%2C+T+L&rft.aulast=Degtyarev&rft.aufirst=M&rft.date=1993-08-17&rft.volume=32&rft.issue=32&rft.spage=8057&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-09-16 N1 - Date created - 1993-09-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phencyclidine, a psychotomimetic agent and drug of abuse, is a suicide inhibitor of brain nitric oxide synthase. AN - 75899672; 7688965 AB - Phencyclidine, 1-(1-phenylcyclohexyl)piperidine, was shown in this study to be an effective irreversible inhibitor of brain nitric oxide synthase, the enzyme responsible for the conversion of L-arginine to nitric oxide. The inactivation of nitric oxide synthase was time- and concentration-dependent and required reduced nicotinamide adenine dinucleotide phosphate, a necessary cofactor for nitric oxide synthesis. These results indicate that phencyclidine is metabolized by nitric oxide synthase to reactive intermediates that irreversibly inactivate the enzyme. The inactivation of nitric oxide synthase by xenobiotics, such as phencyclidine, may be pharmacologically and toxicologically important due to the role of nitric oxide in a variety of physiological processes. JF - Biochemical and biophysical research communications AU - Osawa, Y AU - Davila, J C AD - Laboratory of Chemical Pharmacology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/08/16/ PY - 1993 DA - 1993 Aug 16 SP - 1435 EP - 1439 VL - 194 IS - 3 SN - 0006-291X, 0006-291X KW - Nitric Oxide Synthase KW - EC 1.14.13.39 KW - Amino Acid Oxidoreductases KW - EC 1.4.- KW - Phencyclidine KW - J1DOI7UV76 KW - Index Medicus KW - Rats KW - Animals KW - Dose-Response Relationship, Drug KW - Cytosol -- enzymology KW - Rats, Wistar KW - Brain -- enzymology KW - Amino Acid Oxidoreductases -- antagonists & inhibitors KW - Phencyclidine -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75899672?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+and+biophysical+research+communications&rft.atitle=Phencyclidine%2C+a+psychotomimetic+agent+and+drug+of+abuse%2C+is+a+suicide+inhibitor+of+brain+nitric+oxide+synthase.&rft.au=Osawa%2C+Y%3BDavila%2C+J+C&rft.aulast=Osawa&rft.aufirst=Y&rft.date=1993-08-16&rft.volume=194&rft.issue=3&rft.spage=1435&rft.isbn=&rft.btitle=&rft.title=Biochemical+and+biophysical+research+communications&rft.issn=0006291X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-09-15 N1 - Date created - 1993-09-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dopamine transporter gene polymorphisms are not associated with polysubstance abuse. AN - 75973232; 8399824 JF - Biological psychiatry AU - Persico, A M AU - Vandenbergh, D J AU - Smith, S S AU - Uhl, G R AD - Molecular Neurobiology Branch, National Institute on Drug Abuse, Baltimore, MD 21224. Y1 - 1993/08/15/ PY - 1993 DA - 1993 Aug 15 SP - 265 EP - 267 VL - 34 IS - 4 SN - 0006-3223, 0006-3223 KW - Biomarkers KW - 0 KW - DNA KW - 9007-49-2 KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Dopamine -- genetics KW - Psychiatric Status Rating Scales KW - Polymorphism, Genetic -- genetics KW - Humans KW - DNA -- genetics KW - Gene Expression KW - Biological Transport KW - Dopamine -- metabolism KW - DNA -- physiology KW - Male KW - Female KW - Substance-Related Disorders -- diagnosis KW - Substance-Related Disorders -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75973232?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biological+psychiatry&rft.atitle=Dopamine+transporter+gene+polymorphisms+are+not+associated+with+polysubstance+abuse.&rft.au=Persico%2C+A+M%3BVandenbergh%2C+D+J%3BSmith%2C+S+S%3BUhl%2C+G+R&rft.aulast=Persico&rft.aufirst=A&rft.date=1993-08-15&rft.volume=34&rft.issue=4&rft.spage=265&rft.isbn=&rft.btitle=&rft.title=Biological+psychiatry&rft.issn=00063223&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-11-17 N1 - Date created - 1993-11-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Replication of UV-irradiated DNA in human cell extracts: evidence for mutagenic bypass of pyrimidine dimers. AN - 75912776; 8356079 AB - We have examined the efficiency and fidelity of simian virus 40-origin-dependent replication of UV-irradiated double-stranded DNA in extracts of human cells. Using as a mutational target the alpha-complementation domain of the Escherichia coli lacZ gene in bacteriophage M13mp2 DNA, replication of undamaged DNA in HeLa cell extracts was highly accurate, whereas replication of DNA irradiated with UV light (280-320 nm) was both less efficient and less accurate. Replication was inhibited by irradiation in a dose-dependent manner. Nonetheless, covalently closed, monomer-length circular products were generated that were resistant to digestion by Dpn I, showing that they resulted from semiconservative replication. These products were incised by T4 endonuclease V, whereas the undamaged replication products were not, suggesting that pyrimidine dimers were bypassed during replication. When replicated, UV-irradiated DNA was used to transfect an E. coli alpha-complementation host strain to score mutant M13mp2 plaques, the mutant plaque frequency was substantially higher than that obtained with either unirradiated, replicated DNA, or unreplicated, UV-irradiated DNA. Both the increased mutagenicity and the inhibition of replication associated with UV irradiation were reversed by treatment of the irradiated DNA with photolyase before replication. Sequence analysis of mutants resulting from replication of UV-irradiated DNA demonstrated that most mutants contained C-->T transition errors at dipyrimidine sites. A few mutants contained 1-nt frameshift errors or tandem double CC-->TT substitutions. The data are consistent with the interpretation that pyrimidine dimers are bypassed during replication by the multiprotein replication apparatus in human cell extracts and that this bypass is mutagenic primarily via misincorporation of dAMP opposite a cytosine (or uracil) in the dimer. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Thomas, D C AU - Kunkel, T A AD - Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1993/08/15/ PY - 1993 DA - 1993 Aug 15 SP - 7744 EP - 7748 VL - 90 IS - 16 SN - 0027-8424, 0027-8424 KW - Deoxycytosine Nucleotides KW - 0 KW - Pyrimidine Dimers KW - 2'-deoxycytidine 5'-triphosphate KW - 2056-98-6 KW - DNA KW - 9007-49-2 KW - Deoxyribodipyrimidine Photo-Lyase KW - EC 4.1.99.3 KW - Index Medicus KW - Deoxycytosine Nucleotides -- metabolism KW - Deoxyribodipyrimidine Photo-Lyase -- metabolism KW - HeLa Cells KW - Electrophoresis, Polyacrylamide Gel KW - Humans KW - Restriction Mapping KW - Electrophoresis, Agar Gel KW - Escherichia coli -- genetics KW - Escherichia coli -- enzymology KW - Dose-Response Relationship, Radiation KW - DNA -- isolation & purification KW - Ultraviolet Rays KW - DNA Replication -- radiation effects KW - Pyrimidine Dimers -- metabolism KW - DNA -- radiation effects KW - DNA -- biosynthesis KW - Mutagenesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75912776?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Replication+of+UV-irradiated+DNA+in+human+cell+extracts%3A+evidence+for+mutagenic+bypass+of+pyrimidine+dimers.&rft.au=Thomas%2C+D+C%3BKunkel%2C+T+A&rft.aulast=Thomas&rft.aufirst=D&rft.date=1993-08-15&rft.volume=90&rft.issue=16&rft.spage=7744&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 - 1993-09-23 N1 - Date created - 1993-09-23 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Genetics. 1974 Sep;78(1):139-48 [4442699] Mol Cell Biol. 1993 Jan;13(1):533-42 [8417349] Photochem Photobiol. 1978 Mar;27(3):297-307 [733927] J Mol Biol. 1980 Apr;138(2):299-319 [6251226] Proc Natl Acad Sci U S A. 1983 Mar;80(6):1541-5 [6340105] J Mol Biol. 1984 Mar 5;173(3):293-305 [6230459] J Mol Biol. 1984 Dec 5;180(2):217-37 [6439876] J Biol Chem. 1985 May 10;260(9):5787-96 [3988773] J Mol Biol. 1985 Mar 5;182(1):65-8 [2987509] Mol Cell Biol. 1985 Jun;5(6):1238-46 [2993858] Proc Natl Acad Sci U S A. 1986 Jul;83(13):4599-603 [2941756] J Biol Chem. 1986 Nov 5;261(31):14496-505 [3533921] Proc Natl Acad Sci U S A. 1986 Nov;83(21):8273-7 [3464953] Mol Cell Biol. 1986 Jan;6(1):277-85 [3537686] Mol Cell Biol. 1986 Oct;6(10):3349-56 [3540589] Mol Cell Biol. 1986 Oct;6(10):3443-50 [3025594] Proc Natl Acad Sci U S A. 1987 Dec;84(24):9103-7 [3480533] J Mol Biol. 1987 Nov 20;198(2):187-202 [2828636] J Biol Chem. 1988 Mar 25;263(9):4450-9 [2831231] Proc Natl Acad Sci U S A. 1988 Oct;85(19):7064-8 [3174620] Annu Rev Biochem. 1988;57:29-67 [3052275] Proc Natl Acad Sci U S A. 1988 Nov;85(21):8141-5 [3054882] J Biol Chem. 1988 Dec 5;263(34):17889-92 [2848017] Carcinogenesis. 1989 Jan;10(1):1-11 [2642748] Proc Natl Acad Sci U S A. 1990 Nov;87(22):9005-9 [2247476] Mol Cell Biol. 1991 Apr;11(4):1927-34 [2005888] Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3465-9 [1901658] J Mol Biol. 1991 Apr 20;218(4):667-73 [1902520] Nucleic Acids Res. 1991 May 11;19(9):2411-5 [1674998] J Biol Chem. 1991 Jun 25;266(18):11766-73 [2050676] Mol Carcinog. 1991;4(3):196-202 [2064725] Proc Natl Acad Sci U S A. 1991 Sep 1;88(17):7810-4 [1652764] Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9685-9 [1946387] Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):10124-8 [1946433] Biochemistry. 1991 Dec 24;30(51):11751-9 [1751492] Proc Natl Acad Sci U S A. 1992 Feb 15;89(4):1159-63 [1741372] Biochemistry. 1992 Apr 14;31(14):3671-81 [1567822] Proc Natl Acad Sci U S A. 1974 Sep;71(9):3363-6 [4530308] Mol Gen Genet. 1988 Nov;214(3):396-404 [3063945] Mol Cell Biol. 1988 Dec;8(12):5425-31 [3072480] Biochemistry. 1989 Jan 24;28(2):775-9 [2713344] Mol Cell Biol. 1989 Mar;9(3):1277-83 [2725498] Mutat Res. 1989 Sep;218(2):49-65 [2671706] J Biol Chem. 1989 Oct 25;264(30):18005-10 [2808361] Proc Natl Acad Sci U S A. 1989 Nov;86(22):8922-6 [2813430] Annu Rev Cell Biol. 1989;5:197-245 [2557059] Biochemistry. 1990 Feb 13;29(6):1624-32 [2185842] J Biol Chem. 1990 Oct 25;265(30):18043-6 [1976634] Mutat Res. 1992 Aug;274(2):135-45 [1378205] Biochemistry. 1992 Jul 28;31(29):6794-800 [1637815] Exp Cell Res. 1992 Aug;201(2):462-9 [1322318] Nucleic Acids Res. 1992 Oct 25;20(20):5403-6 [1359505] Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):11036-40 [1438310] J Mol Biol. 1977 Dec 15;117(3):525-67 [609095] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ly-GDI, a GDP-dissociation inhibitor of the RhoA GTP-binding protein, is expressed preferentially in lymphocytes. AN - 75904756; 8356058 AB - The Ras-related small GTP-binding proteins are involved in diverse cellular events, including cell signaling, proliferation, cytoskeletal organization, and secretion. The interconversion of the active, GTP-bound form of the protein to the inactive, GDP-bound form is influenced by two types of regulatory proteins, those that alter the intrinsic GTPase activity of the GTP-binding protein and those that affect the rate of GDP/GTP exchange. By utilizing a subtractive hybridization approach, we have isolated a human gene encoding Ly-GDI, a protein that has striking homology to the product of a previously cloned gene, Rho-GDI, which inhibits GDP/GTP exchange on the Rho family of GTPases. In contrast to Rho-GDI, which is ubiquitously expressed, Ly-GDI is expressed only in hematopoietic tissues and predominantly in B- and T-lymphocyte cell lines. The full-length Ly-GDI cDNA encodes a 27-kDa protein which binds to RhoA and inhibits GDP dissociation from RhoA. Stimulation of T lymphocytes with phorbol ester leads to phosphorylation of Ly-GDI, suggesting an involvement of Ly-GDI in lymphocyte activation pathways. Cell type-specific regulators of the Ras-like GTP-binding proteins may provide one mechanism by which different cell types respond uniquely to signals transduced through the same cell surface receptor or may provide a way by which the GTP-binding proteins can be uniquely engaged by tissue-restricted receptors. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Scherle, P AU - Behrens, T AU - Staudt, L M AD - Metabolism Branch, National Cancer Institute, Bethesda, MD 20892. Y1 - 1993/08/15/ PY - 1993 DA - 1993 Aug 15 SP - 7568 EP - 7572 VL - 90 IS - 16 SN - 0027-8424, 0027-8424 KW - ARHGDIB protein, human KW - 0 KW - Guanine Nucleotide Dissociation Inhibitors KW - Phosphates KW - Proteins KW - Tumor Suppressor Proteins KW - rho Guanine Nucleotide Dissociation Inhibitor beta KW - rho-Specific Guanine Nucleotide Dissociation Inhibitors KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - rhoA GTP-Binding Protein KW - EC 3.6.5.2 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Humans KW - Amino Acid Sequence KW - Plasmids KW - Proteins -- genetics KW - Cloning, Molecular KW - Lymphocyte Activation KW - Phosphates -- metabolism KW - Tumor Cells, Cultured KW - Kinetics KW - Molecular Sequence Data KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Sequence Homology, Amino Acid KW - Cell Line KW - Gene Library KW - Protein Biosynthesis KW - B-Lymphocytes -- drug effects KW - GTP-Binding Proteins -- antagonists & inhibitors KW - B-Lymphocytes -- immunology KW - T-Lymphocytes -- drug effects KW - B-Lymphocytes -- metabolism KW - T-Lymphocytes -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75904756?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Ly-GDI%2C+a+GDP-dissociation+inhibitor+of+the+RhoA+GTP-binding+protein%2C+is+expressed+preferentially+in+lymphocytes.&rft.au=Scherle%2C+P%3BBehrens%2C+T%3BStaudt%2C+L+M&rft.aulast=Scherle&rft.aufirst=P&rft.date=1993-08-15&rft.volume=90&rft.issue=16&rft.spage=7568&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 - 1993-09-23 N1 - Date created - 1993-09-23 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - L20688; GENBANK N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1990 Aug;87(15):5998-6002 [2116014] Proc Natl Acad Sci U S A. 1993 Feb 15;90(4):1479-83 [8434008] Cell. 1984 Jul;37(3):767-78 [6204768] Cell. 1986 Nov 7;47(3):401-12 [3094963] Nucleic Acids Res. 1987 Feb 25;15(4):1869 [3822842] Science. 1987 Oct 23;238(4826):542-5 [2821624] Oncogene. 1988 Aug;3(2):201-4 [3045729] Gene. 1988 Jul 15;67(1):31-40 [3047011] EMBO J. 1988 Aug;7(8):2465-73 [3056717] Science. 1989 Jan 20;243(4889):355-61 [2783497] J Biol Chem. 1989 Jul 25;264(21):12394-401 [2501306] Mol Cell Biol. 1989 May;9(5):2058-66 [2501657] J Biol Chem. 1989 Oct 5;264(28):16378-82 [2674130] Cell. 1990 Feb 9;60(3):375-86 [2302733] Science. 1990 Apr 6;248(4951):67-9 [2181667] Nucleic Acids Res. 1990 Mar 25;18(6):1587-93 [2326198] J Biol Chem. 1990 Jun 5;265(16):9373-80 [2111820] Mol Cell Biol. 1990 Aug;10(8):4116-22 [2115118] Science. 1990 Aug 10;249(4969):635-40 [2116664] Nature. 1990 Aug 23;346(6286):719-23 [2201921] Oncogene. 1990 Sep;5(9):1321-8 [2120668] Nature. 1990 Nov 8;348(6297):125-32 [2122258] Proc Natl Acad Sci U S A. 1990 Oct;87(20):8008-12 [2172971] Oncogene. 1991 Jan;6(1):119-24 [1899476] Oncogene. 1991 Apr;6(4):515-22 [1903193] Anal Biochem. 1991 Feb 1;192(2):262-7 [1852137] Cell. 1991 Jun 14;65(6):1033-42 [1904317] Biochem J. 1991 Jun 15;276 ( Pt 3):833-6 [1905930] J Immunol. 1991 Aug 15;147(4):1139-46 [1907989] Nature. 1991 Oct 17;353(6345):668-70 [1922386] Biochem Biophys Res Commun. 1992 Jan 31;182(2):921-30 [1734890] J Cell Biol. 1992 Mar;116(5):1211-20 [1346786] J Biol Chem. 1992 Mar 5;267(7):4289-91 [1537820] Am J Physiol. 1992 Apr;262(4 Pt 1):C916-26 [1566818] Cell. 1992 May 1;69(3):539-49 [1581965] Cell. 1992 Jul 24;70(2):351-64 [1638635] Nature. 1992 Jul 23;358(6384):351-4 [1379346] Cell. 1992 Aug 7;70(3):389-99 [1643657] Cell. 1992 Aug 7;70(3):401-10 [1643658] Nature. 1992 Sep 10;359(6391):153-4 [1522900] J Immunol. 1992 Oct 1;149(7):2271-80 [1388187] EMBO J. 1992 Dec;11(12):4549-56 [1425589] Science. 1992 Oct 30;258(5083):812-5 [1439791] Nature. 1983 Mar 3;302(5903):33-7 [6298635] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The N-terminal region of the 37-kDa translocated fragment of Pseudomonas exotoxin A aborts translocation by promoting its own export after microsomal membrane insertion. AN - 75902668; 8356083 AB - The 37-kDa C-terminal fragment of Pseudomonas exotoxin A (PE; termed PE37 and composed of aa 280-613 of PE) translocates to the cell cytosol to cause cell death. PE37 requires a C-terminal endoplasmic reticulum retention sequence to be cytotoxic, indicating that the toxin may translocate to the cytosol from the endoplasmic reticulum. We show here that the N-terminal region of nascent PE37 can be inserted into the membrane of canine pancreatic microsomes by the preprocecropin signal sequence but then is exported or released from microsomes. The 34 N-terminal amino acids of the toxin fragment are sufficient to arrest translocation and prevent the microsomal accumulation of nascent chains that otherwise are sequestered into microsomes. These data support a role for the N-terminal region of PE37 in the translocation of the toxin from the endoplasmic reticulum to the cytosol in mammalian cells. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Theuer, C P AU - Buchner, J AU - FitzGerald, D AU - Pastan, I AD - Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/08/15/ PY - 1993 DA - 1993 Aug 15 SP - 7774 EP - 7778 VL - 90 IS - 16 SN - 0027-8424, 0027-8424 KW - Bacterial Toxins KW - 0 KW - Exotoxins KW - Oligopeptides KW - Peptide Fragments KW - RNA, Messenger KW - Virulence Factors KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - toxA protein, Pseudomonas aeruginosa KW - EC 2.4.2.31 KW - Index Medicus KW - Endoplasmic Reticulum -- metabolism KW - Peptide Fragments -- metabolism KW - Protein Biosynthesis KW - Animals KW - Cytosol -- metabolism KW - Peptide Fragments -- toxicity KW - Amino Acid Sequence KW - Cell Death -- drug effects KW - Plasmids KW - Mutagenesis, Site-Directed KW - RNA, Messenger -- metabolism KW - Pancreas -- metabolism KW - Restriction Mapping KW - Polymerase Chain Reaction -- methods KW - Dogs KW - Molecular Sequence Data KW - Templates, Genetic KW - Pseudomonas aeruginosa -- metabolism KW - Exotoxins -- genetics KW - Microsomes -- metabolism KW - Exotoxins -- metabolism KW - Oligopeptides -- metabolism KW - Exotoxins -- toxicity KW - Oligopeptides -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75902668?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=The+N-terminal+region+of+the+37-kDa+translocated+fragment+of+Pseudomonas+exotoxin+A+aborts+translocation+by+promoting+its+own+export+after+microsomal+membrane+insertion.&rft.au=Theuer%2C+C+P%3BBuchner%2C+J%3BFitzGerald%2C+D%3BPastan%2C+I&rft.aulast=Theuer&rft.aufirst=C&rft.date=1993-08-15&rft.volume=90&rft.issue=16&rft.spage=7774&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 - 1993-09-23 N1 - Date created - 1993-09-23 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: FEBS Lett. 1991 Jul 22;285(2):182-8 [1855588] Science. 1991 May 24;252(5009):1171-3 [1851576] Science. 1991 Nov 22;254(5035):1173-7 [1683495] Annu Rev Biochem. 1992;61:331-54 [1497314] J Biol Chem. 1992 Aug 25;267(24):16872-7 [1512230] Science. 1992 Nov 6;258(5084):931-6 [1332192] J Biol Chem. 1992 Dec 5;267(34):24328-32 [1447183] J Biol Chem. 1992 Dec 15;267(35):25396-401 [1460035] J Urol. 1993 Jun;149(6):1626-32 [8501821] Nature. 1970 Aug 15;227(5259):680-5 [5432063] Proc Natl Acad Sci U S A. 1975 Jun;72(6):2284-8 [166383] J Cell Biol. 1975 Dec;67(3):835-51 [811671] Proc Natl Acad Sci U S A. 1977 Dec;74(12):5598-602 [271987] Proc Natl Acad Sci U S A. 1979 Apr;76(4):1795-9 [109833] J Biol Chem. 1979 Sep 25;254(18):9237-46 [479192] J Biol Chem. 1980 Apr 25;255(8):3600-4 [7364760] J Biol Chem. 1982 Jun 25;257(12):6796-801 [7085604] J Cell Biol. 1982 Nov;95(2 Pt 1):463-9 [6292235] J Cell Biol. 1982 Nov;95(2 Pt 1):470-7 [6292236] J Biol Chem. 1983 Aug 10;258(15):9488-95 [6348046] Methods Enzymol. 1983;96:94-111 [6656656] J Biol Chem. 1984 Sep 10;259(17):10700-4 [6206060] Proc Natl Acad Sci U S A. 1986 Feb;83(3):581-5 [3511473] Proc Natl Acad Sci U S A. 1986 Mar;83(5):1320-4 [3006045] J Cell Biol. 1986 Dec;103(6 Pt 1):2253-61 [3097028] Cell. 1987 Jan 16;48(1):129-36 [3098436] J Cell Biol. 1988 Apr;106(4):1093-104 [3283145] Infect Immun. 1988 Dec;56(12):3095-8 [2460407] J Biol Chem. 1988 Nov 15;263(32):17063-70 [3053702] J Biol Chem. 1989 Aug 25;264(24):14256-61 [2503515] Proc Natl Acad Sci U S A. 1990 Jan;87(1):308-12 [2104981] J Biol Chem. 1990 Nov 25;265(33):20678-85 [2122978] Cell. 1991 May 3;65(3):371-80 [1902142] J Biol Chem. 1991 Sep 15;266(26):17376-81 [1910044] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The N-terminal coiled-coil domain of beta is essential for gamma association: a model for G-protein beta gamma subunit interaction. AN - 75902559; 8356073 AB - We have identified the N terminus of the beta subunit as an essential domain for G-protein beta gamma assembly. A C-terminal fragment, beta 1-(130-340), fails to bind gamma unless coexpressed with the complementary N-terminal fragment, beta 1-(1-129). Deletion of the N-terminal 33 residues of beta 1, a region identified by computer algorithm to favor coiled-coil formation, abolishes gamma 2 association. On the basis of these findings, we propose a coiled-coil model of beta gamma interaction and refine this by computer-assisted molecular modeling. The model is tested by further mutagenesis: reversing the charge of residues in beta 1 that are hypothesized to be involved in interhelical salt bridges precludes gamma association. Insertions in the coiled-coil region, which disrupt the proposed hydrophobic interface, prevent gamma association. This structural basis for beta gamma dimerization provides a starting point for the design of beta and gamma mutants that can be used to map regions in beta gamma critical for interactions with the alpha subunit, receptors, and effectors. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Garritsen, A AU - van Galen, P J AU - Simonds, W F AD - Molecular Pathophysiology Branch, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/08/15/ PY - 1993 DA - 1993 Aug 15 SP - 7706 EP - 7710 VL - 90 IS - 16 SN - 0027-8424, 0027-8424 KW - DNA-Binding Proteins KW - 0 KW - Fungal Proteins KW - Macromolecular Substances KW - Peptide Fragments KW - Saccharomyces cerevisiae Proteins KW - Arginine KW - 94ZLA3W45F KW - Protein Kinases KW - EC 2.7.- KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - Index Medicus KW - Animals KW - Electrophoresis, Polyacrylamide Gel KW - Models, Molecular KW - Algorithms KW - Peptide Fragments -- isolation & purification KW - Amino Acid Sequence KW - Fungal Proteins -- chemistry KW - Mutagenesis, Site-Directed KW - Protein Kinases -- metabolism KW - Fungal Proteins -- metabolism KW - Transfection KW - Cell Line KW - Sequence Deletion KW - Protein Kinases -- chemistry KW - Protein Structure, Secondary KW - GTP-Binding Proteins -- metabolism KW - GTP-Binding Proteins -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75902559?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=The+N-terminal+coiled-coil+domain+of+beta+is+essential+for+gamma+association%3A+a+model+for+G-protein+beta+gamma+subunit+interaction.&rft.au=Garritsen%2C+A%3Bvan+Galen%2C+P+J%3BSimonds%2C+W+F&rft.aulast=Garritsen&rft.aufirst=A&rft.date=1993-08-15&rft.volume=90&rft.issue=16&rft.spage=7706&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 - 1993-09-23 N1 - Date created - 1993-09-23 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Biol Chem. 1992 Jul 15;267(20):13807-10 [1629181] Mol Biol Cell. 1992 Jan;3(1):49-61 [1550955] Curr Opin Genet Dev. 1992 Apr;2(2):205-10 [1638114] J Gen Physiol. 1992 Jun;99(6):961-83 [1640222] Nature. 1992 Jul 30;358(6385):424-6 [1322501] Science. 1992 Aug 28;257(5074):1264-7 [1325672] Cell. 1992 Sep 18;70(6):869-72 [1525824] Endocr Rev. 1992 Aug;13(3):536-65 [1425488] J Biol Chem. 1992 Nov 15;267(32):23409-17 [1429682] FEBS Lett. 1992 Dec 14;314(2):105-8 [1459238] EMBO J. 1992 Dec;11(13):4805-13 [1464310] Nature. 1992 Dec 17;360(6405):684-6 [1465133] Science. 1993 Feb 5;259(5096):832-4 [8094261] Cell. 1993 May 21;73(4):631-41 [8388779] J Biol Chem. 1951 Nov;193(1):265-75 [14907713] Nature. 1970 Aug 15;227(5259):680-5 [5432063] Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7 [271968] J Biol Chem. 1983 Sep 10;258(17):10503-10 [6136510] Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387-95 [6546423] Proc Natl Acad Sci U S A. 1984 Nov;81(22):6948-52 [6438626] Proc Natl Acad Sci U S A. 1986 Apr;83(7):2162-6 [3083416] Anal Biochem. 1986 Aug 15;157(1):144-53 [3532863] Proc Natl Acad Sci U S A. 1987 Jun;84(11):3623-7 [3108876] J Biol Chem. 1987 Oct 25;262(30):14683-8 [3117789] Methods Enzymol. 1987;155:335-50 [3431465] Cell. 1989 Feb 10;56(3):467-77 [2536595] Proteins. 1990;7(1):1-15 [2184436] J Biol Chem. 1990 Aug 5;265(22):12995-9 [2115886] J Biol Chem. 1991 Mar 5;266(7):4538-44 [1900295] J Biol Chem. 1991 Mar 25;266(9):5363-6 [1706334] Science. 1991 May 24;252(5009):1162-4 [2031185] Science. 1991 Oct 25;254(5031):539-44 [1948029] Cell. 1992 Feb 21;68(4):699-708 [1739975] Biochemistry. 1992 Mar 24;31(11):2905-11 [1550816] Proc Natl Acad Sci U S A. 1992 Jul 1;89(13):6220-4 [1631113] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A recombinant immunotoxin containing a disulfide-stabilized Fv fragment. AN - 75895989; 8356052 AB - B3(dsFv)-PE38KDEL is a recombinant immunotoxin composed of the Fv region of monoclonal antibody B3 connected to a truncated form of Pseudomonas exotoxin (PE38KDEL), in which the unstable Fv heterodimer (composed of heavy- and light-chain variable regions) is held together and stabilized by a disulfide bond [termed disulfide-stabilized Fv (dsFV)]. A computer modeled structure of the B3(Fv), made by mutating and energy minimizing the amino acid sequence and structure of McPC603, enabled us to identify positions in conserved framework regions that "hypothetically" could be used for disulfide stabilization without changing the structure or affecting antigen binding. This prediction was evaluated experimentally by constructing a disulfide-linked two-chain dsFv-immunotoxin that was produced in Escherichia coli. The activity and specificity of this immunotoxin was indistinguishable from its single-chain Fv (scFv) counterpart, indicating that, as in B3(scFv), the structure of the binding region is retained in B3(dsFv). Because we introduced the stabilizing disulfide bond in between two framework residues in a position that is conserved in most Fv molecules, this method of linkage between the heavy- and light-chain variable regions should be generally applicable to construct immunotoxins and dsFv molecules using other antibodies. Furthermore, the finding that B3(dsFv) was much more stable at 37 degrees C in human plasma than B3(scFv) indicates that dsFvs are possibly more versatile for therapeutic application than scFvs. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Brinkmann, U AU - Reiter, Y AU - Jung, S H AU - Lee, B AU - Pastan, I AD - Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/08/15/ PY - 1993 DA - 1993 Aug 15 SP - 7538 EP - 7542 VL - 90 IS - 16 SN - 0027-8424, 0027-8424 KW - Antibodies, Monoclonal KW - 0 KW - Bacterial Toxins KW - Disulfides KW - Exotoxins KW - Immunotoxins KW - Macromolecular Substances KW - Oligodeoxyribonucleotides KW - Recombinant Proteins KW - Virulence Factors KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - toxA protein, Pseudomonas aeruginosa KW - EC 2.4.2.31 KW - Index Medicus KW - Drug Stability KW - Computer Simulation KW - Recombinant Proteins -- biosynthesis KW - Humans KW - Cloning, Molecular KW - Recombinant Proteins -- toxicity KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Disulfides -- analysis KW - Tumor Cells, Cultured KW - Cell Survival -- drug effects KW - Restriction Mapping KW - Molecular Sequence Data KW - Recombinant Proteins -- chemistry KW - Pseudomonas aeruginosa KW - Cell Line KW - Antibodies, Monoclonal -- biosynthesis KW - Immunotoxins -- toxicity KW - Immunotoxins -- biosynthesis KW - Exotoxins -- chemistry KW - Antibodies, Monoclonal -- chemistry KW - Immunotoxins -- chemistry KW - Antibodies, Monoclonal -- toxicity KW - Exotoxins -- biosynthesis KW - Exotoxins -- toxicity KW - Protein Conformation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75895989?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+recombinant+immunotoxin+containing+a+disulfide-stabilized+Fv+fragment.&rft.au=Brinkmann%2C+U%3BReiter%2C+Y%3BJung%2C+S+H%3BLee%2C+B%3BPastan%2C+I&rft.aulast=Brinkmann&rft.aufirst=U&rft.date=1993-08-15&rft.volume=90&rft.issue=16&rft.spage=7538&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 - 1993-09-23 N1 - Date created - 1993-09-23 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1985 Jan;82(2):488-92 [3881765] J Immunol. 1993 Apr 1;150(7):2774-82 [8454854] Cell. 1987 Jan 16;48(1):129-36 [3098436] Proc Natl Acad Sci U S A. 1988 Aug;85(16):5879-83 [3045807] Science. 1988 Oct 21;242(4877):423-6 [3140379] Nature. 1989 Jun 1;339(6223):394-7 [2498664] Proc Natl Acad Sci U S A. 1990 Feb;87(3):1066-70 [2105495] Biochemistry. 1990 Feb 13;29(6):1362-7 [2110478] Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3358-62 [2014255] Cancer Res. 1991 Jul 15;51(14):3781-7 [1648444] Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8616-20 [1924323] Biochemistry. 1991 Oct 22;30(42):10117-25 [1931943] Cancer Res. 1991 Dec 1;51(23 Pt 1):6363-71 [1933899] Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):10134-7 [1719545] Science. 1991 Nov 22;254(5035):1173-7 [1683495] Cancer Res. 1992 Jun 15;52(12):3402-8 [1596900] Proc Natl Acad Sci U S A. 1992 Jul 1;89(13):5867-71 [1352878] Anal Biochem. 1992 Sep;205(2):263-70 [1332541] Biotechniques. 1993 Feb;14(2):256-65 [8431292] J Mol Biol. 1986 Aug 20;190(4):593-604 [3097327] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Polyamine-like actions of peptides derived from conantokin-G, an N-methyl-D-aspartate (NMDA) antagonist. AN - 75889957; 8349604 AB - Conantokins-T and -G are highly conserved polypeptides derived from Conus venoms. The N-methyl-D-aspartate (NMDA) antagonist properties of these compounds have been attributed to a potent noncompetitive inhibition of polyamine responses. Substitution of the highly conserved gamma-carboxyglutamate residues as well as modification of the N and C termini of conantokin-G abolished the inhibition of polyamine responses at the NMDA receptor complex. However, several of these modified polypeptides closely mimicked the neurochemical profile of polyamines at the NMDA receptor complex. One of these derivatives, Tyr0-conantokin-G, was found to be the most potent compound exhibiting polyamine-like actions at the NMDA receptor complex described to date, approximately 7-fold more potent than spermine. Circular dichroism studies demonstrate a significant alpha-helical content in conantokin-G (27% in aqueous medium). However, this alpha-helicity is not sufficient for the NMDA antagonist action of the parent peptide and is neither necessary nor sufficient for the polyamine-like behavior of several conantokin-G analogs. The modified conantokin-G derivatives described in this report should be useful probes for examining the role of both polyamines and the polyamine recognition site in the operation of the NMDA receptor complex. JF - The Journal of biological chemistry AU - Chandler, P AU - Pennington, M AU - Maccecchini, M L AU - Nashed, N T AU - Skolnick, P AD - Laboratory of Neuroscience, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/08/15/ PY - 1993 DA - 1993 Aug 15 SP - 17173 EP - 17178 VL - 268 IS - 23 SN - 0021-9258, 0021-9258 KW - Biguanides KW - 0 KW - Conotoxins KW - Peptides, Cyclic KW - Polyamines KW - Spermine KW - 2FZ7Y3VOQX KW - arcaine KW - 544-05-8 KW - N-Methylaspartate KW - 6384-92-5 KW - conotoxin GV KW - 93438-65-4 KW - Magnesium KW - I38ZP9992A KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Spermine -- antagonists & inhibitors KW - Molecular Sequence Data KW - Magnesium -- pharmacology KW - Circular Dichroism KW - Amino Acid Sequence KW - Biguanides -- pharmacology KW - Male KW - Polyamines -- pharmacology KW - N-Methylaspartate -- antagonists & inhibitors KW - Peptides, Cyclic -- chemistry KW - Peptides, Cyclic -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75889957?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Polyamine-like+actions+of+peptides+derived+from+conantokin-G%2C+an+N-methyl-D-aspartate+%28NMDA%29+antagonist.&rft.au=Chandler%2C+P%3BPennington%2C+M%3BMaccecchini%2C+M+L%3BNashed%2C+N+T%3BSkolnick%2C+P&rft.aulast=Chandler&rft.aufirst=P&rft.date=1993-08-15&rft.volume=268&rft.issue=23&rft.spage=17173&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 - 1993-09-15 N1 - Date created - 1993-09-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characterization of two allelic variants of a human pregnancy-specific glycoprotein gene. AN - 75879194; 8349632 AB - The pregnancy-specific glycoproteins (PSGs) of the human placenta are a group of proteins that together with the carcinoembryonic antigens comprise a subfamily within the immunoglobulin superfamily. To study the control of PSG expression, we isolated and characterized PSG genes and identified cis-acting DNA elements in the 5'-flanking gene regions essential for PSG expression. Two overlapping PSG cosmid clones, which contain two allelic variants of a PSG gene (PSG12 and PSG12 psi), were isolated from an unamplified library made from a single individual. Cosmid 1 contains exons 1 (5'/L) and 2 (L/N) of the PSG12 gene located downstream of a previously identified PSG1-I gene. Cosmid 6 contains a portion of the PSG1-I gene lacking exons 1 and 2 upstream of a complete PSG12 psi transcription unit. Sequence comparison indicates that exons 5'/L and L/N in PSG12 and PSG12 psi are 99% identical, except that the L/N exon in the PSG12 psi gene contains a stop codon. Both PSG12 and PSG12 psi transcripts were detected in the human placenta, indicating that both genes are actively transcribed. However, the PSG12 psi gene may represent an allelic pseudogene variant of the PSG12 gene, because all identified PSGs contain a functional N-domain. Primer extension analysis showed that the PSG12 gene starts at a cluster of sites located at -106 to -104 base pairs with respect to the translation start site. In transient transfection assays using a chloramphenicol acetyltransferase reporter gene, we demonstrated that the -835 to -34 DNA region upstream of the translation start site of PSG12 or PSG12 psi contained both positive and negative elements that control PSG expression. Deletion analysis showed that nucleotides -172 to -34 in the PSG12 gene could function as a promoter. Gel retardation analysis showed that protein factors in human placental cell extract formed four complexes (I, II, IIa, and III) with the PSG12(-172/-34) DNA. Site-directed mutagenesis that prevents protein factor binding to the PSG12 promoter resulted in a marked reduction in transcription activation, locating the core enhancers at nucleotides -148 to -141 and -60 to -55. Mutagenesis studies also showed that the ACAGC repeats at nucleotides -84 to -68 in the PSG12 5'-flanking are essential for expression of the PSG12 gene in human placental cells. JF - The Journal of biological chemistry AU - Lei, K J AU - Wang, C AU - Chamberlin, M E AU - Liu, J L AU - Pan, C J AU - Chou, J Y AD - Human Genetics Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/08/15/ PY - 1993 DA - 1993 Aug 15 SP - 17528 EP - 17538 VL - 268 IS - 23 SN - 0021-9258, 0021-9258 KW - Glycoproteins KW - 0 KW - Pregnancy Proteins KW - Pregnancy-Specific beta 1-Glycoproteins KW - RNA Caps KW - pregnancy-specific beta-1-glycoprotein 12 KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Pseudogenes KW - Sequence Homology, Nucleic Acid KW - Humans KW - Transcription, Genetic KW - Amino Acid Sequence KW - Alleles KW - Base Sequence KW - Promoter Regions, Genetic KW - Restriction Mapping KW - Molecular Sequence Data KW - Placenta -- metabolism KW - Genetic Variation KW - Glycoproteins -- biosynthesis KW - Pregnancy Proteins -- genetics KW - Glycoproteins -- genetics KW - Pregnancy Proteins -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75879194?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Characterization+of+two+allelic+variants+of+a+human+pregnancy-specific+glycoprotein+gene.&rft.au=Lei%2C+K+J%3BWang%2C+C%3BChamberlin%2C+M+E%3BLiu%2C+J+L%3BPan%2C+C+J%3BChou%2C+J+Y&rft.aulast=Lei&rft.aufirst=K&rft.date=1993-08-15&rft.volume=268&rft.issue=23&rft.spage=17528&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 - 1993-09-15 N1 - Date created - 1993-09-15 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - L14723; GENBANK; L14724; L14725; L14726; L14727; L14728; M62717; L14729 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Orientation of cholera toxin bound to target cells. AN - 75876647; 8349592 AB - Cholera toxin (CT) consists of a pentameric B subunit that binds to specific cell surface receptors identified as ganglioside GM1 and an A subunit that activates adenylylcyclase. The A subunit consists of A1 and A2 peptides linked by a disulfide bond; A2 acts to connect A to B, whereas A1 is an ADP-ribosyltransferase that modifies the alpha subunit of the stimulatory G protein (Gs). How the toxin is oriented when it binds to the cell surface and the related issue of the mechanism by which A1 gains access to Gs alpha are not known. In the present study, we used subunit-specific antibodies and their corresponding Fab fragments to assess their affects on holotoxin binding to target cells and their immunoreactivity to cell-bound toxin. Our results suggest that CT binds with A1 facing away from the membrane. Our hypothesis is further supported by the ability to assemble active CT on the cell surface of cultured human intestinal and neurotumor cells by the sequential addition of purified B and A subunits. We also observed that when cells containing bound CT were incubated at 37 degrees C, both subunits rapidly became inaccessible to their respective antibodies. We propose that the holotoxin binds with its A subunit facing away from the membrane and must enter the cell in order for A1 to be released, gain access to Gs alpha, and activate adenylylcyclase. JF - The Journal of biological chemistry AU - Orlandi, P A AU - Fishman, P H AD - Membrane Biochemistry Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/08/15/ PY - 1993 DA - 1993 Aug 15 SP - 17038 EP - 17044 VL - 268 IS - 23 SN - 0021-9258, 0021-9258 KW - Immune Sera KW - 0 KW - Immunoglobulin Fab Fragments KW - Cholera Toxin KW - 9012-63-9 KW - Index Medicus KW - Tumor Cells, Cultured KW - Kinetics KW - Humans KW - Temperature KW - Immune Sera -- immunology KW - Immunoglobulin Fab Fragments -- immunology KW - Cell Membrane -- metabolism KW - Cell Line KW - Protein Conformation KW - Cholera Toxin -- immunology KW - Cholera Toxin -- chemistry KW - Cholera Toxin -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75876647?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Orientation+of+cholera+toxin+bound+to+target+cells.&rft.au=Orlandi%2C+P+A%3BFishman%2C+P+H&rft.aulast=Orlandi&rft.aufirst=P&rft.date=1993-08-15&rft.volume=268&rft.issue=23&rft.spage=17038&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 - 1993-09-15 N1 - Date created - 1993-09-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of the major phosphorylation sites of the Raf-1 kinase. AN - 75874564; 8349614 AB - Treatment of cells with various growth factors and mitogens results in the rapid hyperphosphorylation and activation of the Raf-1 kinase. To determine if phosphorylation events affect Raf-1 activity, we have initiated experiments to identify the phosphorylation sites of Raf-1. In this report, we find that Ser43, Ser259, and Ser621 are the major sites of Raf-1 which are phosphorylated in mammalian cells and in Sf9 insect cells infected with a recombinant baculovirus encoding human Raf-1. Mutant Raf-1 proteins lacking kinase activity are also phosphorylated on these sites in vivo, indicating that these phosphorylation events are not a consequence of autophosphorylation. Furthermore, we find that Thr268 is the predominant Raf-1 residue phosphorylated in in vitro autokinase assays. In addition, we have examined the biochemical activity of baculovirus-expressed Raf-1 proteins containing mutations at these phosphorylation sites. In in vitro protein kinase assays Ser259 mutant proteins were 2-fold more active than wild-type Raf-1 and Ser621 mutant proteins were inactive as kinases. Analysis of the residues surrounding Ser259 and Ser621 indicates that RSXSXP may be a consensus sequence for the kinase responsible for phosphorylation of Raf-1 at these sites. Interestingly, these RSXSXP sequences are completely conserved throughout evolution in all Raf family members. JF - The Journal of biological chemistry AU - Morrison, D K AU - Heidecker, G AU - Rapp, U R AU - Copeland, T D AD - ABL-Basic Research Program, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland 21702. Y1 - 1993/08/15/ PY - 1993 DA - 1993 Aug 15 SP - 17309 EP - 17316 VL - 268 IS - 23 SN - 0021-9258, 0021-9258 KW - Proto-Oncogene Proteins KW - 0 KW - Serine KW - 452VLY9402 KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - Proto-Oncogene Proteins c-raf KW - Index Medicus KW - 3T3 Cells KW - Animals KW - Humans KW - Amino Acid Sequence KW - Mice KW - Moths KW - Serine -- metabolism KW - Chromatography, High Pressure Liquid KW - Cloning, Molecular KW - Rats KW - Mutagenesis, Site-Directed KW - Baculoviridae KW - Phosphorylation KW - Electrophoresis, Gel, Two-Dimensional KW - Molecular Sequence Data KW - Cell Line KW - Protein-Serine-Threonine Kinases -- metabolism KW - Proto-Oncogene Proteins -- metabolism KW - Protein-Serine-Threonine Kinases -- genetics KW - Proto-Oncogene Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75874564?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Identification+of+the+major+phosphorylation+sites+of+the+Raf-1+kinase.&rft.au=Morrison%2C+D+K%3BHeidecker%2C+G%3BRapp%2C+U+R%3BCopeland%2C+T+D&rft.aulast=Morrison&rft.aufirst=D&rft.date=1993-08-15&rft.volume=268&rft.issue=23&rft.spage=17309&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 - 1993-09-15 N1 - Date created - 1993-09-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - 'Cold SSCP': a simple, rapid and non-radioactive method for optimized single-strand conformation polymorphism analyses. AN - 75930426; 8367279 AB - A rapid (< 2.5 hrs) method for single-strand conformation polymorphism (SSCP) analysis of PCR products that allows the use of ethidium bromide staining is described. PCR products ranging in size from 117 to 256 bp were evaluated for point mutations and polymorphisms by 'cold SSCP' in commercially available pre-cast polyacrylamide mini-gels. Several electrophoretic parameters (running temperature, buffers, denaturants, DNA concentration, and gel polyacrylamide concentration) were found to influence the degree of strand separation and appeared to be PCR fragment specific. Use of the 'cold' SSCP technique and the mini-gel format allowed us to readily optimize the electrophoretic conditions for each PCR fragment. This greatly increased our ability to detect polymorphisms compared to conventional, radioisotope-labeled 'hot' SSCP, typically run under two standard temperature conditions. Excellent results have been obtained in resolving mutant PCR fragments from human p53 exons 5 through 8, human HLA-DQA, human K-ras exons 1 and 2, and rat K-ras exon 3. Polymorphisms could be detected when mutant DNA comprised as little as 3% of the total gene copies in a PCR mixture. Compared to standard 'hot' SSCP, this novel non-isotopic method has additional advantages of dramatically increased speed, precise temperature control, reproducibility, and easily and inexpensively obtainable reagents and equipment. This new method also lacks the safety and hazardous waste management concerns associated with radioactive methods. JF - Nucleic acids research AU - Hongyo, T AU - Buzard, G S AU - Calvert, R J AU - Weghorst, C M AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick, MD. Y1 - 1993/08/11/ PY - 1993 DA - 1993 Aug 11 SP - 3637 EP - 3642 VL - 21 IS - 16 SN - 0305-1048, 0305-1048 KW - Buffers KW - 0 KW - DNA, Single-Stranded KW - Index Medicus KW - Rats KW - Genes, ras KW - Animals KW - Nucleic Acid Denaturation KW - Genes, p53 KW - Electrophoresis, Polyacrylamide Gel KW - Humans KW - Temperature KW - Indicator Dilution Techniques KW - Nucleic Acid Conformation KW - Cell Line KW - Polymorphism, Genetic KW - DNA, Single-Stranded -- analysis KW - Polymerase Chain Reaction -- methods KW - DNA, Single-Stranded -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75930426?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nucleic+acids+research&rft.atitle=%27Cold+SSCP%27%3A+a+simple%2C+rapid+and+non-radioactive+method+for+optimized+single-strand+conformation+polymorphism+analyses.&rft.au=Hongyo%2C+T%3BBuzard%2C+G+S%3BCalvert%2C+R+J%3BWeghorst%2C+C+M&rft.aulast=Hongyo&rft.aufirst=T&rft.date=1993-08-11&rft.volume=21&rft.issue=16&rft.spage=3637&rft.isbn=&rft.btitle=&rft.title=Nucleic+acids+research&rft.issn=03051048&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-10-01 N1 - Date created - 1993-10-01 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Genomics. 1989 Nov;5(4):874-9 [2687159] Hum Mutat. 1992;1(2):91-6 [1301206] Nucleic Acids Res. 1991 May 11;19(9):2500 [2041788] Nucleic Acids Res. 1991 Jun 11;19(11):3154 [2057373] Nature. 1991 Jul 4;352(6330):77-9 [2062380] Biochem Biophys Res Commun. 1991 Oct 15;180(1):380-5 [1656975] Nucleic Acids Res. 1992 Jan 11;20(1):145 [1738597] Nature. 1992 Feb 6;355(6360):548-51 [1346925] Nucleic Acids Res. 1992 Feb 25;20(4):871-8 [1371869] Trends Genet. 1992 Feb;8(2):49 [1373540] Biochem Biophys Res Commun. 1992 Apr 15;184(1):73-9 [1373618] Mol Cell Probes. 1992 Oct;6(5):357-9 [1282203] Hum Genet. 1992 Nov;90(3):303-4 [1283151] PCR Methods Appl. 1992 Aug;2(1):10-3 [1490170] Lab Invest. 1993 Mar;68(3):361-6 [8450652] Cell. 1993 Mar 26;72(6):971-83 [8458085] Hum Genet. 1993 Mar;91(2):151-6 [8385067] Hum Genet. 1993 Mar;91(2):163-8 [8462975] Nucleic Acids Res. 1991 Jan 25;19(2):405-6 [2014179] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cloning, sequencing, and mutation of thiol-specific antioxidant gene of Saccharomyces cerevisiae. AN - 75892723; 8344960 AB - We have previously shown that the yeast Saccharomyces cerevisiae contains an antioxidant enzyme that can provide protection against a thiol-containing oxidation system but not against an oxidation system without thiol. This 25-kDa enzyme was thus named thiol-specific antioxidant (TSA). We have now isolated and sequenced a yeast genomic DNA fragment that encodes TSA. Comparison of the predicted amino acid sequence of TSA with those of conventional antioxidant enzymes, including catalases, peroxidases, and superoxide dismutases, revealed no sequence homology. The 195-amino acid TSA sequence contains 2 cysteine residues. Southern blot analysis of petite yeast DNA, studies with protein synthesis inhibitors, and protein immunoblot analyses of cytosolic and mitochondrial proteins suggest that TSA is a cytosolic protein encoded by nuclear DNA (chromosome XIII). The yeast TSA gene was selectively disrupted by homologous recombination. The haploid tsa mutant was viable under air, suggesting that TSA is not essential for cell viability. The growth rates of the tsa mutant and wild-type strains were identical under anaerobic conditions. However, under aerobic conditions, especially in the presence of methyl viologen or a peroxide (t-butyl hydroperoxide or H2O2), the growth rate of the mutant was significantly less than that of wild-type cells. This result suggests that TSA is a physiologically important antioxidant. JF - The Journal of biological chemistry AU - Chae, H Z AU - Kim, I H AU - Kim, K AU - Rhee, S G AD - Laboratory of Biochemistry, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/08/05/ PY - 1993 DA - 1993 Aug 05 SP - 16815 EP - 16821 VL - 268 IS - 22 SN - 0021-9258, 0021-9258 KW - TSA KW - Antioxidants KW - 0 KW - DNA, Fungal KW - Fungal Proteins KW - Chloramphenicol KW - 66974FR9Q1 KW - Peroxidases KW - EC 1.11.1.- KW - Peroxiredoxins KW - EC 1.11.1.15 KW - Index Medicus KW - Immunoblotting KW - Base Sequence KW - Blotting, Northern KW - Blotting, Southern KW - Kinetics KW - Restriction Mapping KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Mutagenesis KW - Cloning, Molecular KW - Saccharomyces cerevisiae -- genetics KW - Genes, Fungal KW - Saccharomyces cerevisiae -- growth & development KW - Saccharomyces cerevisiae -- enzymology KW - Fungal Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75892723?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cloning%2C+sequencing%2C+and+mutation+of+thiol-specific+antioxidant+gene+of+Saccharomyces+cerevisiae.&rft.au=Chae%2C+H+Z%3BKim%2C+I+H%3BKim%2C+K%3BRhee%2C+S+G&rft.aulast=Chae&rft.aufirst=H&rft.date=1993-08-05&rft.volume=268&rft.issue=22&rft.spage=16815&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 - 1993-09-07 N1 - Date created - 1993-09-07 N1 - Date revised - 2017-01-13 N1 - Gene symbol - TSA N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Specific glycosylation site mutations of the insulin receptor alpha subunit impair intracellular transport. AN - 75907069; 8347587 AB - The insulin receptor is a transmembrane protein found on multiple cell types. This receptor is synthesized as a 190-kDa proreceptor which is cleaved to produce mature alpha and beta subunits. The proreceptor contains 18 potential sites for N-linked glycosylation: 14 on the alpha subunit and 4 on the beta subunit. The codons for asparagine in the first four sites at the amino terminus of the alpha subunit were mutated to code for glutamine. This mutant receptor cDNA was stably transfected into NIH 3T3 cells. The insulin receptor produced in these cells remained in the proreceptor form; no mature alpha and beta subunits were produced. The proreceptor was slightly smaller on SDS-PAGE gels than the wild-type proreceptor and contained four less oligosaccharide chains by tryptic peptide mapping. The carbohydrate chains on the mutant proreceptor remained endoglycosidase H sensitive. However, in the presence of brefeldin A, these oligosaccharide chains could be processed to endoglycosidase H resistant chains. By immunofluorescence, the mutant proreceptor was shown to be localized to the endoplasmic reticulum. No insulin receptors could be found on the cell-surface either with cell surface labeling with biotin or with 125I-insulin binding. Thus, glycosylation of the first four N-linked glycosylation sites of the insulin receptor is necessary for the proper processing and intracellular transport of the receptor. This is in contrast to glycosylation at the four sites on the beta subunit which appear not to be important for processing but necessary for signal transduction. Therefore, N-linked glycosylation of the insulin receptor at specific sites has multiple distinctive roles. JF - Biochemistry AU - Collier, E AU - Carpentier, J L AU - Beitz, L AU - Carol, H AU - Taylor, S I AU - Gorden, P AD - Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/08/03/ PY - 1993 DA - 1993 Aug 03 SP - 7818 EP - 7823 VL - 32 IS - 30 SN - 0006-2960, 0006-2960 KW - Insulin KW - 0 KW - Glutamine KW - 0RH81L854J KW - Asparagine KW - 7006-34-0 KW - DNA KW - 9007-49-2 KW - Receptor, Insulin KW - EC 2.7.10.1 KW - Index Medicus KW - 3T3 Cells KW - Animals KW - Peptide Mapping KW - Electrophoresis, Polyacrylamide Gel KW - Glutamine -- metabolism KW - Humans KW - Asparagine -- metabolism KW - Biological Transport KW - Insulin -- metabolism KW - Mice KW - Glycosylation KW - Mutagenesis, Site-Directed KW - Transfection KW - Fluorescent Antibody Technique KW - Receptor, Insulin -- genetics KW - Receptor, Insulin -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75907069?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Specific+glycosylation+site+mutations+of+the+insulin+receptor+alpha+subunit+impair+intracellular+transport.&rft.au=Collier%2C+E%3BCarpentier%2C+J+L%3BBeitz%2C+L%3BCarol%2C+H%3BTaylor%2C+S+I%3BGorden%2C+P&rft.aulast=Collier&rft.aufirst=E&rft.date=1993-08-03&rft.volume=32&rft.issue=30&rft.spage=7818&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-09-10 N1 - Date created - 1993-09-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nephrotoxicity and hydration management for cisplatin, carboplatin, and ormaplatin. AN - 85256329; pmid-8375728 AB - Renal toxicity is a prominent component of the toxicity profile of platinum-based chemotherapy. Kidney damage, once dose limiting for cisplatin, occurs in some patients who receive carboplatin and may occur with the third-generation platinum analog ormaplatin. Herein, we review what is known about the pathophysiology of therapy-induced renal toxicity for each of these agents and what is known about appropriate maneuvers to circumvent this toxicity. For cisplatin, hydration is always indicated and mannitol may be useful in selected settings. Furosemide is probably not generally useful. For carboplatin, hydration is important for patients with impaired renal function and for patients receiving high doses of drug (> or = 800 mg/m2). For ormplatin, renal toxicity appears not be prominent when hydration is administered in a fashion similar to cisplatin hydration. Detailed suggestions regarding the protection of kidney function when using these compounds are presented. JF - Gynecologic Oncology AU - Cornelison, T L AU - Reed, E AD - Medicine Branch, National Cancer Institute, Bethesda, Maryland 20892. PY - 1993 SP - 147 EP - 158 VL - 50 IS - 2 SN - 0090-8258, 0090-8258 KW - Cisplatin KW - Antineoplastic Agents KW - Mannitol KW - Human KW - Animal KW - Kidney KW - Organoplatinum Compounds KW - Saline Solution, Hypertonic KW - Carboplatin KW - Furosemide KW - Fluid Therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85256329?accountid=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=Gynecologic+Oncology&rft.atitle=Nephrotoxicity+and+hydration+management+for+cisplatin%2C+carboplatin%2C+and+ormaplatin.&rft.au=Cornelison%2C+T+L%3BReed%2C+E&rft.aulast=Cornelison&rft.aufirst=T&rft.date=1993-08-01&rft.volume=50&rft.issue=2&rft.spage=147&rft.isbn=&rft.btitle=&rft.title=Gynecologic+Oncology&rft.issn=00908258&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Memory in patients with cerebellar degeneration. AN - 85162918; pmid-8351008 AB - Eleven patients with relatively selective cerebellar degeneration and 11 normal control subjects underwent a comprehensive neurologic and neuropsychological examination. The neuropsychological tests assessed general intellectual ability, different aspects of memory (effortful, automatic, and implicit memory processes), speed of information processing, and verbal fluency (using both category and letter fluency tasks). The results indicated that cerebellar patients were significantly impaired only on tasks requiring the use of executive functions, such as the initiation/perseveration subtest of the Mattis Dementia Rating Scale or the fluency tests, and on memory measures requiring greater processing effort. They performed normally on automatic and implicit measures of memory. Performance on the effortful memory and executive measures was not associated with neurologic variables or mood state. After controlling for the initiation/perseveration deficit, the effortful memory scores of the cerebellar patients were no longer different from those of controls. The present study suggests that memory in patients with relatively pure cerebellar dysfunction is only partially compromised and that the impairment is secondary to a deficit in executive functions. JF - Neurology AU - Appollonio, I M AU - Grafman, J AU - Schwartz, V AU - Massaquoi, S AU - Hallett, M AD - Cognitive Neuroscience Section, NINDS, NIH, Bethesda, MD 20892. PY - 1993 SP - 1536 EP - 1544 VL - 43 IS - 8 SN - 0028-3878, 0028-3878 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85162918?accountid=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=Neurology&rft.atitle=Memory+in+patients+with+cerebellar+degeneration.&rft.au=Appollonio%2C+I+M%3BGrafman%2C+J%3BSchwartz%2C+V%3BMassaquoi%2C+S%3BHallett%2C+M&rft.aulast=Appollonio&rft.aufirst=I&rft.date=1993-08-01&rft.volume=43&rft.issue=8&rft.spage=1536&rft.isbn=&rft.btitle=&rft.title=Neurology&rft.issn=00283878&rft_id=info:doi/ LA - English DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Conformationally constrained analogues of diacylglycerol (DAG)--II. Differential interaction of delta-lactones and gamma-lactones with protein kinase C (PK-C). AN - 76306851; 8081841 AB - Starting with L- or D-tri-O-acetylglucal, the corresponding L- and D-isomers of 4-O-tetradecanoyl-2,3-dideoxyglucono-1,5-lactone (2a and 2b) were synthesized as rigid diacylglycerol (DAG) analogues. Consistent with results obtained previously with the equivalent L- and D-1,4-lactones (1a and 1b), the L-isomer (2a) was more potent in activating protein kinase C (PK-C) and inhibiting the binding of [3H]phorbol-12,13-dibutyrate to the enzyme's regulatory domain. In these experiments the difference in potency observed between the optical antipodes of the gluconolactones (2a and 2b) was greatly increased relative to the corresponding ribonolactones (1a and 1b). These results indicate that PK-C is more able to discriminate between optical antipodes, in favor of the L-isomer, as the lactone ring increases from five to six. JF - Bioorganic & medicinal chemistry AU - Lee, J AU - Marquez, V E AU - Blumberg, P M AU - Krausz, K W AU - Kazanietz, M G AD - Laboratory of Medicinal Chemistry, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/08// PY - 1993 DA - August 1993 SP - 119 EP - 123 VL - 1 IS - 2 SN - 0968-0896, 0968-0896 KW - Diglycerides KW - 0 KW - Myristates KW - Pyrones KW - 4-O-tetradecanoyl-2,3-dideoxyglucono-1,5-lactone KW - 153764-21-7 KW - Phorbol 12,13-Dibutyrate KW - 37558-16-0 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Index Medicus KW - Stereoisomerism KW - Phosphorylation KW - Enzyme Activation KW - Kinetics KW - Chromatography, Thin Layer KW - Magnetic Resonance Spectroscopy KW - Binding Sites KW - Pyrones -- pharmacology KW - Protein Kinase C -- metabolism KW - Diglycerides -- chemistry KW - Myristates -- chemistry KW - Diglycerides -- pharmacology KW - Myristates -- metabolism KW - Phorbol 12,13-Dibutyrate -- metabolism KW - Myristates -- pharmacology KW - Pyrones -- chemistry KW - Pyrones -- metabolism KW - Diglycerides -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76306851?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Bioorganic+%26+medicinal+chemistry&rft.atitle=Conformationally+constrained+analogues+of+diacylglycerol+%28DAG%29--II.+Differential+interaction+of+delta-lactones+and+gamma-lactones+with+protein+kinase+C+%28PK-C%29.&rft.au=Lee%2C+J%3BMarquez%2C+V+E%3BBlumberg%2C+P+M%3BKrausz%2C+K+W%3BKazanietz%2C+M+G&rft.aulast=Lee&rft.aufirst=J&rft.date=1993-08-01&rft.volume=1&rft.issue=2&rft.spage=119&rft.isbn=&rft.btitle=&rft.title=Bioorganic+%26+medicinal+chemistry&rft.issn=09680896&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-10-13 N1 - Date created - 1994-10-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Seizures associated with antidepressants: a review. AN - 76115870; 8253696 AB - Seizures are uncommon, but serious, adverse effects of antidepressant drugs. A better understanding of drug-related seizure risk, its predictors, and its neurophysiologic basis might help clinicians avoid this adverse event. A better understanding of the factors involved in the determination of seizure risk would be helpful for interpretation of seizure rates reported. The authors review case reports, series of cases, and information from clinical trials of antidepressants to determine antidepressant-related seizure risk. Predisposing factors are identified. Effects of dose, blood levels, and duration of treatment on seizure risk are examined. Electrophysiologic and in vitro models of drug-related seizure induction are discussed. A significant proportion of drug-related seizures occurs in individuals with an identifiable predisposition, such as previous seizures, sedative or alcohol withdrawal, and multiple concomitant medications. Seizure risk for most antidepressants increases with dose (or blood level), and comparisons between drugs should consider seizure rates at the effective dose (or blood level) for each drug. For imipramine, the most frequently studied tricyclic, the literature indicates a seizure rate between 0.3% and 0.6% at effective doses. In unselected patients and at higher doses, these rates may be higher. Fluoxetine, sertraline, fluvoxamine, trazodone, nomifensine, and the monoamine oxidase inhibitors have a lower seizure risk. Estimates for recently marketed antidepressants with intermediate seizure risk are complicated by the fact that effective doses and blood levels are not well established. Assessment of seizure risk in individuals involves consideration of predisposing factors, the antidepressant selected, and the bioavailability of the drug. Future studies of seizure risk would benefit from the use of specified criteria for determination of probable seizure events, a priori definition of predisposing exclusions, samples sufficiently large to provide adequate power, blood level monitoring, and inclusion of duration of drug treatment in the calculation of risk. JF - The Journal of clinical psychiatry AU - Rosenstein, D L AU - Nelson, J C AU - Jacobs, S C AD - National Institute of Mental Health, Bethesda, Md. Y1 - 1993/08// PY - 1993 DA - August 1993 SP - 289 EP - 299 VL - 54 IS - 8 SN - 0160-6689, 0160-6689 KW - Antidepressive Agents KW - 0 KW - Imipramine KW - OGG85SX4E4 KW - Index Medicus KW - Causality KW - Imipramine -- adverse effects KW - Epilepsy -- chemically induced KW - Imipramine -- blood KW - Imipramine -- pharmacokinetics KW - Dose-Response Relationship, Drug KW - Risk Factors KW - Humans KW - Incidence KW - Depressive Disorder -- drug therapy KW - Epilepsy -- epidemiology KW - Biological Availability KW - Seizures -- chemically induced KW - Antidepressive Agents -- pharmacokinetics KW - Antidepressive Agents -- blood KW - Seizures -- epidemiology KW - Antidepressive Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76115870?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+psychiatry&rft.atitle=Seizures+associated+with+antidepressants%3A+a+review.&rft.au=Rosenstein%2C+D+L%3BNelson%2C+J+C%3BJacobs%2C+S+C&rft.aulast=Rosenstein&rft.aufirst=D&rft.date=1993-08-01&rft.volume=54&rft.issue=8&rft.spage=289&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+clinical+psychiatry&rft.issn=01606689&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-01-07 N1 - Date created - 1994-01-07 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Clin Psychiatry. 1994 Jun;55(6):267 [8071288] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular basis of muscarinic acetylcholine receptor function. AN - 76085232; 8249149 AB - Muscarinic acetylcholine receptors play important roles in numerous physiological functions including higher cognitive processes such as memory and learning. Consistent with the well-documented pharmacological heterogeneity of muscarinic receptors, molecular cloning studies have revealed the existence of five distinct muscarinic receptor proteins (M1-M5). Structure-function relationship studies of the cloned receptors have been greatly aided by the high degree of structural homology that muscarinic receptors share with other G protein-coupled receptors. In this review, Jürgen Wess discusses recent mutagenesis studies that have considerably advanced our knowledge of the molecular details underlying muscarinic receptor function. JF - Trends in pharmacological sciences AU - Wess, J AD - National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Laboratory of Bio-organic Chemistry, Bethesda, MD 20892. Y1 - 1993/08// PY - 1993 DA - August 1993 SP - 308 EP - 313 VL - 14 IS - 8 SN - 0165-6147, 0165-6147 KW - Receptors, Muscarinic KW - 0 KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - Index Medicus KW - Animals KW - GTP-Binding Proteins -- metabolism KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Protein Binding KW - Structure-Activity Relationship KW - Protein Conformation KW - Receptors, Muscarinic -- drug effects KW - Receptors, Muscarinic -- chemistry KW - Receptors, Muscarinic -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76085232?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Molecular+basis+of+muscarinic+acetylcholine+receptor+function.&rft.au=Wess%2C+J&rft.aulast=Wess&rft.aufirst=J&rft.date=1993-08-01&rft.volume=14&rft.issue=8&rft.spage=308&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 - 1993-12-30 N1 - Date created - 1993-12-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Billion-fold difference in the toxic potencies of two excitatory plant amino acids, L-BOAA and L-BMAA: biochemical and morphological studies using mouse brain slices. AN - 76067496; 7901822 AB - Plant amino acids beta-N-oxalylamino-L-alanine (L-BOAA, present in Lathyrus sativus) and beta-N-methylamino-L-alanine (L-BMAA, present in Cycas circinalis) have been implicated in the pathogenesis of human neurological disorders lathyrism and amyotrophic lateral sclerosis-Parkinson's dementia complex of Guam (ALS-PD), respectively. In view of the conflicting reports that have emerged on the role of L-BMAA in ALS-PD, we reinvestigated the comparative toxicity of L-BMAA and L-BOAA. We report here the potent toxicity of L-BOAA as examined in an in vitro model consisting of sagittal slices of mouse brain. Incubation of sagittal slices of mouse brain with L-BOAA (1 pM) resulted in significant leakage of lactate dehydrogenase (LDH) and potassium from the slices into the medium. Under similar conditions, L-BMAA-induced LDH leakage from the slices into the medium was observed only at very high concentration of the toxin, namely 1 mM. N-Methyl-D-aspartate (NMDA) receptor antagonists ameliorated the toxic effects of L-BMAA, while non-NMDA receptor antagonists (quinoxalinediones) protected against the toxicity of L-BOAA. Incubation of slices with L-BOAA for 1 h resulted in extensive vacuolation and degeneration of neurons in the thalamus and brain stem, and to a lesser extent in the hippocampus and cerebellar nuclei. The large sized neurons appeared to be affected to a greater extent than the smaller ones. The neurons in other areas of the brain also revealed variable degree of degeneration with swelling of axons and dendrites.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Neuroscience research AU - Pai, K S AU - Shankar, S K AU - Ravindranath, V AD - Department of Neurochemistry, National Institute of Mental Health and Neuro Sciences, Bangalore, India. Y1 - 1993/08// PY - 1993 DA - August 1993 SP - 241 EP - 248 VL - 17 IS - 3 SN - 0168-0102, 0168-0102 KW - Amino Acids, Diamino KW - 0 KW - Excitatory Amino Acid Antagonists KW - Neurotoxins KW - Quinoxalines KW - beta-N-methylamino-L-alanine KW - 108SA6URTV KW - 2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline KW - 118876-58-7 KW - beta-Alanine KW - 11P2JDE17B KW - Dizocilpine Maleate KW - 6LR8C1B66Q KW - 6-Cyano-7-nitroquinoxaline-2,3-dione KW - 6OTE87SCCW KW - oxalyldiaminopropionic acid KW - 7554-90-7 KW - L-Lactate Dehydrogenase KW - EC 1.1.1.27 KW - Potassium KW - RWP5GA015D KW - Index Medicus KW - Animals KW - Paraffin Embedding KW - In Vitro Techniques KW - Mice KW - Histocytochemistry KW - Quinoxalines -- pharmacology KW - Potassium -- metabolism KW - L-Lactate Dehydrogenase -- metabolism KW - Dizocilpine Maleate -- pharmacology KW - Plants -- chemistry KW - Brain -- enzymology KW - beta-Alanine -- analogs & derivatives KW - Brain Chemistry -- drug effects KW - Brain -- drug effects KW - Brain -- anatomy & histology KW - Amino Acids, Diamino -- toxicity KW - beta-Alanine -- toxicity KW - Neurotoxins -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76067496?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Billion-fold+difference+in+the+toxic+potencies+of+two+excitatory+plant+amino+acids%2C+L-BOAA+and+L-BMAA%3A+biochemical+and+morphological+studies+using+mouse+brain+slices.&rft.au=Pai%2C+K+S%3BShankar%2C+S+K%3BRavindranath%2C+V&rft.aulast=Pai&rft.aufirst=K&rft.date=1993-08-01&rft.volume=17&rft.issue=3&rft.spage=241&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 - 1993-12-13 N1 - Date created - 1993-12-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inducible accessory function of a macrophage cell line. AN - 76053008; 7901265 AB - Costimulatory molecules in addition to occupancy of the T-cell antigen receptor, are required to induce T-cell proliferation. Previous work suggested that membrane molecules responsible for costimulatory activity were not constitutively expressed on the antigen presenting cell (APC) surface. In the present study, we have identified a cloned macrophage cell line (FLJ2) with inducible APC function. The unactivated FLJ2 line could not induce T-cell proliferation. FLJ2 could present alloantigen, and stimulate proliferation of either a T-cell clone or normal resting T cells following activation with IFN gamma or unexpectedly with lipopolysaccharide (LPS)-Activated FLJ2 cells could be fixed and APC function was preserved. The relevant inducible molecules required for APC function appeared distinct from Ia and IL1. The expression of ICAM-1 and LFA-1 was increased during activation and anti-LFA-1 antibody blocked APC function. This suggests that one important feature of the activation process may be improvement of cellular adhesion. JF - Immunopharmacology and immunotoxicology AU - Aiello, F B AU - Gusella, L AU - Longo, D L AU - Birchenall-Roberts, M AU - Takacs, L AU - Takei, F AU - Ruscetti, F AU - Musiani, P AU - Durum, S K AD - Biological Carcinogenesis and Development Program, Program Resources Inc./DynCorp, NCI-Frederick Cancer Research and Development Center, MD. Y1 - 1993/08// PY - 1993 DA - August 1993 SP - 327 EP - 353 VL - 15 IS - 4 SN - 0892-3973, 0892-3973 KW - Cell Adhesion Molecules KW - 0 KW - Histocompatibility Antigens Class II KW - Interleukin-1 KW - Lipopolysaccharides KW - Lymphocyte Function-Associated Antigen-1 KW - Recombinant Proteins KW - Intercellular Adhesion Molecule-1 KW - 126547-89-5 KW - Interferon-gamma KW - 82115-62-6 KW - Index Medicus KW - Animals KW - Interleukin-1 -- biosynthesis KW - Lymphocyte Function-Associated Antigen-1 -- metabolism KW - Lipopolysaccharides -- pharmacology KW - Interferon-gamma -- pharmacology KW - Mice KW - Mice, Inbred BALB C KW - Lymphocyte Activation KW - Mice, Inbred C57BL KW - Mice, Inbred C3H KW - Cell Adhesion Molecules -- metabolism KW - T-Lymphocytes -- immunology KW - Cell Line KW - Female KW - Macrophages -- immunology KW - Antigen-Presenting Cells -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76053008?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Immunopharmacology+and+immunotoxicology&rft.atitle=Inducible+accessory+function+of+a+macrophage+cell+line.&rft.au=Aiello%2C+F+B%3BGusella%2C+L%3BLongo%2C+D+L%3BBirchenall-Roberts%2C+M%3BTakacs%2C+L%3BTakei%2C+F%3BRuscetti%2C+F%3BMusiani%2C+P%3BDurum%2C+S+K&rft.aulast=Aiello&rft.aufirst=F&rft.date=1993-08-01&rft.volume=15&rft.issue=4&rft.spage=327&rft.isbn=&rft.btitle=&rft.title=Immunopharmacology+and+immunotoxicology&rft.issn=08923973&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-12-03 N1 - Date created - 1993-12-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Substitutions of different regions of the third cytoplasmic loop of the thyrotropin (TSH) receptor have selective effects on constitutive, TSH-, and TSH receptor autoantibody-stimulated phosphoinositide and 3',5'-cyclic adenosine monophosphate signal generation. AN - 76050454; 7901757 AB - TSH and immunoglobulin G (IgG) preparations from patients with Graves' disease increase inositol phosphate as well as cAMP formation in Cos-7 cells transfected with rat TSH receptor (TSHR) cDNA. In a previous report, we mutated alanine 623 of the third cytoplasmic loop (residues 605-625) of the TSHR and showed it was critical for TSH and Graves' IgG initiation of phosphatidylinositol bisphosphate (PIP2) but not cAMP signaling. In this report, we substituted residues in the third loop of the TSHR with sequences from the N- and C-termini of the third loop of the alpha 1- and beta 2-adrenergic receptors (ARs), which computer analysis has identified as homologous to those in the TSHR. Alanine 623 is conserved in most ARs as well as in glycoprotein hormone receptors; there is, therefore, no change in alanine 623. After transfection of the mutant TSHR cDNAs into Cos-7 cells, we show that the mutant proteins are normally synthesized, processed, and incorporated into the membrane bilayer by Western blotting with a specific receptor antibody. We also show that the dissociation constant for TSH binding in all mutants is the same or lower than wild type TSHR. We then evaluated the ability of TSH or Graves' IgG to increase PIP2 and cAMP signals in each transfectant. Mutants A622 and B621 replace, respectively, residues 622-625 and 621-625 of the TSHR with alpha 1- and beta 2-AR residues from the C-terminus of the third cytoplasmic loop; mutants A607 and B605 replace, respectively, TSHR residues 607-609 and 605-609 with N-terminus residues from alpha 1- and beta 2-AR. All four mutants, like the alanine 623 mutant, result in transfected cells which lose TSH and Graves' IgG initiation of PIP2 but not cAMP signalling. Like the alanine 623 mutation to glutamic acid, the A607, B605, A622, and B621 mutants also result in decreased basal cAMP, but not inositol phosphate levels, relative to wild type receptor. In contrast to these results, mutants A610, B610, A617, and B617, which replace residues 610-613 or 617-620 of the TSHR with corresponding residues of the alpha 1- and beta 2-AR, retain TSH and Graves' IgG responsiveness in both inositol phosphate and cAMP assays. Mutation of residues 610-613, in fact, potentiates TSH-increased inositol phosphate production, despite having no effect on TSH-increased cAMP production.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Molecular endocrinology (Baltimore, Md.) AU - Kosugi, S AU - Okajima, F AU - Ban, T AU - Hidaka, A AU - Shenker, A AU - Kohn, L D AD - Cell Regulation Section, National Institute of Diabetes and Digestive and Kidney Diseases Bethesda, Maryland 20892. Y1 - 1993/08// PY - 1993 DA - August 1993 SP - 1009 EP - 1020 VL - 7 IS - 8 SN - 0888-8809, 0888-8809 KW - Autoantibodies KW - 0 KW - Immunoglobulin G KW - Immunoglobulins, Thyroid-Stimulating KW - Phosphatidylinositol 4,5-Diphosphate KW - Phosphatidylinositol Phosphates KW - Receptors, Adrenergic KW - Receptors, Thyrotropin KW - Recombinant Fusion Proteins KW - Thyrotropin KW - 9002-71-5 KW - Cyclic AMP KW - E0399OZS9N KW - Index Medicus KW - Animals KW - Models, Molecular KW - Humans KW - Immunoglobulin G -- pharmacology KW - Receptors, Adrenergic -- genetics KW - Amino Acid Sequence KW - Fibroblasts KW - Recombinant Fusion Proteins -- metabolism KW - Mutagenesis, Site-Directed KW - Transfection KW - Cercopithecus aethiops KW - Molecular Sequence Data KW - Graves Disease -- immunology KW - Cell Line KW - Receptors, Thyrotropin -- chemistry KW - Thyrotropin -- pharmacology KW - Receptors, Thyrotropin -- physiology KW - Receptors, Thyrotropin -- immunology KW - Autoantibodies -- pharmacology KW - Phosphatidylinositol Phosphates -- physiology KW - Cyclic AMP -- physiology KW - Protein Structure, Tertiary KW - Signal Transduction KW - Receptors, Thyrotropin -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76050454?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Substitutions+of+different+regions+of+the+third+cytoplasmic+loop+of+the+thyrotropin+%28TSH%29+receptor+have+selective+effects+on+constitutive%2C+TSH-%2C+and+TSH+receptor+autoantibody-stimulated+phosphoinositide+and+3%27%2C5%27-cyclic+adenosine+monophosphate+signal+generation.&rft.au=Kosugi%2C+S%3BOkajima%2C+F%3BBan%2C+T%3BHidaka%2C+A%3BShenker%2C+A%3BKohn%2C+L+D&rft.aulast=Kosugi&rft.aufirst=S&rft.date=1993-08-01&rft.volume=7&rft.issue=8&rft.spage=1009&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 - 1993-12-16 N1 - Date created - 1993-12-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Large granular lymphocytosis in a patient infected with HTLV-II. AN - 76020675; 8217341 AB - HTLV-II has been associated with a variety of lymphoproliferative disorders, including atypical hairy cell leukemia, chronic T cell leukemia, T prolymphocytic leukemia, and large granular lymphocytic leukemia. However, a direct or indirect role for HTLV-II in these disorders is not yet firmly established. We studied a patient diagnosed as having leukemia of the large granular lymphocyte (LGL) type who was HTLV-II seropositive, to determine if the expanded cell population was infected. Two populations of CD3-CD16+ LGL were identified; one was CD8+, the other CD8-. Populations of cells with these surface markers as well as normal CD3+CD4+ and CD3+CD8+ cells were separated by flow cytometric methods, DNA extracted, and gene regions of HTLV-II pol and tax amplified, using the polymerase chain reaction, and probed after Southern blotting. HTLV-II was detected in the CD3+CD8+ population, and not in the CD3-CD16+ large granular lymphocyte population. This finding indicates that the role of HTLV-II, if any, in LGL proliferation is indirect. JF - AIDS research and human retroviruses AU - Martin, M P AU - Biggar, R J AU - Hamlin-Green, G AU - Staal, S AU - Mann, D AD - Laboratory of Viral Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland 21702-1201. Y1 - 1993/08// PY - 1993 DA - August 1993 SP - 715 EP - 719 VL - 9 IS - 8 SN - 0889-2229, 0889-2229 KW - pol KW - tax KW - Antigens, CD KW - 0 KW - DNA, Viral KW - Index Medicus KW - AIDS/HIV KW - Genes, pX KW - Antigens, CD -- analysis KW - Human T-lymphotropic virus 2 -- genetics KW - DNA, Viral -- analysis KW - Humans KW - Middle Aged KW - Flow Cytometry KW - Immunophenotyping KW - Male KW - Genes, pol KW - Leukemia, Lymphoid -- complications KW - HTLV-II Infections -- complications KW - Lymphocytosis -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76020675?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Large+granular+lymphocytosis+in+a+patient+infected+with+HTLV-II.&rft.au=Martin%2C+M+P%3BBiggar%2C+R+J%3BHamlin-Green%2C+G%3BStaal%2C+S%3BMann%2C+D&rft.aulast=Martin&rft.aufirst=M&rft.date=1993-08-01&rft.volume=9&rft.issue=8&rft.spage=715&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 - 1993-12-08 N1 - Date created - 1993-12-08 N1 - Date revised - 2017-01-13 N1 - Gene symbol - pol; tax N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Detection of DNA damage-recognition proteins using the band-shift assay and southwestern hybridization. AN - 76001949; 8404810 AB - We describe electrophoresis and biochemical conditions that allow detection of damaged DNA-binding proteins in cell extracts. In addition, we present an overview of the damage-recognition DNA-binding proteins from eukaryotic cells and discuss their hypothetical role in DNA repair. JF - Electrophoresis AU - Protić, M AU - Levine, A S AD - Section on DNA Replication, Repair and Mutagenesis, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/08// PY - 1993 DA - August 1993 SP - 682 EP - 692 VL - 14 IS - 8 SN - 0173-0835, 0173-0835 KW - DNA-Binding Proteins KW - 0 KW - Transcription Factors KW - Index Medicus KW - Base Sequence KW - Nucleic Acid Hybridization -- methods KW - Molecular Sequence Data KW - Transcription Factors -- analysis KW - Binding Sites KW - DNA-Binding Proteins -- analysis KW - Blotting, Western KW - DNA Repair KW - DNA Damage KW - Blotting, Southern UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76001949?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Electrophoresis&rft.atitle=Detection+of+DNA+damage-recognition+proteins+using+the+band-shift+assay+and+southwestern+hybridization.&rft.au=Proti%C4%87%2C+M%3BLevine%2C+A+S&rft.aulast=Proti%C4%87&rft.aufirst=M&rft.date=1993-08-01&rft.volume=14&rft.issue=8&rft.spage=682&rft.isbn=&rft.btitle=&rft.title=Electrophoresis&rft.issn=01730835&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-11-19 N1 - Date created - 1993-11-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Comparative carcinogenicity of 5,5-diphenylhydantoin with or without perinatal exposure in rats and mice. AN - 76000669; 8405780 AB - Chronic toxicity and carcinogenicity studies of 5,5-diphenylhydantoin (DPH), were conducted in F344/N rats and B6C3F1 mice of each sex. The major objective of the study was to determine if incorporating exposure to DPH during the perinatal period, in addition to conventional exposure of animals for 2 years, enhances the sensitivity of the bioassay to identify the carcinogenic potential of chemical. The studies were designed to determine the toxic and carcinogenic effects of dietary DPH in rats and mice receiving; (1) the perinatal administration including exposure of maternal animals prior to breeding, through gestation, lactation, weaning, and continued dietary exposure of offspring to the age of 8 weeks followed by control diet for 2 years, (2) exposure for 2 years beginning at the age of 8 weeks, and (3) of combined perinatal/adult exposure to DPH (perinatal exposure to 8 weeks of age followed by the adult exposure for 2 years). During the perinatal period, rats were exposed to DPH at dose levels ranging from 63 to 630 ppm and adult exposure concentrations ranged from 240 to 2400 ppm in diet. In the mice, the perinatal exposure ranged from 21 to 210 ppm in both males and females. In the adult exposure portion of the mouse studies, the dietary levels ranged from 30 to 300 ppm in males and 60 to 600 ppm in females. A total of eight dose groups (including controls) were used with 60 animals in each group. The only effect of perinatal exposure alone on tumor rate was a marginal increase in the incidence of hepatocellular neoplasms in female mice. The adult exposure to DPH significantly increased the incidence of hepatocellular neoplasms in female mice. There were also marginal increases in the incidence of liver tumors in male rats exposed to high DPH dietary concentrations during the adult-only regimen. Combined perinatal and adult dietary exposure to 5,5-diphenylhydantoin confirmed the findings for the increased incidences of hepatocellular neoplasms in male rats and female mice, although combined exposure did not enhance these effects. However, in male mice, perinatal and adult exposure resulted in an increase in the incidence of hepatocellular neoplasms that was not seen when dietary exposure was limited to the adult period only. JF - Fundamental and applied toxicology : official journal of the Society of Toxicology AU - Chhabra, R S AU - Bucher, J R AU - Haseman, J K AU - Elwell, M R AU - Kurtz, P J AU - Carlton, B D AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1993/08// PY - 1993 DA - August 1993 SP - 174 EP - 186 VL - 21 IS - 2 SN - 0272-0590, 0272-0590 KW - Carcinogens KW - 0 KW - Phenytoin KW - 6158TKW0C5 KW - Index Medicus KW - Rats KW - Litter Size -- drug effects KW - Animals KW - Rats, Inbred F344 KW - Body Weight -- drug effects KW - Mice, Inbred C57BL KW - Liver Neoplasms, Experimental -- chemically induced KW - Mice KW - Adenoma, Liver Cell -- chemically induced KW - Male KW - Female KW - Carcinoma, Hepatocellular -- chemically induced KW - Pregnancy KW - Fetal Death KW - Phenytoin -- toxicity KW - Carcinogens -- toxicity KW - Prenatal Exposure Delayed Effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76000669?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.atitle=Comparative+carcinogenicity+of+5%2C5-diphenylhydantoin+with+or+without+perinatal+exposure+in+rats+and+mice.&rft.au=Chhabra%2C+R+S%3BBucher%2C+J+R%3BHaseman%2C+J+K%3BElwell%2C+M+R%3BKurtz%2C+P+J%3BCarlton%2C+B+D&rft.aulast=Chhabra&rft.aufirst=R&rft.date=1993-08-01&rft.volume=21&rft.issue=2&rft.spage=174&rft.isbn=&rft.btitle=&rft.title=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.issn=02720590&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-11-02 N1 - Date created - 1993-11-02 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Fundam Appl Toxicol 1994 Jan;22(1):159 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Gender-related behavior in women exposed prenatally to diethylstilbestrol. AN - 75994446; 8404755 AB - Accumulating evidence in experimental animals over the past three decades suggests that mammalian brain development and differentiation of the central nervous system are influenced by perinatal exposure to sex hormones. Hence, changes in human behavioral patterns may be associated with prenatal exposure to estrogenic substances such as diethylstilbestrol (DES). This paper reviews relevant studies from a series of laboratories and finds that no clear-cut differences can be demonstrated to date between unexposed and DES-exposed women in gender-related behavior, although the physical and psychological impact of the problems associated with exposure to DES are well documented. If both prenatal and postnatal influences such as social, economic, and environmental factors are taken into consideration, individual variation is more apparent than differences in gender-related behavior between unexposed and DES-exposed women. In summary, gender-related behavior is determined by a complex array of interacting factors, and prenatal influences are only one of many developmental events. More studies are needed using larger populations with carefully controlled selection criteria to suggest a direct role of prenatal DES exposure on subsequent gender-related behavior. JF - Environmental health perspectives AU - Newbold, R R AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1993/08// PY - 1993 DA - August 1993 SP - 208 EP - 213 VL - 101 IS - 3 SN - 0091-6765, 0091-6765 KW - Diethylstilbestrol KW - 731DCA35BT KW - Index Medicus KW - Humans KW - Adult KW - Child KW - Adolescent KW - Male KW - Female KW - Prenatal Exposure Delayed Effects KW - Pregnancy KW - Diethylstilbestrol -- adverse effects KW - Sex Characteristics KW - Sexual Behavior -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75994446?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Gender-related+behavior+in+women+exposed+prenatally+to+diethylstilbestrol.&rft.au=Newbold%2C+R+R&rft.aulast=Newbold&rft.aufirst=R&rft.date=1993-08-01&rft.volume=101&rft.issue=3&rft.spage=208&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 - 1993-11-18 N1 - Date created - 1993-11-18 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Comp Neurol. 1990 Dec 22;302(4):697-706 [1707064] J Neurosci. 1991 Apr;11(4):933-42 [2010816] Cancer Res. 1980 Nov;40(11):3988-99 [7193511] N Engl J Med. 1980 Mar 13;302(11):609-13 [7351908] Endocrinology. 1978 Aug;103(2):501-12 [744098] Fertil Steril. 1979 Feb;31(2):142-6 [761676] Pediatrics. 1978 Dec;62(6 Pt 2):1166-70 [724354] Nature. 1977 Apr 7;266(5602):561-2 [859624] Am J Obstet Gynecol. 1977 May 1;128(1):51-9 [851159] Psychoneuroendocrinology. 1980 Dec;5(4):269-85 [7208750] J Comp Neurol. 1991 Oct 1;312(1):97-104 [1744245] Horm Behav. 1981 Dec;15(4):325-76 [7035327] J Pharmacol Exp Ther. 1982 Apr;221(1):173-82 [7062281] Am J Obstet Gynecol. 1982 Apr 1;142(7):905-21 [6121486] Cancer Res. 1982 May;42(5):2003-11 [7066910] J Steroid Biochem. 1981 Dec;15:497-500 [6803070] Obstet Gynecol. 1982 Jun;59(6 Suppl):68S-72S [7088431] Fertil Steril. 1982 Sep;38(3):364-71 [7117561] Psychol Bull. 1982 Jul;92(1):56-80 [7134329] Biol Reprod. 1983 Apr;28(3):735-44 [6850046] Teratology. 1983 Jun;27(3):417-26 [6879463] J Reprod Med. 1983 Dec;28(12):851-6 [6663585] Biol Reprod. 1984 Mar;30(2):471-8 [6704476] Am J Obstet Gynecol. 1984 Apr 1;148(7):973-84 [6711635] Am J Obstet Gynecol. 1977 May 1;128(1):43-50 [851158] Obstet Gynecol. 1977 Jan;49(1):1-8 [318736] Med Clin North Am. 1974 Jul;58(4):793-810 [4276416] Arch Gen Psychiatry. 1973 Apr;28(4):554-61 [4734959] N Engl J Med. 1972 Dec 21;287(25):1259-64 [4636892] N Engl J Med. 1971 Apr 15;284(15):878-81 [5549830] Neuroendocrinology. 1971;7(3):146-55 [5101953] J Am Acad Child Adolesc Psychiatry. 1991 Jan;30(1):29-37 [2005061] Horm Behav. 1989 Dec;23(4):526-41 [2606466] J Neurosci. 1989 Feb;9(2):497-506 [2918374] Brain Res. 1988 Jul 26;456(2):271-4 [3208082] Horm Behav. 1987 Sep;21(3):402-17 [3666690] Psychosom Med. 1987 Mar-Apr;49(2):183-96 [3575605] Teratog Carcinog Mutagen. 1985;5(6):473-80 [2874632] Psychosom Med. 1985 Nov-Dec;47(6):497-511 [4070521] Horm Behav. 1985 Sep;19(3):331-47 [4054856] Nebr Symp Motiv. 1984;32:37-57 [6398858] Arch Sex Behav. 1985 Feb;14(1):57-77 [3977584] Arch Sex Behav. 1984 Oct;13(5):457-77 [6240240] Science. 1981 Mar 20;211(4488):1294-302 [6163211] Horm Behav. 1984 Sep;18(3):359-66 [6489946] Fundam Appl Toxicol. 1984 Oct;4(5):686-91 [6510599] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Leucovorin modulation of fluorouracil. AN - 75982338; 8398636 AB - Fluorouracil remains the single most active chemotherapy agent in colorectal cancer. One of its principal mechanisms of action is inhibition of the enzyme thymidylate synthase (TS), a central enzymatic step in de novo pyrimidine synthesis. Leucovorin, which is metabolized intracellularly to polyglutamated 5,10-methylenetetrahydrofolate, modulates the cellular cytotoxicity of fluorouracil by increasing TS inhibition in vitro and in vivo. Leucovorin modulation of fluorouracil has been studied in preclinical systems and in a large number of clinical trials using various doses and schedules of both drugs. The collective data support the use of continuous infusion or repetitive low-dose schedules of leucovorin. Furthermore, these schedules appear to be less dependent on the leucovorin dose to achieve maximal clinical efficacy than does intermittent single bolus therapy. These schedules appear to be the most effective in the generation of the higher polyglutamates of 5,10-methylenetetrahydrofolate, the most efficient intracellular folate metabolite for ternary complex formation and TS inhibition. JF - Oncology (Williston Park, N.Y.) AU - Grogan, L AU - Sotos, G A AU - Allegra, C J AD - NCI-Navy Medical Oncology Branch, National Cancer Institute, Bethesda, Maryland. Y1 - 1993/08// PY - 1993 DA - August 1993 SP - 63 EP - 72; discussion 75-6 VL - 7 IS - 8 SN - 0890-9091, 0890-9091 KW - Leucovorin KW - Q573I9DVLP KW - Fluorouracil KW - U3P01618RT KW - Index Medicus KW - Neoplasms -- drug therapy KW - Humans KW - Drug Synergism KW - Fluorouracil -- administration & dosage KW - Leucovorin -- administration & dosage KW - Fluorouracil -- pharmacology KW - Leucovorin -- pharmacology KW - Fluorouracil -- pharmacokinetics KW - Leucovorin -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75982338?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncology+%28Williston+Park%2C+N.Y.%29&rft.atitle=Leucovorin+modulation+of+fluorouracil.&rft.au=Grogan%2C+L%3BSotos%2C+G+A%3BAllegra%2C+C+J&rft.aulast=Grogan&rft.aufirst=L&rft.date=1993-08-01&rft.volume=7&rft.issue=8&rft.spage=63&rft.isbn=&rft.btitle=&rft.title=Oncology+%28Williston+Park%2C+N.Y.%29&rft.issn=08909091&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-11-08 N1 - Date created - 1993-11-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chemotherapy agents: Part I. AN - 75981707; 8402608 JF - Cancer nursing AU - Levy, W AU - Meadows, B S AU - Quint-Kasner, S AU - Carroll, R AU - Gorrell, C R AD - Clinical Center Nursing Department, National Institutes of Health, Bethesda, Maryland. Y1 - 1993/08// PY - 1993 DA - August 1993 SP - 321 EP - 325 VL - 16 IS - 4 SN - 0162-220X, 0162-220X KW - Alkylating Agents KW - 0 KW - Antibiotics, Antineoplastic KW - Antimetabolites, Antineoplastic KW - Antineoplastic Agents KW - Index Medicus KW - Nursing KW - Alkylating Agents -- therapeutic use KW - Antibiotics, Antineoplastic -- pharmacology KW - Humans KW - Education, Nursing, Continuing KW - Alkylating Agents -- pharmacology KW - Antimetabolites, Antineoplastic -- therapeutic use KW - Antimetabolites, Antineoplastic -- pharmacology KW - Antibiotics, Antineoplastic -- therapeutic use KW - Antineoplastic Agents -- administration & dosage KW - Programmed Instruction as Topic KW - Antineoplastic Agents -- therapeutic use KW - Oncology Nursing -- education UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75981707?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+nursing&rft.atitle=Chemotherapy+agents%3A+Part+I.&rft.au=Levy%2C+W%3BMeadows%2C+B+S%3BQuint-Kasner%2C+S%3BCarroll%2C+R%3BGorrell%2C+C+R&rft.aulast=Levy&rft.aufirst=W&rft.date=1993-08-01&rft.volume=16&rft.issue=4&rft.spage=321&rft.isbn=&rft.btitle=&rft.title=Cancer+nursing&rft.issn=0162220X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-11-15 N1 - Date created - 1993-11-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Prospects for prevention of neural tube defects by vitamin supplementation. AN - 75980783; 8400468 AB - Recent studies have resolved the debate over the role of vitamins in preventing neural tube defects. The British Medical Research Council trial demonstrated that 4 mg of folate daily, but not other vitamins, prevented 72% of recurrences. The Hungarian trial prevented neural tube defects in women who had not previously had affected children by giving multivitamins containing 0.8 mg of folate. The US Public Health Service currently recommends that women at risk for becoming pregnant take 0.4 mg of folate daily. Unfortunately, most pregnancies are unplanned, and women not planning to become pregnant may not follow this recommendation. Therefore, the US Food and Drug Administration is exploring methods of food fortification. Because large doses of folate have been reported to ameliorate B12 deficiency anemia while allowing neurologic damage to progress, and to cause electroencephalogram abnormalities in epileptics, it is important to plan fortification carefully and to monitor both toxicity and benefits. JF - Current opinion in neurology and neurosurgery AU - Mills, J L AU - Simpson, J L AD - National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/08// PY - 1993 DA - August 1993 SP - 554 EP - 558 VL - 6 IS - 4 SN - 0951-7383, 0951-7383 KW - Vitamins KW - 0 KW - Folic Acid KW - 935E97BOY8 KW - Ascorbic Acid KW - PQ6CK8PD0R KW - Index Medicus KW - Ascorbic Acid -- administration & dosage KW - Vitamin B 12 Deficiency -- prevention & control KW - Dose-Response Relationship, Drug KW - Humans KW - Food, Fortified KW - Infant, Newborn KW - Ascorbic Acid -- adverse effects KW - Folic Acid -- adverse effects KW - Female KW - Pregnancy KW - Folic Acid -- administration & dosage KW - Vitamins -- adverse effects KW - Vitamins -- administration & dosage KW - Neural Tube Defects -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75980783?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+neurology+and+neurosurgery&rft.atitle=Prospects+for+prevention+of+neural+tube+defects+by+vitamin+supplementation.&rft.au=Mills%2C+J+L%3BSimpson%2C+J+L&rft.aulast=Mills&rft.aufirst=J&rft.date=1993-08-01&rft.volume=6&rft.issue=4&rft.spage=554&rft.isbn=&rft.btitle=&rft.title=Current+opinion+in+neurology+and+neurosurgery&rft.issn=09517383&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-11-05 N1 - Date created - 1993-11-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Postpubertal emergence of hyperresponsiveness to stress and to amphetamine after neonatal excitotoxic hippocampal damage: a potential animal model of schizophrenia. AN - 75964830; 8397725 AB - The constellation of major phenomena associated with schizophrenia (e.g., postpubertal onset, congenital hippocampal area damage, cortical functional deficits, limbic dopamine (DA) dysregulation, and vulnerability to stress) have been difficult to explain with a unitary animal model. Although it has been shown that rats develop increased mesolimbic DA transmission and reduced cortical DA turnover following adult excitotoxic lesions of the ventral hippocampus (VH), the implications of early developmental VH lesions are not known. To determine the developmental sequelae of such changes, we produced ibotenic acid lesions of the ventral hippocampal formation in rats on the 7th day after birth (PD7). Motor activity in a novel environment, after saline injection and after d-amphetamine administration were similar in control and lesioned rats at PD35. However, in early adulthood, at PD56, animals with the hippocampal lesion were hyperactive in each of these conditions. The emergence of the hyperactivity at PD56 could be prevented by pretreatment with haloperidol. Moreover, rats lesioned as neonates, in contrast to a similar lesion induced in adult animals, were also hyperresponsive to stress evaluated with a swim test. This latter effect is analogous to that seen after adult lesions of the medial prefrontal cortex, rather than after adult lesions of VH, suggesting that the neonatal VH lesion may affect functional development of the medial prefrontal cortex. These results demonstrate that in rats with neonatally induced excitotoxic VH lesions, behavioral indices consistent with increased mesolimbic DA responsivity to stressful and to pharmacologic stimuli emerge only in early adulthood. Homologous mechanisms may underlie certain aspects of the pathophysiology of schizophrenia. JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology AU - Lipska, B K AU - Jaskiw, G E AU - Weinberger, D R AD - Clinical Brain Disorders Branch, National Institute of Mental Health, Washington, DC 20032. Y1 - 1993/08// PY - 1993 DA - August 1993 SP - 67 EP - 75 VL - 9 IS - 1 SN - 0893-133X, 0893-133X KW - Ibotenic Acid KW - 2552-55-8 KW - Haloperidol KW - J6292F8L3D KW - Dextroamphetamine KW - TZ47U051FI KW - Index Medicus KW - Rats KW - Animals KW - Swimming KW - Rats, Sprague-Dawley KW - Haloperidol -- pharmacology KW - Disease Models, Animal KW - Motor Activity -- drug effects KW - Ibotenic Acid -- toxicity KW - Female KW - Pregnancy KW - Hippocampus -- physiology KW - Animals, Newborn -- psychology KW - Hippocampus -- pathology KW - Schizophrenia -- physiopathology KW - Stress, Psychological -- psychology KW - Hippocampus -- drug effects KW - Dextroamphetamine -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75964830?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuropsychopharmacology+%3A+official+publication+of+the+American+College+of+Neuropsychopharmacology&rft.atitle=Postpubertal+emergence+of+hyperresponsiveness+to+stress+and+to+amphetamine+after+neonatal+excitotoxic+hippocampal+damage%3A+a+potential+animal+model+of+schizophrenia.&rft.au=Lipska%2C+B+K%3BJaskiw%2C+G+E%3BWeinberger%2C+D+R&rft.aulast=Lipska&rft.aufirst=B&rft.date=1993-08-01&rft.volume=9&rft.issue=1&rft.spage=67&rft.isbn=&rft.btitle=&rft.title=Neuropsychopharmacology+%3A+official+publication+of+the+American+College+of+Neuropsychopharmacology&rft.issn=0893133X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-11-08 N1 - Date created - 1993-11-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Directionality of fission yeast mating-type interconversion is controlled by the location of the donor loci. AN - 75956078; 8375648 AB - Cells of homothallic strains of Schizosaccharomyces pombe efficiently switch between two mating types called P and M. The phenotypic switches are due to conversion of the expressed mating-type locus (mat1) by two closely linked silent loci, mat2-P and mat3-M, that contain unexpressed information for the P and M mating types, respectively. In this process, switching-competent cells switch to the opposite mating type in 72-90% of the cell divisions. Hence, mat2-P is a preferred donor of information to mat1 in M cells, whereas mat3-M is a preferred donor in P cells. We investigated the reason for the donor preference by constructing a strain in which the genetic contents of the donor loci were swapped. We found that switching to the opposite mating type was very inefficient in that strain. This shows that the location of the silent cassettes in the chromosome, rather than their content, is the deciding factor for recognition of the donor for each cell type. We propose a model in which switching is achieved by regulating accessibility of the donor loci, perhaps by changing the chromatin structure in the mating-type region, thus promoting an intrachromosomal folding of mat2 or mat3 onto mat1 in a cell type-specific fashion. We also present evidence for the involvement of the Swi6 and Swi6-mod trans-acting factors in the donor-choice mechanism. We suggest that these factors participate in forming the proposed folded structure. JF - Genetics AU - Thon, G AU - Klar, A J AD - NCI-Frederick Cancer Research and Development Center, ABL-Basic Research Program, Maryland 21702-1201. Y1 - 1993/08// PY - 1993 DA - August 1993 SP - 1045 EP - 1054 VL - 134 IS - 4 SN - 0016-6731, 0016-6731 KW - DNA, Fungal KW - 0 KW - Fungal Proteins KW - SWI6 protein, S cerevisiae KW - Saccharomyces cerevisiae Proteins KW - Trans-Activators KW - Transcription Factors KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Trans-Activators -- metabolism KW - Fungal Proteins -- metabolism KW - Base Sequence KW - Genes, Switch KW - Transcription Factors -- metabolism KW - Restriction Mapping KW - Recombination, Genetic KW - Schizosaccharomyces -- genetics KW - Gene Conversion KW - Genes, Fungal KW - Genes, Mating Type, Fungal UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75956078?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Directionality+of+fission+yeast+mating-type+interconversion+is+controlled+by+the+location+of+the+donor+loci.&rft.au=Thon%2C+G%3BKlar%2C+A+J&rft.aulast=Thon&rft.aufirst=G&rft.date=1993-08-01&rft.volume=134&rft.issue=4&rft.spage=1045&rft.isbn=&rft.btitle=&rft.title=Genetics&rft.issn=00166731&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-10-18 N1 - Date created - 1993-10-18 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Mol Gen Genet. 1968;102(4):301-6 [5743433] Mol Gen Genet. 1979 Feb 26;170(2):145-8 [285317] J Bacteriol. 1983 Jan;153(1):163-8 [6336730] EMBO J. 1984 Mar;3(3):603-10 [6325178] Proc Natl Acad Sci U S A. 1984 Jun;81(11):3481-5 [6587363] Mol Cell Biol. 1986 Jan;6(1):80-9 [3023839] EMBO J. 1988 May;7(5):1537-47 [2900761] EMBO J. 1989 Jan;8(1):269-76 [2714252] EMBO J. 1990 May;9(5):1407-15 [2328720] Methods Enzymol. 1991;194:795-823 [2005825] EMBO J. 1991 Oct;10(10):3025-32 [1915277] Genetics. 1991 Dec;129(4):1033-42 [1783290] Curr Genet. 1991 Nov;20(5):379-83 [1807828] Mol Gen Genet. 1992 Jun;233(3):436-42 [1620099] Genetics. 1992 Jun;131(2):287-96 [1644273] Genetics. 1992 Dec;132(4):929-42 [1459444] Nature. 1993 Jan 21;361(6409):271-3 [8423854] Cold Spring Harb Symp Quant Biol. 1958;23:161-70 [13635553] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutants of Escherichia coli with increased fidelity of DNA replication. AN - 75953992; 8375645 AB - To improve our understanding of the role of DNA replication fidelity in mutagenesis, we undertook a search for Escherichia coli antimutator strains with increased fidelity of DNA replication. The region between 4 and 5 min of the E. coli chromosome was mutagenized using localized mutagenesis mediated by bacteriophage P1. This region contains the dnaE and dnaQ genes, which encode, respectively, the DNA polymerase (alpha subunit) and 3' exonucleolytic proofreading activity (epsilon subunit) of DNA polymerase III holoenzyme, the enzyme primarily responsible for replicating the bacterial chromosome. The mutated bacteria were screened for antimutator phenotype in a strain defective in DNA mismatch repair (mutL), using a papillation assay based on the reversion of the galK2 mutation. In a mutL strain, mutations result primarily from DNA replication errors. Among 10,000 colonies, seven mutants were obtained whose level of papillation was reduced 5-30-fold. These mutants also displayed decreased mutation frequencies for rifampicin or nalidixic acid resistance as well as for other markers. Mapping by P1 transduction and complementation showed each to reside in dnaE. These observations support the idea that the mutants represent antimutators which replicate their DNA with increased fidelity. Mutation rates were reduced in both mutL and mutT backgrounds, but mutagenesis by ultraviolet light was not significantly affected, suggesting that the antimutator effect may be largely restricted to normal DNA replication. JF - Genetics AU - Fijalkowska, I J AU - Dunn, R L AU - Schaaper, R M AD - Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1993/08// PY - 1993 DA - August 1993 SP - 1023 EP - 1030 VL - 134 IS - 4 SN - 0016-6731, 0016-6731 KW - dnaE KW - dnaQ KW - Bacterial Proteins KW - 0 KW - DNA, Bacterial KW - Escherichia coli Proteins KW - DNA Polymerase III KW - EC 2.7.7.- KW - DNA polymerase III, alpha subunit KW - Phosphoric Monoester Hydrolases KW - EC 3.1.3.2 KW - Pyrophosphatases KW - EC 3.6.1.- KW - mutT protein, E coli KW - Index Medicus KW - Bacterial Proteins -- genetics KW - SOS Response (Genetics) KW - Genetic Complementation Test KW - DNA Polymerase III -- genetics KW - DNA Polymerase III -- metabolism KW - Chromosome Mapping KW - Mutagenesis KW - DNA, Bacterial -- genetics KW - DNA, Bacterial -- biosynthesis KW - Escherichia coli -- genetics KW - Escherichia coli -- enzymology KW - Mutation KW - DNA Replication UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75953992?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mutants+of+Escherichia+coli+with+increased+fidelity+of+DNA+replication.&rft.au=Fijalkowska%2C+I+J%3BDunn%2C+R+L%3BSchaaper%2C+R+M&rft.aulast=Fijalkowska&rft.aufirst=I&rft.date=1993-08-01&rft.volume=134&rft.issue=4&rft.spage=1023&rft.isbn=&rft.btitle=&rft.title=Genetics&rft.issn=00166731&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-10-18 N1 - Date created - 1993-10-18 N1 - Date revised - 2017-01-13 N1 - Gene symbol - dnaE; dnaQ N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1966 Feb;55(2):274-81 [5328724] Cold Spring Harb Symp Quant Biol. 1968;33:339-44 [5254574] Proc Natl Acad Sci U S A. 1970 Jul;66(3):823-9 [5269245] Mol Gen Genet. 1971;113(3):273-84 [4946856] Mol Gen Genet. 1975 Aug 5;139(1):9-18 [1101031] Mol Gen Genet. 1977 May 20;153(1):87-97 [329107] J Bacteriol. 1978 Mar;133(3):1197-202 [346561] Mutat Res. 1978 Oct;52(1):11-24 [366396] Genetics. 1980 Dec;96(4):819-39 [7021317] Mol Gen Genet. 1982;185(1):43-50 [6211591] J Bacteriol. 1983 Mar;153(3):1361-7 [6337996] J Mol Biol. 1983 Jul 15;167(4):757-71 [6224021] Proc Natl Acad Sci U S A. 1987 Sep;84(17):6220-4 [3306672] Annu Rev Biochem. 1988;57:519-50 [3052282] Proc Natl Acad Sci U S A. 1988 Nov;85(21):8126-30 [3054881] J Bacteriol. 1989 Oct;171(10):5572-80 [2551891] Microbiol Rev. 1990 Jun;54(2):130-97 [2194094] J Bacteriol. 1991 Jan;173(1):334-44 [1987124] J Biol Chem. 1991 Mar 15;266(8):5055-61 [2002048] J Biol Chem. 1991 Oct 15;266(29):19127-30 [1918028] Genetics. 1991 Oct;129(2):317-26 [1660424] Nature. 1992 Jan 16;355(6357):273-5 [1309939] Annu Rev Genet. 1991;25:229-53 [1812808] Genetics. 1993 Aug;134(4):1031-8 [8375646] Genetics. 1993 Aug;134(4):1039-44 [8375647] J Gen Microbiol. 1954 Dec;11(3):364-79 [13221757] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Stopping a clinical trial very early because of toxicity: summarizing the evidence. AN - 75932560; 7689943 AB - When a trial is stopped early because of a specific toxicity, it may be important to summarize the statistical evidence for stopping. Such a summary needs to take into account the sequential nature of the stopping rule. We address some practical issues involved in analyzing such toxicity data coming from a trial that was stopped after the fourth patient was evaluated. JF - Controlled clinical trials AU - Korn, E L AU - Yu, K F AU - Miller, L L AD - Biometric Research Branch, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1993/08// PY - 1993 DA - August 1993 SP - 286 EP - 295 VL - 14 IS - 4 SN - 0197-2456, 0197-2456 KW - Granulocyte Colony-Stimulating Factor KW - 143011-72-7 KW - Index Medicus KW - Humans KW - Granulocyte Colony-Stimulating Factor -- adverse effects KW - Bayes Theorem KW - Confidence Intervals KW - Leukopenia -- etiology KW - Drug-Related Side Effects and Adverse Reactions KW - Clinical Trials as Topic -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75932560?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Controlled+clinical+trials&rft.atitle=Stopping+a+clinical+trial+very+early+because+of+toxicity%3A+summarizing+the+evidence.&rft.au=Korn%2C+E+L%3BYu%2C+K+F%3BMiller%2C+L+L&rft.aulast=Korn&rft.aufirst=E&rft.date=1993-08-01&rft.volume=14&rft.issue=4&rft.spage=286&rft.isbn=&rft.btitle=&rft.title=Controlled+clinical+trials&rft.issn=01972456&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-10-06 N1 - Date created - 1993-10-06 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Control Clin Trials. 1995 Apr;16(2):131-2 [7789136] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Parkinson's disease: past, present, and future. AN - 75932400; 8397719 AB - The development of understanding of the pathophysiology and modes of treatment of Parkinson's disease represents one of the triumphs of modern medicine, encompassing astute clinical observation, utilization of basic research findings regarding dopamine to develop the first rational treatment of a degenerative disorder of the central nervous system, and remains at the frontiers of neurologic science. After characterization of the clinical and pathologic features of Parkinson's disease, rational treatment awaited the discovery of the deficit in basal ganglia dopamine. On the basis of this observation and the known biosynthetic pathways for dopamine formation, levodopa was introduced. Use of metabolic inhibitors to prolong and potentiate the effects and avoid the deleterious side effects of levodopa enhanced the efficacy of this neurotransmitter replacement strategy. The discovery and characterization of dopamine receptor subtypes and the availability of selective dopamine agonists provided additional therapeutic approaches, but failed to address the underlying cause of the degenerative process. The discovery and disclosure of the mechanisms of toxicity of the relatively selective nigrostriatal neurotoxin, 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP), triggered a resurgence of interest in etiological factors which might contribute to the development of parkinsonism and together with the report that inhibition of monoamine oxidase B with deprenyl not only potentiated the effects of levodopa, but appeared to prolong the life of parkinsonian patients, resulted in a large-scale trial of drugs that might arrest the degenerative process. Furthermore, the MPTP primate model of Parkinson's disease has encouraged development of fetal mesencephalic and other tissue implant approaches to reversal of parkinsonism. Although much of this is still in the experimental stages, hopes are high that new and more effective therapies will be developed and that similar techniques might be applicable to a wide variety of neuropsychiatric disorders. JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology AU - Kopin, I J AD - Intramural Research, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/08// PY - 1993 DA - August 1993 SP - 1 EP - 12 VL - 9 IS - 1 SN - 0893-133X, 0893-133X KW - Index Medicus KW - History of medicine KW - Animals KW - History, 20th Century KW - Humans KW - Parkinson Disease -- physiopathology KW - Parkinson Disease -- history UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75932400?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuropsychopharmacology+%3A+official+publication+of+the+American+College+of+Neuropsychopharmacology&rft.atitle=Parkinson%27s+disease%3A+past%2C+present%2C+and+future.&rft.au=Kopin%2C+I+J&rft.aulast=Kopin&rft.aufirst=I&rft.date=1993-08-01&rft.volume=9&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Neuropsychopharmacology+%3A+official+publication+of+the+American+College+of+Neuropsychopharmacology&rft.issn=0893133X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-11-08 N1 - Date created - 1993-11-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of P-glycoprotein/multidrug resistance genes from model organisms. AN - 75928050; 8361216 AB - Using degenerate oligonucleotides from conserved portions of the ATP-binding domain of the active transporter genes, several new members of this gene superfamily have been cloned from Drosophila, Saccharomyces cerevisiae, and E. coli DNA. The Drosophila and E. coli genes contain two sets of transmembrane domains and two ATP-binding domains, whereas the yeast gene contains single transmembrane and ATP-binding domains. All three genes show a high degree of similarity to the mammalian P-glycoprotein/multidrug resistance (MDR) genes. The E. coli sequence is the only known transporter gene containing both ATP and transmembrane domains in a single open reading frame. While the function of these sequences has not been determined, they may prove to be useful for developing a model to study the function of P-glycoproteins. JF - Leukemia AU - Allikmets, R AU - Gerrard, B AU - Stewart, C AU - White, M AU - Dean, M AD - Laboratory of Viral Carcinogenesis, Program Resources Inc./DynCorp, National Cancer Institute, Frederick Cancer Research and Development Center, MD 21702. Y1 - 1993/08// PY - 1993 DA - August 1993 SP - S13 EP - S17 VL - 7 Suppl 2 SN - 0887-6924, 0887-6924 KW - MDR KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - Index Medicus KW - Polymerase Chain Reaction KW - Animals KW - Base Sequence KW - Sequence Alignment KW - Chromosome Banding KW - Adenosine Triphosphate -- metabolism KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Adenosine Triphosphate -- genetics KW - Saccharomyces cerevisiae -- genetics KW - Drug Resistance -- genetics KW - Conserved Sequence -- genetics KW - Drosophila melanogaster -- genetics KW - Escherichia coli -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75928050?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Leukemia&rft.atitle=Identification+of+P-glycoprotein%2Fmultidrug+resistance+genes+from+model+organisms.&rft.au=Allikmets%2C+R%3BGerrard%2C+B%3BStewart%2C+C%3BWhite%2C+M%3BDean%2C+M&rft.aulast=Allikmets&rft.aufirst=R&rft.date=1993-08-01&rft.volume=7+Suppl+2&rft.issue=&rft.spage=S13&rft.isbn=&rft.btitle=&rft.title=Leukemia&rft.issn=08876924&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-09-30 N1 - Date created - 1993-09-30 N1 - Date revised - 2017-01-13 N1 - Gene symbol - MDR N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - 1992 Stohlman Memorial Lecture: targeting the IL-2 receptor. AN - 75921560; 8361223 AB - Patients with human T-cell lymphotropic virus I (HTLV-I)-associated leukemia/lymphoma were treated with different forms of IL-2 receptor (IL-2R)-directed therapy that exploit the difference in IL-2R expression between normal and malignant cells. Using unmodified anti-Tac monoclonal antibody, one-third of the patients with adult T-cell leukemia (ATL) treated have undergone a remission, in two cases complete. There was little toxicity observed; however, unmodified monoclonal antibodies are limited by their immunogenicity and their poor effector functions. To address these issues, "humanized" anti-Tac was produced that contains the complementarity-determining regions from the mouse with the remainder of the molecule derived from human IgG1 kappa. This antibody is dramatically less immunogenic than the murine version, has improved pharmacokinetics, and, in contrast to the parent antibody, manifests antibody-dependent cellular cytotoxicity (ADCC). To enhance its effector function, anti-Tac was armed with toxins and alpha- and beta-emitting radionuclides. In a clinical trial of 90Y-anti-Tac in ATL patients, at the doses used (5, 10, and 15 mCi 90Y-anti-Tac per patient), 10 of the 15 patients with ATL treated to date underwent sustained partial or complete remission. Thus, the clinical application of IL-2R-directed therapy represents a new perspective for the prevention of allograft rejection and for the treatment of graft-versus-host disease, select autoimmune disorders, and leukemia/lymphoma. JF - Leukemia AU - Waldmann, T A AD - Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/08// PY - 1993 DA - August 1993 SP - S151 EP - S156 VL - 7 Suppl 2 SN - 0887-6924, 0887-6924 KW - Antibodies, Monoclonal KW - 0 KW - Immunotoxins KW - Receptors, Interleukin-2 KW - Index Medicus KW - AIDS/HIV KW - Humans KW - Immunotoxins -- therapeutic use KW - Lymphocyte Activation KW - Receptors, Interleukin-2 -- metabolism KW - Leukemia-Lymphoma, Adult T-Cell -- therapy KW - Leukemia-Lymphoma, Adult T-Cell -- radiotherapy KW - Receptors, Interleukin-2 -- immunology KW - Immunotherapy -- methods KW - Antibodies, Monoclonal -- therapeutic use KW - Antibodies, Monoclonal -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75921560?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Leukemia&rft.atitle=1992+Stohlman+Memorial+Lecture%3A+targeting+the+IL-2+receptor.&rft.au=Waldmann%2C+T+A&rft.aulast=Waldmann&rft.aufirst=T&rft.date=1993-08-01&rft.volume=7+Suppl+2&rft.issue=&rft.spage=S151&rft.isbn=&rft.btitle=&rft.title=Leukemia&rft.issn=08876924&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-09-30 N1 - Date created - 1993-09-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A decomposition product of a contaminant implicated in L-tryptophan eosinophilia myalgia syndrome affects spinal cord neuronal cell death and survival through stereospecific, maturation and partly interleukin-1-dependent mechanisms. AN - 75916798; 8355179 AB - The L-tryptophan eosinophilia myalgia syndrome (L-TRP-EMS), an inflammatory syndrome characterized by eosinophilia, myalgias, perimyositis, fasciitis and neuropathies, occurred in epidemic proportions in the United States in the summer and fall of 1989. The neuropathic clinical features in L-TRP EMS are complex and mixed. In the present study, one of the impurities most highly associated with development of L-TRP EMS, 1,1'-ethylidenebis[L-tryptophan] (EBT), and two of its diastereoisomeric breakdown products, were compared for evidence of neurotoxicity in vitro. In 1-month-old spinal cord cultures derived from fetal mice, synthetic (-)-(1S,3S)-1-methyl-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid (1S-beta-C) produced a 30 to 35% loss in numbers of neurons. Toxicity was not apparent after treatment with the R-isomer of the same compound or with the parent compound, EBT. Cotreatment of cultures with 1S-beta-C and neutralizing antiserum to interleukin-1 alpha (IL-1 alpha), or with 1S-beta-C and neutralizing antiserum against the murine IL-1 receptor, prevented neuronal cell death associated with 1S-beta-C. Recombinant IL-1 alpha also produced neuronal killing that was not additive to that observed with the 1S-beta-C treatment. In contrast, in immature spinal cord neuronal cultures, the 1S-beta-C, but not the 1R-beta-C or EBT, prevented the 30% cell death which normally occurs in these cultures. Neither neutralizing anti-IL-1 antibody, nor anti-IL-1 receptor antibody blocked the neuronal survival effect, suggesting that 1S-beta-C induces neuronal survival through a receptor-mediated mechanism independent of IL-1.(ABSTRACT TRUNCATED AT 250 WORDS) JF - The Journal of pharmacology and experimental therapeutics AU - Brenneman, D E AU - Page, S W AU - Schultzberg, M AU - Thomas, F S AU - Zelazowski, P AU - Burnet, P AU - Avidor, R AU - Sternberg, E M AD - Section on Developmental and Molecular Pharmacology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland. Y1 - 1993/08// PY - 1993 DA - August 1993 SP - 1029 EP - 1035 VL - 266 IS - 2 SN - 0022-3565, 0022-3565 KW - Carbolines KW - 0 KW - Interleukin-1 KW - Receptors, Interleukin-1 KW - Recombinant Proteins KW - 1,1'-ethylidene bis(tryptophan) KW - 132685-02-0 KW - 1-methyl-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid KW - 5470-37-1 KW - Tryptophan KW - 8DUH1N11BX KW - Index Medicus KW - Animals KW - Stereoisomerism KW - Recombinant Proteins -- pharmacology KW - Cell Survival -- drug effects KW - Cells, Cultured KW - Mice KW - Receptors, Interleukin-1 -- physiology KW - Cell Death -- drug effects KW - Female KW - Pregnancy KW - Interleukin-1 -- physiology KW - Tryptophan -- analogs & derivatives KW - Tryptophan -- toxicity KW - Drug Contamination KW - Spinal Cord -- drug effects KW - Eosinophilia-Myalgia Syndrome -- etiology KW - Carbolines -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75916798?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+decomposition+product+of+a+contaminant+implicated+in+L-tryptophan+eosinophilia+myalgia+syndrome+affects+spinal+cord+neuronal+cell+death+and+survival+through+stereospecific%2C+maturation+and+partly+interleukin-1-dependent+mechanisms.&rft.au=Brenneman%2C+D+E%3BPage%2C+S+W%3BSchultzberg%2C+M%3BThomas%2C+F+S%3BZelazowski%2C+P%3BBurnet%2C+P%3BAvidor%2C+R%3BSternberg%2C+E+M&rft.aulast=Brenneman&rft.aufirst=D&rft.date=1993-08-01&rft.volume=266&rft.issue=2&rft.spage=1029&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 - 1993-09-17 N1 - Date created - 1993-09-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genotype/phenotype discordance for human arylamine N-acetyltransferase (NAT2) reveals a new slow-acetylator allele common in African-Americans. AN - 75914060; 8102597 AB - Carcinogenic arylamines are acetylated by the hepatic N-acetyltransferase. This enzyme is polymorphic in humans and in some epidemiological studies, the slow-acetylator phenotype has been associated with higher risk of bladder cancer and lower risk of colorectal cancer. The presence of two germline copies of any of several mutant alleles of the NAT2 gene produces a slow-acetylation phenotype. We used a PCR-RFLP technique to identify three known slow-acetylator alleles (M1, M2 and M3). Comparison of results from PCR-RFLP genotyping with caffeine metabolism phenotyping in 42 individuals suggested that an additional slow-acetylator allele was present in our sampled population. We sequenced the NAT2 gene for several discordant slow-acetylator individuals and found a G > A base-change in codon 64 that caused a Arg > Glu amino acid substitution. This sequence change, termed the 'M4' allele, was found in all of the discordant individuals in our population and apparently causes a slow-acetylation phenotype. In addition, we have determined that NAT2 allele frequencies in 372 Caucasian-Americans (WT = 0.25, M1 = 0.45, M2 = 0.28, M3 = 0.02, and M4 = 0.00) and in 128 African-Americans (WT = 0.36, M1 = 0.30, M2 = 0.22, M3 = 0.02 and M4 = 0.09) are significantly different (P < 0.0001). The M4 allele was not found in 372 unrelated Caucasians and appears to be of African origin. JF - Carcinogenesis AU - Bell, D A AU - Taylor, J A AU - Butler, M A AU - Stephens, E A AU - Wiest, J AU - Brubaker, L H AU - Kadlubar, F F AU - Lucier, G W AD - Laboratory of Biochemical Risk Analysis, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1993/08// PY - 1993 DA - August 1993 SP - 1689 EP - 1692 VL - 14 IS - 8 SN - 0143-3334, 0143-3334 KW - NAT2 KW - Xanthines KW - 0 KW - Caffeine KW - 3G6A5W338E KW - Uracil KW - 56HH86ZVCT KW - 1-methylxanthine KW - 7EE8WCA32U KW - 5-acetylamino-6-formylamino-3-methyluracil KW - 85438-96-6 KW - Arylamine N-Acetyltransferase KW - EC 2.3.1.5 KW - Index Medicus KW - United States KW - Caffeine -- metabolism KW - Uracil -- analogs & derivatives KW - Humans KW - Amino Acid Sequence KW - Xanthines -- urine KW - Caffeine -- urine KW - Genotype KW - Phenotype KW - Acetylation KW - Polymerase Chain Reaction KW - Base Sequence KW - Polymorphism, Restriction Fragment Length KW - Molecular Sequence Data KW - Sequence Homology, Amino Acid KW - Uracil -- urine KW - Alleles KW - African Continental Ancestry Group -- genetics KW - Arylamine N-Acetyltransferase -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75914060?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Genotype%2Fphenotype+discordance+for+human+arylamine+N-acetyltransferase+%28NAT2%29+reveals+a+new+slow-acetylator+allele+common+in+African-Americans.&rft.au=Bell%2C+D+A%3BTaylor%2C+J+A%3BButler%2C+M+A%3BStephens%2C+E+A%3BWiest%2C+J%3BBrubaker%2C+L+H%3BKadlubar%2C+F+F%3BLucier%2C+G+W&rft.aulast=Bell&rft.aufirst=D&rft.date=1993-08-01&rft.volume=14&rft.issue=8&rft.spage=1689&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-09-21 N1 - Date created - 1993-09-21 N1 - Date revised - 2017-01-13 N1 - Gene symbol - NAT2 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Prolactin induces maturation of glucose sensing mechanisms in cultured neonatal rat islets. AN - 75911525; 8344197 AB - The effects of PRL treatment on insulin content and secretion, and 86Rb and 45Ca fluxes from neonatal rat islets maintained in culture for 7-9 days were studied. PRL treatment enhanced islet insulin content by 40% and enhanced early insulin secretion evoked by 16.7 mM glucose. Insulin release stimulated by oxotremorine-M, a muscarinic agonist, in the presence of glucose (8.3 or 16.7 mM) was unchanged by PRL treatment. However, PRL treatment potentiated phorbol 12,13-dibutyrate-stimulated insulin secretion in the presence of the above glucose concentrations. PRL treatment potentiated the reduction in 86Rb efflux induced by glucose or tolbutamide and enhanced the increase in 86Rb efflux evoked by diazoxide. PRL treatment slightly potentiated the increment in 45Ca uptake induced by high concentrations of K+, but failed to affect the increment evoked by 16.7 mM glucose. Since glucose-induced 45Ca uptake was not affected by PRL, we suggest that the enhancement in first phase insulin secretion evoked by glucose in the PRL-treated islets occurs at a step in the secretory process that may involve protein kinase-C. These data further support observations that PRL treatment increases islet sensitivity to glucose. JF - Endocrinology AU - Boschero, A C AU - Crepaldi, S C AU - Carneiro, E M AU - Delattre, E AU - Atwater, I AD - Laboratory of Cell Biology and Genetics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/08// PY - 1993 DA - August 1993 SP - 515 EP - 520 VL - 133 IS - 2 SN - 0013-7227, 0013-7227 KW - Calcium Radioisotopes KW - 0 KW - Insulin KW - Rubidium Radioisotopes KW - Phorbol 12,13-Dibutyrate KW - 37558-16-0 KW - Oxotremorine KW - 5RY0UWH1JL KW - oxotremorine M KW - 63939-65-1 KW - Prolactin KW - 9002-62-4 KW - Tolbutamide KW - 982XCM1FOI KW - Glucose KW - IY9XDZ35W2 KW - Potassium KW - RWP5GA015D KW - Abridged Index Medicus KW - Index Medicus KW - Rats KW - Calcium Radioisotopes -- metabolism KW - Animals KW - Oxotremorine -- pharmacology KW - Cells, Cultured KW - Tolbutamide -- pharmacology KW - Rubidium Radioisotopes -- metabolism KW - Potassium -- pharmacology KW - Insulin -- secretion KW - Oxotremorine -- analogs & derivatives KW - Drug Synergism KW - Phorbol 12,13-Dibutyrate -- pharmacology KW - Animals, Newborn KW - Islets of Langerhans -- growth & development KW - Glucose -- pharmacology KW - Islets of Langerhans -- drug effects KW - Prolactin -- pharmacology KW - Islets of Langerhans -- secretion UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75911525?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Prolactin+induces+maturation+of+glucose+sensing+mechanisms+in+cultured+neonatal+rat+islets.&rft.au=Boschero%2C+A+C%3BCrepaldi%2C+S+C%3BCarneiro%2C+E+M%3BDelattre%2C+E%3BAtwater%2C+I&rft.aulast=Boschero&rft.aufirst=A&rft.date=1993-08-01&rft.volume=133&rft.issue=2&rft.spage=515&rft.isbn=&rft.btitle=&rft.title=Endocrinology&rft.issn=00137227&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-09-03 N1 - Date created - 1993-09-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Repair of ribosomal RNA genes in hamster cells after UV irradiation, or treatment with cisplatin or alkylating agents. AN - 75910243; 8353843 AB - We have measured the DNA damage formation and repair in the ribosomal and the dihydrofolate reductase (DHFR) genes after treatment of hamster cells with different types of DNA damaging agents. In mammalian cells, the ribosomal DNA (rDNA) is transcribed by RNA polymerase I, whereas the DHFR is transcribed by RNA polymerase II, whereas the DHFR is transcribed by RNA polymerase II. Cells were treated with agents that induce different types of lesions, and that are known to be repaired via different pathways. We used UV (254 nm) irradiation, treatment with cisplatin and treatment with the alkylating agents nitrogen mustard (HN2) and methyl methanesulphonate (MMS). UV induced pyrimidine dimers were detected with the enzyme T4 endonuclease V, which creates nicks at the dimer sites; the breaks are then resolved and identified by denaturing electrophoresis and Southern blot. Intrastrand adducts formed by the alkylating agents HN2 and MMS were quantitated by generating strand breaks at abasic sites after neutral depurination. Interstrand crosslinks (ICL) formed by HN2 and cisplatin were detected by a denaturation-reannealing reaction before neutral agarose gel-electrophoresis. We find that the repair of the pyrimidine dimers is significantly less efficient in the RNA polymerase I transcribed rDNA genes than in RNA polymerase II transcribed DHFR gene at 8 and 24 h after irradiation. ICL and intrastrand adducts induced by HN2 are also removed more slowly from the rDNA than from the DHFR gene. In contrast, MMS induced intrastrand adducts and cisplatin induced ICL are repaired equally efficiently in the RNA polymerase I and RNA polymerase II transcribed genes. We conclude that for some types of DNA damage, there is less repair in the ribosomal genes than in the DHFR; but for other DNA lesions there is no difference. The difference in repair efficiency between the rDNA and the DHFR genes may reflect the different RNA polymerase involved in their transcription. It may, however, alternatively, reflect the different nuclear localization of these genes. JF - Carcinogenesis AU - Stevnsner, T AU - May, A AU - Petersen, L N AU - Larminat, F AU - Pirsel, M AU - Bohr, V A AD - Laboratory of Molecular Pharmacology, National Cancer Institute, NIH, Bethesda, MD 20892. Y1 - 1993/08// PY - 1993 DA - August 1993 SP - 1591 EP - 1596 VL - 14 IS - 8 SN - 0143-3334, 0143-3334 KW - DHFR KW - rRNA KW - Alkylating Agents KW - 0 KW - DNA, Ribosomal KW - Pyrimidine Dimers KW - RNA, Ribosomal KW - Mechlorethamine KW - 50D9XSG0VR KW - Guanine KW - 5Z93L87A1R KW - Methyl Methanesulfonate KW - AT5C31J09G KW - Tetrahydrofolate Dehydrogenase KW - EC 1.5.1.3 KW - RNA Polymerase II KW - EC 2.7.7.- KW - RNA Polymerase I KW - EC 2.7.7.6 KW - Cisplatin KW - Q20Q21Q62J KW - Index Medicus KW - Animals KW - DNA Damage KW - Pyrimidine Dimers -- metabolism KW - CHO Cells -- drug effects KW - Transcription, Genetic -- genetics KW - RNA Polymerase I -- genetics KW - Guanine -- metabolism KW - Mechlorethamine -- toxicity KW - RNA Polymerase II -- genetics KW - CHO Cells -- physiology KW - CHO Cells -- radiation effects KW - DNA, Ribosomal -- genetics KW - Tetrahydrofolate Dehydrogenase -- genetics KW - Cricetinae KW - DNA Repair -- genetics KW - Cisplatin -- toxicity KW - Genes -- drug effects KW - Ultraviolet Rays -- adverse effects KW - RNA, Ribosomal -- genetics KW - RNA, Ribosomal -- radiation effects KW - Alkylating Agents -- toxicity KW - Genes -- radiation effects KW - Genes -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75910243?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Repair+of+ribosomal+RNA+genes+in+hamster+cells+after+UV+irradiation%2C+or+treatment+with+cisplatin+or+alkylating+agents.&rft.au=Stevnsner%2C+T%3BMay%2C+A%3BPetersen%2C+L+N%3BLarminat%2C+F%3BPirsel%2C+M%3BBohr%2C+V+A&rft.aulast=Stevnsner&rft.aufirst=T&rft.date=1993-08-01&rft.volume=14&rft.issue=8&rft.spage=1591&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-09-21 N1 - Date created - 1993-09-21 N1 - Date revised - 2017-01-13 N1 - Gene symbol - DHFR; rRNA N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tityustoxin-K alpha, a structurally novel and highly potent K+ channel peptide toxin, interacts with the alpha-dendrotoxin binding site on the cloned Kv1.2 K+ channel. AN - 75907059; 8355670 AB - The interaction between two nonhomologous K+ channel toxins, Tityus serrulatus (scorpion) toxin tityustoxin-K alpha (TsTX-K alpha) and Dendroaspis angusticeps (snake) toxin dendrotoxin (alpha-DTX), was investigated on K+ currents in B82 fibroblast cells transformed to express the Kv1.2 K+ channel. As demonstrated previously, alpha-DTX was a potent blocker of the K+ current (Kd, 2.8 nM). Recombinant TsTX-K alpha produced a similar block of the current but was 1 order of magnitude more potent (Kd, 0.21 nM). TsTX-K alpha did not affect the kinetic properties of the current or its voltage dependence of activation. Experiments with excised and cell-attached patch recordings demonstrated that TsTX-K alpha blocks the K+ channel by binding to an extracellular site. In the presence of TsTX-K alpha the blocking potency of alpha-DTX was reduced, whereas the potency of 4-aminopyridine, which also blocks the channel, was unaffected. alpha-DTX caused a rightward shift in the scaled concentration-response curve for TsTX-K alpha, the magnitude of which was reasonably well predicted by a model in which there is a competitive interaction between the two peptide toxins. We conclude that TsTX-K alpha and alpha-DTX block the Kv1.2 K+ channel by binding to the same or closely related sites. JF - Molecular pharmacology AU - Werkman, T R AU - Gustafson, T A AU - Rogowski, R S AU - Blaustein, M P AU - Rogawski, M A AD - Neuronal Excitability Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/08// PY - 1993 DA - August 1993 SP - 430 EP - 436 VL - 44 IS - 2 SN - 0026-895X, 0026-895X KW - Elapid Venoms KW - 0 KW - Neurotoxins KW - Potassium Channels KW - Recombinant Proteins KW - Scorpion Venoms KW - tityustoxin KW - 39465-37-7 KW - dendrotoxin KW - 74811-93-1 KW - Index Medicus KW - Animals KW - Base Sequence KW - Recombinant Proteins -- pharmacology KW - Recombinant Proteins -- metabolism KW - Dose-Response Relationship, Drug KW - Binding, Competitive KW - Molecular Sequence Data KW - Electrophysiology KW - Cell Line KW - Binding Sites KW - Elapid Venoms -- pharmacology KW - Scorpion Venoms -- pharmacology KW - Neurotoxins -- metabolism KW - Scorpion Venoms -- metabolism KW - Neurotoxins -- pharmacology KW - Potassium Channels -- drug effects KW - Elapid Venoms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75907059?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Tityustoxin-K+alpha%2C+a+structurally+novel+and+highly+potent+K%2B+channel+peptide+toxin%2C+interacts+with+the+alpha-dendrotoxin+binding+site+on+the+cloned+Kv1.2+K%2B+channel.&rft.au=Werkman%2C+T+R%3BGustafson%2C+T+A%3BRogowski%2C+R+S%3BBlaustein%2C+M+P%3BRogawski%2C+M+A&rft.aulast=Werkman&rft.aufirst=T&rft.date=1993-08-01&rft.volume=44&rft.issue=2&rft.spage=430&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 - 1993-09-23 N1 - Date created - 1993-09-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characterization of ligand and substrate specificity for the calcium-dependent and calcium-independent protein kinase C isozymes. AN - 75906670; 8355667 AB - Analysis of [3H]phorbol-12,13-dibutyrate (PDBu) binding was performed with protein kinase C (PKC)-alpha, -beta 1, -gamma, -delta, -epsilon, -eta, and -zeta produced in Sf9 insect cells using the baculovirus expression system. With the exception of PKC-zeta, all of the PKC isozymes bound [3H]PDBu with high affinity (Kd < 1 nM), either in the presence or in the absence of calcium. Scatchard analysis using 100% phosphatidylserine vesicles revealed slightly lower affinity for the calcium-independent isozymes (PKC-delta, -epsilon, and -eta) than for the calcium-dependent isozymes (PKC-alpha, -beta, and -gamma). Competition for [3H]PDBu binding by different classes of PKC activators showed that 12-deoxyphorbol esters, mezerein, and octahydromezerein likewise possessed lower affinity for the calcium-independent isozymes. The mezerein analog thymeleatoxin was the most marked example, being almost 20-fold less potent for binding to PKC-epsilon and -eta than to PKC-beta 1. In contrast, the indole alkaloids (-)-indolactam V and (-)-octylindolactam V and the postulated endogenous activator 1,2-diacylglycerol bound with similar affinities to all of the PKC isoforms, suggesting that different residues/configurations in the binding sites of the different PKC isozymes might be involved in interaction with the pharmacophore of the activators. The seven PKC isozymes also showed clearly different substrate specificities with exogenous peptide and protein substrates. The heterogeneous behavior of the different members of the PKC family with ligands and substrates may contribute to the heterogeneity of PKC-mediated pathways at the cellular level. JF - Molecular pharmacology AU - Kazanietz, M G AU - Areces, L B AU - Bahador, A AU - Mischak, H AU - Goodnight, J AU - Mushinski, J F AU - Blumberg, P M AD - Molecular Mechanisms of Tumor Promotion Section, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1993/08// PY - 1993 DA - August 1993 SP - 298 EP - 307 VL - 44 IS - 2 SN - 0026-895X, 0026-895X KW - Isoenzymes KW - 0 KW - Recombinant Proteins KW - Phorbol 12,13-Dibutyrate KW - 37558-16-0 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Baculoviridae -- genetics KW - Animals KW - Base Sequence KW - Recombinant Proteins -- metabolism KW - Enzyme Activation KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Substrate Specificity KW - Recombinant Proteins -- chemistry KW - Moths KW - Cell Line KW - Structure-Activity Relationship KW - Protein Kinase C -- metabolism KW - Calcium -- metabolism KW - Phorbol 12,13-Dibutyrate -- metabolism KW - Protein Kinase C -- chemistry KW - Isoenzymes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75906670?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Characterization+of+ligand+and+substrate+specificity+for+the+calcium-dependent+and+calcium-independent+protein+kinase+C+isozymes.&rft.au=Kazanietz%2C+M+G%3BAreces%2C+L+B%3BBahador%2C+A%3BMischak%2C+H%3BGoodnight%2C+J%3BMushinski%2C+J+F%3BBlumberg%2C+P+M&rft.aulast=Kazanietz&rft.aufirst=M&rft.date=1993-08-01&rft.volume=44&rft.issue=2&rft.spage=298&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 - 1993-09-23 N1 - Date created - 1993-09-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Generation of varicella-zoster virus (VZV) and viral mutants from cosmid DNAs: VZV thymidylate synthetase is not essential for replication in vitro. AN - 75906322; 8394020 AB - Four overlapping cosmid clones were constructed that contain the complete genome of the attenuated Oka strain of VZV. Transfection of human melanoma cells with the four cosmids resulted in production of infectious VZV. A double-stranded oligonucleotide, encoding a stop codon in all three open reading frames, was inserted into one of the cosmids at the 5' end of the viral thymidylate synthetase gene. Transfection of melanoma cells with the mutant cosmid, along with the other three cosmids, resulted in VZV that does not express the viral thymidylate synthetase protein. The mutant virus grew at a rate similar to that of the parental Oka strain virus. Production of recombinant VZV using cosmid DNAs will be useful for studying the function of viral genes in VZV replication and establishment of latency. Furthermore, manipulation of the Oka strain of VZV might allow one to produce a vaccine virus that does not establish latency in the central nervous system or a virus that encodes foreign antigens for use as a polyvalent live virus vaccine. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Cohen, J I AU - Seidel, K E AD - Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/08/01/ PY - 1993 DA - 1993 Aug 01 SP - 7376 EP - 7380 VL - 90 IS - 15 SN - 0027-8424, 0027-8424 KW - DNA, Viral KW - 0 KW - Oligodeoxyribonucleotides KW - Viral Structural Proteins KW - Thymidylate Synthase KW - EC 2.1.1.45 KW - Acyclovir KW - X4HES1O11F KW - Index Medicus KW - Humans KW - Cosmids KW - Cloning, Molecular KW - Structure-Activity Relationship KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Acyclovir -- pharmacology KW - Tumor Cells, Cultured KW - Transfection KW - Oligodeoxyribonucleotides -- chemistry KW - In Vitro Techniques KW - Molecular Sequence Data KW - Genes, Viral KW - Viral Structural Proteins -- genetics KW - DNA, Viral -- genetics KW - Virus Replication KW - Thymidylate Synthase -- genetics KW - Herpesvirus 3, Human -- growth & development KW - Herpesvirus 3, Human -- genetics KW - Herpesvirus 3, Human -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75906322?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Generation+of+varicella-zoster+virus+%28VZV%29+and+viral+mutants+from+cosmid+DNAs%3A+VZV+thymidylate+synthetase+is+not+essential+for+replication+in+vitro.&rft.au=Cohen%2C+J+I%3BSeidel%2C+K+E&rft.aulast=Cohen&rft.aufirst=J&rft.date=1993-08-01&rft.volume=90&rft.issue=15&rft.spage=7376&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 - 1993-09-07 N1 - Date created - 1993-09-07 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Virol. 1992 Sep;66(9):5298-304 [1323696] Proc Natl Acad Sci U S A. 1986 Jun;83(11):3604-8 [3012520] J Gen Virol. 1986 Sep;67 ( Pt 9):1759-816 [3018124] J Gen Virol. 1987 May;68 ( Pt 5):1449-55 [3033144] Proc Natl Acad Sci U S A. 1987 Jun;84(11):3896-900 [3035557] Nucleic Acids Res. 1988 Mar 25;16(6):2601-12 [2834694] J Virol. 1988 Jun;62(6):2191-5 [2835520] J Virol. 1988 Sep;62(9):3530-5 [3404583] Proc Natl Acad Sci U S A. 1989 Feb;86(3):1051-5 [2536930] J Virol. 1989 May;63(5):2392-5 [2539528] J Virol. 1990 Oct;64(10):4691-6 [2168958] J Gen Virol. 1991 Mar;72 ( Pt 3):475-86 [1848588] J Virol. 1991 May;65(5):2761-5 [1850051] J Gen Virol. 1991 Jun;72 ( Pt 6):1393-9 [1646279] N Engl J Med. 1991 Nov 28;325(22):1545-50 [1658650] J Virol. 1992 Jan;66(1):359-66 [1309252] J Infect Dis. 1992 Aug;166 Suppl 1:S63-8 [1320652] Biken J. 1975 Mar;18(1):25-33 [167707] Infect Immun. 1978 Jan;19(1):199-203 [203532] J Virol. 1981 Nov;40(2):516-25 [6275100] J Virol. 1983 Nov;48(2):377-83 [6312095] J Virol. 1984 Mar;49(3):938-46 [6321774] J Virol. 1992 Dec;66(12):7303-8 [1366099] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Depression of catalase gene expression after immortalization and transformation of mouse liver cells. AN - 75905676; 8353835 AB - To understand the molecular basis of the remarkable decrease of catalase activity after immortalization and malignant transformation of mouse liver cells, expression of the catalase gene was studied in in vivo mouse liver cells and nontransformed normal mouse liver cell line as well as liver cell lines transformed by N-methyl-N-nitro-N-nitrosoguanidine, SV40 virus or by conventional subcultivation. In vivo liver cells had much greater levels of catalase mRNA and immunoreactive protein than in vitro cell lines, which correlates with elevated enzyme activity. Among the cell lines, normal cells had in general higher mRNA levels and more catalase protein than that of the transformed cell lines, also correlating with enzyme activity. The down regulation of catalase gene expression seen in transformed lines may occur transcriptionally rather than posttranscriptionally as demonstrated by cycloheximide and/or actinomycin D treatment. The striking difference in catalase gene expression seen between liver tissue and liver cell lines was unlikely due to gross structural alterations in the catalase gene, but might be explained by a remarkable difference in methylation status of the catalase gene, as demonstrated by Southern blot analysis following HpaII digestion. Our results suggested that during cellular immortalization and malignant transformation, a change in the oxidant stress ultimately led to a cellular response that, in turn, led to down regulation of the catalase gene. JF - Carcinogenesis AU - Sun, Y AU - Colburn, N H AU - Oberley, L W AD - Cell Biology Section, National Cancer Institute, Frederick Cancer Research and Development Center, MD. Y1 - 1993/08// PY - 1993 DA - August 1993 SP - 1505 EP - 1510 VL - 14 IS - 8 SN - 0143-3334, 0143-3334 KW - Neoplasm Proteins KW - 0 KW - Catalase KW - EC 1.11.1.6 KW - Index Medicus KW - Animals KW - Down-Regulation -- physiology KW - Neoplasm Proteins -- immunology KW - Neoplasm Proteins -- genetics KW - Transcription, Genetic -- genetics KW - Mice, Nude KW - Mice KW - Cell Line, Transformed KW - Mice, Inbred BALB C KW - Neoplasm Proteins -- metabolism KW - Methylation KW - Cell Line KW - Catalase -- metabolism KW - Liver -- enzymology KW - Liver -- cytology KW - Gene Expression Regulation, Enzymologic -- genetics KW - Cell Transformation, Neoplastic -- metabolism KW - Catalase -- genetics KW - Liver -- physiology KW - Cell Transformation, Neoplastic -- genetics KW - Gene Expression Regulation, Neoplastic -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75905676?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Depression+of+catalase+gene+expression+after+immortalization+and+transformation+of+mouse+liver+cells.&rft.au=Sun%2C+Y%3BColburn%2C+N+H%3BOberley%2C+L+W&rft.aulast=Sun&rft.aufirst=Y&rft.date=1993-08-01&rft.volume=14&rft.issue=8&rft.spage=1505&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-09-21 N1 - Date created - 1993-09-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of the selective sigma receptor ligand, 6-[6-(4-hydroxypiperidinyl)hexyloxy]-3-methylflavone (NPC 16377), on behavioral and toxic effects of cocaine. AN - 75905634; 8355185 AB - Certain sigma receptor ligands have been shown to block locomotor stimulation produced by cocaine at doses that do not have significant behavioral activity when given alone. Using a potent and selective ligand of sigma binding sites, 6-[6-(4-hydroxypiperidinyl)hexyloxy]-3-methylflavone (NPC 16377), we further investigated the influence of sigma ligands on additional behavioral and toxic effects of cocaine in mice. A behaviorally inactive dose of NPC 16377 shifted the dose-effect function for the locomotor stimulant effects of cocaine to the right by a factor of 2.5. A higher dose of NPC 16377 produced an insurmountable blockade of this stimulant effect of cocaine. Prior exposure to cocaine enhances the locomotor stimulant effects of cocaine (sensitization). NPC 16377 prevented the development of cocaine sensitization without producing behavioral effects of its own. However, NPC 16377 was unable to block the expression of sensitization in mice previously exposed to cocaine. NPC 16377 also did not consistently alter the discriminative stimulus effects of cocaine or methamphetamine in rats discriminating either 3 or 10 mg/kg of cocaine, or 1 mg/kg of methamphetamine from saline. The potential phencyclidine-like behavioral effects of NPC 16377 were also evaluated. Unlike the NMDA channel ligand, dizocilpine, NPC 16377 did not increase responding under a fixed-interval schedule of food presentation in rats nor did it substitute for the discriminative stimulus effects of either 1.5 mg/kg of phencyclidine or 0.2 mg/kg of dizocilpine in rats discriminating these drugs from saline. NPC 16377 displayed limited but significant anticonvulsant activity against diazepam-sensitive cocaine convulsions. The lethal effects of higher doses of cocaine were neither significantly blocked nor enhanced in rats or mice with NPC 16377. These findings extend earlier observations on the cocaine-blocking effects of sigma ligands to a novel structure with exceptional selectivity for sigma sites. These data indicate that some sigma ligands may be capable of altering certain behavioral and toxic actions of cocaine without notable behavioral side effects as evidenced in preclinical tests. As such, these compounds may ultimately be useful in the treatment of cocaine abuse. JF - The Journal of pharmacology and experimental therapeutics AU - Witkin, J M AU - Terry, P AU - Menkel, M AU - Hickey, P AU - Pontecorvo, M AU - Ferkany, J AU - Katz, J L AD - Psychobiology Section, National Institute on Drug Abuse, Baltimore, Maryland. Y1 - 1993/08// PY - 1993 DA - August 1993 SP - 473 EP - 482 VL - 266 IS - 2 SN - 0022-3565, 0022-3565 KW - Flavonoids KW - 0 KW - Piperidines KW - Receptors, sigma KW - 6-(6-(4-hydroxypiperidinyl)hexyloxy)-3-methylflavone hydrochloride KW - 139652-86-1 KW - Methamphetamine KW - 44RAL3456C KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Seizures -- chemically induced KW - Rats KW - Discrimination Learning -- drug effects KW - Animals KW - Rats, Sprague-Dawley KW - Methamphetamine -- pharmacology KW - Mice KW - Male KW - Conditioning (Psychology) -- drug effects KW - Piperidines -- pharmacology KW - Receptors, sigma -- drug effects KW - Cocaine -- toxicity KW - Motor Activity -- drug effects KW - Flavonoids -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75905634?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Effects+of+the+selective+sigma+receptor+ligand%2C+6-%5B6-%284-hydroxypiperidinyl%29hexyloxy%5D-3-methylflavone+%28NPC+16377%29%2C+on+behavioral+and+toxic+effects+of+cocaine.&rft.au=Witkin%2C+J+M%3BTerry%2C+P%3BMenkel%2C+M%3BHickey%2C+P%3BPontecorvo%2C+M%3BFerkany%2C+J%3BKatz%2C+J+L&rft.aulast=Witkin&rft.aufirst=J&rft.date=1993-08-01&rft.volume=266&rft.issue=2&rft.spage=473&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 - 1993-09-17 N1 - Date created - 1993-09-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Frequent cocaine users and their use of treatment. AN - 75903735; 8342725 AB - Despite decreases in the number of cocaine users since 1985, the consequences of cocaine use continue to rise. This paper provides descriptive data on frequent cocaine users that will help to explain these diverging trends and enable treatment planners to better predict the types of cocaine users who are likely to seek treatment. Data from the National Household Survey on Drug Abuse were used to study the characteristics of frequent cocaine users since 1985. The 1991 data were used to compare frequent users with infrequent users and nonusers. Since 1985, frequent cocaine users have become older. In 1991, they were likely to be unemployed (32.4%), unmarried (82.3%), and without health insurance (39.4%). Most were cigarette smokers (86.8%) and marijuana users (88.4%), and 32.0% reported getting drunk weekly. Criminal behavior was more likely among frequent cocaine users than among frequent cocaine users than among infrequent users and nonusers. Almost a third (30.0%) reported drug abuse treatment experience in the past year. Despite the recent decreases in overall prevalence of cocaine use, the need for treatment of cocaine abusers will continue. Treatment must address multiple problems that occur in conjunction with cocaine abuse. JF - American journal of public health AU - Gfroerer, J C AU - Brodsky, M D AD - National Institute on Drug Abuse, Rockville, Md. Y1 - 1993/08// PY - 1993 DA - August 1993 SP - 1149 EP - 1154 VL - 83 IS - 8 SN - 0090-0036, 0090-0036 KW - Cocaine KW - I5Y540LHVR KW - Abridged Index Medicus KW - Index Medicus KW - Socioeconomic Factors KW - Crime KW - Humans KW - Health Status KW - Health Services -- utilization KW - Adult KW - Child KW - Adolescent KW - United States -- epidemiology KW - Male KW - Female KW - Substance-Related Disorders -- rehabilitation KW - Substance-Related Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75903735?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+public+health&rft.atitle=Frequent+cocaine+users+and+their+use+of+treatment.&rft.au=Gfroerer%2C+J+C%3BBrodsky%2C+M+D&rft.aulast=Gfroerer&rft.aufirst=J&rft.date=1993-08-01&rft.volume=83&rft.issue=8&rft.spage=1149&rft.isbn=&rft.btitle=&rft.title=American+journal+of+public+health&rft.issn=00900036&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-09-02 N1 - Date created - 1993-09-02 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Int J Addict. 1990-1991;25(3A):377-409 [2289843] Br J Addict. 1992 Sep;87(9):1345-51 [1392556] Int J Addict. 1992;27(7):817-47 [1618584] JAMA. 1991 Oct 23-30;266(16):2272-3 [1920728] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evolving risk factors for infectious complications of cancer therapy. AN - 75901292; 8354656 AB - Advances in the supportive care of cancer patients have led to improved long-term outcomes. Infection, however, remains the most significant complication of cancer therapy. The author reviews the impact of new cancer therapies on the risk factors for infectious complications and the impact of therapy on the alterations in host defense. The relative importance of therapy-induced changes are contrasted with immunologic abnormalities associated with specific cancers. In addition, the author contrasts these changes with the infectious complications of human immunodeficiency virus infection, highlighting common themes in immunocompromised patients. JF - Hematology/oncology clinics of North America AU - Chanock, S AD - Pediatric Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland. Y1 - 1993/08// PY - 1993 DA - August 1993 SP - 771 EP - 793 VL - 7 IS - 4 SN - 0889-8588, 0889-8588 KW - Anti-Bacterial Agents KW - 0 KW - Antineoplastic Agents KW - Cytokines KW - Index Medicus KW - AIDS/HIV KW - Streptococcal Infections -- etiology KW - Anti-Bacterial Agents -- therapeutic use KW - Acquired Immunodeficiency Syndrome -- complications KW - Cytokines -- therapeutic use KW - Risk Factors KW - Humans KW - Drug Resistance, Microbial KW - Pneumonia, Pneumocystis -- etiology KW - Neutropenia -- chemically induced KW - Infection Control KW - Cross Infection -- prevention & control KW - Antineoplastic Agents -- adverse effects KW - Infection -- etiology KW - Neoplasms -- complications KW - Immunocompromised Host KW - Neoplasms -- etiology KW - Neoplasms -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75901292?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Hematology%2Foncology+clinics+of+North+America&rft.atitle=Evolving+risk+factors+for+infectious+complications+of+cancer+therapy.&rft.au=Chanock%2C+S&rft.aulast=Chanock&rft.aufirst=S&rft.date=1993-08-01&rft.volume=7&rft.issue=4&rft.spage=771&rft.isbn=&rft.btitle=&rft.title=Hematology%2Foncology+clinics+of+North+America&rft.issn=08898588&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-09-21 N1 - Date created - 1993-09-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ultraviolet-induced mutations in Cockayne syndrome cells are primarily caused by cyclobutane dimer photoproducts while repair of other photoproducts is normal. AN - 75900615; 8346243 AB - We compared the contribution to mutagenesis in Cockayne syndrome (CS) cells of the major class of UV photoproducts, the cyclobutane pyrimidine dimer, to that of other DNA photoproducts by using the mutagenesis shuttle vector pZ189. Lymphoblastoid cell lines from the DNA repair-deficient disorders CS and xeroderma pigmentosum (XP) and a normal line were transfected with UV-treated pZ189. Cyclobutane dimers were selectively removed before transfection by photoreactivation (PR), leaving nondimer photoproducts intact. After UV exposure and replication in CS and XP cells, plasmid survival was abnormally reduced and mutation frequency was abnormally elevated. After PR, plasmid survival increased and mutation frequency in CS cells decreased to normal levels but remained abnormal in XP cells. Sequence analysis of > 200 mutant plasmids showed that with CS cells a major mutational hot spot was caused by unrepaired cyclobutane dimers. These data indicate that with both CS and XP cyclobutane dimers are major photoproducts generating reduced plasmid survival and increased mutation frequency. However, unlike XP, CS cells are proficient in repair of nondimer photoproducts. Since XP but not CS patients have a high frequency of UV-induced skin cancers, our data suggest that prevention of UV-induce skin cancers is associated with proficient repair of nondimer photoproducts. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Parris, C N AU - Kraemer, K H AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/08/01/ PY - 1993 DA - 1993 Aug 01 SP - 7260 EP - 7264 VL - 90 IS - 15 SN - 0027-8424, 0027-8424 KW - supF KW - Pyrimidine Dimers KW - 0 KW - Index Medicus KW - Ultraviolet Rays KW - Genes, Bacterial KW - Base Sequence KW - Cells, Cultured KW - Humans KW - In Vitro Techniques KW - Molecular Sequence Data KW - Xeroderma Pigmentosum -- genetics KW - Plasmids KW - DNA Repair KW - Cockayne Syndrome -- genetics KW - Mutagenesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75900615?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Generation+of+varicella-zoster+virus+%28VZV%29+and+viral+mutants+from+cosmid+DNAs%3A+VZV+thymidylate+synthetase+is+not+essential+for+replication+in+vitro.&rft.au=Cohen%2C+J+I%3BSeidel%2C+K+E&rft.aulast=Cohen&rft.aufirst=J&rft.date=1993-08-01&rft.volume=90&rft.issue=15&rft.spage=7376&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 - 1993-09-07 N1 - Date created - 1993-09-07 N1 - Date revised - 2017-01-13 N1 - Gene symbol - supF N1 - SuppNotes - Cited By: Am J Med Genet. 1992 Jan 1;42(1):68-84 [1308368] Biochemistry. 1993 Jan 19;32(2):472-81 [8422356] J Invest Dermatol. 1978 May;70(5):237-9 [641373] Arch Neurol. 1978 Jun;35(6):337-45 [655905] Am J Hum Genet. 1978 Nov;30(6):590-601 [747187] Cancer Res. 1979 Oct;39(10):4237-41 [157803] Mutat Res. 1980 Jan;69(1):107-12 [7360141] Science. 1980 Sep 19;209(4463):1392-6 [6251547] Cancer Res. 1982 Apr;42(4):1473-8 [6174225] Mutat Res. 1982 Dec;106(2):347-56 [6185841] Mutat Res. 1984 Feb;131(2):61-70 [6700618] J Invest Dermatol. 1984 May;82(5):480-4 [6096450] J Biol Chem. 1985 Sep 25;260(21):11438-41 [3900062] Gene. 1985;38(1-3):233-7 [2998945] Cancer Res. 1986 Feb;46(2):1005-9 [3940625] Photochem Photobiol. 1986 May;43(5):509-13 [3526363] Proc Natl Acad Sci U S A. 1986 Sep;83(18):6945-9 [3529093] Proc Natl Acad Sci U S A. 1986 Nov;83(21):8273-7 [3464953] Carcinogenesis. 1987 Jan;8(1):53-7 [3802395] Arch Dermatol. 1987 Feb;123(2):241-50 [3545087] Proc Natl Acad Sci U S A. 1987 Jun;84(11):3782-6 [3473483] Mutat Res. 1989 Mar-May;220(2-3):55-60 [2538741] Mutat Res. 1989 Mar-May;220(2-3):61-72 [2494447] Birth Defects Orig Artic Ser. 1989;25(2):61-82 [2655741] Photodermatol. 1989 Feb;6(1):1-15 [2660122] Photochem Photobiol. 1989 Jun;49(6):805-19 [2672059] J Mol Biol. 1990 Apr 5;212(3):433-6 [2182882] Proc Natl Acad Sci U S A. 1990 Jun;87(12):4707-11 [2352945] Mutat Res. 1991 Jan;254(1):97-105 [1986277] Mutat Res. 1991 Mar;254(2):119-23 [1848350] Br J Dermatol. 1991 May;124(5):453-60 [2039722] Mutat Res. 1991 Nov;255(3):281-91 [1719400] Exp Cell Res. 1992 Aug;201(2):462-9 [1322318] Cancer Res. 1977 Mar;37(3):904-10 [837385] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutations in the alpha subunit of eukaryotic translation initiation factor 2 (eIF-2 alpha) that overcome the inhibitory effect of eIF-2 alpha phosphorylation on translation initiation. AN - 75900558; 8102207 AB - Phosphorylation of eIF-2 alpha in Saccharomyces cerevisiae by the protein kinase GCN2 leads to inhibition of general translation initiation and a specific increase in translation of GCN4 mRNA. We isolated mutations in the eIF-2 alpha structural gene that do not affect the growth rate of wild-type yeast but which suppress the toxic effects of eIF-2 alpha hyperphosphorylation catalyzed by mutationally activated forms of GCN2. These eIF-2 alpha mutations also impair translational derepression of GCN4 in strains expressing wild-type GCN2 protein. All four mutations alter single amino acids within 40 residues of the phosphorylation site in eIF-2 alpha; however, three alleles do not decrease the level of eIF-2 alpha phosphorylation. We propose that these mutations alter the interaction between eIF-2 and its recycling factor eukaryotic translation initiation factor 2B (eIF-2B) in a way that diminishes the inhibitory effect of phosphorylated eIF-2 on the essential function of eIF-2B in translation initiation. These mutations may identify a region in eIF-2 alpha that participates directly in a physical interaction with the GCN3 subunit of eIF-2B. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Vazquez de Aldana, C R AU - Dever, T E AU - Hinnebusch, A G AD - Section on Molecular Genetics of Lower Eukaryotes, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/08/01/ PY - 1993 DA - 1993 Aug 01 SP - 7215 EP - 7219 VL - 90 IS - 15 SN - 0027-8424, 0027-8424 KW - Eukaryotic Initiation Factor-2 KW - 0 KW - Guanine Nucleotide Exchange Factors KW - Oligodeoxyribonucleotides KW - Proteins KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - eIF-2 Kinase KW - Index Medicus KW - Gene Expression Regulation, Fungal KW - Base Sequence KW - Protein-Serine-Threonine Kinases -- metabolism KW - Phosphorylation KW - Oligodeoxyribonucleotides -- chemistry KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Proteins -- metabolism KW - Genes, Suppressor KW - Structure-Activity Relationship KW - Saccharomyces cerevisiae -- genetics KW - Peptide Chain Initiation, Translational KW - Eukaryotic Initiation Factor-2 -- metabolism KW - Eukaryotic Initiation Factor-2 -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75900558?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mutations+in+the+alpha+subunit+of+eukaryotic+translation+initiation+factor+2+%28eIF-2+alpha%29+that+overcome+the+inhibitory+effect+of+eIF-2+alpha+phosphorylation+on+translation+initiation.&rft.au=Vazquez+de+Aldana%2C+C+R%3BDever%2C+T+E%3BHinnebusch%2C+A+G&rft.aulast=Vazquez+de+Aldana&rft.aufirst=C&rft.date=1993-08-01&rft.volume=90&rft.issue=15&rft.spage=7215&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 - 1993-09-07 N1 - Date created - 1993-09-07 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7 [271968] Proc Natl Acad Sci U S A. 1993 Jun 1;90(11):5350-4 [8506384] Mol Cell Biol. 1984 Jul;4(7):1326-33 [6095062] J Biol Chem. 1987 Jan 25;262(3):1206-12 [2948954] Methods Enzymol. 1987;154:164-75 [3323810] Microbiol Rev. 1988 Jun;52(2):248-73 [3045517] Proc Natl Acad Sci U S A. 1989 Apr;86(8):2784-8 [2649894] Genetics. 1989 May;122(1):19-27 [2659436] Mol Cell Biol. 1990 Jun;10(6):2820-31 [2188100] Genetics. 1990 Nov;126(3):549-62 [2249755] Mol Cell Biol. 1991 Jan;11(1):486-96 [1986242] Methods Enzymol. 1991;194:195-230 [2005788] Mol Cell Biol. 1991 Jun;11(6):3203-16 [2038326] Mol Cell Biol. 1991 Jun;11(6):3217-28 [2038327] Annu Rev Biochem. 1991;60:717-55 [1883206] Cell. 1992 Feb 7;68(3):585-96 [1739968] EMBO J. 1992 Apr;11(4):1553-62 [1348691] Mol Cell Biol. 1992 Dec;12(12):5801-15 [1448107] Mol Cell Biol. 1993 Mar;13(3):1920-32 [8441423] Proc Natl Acad Sci U S A. 1993 May 15;90(10):4616-20 [8099443] J Bacteriol. 1983 Jan;153(1):163-8 [6336730] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Expression of transduced tropomyosin 1 cDNA suppresses neoplastic growth of cells transformed by the ras oncogene. AN - 75899265; 8346214 AB - Synthesis of certain members of the tropomyosin family of microfilament-associated proteins is suppressed in fibroblasts neoplastically transformed by a number of retroviral oncogenes, by transforming growth factor alpha, and by chemical mutagens. To test whether tropomyosin suppression is a required event in neoplastic transformation, expression of one of two suppressed tropomyosins in NIH 3T3 mouse cells transformed by the ras oncogene was restored by retrovirally mediated cDNA transfer. Cells expressing the inserted cDNA showed partial restoration of microfilament bundle formation (which is typically deranged in transformed cells) together with increased cytoplasmic spreading. More importantly, they lost anchorage-independent growth capability, and the onset of tumor growth in athymic mice was delayed. When tumors arose they no longer expressed the inserted cDNA. These observations support the conclusion that tropomyosin suppression is a necessary event for the expression of components of the transformed phenotype, particularly with respect to anchorage-independent growth and tumorigenesis, which correlate closely with neoplastic potential. This potentially reversible requirement may link different initial events produced by a variety of oncogenic modalities to a common pathway leading to neoplastic growth. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Prasad, G L AU - Fuldner, R A AU - Cooper, H L AD - Cell and Molecular Physiology Section, National Cancer Institute, Bethesda, MD 20892. Y1 - 1993/08/01/ PY - 1993 DA - 1993 Aug 01 SP - 7039 EP - 7043 VL - 90 IS - 15 SN - 0027-8424, 0027-8424 KW - TM1 KW - RNA, Messenger KW - 0 KW - Tropomyosin KW - Index Medicus KW - Animals KW - 3T3 Cells KW - Transfection KW - Neoplasms, Experimental -- genetics KW - In Vitro Techniques KW - Gene Expression KW - Mice, Nude KW - Mice KW - RNA, Messenger -- genetics KW - Cell Division KW - Cell Adhesion KW - Genes, ras KW - Tropomyosin -- metabolism KW - Tropomyosin -- genetics KW - Cell Transformation, Neoplastic -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75899265?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Expression+of+transduced+tropomyosin+1+cDNA+suppresses+neoplastic+growth+of+cells+transformed+by+the+ras+oncogene.&rft.au=Prasad%2C+G+L%3BFuldner%2C+R+A%3BCooper%2C+H+L&rft.aulast=Prasad&rft.aufirst=G&rft.date=1993-08-01&rft.volume=90&rft.issue=15&rft.spage=7039&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 - 1993-09-07 N1 - Date created - 1993-09-07 N1 - Date revised - 2017-01-13 N1 - Gene symbol - TM1 N1 - SuppNotes - Cited By: Crit Rev Oncog. 1991;2(2):125-60 [1854833] Cancer Res. 1991 Jul 15;51(14):3657-62 [1712245] Biochem Biophys Res Commun. 1991 Jun 28;177(3):1068-75 [2059197] Bioessays. 1991 Sep;13(9):429-37 [1796905] Oncogene. 1992 Mar;7(3):553-61 [1549369] Oncogene. 1992 Apr;7(4):769-73 [1565472] Proc Natl Acad Sci U S A. 1992 May 1;89(9):3952-6 [1570319] J Cell Biol. 1992 Oct;119(2):427-38 [1400584] Proc Natl Acad Sci U S A. 1993 Jan 15;90(2):383-7 [8380636] Cancer Lett. 1993 Feb;68(2-3):95-104 [8443798] J Mol Biol. 1972 Jul 21;68(2):383-7 [5069793] Proc Natl Acad Sci U S A. 1975 Mar;72(3):994-8 [165499] J Cell Biol. 1979 Jul;82(1):1-16 [383723] Proc Natl Acad Sci U S A. 1981 Sep;78(9):5633-7 [6272310] Biochim Biophys Acta. 1982 Apr 29;720(2):154-62 [6282338] Cancer Res. 1982 Dec;42(12):5183-90 [7139623] Cell. 1982 Jul;29(3):791-7 [6817926] Proc Natl Acad Sci U S A. 1983 Sep;80(18):5602-6 [6604274] J Biol Chem. 1983 Nov 25;258(22):13954-64 [6315714] Cell. 1983 May;33(1):153-9 [6678608] CRC Crit Rev Biochem. 1984;16(3):235-305 [6383715] Gene. 1984 Oct;30(1-3):211-7 [6096215] Mol Cell Biol. 1985 May;5(5):972-83 [4000123] Cancer Invest. 1986;4(1):43-60 [3006881] Mol Cell Biol. 1986 Jul;6(7):2721-6 [3785208] Mol Cell Biol. 1986 Nov;6(11):3582-95 [2432392] Annu Rev Cell Biol. 1985;1:353-402 [3030380] Cancer Res. 1987 Aug 15;47(16):4493-500 [3496963] Oncogene Res. 1988;3(1):51-65 [3060798] Prog Clin Biol Res. 1989;288:25-34 [2541449] Anticancer Res. 1989 Sep-Oct;9(5):1367-76 [2556070] Cancer Res. 1990 Apr 1;50(7):2105-12 [2317800] Anticancer Res. 1990 Jan-Feb;10(1):1-22 [2185684] Curr Opin Cell Biol. 1990 Apr;2(2):241-5 [2163659] J Cell Biol. 1990 Jul;111(1):95-102 [2164032] Cancer Treat Res. 1989;47:177-95 [2576997] Acta Physiol Scand Suppl. 1990;592:93-133 [2267948] Cell. 1991 Jan 25;64(2):235-48 [1988146] Cell. 1991 Jan 25;64(2):249-70 [1988147] J Biol Chem. 1991 Mar 25;266(9):5891-7 [2005125] Biochemistry. 1991 Jun 11;30(23):5682-8 [2043610] Curr Opin Biotechnol. 1991 Oct;2(5):708-12 [1367722] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interleukin 1 induction of the c-jun promoter. AN - 75891268; 8346217 AB - Interleukin 1 (IL-1) induces pleiotropic effects in many cell types during inflammation and immunity. We have recently shown how the IL-1 signal is transmitted to the nucleus: In T cells and in pituitary cells, IL-1 induced genes via activation of the nuclear factor AP-1. We now demonstrate how IL-1 activates the AP-1 factor in liver cells, which are a major target for IL-1 during the acute phase response in vivo. IL-1 induced gene transcription of both AP-1 components, c-jun and c-fos. IL-1 also increased the stability of c-jun mRNA. We define two enhancer sites in the jun promoter that are required for induction by IL-1. Although the binding sites share some similarity with the AP-1 binding site, the nuclear factors binding the jun motifs are not composed of Jun or Fos proteins. Thus these data identify two binding proteins that serve as one of the first nuclear targets for IL-1 signal transduction. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Muegge, K AU - Vila, M AU - Gusella, G L AU - Musso, T AU - Herrlich, P AU - Stein, B AU - Durum, S K AD - Biological Carcinogenesis and Development Program, Program Resources Inc./Dyncorp, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702-1201. Y1 - 1993/08/01/ PY - 1993 DA - 1993 Aug 01 SP - 7054 EP - 7058 VL - 90 IS - 15 SN - 0027-8424, 0027-8424 KW - c-jun KW - jun1 KW - jun2 KW - DNA-Binding Proteins KW - 0 KW - Interleukin-1 KW - Nuclear Proteins KW - Oligodeoxyribonucleotides KW - Proto-Oncogene Proteins c-jun KW - RNA, Messenger KW - Index Medicus KW - Protein Biosynthesis KW - Base Sequence KW - Tumor Cells, Cultured KW - RNA, Messenger -- metabolism KW - Oligodeoxyribonucleotides -- chemistry KW - Humans KW - In Vitro Techniques KW - Molecular Sequence Data KW - Transcription, Genetic KW - Proto-Oncogene Proteins c-jun -- metabolism KW - Nuclear Proteins -- metabolism KW - DNA-Binding Proteins -- metabolism KW - Interleukin-1 -- physiology KW - Promoter Regions, Genetic KW - Gene Expression Regulation KW - Liver -- physiology KW - Genes, jun UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75891268?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Interleukin+1+induction+of+the+c-jun+promoter.&rft.au=Muegge%2C+K%3BVila%2C+M%3BGusella%2C+G+L%3BMusso%2C+T%3BHerrlich%2C+P%3BStein%2C+B%3BDurum%2C+S+K&rft.aulast=Muegge&rft.aufirst=K&rft.date=1993-08-01&rft.volume=90&rft.issue=15&rft.spage=7054&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 - 1993-09-07 N1 - Date created - 1993-09-07 N1 - Date revised - 2017-01-13 N1 - Gene symbol - c-jun; jun1; jun2 N1 - SuppNotes - Cited By: Mol Cell Biol. 1987 Jun;7(6):2256-66 [3037355] Mol Cell Biol. 1992 Oct;12(10):4472-7 [1406636] Science. 1988 Jul 29;241(4865):585-9 [2969618] Cell. 1988 Nov 4;55(3):395-7 [3141060] Cell. 1988 Dec 2;55(5):875-85 [3142689] Anal Biochem. 1988 Oct;174(1):209-14 [3218734] Nature. 1989 Feb 16;337(6208):661-3 [2537468] Mol Cell Biol. 1989 Mar;9(3):959-64 [2542770] Science. 1989 Oct 13;246(4927):249-51 [2799385] Cell. 1989 Dec 22;59(6):979-86 [2513128] EMBO J. 1990 Jun;9(6):1897-906 [2112087] Eur J Biochem. 1990 Aug 28;192(1):75-9 [2169419] Mol Cell Biol. 1990 Nov;10(11):5857-64 [2172787] Proc Natl Acad Sci U S A. 1990 Oct;87(20):7871-4 [1978316] New Biol. 1989 Dec;1(3):239-46 [2487289] Mol Endocrinol. 1990 Jul;4(7):973-80 [2178224] New Biol. 1990 Feb;2(2):143-50 [2150599] Mol Cell Biol. 1991 May;11(5):2804-11 [1901948] J Biol Chem. 1991 May 25;266(15):9363-6 [1851743] Nature. 1991 Oct 17;353(6345):670-4 [1922387] J Biol Chem. 1991 Nov 25;266(33):22661-70 [1658005] Biochemistry. 1979 Nov 27;18(24):5294-9 [518835] Nucleic Acids Res. 1992 Feb 25;20(4):897-902 [1542579] Photochem Photobiol. 1992 Mar;55(3):409-15 [1561239] Annu Rev Biochem. 1992;61:1053-95 [1497306] Mol Cell Biol. 1982 Sep;2(9):1044-51 [6960240] Nature. 1984 Oct 4-10;311(5985):433-8 [6090941] FEBS Lett. 1985 Oct 21;191(1):7-12 [2996929] Mol Cell Biol. 1985 Oct;5(10):2866-9 [3879767] Cell. 1987 Jun 19;49(6):729-39 [3034432] Cell. 1987 Jun 19;49(6):741-52 [3034433] DNA. 1988 Jan-Feb;7(1):47-55 [3349904] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chromatin disruption in the promoter of human immunodeficiency virus type 1 during transcriptional activation. AN - 75889653; 8344262 AB - Chromatin organization of eukaryotic promoters is increasingly recognized as an important factor in the regulation of transcription in vivo. To determine the role of chromatin in HIV-1 expression, we have examined the nucleosome organization of the promoter of HIV-1 under low and high transcription rates. Independently of the cell line examined, nucleosomes are precisely positioned in the viral 5' long terminal repeat (5' LTR) and define two large nucleosome-free regions encompassing nt 200-450 and 610-720. A nucleosome positioned between these two regions, immediately after the transcription initiation site (nuc-1), is disrupted following TPA or TNF-alpha treatment. The disruption of nuc-1 from DNA is independent of DNA replication since it is completed in 20 min and independent of transcription as it is alpha-amanitin insensitive. A model is proposed in which nuc-1 plays an organizing role in the HIV-1 promoter to bring in close proximity factors bound to DNA in the two nucleosome-free regions, upstream and downstream of the site of transcription initiation. These results define chromatin as an integral component of the HIV-1 transcriptional regulatory machinery and identify a chromatin transition associated with activation of viral gene expression. JF - The EMBO journal AU - Verdin, E AU - Paras, P AU - Van Lint, C AD - Laboratory of Viral and Molecular Pathogenesis, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892. Y1 - 1993/08// PY - 1993 DA - August 1993 SP - 3249 EP - 3259 VL - 12 IS - 8 SN - 0261-4189, 0261-4189 KW - Alkylating Agents KW - 0 KW - Amanitins KW - Chromatin KW - DNA, Viral KW - Nucleosomes KW - Sulfuric Acid Esters KW - Deoxyribonuclease I KW - EC 3.1.21.1 KW - Micrococcal Nuclease KW - EC 3.1.31.1 KW - dimethyl sulfate KW - JW5CW40Z50 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - AIDS/HIV KW - Alkylating Agents -- pharmacology KW - HIV Long Terminal Repeat -- genetics KW - Nucleosomes -- metabolism KW - Sulfuric Acid Esters -- pharmacology KW - Deoxyribonuclease I -- pharmacology KW - Base Sequence KW - Amanitins -- pharmacology KW - Restriction Mapping KW - Molecular Sequence Data KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Micrococcal Nuclease -- pharmacology KW - Cell Line KW - DNA Replication KW - HIV-1 -- genetics KW - Promoter Regions, Genetic KW - Transcriptional Activation -- physiology KW - Chromatin -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75889653?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Chromatin+disruption+in+the+promoter+of+human+immunodeficiency+virus+type+1+during+transcriptional+activation.&rft.au=Verdin%2C+E%3BParas%2C+P%3BVan+Lint%2C+C&rft.aulast=Verdin&rft.aufirst=E&rft.date=1993-08-01&rft.volume=12&rft.issue=8&rft.spage=3249&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 - 1993-09-08 N1 - Date created - 1993-09-08 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Virol. 1991 Sep;65(9):4645-53 [1678437] Annu Rev Biochem. 1991;60:577-630 [1883204] J Virol. 1991 Dec;65(12):6790-9 [1942252] Science. 1991 Nov 8;254(5033):815-20 [1658933] Cell. 1991 Nov 29;67(5):833-6 [1959130] Nature. 1992 Jan 16;355(6357):219-24 [1731219] EMBO J. 1991 Mar;10(3):607-15 [2001676] Trends Genet. 1991 Jan;7(1):9-14 [2003337] New Biol. 1990 Jan;2(1):20-31 [2078551] Genes Dev. 1991 Apr;5(4):683-96 [2010092] New Biol. 1989 Nov;1(2):127-35 [2562218] Cell. 1991 Apr 19;65(2):241-8 [2015625] J Virol. 1992 Mar;66(3):1809-13 [1738210] Nucleic Acids Res. 1992 Jan 25;20(2):273-8 [1311071] Proc Natl Acad Sci U S A. 1992 Feb 15;89(4):1229-33 [1741376] J Virol. 1992 Jul;66(7):4488-96 [1602555] AIDS. 1992 Apr;6(4):347-63 [1616633] Curr Opin Genet Dev. 1992 Apr;2(2):293-8 [1638124] Cell. 1992 Oct 2;71(1):11-22 [1394427] Cell. 1992 Nov 27;71(5):853-64 [1423633] Trends Genet. 1992 Nov;8(11):365-8 [1440870] Science. 1992 Dec 11;258(5089):1780-4 [1465613] Cell. 1993 Jan 15;72(1):73-84 [8422685] EMBO J. 1993 Feb;12(2):423-33 [8440235] EMBO J. 1987 Aug;6(8):2321-8 [2822386] Science. 1987 Nov 6;238(4828):800-2 [3313729] Nature. 1987 Dec 3-9;330(6147):489-93 [2825027] EMBO J. 1987 Dec 1;6(12):3761-70 [3428273] EMBO J. 1988 Jul;7(7):2221-8 [3046934] Annu Rev Biochem. 1988;57:159-97 [3052270] Genes Dev. 1988 Sep;2(9):1101-14 [2847959] J Biol Chem. 1988 Dec 25;263(36):19259-62 [3198625] Cell. 1988 Dec 23;55(6):1137-45 [2849508] J Immunol. 1989 Jan 15;142(2):431-8 [2463307] Proc Natl Acad Sci U S A. 1989 Apr;86(7):2336-40 [2494664] Nature. 1989 May 4;339(6219):70-3 [2654643] J Virol. 1989 Aug;63(8):3213-9 [2545899] Cell. 1989 Jul 14;58(1):27-36 [2502314] Methods Enzymol. 1989;170:269-89 [2770542] EMBO J. 1989 Aug;8(8):2343-51 [2792088] J Virol. 1989 Nov;63(11):4919-24 [2795721] Science. 1989 Nov 10;246(4931):780-6 [2814500] Genes Dev. 1989 Nov;3(11):1814-22 [2558048] Nature. 1990 Jan 25;343(6256):387-9 [2405281] Bioessays. 1992 Sep;14(9):597-603 [1365915] J Mol Biol. 1984 Jul 15;176(4):535-57 [6086935] Cell. 1984 Aug;38(1):29-38 [6088072] Cell. 1985 Jul;41(3):813-23 [2988790] J Biol Chem. 1985 Dec 5;260(28):15318-24 [2415517] Science. 1986 May 9;232(4751):755-9 [3008338] J Exp Med. 1986 Jul 1;164(1):280-90 [3014036] Mol Cell Biol. 1986 Mar;6(3):779-91 [3022129] EMBO J. 1986 Oct;5(10):2689-96 [3536481] Cell. 1987 Apr 24;49(2):203-10 [3568125] J Mol Biol. 1987 May 5;195(1):143-73 [3656408] Cell. 1990 Mar 9;60(5):719-31 [2155706] J Biol Chem. 1990 Apr 5;265(10):5736-46 [2180934] J Mol Biol. 1990 Apr 5;212(3):481-93 [2325130] Immunol Today. 1990 May;11(5):176-80 [2186752] Nucleic Acids Res. 1990 May 11;18(9):2739-47 [2339060] Annu Rev Immunol. 1990;8:453-75 [2188670] Cell. 1990 Jun 29;61(7):1271-6 [2364429] EMBO J. 1990 Aug;9(8):2523-8 [2196175] Proc Natl Acad Sci U S A. 1990 Oct;87(19):7405-9 [2170977] Cell. 1990 Nov 16;63(4):655-7 [2225069] Genes Dev. 1990 Dec;4(12A):2061-74 [2269426] Genes Dev. 1990 Dec;4(12B):2397-408 [2149119] New Biol. 1990 Aug;2(8):712-8 [2282368] Proc Natl Acad Sci U S A. 1991 May 1;88(9):4045-9 [2023953] Genes Dev. 1991 May;5(5):820-6 [1851121] Genes Dev. 1991 Jun;5(6):1102-13 [2044957] Proc Natl Acad Sci U S A. 1991 Jul 1;88(13):5670-4 [2062845] Genes Dev. 1991 Jul;5(7):1285-98 [2065977] J Virol. 1991 Aug;65(8):4350-8 [2072454] EMBO J. 1991 Sep;10(9):2569-76 [1678348] Erratum In: EMBO J 1993 Dec;12(12):4900 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Lack of effect of carcinogen treatment on development of tumors arising spontaneously in Fischer 344 rats. AN - 75888819; 8345536 AB - The incidence of a set of neoplasms arising "spontaneously" in Fischer 344 (F344) rats was determined in control and carcinogen-treated animals. Data were obtained from approximately 9000 rats (4000 males and 5000 females) used to study the carcinogenicity of a variety of alkylating compounds, including N-nitroso compounds, azoxyalkanes, and triazenes. In these experiments treated rats and controls were allowed to die naturally and were necropsied, and the tissues were examined histopathologically. The spontaneous neoplasms of interest were mononuclear cell leukemia and neoplasms of the anterior pituitary, adrenal medulla, pancreas, thyroid gland, mammary gland, and testis. These tumors were generally absent from control animals that (rarely) died before 70 wk of age. Although many carcinogen-treated rats died early with treatment-related tumors, a substantial number (1700 males and 2300 females) survived as long as controls. The incidence of spontaneous neoplasms was determined among controls and chemically treated rats at 10-wk intervals from 0 to 140 wk. The incidence of spontaneous tumors was not higher and was frequently statistically lower among treated rats than the corresponding incidence in controls, with the exception of leukemia in female rats. The same result was obtained with the subset of carcinogens not requiring metabolic activation (mostly alkylnitrosoureas). These data indicate that in this rat tumor model system, the alkylating carcinogens, while capable collectively of tumor induction at more than 20 sites, did not accelerate the development of any of the six spontaneously arising solid tumors. This suggests that these spontaneous tumors might arise by a mechanism that is unresponsive to the actions of the alkylating carcinogens. JF - Journal of toxicology and environmental health AU - Lijinsky, W AU - Riggs, C W AU - Walters, P T AD - ABL-Basic Research Program, NCI Frederick Cancer Research and Development Center, Maryland. Y1 - 1993/08// PY - 1993 DA - August 1993 SP - 527 EP - 538 VL - 39 IS - 4 SN - 0098-4108, 0098-4108 KW - Carcinogens KW - 0 KW - Nitroso Compounds KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Databases, Factual KW - Nitroso Compounds -- toxicity KW - Male KW - Female KW - Neoplasms, Experimental -- chemically induced KW - Carcinogens -- toxicity KW - Neoplasms, Experimental -- mortality KW - Neoplasms, Experimental -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75888819?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+toxicology+and+environmental+health&rft.atitle=Lack+of+effect+of+carcinogen+treatment+on+development+of+tumors+arising+spontaneously+in+Fischer+344+rats.&rft.au=Lijinsky%2C+W%3BRiggs%2C+C+W%3BWalters%2C+P+T&rft.aulast=Lijinsky&rft.aufirst=W&rft.date=1993-08-01&rft.volume=39&rft.issue=4&rft.spage=527&rft.isbn=&rft.btitle=&rft.title=Journal+of+toxicology+and+environmental+health&rft.issn=00984108&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-09-08 N1 - Date created - 1993-09-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hippocampal neurons exhibit cyclothiazide-sensitive rapidly desensitizing responses to kainate. AN - 75879524; 7688040 AB - In whole-cell recordings from mammalian CNS neurons, AMPA-preferring glutamate receptors exhibit strong desensitization in response to AMPA, glutamate, and quisqualate, but not to kainate or domoate. Such desensitization is reduced by lectins, by the nootropic drug aniracetam, and by diazoxide. None of these compounds strongly modulate responses to kainate and domoate, consistent with the apparent lack of desensitization to these agonists. We now report experiments on hippocampal neurons in which responses to kainate were strongly potentiated by cyclothiazide, a benzothiadiazine diuretic and antihypertensive drug structurally related to diazoxide. Cyclothiazide increased the maximum response to a saturating concentration of kainate by approximately 300% and produced a shift to the left in the kainate dose-response curve. Because cyclothiazide was considerably more effective than aniracetam in reducing desensitization evoked by glutamate, we tested the possibility that potentiation of responses to kainate was due to block of a previously undetected component of desensitization in the response to kainate itself. In outside-out patches responses to rapid perfusion of 3 mM kainate showed 34% desensitization, the onset of which developed with a time constant of 2.2 msec. Desensitization of responses to kainate was abolished by 100 microM cyclothiazide, as was the much stronger desensitization evoked by glutamate and AMPA. Cyclothiazide also slowed the rate of deactivation of responses to kainate recorded after return to agonist-free solution. Current-voltage plots for control responses to kainate exhibited outward rectification that was associated with a reduction in the amount of desensitization on depolarization. Both effects were absent in the presence of cyclothiazide, suggesting that rectification of responses to kainate was due to the voltage dependence of desensitization. The complete block of desensitization produced by cyclothiazide provides a powerful new tool for analysis of allosteric regulatory mechanisms at AMPA-preferring glutamate receptors. JF - The Journal of neuroscience : the official journal of the Society for Neuroscience AU - Patneau, D K AU - Vyklicky, L AU - Mayer, M L AD - Laboratory of Cellular and Molecular Neurophysiology, NICHD, NIH, Bethesda, Maryland 20892. Y1 - 1993/08// PY - 1993 DA - August 1993 SP - 3496 EP - 3509 VL - 13 IS - 8 SN - 0270-6474, 0270-6474 KW - Benzothiadiazines KW - 0 KW - Glutamates KW - Ibotenic Acid KW - 2552-55-8 KW - Glutamic Acid KW - 3KX376GY7L KW - alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid KW - 77521-29-0 KW - Quisqualic Acid KW - 8OC22C1B99 KW - cyclothiazide KW - P71U09G5BW KW - Kainic Acid KW - SIV03811UC KW - Index Medicus KW - Animals KW - Dose-Response Relationship, Drug KW - Electrophysiology KW - Ibotenic Acid -- pharmacology KW - Rats KW - Quisqualic Acid -- pharmacology KW - Animals, Newborn KW - Drug Tolerance KW - Rats, Sprague-Dawley KW - Cells, Cultured KW - Evoked Potentials KW - Glutamates -- pharmacology KW - Ibotenic Acid -- analogs & derivatives KW - Kinetics KW - Drug Synergism KW - Kainic Acid -- pharmacology KW - Hippocampus -- physiology KW - Benzothiadiazines -- pharmacology KW - Neurons -- drug effects KW - Hippocampus -- cytology KW - Neurons -- physiology KW - Hippocampus -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75879524?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Hippocampal+neurons+exhibit+cyclothiazide-sensitive+rapidly+desensitizing+responses+to+kainate.&rft.au=Patneau%2C+D+K%3BVyklicky%2C+L%3BMayer%2C+M+L&rft.aulast=Patneau&rft.aufirst=D&rft.date=1993-08-01&rft.volume=13&rft.issue=8&rft.spage=3496&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+neuroscience+%3A+the+official+journal+of+the+Society+for+Neuroscience&rft.issn=02706474&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-09-02 N1 - Date created - 1993-09-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - ENU-induced mutagenesis at a single A: T base pair in transgenic mice containing phi X174. AN - 75879106; 7688099 AB - Transgenic mice containing the bacteriophage phi X174 am3 as a chromosomally integrated and recoverable marker for in vivo mutation have been produced to measure spontaneous and induced substitutions at an A:T base pair among single copies. phi X174 was chosen for its small size (5 kb), unique sequence, and the opportunity to take advantage of previously reported in vitro data on mutation and repair; the am3 site provides sequence specificity in a reversion assay for mutation of an A:T base pair. Inbred C57Bl/6 mice have been made homozygous for approximately 100 copies of the the phage sequence without any apparent detrimental effects on the homozygous individuals. Recoveries of phage from mouse tissues are in the range of 1-5 x 10(7) PFU per micrograms mouse DNA; both recovery and mutation are independent of endogenous CpG methylation. Background mutation frequencies are 2-4 x 10(-7) among phage recovered from liver, brain, spleen, and kidney. Adult mice were treated with 200 mg/kg N-ethyl-N-nitrosourea, and phage were recovered at 2 and 14 days after treatment. At 2 days after treatment we observed a slight increase only among phage isolated from the brain of one mouse out of four. At 14 days after ENU treatment, there were significant increases in mutation frequencies among phage recovered from the liver (6 x) and spleen (10 x). These results demonstrate (1) response of a single A:T base pair to alkylation-induced mutation in a nonexpressed gene, (2) the role of cell proliferation in somatic mutagenesis, and (3) provide a model for a transgenic approach for study of site-specific mutagenesis in vivo in higher eukaryotes. JF - Mutation research AU - Burkhart, J G AU - Burkhart, B A AU - Sampson, K S AU - Malling, H V AD - Laboratory of Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1993/08// PY - 1993 DA - August 1993 SP - 69 EP - 81 VL - 292 IS - 1 SN - 0027-5107, 0027-5107 KW - Dinucleoside Phosphates KW - 0 KW - Mutagens KW - cytidylyl-3'-5'-guanosine KW - 2382-65-2 KW - DNA KW - 9007-49-2 KW - Adenine KW - JAC85A2161 KW - Ethylnitrosourea KW - P8M1T4190R KW - Thymine KW - QR26YLT7LT KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Animals KW - Base Sequence KW - Homozygote KW - Molecular Sequence Data KW - Mice, Inbred C57BL KW - Mice KW - Dinucleoside Phosphates -- metabolism KW - Mice, Transgenic KW - Methylation KW - Male KW - Female KW - Bacteriophage phi X 174 -- isolation & purification KW - Mutagenicity Tests KW - Ethylnitrosourea -- toxicity KW - Mutagens -- toxicity KW - Bacteriophage phi X 174 -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75879106?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=ENU-induced+mutagenesis+at+a+single+A%3A+T+base+pair+in+transgenic+mice+containing+phi+X174.&rft.au=Burkhart%2C+J+G%3BBurkhart%2C+B+A%3BSampson%2C+K+S%3BMalling%2C+H+V&rft.aulast=Burkhart&rft.aufirst=J&rft.date=1993-08-01&rft.volume=292&rft.issue=1&rft.spage=69&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 - 1993-08-30 N1 - Date created - 1993-08-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Current dosage and schedule issues in the development of paclitaxel (Taxol). AN - 75864441; 8102016 AB - Basic questions regarding optimal dose and schedule of anticancer drug administration frequently persist long after regulatory approval and commercial availability of a drug. For paclitaxel (TAXOL), these questions were considered early in drug development. This paper reviews the available preclinical studies that assessed different drug concentrations and durations of drug exposure. The current status of clinical trials designed to help resolve these issues is also reviewed. JF - Seminars in oncology AU - Arbuck, S G AU - Canetta, R AU - Onetto, N AU - Christian, M C AD - Developmental Chemotherapy Section, National Cancer Institute, Bethesda, MD 20892. Y1 - 1993/08// PY - 1993 DA - August 1993 SP - 31 EP - 39 VL - 20 IS - 4 Suppl 3 SN - 0093-7754, 0093-7754 KW - Paclitaxel KW - P88XT4IS4D KW - Index Medicus KW - Animals KW - Bone Marrow Diseases -- chemically induced KW - Dose-Response Relationship, Drug KW - Humans KW - Clinical Trials as Topic KW - Mice KW - Microtubules -- drug effects KW - Peripheral Nervous System Diseases -- chemically induced KW - Rats KW - Drug Evaluation KW - Drug Hypersensitivity -- etiology KW - Dogs KW - Time Factors KW - Drug Evaluation, Preclinical KW - Paclitaxel -- administration & dosage KW - Neoplasms -- drug therapy KW - Paclitaxel -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75864441?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Current+dosage+and+schedule+issues+in+the+development+of+paclitaxel+%28Taxol%29.&rft.au=Arbuck%2C+S+G%3BCanetta%2C+R%3BOnetto%2C+N%3BChristian%2C+M+C&rft.aulast=Arbuck&rft.aufirst=S&rft.date=1993-08-01&rft.volume=20&rft.issue=4+Suppl+3&rft.spage=31&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 - 1993-08-27 N1 - Date created - 1993-08-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Suppression of arthritis by an inhibitor of nitric oxide synthase. AN - 75862262; 7688035 AB - Nitric oxide (NO), a toxic radical gas produced during the metabolism of L-arginine by NO synthase (NOS), has been implicated as a mediator of immune and inflammatory responses. A single injection of streptococcal cell wall fragments (SCW) induces the accumulation of inflammatory cells within the synovial tissue and a cell-mediated immune response that leads destructive lesions. We show here that NO production is elevated in the inflamed joints of SCW-treated rats. Administration of NG-monomethyl-L-arginine, an inhibitor of NOS, profoundly reduced the synovial inflammation and tissue damage as measured by an articular index and reflected in the histopathology. These studies implicate the NO pathway in the pathogenesis of an inflammatory arthritis and demonstrate the ability of a NOS inhibitor to modulate the disease. JF - The Journal of experimental medicine AU - McCartney-Francis, N AU - Allen, J B AU - Mizel, D E AU - Albina, J E AU - Xie, Q W AU - Nathan, C F AU - Wahl, S M AD - Laboratory of Immunology, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/08/01/ PY - 1993 DA - 1993 Aug 01 SP - 749 EP - 754 VL - 178 IS - 2 SN - 0022-1007, 0022-1007 KW - omega-N-Methylarginine KW - 27JT06E6GR KW - Nitric Oxide KW - 31C4KY9ESH KW - Arginine KW - 94ZLA3W45F KW - Nitric Oxide Synthase KW - EC 1.14.13.39 KW - Amino Acid Oxidoreductases KW - EC 1.4.- KW - Index Medicus KW - Streptococcus KW - Rats KW - Acute Disease KW - Animals KW - Rats, Sprague-Dawley KW - Culture Techniques KW - Cell Wall KW - Nitric Oxide -- metabolism KW - Synovial Membrane -- metabolism KW - Female KW - Synovial Membrane -- pathology KW - Arginine -- therapeutic use KW - Arthritis -- etiology KW - Amino Acid Oxidoreductases -- antagonists & inhibitors KW - Arthritis -- drug therapy KW - Arginine -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75862262?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+experimental+medicine&rft.atitle=Suppression+of+arthritis+by+an+inhibitor+of+nitric+oxide+synthase.&rft.au=McCartney-Francis%2C+N%3BAllen%2C+J+B%3BMizel%2C+D+E%3BAlbina%2C+J+E%3BXie%2C+Q+W%3BNathan%2C+C+F%3BWahl%2C+S+M&rft.aulast=McCartney-Francis&rft.aufirst=N&rft.date=1993-08-01&rft.volume=178&rft.issue=2&rft.spage=749&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+experimental+medicine&rft.issn=00221007&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-08-30 N1 - Date created - 1993-08-30 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Science. 1987 Jan 23;235(4787):473-6 [2432665] Proc Natl Acad Sci U S A. 1993 Apr 1;90(7):3024-7 [7681993] Am J Physiol. 1988 Apr;254(4 Pt 1):E459-67 [3354662] J Immunol. 1988 Oct 1;141(7):2407-12 [3139757] Proc Natl Acad Sci U S A. 1990 May;87(9):3629-32 [2333306] J Immunol. 1990 Oct 1;145(7):2220-6 [2144548] Rheum Dis Clin North Am. 1990 Aug;16(3):513-37 [2217956] J Immunol. 1991 Feb 15;146(4):1294-302 [1991968] J Immunol. 1991 Apr 15;146(8):2719-23 [1707918] J Immunol. 1991 Jul 1;147(1):144-8 [1904899] Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):4651-5 [1675786] Pharmacol Rev. 1991 Jun;43(2):109-42 [1852778] Biochem Biophys Res Commun. 1991 Aug 15;178(3):913-20 [1831356] J Immunol. 1991 Oct 15;147(8):2559-64 [1655894] J Immunol. 1991 Dec 1;147(11):3915-20 [1658153] Agents Actions Suppl. 1991;35:29-34 [1781421] Biochem J. 1992 Feb 1;281 ( Pt 3):627-30 [1371384] Proc Natl Acad Sci U S A. 1992 Mar 15;89(6):2051-5 [1372433] Science. 1992 Apr 10;256(5054):225-8 [1373522] J Exp Med. 1992 Jul 1;176(1):303-7 [1319459] J Clin Invest. 1992 Aug;90(2):679-83 [1379617] FASEB J. 1992 Sep;6(12):3051-64 [1381691] Inflammation. 1992 Aug;16(4):295-305 [1526662] J Biol Chem. 1992 Dec 5;267(34):24173-6 [1280257] Ann Rheum Dis. 1992 Nov;51(11):1219-22 [1466599] Anal Biochem. 1987 Apr;162(1):156-9 [2440339] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Synergistic increase of phorbol ester-induced c-fos mRNA expression by retinoic acid through stabilization of the c-fos message. AN - 75859347; 8336949 AB - Retinoic acid (RA) has been shown to be able to antagonize or synergize with phorbol 12-myristate 13-acetate (PMA). In contrast to its antagonistic effects on PMA-dependent gene expression, no molecular target or mechanism of synergism has been characterized yet. We now report, that RA synergistically enhances the induction of c-fos, but not c-jun mRNA by PMA in cells whose growth was stimulated by RA alone. The responding cells were hybrids of tumor cell lines whose growth and PMA-dependent c-fos mRNA expression remained unaffected by RA. The increase in PMA-dependent c-fos expression required pretreatment of cells with RA for at least 2-4 h and was achieved at doses as low as 10(-10) M. Nuclear run-on experiments and transient transfection assays using a chimeric reporter gene construct with sequences from the c-fos promoter indicated that RA did not affect PMA-dependent c-fos transcription. Instead, RA stabilized the c-fos message after induction by PMA as assessed by measuring the half-life of c-fos mRNA in actinomycin D-treated cells. This post-transcriptional regulation provides a mechanism whereby RA can synergistically enhance gene expression by PMA. JF - Oncogene AU - Busam, K J AU - Geiser, A G AU - Roberts, A B AU - Sporn, M B AD - Laboratory of Chemoprevention, National Cancer Institute, NIH, Bethesda, Maryland 20892. Y1 - 1993/08// PY - 1993 DA - August 1993 SP - 2267 EP - 2273 VL - 8 IS - 8 SN - 0950-9232, 0950-9232 KW - c-fos KW - RNA, Messenger KW - 0 KW - Tretinoin KW - 5688UTC01R KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Tumor Cells, Cultured KW - Dose-Response Relationship, Drug KW - Humans KW - Transcription, Genetic KW - Drug Synergism KW - Genes, jun KW - Tretinoin -- pharmacology KW - RNA, Messenger -- analysis KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Genes, fos KW - Gene Expression Regulation -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75859347?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Synergistic+increase+of+phorbol+ester-induced+c-fos+mRNA+expression+by+retinoic+acid+through+stabilization+of+the+c-fos+message.&rft.au=Busam%2C+K+J%3BGeiser%2C+A+G%3BRoberts%2C+A+B%3BSporn%2C+M+B&rft.aulast=Busam&rft.aufirst=K&rft.date=1993-08-01&rft.volume=8&rft.issue=8&rft.spage=2267&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-08-25 N1 - Date created - 1993-08-25 N1 - Date revised - 2017-01-13 N1 - Gene symbol - c-fos N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Polycyclic aromatic hydrocarbon-DNA adducts in human lung and cancer susceptibility genes. AN - 75858591; 8339251 AB - Molecular dosimetry for polycyclic aromatic hydrocarbon-DNA adducts, genetic predisposition to cancer, and their interrelationships are under study in numerous laboratories. This report describes a modified 32P-postlabeling assay for the detection of polycyclic aromatic hydrocarbon-DNA adducts that uses immunoaffinity chromatography to enhance chemical specificity and quantitative reliability. The assay incorporates internal standards to determine direct molar ratios of adducts to unmodified nucleotides and to assess T4 polynucleotide kinase labeling efficiency. High performance liquid chromatography is used to assure adequacy of DNA enzymatic digestion. The assay was validated using radiolabeled benzo(a)pyrene-diol-epoxide modified DNA (r = 0.76, P < 0.05) thereby assessing all variables from enzymatic digestion to detection. Thirty-eight human lung samples were examined and adducts were detected in seven. A subset of samples also was examined for benzo(a)pyrene-diol-epoxide-DNA adducts by immunoaffinity chromatography, high performance liquid chromatography, and synchronous fluorescence spectroscopy. A high correlation between the two assays was found (P = 0.006). The lung samples were then analyzed by the polymerase chain reaction for the presence of mutations in the cytochrome P-450 (CYP) 1A1 and glutathione S-transferase mu (GST mu) genes. A positive association was identified for adduct levels and GST mu null genotypes (P = 0.038). No correlation was found between polycyclic aromatic hydrocarbon-adduct levels and CYP1A1 exon 7 mutations. Age, race, and serum cotinine were not related to adduct levels. Multivariate analysis indicated that only the GST mu genotype was associated with polycyclic aromatic hydrocarbon-DNA adduct levels. This work demonstrates that the 32P-postlabeling assay can be modified for chemically specific adduct detection and that it can be used in the assessment of potentially important genetic factors for cancer risk. The absence of a functional GST mu gene in humans is likely one such factor. JF - Cancer research AU - Shields, P G AU - Bowman, E D AU - Harrington, A M AU - Doan, V T AU - Weston, A AD - Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1993/08/01/ PY - 1993 DA - 1993 Aug 01 SP - 3486 EP - 3492 VL - 53 IS - 15 SN - 0008-5472, 0008-5472 KW - CYPA1 KW - GST&mgr; KW - DNA Adducts KW - 0 KW - Polycyclic Compounds KW - benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide-DNA KW - 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide KW - 55097-80-8 KW - 7,8-dihydroxy-9,10-epoxide-7,8,9,10-tetrahydrobenzo(a)pyrene-10-deoxyguanosine KW - 62698-04-8 KW - DNA KW - 9007-49-2 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Deoxyguanosine KW - G9481N71RO KW - Index Medicus KW - Genotype KW - Base Sequence KW - Disease Susceptibility KW - Polymorphism, Genetic KW - Humans KW - Molecular Sequence Data KW - Deoxyguanosine -- analysis KW - Mutation KW - Deoxyguanosine -- analogs & derivatives KW - 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide -- analogs & derivatives KW - 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide -- analysis KW - Cytochrome P-450 Enzyme System -- genetics KW - DNA -- metabolism KW - Lung -- chemistry KW - DNA -- analysis KW - Glutathione Transferase -- genetics KW - Polycyclic Compounds -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75858591?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Polycyclic+aromatic+hydrocarbon-DNA+adducts+in+human+lung+and+cancer+susceptibility+genes.&rft.au=Shields%2C+P+G%3BBowman%2C+E+D%3BHarrington%2C+A+M%3BDoan%2C+V+T%3BWeston%2C+A&rft.aulast=Shields&rft.aufirst=P&rft.date=1993-08-01&rft.volume=53&rft.issue=15&rft.spage=3486&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 - 1993-09-02 N1 - Date created - 1993-09-02 N1 - Date revised - 2017-01-13 N1 - Gene symbol - CYPA1; GST&mgr; N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chimeric tick-borne encephalitis and dengue type 4 viruses: effects of mutations on neurovirulence in mice. AN - 75858358; 8331735 AB - Two new chimeric flaviviruses were constructed from full-length cDNAs that contained tick-borne encephalitis virus (TBEV) CME or ME structural protein genes and the remaining genes derived from dengue type 4 virus (DEN4). Studies involving mice inoculated intracerebrally with the ME chimeric virus indicated that it retained the neurovirulence of its TBEV parent from which its pre-M and E genes were derived. However, unlike parental TBEV, the chimeric virus did not produce encephalitis when mice were inoculated peripherally, indicating a loss of neuroinvasiveness. In the present study, the ME chimeric virus (vME) was subjected to mutational analysis in an attempt to reduce or ablate neurovirulence measured by direct inoculation of virus into the brain. We identified three distinct mutations that were each associated independently with a significant reduction of mouse neurovirulence of vME. These mutations ablated (i) the TBEV pre-M cleavage site, (ii) the TBEV E glycosylation site, or (iii) the first DEN4 NS1 glycosylation site. In contrast, ablation of the second DEN4 NS1 glycosylation site or the TBE pre-M glycosylation site or amino acid substitution at two positions in the TBEV E protein increased neurovirulence. The only conserved feature of the three attenuated mutants was restriction of virus yield in both simian and mosquito cells. Following parenteral inoculation, these attenuated mutants induced complete resistance in mice to fatal encephalitis caused by the highly neurovirulent vME. JF - Journal of virology AU - Pletnev, A G AU - Bray, M AU - Lai, C J AD - Molecular Viral Biology Section, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892. Y1 - 1993/08// PY - 1993 DA - August 1993 SP - 4956 EP - 4963 VL - 67 IS - 8 SN - 0022-538X, 0022-538X KW - Oligodeoxyribonucleotides KW - 0 KW - Viral Proteins KW - Methionine KW - AE28F7PNPL KW - Index Medicus KW - Viral Proteins -- genetics KW - Animals KW - Viral Plaque Assay KW - Methionine -- metabolism KW - Viral Proteins -- biosynthesis KW - Amino Acid Sequence KW - Mice KW - Glycosylation KW - Plasmids KW - Mice, Inbred BALB C KW - Base Sequence KW - Chimera KW - Transfection KW - Cells, Cultured KW - Kinetics KW - Restriction Mapping KW - Molecular Sequence Data KW - Cell Line KW - Encephalitis Viruses, Tick-Borne -- pathogenicity KW - Dengue -- physiopathology KW - Brain -- microbiology KW - Dengue Virus -- genetics KW - Mutagenesis, Site-Directed KW - Encephalitis Viruses, Tick-Borne -- genetics KW - Dengue Virus -- growth & development KW - Virulence -- genetics KW - Brain -- pathology KW - Encephalitis Viruses, Tick-Borne -- growth & development KW - Point Mutation KW - Dengue Virus -- pathogenicity KW - Encephalitis, Tick-Borne -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75858358?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Chimeric+tick-borne+encephalitis+and+dengue+type+4+viruses%3A+effects+of+mutations+on+neurovirulence+in+mice.&rft.au=Pletnev%2C+A+G%3BBray%2C+M%3BLai%2C+C+J&rft.aulast=Pletnev&rft.aufirst=A&rft.date=1993-08-01&rft.volume=67&rft.issue=8&rft.spage=4956&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 - 1993-08-16 N1 - Date created - 1993-08-16 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1987 Apr;84(7):2019-23 [3470774] Virology. 1992 Dec;191(2):921-31 [1280384] Virology. 1987 Aug;159(2):237-43 [2441520] Virology. 1988 Sep;166(1):197-205 [3413985] Virology. 1989 Mar;169(1):90-9 [2466373] J Virol. 1989 Jun;63(6):2853-6 [2724416] Virology. 1990 Jan;174(1):250-63 [2136778] Virology. 1990 Feb;174(2):450-8 [2154882] Virology. 1990 Aug;177(2):541-52 [2371768] J Virol. 1990 Sep;64(9):4356-63 [2143542] Virology. 1991 Jan;180(1):411-5 [1845834] J Gen Virol. 1991 Jun;72 ( Pt 6):1323-9 [1710648] Proc Natl Acad Sci U S A. 1991 Jun 15;88(12):5139-43 [2052593] Virus Genes. 1991 Apr;5(2):95-109 [1829286] Nature. 1970 Aug 15;227(5259):680-5 [5432063] Virology. 1979 May;95(1):197-207 [442540] FEBS Lett. 1986 May 12;200(2):317-21 [3709796] Virology. 1986 Nov;155(1):77-88 [3022479] Bioorg Khim. 1991 Mar;17(3):334-42 [1712201] Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):10342-6 [1682924] Virology. 1991 Dec;185(2):891-5 [1720591] Virology. 1992 Apr;187(2):573-90 [1312269] Virology. 1992 Sep;190(1):515-21 [1326816] Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10532-6 [1438242] Virology. 1987 Aug;159(2):217-28 [3039728] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - EPOCH chemotherapy: toxicity and efficacy in relapsed and refractory non-Hodgkin's lymphoma. AN - 75856389; 7687667 AB - Based on in vitro evidence that tumor cells are less resistant to prolonged exposure to low concentrations of the natural product class, compared with brief higher concentration exposure, we developed a chemotherapy regimen (etoposide, vincristine, doxorubicin, cyclophosphamide, and prednisone [EPOCH]) in which the natural products are administered as a continuous infusion. This is a phase II study of etoposide, vincristine, and doxorubicin, administered as a 96-hour continuous infusion, with intravenous (IV) bolus cyclophosphamide and oral prednisone (EPOCH) in 74 consecutive patients who relapsed from or failed to respond to most of the same drugs administered on a bolus schedule. Patients with aggressive lymphomas who achieved a good response after EPOCH were eligible to undergo bone marrow transplantation. Patients with intermediate- or high-grade lymphoma comprised 76% of this series and 77% had stage IV disease. Seventy-one percent had previously received all of the drugs contained in the EPOCH regimen and 92% had received at least four of the drugs. Seventy patients were assessable for response, of whom 19 (27%) achieved a complete remission (CR) and 42 (60%) a partial remission (PR). Among 21 patients who had no response to prior chemotherapy, 15 (71%) responded, but only one achieved a CR. Patients who relapsed from an initial CR had a 100% response rate, with 76% CRs. With a median potential follow-up duration of 19 months, there was a 28% probability of being event-free at 1 year. Toxicity was primarily hematologic with neutropenia during 51% of cycles, but only a 17% incidence of febrile neutropenia. Gastrointestinal, neurologic, and cardiac toxicity were minimal. EPOCH chemotherapy was well tolerated and highly effective in patients who were resistant to or relapsed from the same drugs administered on a bolus schedule, suggesting that continuous infusion of the natural drug component of this regimen is capable of partially reversing drug resistance and reducing toxicity. Dose-intensity (DI) was > or = that achieved in primary treatment regimens for aggressive lymphomas. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Wilson, W H AU - Bryant, G AU - Bates, S AU - Fojo, A AU - Wittes, R E AU - Steinberg, S M AU - Kohler, D R AU - Jaffe, E S AU - Herdt, J AU - Cheson, B D AD - Medicine Branch, National Cancer Institute, Bethesda, MD 20892. Y1 - 1993/08// PY - 1993 DA - August 1993 SP - 1573 EP - 1582 VL - 11 IS - 8 SN - 0732-183X, 0732-183X KW - Granulocyte Colony-Stimulating Factor KW - 143011-72-7 KW - Vincristine KW - 5J49Q6B70F KW - Etoposide KW - 6PLQ3CP4P3 KW - Doxorubicin KW - 80168379AG KW - Cyclophosphamide KW - 8N3DW7272P KW - Prednisone KW - VB0R961HZT KW - Index Medicus KW - Cyclophosphamide -- administration & dosage KW - Drug Administration Schedule KW - Granulocyte Colony-Stimulating Factor -- therapeutic use KW - Infusions, Intravenous KW - Humans KW - Vincristine -- administration & dosage KW - Neutropenia -- chemically induced KW - Aged KW - Drug Resistance KW - Doxorubicin -- administration & dosage KW - Recurrence KW - Etoposide -- administration & dosage KW - Adult KW - Treatment Outcome KW - Middle Aged KW - Neutropenia -- drug therapy KW - Prednisone -- administration & dosage KW - Female KW - Male KW - Survival Analysis KW - Lymphoma, Non-Hodgkin -- 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/75856389?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=EPOCH+chemotherapy%3A+toxicity+and+efficacy+in+relapsed+and+refractory+non-Hodgkin%27s+lymphoma.&rft.au=Wilson%2C+W+H%3BBryant%2C+G%3BBates%2C+S%3BFojo%2C+A%3BWittes%2C+R+E%3BSteinberg%2C+S+M%3BKohler%2C+D+R%3BJaffe%2C+E+S%3BHerdt%2C+J%3BCheson%2C+B+D&rft.aulast=Wilson&rft.aufirst=W&rft.date=1993-08-01&rft.volume=11&rft.issue=8&rft.spage=1573&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 - 1993-08-26 N1 - Date created - 1993-08-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Requirement for Raf and MAP kinase function during the meiotic maturation of Xenopus oocytes. AN - 75854196; 8335690 AB - The role of Raf and MAPK (mitogen-activated protein kinase) during the maturation of Xenopus oocytes was investigated. Treatment of oocytes with progesterone resulted in a shift in the electrophoretic mobility of Raf at the onset of germinal vesicle breakdown (GVBD), which was coincident with the activation of MAPK. Expression of a kinase-defective mutant of the human Raf-1 protein (KD-RAF) inhibited progesterone-mediated MAPK activation. MAPK activation was also inhibited by KD-Raf in oocytes expressing signal transducers of the receptor tyrosine kinase (RTK) pathway, including an activated tyrosine kinase (Tpr-Met), a receptor tyrosine kinase (EGFr), and Ha-RasV12. KD-RAF completely inhibited GVBD induced by the RTK pathway. In contrast, KD-RAF did not inhibit GVBD and the progression to Meiosis II in progesterone-treated oocytes. Injection of Mos-specific antisense oligodeoxyribonucleotides inhibited MAPK activation in response to progesterone and Tpr-Met, but failed to inhibit these events in oocytes expressing an oncogenic deletion mutant of Raf-1 (delta N'Raf). Injection of antisense oligodeoxyribonucleotides to Mos also reduced the progesterone- and Tpr-Met-induced electrophoretic mobility shift of Xenopus Raf. These results demonstrate that RTKs and progesterone participate in distinct yet overlapping signaling pathways resulting in the activation of maturation or M-phase promoting factor (MPF). Maturation induced by the RTK pathway requires activation of Raf and MAPK, while progesterone-induced maturation does not. Furthermore, the activation of MAPK in oocytes appears to require the expression of Mos. JF - The Journal of cell biology AU - Fabian, J R AU - Morrison, D K AU - Daar, I O AD - Molecular Mechanisms of Carcinogenesis Laboratory, NCI-Frederick Cancer Research and Development Center, Maryland 21702. Y1 - 1993/08// PY - 1993 DA - August 1993 SP - 645 EP - 652 VL - 122 IS - 3 SN - 0021-9525, 0021-9525 KW - Oligodeoxyribonucleotides KW - 0 KW - Proto-Oncogene Proteins KW - Progesterone KW - 4G7DS2Q64Y KW - Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - Proto-Oncogene Proteins c-mos KW - Proto-Oncogene Proteins c-raf KW - Mitogen-Activated Protein Kinase 1 KW - EC 2.7.11.24 KW - Index Medicus KW - Xenopus laevis KW - Animals KW - Base Sequence KW - Enzyme Activation KW - Progesterone -- pharmacology KW - Molecular Sequence Data KW - Signal Transduction KW - Female KW - Proto-Oncogene Proteins c-mos -- biosynthesis KW - Protein-Serine-Threonine Kinases -- metabolism KW - Meiosis -- drug effects KW - Proto-Oncogene Proteins -- metabolism KW - Oocytes -- drug effects KW - Oocytes -- physiology KW - Protein-Tyrosine Kinases -- metabolism KW - Proto-Oncogene Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75854196?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Molecular+basis+of+muscarinic+acetylcholine+receptor+function.&rft.au=Wess%2C+J&rft.aulast=Wess&rft.aufirst=J&rft.date=1993-08-01&rft.volume=14&rft.issue=8&rft.spage=308&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 - 1993-08-24 N1 - Date created - 1993-08-24 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Cell Biol. 1991 Jul;114(2):329-35 [1830055] EMBO J. 1991 Sep;10(9):2661-8 [1714387] J Biol Chem. 1991 Aug 15;266(23):14964-9 [1869534] Nature. 1991 Sep 12;353(6340):170-3 [1716348] Nature. 1991 Oct 17;353(6345):670-4 [1922387] Mol Cell Biol. 1991 Dec;11(12):5985-91 [1719375] Biol Cell. 1991;72(1-2):39-45 [1721855] Cancer Cells. 1991 Nov;3(11):445-9 [1662059] J Biol Chem. 1992 Mar 5;267(7):4408-15 [1311309] Nature. 1992 Feb 13;355(6361):649-52 [1531698] Science. 1992 Sep 4;257(5075):1404-7 [1326789] Cell. 1992 Oct 16;71(2):335-42 [1330321] J Biol Chem. 1992 Dec 5;267(34):24796-804 [1332967] Nature. 1992 Dec 10;360(6404):534-5 [1334231] Nature. 1992 Dec 10;360(6404):600-3 [1461284] Mol Cell Biol. 1993 Feb;13(2):1163-72 [8423783] Science. 1993 Jan 22;259(5094):525-8 [7678707] Cell. 1993 Feb 12;72(3):407-14 [8381718] EMBO J. 1993 Feb;12(2):787-94 [8440264] Mol Cell Biol. 1993 Apr;13(4):2546-53 [8384311] EMBO J. 1988 Mar;7(3):775-81 [3135183] Nature. 1988 Oct 6;335(6190):519-25 [2971141] Dev Biol. 1988 Nov;130(1):28-36 [3181631] Proc Natl Acad Sci U S A. 1988 Dec;85(23):8855-9 [3057494] J Biol Chem. 1989 Jan 15;264(2):856-61 [2463250] Mol Cell Biol. 1989 Feb;9(2):639-47 [2710120] Cell. 1989 Aug 25;58(4):649-57 [2475255] Proc Natl Acad Sci U S A. 1989 Sep;86(18):6940-3 [2550926] Nature. 1989 Nov 30;342(6249):512-8 [2531292] J Biol Chem. 1990 Feb 15;265(5):2713-9 [2154457] J Biol Chem. 1990 Mar 15;265(8):4730-5 [2155237] Exp Cell Res. 1975 Mar 15;91(2):381-8 [165088] Science. 1979 Sep 28;205(4413):1397-9 [472755] Int Rev Cytol. 1979;57:185-282 [385540] Dev Biol. 1981 Jul 30;85(2):309-16 [6266902] Proc Natl Acad Sci U S A. 1983 Jul;80(14):4218-22 [6308607] Nucleic Acids Res. 1984 Sep 25;12(18):7057-70 [6207484] Virology. 1985 Oct 15;146(1):78-89 [2994296] Cell. 1985 Dec;43(3 Pt 2):615-21 [2416466] Cell. 1986 Jun 20;45(6):895-904 [2423252] Mol Cell Biol. 1987 Mar;7(3):1171-9 [3561413] Mol Cell Biol. 1987 Mar;7(3):1285-8 [3550436] Science. 1987 May 15;236(4803):840-3 [3554510] J Biol Chem. 1988 Apr 15;263(11):5396-401 [3258598] Cell. 1988 Apr 22;53(2):185-95 [2834064] J Cell Biol. 1990 Mar;110(3):731-42 [1689732] Mol Cell Biol. 1990 Jun;10(6):2503-12 [2188091] J Biol Chem. 1990 Jul 15;265(20):11487-94 [2142153] J Biol Chem. 1990 Jul 15;265(20):11495-501 [2142154] Science. 1990 Jul 6;249(4964):64-7 [2164259] J Biol Chem. 1990 Sep 15;265(26):15471-80 [2394735] FEBS Lett. 1990 Oct 1;271(1-2):119-22 [2171996] Eur J Biochem. 1990 Nov 13;193(3):661-9 [2174361] Nature. 1991 Jan 17;349(6306):251-4 [1702878] Cell. 1991 Feb 8;64(3):479-82 [1846778] Nature. 1991 Jan 31;349(6308):426-8 [1992343] J Biol Chem. 1991 Mar 5;266(7):4220-7 [1705548] Mol Cell Biol. 1991 Apr;11(4):1965-71 [2005892] Biochem Cell Biol. 1990 Dec;68(12):1297-330 [2085430] Mol Cell Biol. 1991 May;11(5):2517-28 [1708093] Adv Cancer Res. 1992;58:53-73 [1312290] Cell. 1992 Mar 20;68(6):1041-50 [1312393] EMBO J. 1992 Mar;11(3):973-82 [1312468] Science. 1992 Jan 10;255(5041):212-5 [1313186] Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):2922-6 [1372995] Genes Dev. 1992 Apr;6(4):545-56 [1313769] Nature. 1992 Jul 30;358(6385):417-21 [1322500] Trends Biochem Sci. 1992 Jun;17(6):233-8 [1323888] Cell Growth Differ. 1992 Feb;3(2):135-42 [1504018] Mol Cell Biol. 1992 Sep;12(9):3776-83 [1508183] Cancer Cells. 1990 Dec;2(12):377-82 [2150916] Science. 1991 Apr 26;252(5005):558-61 [1850550] Cell. 1991 May 17;65(4):663-75 [2032290] Proc Natl Acad Sci U S A. 1991 Jul 1;88(13):5794-8 [1648231] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Analysis of the functional and host range-determining regions of the murine ectropic and amphotropic retrovirus envelope proteins. AN - 75854106; 8331726 AB - A series of Moloney murine leukemia virus (Mo-MuLV) envelope gene constructs were analyzed for biological activity. Three classes of recombinant envelopes were examined: insertions, deletions, and chimeras. Insertion (4 to 5 amino acids) and deletion (31 to 62 amino acids) mutants spanned most of the SU (gp70)-coding region and were all biologically inactive. Radioimmunoprecipitation demonstrated that the mutant envelope proteins were incorrectly processed. The Pr80env envelope precursor proteins failed to obtain the proper posttranslational modifications and were not cleaved into SU (gp70) and TM (p15E), suggesting that disruption of Pr80env structure prevents intracellular transport and processing. To analyze the functional domains of the SU portion of the Env protein, we assembled several chimeric constructs. In these constructs, portions of the ecotropic Mo-MuLV envelope gene were replaced with corresponding sequences from the 4070A amphotropic MuLV envelope. Using a retroviral vector pseudotyping assay, 5 of 12 chimeric envelope proteins were shown to be biologically active. Host range was determined by retroviral vector transduction of the appropriate cell, by viral interference studies, and by the productive infection of Chinese hamster ovary cells expressing the murine ecotropic receptor. These results permit assignment of the amino acids responsible for host range determination. Ecotropic host range is determined by the first 88 amino acids of the Mo-MuLV SU, while the amphotropic host range-determining region spans the first 157 amino acids of the 4070A SU. JF - Journal of virology AU - Morgan, R A AU - Nussbaum, O AU - Muenchau, D D AU - Shu, L AU - Couture, L AU - Anderson, W F AD - Molecular Hematology Branch, National Heart, Lung, and Blood Institute, Bethesda, Maryland 20892. Y1 - 1993/08// PY - 1993 DA - August 1993 SP - 4712 EP - 4721 VL - 67 IS - 8 SN - 0022-538X, 0022-538X KW - env KW - Gene Products, env KW - 0 KW - Recombinant Fusion Proteins KW - Recombinant Proteins KW - beta-Galactosidase KW - EC 3.2.1.23 KW - Index Medicus KW - AIDS/HIV KW - 3T3 Cells KW - Animals KW - Recombinant Fusion Proteins -- isolation & purification KW - Amino Acid Sequence KW - Mice KW - Cloning, Molecular KW - Recombinant Fusion Proteins -- metabolism KW - Recombinant Proteins -- isolation & purification KW - beta-Galactosidase -- metabolism KW - Transfection KW - Recombinant Proteins -- metabolism KW - Restriction Mapping KW - Molecular Sequence Data KW - beta-Galactosidase -- genetics KW - Cell Line KW - Mutagenesis, Insertional KW - Sequence Deletion KW - Gene Products, env -- metabolism KW - Gene Products, env -- isolation & purification KW - Defective Viruses -- genetics KW - Genes, env KW - Defective Viruses -- metabolism KW - Moloney murine leukemia virus -- genetics KW - Gene Products, env -- genetics KW - Moloney murine leukemia virus -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75854106?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Analysis+of+the+functional+and+host+range-determining+regions+of+the+murine+ectropic+and+amphotropic+retrovirus+envelope+proteins.&rft.au=Morgan%2C+R+A%3BNussbaum%2C+O%3BMuenchau%2C+D+D%3BShu%2C+L%3BCouture%2C+L%3BAnderson%2C+W+F&rft.aulast=Morgan&rft.aufirst=R&rft.date=1993-08-01&rft.volume=67&rft.issue=8&rft.spage=4712&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 - 1993-08-16 N1 - Date created - 1993-08-16 N1 - Date revised - 2017-01-13 N1 - Gene symbol - env N1 - SuppNotes - Cited By: EMBO J. 1986 Dec 1;5(12):3133-42 [3102226] J Virol. 1986 May;58(2):359-66 [3009853] J Virol. 1987 Sep;61(9):2659-69 [3039159] Methods Enzymol. 1987;152:684-704 [3657593] J Virol. 1988 Jan;62(1):168-75 [2824845] J Virol. 1988 Mar;62(3):1016-21 [2828650] J Virol. 1988 Apr;62(4):1120-4 [2831375] Proc Natl Acad Sci U S A. 1988 Nov;85(22):8688-92 [2847170] J Virol. 1989 Feb;63(2):647-58 [2911118] Cell. 1989 May 19;57(4):659-66 [2541919] J Virol. 1989 Sep;63(9):3561-8 [2547985] Ann N Y Acad Sci. 1989;567:39-49 [2552892] J Virol. 1990 Feb;64(2):757-66 [2153240] J Virol. 1991 Aug;65(8):4026-32 [2072445] Virology. 1991 Aug;183(2):545-54 [1853560] Nature. 1991 Aug 22;352(6337):725-8 [1652100] Virology. 1992 Jan;186(1):161-6 [1309273] J Virol. 1992 Mar;66(3):1468-75 [1310758] J Virol. 1992 Apr;66(4):2281-7 [1312632] J Virol. 1992 Aug;66(8):4632-8 [1321266] J Natl Cancer Inst. 1960 Apr;24:933-51 [14423465] Proc Natl Acad Sci U S A. 1969 Jul;63(3):753-8 [4186808] Nature. 1970 Aug 15;227(5259):680-5 [5432063] Cell. 1975 Jan;4(1):31-6 [803875] Virology. 1977 Feb;76(2):539-53 [190766] J Virol. 1977 Sep;23(3):787-98 [894795] J Virol. 1978 Jun;26(3):750-61 [78989] J Virol. 1979 Feb;29(2):735-43 [430608] J Virol. 1979 Apr;30(1):157-65 [225513] J Virol. 1979 Jun;30(3):720-8 [225541] Proc Natl Acad Sci U S A. 1980 Nov;77(11):6420-4 [6935656] Nature. 1981 Oct 15-21;293(5833):543-8 [6169994] J Virol. 1982 May;42(2):519-29 [6283170] J Virol. 1982 Oct;44(1):19-31 [7143566] Virology. 1983 Mar;125(2):513-8 [6836918] J Virol. 1983 Jun;46(3):1056-60 [6190011] J Virol. 1983 Jun;46(3):718-25 [6574260] J Virol. 1984 Jan;49(1):214-22 [6197537] J Virol. 1984 Feb;49(2):452-8 [6198530] J Virol. 1984 Jun;50(3):864-71 [6328017] J Virol. 1985 Jan;53(1):32-9 [2981357] Cell. 1986 May 9;45(3):365-74 [3009025] J Virol. 1987 May;61(5):1639-46 [3502707] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A phase II study of continuous infusion 5-fluorouracil and leucovorin with weekly cisplatin in metastatic colorectal carcinoma. AN - 75852480; 8334622 AB - Prolonged infusional 5-fluorouracil (5-FU) and bolus 5-FU modulated by leucovorin are associated with higher response rates than bolus 5-FU alone. Cisplatin enhances 5-FU cytotoxicity in some preclinical models. The authors tested the feasibility of combining concurrent infusional leucovorin (500 mg/m2/d) with protracted infusional 5-FU (200 mg/m2/d) and weekly bolus cisplatin (20 mg/m2) in 22 patients with metastatic colorectal cancer. Four partial responses (PR) were noticed among 21 evaluable patients (19%). The median time to treatment failure and median survival were 6 months and 11 months, respectively. All but two patients required 5-FU dose reduction after a median of 2 weeks because of mucositis. However, severe mucositis and diarrhea occurred in only 18% and 5% of the patients, respectively. Palmar-plantar erythrodysesthesia of mild to moderate severity occurred in 55% of patients. Megaloblastic changes were evident in the peripheral blood during therapy, and may reflect prolonged DNA-directed toxicity of 5-FU. The median tolerated dose level of 5-FU was 113 mg/m2/d (range, 64-150 mg/m2/d). Mean steady-state plasma concentrations (Cpss) of 5-FU appeared to increase linearly from 0.19 microM to 0.39 microM over the dose range 64 to 200 mg/m2/d. Patients with grade 2 gastrointestinal toxicity had significantly higher 5-FU Cpss than patients with grade 0 or 1 toxicity. The early onset of toxicity with this regimen of protracted infusional 5-FU/high-dose leucovorin and weekly cisplatin required marked attenuation of the 5-FU dose intensity, and the results were no better than that expected with infusional 5-FU alone. JF - Cancer AU - Grem, J L AU - McAtee, N AU - Balis, F AU - Murphy, R AU - Venzon, D AU - Kramer, B AU - Goldspiel, B AU - Begley, M AU - Allegra, C J AD - National Cancer Institute-Navy Medical Oncology Branch, National Naval Medical Center, Bethesda, Maryland 20889. Y1 - 1993/08/01/ PY - 1993 DA - 1993 Aug 01 SP - 663 EP - 668 VL - 72 IS - 3 SN - 0008-543X, 0008-543X KW - Cisplatin KW - Q20Q21Q62J KW - Leucovorin KW - Q573I9DVLP KW - Fluorouracil KW - U3P01618RT KW - Abridged Index Medicus KW - Index Medicus KW - Treatment Failure KW - Infusions, Intravenous KW - Dose-Response Relationship, Drug KW - Humans KW - Leucovorin -- administration & dosage KW - Leucovorin -- adverse effects KW - Aged KW - Cisplatin -- administration & dosage KW - Fluorouracil -- administration & dosage KW - Fluorouracil -- adverse effects KW - Adult KW - Neoplasm Metastasis KW - Middle Aged KW - Cisplatin -- adverse effects KW - Fluorouracil -- pharmacokinetics KW - Male KW - Female KW - Survival Analysis KW - Rectal Neoplasms -- mortality KW - Rectal Neoplasms -- drug therapy KW - Colonic Neoplasms -- mortality KW - Colonic Neoplasms -- drug therapy KW - Rectal Neoplasms -- pathology KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Colonic Neoplasms -- pathology KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75852480?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+phase+II+study+of+continuous+infusion+5-fluorouracil+and+leucovorin+with+weekly+cisplatin+in+metastatic+colorectal+carcinoma.&rft.au=Grem%2C+J+L%3BMcAtee%2C+N%3BBalis%2C+F%3BMurphy%2C+R%3BVenzon%2C+D%3BKramer%2C+B%3BGoldspiel%2C+B%3BBegley%2C+M%3BAllegra%2C+C+J&rft.aulast=Grem&rft.aufirst=J&rft.date=1993-08-01&rft.volume=72&rft.issue=3&rft.spage=663&rft.isbn=&rft.btitle=&rft.title=Cancer&rft.issn=0008543X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-08-24 N1 - Date created - 1993-08-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mechanism of developmental regulation of alpha pi, the chicken embryonic alpha-globin gene. AN - 75852019; 8336706 AB - The chicken alpha pi-globin gene is expressed during development only in the primitive erythrocyte lineage and not in the definitive lineage. We show that stage-specific expression is maintained when plasmids containing the alpha pi promoter are transfected into primitive and definitive lineage primary erythroid cells and that the information contained in the promoter is sufficient to confer this specificity. Detailed analysis of binding sites in the promoter for trans-acting factors, together with studies of the effects of mutagenesis on expression, reveals that the factors critical to stage-specific expression are all present in both primitive and definitive lineages, but at various concentrations. We identify three proteins, an NF1 family member, a Y-box factor, and an Sp1-like factor, which interact to stimulate or inhibit transcription. We propose that the concentration-dependent action of these factors, together with the general erythroid factor GATA-1, is responsible for the stage-specific expression of the alpha pi-globin gene. JF - Molecular and cellular biology AU - Knezetic, J A AU - Felsenfeld, G AD - Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892. Y1 - 1993/08// PY - 1993 DA - August 1993 SP - 4632 EP - 4639 VL - 13 IS - 8 SN - 0270-7306, 0270-7306 KW - DNA-Binding Proteins KW - 0 KW - Nuclear Proteins KW - RNA, Messenger KW - Globins KW - 9004-22-2 KW - Index Medicus KW - Animals KW - Chick Embryo KW - DNA Mutational Analysis KW - RNA, Messenger -- genetics KW - Cloning, Molecular KW - Promoter Regions, Genetic KW - Base Sequence KW - Genes KW - Transfection KW - Cells, Cultured KW - Enhancer Elements, Genetic KW - In Vitro Techniques KW - Molecular Sequence Data KW - Nuclear Proteins -- metabolism KW - Sequence Deletion KW - DNA-Binding Proteins -- metabolism KW - Globins -- genetics KW - Gene Expression Regulation KW - Chickens -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75852019?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mechanism+of+developmental+regulation+of+alpha+pi%2C+the+chicken+embryonic+alpha-globin+gene.&rft.au=Knezetic%2C+J+A%3BFelsenfeld%2C+G&rft.aulast=Knezetic&rft.aufirst=J&rft.date=1993-08-01&rft.volume=13&rft.issue=8&rft.spage=4632&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 - 1993-08-24 N1 - Date created - 1993-08-24 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Philos Trans R Soc Lond B Biol Sci. 1973 Oct 25;266(877):225-305 [4147843] Development. 1992 Aug;115(4):1149-64 [1451662] Cell. 1981 May;24(2):333-44 [7237551] Proc Natl Acad Sci U S A. 1986 Jun;83(12):4312-6 [3459175] Cell. 1987 Jul 31;50(3):347-59 [3607873] Proc Natl Acad Sci U S A. 1988 Apr;85(8):2548-52 [3357880] Nucleic Acids Res. 1988 May 25;16(10):4419-35 [3380685] Proc Natl Acad Sci U S A. 1988 Aug;85(16):5976-80 [3413070] Mol Cell Biol. 1989 Mar;9(3):893-901 [2725505] Genes Dev. 1989 Dec;3(12A):1845-59 [2620825] Genes Dev. 1989 Dec;3(12A):1860-73 [2620826] Nucleic Acids Res. 1990 May 11;18(9):2607-16 [2339052] Proc Natl Acad Sci U S A. 1990 Nov;87(22):9028-32 [2247479] Annu Rev Cell Biol. 1990;6:95-124 [2275826] Mol Cell Biol. 1991 Feb;11(2):843-53 [1990287] Cell. 1991 May 3;65(3):493-505 [1850324] Proc Natl Acad Sci U S A. 1980 May;77(5):2596-600 [6248855] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Deletion of the vaccinia virus B5R gene encoding a 42-kilodalton membrane glycoprotein inhibits extracellular virus envelope formation and dissemination. AN - 75847946; 8331727 AB - The structure, formation, and function of the virion membranes are among the least well understood aspects of vaccinia virus replication. In this study, we investigated the role of gp42, a glycoprotein component of the extracellular enveloped form of vaccinia virus (EEV) encoded by the B5R gene. The B5R gene was deleted by homologous recombination from vaccinia virus strains IHD-J and WR, which produce high and low levels of EEV, respectively. Isolation of recombinant viruses was facilitated by the insertion into the genome of a cassette containing the Escherichia coli gpt and lacZ genes flanked by the ends of the B5R gene to provide simultaneous antibiotic selection and color screening. Deletion mutant viruses of both strains formed tiny plaques, and those of the IHD-J mutant lacked the characteristic comet shape caused by release of EEV. Nevertheless, similar yields of intracellular infectious virus were obtained whether cells were infected with the B5R deletion mutants or their parental strains. In the case of IHD-J, however, this deletion severely reduced the amount of infectious extracellular virus. Metabolic labeling studies demonstrated that the low extracellular infectivity corresponded with a decrease in EEV particles in the medium. Electron microscopic examination revealed that mature intracellular naked virions (INV) were present in cells infected with mutant virus, but neither membrane-wrapped INV nor significant amounts of plasma membrane-associated virus were observed. Syncytium formation, which occurs in cells infected with wild-type WR and IHD-J virus after brief low-pH treatment, did not occur in cells infected with the B5R deletion mutants. By contrast, syncytium formation induced by antibody to the viral hemagglutinin occurred, suggesting that different mechanisms are involved. When assayed by intracranial injection into weanling mice, both IHD-J and WR mutant viruses were found to be significantly attenuated. These findings demonstrate that the 42-kDa glycoprotein of the EEV is required for efficient membrane enwrapment of INV, externalization of the virus, and transmission and that gp42 contributes to viral virulence in strains producing both low and high levels of EEV. JF - Journal of virology AU - Wolffe, E J AU - Isaacs, S N AU - Moss, B AD - Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892. Y1 - 1993/08// PY - 1993 DA - August 1993 SP - 4732 EP - 4741 VL - 67 IS - 8 SN - 0022-538X, 0022-538X KW - B5R KW - gpt KW - lacZ KW - DNA, Viral KW - 0 KW - Gene Products, env KW - Membrane Glycoproteins KW - Index Medicus KW - AIDS/HIV KW - Animals KW - Genes, Bacterial KW - Viral Plaque Assay KW - Virion -- genetics KW - HeLa Cells KW - Humans KW - Escherichia coli -- genetics KW - Virion -- metabolism KW - Plasmids KW - Virion -- ultrastructure KW - Blotting, Southern KW - Giant Cells -- physiology KW - Restriction Mapping KW - Recombination, Genetic KW - DNA, Viral -- isolation & purification KW - Giant Cells -- cytology KW - Microscopy, Electron KW - DNA, Viral -- genetics KW - Mutagenesis, Insertional KW - Cell Line KW - Sequence Deletion KW - Gene Products, env -- metabolism KW - Vaccinia virus -- genetics KW - Vaccinia virus -- ultrastructure KW - Vaccinia virus -- metabolism KW - Genes, Viral KW - Gene Products, env -- biosynthesis KW - Membrane Glycoproteins -- metabolism KW - Membrane Glycoproteins -- genetics KW - Gene Deletion UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75847946?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Deletion+of+the+vaccinia+virus+B5R+gene+encoding+a+42-kilodalton+membrane+glycoprotein+inhibits+extracellular+virus+envelope+formation+and+dissemination.&rft.au=Wolffe%2C+E+J%3BIsaacs%2C+S+N%3BMoss%2C+B&rft.aulast=Wolffe&rft.aufirst=E&rft.date=1993-08-01&rft.volume=67&rft.issue=8&rft.spage=4732&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 - 1993-08-16 N1 - Date created - 1993-08-16 N1 - Date revised - 2017-01-13 N1 - Gene symbol - B5R; gpt; lacZ N1 - SuppNotes - Cited By: J Virol. 1992 Dec;66(12):7217-24 [1433514] Virology. 1990 Nov;179(1):247-66, 517-63 [2219722] J Virol. 1993 Jun;67(6):3319-25 [8497053] J Gen Virol. 1971 Oct;13(1):19-25 [5130569] J Gen Virol. 1971 Oct;13(1):9-17 [4108676] Virology. 1971 Dec;46(3):507-32 [4944855] Virology. 1971 Dec;46(3):533-43 [4109523] J Clin Invest. 1973 Mar;52(3):535-42 [4685079] Prog Med Virol. 1973;16:86-108 [4356899] J Gen Virol. 1974 May;23(2):197-200 [4833605] J Gen Virol. 1976 Jul;32(1):63-72 [986420] Virology. 1976 Aug;73(1):43-58 [960564] J Virol. 1978 Jul;27(1):28-37 [691112] J Virol. 1979 Jul;31(1):147-55 [501796] J Cell Biol. 1993 May;121(3):521-41 [8486734] Virology. 1991 Mar;181(1):158-64 [1994573] J Virol. 1991 Jul;65(7):3435-42 [2041074] J Gen Virol. 1991 Jun;72 ( Pt 6):1349-76 [2045793] J Virol. 1991 Nov;65(11):5910-20 [1920620] Virology. 1992 Mar;187(1):251-60 [1736527] J Virol. 1992 Mar;66(3):1610-21 [1738204] J Virol. 1992 May;66(5):2617-30 [1560521] Virology. 1992 Jun;188(2):801-10 [1585649] J Virol. 1992 Jul;66(7):4170-9 [1602540] J Gen Virol. 1980 Sep;50(1):89-100 [7441216] J Virol. 1981 Sep;39(3):903-13 [7288920] J Gen Virol. 1985 Mar;66 ( Pt 3):643-6 [3973566] Nature. 1985 Oct 31-Nov 6;317(6040):813-5 [4058585] Virology. 1986 Apr 30;150(2):451-62 [3008418] J Virol. 1986 Jun;58(3):757-64 [3701927] J Virol. 1987 Feb;61(2):395-404 [3806791] J Virol. 1987 Nov;61(11):3550-4 [2822962] J Virol. 1988 Mar;62(3):866-74 [3339716] Virology. 1988 Mar;163(1):133-44 [2450423] J Virol. 1988 Jun;62(6):1849-54 [3130492] Virology. 1990 Apr;175(2):372-84 [2183466] Virology. 1990 Sep;178(1):81-91 [2389560] J Virol. 1990 Oct;64(10):4884-92 [2398531] Erratum In: J Virol 1993 Sep;67(9):5709-11 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Prevention of tobacco use during childhood and adolescence. Five steps to prevent the onset of smoking. AN - 75847184; 8334651 AB - Most tobacco users become addicted during childhood and adolescence. To reduce the prevalence of tobacco-related illnesses, more emphasis must be placed on preventing the onset of tobacco use. Physicians can play a major role. Based on a series of clinical trials, the National Cancer Institute (NCI) developed recommendations to help patients stop smoking. Behavioral and developmental research have identified factors that contribute to the onset of smoking. The American Academy of Pediatrics (AAP) has developed guidelines for health supervision from birth to adulthood, including engaging parents and children as partners in health care. The NCI recommendations, behavioral research results, and AAP guidelines were integrated to develop a strategy to prevent the onset of tobacco use. The NCI proposes five steps to prevent tobacco use during childhood and adolescence. There are five physician activities, beginning with the letter A, including anticipatory guidance, ask, advise, assist, and arrange follow-up. Anticipatory guidance, the practice of counseling for potential problems, is a key part of health care for the young. The nature of these steps varies, depending on the child's age, developmental stage, and behavior, as well as smoking habits of family members. Despite the long-term consequences of smoking, onset and addiction to tobacco use usually begins in childhood. Therefore, physicians who care for children have a major role in eliminating tobacco use by preventing its onset. JF - Cancer AU - Epps, R P AU - Manley, M W AD - National Cancer Institute, Bethesda, Maryland. Y1 - 1993/08/01/ PY - 1993 DA - 1993 Aug 01 SP - 1002 EP - 1004 VL - 72 IS - 3 Suppl SN - 0008-543X, 0008-543X KW - Abridged Index Medicus KW - Index Medicus KW - Humans KW - Health Behavior KW - Child KW - Adolescent KW - Child, Preschool KW - Health Promotion -- methods KW - Tobacco Use Disorder -- prevention & control KW - Smoking -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75847184?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Prevention+of+tobacco+use+during+childhood+and+adolescence.+Five+steps+to+prevent+the+onset+of+smoking.&rft.au=Epps%2C+R+P%3BManley%2C+M+W&rft.aulast=Epps&rft.aufirst=R&rft.date=1993-08-01&rft.volume=72&rft.issue=3+Suppl&rft.spage=1002&rft.isbn=&rft.btitle=&rft.title=Cancer&rft.issn=0008543X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-08-23 N1 - Date created - 1993-08-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A major transactivator of varicella-zoster virus, the immediate-early protein IE62, contains a potent N-terminal activation domain. AN - 75846223; 8392592 AB - Accumulating evidence indicates that the product of the putative immediate-early gene ORF62 (IE62) activates varicella-zoster virus (VZV) genes thought to represent all three kinetic classes, namely, immediate-early (alpha), early (beta), and late (gamma) classes, of VZV genes as well as a variety heterologous gene promoters. However, the mechanism(s) by which IE62 protein mediates transactivation of these diverse VZV and heterologous gene promoters remains to be elucidated. In this study, by using yeast GAL4 protein chimeras, the coding regions of VZV ORF62 possessing activation domains have been assessed. We demonstrate that the VZV IE62 protein contains a potent activation domain in the N-terminal portion of the molecule, encoded within the first 86 codons of ORF62. The predicted secondary structure profile and the acid-base composition of this IE62 domain resemble those of other transregulatory proteins whose activation is mediated through acidic, hydrophobic elements. In addition, we show that deletion of this activation domain from the 1,310-residue native IE62 protein results in ablation of the transactivator function of IE62. We also present evidence that the mutant IE62 protein lacking the activation domain, though devoid of transactivation ability, was still capable of interfering with the activation of target promoters by the native, full-length IE62. JF - Journal of virology AU - Perera, L P AU - Mosca, J D AU - Ruyechan, W T AU - Hayward, G S AU - Straus, S E AU - Hay, J AD - Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892. Y1 - 1993/08// PY - 1993 DA - August 1993 SP - 4474 EP - 4483 VL - 67 IS - 8 SN - 0022-538X, 0022-538X KW - IE62 KW - ORF62 KW - Codon KW - 0 KW - DNA-Binding Proteins KW - Fungal Proteins KW - GAL4 protein, S cerevisiae KW - IE62 protein, Human herpesvirus 3 KW - Immediate-Early Proteins KW - Oligodeoxyribonucleotides KW - Recombinant Fusion Proteins KW - Saccharomyces cerevisiae Proteins KW - Trans-Activators KW - Transcription Factors KW - Viral Envelope Proteins KW - Index Medicus KW - Codon -- genetics KW - Humans KW - Amino Acid Sequence KW - Fungal Proteins -- genetics KW - Plasmids KW - Recombinant Fusion Proteins -- metabolism KW - Mutagenesis, Site-Directed KW - Promoter Regions, Genetic KW - Base Sequence KW - Fungal Proteins -- metabolism KW - Restriction Mapping KW - Molecular Sequence Data KW - Cell Line KW - T-Lymphocytes KW - Trans-Activators -- metabolism KW - Herpesvirus 3, Human -- genetics KW - Gene Expression Regulation, Viral KW - Trans-Activators -- genetics KW - Genes, Viral KW - Viral Envelope Proteins -- metabolism KW - Herpesvirus 3, Human -- metabolism KW - Transcriptional Activation KW - Viral Envelope Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75846223?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+major+transactivator+of+varicella-zoster+virus%2C+the+immediate-early+protein+IE62%2C+contains+a+potent+N-terminal+activation+domain.&rft.au=Perera%2C+L+P%3BMosca%2C+J+D%3BRuyechan%2C+W+T%3BHayward%2C+G+S%3BStraus%2C+S+E%3BHay%2C+J&rft.aulast=Perera&rft.aufirst=L&rft.date=1993-08-01&rft.volume=67&rft.issue=8&rft.spage=4474&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 - 1993-08-16 N1 - Date created - 1993-08-16 N1 - Date revised - 2017-01-13 N1 - Gene symbol - IE62; ORF62 N1 - SuppNotes - Cited By: Virology. 1987 Feb;156(2):423-6 [3027986] J Virol. 1987 Jan;61(1):225-8 [3023701] Microbiol Rev. 1987 Dec;51(4):458-76 [2830478] J Virol. 1988 Jun;62(6):2076-82 [2835512] J Gen Virol. 1988 Jul;69 ( Pt 7):1531-74 [2839594] Cell. 1988 Aug 26;54(5):659-64 [3044607] Nature. 1988 Oct 6;335(6190):563-4 [3047590] Nature. 1988 Oct 20;335(6192):683-9 [3050531] Cell. 1988 Dec 23;55(6):1137-45 [2849508] Nature. 1989 Mar 2;338(6210):39-44 [2521923] Nucleic Acids Res. 1989 Jun 26;17(12):4637-46 [2546124] Science. 1989 Jul 28;245(4916):371-8 [2667136] Virology. 1989 Sep;172(1):223-36 [2549711] Annu Rev Biochem. 1989;58:799-839 [2673023] Nucleic Acids Res. 1989 Sep 25;17(18):7539 [2798115] Virology. 1989 Dec;173(2):700-9 [2556848] Science. 1990 Feb 9;247(4943):710-2 [2405489] Cell. 1990 Jun 29;61(7):1199-208 [2163758] Cell. 1990 Jun 29;61(7):1209-15 [2163759] J Gen Virol. 1990 Nov;71 ( Pt 11):2681-9 [2174959] J Bacteriol. 1991 Feb;173(3):1151-60 [1991714] J Virol. 1991 Mar;65(3):1149-59 [1847444] J Virol. 1991 Jul;65(7):3839-52 [1645794] J Virol. 1992 Jan;66(1):359-66 [1309252] J Virol. 1992 Jun;66(6):3811-22 [1316484] Virology. 1992 Jul;189(1):304-16 [1318606] J Virol. 1992 Sep;66(9):5298-304 [1323696] Virology. 1992 Nov;191(1):346-54 [1329324] J Exp Med. 1958 Dec 1;108(6):945-56 [13598821] J Virol. 1974 Jul;14(1):8-19 [4365321] Virology. 1974 Jul;60(1):302-7 [4366499] Proc Natl Acad Sci U S A. 1975 Apr;72(4):1276-80 [165503] J Virol. 1977 Mar;21(3):996-1001 [191658] Cell. 1977 Sep;12(1):275-85 [198141] J Virol. 1979 Jan;29(1):275-84 [219222] J Virol. 1979 Aug;31(2):447-62 [225564] J Virol. 1979 Nov;32(2):357-69 [228063] Nature. 1980 May 29;285(5763):329-30 [6246451] J Virol. 1980 Oct;36(1):189-203 [6255206] J Virol. 1982 Dec;44(3):939-49 [6294341] Mol Cell Biol. 1982 Sep;2(9):1044-51 [6960240] J Virol. 1983 May;46(2):371-7 [6302308] Proc Natl Acad Sci U S A. 1984 Jul;81(13):4065-9 [6330737] J Mol Biol. 1984 Nov 25;180(1):1-19 [6096556] Cell. 1985 Apr;40(4):767-74 [3886158] Proc Natl Acad Sci U S A. 1985 Jul;82(13):4539-43 [2989831] Proc Natl Acad Sci U S A. 1985 Sep;82(17):5870-4 [2994050] J Virol. 1985 Nov;56(2):558-70 [2997476] J Virol. 1985 Dec;56(3):723-33 [2999428] Nucleic Acids Res. 1986 Feb 25;14(4):1727-45 [3005980] J Gen Virol. 1986 Sep;67 ( Pt 9):1759-816 [3018124] Nature. 1986 Aug 21-27;322(6081):697-701 [3018583] Nucleic Acids Res. 1987 Jun 11;15(11):4491-511 [3035496] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inhibition of endogenous phosphatase in a postsynaptic density fraction allows extensive phosphorylation of the major postsynaptic density protein. AN - 75836729; 8393087 AB - The major postsynaptic density protein, proposed to be a calcium/calmodulin-dependent protein kinase, becomes phosphorylated when a postsynaptic density preparation from rat cerebral cortex is incubated in medium containing calcium and calmodulin. Upon longer incubation, however, the level of phosphorylation declines, suggesting the presence of a phosphatase activity. When Microcystin-LR, a phosphatase inhibitor, is included in the phosphorylation medium, the decline in phosphorylation is prevented and a higher maximal level of phosphorylation can be achieved. Under these conditions, the maximal phosphorylation of major postsynaptic density protein is accompanied by a nearly complete shift in its electrophoretic mobility from 50 kDa to 54 kDa, similar to that described for the alpha subunit of the soluble calcium/calmodulin-dependent protein kinase II. Of the four major groups of serine/threonine protein phosphatases, the enzyme responsible for the dephosphorylation of major postsynaptic density protein is neither type 2C, which is insensitive to Microcystin-LR, nor type 2B, which is calcium-dependent. As Microcystin-LR is much more potent than okadaic acid in inhibiting the dephosphorylation of major postsynaptic density protein, it is likely that the postsynaptic density-associated phosphatase is a type 1. The above results indicate that the relatively low level of phosphorylation of the major postsynaptic density protein observed in preparations containing postsynaptic densities is not due to a difference between the cytoplasmic and postsynaptic density-associated calcium/calmodulin-dependent kinases as previously proposed, but to a phosphatase activity, presumably belonging to the type 1 group. JF - Journal of neurochemistry AU - Dosemeci, A AU - Reese, T S AD - Laboratory of Neurobiology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/08// PY - 1993 DA - August 1993 SP - 550 EP - 555 VL - 61 IS - 2 SN - 0022-3042, 0022-3042 KW - Calmodulin KW - 0 KW - Ethers, Cyclic KW - Microcystins KW - Nerve Tissue Proteins KW - Peptides, Cyclic KW - postsynaptic density proteins KW - Okadaic Acid KW - 1W21G5Q4N2 KW - Egtazic Acid KW - 526U7A2651 KW - Phosphoric Monoester Hydrolases KW - EC 3.1.3.2 KW - cyanoginosin LR KW - EQ8332842Y KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Rats KW - Cell Fractionation KW - Animals KW - Rats, Sprague-Dawley KW - Phosphorylation KW - Microscopy, Electron KW - Calcium -- pharmacology KW - Ethers, Cyclic -- pharmacology KW - Peptides, Cyclic -- pharmacology KW - Egtazic Acid -- pharmacology KW - Calmodulin -- pharmacology KW - Cerebral Cortex -- metabolism KW - Synaptosomes -- ultrastructure KW - Cerebral Cortex -- ultrastructure KW - Nerve Tissue Proteins -- metabolism KW - Synaptosomes -- metabolism KW - Phosphoric Monoester Hydrolases -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75836729?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Inhibition+of+endogenous+phosphatase+in+a+postsynaptic+density+fraction+allows+extensive+phosphorylation+of+the+major+postsynaptic+density+protein.&rft.au=Dosemeci%2C+A%3BReese%2C+T+S&rft.aulast=Dosemeci&rft.aufirst=A&rft.date=1993-08-01&rft.volume=61&rft.issue=2&rft.spage=550&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 - 1993-08-24 N1 - Date created - 1993-08-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - TnphoA-mediated disruption of K54 capsular polysaccharide genes in Escherichia coli confers serum sensitivity. AN - 75833333; 8392976 AB - To assess whether non-K1, group 2 capsular serotypes are important in conferring serum resistance to extraintestinal isolates of Escherichia coli, a K54 blood isolate (CP9) was evaluated as a model pathogen. Transposon mutagenesis (TnphoA) was used to generate isogenic capsule-negative mutants. CP9 was resistant to the bactericidal effects of serum, growing in 80% serum. In contrast, all of the capsule-negative mutants had an increased sensitivity to 80% normal human serum, undergoing a 2- to 3-log kill over 3 h when starting inocula of 10(4) to 10(7) CFU/ml were used. The killing of the capsule-negative strains was mediated through the alternative complement pathway and not by lysozyme or beta-lysins. The protective effect of the K54 capsule against the bactericidal activity of serum was not through inhibition of the complement cascade, nor did it appear to be through a difference in the binding of C3. JF - Infection and immunity AU - Russo, T A AU - Moffitt, M C AU - Hammer, C H AU - Frank, M M AD - Bacterial Pathogenesis Unit, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892. Y1 - 1993/08// PY - 1993 DA - August 1993 SP - 3578 EP - 3582 VL - 61 IS - 8 SN - 0019-9567, 0019-9567 KW - Antimicrobial Cationic Peptides KW - 0 KW - Blood Proteins KW - Complement C3 KW - DNA Transposable Elements KW - Proteins KW - beta lysin, human KW - Muramidase KW - EC 3.2.1.17 KW - Index Medicus KW - Muramidase -- physiology KW - Humans KW - Complement Pathway, Alternative KW - Complement C3 -- metabolism KW - Proteins -- physiology KW - Genes, Bacterial KW - Bacterial Capsules -- genetics KW - Escherichia coli -- immunology KW - Blood Bactericidal Activity KW - Escherichia coli -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75833333?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=TnphoA-mediated+disruption+of+K54+capsular+polysaccharide+genes+in+Escherichia+coli+confers+serum+sensitivity.&rft.au=Russo%2C+T+A%3BMoffitt%2C+M+C%3BHammer%2C+C+H%3BFrank%2C+M+M&rft.aulast=Russo&rft.aufirst=T&rft.date=1993-08-01&rft.volume=61&rft.issue=8&rft.spage=3578&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 - 1993-08-26 N1 - Date created - 1993-08-26 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Curr Top Microbiol Immunol. 1985;121:99-133 [3910367] Carbohydr Res. 1985 Jun 15;139:261-71 [3896488] Infect Immun. 1987 May;55(5):1224-32 [3552994] Infect Immun. 1987 Nov;55(11):2662-8 [3312006] Rev Infect Dis. 1987 Sep-Oct;9 Suppl 5:S517-26 [2446369] Adv Intern Med. 1988;33:231-52 [2830769] Infect Immun. 1988 Oct;56(10):2723-30 [3047064] Rev Infect Dis. 1988 Jul-Aug;10 Suppl 2:S282-6 [3055198] J Infect Dis. 1989 Mar;159(3):400-6 [2644378] Infect Immun. 1990 Jan;58(1):222-7 [2403532] Rev Infect Dis. 1990 Nov-Dec;12(6):1008-18 [2267481] Clin Microbiol Rev. 1991 Jan;4(1):80-128 [1672263] Infect Immun. 1992 Dec;60(12):5048-56 [1452337] Proc Soc Exp Biol Med. 1960 Mar;103:632-6 [14425475] Immunology. 1967 Jun;12(6):639-53 [5338688] Am J Med Sci. 1970 Feb;259(2):114-9 [4905231] Immunology. 1970 Mar;18(3):331-46 [4986073] N Engl J Med. 1974 May 30;290(22):1216-20 [4133095] Immunology. 1971 May;20(5):767-77 [4950867] Infect Immun. 1974 Sep;10(3):657-66 [4609906] J Lab Clin Med. 1975 Jun;85(6):904-12 [805816] J Gen Microbiol. 1975 Jul;89(1):57-66 [1097595] Proc Natl Acad Sci U S A. 1978 Apr;75(4):1971-5 [273923] Proc Natl Acad Sci U S A. 1978 May;75(5):2416-20 [276881] J Infect Dis. 1978 Jul;138(1):33-41 [355575] J Med Microbiol. 1980 Feb;13(1):57-68 [6102156] J Immunol. 1981 Sep;127(3):1146-51 [6267132] Nature. 1982 Sep 16;299(5880):261-3 [7110347] Infect Immun. 1983 Apr;40(1):359-68 [6339405] J Med Microbiol. 1983 May;16(2):147-55 [6341596] Microbiol Rev. 1983 Mar;47(1):46-83 [6343827] Infect Immun. 1983 Dec;42(3):907-13 [6196296] J Infect Dis. 1984 Feb;149(2):184-93 [6199436] J Bacteriol. 1984 Sep;159(3):877-82 [6207166] Infect Immun. 1987 Feb;55(2):320-8 [3804440] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Community nutrition intervention strategies for cancer risk reduction AN - 1434033920; 18537524 AB - As the accumulated evidence continues to indicate a need for Americans to modify current eating patterns and other lifestyle factors to reduce the risk of chronic diseases, the demand for community nutrition interventions will accelerate. All interventions require certain basic elements, such as measurable objectives and robust evaluation designs. However, there are other overarching strategies whose application will contribute to the research knowledge base for community interventions. This article focuses on three such strategies: use of the national health objectives, use of community channels, and development of interventions based on theories of health behavior. The application of these strategies to the National 5 A Day for Better Health Program is illustrated. JF - Cancer AU - Heimendinger, Jerianne AD - National Cancer Institute, National Institutes of Health, Division of Cancer Prevention and Control, 9000 Rockville Pike, EPN 330, Bethesda, MD 20892. Y1 - 1993/08// PY - 1993 DA - Aug 1993 SP - 1019 EP - 1023 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 72 IS - S3 SN - 0008-543X, 0008-543X KW - Risk Abstracts; Health & Safety Science Abstracts KW - intervention KW - nutrition KW - risk reduction KW - cancer KW - Health risks KW - Intervention KW - Nutrition 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/1434033920?accountid=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&rft.atitle=Community+nutrition+intervention+strategies+for+cancer+risk+reduction&rft.au=Heimendinger%2C+Jerianne&rft.aulast=Heimendinger&rft.aufirst=Jerianne&rft.date=1993-08-01&rft.volume=72&rft.issue=S3&rft.spage=1019&rft.isbn=&rft.btitle=&rft.title=Cancer&rft.issn=0008543X&rft_id=info:doi/10.1002%2F1097-0142%2819930801%2972%3A3%2B3.0.CO%3B2+-B LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2013-09-01 N1 - Last updated - 2015-08-05 N1 - SubjectsTermNotLitGenreText - Health risks; Intervention; Nutrition; Cancer DO - http://dx.doi.org/10.1002/1097-0142(19930801)72:3+<1019::AID-CNCR2820721313>3.0.CO;2 ER - TY - JOUR T1 - The canadian national breast screening study. An appraisal and implications for early detection policy AN - 1434022341; 18537543 AB - The recent reports from the Canadian National Breast Screening Study (CNBSS) address the effectiveness of breast cancer screening for women in the 40-49 age group and the benefit of adding mammography to standard clinical breast examination in women aged 50-59. Overall, the CNBSS results do not show reductions in breast cancer mortality after seven years of follow-up in either age group. The CNBSS is an important study that includes a large number of women, rigorous procedures, and thorough follow-up, but there are several caveats to interpreting these results. The study results reported to date are based on small numbers of end point events. There are questions about the effectiveness of the randomization procedures in creating cohorts that initially were at equal risk of breast cancer-related death. It also has been observed that the quality level of mammographic screens obtained at the beginning of the study were not as high as those obtained later. Future reports from the CNBSS are planned and may provide additional data helpful in interpreting the results. JF - Cancer AU - Mettlin, Curtis J AU - Smart, Charles R AD - Retired Chief, Early Detection Branch, NCI, HHS. Y1 - 1993/08// PY - 1993 DA - Aug 1993 SP - 1461 EP - 1465 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 72 IS - S4 SN - 0008-543X, 0008-543X KW - Risk Abstracts; Health & Safety Science Abstracts KW - Health risks KW - Mortality KW - Age KW - Breast cancer KW - H 8000:Radiation Safety/Electrical Safety KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1434022341?accountid=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&rft.atitle=The+canadian+national+breast+screening+study.+An+appraisal+and+implications+for+early+detection+policy&rft.au=Mettlin%2C+Curtis+J%3BSmart%2C+Charles+R&rft.aulast=Mettlin&rft.aufirst=Curtis&rft.date=1993-08-01&rft.volume=72&rft.issue=S4&rft.spage=1461&rft.isbn=&rft.btitle=&rft.title=Cancer&rft.issn=0008543X&rft_id=info:doi/10.1002%2F1097-0142%2819930815%2972%3A4%2B3.0.CO%3B2+-S LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2013-09-01 N1 - Last updated - 2013-10-21 N1 - SubjectsTermNotLitGenreText - Mortality; Health risks; Age; Breast cancer DO - http://dx.doi.org/10.1002/1097-0142(19930815)72:4+<1461::AID-CNCR2820721408>3.0.CO;2 ER - TY - JOUR T1 - Data monitoring in the cardiac arrhythmia suppression trial. AN - 76203731; 8306012 AB - This report discusses practical aspects of data monitoring in a clinical trial which stopped ahead of schedule due to adverse findings. A review of the considerations and decisions made by the data-monitoring committee of the Cardiac Arrhythmia Suppression Trial (CAST), a randomized, double-blind clinical trial. CAST consisted of men and women with a recent myocardial infarction, asymptomatic or minimally symptomatic ventricular arrhythmias, and reduced left ventricular ejection fraction. In CAST, 3 antiarrhythmic agents, encainide, flecainide, and moricizine, were compared against placebo. The main outcome measures in CAST were arrhythmic death and total mortality. CAST found the 3 agents to be harmful. Encainide and flecainide were stopped first. Subsequently, moricizine was discontinued ahead of schedule. The complexity of the study design and a midcourse protocol modification raise several data-monitoring issues not previously discussed. These include how to handle apparently dramatic yet unexpected results, the need for flexibility in modifying study design and goals, and the conflict between existing study data and both conventional wisdom and medical practice. JF - The Online journal of current clinical trials AU - Friedman, L M AU - Bristow, J D AU - Hallstrom, A AU - Schron, E AU - Proschan, M AU - Verter, J AU - DeMets, D AU - Fisch, C AU - Nies, A S AU - Ruskin, J AD - National Heart, Lung, and Blood Institute, Bethesda, MD 20892. Y1 - 1993/07/31/ PY - 1993 DA - 1993 Jul 31 VL - Doc No 79 KW - Anti-Arrhythmia Agents KW - 0 KW - Index Medicus KW - Multicenter Studies as Topic KW - Randomized Controlled Trials as Topic KW - Myocardial Infarction -- complications KW - Humans KW - Data Interpretation, Statistical KW - Research Design KW - Male KW - Female KW - Professional Staff Committees KW - Clinical Trials as Topic KW - Arrhythmias, Cardiac -- drug therapy KW - Decision Making KW - Anti-Arrhythmia Agents -- adverse effects KW - Anti-Arrhythmia Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76203731?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Online+journal+of+current+clinical+trials&rft.atitle=Data+monitoring+in+the+cardiac+arrhythmia+suppression+trial.&rft.au=Friedman%2C+L+M%3BBristow%2C+J+D%3BHallstrom%2C+A%3BSchron%2C+E%3BProschan%2C+M%3BVerter%2C+J%3BDeMets%2C+D%3BFisch%2C+C%3BNies%2C+A+S%3BRuskin%2C+J&rft.aulast=Friedman&rft.aufirst=L&rft.date=1993-07-31&rft.volume=Doc+No+79&rft.issue=&rft.spage=%5B5870+words%3B+53+paragraphs%5D&rft.isbn=&rft.btitle=&rft.title=The+Online+journal+of+current+clinical+trials&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-03-17 N1 - Date created - 1994-03-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Alterations in populations of GST-p-immunoreactive single hepatocytes and hepatocellular foci after a single injection of N-nitrosodiethylamine with or without phenobarbital promotion in male F344/NCr rats. AN - 75942353; 8364903 AB - The fate of placental glutathione S-transferase (GST-P)-immunoreactive hepatocytes, detectable in livers of rats soon after treatment with N-nitrosodiethylamine (DEN), was examined sequentially with or without phenobarbital (PB) promotion. Group 1 male F344/NCr rats were administered a single i.p. injection of 200 mg DEN per kg body weight at 5 weeks of age. Group 2 rats were given 500 ppm PB in the diet two weeks after the DEN treatment. Groups of six rats were sequentially sacrificed 16, 42, 70, 126 and 238 days after DEN injection. In DEN-treated rats, GST-P immunoreactive hepatocytes (single cells and multiple cell foci) were detectable 16 days after DEN, the total numbers decreasing by day 70 and thereafter rising again. In the early stages the proportion of single immunoreactive hepatocytes was prominent, but with time a gradual increase in small GST-P+ hepatocellular foci and larger foci became evident. Feeding of PB to rats for 16-238 days after a single DEN injection resulted in increases of both single cells and foci, especially foci composed of more than three hepatocytes. The growth response was increasingly pronounced with time. Adenomas or carcinomas were only observed at 126 or 238 days. Numbers of GST-P+ foci far exceeded the numbers of foci visible in hematoxylin-eosin (H & E) stained sections, and a few H & E foci were negative for GST-P. Many GST-P+ foci smaller than ten cells were composed of histologically normal hepatocytes. Almost all GST-P+ foci identifiable in H&E stained sections were larger than ten cells, consisted of clear cells (in both groups) or mixed (clear-eosinophilic) cells in PB-exposed rats, and appeared to be evenly distributed throughout the three zones of the liver. These results suggest that the promotive effect of PB is most evident as an increase in larger hepatocyte populations composed of more than three GST-P+ hepatocytes, rather than in increasing the populations of single GST-P immunoreactive cells. PB may cause clonal expansion of these single GST-P reactive hepatocytes. This study provides evidence for the hypothesis that some of the GST-P reactive hepatocytes are initiated cells. JF - Cancer letters AU - Jang, J J AU - Henneman, J R AU - Kurata, Y AU - Uno, H AU - Ward, J M AD - Tumor Pathology and Pathogenesis Section, NCI-FCRDC, Frederick, Maryland 21702-1201. Y1 - 1993/07/30/ PY - 1993 DA - 1993 Jul 30 SP - 89 EP - 95 VL - 71 IS - 1-3 SN - 0304-3835, 0304-3835 KW - Diethylnitrosamine KW - 3IQ78TTX1A KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Phenobarbital KW - YQE403BP4D KW - Index Medicus KW - Rats KW - Body Weight KW - Animals KW - Rats, Inbred F344 KW - Placenta -- enzymology KW - Cells, Cultured KW - Time Factors KW - Organ Size KW - Male KW - Diethylnitrosamine -- toxicity KW - Liver -- enzymology KW - Liver -- cytology KW - Liver -- drug effects KW - Glutathione Transferase -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75942353?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+letters&rft.atitle=Alterations+in+populations+of+GST-p-immunoreactive+single+hepatocytes+and+hepatocellular+foci+after+a+single+injection+of+N-nitrosodiethylamine+with+or+without+phenobarbital+promotion+in+male+F344%2FNCr+rats.&rft.au=Jang%2C+J+J%3BHenneman%2C+J+R%3BKurata%2C+Y%3BUno%2C+H%3BWard%2C+J+M&rft.aulast=Jang&rft.aufirst=J&rft.date=1993-07-30&rft.volume=71&rft.issue=1-3&rft.spage=89&rft.isbn=&rft.btitle=&rft.title=Cancer+letters&rft.issn=03043835&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-10-06 N1 - Date created - 1993-10-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutations at the mouse microphthalmia locus are associated with defects in a gene encoding a novel basic-helix-loop-helix-zipper protein. AN - 75854920; 8343963 AB - Mice with mutations at the microphthalmia (mi) locus have some or all of the following defects: loss of pigmentation, reduced eye size, failure of secondary bone resorption, reduced numbers of mast cells, and early onset of deafness. Using a transgenic insertional mutation at this locus, we have identified a gene whose expression is disrupted in transgenic animals. This gene encodes a novel member of the basic-helix-loop-helix-leucine zipper (bHLH-ZIP) protein family of transcription factors, is altered in mice carrying two independent mi alleles (mi and miws), and is expressed in the developing eye, ear, and skin, all anatomical sites affected by mi. The multiple spontaneous and induced mutations available at mi provide a unique biological resource for studying the role of a bHLH-ZIP protein in mammalian development. JF - Cell AU - Hodgkinson, C A AU - Moore, K J AU - Nakayama, A AU - Steingrímsson, E AU - Copeland, N G AU - Jenkins, N A AU - Arnheiter, H AD - Laboratory of Viral and Molecular Pathogenesis, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/07/30/ PY - 1993 DA - 1993 Jul 30 SP - 395 EP - 404 VL - 74 IS - 2 SN - 0092-8674, 0092-8674 KW - mi KW - DNA-Binding Proteins KW - 0 KW - MITF protein, human KW - Microphthalmia-Associated Transcription Factor KW - Mitf protein, mouse KW - Transcription Factors KW - Index Medicus KW - Animals KW - Protein Structure, Secondary KW - Mice, Transgenic -- embryology KW - Humans KW - Gene Expression KW - Amino Acid Sequence KW - Mice KW - Tissue Distribution KW - Transcription Factors -- genetics KW - Cloning, Molecular KW - Alleles KW - Base Sequence KW - Molecular Sequence Data KW - Genetic Complementation Test KW - Mice, Inbred C3H KW - Mice, Inbred C57BL KW - Sequence Homology, Amino Acid KW - Waardenburg Syndrome -- genetics KW - Vitiligo -- genetics KW - Mutagenesis, Insertional KW - Protein Conformation KW - DNA-Binding Proteins -- genetics KW - Microphthalmos -- genetics KW - Leucine Zippers UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75854920?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cell&rft.atitle=Mutations+at+the+mouse+microphthalmia+locus+are+associated+with+defects+in+a+gene+encoding+a+novel+basic-helix-loop-helix-zipper+protein.&rft.au=Hodgkinson%2C+C+A%3BMoore%2C+K+J%3BNakayama%2C+A%3BSteingr%C3%ADmsson%2C+E%3BCopeland%2C+N+G%3BJenkins%2C+N+A%3BArnheiter%2C+H&rft.aulast=Hodgkinson&rft.aufirst=C&rft.date=1993-07-30&rft.volume=74&rft.issue=2&rft.spage=395&rft.isbn=&rft.btitle=&rft.title=Cell&rft.issn=00928674&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-09-03 N1 - Date created - 1993-09-03 N1 - Date revised - 2017-01-13 N1 - Gene symbol - mi N1 - Genetic sequence - L19248; GENBANK; L19249; S60905; S60904; S60902; Z23066; S60903; L33709; S60924; L14569 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ascorbic acid recycling in human neutrophils. AN - 75863259; 8340380 AB - Ascorbic acid (vitamin C) accumulation in activated human neutrophils is increased as much as 10-fold above the mM concentrations present in normal neutrophils. Internal concentrations as high as 14 mM are achieved when external vitamin is at physiologic concentration. The mechanism is by oxidation of external vitamin to dehydroascorbic acid, preferential transmembrane translocation of dehydroascorbic acid, and intracellular reduction to ascorbic acid within minutes. These data indicate that vitamin C accumulation is enhanced in activated human neutrophils and that human neutrophils utilize and recycle oxidized external vitamin C under physiologic conditions. JF - The Journal of biological chemistry AU - Washko, P W AU - Wang, Y AU - Levine, M AD - Section of Cell Biology and Biochemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/07/25/ PY - 1993 DA - 1993 Jul 25 SP - 15531 EP - 15535 VL - 268 IS - 21 SN - 0021-9258, 0021-9258 KW - Antioxidants KW - 0 KW - Xanthines KW - Xanthine KW - 1AVZ07U9S7 KW - N-Formylmethionine Leucyl-Phenylalanine KW - 59880-97-6 KW - Sodium Fluoride KW - 8ZYQ1474W7 KW - Catalase KW - EC 1.11.1.6 KW - Superoxide Dismutase KW - EC 1.15.1.1 KW - Xanthine Oxidase KW - EC 1.17.3.2 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Ascorbic Acid KW - PQ6CK8PD0R KW - Dehydroascorbic Acid KW - Y2Z3ZTP9UM KW - Index Medicus KW - Xanthine Oxidase -- metabolism KW - Humans KW - Superoxide Dismutase -- metabolism KW - Xanthines -- metabolism KW - Catalase -- metabolism KW - N-Formylmethionine Leucyl-Phenylalanine -- pharmacology KW - Oxidation-Reduction KW - Dehydroascorbic Acid -- metabolism KW - Antioxidants -- pharmacology KW - Cells, Cultured KW - Adult KW - Sodium Fluoride -- pharmacology KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Male KW - Neutrophils -- metabolism KW - Neutrophils -- drug effects KW - Ascorbic Acid -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75863259?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Ascorbic+acid+recycling+in+human+neutrophils.&rft.au=Washko%2C+P+W%3BWang%2C+Y%3BLevine%2C+M&rft.aulast=Washko&rft.aufirst=P&rft.date=1993-07-25&rft.volume=268&rft.issue=21&rft.spage=15531&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 - 1993-08-30 N1 - Date created - 1993-08-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Electroporation enhances c-myc antisense oligodeoxynucleotide efficacy. AN - 19713586; 8734186 AB - Obtaining high transfection efficiencies and achieving appropriate intracellular concentrations and localization are two of the most important barriers to the implementation of gene targeted therapy. The efficiency of endogenous uptake of oligodeoxynucleotides (ODNs) varies from cell type to cell type and may be a limiting factor of antisense efficacy. The use of electroporation to obtain high intracellular concentrations of a synthetic ODN in essentially 100% of viable cells is described. It is also shown that the transfected ODNs initially localize to the nucleus and remain there for at least 48 hours. The cellular trafficking of electroporated ODNs is shown to be an energy dependent process. Targeting of the c-myc proto-oncogene of U937 cells by electroporation of phosphorothioate-modified ODNs results in rapid and specific suppression of this gene at ODN concentrations much lower than would otherwise be required. This technique appears to be applicable to a variety of cell types and may represent a powerful new investigate tool as well as a promising approach to the ex vivo treatment of hematologic disorders. Images JF - Nucleic Acids Research AU - Bergan, R AU - Connell, Y AU - Fahmy, B AU - Neckers, L AD - Clinical Pharmacology Branch, NCI, NIH, Bethesda, MD 20892. Y1 - 1993/07/25/ PY - 1993 DA - 1993 Jul 25 SP - 3567 EP - 3573 PB - Oxford University Press, Oxford Journals, Great Clarendon Street VL - 21 IS - 15 SN - 0305-1048, 0305-1048 KW - Biotechnology and Bioengineering Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - Antisense oligonucleotides KW - Electroporation KW - Transfection KW - Energy KW - Limiting factors KW - Nuclei KW - Oligonucleotides KW - c-Myc protein KW - Proto-oncogenes KW - W 30905:Medical Applications KW - N 14840:Antisense, Nucleotide Analogs UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19713586?accountid=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=Nucleic+Acids+Research&rft.atitle=Electroporation+enhances+c-myc+antisense+oligodeoxynucleotide+efficacy.&rft.au=Bergan%2C+R%3BConnell%2C+Y%3BFahmy%2C+B%3BNeckers%2C+L&rft.aulast=Bergan&rft.aufirst=R&rft.date=1993-07-25&rft.volume=21&rft.issue=15&rft.spage=3567&rft.isbn=&rft.btitle=&rft.title=Nucleic+Acids+Research&rft.issn=03051048&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2008-12-01 N1 - Last updated - 2015-03-27 N1 - SubjectsTermNotLitGenreText - Antisense oligonucleotides; Electroporation; Transfection; Energy; Limiting factors; Nuclei; Oligonucleotides; Proto-oncogenes; c-Myc protein ER - TY - JOUR T1 - Sympathetic nerves, but not the adrenal gland, contribute to elevated plasma levels of met-enkephalin in rats with acute cholestatic hepatitis. AN - 76029802; 8210512 AB - Met-enkephalin is known to circulate in human and animal plasma in low levels. However, the source(s) of plasma met-enkephalin have not been completely elucidated. It has been proposed that the adrenal gland, sympathetic nerves, pancreas and the gut might be implicated. Recently, markedly elevated levels of met-enkephalin have been documented in the presence of liver disease. To investigate potential sources of met-enkephalin in liver disease, rats with acute cholestatic hepatitis 24 h after gavage with alpha naphthylisothiocyanate (ANIT) 100 mg/kg were studied. Plasma met-enkephalin levels were determined by radioimmunoassay in plasma samples from normal, adrenalectomized, or chemically sympathectomized animals. In control rats, ANIT treatment resulted in a striking 8.7-fold increase in systemic venous met-enkephalin levels (inferior vena cava) (P < or = 0.0005) and a significant increase in peptidase-derived met-enkephalin levels (determined after trypsin/carboxypeptidase B digestion of plasma samples) (P < or = 0.05). ANIT-treatment also resulted in a 5.6-fold increase in portal vein met-enkephalin levels (P < or = 0.005). Portal vein met-enkephalin levels were only 1.2-fold higher than IVC levels in ANIT-treated rats (P < or = 0.05). Plasma activities of the two main enkephalin degrading enzymes, aminopeptidase and enkephalinase, were similar in control and ANIT-treated rats. Chemical sympathectomy, prior to ANIT treatment, decreased the elevation in inferior vena caval met-enkephalin levels by 35% (P < or = 0.005). Adrenalectomy did not alter ANIT-induced increases in circulating met-enkephalin levels (pNS).(ABSTRACT TRUNCATED AT 250 WORDS) JF - Regulatory peptides AU - Swain, M G AU - Vergalla, J AU - Bergasa, N V AU - Jones, E A AD - Liver Diseases Section, NIDDK, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/07/23/ PY - 1993 DA - 1993 Jul 23 SP - 535 EP - 542 VL - 46 IS - 3 SN - 0167-0115, 0167-0115 KW - 1-Naphthylisothiocyanate KW - 551-06-4 KW - Enkephalin, Methionine KW - 58569-55-4 KW - Aminopeptidases KW - EC 3.4.11.- KW - Neprilysin KW - EC 3.4.24.11 KW - Index Medicus KW - Animals KW - Portal Vein -- metabolism KW - Aminopeptidases -- blood KW - Sympathectomy, Chemical KW - Disease Models, Animal KW - Adrenalectomy KW - Radioimmunoassay KW - Chromatography, High Pressure Liquid KW - Rats KW - Rats, Sprague-Dawley KW - Neprilysin -- blood KW - Male KW - Enkephalin, Methionine -- blood KW - Sympathetic Nervous System -- secretion KW - Hepatitis, Animal -- chemically induced KW - Hepatitis, Animal -- blood KW - Adrenal Glands -- secretion KW - Cholestasis, Intrahepatic -- chemically induced KW - Cholestasis, Intrahepatic -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76029802?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Regulatory+peptides&rft.atitle=Sympathetic+nerves%2C+but+not+the+adrenal+gland%2C+contribute+to+elevated+plasma+levels+of+met-enkephalin+in+rats+with+acute+cholestatic+hepatitis.&rft.au=Swain%2C+M+G%3BVergalla%2C+J%3BBergasa%2C+N+V%3BJones%2C+E+A&rft.aulast=Swain&rft.aufirst=M&rft.date=1993-07-23&rft.volume=46&rft.issue=3&rft.spage=535&rft.isbn=&rft.btitle=&rft.title=Regulatory+peptides&rft.issn=01670115&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-11-01 N1 - Date created - 1993-11-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetic risk and carcinogen exposure: a common inherited defect of the carcinogen-metabolism gene glutathione S-transferase M1 (GSTM1) that increases susceptibility to bladder cancer. AN - 75827798; 8320745 AB - Numerous studies have associated bladder cancer with exposure to carcinogens present in tobacco smoke and other environmental or occupational exposures. Approximately 50% of all humans inherit two deleted copies of the GSTM1 gene which encodes for the carcinogen-detoxification enzyme glutathione S-transferase M1. Recent findings suggest that the GSTM1 gene may modulate the internal dose of environmental carcinogens and thereby affect the risk of developing bladder cancer. We investigated whether the absence of the GSTM1 gene affects bladder cancer risk and whether there are racial differences in GSTM1 genotype frequency. Using a polymerase chain reaction (PCR)-based method, we examined the frequency of the homozygous deleted genotype (GSTM1 0/0) in 229 patients with transitional cell carcinoma of the bladder and 211 control subjects who were enrolled from the Urology Clinics at Duke University Medical Center and the University of North Carolina Hospitals. Control subjects were urology clinic patients who primarily presented with benign prostatic hypertrophy or impotence, who had no history of any cancer other than nonmelanoma skin cancer, and who were frequency matched to case patients on race, sex, and age (10-year age intervals). In order to explore racial differences in GSTM1 gene frequency, genotype was also determined in a community-based sample of 466 paid, healthy, unrelated volunteers from Durham and Chapel Hill, N.C. The presence or absence of the GSTM1 gene locus was determined by using a differential PCR, a semiquantitative technique in which multiple genes are coamplified. Overall, the GSTM1 0/0 genotype conferred a 70% increased risk of bladder cancer (odds ratio [OR] = 1.7; 95% confidence interval [CI] = 1.2-2.5; P = .004). Absence of the GSTM1 gene encoding the glutathione S-transferase M1 enzyme significantly increased risk to persons with exposure to the carcinogens in tobacco smoke (OR = 1.8; 95% CI = 1.2-3.0; P = .01) but poses little increased risk to persons without such exposure. Persons with smoking exposure of more than 50 pack-years who had the GSTM1 0/0 genotype had a sixfold greater risk relative to persons in the lowest risk group (i.e., nonsmokers who were GSTM1 +/+ or +/0). In the pooled clinic control and community sample groups (677 individuals), the GSTM1 0/0 genotype occurred less frequently among Blacks (35%) than among Whites (49%, P < .001). These findings support a protective role for the GSTM1 gene in bladder cancer. From these findings, it is estimated that 25% of all bladder cancer may be attributable to the at-risk GSTM1 0/0 genotype. JF - Journal of the National Cancer Institute AU - Bell, D A AU - Taylor, J A AU - Paulson, D F AU - Robertson, C N AU - Mohler, J L AU - Lucier, G W AD - Laboratory of Biochemical Risk Analysis, National Institute of Environmental Health-Sciences (NIEHS), Research Triangle Park, N.C. 27709. Y1 - 1993/07/21/ PY - 1993 DA - 1993 Jul 21 SP - 1159 EP - 1164 VL - 85 IS - 14 SN - 0027-8874, 0027-8874 KW - GSTM1 KW - Isoenzymes KW - 0 KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Index Medicus KW - Genotype KW - Polymerase Chain Reaction KW - Continental Population Groups -- genetics KW - Base Sequence KW - Humans KW - Molecular Sequence Data KW - Smoking -- adverse effects KW - Genetic Predisposition to Disease KW - Male KW - Female KW - Urinary Bladder Neoplasms -- genetics KW - Urinary Bladder Neoplasms -- enzymology KW - Glutathione Transferase -- genetics KW - Isoenzymes -- genetics KW - Carcinoma, Transitional Cell -- genetics KW - Carcinoma, Transitional Cell -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75827798?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+National+Cancer+Institute&rft.atitle=Genetic+risk+and+carcinogen+exposure%3A+a+common+inherited+defect+of+the+carcinogen-metabolism+gene+glutathione+S-transferase+M1+%28GSTM1%29+that+increases+susceptibility+to+bladder+cancer.&rft.au=Bell%2C+D+A%3BTaylor%2C+J+A%3BPaulson%2C+D+F%3BRobertson%2C+C+N%3BMohler%2C+J+L%3BLucier%2C+G+W&rft.aulast=Bell&rft.aufirst=D&rft.date=1993-07-21&rft.volume=85&rft.issue=14&rft.spage=1159&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+National+Cancer+Institute&rft.issn=00278874&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-08-05 N1 - Date created - 1993-08-05 N1 - Date revised - 2017-01-13 N1 - Gene symbol - GSTM1 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Crystal structures of native and inhibited forms of human cathepsin D: implications for lysosomal targeting and drug design. AN - 75862919; 8393577 AB - Cathepsin D (EC 3.4.23.5) is a lysosomal protease suspected to play important roles in protein catabolism, antigen processing, degenerative diseases, and breast cancer progression. Determination of the crystal structures of cathepsin D and a complex with pepstatin at 2.5 A resolution provides insights into inhibitor binding and lysosomal targeting for this two-chain, N-glycosylated aspartic protease. Comparison with the structures of a complex of pepstatin bound to rhizopuspepsin and with a human renin-inhibitor complex revealed differences in subsite structures and inhibitor-enzyme interactions that are consistent with affinity differences and structure-activity relationships and suggest strategies for fine-tuning the specificity of cathepsin D inhibitors. Mutagenesis studies have identified a phosphotransferase recognition region that is required for oligosaccharide phosphorylation but is 32 A distant from the N-domain glycosylation site at Asn-70. Electron density for the crystal structure of cathepsin D indicated the presence of an N-linked oligosaccharide that extends from Asn-70 toward Lys-203, which is a key component of the phosphotransferase recognition region, and thus provides a structural explanation for how the phosphotransferase can recognize apparently distant sites on the protein surface. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Baldwin, E T AU - Bhat, T N AU - Gulnik, S AU - Hosur, M V AU - Sowder, R C AU - Cachau, R E AU - Collins, J AU - Silva, A M AU - Erickson, J W AD - Structural Biochemistry Program, Program Resources Inc./DynCorp, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702. Y1 - 1993/07/15/ PY - 1993 DA - 1993 Jul 15 SP - 6796 EP - 6800 VL - 90 IS - 14 SN - 0027-8424, 0027-8424 KW - Pepstatins KW - 0 KW - Streptomyces pepsin inhibitor KW - 11076-29-2 KW - Phosphotransferases KW - EC 2.7.- KW - Aspartic Acid Endopeptidases KW - EC 3.4.23.- KW - Renin KW - EC 3.4.23.15 KW - rhizopuspepsin KW - EC 3.4.23.21 KW - Cathepsin D KW - EC 3.4.23.5 KW - pepstatin KW - V6Y2T27Q1U KW - Index Medicus KW - Renin -- chemistry KW - X-Ray Diffraction KW - Models, Molecular KW - Humans KW - Biological Transport KW - Amino Acid Sequence KW - Aspartic Acid Endopeptidases -- chemistry KW - Glycosylation KW - Drug Design KW - Molecular Sequence Data KW - Lysosomes KW - Protein Conformation KW - Cathepsin D -- antagonists & inhibitors KW - Pepstatins -- chemistry KW - Cathepsin D -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75862919?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Crystal+structures+of+native+and+inhibited+forms+of+human+cathepsin+D%3A+implications+for+lysosomal+targeting+and+drug+design.&rft.au=Baldwin%2C+E+T%3BBhat%2C+T+N%3BGulnik%2C+S%3BHosur%2C+M+V%3BSowder%2C+R+C%3BCachau%2C+R+E%3BCollins%2C+J%3BSilva%2C+A+M%3BErickson%2C+J+W&rft.aulast=Baldwin&rft.aufirst=E&rft.date=1993-07-15&rft.volume=90&rft.issue=14&rft.spage=6796&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 - 1993-08-30 N1 - Date created - 1993-08-30 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Biochem Biophys Res Commun. 1967 Apr 20;27(2):157-62 [6035483] J Mol Biol. 1990 Jul 5;214(1):143-70 [2115087] Proteins. 1990;8(1):62-81 [2217165] Nature. 1991 Feb 21;349(6311):669-76 [1847504] Semin Cancer Biol. 1990 Apr;1(2):153-60 [2103491] Semin Cancer Biol. 1990 Apr;1(2):99-106 [2103492] Science. 1991 Nov 8;254(5033):862-6 [1948067] J Biol Chem. 1991 Dec 5;266(34):23365-72 [1660471] Sci Am. 1992 Feb;266(2):54-9, 62-3 [1373003] Proteins. 1992 Jul;13(3):195-205 [1603809] Nature. 1992 Jun 11;357(6378):466-72 [1608447] J Mol Biol. 1992 Jul 20;226(2):555-7 [1640466] J Mol Biol. 1992 Sep 5;227(1):265-70 [1522590] J Biol Chem. 1992 Nov 15;267(32):23342-8 [1331081] J Biol Chem. 1992 Nov 15;267(32):23349-56 [1331082] J Biol Chem. 1992 Nov 15;267(32):23357-63 [1331083] J Mol Biol. 1992 Oct 20;227(4):1265-8 [1433300] Protein Sci. 1993 Feb;2(2):264-76 [8443603] J Mol Biol. 1977 May 25;112(3):535-42 [875032] Methods Enzymol. 1979;63:437-67 [502865] Annu Rev Biochem. 1986;55:167-93 [2943218] J Med Chem. 1986 Dec;29(12):2519-24 [3783611] Can J Physiol Pharmacol. 1987 Feb;65(2):124-9 [3552162] Biochemistry. 1987 Dec 15;26(25):8083-6 [3327517] J Biol Chem. 1988 Nov 5;263(31):16504-11 [3182800] Science. 1989 Mar 10;243(4896):1346-51 [2493678] J Biol Chem. 1989 Aug 25;264(24):14159-64 [2474542] J Neurosci Res. 1989 Aug;23(4):454-6 [2769800] EMBO J. 1989 Aug;8(8):2179-88 [2676515] Annu Rev Cell Biol. 1989;5:483-525 [2557062] Nature. 1990 Jan 11;343(6254):133-9 [2404209] Biochem J. 1990 Feb 1;265(3):871-8 [2407237] Proc Natl Acad Sci U S A. 1990 May;87(10):3861-5 [1692625] Annu Rev Biophys Biophys Chem. 1990;19:189-215 [2194475] Cell. 1990 Oct 19;63(2):281-91 [2170024] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Fidelity of DNA replication by extracts of normal and malignantly transformed human cells. AN - 75861597; 8391921 AB - To test the hypothesis that a mutator phenotype may be associated with carcinogenesis (L. A. Loeb, Cancer Res., 51: 3074-3079, 1991), we have compared the fidelity of double-stranded DNA replication and the efficiency of mismatch repair in extracts from normal diploid and malignantly transformed human cells. Included was a diploid fibroblast strain and its transformed derivative, as well as a second diploid fibroblast strain and HeLa cells. The fidelity of DNA replication by cytoplasmic extracts in the presence of simian virus 40 large tumor antigen (SV40 T-antigen) was measured using a forward mutagenesis assay. The replicated DNA consisted of double-stranded M13 mp2 DNA containing the SV40 origin of replication and the lacZ alpha complementation gene as a target sequence for scoring mutations. T-antigen-dependent replication was detected in all cell extracts, with those from transformed cells having the greatest activity. No differences in replication fidelity were detected between normal and transformed cell extracts. Using a heteroduplex containing a G.G mispair, we also detected mismatch repair activity in the cell extracts, including efficient repair in extracts from malignantly transformed cells. While these data do not eliminate the possibility that a mutator phenotype may be associated with carcinogenesis, they do suggest that genetic instability associated with transformation does not involve reduced fidelity of replication of undamaged DNA or reduced mismatch repair efficiency. JF - Cancer research AU - Boyer, J C AU - Thomas, D C AU - Maher, V M AU - McCormick, J J AU - Kunkel, T A AD - Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1993/07/15/ PY - 1993 DA - 1993 Jul 15 SP - 3270 EP - 3275 VL - 53 IS - 14 SN - 0008-5472, 0008-5472 KW - DNA, Neoplasm KW - 0 KW - Index Medicus KW - Phenotype KW - HeLa Cells KW - Simian virus 40 -- genetics KW - Humans KW - Escherichia coli -- genetics KW - Cell Line, Transformed KW - Male KW - Fibroblasts KW - DNA Repair KW - Mutation -- genetics KW - Neoplasms -- genetics KW - DNA Replication UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75861597?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Fidelity+of+DNA+replication+by+extracts+of+normal+and+malignantly+transformed+human+cells.&rft.au=Boyer%2C+J+C%3BThomas%2C+D+C%3BMaher%2C+V+M%3BMcCormick%2C+J+J%3BKunkel%2C+T+A&rft.aulast=Boyer&rft.aufirst=J&rft.date=1993-07-15&rft.volume=53&rft.issue=14&rft.spage=3270&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 - 1993-08-10 N1 - Date created - 1993-08-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Functionally anergic lpr and gld B220+ T cell receptor (TCR)-alpha/beta+ double-negative T cells express CD28 and respond to costimulation with phorbol myristate acetate and antibodies to CD28 and the TCR. AN - 75859253; 7687618 AB - Mice homozygous for lpr and gld develop lymphadenopathy characterized by the progressive accumulation of an unusual population of CD4-, CD8-, CD2-, IL-2R- double-negative (DN) T cells that express reduced levels of TCR-alpha/beta, high levels of CD45 (B220) and Ly-6C and variable levels of CD69. These cells are refractory to most stimuli, including staphylococcal entertoxins and cross-linking of the TCR, Ly-6C, and CD69. For normal T cells, the binding of ligand to the TCR alone is insufficient to induce a proliferative response and can result in the induction of a state of prolonged anergy. Efficient stimulation is dependent on the delivery of a second or costimulatory signal. Recently it was reported that CD28 can provide costimulatory signals to T cells and, that these signals can prevent anergy induction in T cell clones. We investigated the possibility that lpr and gld DN T cells are unresponsive because they fail to transduce signals via CD28. These studies showed that highly purified B220+ TCR-alpha/beta+ DN T cells expressed high levels of CD28, responded weakly to stimulation with PMA and anti-CD28 mAb and quite strongly to PMA, anti-CD28 antibody and high concentrations of immobilized anti-TCR-alpha/beta antibodies. The latter stimulus also induced low levels of expression of CD2 and IL-2R and secretion of modest amounts of IL-2. Although DN T cells proliferated and secreted IL-2, these responses differed qualitatively and quantitatively from those of +/+ and lprB220- T cells. Consistent with its effects on normal T cells, cyclosporin A partially inhibited the response of DN T cells to TCR cross-linking and CD28 ligation. Studies of synergism between CD28-, Ly-6C-, and CD69-mediated signals revealed that ligation of CD28 enhanced the proliferative response induced by cross-linking of Ly-6C or CD69 on +/+, lpr and gld B220- T cells but had no effect on the unresponsiveness of DN T cells to these stimuli. Ligation of CD28 did not reverse the unresponsiveness of DN T cells to SEB and had only a weak synergistic effect on the response of B220- T cells. Together, these observations suggest that the mechanisms leading to immunosuppression of DN T cells are complex and appear to involve abnormalities in signal transduction via the TCR and CD28 and possibly via Ly-6C and CD69 as well. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Giese, T AU - Allison, J P AU - Davidson, W F AD - Laboratory of Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/07/15/ PY - 1993 DA - 1993 Jul 15 SP - 597 EP - 609 VL - 151 IS - 2 SN - 0022-1767, 0022-1767 KW - gld KW - lpr KW - Antibodies, Monoclonal KW - 0 KW - Antigens, CD KW - Antigens, CD28 KW - Antigens, CD4 KW - Antigens, CD8 KW - Antigens, Differentiation, T-Lymphocyte KW - Antigens, Surface KW - Enterotoxins KW - Interleukin-2 KW - Receptors, Antigen, T-Cell, alpha-beta KW - enterotoxin B, staphylococcal KW - 39424-53-8 KW - Cyclosporine KW - 83HN0GTJ6D KW - Antigens, CD45 KW - EC 3.1.3.48 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Abridged Index Medicus KW - Index Medicus KW - Enterotoxins -- immunology KW - Animals KW - Cyclosporine -- pharmacology KW - Mice, Inbred C3H KW - Mice KW - Interleukin-2 -- secretion KW - Antibodies, Monoclonal -- immunology KW - Antigens, CD -- analysis KW - Antigens, CD -- physiology KW - Antigens, CD8 -- analysis KW - Lymphoproliferative Disorders -- immunology KW - Immune Tolerance KW - Receptors, Antigen, T-Cell, alpha-beta -- physiology KW - Lymphocyte Activation KW - Antigens, Differentiation, T-Lymphocyte -- analysis KW - Antigens, CD4 -- analysis KW - Antigens, Differentiation, T-Lymphocyte -- physiology KW - T-Lymphocyte Subsets -- immunology KW - Receptors, Antigen, T-Cell, alpha-beta -- analysis KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Antigens, Surface -- analysis KW - Autoimmune Diseases -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75859253?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Functionally+anergic+lpr+and+gld+B220%2B+T+cell+receptor+%28TCR%29-alpha%2Fbeta%2B+double-negative+T+cells+express+CD28+and+respond+to+costimulation+with+phorbol+myristate+acetate+and+antibodies+to+CD28+and+the+TCR.&rft.au=Giese%2C+T%3BAllison%2C+J+P%3BDavidson%2C+W+F&rft.aulast=Giese&rft.aufirst=T&rft.date=1993-07-15&rft.volume=151&rft.issue=2&rft.spage=597&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 - 1993-08-25 N1 - Date created - 1993-08-25 N1 - Date revised - 2017-01-13 N1 - Gene symbol - gld; lpr N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Oxygen tension distributions are sufficient to explain the local response of human breast tumors treated with radiation alone. AN - 75845023; 8330993 AB - Several factors are known to influence the probability of tumor control after radiation. These include tumor oxygen tension distribution, glutathione content, intrinsic radiation sensitivity, rate of repopulation, tumor size, physician skill, etc. The relative impact of oxygen on human tumor response is unknown. The purpose of this analysis is to determine to what extent the observed shape of the radiation response curve for human tumors can be predicted by the tumor oxygenation status. The radiation dose response curve for patients treated with radiation alone for breast cancer was calculated based on pooled data. Tumor control rates as a function of radiation dose were fitted to a probit curve. Twenty-two women with breast cancer in Mainz (Germany) and at Stanford University had pO2 measurements made of their tumors. An average of 87 +/- 58 (range 21 to 300) measurements were made from each patient. Hypoxia was assumed to be a purely dose modifying factor with a maximum oxygen enhancement ratio of 2.5. Assuming patients are treated with daily radiation doses of 2 Gy, the breast cancer alpha/beta ratio is 10 Gy, tumors have a mean of 10(8) stem cells, and using the linear quadratic formula for modelling surviving fraction, it was possible to estimate tumor control probability. Tumor oxygenation was an extremely important modifier of the shape of the dose response curve and alone was sufficient to account for the slope of the observed dose response curve for human breast carcinoma. Tumor size distribution had a smaller effect on the shape and the slope of the dose response curve. Two models of radiation induced reoxygenation were tested, one that allowed full reoxygenation to the baseline state between the daily radiation fractions and another with no reoxygenation between fractions. The clinical data fell between these two models in accordance with the expected incomplete reoxygenation between treatments. The results support the conclusion that in human breast carcinoma, oxygen tension distribution is a critical modifier of radiation treatment response. JF - International journal of radiation oncology, biology, physics AU - Okunieff, P AU - Hoeckel, M AU - Dunphy, E P AU - Schlenger, K AU - Knoop, C AU - Vaupel, P AD - Radiation Oncology Branch, National Cancer Institute, Bethesda, MD 20892. Y1 - 1993/07/15/ PY - 1993 DA - 1993 Jul 15 SP - 631 EP - 636 VL - 26 IS - 4 SN - 0360-3016, 0360-3016 KW - Oxygen KW - S88TT14065 KW - Index Medicus KW - Humans KW - Dose-Response Relationship, Radiation KW - Partial Pressure KW - Female KW - Breast Neoplasms -- physiopathology KW - Breast Neoplasms -- radiotherapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75845023?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+radiation+oncology%2C+biology%2C+physics&rft.atitle=Oxygen+tension+distributions+are+sufficient+to+explain+the+local+response+of+human+breast+tumors+treated+with+radiation+alone.&rft.au=Okunieff%2C+P%3BHoeckel%2C+M%3BDunphy%2C+E+P%3BSchlenger%2C+K%3BKnoop%2C+C%3BVaupel%2C+P&rft.aulast=Okunieff&rft.aufirst=P&rft.date=1993-07-15&rft.volume=26&rft.issue=4&rft.spage=631&rft.isbn=&rft.btitle=&rft.title=International+journal+of+radiation+oncology%2C+biology%2C+physics&rft.issn=03603016&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-08-19 N1 - Date created - 1993-08-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The fifth transmembrane segment of the neuromedin B receptor is critical for high affinity neuromedin B binding. AN - 75834306; 8392057 AB - The two bombesin receptor subtypes, neuromedin B (NMB-R) and gastrin releasing peptide (GRP-R) receptors, bind their respective ligands with high affinity. To identify molecular components mediating high affinity NMB binding, four mutant receptors were constructed, in which different parts of the NMB-R were replaced with the corresponding regions of the GRP-R. When stably expressed in Balb 3T3 fibroblasts, all four NMB-R/GRP-R chimeras were functional and showed NMB-induced stimulation of inositol phosphate (IP) formation. Results of 125I-[D-Tyr0]NMB displacement assays using unlabeled NMB for competition indicated that high affinity NMB binding was determined by amino acid sequences in transmembrane domain V (TM-V) of the NMB-R. To identify which amino acid(s) in TM-V of NMB-R contributed to high affinity NMB binding, four additional NMB-R mutants were constructed where non-conserved amino acids in TM-V of NMB-R were replaced by the corresponding GRP-R amino acids. Three of the mutations, TyrPheLeu220-222-->PheTyrVal, Ile230-->Val, and His234-->Phe, did not affect high affinity NMB binding. The Ile216-->Ser substitution, however, abolished high affinity NMB binding and severely impaired the ability of the mutant receptor to stimulate NMB-dependent inositol phosphate formation. These results suggest that ILe216 in TM-V of NMB-R may be critical for high affinity NMB binding. JF - The Journal of biological chemistry AU - Fathi, Z AU - Benya, R V AU - Shapira, H AU - Jensen, R T AU - Battey, J F AD - Laboratory of Biological Chemistry, Development Therapeutics Program, Division of Cancer Treatment, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1993/07/15/ PY - 1993 DA - 1993 Jul 15 SP - 14622 EP - 14626 VL - 268 IS - 20 SN - 0021-9258, 0021-9258 KW - Receptors, Bombesin KW - 0 KW - Receptors, Neurotransmitter KW - Neurokinin B KW - 86933-75-7 KW - neuromedin B KW - 87096-84-2 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Animals KW - 3T3 Cells KW - Sequence Alignment KW - Humans KW - Molecular Sequence Data KW - Cell Membrane -- chemistry KW - Mice KW - Amino Acid Sequence KW - Cell Membrane -- metabolism KW - Mice, Inbred BALB C KW - Binding Sites KW - Receptors, Neurotransmitter -- chemistry KW - Neurokinin B -- genetics KW - Receptors, Neurotransmitter -- metabolism KW - Receptors, Neurotransmitter -- genetics KW - Neurokinin B -- metabolism KW - Neurokinin B -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75834306?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+fifth+transmembrane+segment+of+the+neuromedin+B+receptor+is+critical+for+high+affinity+neuromedin+B+binding.&rft.au=Fathi%2C+Z%3BBenya%2C+R+V%3BShapira%2C+H%3BJensen%2C+R+T%3BBattey%2C+J+F&rft.aulast=Fathi&rft.aufirst=Z&rft.date=1993-07-15&rft.volume=268&rft.issue=20&rft.spage=14622&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 - 1993-08-12 N1 - Date created - 1993-08-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A wide range of human cancers express interleukin 4 (IL4) receptors that can be targeted with chimeric toxin composed of IL4 and Pseudomonas exotoxin. AN - 75807973; 8314773 AB - A chimeric toxin has been constructed by fusion of a gene encoding human interleukin 4 (hIL4) to a gene encoding a mutant form of Pseudomonas exotoxin A (PE) which cannot bind to its receptors (PE4E). The chimeric gene was expressed in Escherichia coli where large amounts of the chimeric toxin, hIL4-PE4E, was produced. Purified hIL4-PE4E was very cytotoxic to cancer cell lines of both hematopoietic and solid tumor origin. In the HUT 102 T cell leukemia and Daudi B cell lymphoma cell lines, protein synthesis was inhibited by 50% (ID50) at a hIL4-PE4E concentration of 2 and 7 ng/ml (25 and 86 pM, respectively). hIL4-PE4E was also very cytotoxic to cell lines derived from carcinomas of the colon, breast, stomach, liver, adrenals, and prostate, as well as melanoma and epidermoid carcinoma, indicating that hIL4 receptors are widely expressed on human malignancies. We also found that human phytohemagglutinin-activated peripheral blood lymphocytes were extremely sensitive to hIL4-PE4E with an ID50 of 0.2 ng/ml (2.5 pM). The cytotoxic action of hIL4-PE4E was specific because it was blocked by an excess of hIL4 and not of human interleukin 2. In addition, hIL4-PE4ED553, an enzymatically inactive form of the chimeric toxin, was not cytotoxic. These results suggest that the hIL4 receptor may be a target for therapy in malignant and immunologic disorders using hIL4 chimeric toxin. JF - The Journal of biological chemistry AU - Debinski, W AU - Puri, R K AU - Kreitman, R J AU - Pastan, I AD - Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/07/05/ PY - 1993 DA - 1993 Jul 05 SP - 14065 EP - 14070 VL - 268 IS - 19 SN - 0021-9258, 0021-9258 KW - Bacterial Toxins KW - 0 KW - Exotoxins KW - Oligodeoxyribonucleotides KW - Protein Synthesis Inhibitors KW - Receptors, Interleukin-4 KW - Receptors, Mitogen KW - Recombinant Fusion Proteins KW - Virulence Factors KW - Interleukin-4 KW - 207137-56-2 KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - toxA protein, Pseudomonas aeruginosa KW - EC 2.4.2.31 KW - Index Medicus KW - Humans KW - Escherichia coli -- genetics KW - Cloning, Molecular KW - Base Sequence KW - Protein Synthesis Inhibitors -- toxicity KW - Tumor Cells, Cultured KW - Cell Survival -- drug effects KW - Binding, Competitive KW - Molecular Sequence Data KW - Pseudomonas aeruginosa KW - Female KW - Male KW - Receptors, Mitogen -- drug effects KW - Interleukin-4 -- toxicity KW - Receptors, Mitogen -- metabolism KW - Exotoxins -- toxicity KW - Recombinant Fusion Proteins -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75807973?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+wide+range+of+human+cancers+express+interleukin+4+%28IL4%29+receptors+that+can+be+targeted+with+chimeric+toxin+composed+of+IL4+and+Pseudomonas+exotoxin.&rft.au=Debinski%2C+W%3BPuri%2C+R+K%3BKreitman%2C+R+J%3BPastan%2C+I&rft.aulast=Debinski&rft.aufirst=W&rft.date=1993-07-05&rft.volume=268&rft.issue=19&rft.spage=14065&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 - 1993-07-27 N1 - Date created - 1993-07-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characterization of upstream activation elements essential for the expression of germ cell alkaline phosphatase in human choriocarcinoma cells. AN - 75807942; 8314767 AB - Expression of the germ cell alkaline phosphatase is a highly regulated process tied to malignant transformation of the human placenta. Human choriocarcinoma cells (malignant trophoblasts) express primarily the germ cell alkaline phosphatase gene and only low or nondetectable levels of the placental alkaline phosphatase normally found in the human placenta. Here, we show that nucleotides -156 to -1 region relative to the gene transcription start site (+1) contain cis-acting DNA elements that direct germ cell alkaline phosphatase expression in choriocarcinoma cells. Within the minimal activator region, at least three nuclear protein-binding sites, I (-63/-44), II (-87/-67), and III (-136/-103), were identified by DNase I footprinting analysis. All three sites are GC-rich. Sites I and II contain a sequence known to bind the transcription factor AP-2; the AP-2 site in site II overlaps a consensus motif for the transcription factor Sp1. Gel retardation experiments showed that similar nuclear protein factor(s) in JEG-3 choriocarcinoma cells bind to all three sites, with highest affinity to sites I and II. Site-directed mutagenesis that prevents binding of nuclear proteins to either site I or II, or both sites I and II, resulted in the loss of factor binding and reduced activator activity. The germ cell alkaline phosphatase promoter that contains an intact binding site III but altered sites I and II had little activator activity, suggesting that protein-protein interaction is important for germ cell alkaline phosphatase gene activation. JF - The Journal of biological chemistry AU - Wada, N AU - Chou, J Y AD - Human Genetics Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/07/05/ PY - 1993 DA - 1993 Jul 05 SP - 14003 EP - 14010 VL - 268 IS - 19 SN - 0021-9258, 0021-9258 KW - Nuclear Proteins KW - 0 KW - Oligodeoxyribonucleotides KW - Alkaline Phosphatase KW - EC 3.1.3.1 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Tumor Cells, Cultured KW - Cell Nucleus -- metabolism KW - Humans KW - Molecular Sequence Data KW - Choriocarcinoma KW - Uterine Neoplasms KW - Transcriptional Activation KW - Female KW - Pregnancy KW - Binding Sites KW - Gene Expression Regulation, Neoplastic KW - Promoter Regions, Genetic KW - Gene Expression Regulation, Enzymologic KW - Alkaline Phosphatase -- biosynthesis KW - Alkaline Phosphatase -- genetics KW - Ovum -- enzymology KW - Nuclear Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75807942?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Characterization+of+upstream+activation+elements+essential+for+the+expression+of+germ+cell+alkaline+phosphatase+in+human+choriocarcinoma+cells.&rft.au=Wada%2C+N%3BChou%2C+J+Y&rft.aulast=Wada&rft.aufirst=N&rft.date=1993-07-05&rft.volume=268&rft.issue=19&rft.spage=14003&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 - 1993-07-27 N1 - Date created - 1993-07-27 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - L12591; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nucleolar targeting signal of Rex protein of human T-cell leukemia virus type I specifically binds to nucleolar shuttle protein B-23. AN - 75806863; 8314759 AB - Rex protein, the post-transcriptional regulator of human T-cell leukemia virus type I, is located predominantly in the cell nucleolus and is associated with the cytoplasmic accumulation of unspliced and singly spliced viral mRNAs. The N-terminal 19-amino acid segment of Rex has been identified as the nucleolar targeting signal (NOS) and shown to be important for Rex function. To study the molecular interaction between the NOS region of Rex and its binding host protein(s) in the nucleolus, we chemically synthesized a functional NOS peptide (wild type) and mutant NOS peptides. Fluorescein isothiocyanate-conjugated functional NOS peptide was rapidly taken up by human cells and was transported to the nucleolus. Using affinity chromatography, we identified nucleolar protein B-23 as the major protein that binds to NOS. We also identified two highly acidic regions of B-23 (amino acids 120-132 and 161-188) as acceptor regions for NOS. Previous experiments have suggested that B-23 functions as a shuttle protein for the nucleolar transport of ribosomal components. Our results suggest that B-23 may also serve as a shuttle for the import of Rex from the cytoplasm to the nucleolus coupled to the export of viral mRNAs containing the Rex-responsive element. JF - The Journal of biological chemistry AU - Adachi, Y AU - Copeland, T D AU - Hatanaka, M AU - Oroszlan, S AD - Laboratory of Molecular Virology and Carcinogenesis, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, Maryland 21702-1201. Y1 - 1993/07/05/ PY - 1993 DA - 1993 Jul 05 SP - 13930 EP - 13934 VL - 268 IS - 19 SN - 0021-9258, 0021-9258 KW - Gene Products, rex KW - 0 KW - Immune Sera KW - Nuclear Proteins KW - Peptides KW - nucleophosmin KW - 117896-08-9 KW - Index Medicus KW - AIDS/HIV KW - Chromatography, Affinity KW - Tumor Cells, Cultured KW - HeLa Cells KW - Cell Nucleus -- metabolism KW - Humans KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Protein Binding KW - Peptides -- chemical synthesis KW - Gene Products, rex -- metabolism KW - Nuclear Proteins -- isolation & purification KW - Peptides -- metabolism KW - Human T-lymphotropic virus 1 -- metabolism KW - Nuclear Proteins -- metabolism KW - Cell Nucleolus -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75806863?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Nucleolar+targeting+signal+of+Rex+protein+of+human+T-cell+leukemia+virus+type+I+specifically+binds+to+nucleolar+shuttle+protein+B-23.&rft.au=Adachi%2C+Y%3BCopeland%2C+T+D%3BHatanaka%2C+M%3BOroszlan%2C+S&rft.aulast=Adachi&rft.aufirst=Y&rft.date=1993-07-05&rft.volume=268&rft.issue=19&rft.spage=13930&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 - 1993-07-27 N1 - Date created - 1993-07-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regional specificity of membrane instability in Alzheimer's disease brain. AN - 75934396; 8364743 AB - We report an inherent tendency towards the destabilisation of cellular membranes in Alzheimer's disease (AD) brain. This tendency is a natural consequence of abnormal membrane lipid composition, which has previously been documented in AD. Membrane destabilisation may contribute to AD pathogenesis in its own right and may also facilitate amyloid beta-protein deposition, which is potentially neurotoxic. The instability was found to co-localise selectively with areas of neurodegeneration in AD brain, thereby possibly accounting for the focal pathology observed in this disorder. JF - Brain research AU - Ginsberg, L AU - Atack, J R AU - Rapoport, S I AU - Gershfeld, N L AD - Laboratory of Physical Biology, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/07/02/ PY - 1993 DA - 1993 Jul 02 SP - 355 EP - 357 VL - 615 IS - 2 SN - 0006-8993, 0006-8993 KW - Membrane Lipids KW - 0 KW - Index Medicus KW - Nerve Degeneration KW - Aged, 80 and over KW - Humans KW - Membrane Lipids -- metabolism KW - Temperature KW - Aged KW - Cell Membrane -- physiology KW - Cell Membrane -- metabolism KW - Male KW - Female KW - Brain -- pathology KW - Brain -- metabolism KW - Alzheimer Disease -- metabolism KW - Alzheimer Disease -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75934396?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Regional+specificity+of+membrane+instability+in+Alzheimer%27s+disease+brain.&rft.au=Ginsberg%2C+L%3BAtack%2C+J+R%3BRapoport%2C+S+I%3BGershfeld%2C+N+L&rft.aulast=Ginsberg&rft.aufirst=L&rft.date=1993-07-02&rft.volume=615&rft.issue=2&rft.spage=355&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 - 1993-10-04 N1 - Date created - 1993-10-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interleukin-7: a cofactor for V(D)J rearrangement of the T cell receptor beta gene. AN - 75806660; 7686307 AB - The diversity of the T cell receptor repertoire is generated by rearrangement of gene elements in immature thymocytes. To identify a thymic signal that induces this rearrangement, a variety of agents were tested for their ability to induce rearrangement of the T cell receptor beta gene in suspensions of thymocytes from mouse embryos at day 14 of gestation. Of 16 agents tested, only interleukin-7 (IL-7) induced V(D)J gene rearrangement and sustained expression of the RAG-1 and RAG-2 genes, which are known to control rearrangement. These data implicate IL-7, a cytokine that is abundantly expressed in embryonic thymus, in driving gene rearrangement during early T cell development. JF - Science (New York, N.Y.) AU - Muegge, K AU - Vila, M P AU - Durum, S K AD - Biological Carcinogenesis and Development Program, Program Resources Inc./Dyncorp, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702. Y1 - 1993/07/02/ PY - 1993 DA - 1993 Jul 02 SP - 93 EP - 95 VL - 261 IS - 5117 SN - 0036-8075, 0036-8075 KW - RAG-1 KW - RAG-2 KW - DNA-Binding Proteins KW - 0 KW - Hematopoietic Cell Growth Factors KW - Interleukin-7 KW - Proteins KW - Rag2 protein, mouse KW - Stem Cell Factor KW - V(D)J recombination activating protein 2 KW - Ionomycin KW - 56092-81-0 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - Gene Expression KW - Hematopoietic Cell Growth Factors -- pharmacology KW - Ionomycin -- pharmacology KW - Mice KW - Proteins -- genetics KW - Thymus Gland -- immunology KW - Base Sequence KW - Tumor Cells, Cultured KW - Cell Survival -- drug effects KW - Cells, Cultured KW - Genes, RAG-1 KW - Molecular Sequence Data KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Thymus Gland -- embryology KW - Organ Culture Techniques KW - Cell Line KW - T-Lymphocytes -- cytology KW - Gene Rearrangement, beta-Chain T-Cell Antigen Receptor KW - Interleukin-7 -- pharmacology KW - T-Lymphocytes -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75806660?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Science+%28New+York%2C+N.Y.%29&rft.atitle=Interleukin-7%3A+a+cofactor+for+V%28D%29J+rearrangement+of+the+T+cell+receptor+beta+gene.&rft.au=Muegge%2C+K%3BVila%2C+M+P%3BDurum%2C+S+K&rft.aulast=Muegge&rft.aufirst=K&rft.date=1993-07-02&rft.volume=261&rft.issue=5117&rft.spage=93&rft.isbn=&rft.btitle=&rft.title=Science+%28New+York%2C+N.Y.%29&rft.issn=00368075&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-07-27 N1 - Date created - 1993-07-27 N1 - Date revised - 2017-01-13 N1 - Gene symbol - RAG-1; RAG-2 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Visual and auditory evoked potentials in early onset Parkinson's disease and their relationship to cerebrospinal fluid monoamine metabolites. AN - 85277265; pmid-7688076 AB - We studied visual (VEP) and brainstem auditory (BAEP) evoked potential changes in 23 patients with early onset Parkinson's disease (EOPD) to establish the nature of the changes as well as their relationship to dopaminergic (DA) and serotonergic (5-HT) disturbances, as determined by cerebrospinal fluid levels of homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA). We also compared these parameters between the young onset (YOPD) and juvenile Parkinsonism (JP), the two subgroups of EOPD, to look for any possible differences between the two. In EOPD, the mean P100 latency of the VEP was significantly prolonged compared to controls (p < 0.001). However, within EOPD the evoked potential parameters were not significantly different between YOPD and the JP subgroups. P100 latency was abnormal in six patients (YOPD: 5, JP: 1) (26%). Six patients (YOPD: 3, JP:3) (26%) had abnormal BAEP. A significant negative correlation (r: -0.89, p < 1%) was observed between the P100 latency and CSF HVA levels. No correlation was observed between the BAEP interpeak latencies and either CSF HVA or 5-HIAA levels. This study suggests that VEP and BAEP abnormalities do occur in EOPD (in both YOPD and JP), and that the prolongation of P100 latency is secondary to DA deficiency as in PD. The cause of BAEP abnormalities is probably independent of DA and 5-HT disturbances. The only difference between EOPD and classical PD was the higher incidence of BAEP abnormalities in EOPD. There was no correlation between the VEP or BAEP changes to either the age at onset or duration of EOPD. JF - Movement Disorders AU - Muthane, U B AU - Satishchandra, P AU - Subhash, M N AD - Department of Neurology, National Institute of Mental Health and Neurosciences, Bangalore, India. PY - 1993 SP - 344 EP - 348 VL - 8 IS - 3 SN - 0885-3185, 0885-3185 KW - Hydroxyindoleacetic Acid KW - Human KW - Aged KW - Photic Stimulation KW - Comparative Study KW - Parkinson Disease KW - Adult KW - Middle Age KW - Acoustic Stimulation KW - Adolescent KW - Homovanillic Acid KW - Male KW - Female KW - Evoked Potentials, Visual KW - Evoked Potentials, Auditory, Brain Stem UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85277265?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Movement+Disorders&rft.atitle=Visual+and+auditory+evoked+potentials+in+early+onset+Parkinson%27s+disease+and+their+relationship+to+cerebrospinal+fluid+monoamine+metabolites.&rft.au=Muthane%2C+U+B%3BSatishchandra%2C+P%3BSubhash%2C+M+N&rft.aulast=Muthane&rft.aufirst=U&rft.date=1993-07-01&rft.volume=8&rft.issue=3&rft.spage=344&rft.isbn=&rft.btitle=&rft.title=Movement+Disorders&rft.issn=08853185&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Inhibition of outer hair cell electromotility by sulfhydryl specific reagents. AN - 85260265; pmid-8233059 AB - Mammalian outer hair cells can change length at acoustic frequencies when they are electrically stimulated. It was postulated that these length changes depend on electromechanical transduction based on voltage dependent conformational changes in a membrane motor protein. In this report, we describe the effect of various sulfhydryl (SH)-specific reagents on the OHC electromotility. p-Chloromercuriphenylsulfonate (pCMPS), in addition to other mercurials that can react with well-protected SH-groups in proteins, inhibits this electromechanical transduction process. In contrast, N-ethylmaleimide and diamide, SH-reagents that only react with exposed SH-groups, showed no effect. These results suggest that one or more reactive SH-groups are present in a functionally important and protected region of the electromechanical transduction protein. Such reactivity can be utilized to identify and characterize this novel membrane motor. JF - Neuroscience Letters AU - Kalinec, F AU - Kachar, B AD - Laboratory of Cellular Biology, National Institute on Deafness and other Communication Disorders, NIDCD-NIH, Bethesda, MD 20892. PY - 1993 SP - 231 EP - 234 VL - 157 IS - 2 SN - 0304-3940, 0304-3940 KW - Cell Movement KW - Ethylmaleimide KW - 4-Chloromercuribenzenesulfonate KW - Sulfhydryl Reagents KW - Ethacrynic Acid KW - Diamide KW - Cysteine KW - Guinea Pigs KW - Hair Cells, Outer KW - Animal KW - Cystine KW - Mersalyl KW - Electric Stimulation KW - Membrane Proteins KW - Nerve Tissue Proteins KW - Protein Conformation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85260265?accountid=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=Neuroscience+Letters&rft.atitle=Inhibition+of+outer+hair+cell+electromotility+by+sulfhydryl+specific+reagents.&rft.au=Kalinec%2C+F%3BKachar%2C+B&rft.aulast=Kalinec&rft.aufirst=F&rft.date=1993-07-01&rft.volume=157&rft.issue=2&rft.spage=231&rft.isbn=&rft.btitle=&rft.title=Neuroscience+Letters&rft.issn=03043940&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Effect of stress on the membrane capacitance of the auditory outer hair cell. AN - 85253923; pmid-8369452 AB - The membrane capacitance of the outer hair cell, which has unique membrane potential-dependent motility, was monitored during application of membrane tension. It was found that the membrane capacitance of the cell decreased when stress was applied to the membrane. This result is the opposite of stretching the lipid bilayer in the plasma membrane. It thus indicates the importance of some other capacitance component that decreases on stretching. It has been known that charge movement across the membrane can appear to be a nonlinear capacitance. If membrane stress at the resting potential restricts the movement of the charge associated with force generation, the nonlinear capacitance will decrease. Furthermore, less capacitance reduction by membrane stretching is expected when the membrane is already extended by the (hyperpolarizing) membrane potential. Indeed, it was found that at hyperpolarized potentials, the reduction of the membrane capacitance due to stretching is less. The capacitance change can be described by a two state model of a force-producing unit in which the free energy difference between the contracted and stretched states has both electrical and mechanical components. From the measured change in capacitance, the estimated difference in the membrane area of the unit between the two states is about 2 nm2. JF - Biophysical Journal AU - Iwasa, Kuni H AD - National Institute on Deafness and Other Communication Disorders PY - 1993 SP - 492 EP - 498 VL - 65 IS - 1 SN - 0006-3495, 0006-3495 KW - Cell Movement KW - In Vitro KW - Hair Cells KW - Guinea Pigs KW - Stress, Mechanical KW - Cell Membrane KW - Electric Impedance KW - Animal KW - Membrane Potentials KW - Models, Neurological KW - Electrophysiology KW - Biomechanics KW - Biophysics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85253923?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biophysical+Journal&rft.atitle=Effect+of+stress+on+the+membrane+capacitance+of+the+auditory+outer+hair+cell.&rft.au=Iwasa%2C+Kuni+H&rft.aulast=Iwasa&rft.aufirst=Kuni&rft.date=1993-07-01&rft.volume=65&rft.issue=1&rft.spage=492&rft.isbn=&rft.btitle=&rft.title=Biophysical+Journal&rft.issn=00063495&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - How independent are the messages carried by adjacent inferior temporal cortical neurons? AN - 85235845; pmid-8331371 AB - There are at least three possibilities for encoding information in a small area of cortex. First, neurons could have identical characteristics, thus conveying redundant information; second, neurons could give different responses to the same stimuli, thus conveying independent information; or third, neurons could cooperate with each other to encode more information jointly than they do separately, that is, synergistically. We recorded from 28 pairs of neurons in inferior temporal cortex of behaving rhesus monkeys. Each pair was recorded from a single microelectrode. Both the magnitude and the temporal modulation of the responses were quantified. We separated the responses into signal (average response to each stimulus) and noise (deviation of each response from the average). Linear regression showed that an average of only 18.7% of the magnitude of the signal carried by one neuron could be predicted from the magnitude of the other, and only 22.0% could be predicted by including the temporal modulation. For the noise, the figures were 5.5% and 6.3%, respectively, even less than for the signal. Information theoretic analysis shows that the pairs of neurons we studied carried an average of 20% redundant information. However, even this relatively small amount of redundancy places a severe upper limit on the information that can be transmitted by a neuronal pool. A pool of neurons for which each pair is mutually redundant to extent y can only carry a maximum of 1/y, here five times, as much information as one neuron alone. Information theoretic analysis gave no evidence for the presence of information as a function of both neurons considered together, that is, synergistic codes. Cross-correlation showed that at least 61% of the neuronal pairs shared connections in some manner. Given these shared connections, if adjacent neurons had had identical characteristics, then the noise on the outputs of these neurons would have been highly correlated, and it would not be possible to separate the signal and noise. The severe impact of correlated noise and information redundancy leads us to propose that the processing carried out by these neurons evolved both to provide a rich description of many stimulus properties and simultaneously to minimize the redundancy in a local group of neurons. These two principles appear to be a major constraint on the organization of inferior temporal, and possibly all, cortex. JF - The Journal of Neuroscience AU - Gawne, T J AU - Richmond, B J AD - Laboratory of Neuropsychology, National Institute of Mental Health, Bethesda, MD 20892. PY - 1993 SP - 2758 EP - 2771 VL - 13 IS - 7 SN - 0270-6474, 0270-6474 KW - Regression Analysis KW - Animal KW - Reward KW - Neurons KW - Temporal Lobe KW - Conditioning, Operant KW - Membrane Potentials KW - Support, U.S. Gov't, Non-P.H.S. KW - Macaca mulatta KW - Models, Neurological KW - Visual Perception KW - Stereotaxic Techniques KW - Microelectrodes KW - Pattern Recognition, Visual UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85235845?accountid=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=How+independent+are+the+messages+carried+by+adjacent+inferior+temporal+cortical+neurons%3F&rft.au=Gawne%2C+T+J%3BRichmond%2C+B+J&rft.aulast=Gawne&rft.aufirst=T&rft.date=1993-07-01&rft.volume=13&rft.issue=7&rft.spage=2758&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 - Appearance of wave III of auditory brainstem response after removal of a cerebellar tumor. AN - 85221447; pmid-8250155 AB - Findings for auditory brainstem response (ABR) before and after surgical removal of a cerebellar tumor in a 10-year-old female are presented. ABR improved markedly, although the tumor showed no direct invasion to the brainstem. The cause of the ABR change and the origin of wave III are discussed. JF - Brain and Development AU - Kaga, M AU - Nihei, K AD - National Institute of Mental Health, National Center of Neurology and Psychiatry, Chiba, Japan. PY - 1993 SP - 305 EP - 307 VL - 15 IS - 4 SN - 0387-7604, 0387-7604 KW - Cerebellar Neoplasms KW - Human KW - Tomography, X-Ray Computed KW - Case Report KW - Child KW - Postoperative Period KW - Female KW - Evoked Potentials, Auditory, Brain Stem UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85221447?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain+and+Development&rft.atitle=Appearance+of+wave+III+of+auditory+brainstem+response+after+removal+of+a+cerebellar+tumor.&rft.au=Kaga%2C+M%3BNihei%2C+K&rft.aulast=Kaga&rft.aufirst=M&rft.date=1993-07-01&rft.volume=15&rft.issue=4&rft.spage=305&rft.isbn=&rft.btitle=&rft.title=Brain+and+Development&rft.issn=03877604&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Carcinogenicity of TCDD in laboratory animals: implications for risk assessment. AN - 76174673; 8296316 JF - Toxicology and industrial health AU - Lucier, G AU - Clark, G AU - Hiermath, C AU - Tritscher, A AU - Sewall, C AU - Huff, J AD - Laboratory of Biochemical Risk Analysis, N.I.E.H.S., Research Triangle Park, NC 27709. PY - 1993 SP - 631 EP - 668 VL - 9 IS - 4 SN - 0748-2337, 0748-2337 KW - Polychlorinated Dibenzodioxins KW - 0 KW - Index Medicus KW - Rats KW - Animals KW - Risk Factors KW - Humans KW - Carcinogenicity Tests KW - Biological Assay KW - Mice KW - Male KW - Female KW - Cricetinae KW - Polychlorinated Dibenzodioxins -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76174673?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+industrial+health&rft.atitle=Carcinogenicity+of+TCDD+in+laboratory+animals%3A+implications+for+risk+assessment.&rft.au=Lucier%2C+G%3BClark%2C+G%3BHiermath%2C+C%3BTritscher%2C+A%3BSewall%2C+C%3BHuff%2C+J&rft.aulast=Lucier&rft.aufirst=G&rft.date=1993-07-01&rft.volume=9&rft.issue=4&rft.spage=631&rft.isbn=&rft.btitle=&rft.title=Toxicology+and+industrial+health&rft.issn=07482337&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-03-01 N1 - Date created - 1994-03-01 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Toxicol Ind Health 1994 May-Jun;10(3):247 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Stigma or legitimation? A historical examination of the social potentials of addiction disease models. AN - 76105623; 8258758 AB - This article presents a historical discussion of disease models of opiate addiction in the United States in the twentieth century. First, several approaches to defining disease are discussed. Then, the shifts in formulations of opiate addiction as a disease in the twentieth century in the U.S. are analysed in light of the preceding theoretical discussion. The period before 1920 is described as heterodox, as researchers attempted to develop scientific models of opiate addiction, while various medically legitimate and quasi-legitimate treatment approaches flourished in an unregulated marketplace. After 1920, a stigmatizing disease model of opiate addiction was based on a psychiatric formulation that linked chronic addiction with psychoneurotic deficits in certain individuals. After 1940, this model dominated medical and scientific thinking about opiate addiction for several decades. After 1970, enormous changes in the demographics of drug use forced changes to the prevailing model of addiction. A new focus on behavioral aspects of addiction allowed the creation of a nonstigmatizing Parsonian disease model. JF - Journal of psychoactive drugs AU - Acker, C J AD - National Institutes of Health Historical Office, National Institutes of Health, Bethesda, Maryland 20892. PY - 1993 SP - 193 EP - 205 VL - 25 IS - 3 SN - 0279-1072, 0279-1072 KW - Index Medicus KW - History of medicine KW - United States KW - Models, Psychological KW - History, 20th Century KW - Legislation, Drug -- history KW - Humans KW - Opioid-Related Disorders -- psychology KW - Opioid-Related Disorders -- history UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76105623?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+psychoactive+drugs&rft.atitle=Stigma+or+legitimation%3F+A+historical+examination+of+the+social+potentials+of+addiction+disease+models.&rft.au=Acker%2C+C+J&rft.aulast=Acker&rft.aufirst=C&rft.date=1993-07-01&rft.volume=25&rft.issue=3&rft.spage=193&rft.isbn=&rft.btitle=&rft.title=Journal+of+psychoactive+drugs&rft.issn=02791072&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-01-19 N1 - Date created - 1994-01-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Is there any relationship between aluminum and Alzheimer's disease? AN - 76052819; 8224045 AB - The controversial role of aluminum in Alzheimer's disease (AD) is reviewed. While current data would suggest the lack of a causative role, alterations in the brain and other organ systems caused by AD might increase the penetration of aluminum as well as other metals into the brain and lead to their contribution to such pathological features as neurofibrillar tangles (NFTs). JF - Experimental gerontology AU - Eichhorn, G L AD - National Institutes of Health, National Institute on Aging, Laboratory of Cellular and Molecular Biology, Baltimore, Maryland 21224. PY - 1993 SP - 493 EP - 498 VL - 28 IS - 4-5 SN - 0531-5565, 0531-5565 KW - Aluminum KW - CPD4NFA903 KW - Silicon KW - Z4152N8IUI KW - Index Medicus KW - Humans KW - Brain -- drug effects KW - Aged KW - Silicon -- toxicity KW - Brain -- metabolism KW - Neurofibrillary Tangles -- drug effects KW - Aluminum -- adverse effects KW - Alzheimer Disease -- chemically induced KW - Alzheimer Disease -- metabolism KW - Aluminum -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76052819?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+gerontology&rft.atitle=Is+there+any+relationship+between+aluminum+and+Alzheimer%27s+disease%3F&rft.au=Eichhorn%2C+G+L&rft.aulast=Eichhorn&rft.aufirst=G&rft.date=1993-07-01&rft.volume=28&rft.issue=4-5&rft.spage=493&rft.isbn=&rft.btitle=&rft.title=Experimental+gerontology&rft.issn=05315565&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-12-22 N1 - Date created - 1993-12-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Reduced interleukin-2 (IL-2) production in common variable immunodeficiency is due to a primary abnormality of CD4+ T cell differentiation. AN - 76042624; 7901231 AB - Common variable immunodeficiency (CVI) is a condition characterized by hypogammaglobulinemia and impaired antibody responses, resulting in recurrent bacterial infections in untreated patients. In addition, affected individuals exhibit an increased incidence of autoimmunity, malignancy, and certain viral infections, suggesting the presence of an underlying generalized immune dysregulation. We have previously described a subgroup of CVI patients in whom T cells within PBMC populations exhibit a selective defect in lymphokine production. IL-2, IL-4, and IL-5 mRNA production was impaired in these patients, while proliferation, IL-2R expression, and c-myc mRNA production were normal. In the present series of experiments, using highly purified CD4+ T cells prepared by negative selection, we show that this lymphokine production defect is a primary abnormality of CVI CD4+ T cells: whereas CD4+ T cells from CVI patients proliferate normally in response to stimulation by PHA, staphylococcal enterotoxin B (SEB), or anti-CD2 antibodies, these stimuli induce significantly less IL-2 production than observed with CD4+ T cells from normal individuals. Furthermore, we show that this IL-2 production defect is not due to an accessory cell abnormality, since it was seen in the presence of normal (allogeneic) accessory cells, and patient accessory cells supported normal amounts of IL-2 production by PHA-stimulated CD4+ T cells obtained from normal individuals. Of interest, we also found that while IL-2 production by CD4+ T cells from CVI patients induced by stimulation with immobilized anti-CD3 antibody was reduced compared to CD4+ T cells from normal control individuals, this reduction was not statistically significant. Furthermore, stimulation of both CVI patient and normal CD4+ T cells with either ionomycin+phorbol myristate acetate or a combination of immobilized anti-CD3 antibody plus anti-CD28 antibody resulted in a 50-fold increase in IL-2 production compared to stimulation with immobilized anti-CD3 antibody alone, and, under these conditions, CVI and normal CD4+ T cells produced equivalent amounts of IL-2. Finally, minor defects in interferon-gamma production by CD4+ T cells from CVI donors were observed, but these were less severe than the IL-2 production defects and were not statistically significant. We conclude that a primary abnormality of lymphokine production exists in the CD4+ T cells of a subset of patients with CVI.(ABSTRACT TRUNCATED AT 400 WORDS) JF - Journal of clinical immunology AU - Eisenstein, E M AU - Jaffe, J S AU - Strober, W AD - Mucosal Immunity Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/07// PY - 1993 DA - July 1993 SP - 247 EP - 258 VL - 13 IS - 4 SN - 0271-9142, 0271-9142 KW - Antibodies, Monoclonal KW - 0 KW - Antigens, CD28 KW - Antigens, CD3 KW - Interleukin-2 KW - Lectins KW - Ionomycin KW - 56092-81-0 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Antigens, CD3 -- immunology KW - Humans KW - Ionomycin -- immunology KW - Enzyme-Linked Immunosorbent Assay KW - Lymphocyte Subsets KW - Antigens, CD28 -- immunology KW - Lymphocyte Activation KW - Common Variable Immunodeficiency -- immunology KW - Interleukin-2 -- biosynthesis KW - CD4-Positive T-Lymphocytes -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76042624?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+human+genetics&rft.atitle=Functional+studies+of+a+germ-line+polymorphism+at+codon+47+within+the+p53+gene.&rft.au=Felley-Bosco%2C+E%3BWeston%2C+A%3BCawley%2C+H+M%3BBennett%2C+W+P%3BHarris%2C+C+C&rft.aulast=Felley-Bosco&rft.aufirst=E&rft.date=1993-09-01&rft.volume=53&rft.issue=3&rft.spage=752&rft.isbn=&rft.btitle=&rft.title=American+journal+of+human+genetics&rft.issn=00029297&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-12-01 N1 - Date created - 1993-12-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Anticonvulsant activity of AMPA/kainate antagonists: comparison of GYKI 52466 and NBOX in maximal electroshock and chemoconvulsant seizure models. AN - 76027104; 7693450 AB - The anticonvulsant activities of a noncompetitive (GYKI 52466) and a competitive (NBQX) AMPA/kainate antagonist were compared in the maximal electroshock (MES) seizure test and various chemoconvulsant models. Both antagonists were protective in the MES and pentylenetetrazol tests. GYKI 52466 was also protective against seizures and lethality induced by 4-aminopyridine, kainate and AMPA, but not by NMDA, whereas NBQX was ineffective in these chemoconvulsant tests. Both GYKI 52466 and NBQX produced motor impairment at doses similar to those that were protective in the MES test. Under some circumstances, noncompetitive AMPA/kainate antagonists could offer advantages over competitive antagonists in seizure therapy. However, neurological toxicity is an obstacle to the potential clinical use of both classes of agents. JF - Epilepsy research AU - Yamaguchi, S AU - Donevan, S D AU - Rogawski, M A AD - Neuronal Excitability Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 29892. Y1 - 1993/07// PY - 1993 DA - July 1993 SP - 179 EP - 184 VL - 15 IS - 3 SN - 0920-1211, 0920-1211 KW - Anti-Anxiety Agents KW - 0 KW - Anticonvulsants KW - Quinoxalines KW - Receptors, AMPA KW - Receptors, Kainic Acid KW - GYKI 52466 KW - 102771-26-6 KW - 2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline KW - 118876-58-7 KW - Benzodiazepines KW - 12794-10-4 KW - alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid KW - 77521-29-0 KW - 4-Aminopyridine KW - BH3B64OKL9 KW - Kainic Acid KW - SIV03811UC KW - Pentylenetetrazole KW - WM5Z385K7T KW - Index Medicus KW - Animals KW - Receptors, AMPA -- antagonists & inhibitors KW - Hindlimb -- physiology KW - Dose-Response Relationship, Drug KW - 4-Aminopyridine -- pharmacology KW - Disease Models, Animal KW - Binding, Competitive -- drug effects KW - Mice KW - Receptors, Kainic Acid -- antagonists & inhibitors KW - Electroshock KW - Male KW - Seizures -- chemically induced KW - Anticonvulsants -- pharmacology KW - Kainic Acid -- antagonists & inhibitors KW - alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid -- antagonists & inhibitors KW - Seizures -- prevention & control KW - Benzodiazepines -- pharmacology KW - Quinoxalines -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76027104?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Epilepsy+research&rft.atitle=Anticonvulsant+activity+of+AMPA%2Fkainate+antagonists%3A+comparison+of+GYKI+52466+and+NBOX+in+maximal+electroshock+and+chemoconvulsant+seizure+models.&rft.au=Yamaguchi%2C+S%3BDonevan%2C+S+D%3BRogawski%2C+M+A&rft.aulast=Yamaguchi&rft.aufirst=S&rft.date=1993-07-01&rft.volume=15&rft.issue=3&rft.spage=179&rft.isbn=&rft.btitle=&rft.title=Epilepsy+research&rft.issn=09201211&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-12-06 N1 - Date created - 1993-12-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Generation of isogenic K54 capsule-deficient Escherichia coli strains through TnphoA-mediated gene disruption. AN - 76008484; 8412686 AB - Transposon mutagenesis, using IS50L::phoA(Tn-phoA), was performed in a K54/O4/H5 blood isolate of Escherichia coli (CP9), to generate a library of random mutants. Five hundred and twenty-six independent CP9 TnphoA mutants were isolated with active gene fusions to alkaline phosphatase. From this mutant library, eight capsule-deficient strains were detected and were found to have a single copy of TnphoA. Sixteen additional capsule deficient mutants with TnphoA inserts were subsequently obtained that did not possess active PhoA fusions. In conjunction with the initial eight capsule-deficient isolates we have defined genes on three different XbaI fragments as being involved in capsule production. Generalized transduction with the bacteriophage T4 established that these insertions were responsible for the loss of capsule and that they are linked. These capsule-deficient strains can be used to assess the pathogenic role of the K54 capsular polysaccharide. JF - Molecular microbiology AU - Russo, T A AU - Guenther, J E AU - Wenderoth, S AU - Frank, M M AD - Bacterial Pathogenesis Unit, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/07// PY - 1993 DA - July 1993 SP - 357 EP - 364 VL - 9 IS - 2 SN - 0950-382X, 0950-382X KW - Antigens, Bacterial KW - 0 KW - Antigens, Surface KW - DNA, Bacterial KW - K antigens KW - Recombinant Fusion Proteins KW - Alkaline Phosphatase KW - EC 3.1.3.1 KW - Index Medicus KW - Genes, Bacterial KW - Transduction, Genetic KW - Alkaline Phosphatase -- genetics KW - Plasmids KW - Escherichia coli Infections -- microbiology KW - DNA, Bacterial -- genetics KW - Chromosomes, Bacterial KW - T-Phages -- genetics KW - Carbohydrate Sequence KW - Molecular Sequence Data KW - Recombinant Fusion Proteins -- genetics KW - Sepsis -- microbiology KW - Mutagenesis, Insertional KW - Gene Library KW - Escherichia coli -- immunology KW - Escherichia coli -- isolation & purification KW - Escherichia coli -- genetics KW - Antigens, Surface -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76008484?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+microbiology&rft.atitle=Generation+of+isogenic+K54+capsule-deficient+Escherichia+coli+strains+through+TnphoA-mediated+gene+disruption.&rft.au=Russo%2C+T+A%3BGuenther%2C+J+E%3BWenderoth%2C+S%3BFrank%2C+M+M&rft.aulast=Russo&rft.aufirst=T&rft.date=1993-07-01&rft.volume=9&rft.issue=2&rft.spage=357&rft.isbn=&rft.btitle=&rft.title=Molecular+microbiology&rft.issn=0950382X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-11-15 N1 - Date created - 1993-11-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Behavioral and neuroendocrine effects of diethyl ether exposure in the mouse. AN - 76000476; 8413074 AB - Diethyl ether has diverse behavioral effects and is known for its ability to stimulate stress hormones, yet little is known of the concentrations in which these effects occur. To more fully characterize these effects, adult male NIH mice were exposed to a range of concentrations of ether (1000-30000 ppm) in an inhalation chamber and both behavioral and neuroendocrine responses were assessed. When responding was maintained under FI-60 s schedules of milk presentation, 30-min exposures to 1000 ppm ether resulted in minimal behavioral effects, 3000-10000 ppm increased rates of responding over two-fold and higher concentrations decreased responding almost completely. Five-min exposures to the same range of concentrations resulted in concentration-related effects which were smaller than those produced by 30-min exposures. Exposure to a similar range of concentrations in naive mice increased adrenocorticotrophic hormone (ACTH) and corticosterone levels in a time- and concentration-dependent manner. Five-min exposures to 10000 ppm ether increased levels of ACTH from a baseline of 25.95 pg/ml to 310.5 pg/ml but did not affect corticosterone. Thirty-min exposures to the full range of concentrations of ether, increased corticosterone from control levels of 70 ng/ml to 418 ng/ml at 30000 ppm, and increased ACTH from control levels of 19.13 pg/ml to 80.5 pg/ml at 30000 ppm, in a concentration-dependent manner. The increase in ACTH for 30-min exposures was not as large as that observed for 5-min exposures at 10000 ppm, nor was it as large as that seen for corticosterone.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Neurotoxicology and teratology AU - Glowa, J R AD - Clinical Neuroendocrinology Branch, NIMH, NIH, Bethesda, MD 20892. PY - 1993 SP - 215 EP - 221 VL - 15 IS - 4 SN - 0892-0362, 0892-0362 KW - Azides KW - 0 KW - Ether KW - 0F5N573A2Y KW - Benzodiazepines KW - 12794-10-4 KW - Adrenocorticotropic Hormone KW - 9002-60-2 KW - Ro 15-4513 KW - 91917-65-6 KW - Corticosterone KW - W980KJ009P KW - Index Medicus KW - Conditioning, Operant -- drug effects KW - Mice, Inbred Strains KW - Animals KW - Reinforcement Schedule KW - Dose-Response Relationship, Drug KW - Corticosterone -- blood KW - Food Deprivation -- physiology KW - Azides -- pharmacology KW - Mice KW - Benzodiazepines -- pharmacology KW - Male KW - Adrenocorticotropic Hormone -- blood KW - Ether -- toxicity KW - Behavior, Animal -- drug effects KW - Neurosecretory Systems -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76000476?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurotoxicology+and+teratology&rft.atitle=Behavioral+and+neuroendocrine+effects+of+diethyl+ether+exposure+in+the+mouse.&rft.au=Glowa%2C+J+R&rft.aulast=Glowa&rft.aufirst=J&rft.date=1993-07-01&rft.volume=15&rft.issue=4&rft.spage=215&rft.isbn=&rft.btitle=&rft.title=Neurotoxicology+and+teratology&rft.issn=08920362&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-11-12 N1 - Date created - 1993-11-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Fish, in and out of water; food, toxins, allergens. AN - 76000371; 8224836 JF - Allergy proceedings : the official journal of regional and state allergy societies AU - Cohen, S G AD - National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD. PY - 1993 SP - 287 EP - 316 VL - 14 IS - 4 SN - 1046-9354, 1046-9354 KW - Allergens KW - 0 KW - Toxins, Biological KW - Index Medicus KW - History of medicine KW - Animals KW - History, 20th Century KW - Fishes, Poisonous KW - History, 18th Century KW - History, 19th Century KW - Europe KW - Israel KW - History, 17th Century KW - History, Medieval KW - Egypt KW - Philately KW - History, 15th Century KW - History, Ancient KW - China KW - History, 16th Century KW - Fishes -- immunology KW - Fish Products -- history KW - Toxins, Biological -- history KW - Allergens -- history UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76000371?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Allergy+proceedings+%3A+the+official+journal+of+regional+and+state+allergy+societies&rft.atitle=Fish%2C+in+and+out+of+water%3B+food%2C+toxins%2C+allergens.&rft.au=Cohen%2C+S+G&rft.aulast=Cohen&rft.aufirst=S&rft.date=1993-07-01&rft.volume=14&rft.issue=4&rft.spage=287&rft.isbn=&rft.btitle=&rft.title=Allergy+proceedings+%3A+the+official+journal+of+regional+and+state+allergy+societies&rft.issn=10469354&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-12-07 N1 - Date created - 1993-12-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Analysis of Mdr50: a Drosophila P-glycoprotein/multidrug resistance gene homolog. AN - 75997730; 7691715 AB - Using degenerate oligonucleotides from conserved portions of the ATP-binding domain of the active transporter genes, a new member of this gene superfamily has been cloned from Drosophila DNA. The gene contains two sets of transmembrane domains and two ATP-binding domains and shows a high degree of similarity to the mammalian P-glycoprotein/multidrug resistance (MDR) genes. The gene is adjacent to Hsc5, a locus mapped to chromosome 2, band 50, and is named Mdr50. Mdr50 represents the third MDR homolog identified in Drosophila. Conservation in the position of intervening sequences between Mdr50 and the human MDR genes provides further evidence for their common origin. JF - Genomics AU - Gerrard, B AU - Stewart, C AU - Dean, M AD - Biological Carcinogenesis and Development Program, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland 21702-1201. Y1 - 1993/07// PY - 1993 DA - July 1993 SP - 83 EP - 88 VL - 17 IS - 1 SN - 0888-7543, 0888-7543 KW - CFTR KW - MDR KW - MDR1 KW - Mdr50 KW - CFTR protein, human KW - 0 KW - Carrier Proteins KW - Drosophila Proteins KW - Insect Hormones KW - Membrane Glycoproteins KW - Membrane Proteins KW - P-Glycoprotein KW - P-Glycoproteins KW - multidrug resistance protein 50, Drosophila KW - Cystic Fibrosis Transmembrane Conductance Regulator KW - 126880-72-6 KW - Index Medicus KW - Animals KW - Carrier Proteins -- genetics KW - Humans KW - Open Reading Frames KW - Amino Acid Sequence KW - Membrane Proteins -- genetics KW - Polymerase Chain Reaction KW - Base Sequence KW - Sequence Alignment KW - Molecular Sequence Data KW - Consensus Sequence KW - Sequence Homology, Amino Acid KW - Species Specificity KW - Membrane Glycoproteins -- genetics KW - Biological Transport, Active -- genetics KW - Drosophila melanogaster -- genetics KW - Multigene Family KW - Insect Hormones -- genetics KW - Genes, Insect UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75997730?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genomics&rft.atitle=Analysis+of+Mdr50%3A+a+Drosophila+P-glycoprotein%2Fmultidrug+resistance+gene+homolog.&rft.au=Gerrard%2C+B%3BStewart%2C+C%3BDean%2C+M&rft.aulast=Gerrard&rft.aufirst=B&rft.date=1993-07-01&rft.volume=17&rft.issue=1&rft.spage=83&rft.isbn=&rft.btitle=&rft.title=Genomics&rft.issn=08887543&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-10-22 N1 - Date created - 1993-10-22 N1 - Date revised - 2017-01-13 N1 - Gene symbol - CFTR; MDR; MDR1; Mdr50 N1 - Genetic sequence - L07065; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Environmental risks to the health of American children. AN - 75996989; 8415509 AB - The major environmental health issue for children today is the extremely high prevalence of unacceptable exposure to lead, especially in inner cities, but occurring throughout the country. It is now generally accepted that lead is toxic to the developing nervous system at levels that were thought only a decade ago to be without effect. Children are more susceptible to the effects of lead than the adults who live in the same environments. Although lead-based paint is no longer used and lead is now removed from gasoline, children will continue to live in housing with the potential for lead poisoning for perhaps another generation. Research into the prevention of exposure and prevention of the consequences of unavoidable exposure is now under way. JF - Preventive medicine AU - Olden, K AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709-2233. Y1 - 1993/07// PY - 1993 DA - July 1993 SP - 576 EP - 578 VL - 22 IS - 4 SN - 0091-7435, 0091-7435 KW - Dust KW - 0 KW - Lead KW - 2P299V784P KW - Index Medicus KW - Urban Population -- statistics & numerical data KW - Humans KW - Child KW - Cross-Sectional Studies KW - Mass Screening KW - Adult KW - Incidence KW - Adolescent KW - Dust -- adverse effects KW - Lead -- pharmacokinetics KW - United States -- epidemiology KW - Female KW - Male KW - Lead Poisoning -- prevention & control KW - Lead Poisoning -- epidemiology KW - Environmental Exposure -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75996989?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Preventive+medicine&rft.atitle=Environmental+risks+to+the+health+of+American+children.&rft.au=Olden%2C+K&rft.aulast=Olden&rft.aufirst=K&rft.date=1993-07-01&rft.volume=22&rft.issue=4&rft.spage=576&rft.isbn=&rft.btitle=&rft.title=Preventive+medicine&rft.issn=00917435&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-11-09 N1 - Date created - 1993-11-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The effects of boric acid (BA) on testicular cells in culture. AN - 75987578; 7691281 AB - High-dose boric acid (BA) exposure produces testicular lesions in adult rats characterized by inhibited spermiation that may progress to nonrecoverable atrophy. The mechanism for the testicular toxicity of BA is unknown. To examine possible direct effects, the present study evaluated selected aspects of various testicular cell culture systems after in vitro BA exposure. Specifically, the hallmarks of the BA testicular toxicity were addressed: the mild hormone effect, the initial inhibition of spermiation, and atrophy. No effect of BA on the steroidogenic function of isolated Leydig cells was observed, supporting the contention of a CNS-mediated rather than a direct hormone effect. Since increased testicular cyclic AMP (cAMP) produces inhibited spermiation, and a role for the serine proteases plasminogen activators (PAs) in spermiation has been proposed, we evaluated both Sertoli cell cAMP accumulation in Sertoli-germ cell cocultures and the stage-specific secretion of PA activity in cultured seminiferous tubules after in vitro BA exposure, respectively. The results showed that the inhibited spermiation is not due to BA effects on either process. To address the atrophy, we evaluated BA effects in Sertoli-germ cell cocultures on 1) morphology/germ cell attachment, which might identify a target cell; 2) Sertoli cell energy metabolism, because lactate, secreted by Sertoli cells, is a preferred energy source for germ cells; and 3) DNA/RNA synthesis, because germ cells synthesize DNA/RNA and BA impairs nucleic acid synthesis in liver and may do so in testis. Despite the absence of overt morphologic changes and germ cell loss, the most sensitive in vitro endpoint was DNA synthesis of mitotic/meiotic germ cells, with energy metabolism in Sertoli or germ cells affected to a lesser extent. A re-evaluation of testis sections from rats exposed to BA revealed a decrease in the early germ cell/Sertoli cell ratio prior to atrophy. Thus, although the mechanism for the inhibited spermiation is still undefined and is the subject of future work, these combined studies revealed some changes offering a plausible explanation for the atrophy aspect of the BA testicular lesion. JF - Reproductive toxicology (Elmsford, N.Y.) AU - Ku, W W AU - Shih, L M AU - Chapin, R E AD - Developmental and Reproductive Toxicology Group, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. PY - 1993 SP - 321 EP - 331 VL - 7 IS - 4 SN - 0890-6238, 0890-6238 KW - Boric Acids KW - 0 KW - Testosterone KW - 3XMK78S47O KW - RNA KW - 63231-63-0 KW - Follicle Stimulating Hormone KW - 9002-68-0 KW - DNA KW - 9007-49-2 KW - Cyclic AMP KW - E0399OZS9N KW - Plasminogen Activators KW - EC 3.4.21.- KW - Bromodeoxyuridine KW - G34N38R2N1 KW - boric acid KW - R57ZHV85D4 KW - Index Medicus KW - Animals KW - Cyclic AMP -- biosynthesis KW - Leydig Cells -- pathology KW - Dose-Response Relationship, Drug KW - Plasminogen Activators -- metabolism KW - DNA -- biosynthesis KW - Leydig Cells -- drug effects KW - RNA -- biosynthesis KW - Rats KW - Rats, Inbred F344 KW - Leydig Cells -- metabolism KW - Cells, Cultured KW - Testosterone -- biosynthesis KW - Follicle Stimulating Hormone -- pharmacology KW - Male KW - Bromodeoxyuridine -- metabolism KW - Testis -- drug effects KW - Boric Acids -- toxicity KW - Testis -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75987578?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Reproductive+toxicology+%28Elmsford%2C+N.Y.%29&rft.atitle=The+effects+of+boric+acid+%28BA%29+on+testicular+cells+in+culture.&rft.au=Ku%2C+W+W%3BShih%2C+L+M%3BChapin%2C+R+E&rft.aulast=Ku&rft.aufirst=W&rft.date=1993-07-01&rft.volume=7&rft.issue=4&rft.spage=321&rft.isbn=&rft.btitle=&rft.title=Reproductive+toxicology+%28Elmsford%2C+N.Y.%29&rft.issn=08906238&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-11-23 N1 - Date created - 1993-11-23 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Reprod Toxicol. 1993 Jul-Aug;7(4):295-6 [8400619] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Activation of hepatic stem cell compartment in the rat: role of transforming growth factor alpha, hepatocyte growth factor, and acidic fibroblast growth factor in early proliferation. AN - 75986214; 7691152 AB - We have demonstrated previously a pronounced increase in the expression of hepatocyte growth factor (HGF) (Z. Hu, R. P. Evarts, K. Fujio, E. R. Marsden, and S. S. Thorgeirsson, Am. J. Pathol., 142: 1823-1830, 1993), transforming growth factor alpha (TGF-alpha) (R. P. Evarts, H. Nakatsukasa, E. R. Marsden, Z. Hu, and S. S. Thorgeirsson, Mol. Carcinog., 5: 25-31, 1992), and acidic fibroblast growth factor (aFGF) (E. R. Marsden, Z. Hu, K. Fujio, H. Nakatsukasa, S. S. Thorgeirsson, and R. P. Evarts, Lab. Invest., 67: 427-433, 1992) that coincided with the proliferation and differentiation of putative hepatic stem cells and perisinusoidal stellate (Ito) cells. Here, we examine the earliest stages of stem cell activation in rat liver using an experimental model involving treatment with acetylaminofluorene and partial hepatectomy (R. P. Evarts, P. Nagy, E. Marsden, and S. S. Thorgeirsson, Carcinogenesis (Lond.), 8: 1737-1740, 1987). Histochemical identification of stem cell progeny and Ito cells was accomplished by OV6 and desmin antibodies, respectively. Expression of the 2.1-kilobase alpha-fetoprotein transcripts and the concomitant DNA synthesis ([3H]thymidine label) were used as indicators for the activation of the stem cell compartment. Expression of HGF, TGF-alpha, and aFGF was analyzed at the time of partial hepatectomy and 4, 12, 24, 48, 72, and 92 h after the operation. [3H]-Thymidine-labeled OV6- and desmin-positive cells were present in the portal space and in the Glisson capsule 4 h after partial hepatectomy.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research AU - Evarts, R P AU - Hu, Z AU - Fujio, K AU - Marsden, E R AU - Thorgeirsson, S S AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/07// PY - 1993 DA - July 1993 SP - 555 EP - 561 VL - 4 IS - 7 SN - 1044-9523, 1044-9523 KW - RNA, Messenger KW - 0 KW - Transforming Growth Factor alpha KW - alpha-Fetoproteins KW - Fibroblast Growth Factor 1 KW - 104781-85-3 KW - Hepatocyte Growth Factor KW - 67256-21-7 KW - Thymidine KW - VC2W18DGKR KW - Index Medicus KW - Thymidine -- metabolism KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Blotting, Northern KW - alpha-Fetoproteins -- biosynthesis KW - Cell Division -- physiology KW - Time Factors KW - Immunohistochemistry KW - RNA, Messenger -- biosynthesis KW - Male KW - Hepatocyte Growth Factor -- physiology KW - Hepatocyte Growth Factor -- biosynthesis KW - Liver -- cytology KW - Transforming Growth Factor alpha -- physiology KW - Transforming Growth Factor alpha -- biosynthesis KW - Liver -- metabolism KW - Fibroblast Growth Factor 1 -- physiology KW - Cell Compartmentation -- physiology KW - Stem Cells -- physiology KW - Fibroblast Growth Factor 1 -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75986214?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cell+growth+%26+differentiation+%3A+the+molecular+biology+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=Activation+of+hepatic+stem+cell+compartment+in+the+rat%3A+role+of+transforming+growth+factor+alpha%2C+hepatocyte+growth+factor%2C+and+acidic+fibroblast+growth+factor+in+early+proliferation.&rft.au=Evarts%2C+R+P%3BHu%2C+Z%3BFujio%2C+K%3BMarsden%2C+E+R%3BThorgeirsson%2C+S+S&rft.aulast=Evarts&rft.aufirst=R&rft.date=1993-07-01&rft.volume=4&rft.issue=7&rft.spage=555&rft.isbn=&rft.btitle=&rft.title=Cell+growth+%26+differentiation+%3A+the+molecular+biology+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10449523&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-11-05 N1 - Date created - 1993-11-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Testicular toxicity of boric acid (BA): relationship of dose to lesion development and recovery in the F344 rat. AN - 75975840; 8400621 AB - High-dose boric acid (BA) produces testicular lesions in adult rats, characterized by inhibited spermiation followed by atrophy. The present study addressed whether inhibited spermiation can be separated from atrophy based on dose, compared testis boron (B) dosimetry to lesion development, determined how inhibited spermiation was reflected by common reproductive endpoints, and examined reversibility of the testicular lesions. Rats were fed 3000, 4500, 6000, or 9000 ppm BA for up to 9 weeks and examined. Recovery was assessed for up to 32 weeks post treatment. Inhibited spermiation could be separated from atrophy based on dose (inhibited spermiation: 3000/4500 ppm; atrophy: 6000/9000 ppm), with each lesion aspect expressed at different threshold testis B concentrations (inhibited spermiation: 5.6 micrograms B/g and atrophy: 11.9 micrograms B/g) with no B accumulation during the 9-week exposure. These data suggest that separate mechanisms may be operating for these lesion aspects based on testis B concentration and that B dose rate was important for testicular toxicity. Inhibited spermiation was most reliably reflected by informed testicular histology, with the more severe cases decreasing epididymal sperm count to levels that could affect fertility. After treatment, serum and testis B levels in all dose groups rapidly fell to background levels at the earliest time points evaluated (7 days and 8 weeks posttreatment, respectively). The severely inhibited spermiation at 4500 ppm was resolved by 16 weeks posttreatment, but areas of focal atrophy were detected that did not recover posttreatment. Also, no signs of recovery from atrophy were observed (6000 and 9000 ppm). Atrophic tubules contained a normal complement of spermatogonia (2.6 to 2.9 germ cells/100 Sertoli cells), with occasional dividing and degenerating germ cells. Elevations in serum FSH and LH levels suggested an intact hormonal response to the atrophy. In summary, 1) the different aspects of the BA-induced testicular lesion can be separated using different doses, 2) inhibited spermiation does not necessarily proceed to atrophy, and 3) there is no recovery from the atrophy despite the absence of testis B after treatment. The ability to separate inhibited spermiation from atrophy based on dose and testis B dosimetry will be useful in evaluating possible mechanisms. Furthermore, the presence of dividing spermatogonia during long-term BA-induced atrophy suggests that this model should be useful for identifying critical components involved in the reinitiation of spermatogenesis. JF - Reproductive toxicology (Elmsford, N.Y.) AU - Ku, W W AU - Chapin, R E AU - Wine, R N AU - Gladen, B C AD - Developmental and Reproductive Toxicology Group, National Institute of Environmental Health Sciences; Research Triangle Park, North Carolina 27709. PY - 1993 SP - 305 EP - 319 VL - 7 IS - 4 SN - 0890-6238, 0890-6238 KW - Boric Acids KW - 0 KW - Luteinizing Hormone KW - 9002-67-9 KW - Follicle Stimulating Hormone KW - 9002-68-0 KW - boric acid KW - R57ZHV85D4 KW - Index Medicus KW - Rats KW - Eating -- drug effects KW - Animals KW - Rats, Inbred F344 KW - Dose-Response Relationship, Drug KW - Luteinizing Hormone -- blood KW - Atrophy KW - Male KW - Follicle Stimulating Hormone -- blood KW - Testis -- drug effects KW - Boric Acids -- toxicity KW - Boric Acids -- metabolism KW - Testis -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75975840?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Reproductive+toxicology+%28Elmsford%2C+N.Y.%29&rft.atitle=Testicular+toxicity+of+boric+acid+%28BA%29%3A+relationship+of+dose+to+lesion+development+and+recovery+in+the+F344+rat.&rft.au=Ku%2C+W+W%3BChapin%2C+R+E%3BWine%2C+R+N%3BGladen%2C+B+C&rft.aulast=Ku&rft.aufirst=W&rft.date=1993-07-01&rft.volume=7&rft.issue=4&rft.spage=305&rft.isbn=&rft.btitle=&rft.title=Reproductive+toxicology+%28Elmsford%2C+N.Y.%29&rft.issn=08906238&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-11-23 N1 - Date created - 1993-11-23 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment On: Reprod Toxicol. 1993 Jul-Aug;7(4):295-6 [8400619] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characterization of 2',3'-dideoxycytidine diphosphocholine and 2',3'-dideoxycytidine diphosphoethanolamine. Prominent phosphodiester metabolites of the anti-HIV nucleoside 2',3'-dideoxycytidine. AN - 75963792; 7690699 AB - 2',3'-Dideoxycytidine (ddCyd) is among the most potent of the anti-human immunodeficiency virus (HIV) agents of the dideoxynucleoside class. Its pharmacologically active metabolite 2',3'-dideoxycytidine 5'-triphosphate (ddCTP) is an effective inhibitor of HIV reverse transcriptase and thus of HIV replication. ddCyd differs, however, from other dideoxynucleoside agents such as 3'-azido-3'-deoxythymidine and 2',3'-dideoxyinosine in its capacity to generate phosphodiester metabolites (i.e. ddCDP choline and ddCDP ethanolamine). We have synthesized and characterized these two diesters, and established their identity with the metabolites formed in ddCyd-treated Molt-4 cells. Toward this end, the biologically generated metabolites have been isolated on a preparative scale and compared with the synthetic compounds mass spectroscopically, chromatographically, and enzymatically (i.e. their relative susceptibility to the catabolic enzymes alkaline phosphatase and venom phosphodiesterase). The concentration reached by each of these two phosphodiesters within cells can, under certain conditions, equal or exceed that of ddCTP, and their half-times of disappearance are long, indicating that they may serve as depot forms of ddCyd. The possible role of these phosphodiesters in contributing to the unusual toxicity of ddCyd is discussed. JF - Drug metabolism and disposition: the biological fate of chemicals AU - Hao, Z AU - Stowe, E E AU - Ahluwalia, G AU - Baker, D C AU - Hebbler, A K AU - Chisena, C AU - Musser, S M AU - Kelley, J A AU - Perno, C F AU - Johns, D G AD - Laboratory of Medicinal Chemistry, National Cancer Institute/National Institutes of Health, Bethesda, MD 20892. PY - 1993 SP - 738 EP - 744 VL - 21 IS - 4 SN - 0090-9556, 0090-9556 KW - Deoxycytosine Nucleotides KW - 0 KW - Dideoxynucleotides KW - Ethanolamines KW - Reverse Transcriptase Inhibitors KW - 2',3'-dideoxycytidine diphosphoethanolamine KW - 130036-23-6 KW - 2',3'-dideoxycytidine diphosphocholine KW - 130036-24-7 KW - Cytidine Diphosphate Choline KW - 536BQ2JVC7 KW - Ethanolamine KW - 5KV86114PT KW - Cytidine Diphosphate KW - 63-38-7 KW - Zalcitabine KW - 6L3XT8CB3I KW - HIV Reverse Transcriptase KW - EC 2.7.7.49 KW - Choline KW - N91BDP6H0X KW - Index Medicus KW - AIDS/HIV KW - Molecular Structure KW - Chromatography, Paper KW - Cells, Cultured KW - Cytidine Diphosphate -- analogs & derivatives KW - Choline -- metabolism KW - Spectrometry, Mass, Fast Atom Bombardment KW - Zalcitabine -- metabolism KW - Deoxycytosine Nucleotides -- metabolism KW - HIV -- drug effects KW - Ethanolamines -- metabolism KW - Cytidine Diphosphate Choline -- analogs & derivatives KW - Cytidine Diphosphate Choline -- chemistry KW - Cytidine Diphosphate Choline -- metabolism KW - Ethanolamines -- chemistry KW - Deoxycytosine Nucleotides -- chemistry KW - Zalcitabine -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75963792?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Drug+metabolism+and+disposition%3A+the+biological+fate+of+chemicals&rft.atitle=Characterization+of+2%27%2C3%27-dideoxycytidine+diphosphocholine+and+2%27%2C3%27-dideoxycytidine+diphosphoethanolamine.+Prominent+phosphodiester+metabolites+of+the+anti-HIV+nucleoside+2%27%2C3%27-dideoxycytidine.&rft.au=Hao%2C+Z%3BStowe%2C+E+E%3BAhluwalia%2C+G%3BBaker%2C+D+C%3BHebbler%2C+A+K%3BChisena%2C+C%3BMusser%2C+S+M%3BKelley%2C+J+A%3BPerno%2C+C+F%3BJohns%2C+D+G&rft.aulast=Hao&rft.aufirst=Z&rft.date=1993-07-01&rft.volume=21&rft.issue=4&rft.spage=738&rft.isbn=&rft.btitle=&rft.title=Drug+metabolism+and+disposition%3A+the+biological+fate+of+chemicals&rft.issn=00909556&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-10-15 N1 - Date created - 1993-10-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Multistep carcinogenesis. AN - 75947646; 8396563 JF - Japanese journal of cancer research : Gann AU - Harris, C C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, MD 20892. Y1 - 1993/07// PY - 1993 DA - July 1993 VL - 84 IS - 7 SN - 0910-5050, 0910-5050 KW - Index Medicus KW - Precancerous Conditions -- genetics KW - Liver Neoplasms -- pathology KW - Carcinoma, Hepatocellular -- etiology KW - Carcinoma, Hepatocellular -- genetics KW - Chromosome Aberrations KW - Carcinoma, Hepatocellular -- pathology KW - Liver Neoplasms -- etiology KW - Precancerous Conditions -- pathology KW - Liver Neoplasms -- genetics KW - Neoplasms -- pathology KW - Neoplasms -- genetics KW - Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75947646?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Japanese+journal+of+cancer+research+%3A+Gann&rft.atitle=Multistep+carcinogenesis.&rft.au=Harris%2C+C+C&rft.aulast=Harris&rft.aufirst=C&rft.date=1993-07-01&rft.volume=84&rft.issue=7&rft.spage=inside+front+cover&rft.isbn=&rft.btitle=&rft.title=Japanese+journal+of+cancer+research+%3A+Gann&rft.issn=09105050&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-10-08 N1 - Date created - 1993-10-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - ADP-ribosylation factors, 20,000 M(r) guanine nucleotide-binding protein activators of cholera toxin and components of intracellular vesicular transport systems. AN - 75945039; 8373721 JF - Cellular signalling AU - Moss, J AU - Vaughan, M AD - Laboratory of Cellular Metabolism, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/07// PY - 1993 DA - July 1993 SP - 367 EP - 379 VL - 5 IS - 4 SN - 0898-6568, 0898-6568 KW - Cholera Toxin KW - 9012-63-9 KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - ADP-Ribosylation Factors KW - EC 3.6.5.2 KW - Adenylyl Cyclases KW - EC 4.6.1.1 KW - Index Medicus KW - Animals KW - Conserved Sequence KW - Humans KW - Molecular Sequence Data KW - Biological Transport KW - Adenylyl Cyclases -- metabolism KW - Amino Acid Sequence KW - Sequence Homology, Amino Acid KW - Signal Transduction KW - Molecular Weight KW - Organelles -- metabolism KW - GTP-Binding Proteins -- metabolism KW - GTP-Binding Proteins -- genetics KW - Cholera Toxin -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75945039?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cellular+signalling&rft.atitle=ADP-ribosylation+factors%2C+20%2C000+M%28r%29+guanine+nucleotide-binding+protein+activators+of+cholera+toxin+and+components+of+intracellular+vesicular+transport+systems.&rft.au=Moss%2C+J%3BVaughan%2C+M&rft.aulast=Moss&rft.aufirst=J&rft.date=1993-07-01&rft.volume=5&rft.issue=4&rft.spage=367&rft.isbn=&rft.btitle=&rft.title=Cellular+signalling&rft.issn=08986568&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-10-19 N1 - Date created - 1993-10-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Assessment of the haemolytic activity of 2-butoxyethanol and its major metabolite, butoxyacetic acid, in various mammals including humans. AN - 75944472; 8104009 AB - 2-Butoxyethanol (BE) is a glycol ether produced in volumes exceeding 335 million pounds/year for industrial and domestic uses. BE causes acute haemolytic anaemia in rats and some other mammals. While BE is inactive in vitro, 2-butoxyacetic acid (BAA) is a potent haemolytic agent in vivo and in vitro. This finding suggests that metabolic activation of BE to BAA is required for haemolysis of erythrocytes to occur in vivo. Haemolysis of red blood cells (RBC) by BAA is preceded by swelling (increased mean cell volume [MCV] and haematocrit [HCT]). In an attempt to assess the potential risk to humans exposed to BE, studies were designed to determine the in vitro effect of BAA on RBCs from 10 mammalian species including humans. Blood samples from each mammalian species (n = 3-5) were incubated with BAA at a final concentration of 0 (vehicle), 1 or 2 mM and kept at 37 degrees C in a gently shaking water bath. Complete blood counts (CBCs) were measured at 0, 1, 2 and 4 h, BAA caused a time- and concentration-dependent increase in MCV and HCT of blood from rats, mice and hamsters (rodents), rabbits (lagomorphs), and baboons (primates). In contrast, blood from pigs (artiodactyls), dogs and cats (carnivores), guinea pigs (rodents/marsupials), and humans (primates), was minimally affected by BAA. These results were confirmed in guinea pigs and rats in vivo. Gavage administration of BE (250 mg kg-1) to rats resulted in increased MCV and HCT followed by haemolysis (decreased RBCs). Identical treatment with BE resulted in no significant change in these parameters in guinea pigs.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Human & experimental toxicology AU - Ghanayem, B I AU - Sullivan, C A AD - National Institute of Environmental Health Sciences, National Institutes of Health Research Triangle Park, NC 27709. Y1 - 1993/07// PY - 1993 DA - July 1993 SP - 305 EP - 311 VL - 12 IS - 4 SN - 0960-3271, 0960-3271 KW - Ethylene Glycols KW - 0 KW - Glycolates KW - n-butoxyacetic acid KW - 2516-93-0 KW - n-butoxyethanol KW - I0P9XEZ9WV KW - Index Medicus KW - Swine KW - Papio KW - Animals KW - Erythrocyte Count -- drug effects KW - Humans KW - In Vitro Techniques KW - Cats KW - Dogs KW - Hematocrit KW - Rabbits KW - Rodentia KW - Male KW - Hemolysis -- drug effects KW - Anemia, Hemolytic -- chemically induced KW - Ethylene Glycols -- toxicity KW - Ethylene Glycols -- metabolism KW - Glycolates -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75944472?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Assessment+of+the+haemolytic+activity+of+2-butoxyethanol+and+its+major+metabolite%2C+butoxyacetic+acid%2C+in+various+mammals+including+humans.&rft.au=Ghanayem%2C+B+I%3BSullivan%2C+C+A&rft.aulast=Ghanayem&rft.aufirst=B&rft.date=1993-07-01&rft.volume=12&rft.issue=4&rft.spage=305&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 - 1993-10-20 N1 - Date created - 1993-10-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Are mouse strains differentially susceptible to the reproductive toxicity of ethylene glycol monomethyl ether? A study of three strains. AN - 75931428; 8365589 AB - Most rodent reproductive toxicology studies utilize strains of high fecundity. These studies were conducted to examine the possibility that mouse strains of differing fecundity would respond differently to a known reproductive toxicant. Thirty pairs each of Swiss CD-1, C57B1, and C3H mice were cohabited for 14 weeks while consuming 0, 0.03, 0.10, or 0.30% EGME in the drinking water. Litter data were collected during cohabitation. Body and organ weights, and various sperm data, were collected at necropsy, and second-generation fertility was evaluated. The data show that the most fecund strain (Swiss) was affected the least by exposure to EGME, while the least fecund strain (C3H) suffered the greatest declines in fertility. These differences might alter interspecies extrapolation factors, or the permissible exposure levels for humans. JF - Fundamental and applied toxicology : official journal of the Society of Toxicology AU - Chapin, R E AU - Morrissey, R E AU - Gulati, D K AU - Hope, E AU - Barnes, L H AU - Russell, S A AU - Kennedy, S R AD - National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1993/07// PY - 1993 DA - July 1993 SP - 8 EP - 14 VL - 21 IS - 1 SN - 0272-0590, 0272-0590 KW - Ethylene Glycols KW - 0 KW - methyl cellosolve KW - EK1L6XWI56 KW - Index Medicus KW - Mice, Inbred Strains KW - Litter Size -- drug effects KW - Animals KW - Body Weight -- drug effects KW - Mice KW - Sperm Motility -- drug effects KW - Species Specificity KW - Male KW - Female KW - Organ Size -- drug effects KW - Ethylene Glycols -- toxicity KW - Fertility -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75931428?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.atitle=Are+mouse+strains+differentially+susceptible+to+the+reproductive+toxicity+of+ethylene+glycol+monomethyl+ether%3F+A+study+of+three+strains.&rft.au=Chapin%2C+R+E%3BMorrissey%2C+R+E%3BGulati%2C+D+K%3BHope%2C+E%3BBarnes%2C+L+H%3BRussell%2C+S+A%3BKennedy%2C+S+R&rft.aulast=Chapin&rft.aufirst=R&rft.date=1993-07-01&rft.volume=21&rft.issue=1&rft.spage=8&rft.isbn=&rft.btitle=&rft.title=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.issn=02720590&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-10-05 N1 - Date created - 1993-10-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Risk assessment in immunotoxicology. II. Relationships between immune and host resistance tests. AN - 75931388; 8365588 AB - We have reported on the design and content of a screening battery using a "tier" approach for detecting potential immunotoxic compounds in mice (Luster et al., Fundam. Appl. Toxicol., 10, 2-19, 1988). The data base generated from these studies, which consists of over 50 selected compounds, has been collected and analyzed in an attempt to improve future testing strategies and provide information to aid in developing future quantitative risk assessment for immunotoxicity. In a recent study it was shown that as few as two or three immune parameters were needed to predict immunotoxicants in mice (Luster et al., Fundam. Appl. Toxicol., 18, 200-210, 1992). In particular, enumeration of lymphocyte populations and quantitation of the T-dependent antibody response were particularly beneficial. Furthermore, commonly employed apical measures (e.g., leukocyte counts, lymphoid organ weights) were fairly insensitive. The present analyses focus on the use of this data base to develop statistical models that examine the qualitative and quantitative relationship(s) between the immune function and host resistance tests. The conclusion derived from these analyses are: (1) A good correlation exists between changes in the immune tests and altered host resistance in that there were no instances where host resistance was altered without affecting an immune test(s). However, in some instances immune changes occurred without corresponding changes in host resistance. (2) No single immune test could be identified which was fully predictive for altered host resistance, although most assays were relatively good indicators (i.e., > 70%). Several others, such as proliferative response to lipopolysaccharide and leukocyte counts, were found to be relatively poor indicators for host resistance changes. (3) The ability to resist infectious agent challenge is dependent upon the degrees of immunosuppression and the quantity of infectious agent administered. (4) Logistic and standard regression modeling using one extensive chemical data set from the immunosuppressive agent, cyclophosphamide, indicated that most immune function-host resistance relationships followed linear rather than linear-quadratic (threshold-like) models. For most of the relationships this could not be confirmed using a large chemical data set and, thus, a more mechanistically based approach for modeling will need to be developed. (5) Using this limited data set, methods were developed for modeling the precise quantitative relationships between changes in selected immune tests and host resistance tests. JF - Fundamental and applied toxicology : official journal of the Society of Toxicology AU - Luster, M I AU - Portier, C AU - Pait, D G AU - Rosenthal, G J AU - Germolec, D R AU - Corsini, E AU - Blaylock, B L AU - Pollock, P AU - Kouchi, Y AU - Craig, W AD - Environmental Immunology and Neurobiology Section, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1993/07// PY - 1993 DA - July 1993 SP - 71 EP - 82 VL - 21 IS - 1 SN - 0272-0590, 0272-0590 KW - Cyclophosphamide KW - 8N3DW7272P KW - Index Medicus KW - Regression Analysis KW - Animals KW - Dose-Response Relationship, Drug KW - Mice, Inbred C57BL KW - Models, Statistical KW - Mice KW - Immunity, Innate KW - Cyclophosphamide -- toxicity KW - Female KW - Immune System -- drug effects KW - Risk Factors KW - Toxicology -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75931388?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.atitle=Risk+assessment+in+immunotoxicology.+II.+Relationships+between+immune+and+host+resistance+tests.&rft.au=Luster%2C+M+I%3BPortier%2C+C%3BPait%2C+D+G%3BRosenthal%2C+G+J%3BGermolec%2C+D+R%3BCorsini%2C+E%3BBlaylock%2C+B+L%3BPollock%2C+P%3BKouchi%2C+Y%3BCraig%2C+W&rft.aulast=Luster&rft.aufirst=M&rft.date=1993-07-01&rft.volume=21&rft.issue=1&rft.spage=71&rft.isbn=&rft.btitle=&rft.title=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.issn=02720590&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-10-05 N1 - Date created - 1993-10-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Non-conservation of a catalytic residue in a dipeptidyl aminopeptidase IV-related protein encoded by a gene on human chromosome 7. AN - 75929119; 8103397 JF - Human molecular genetics AU - Yokotani, N AU - Doi, K AU - Wenthold, R J AU - Wada, K AD - Laboratory of Neurochemistry, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/07// PY - 1993 DA - July 1993 SP - 1037 EP - 1039 VL - 2 IS - 7 SN - 0964-6906, 0964-6906 KW - DPPX KW - DNA KW - 9007-49-2 KW - Dipeptidyl-Peptidases and Tripeptidyl-Peptidases KW - EC 3.4.14.- KW - Dipeptidyl Peptidase 4 KW - EC 3.4.14.5 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Conserved Sequence KW - Humans KW - DNA -- genetics KW - Molecular Sequence Data KW - Hybrid Cells KW - Binding Sites -- genetics KW - Chromosome Mapping KW - Dipeptidyl-Peptidases and Tripeptidyl-Peptidases -- genetics KW - Chromosomes, Human, Pair 7 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75929119?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+molecular+genetics&rft.atitle=Non-conservation+of+a+catalytic+residue+in+a+dipeptidyl+aminopeptidase+IV-related+protein+encoded+by+a+gene+on+human+chromosome+7.&rft.au=Yokotani%2C+N%3BDoi%2C+K%3BWenthold%2C+R+J%3BWada%2C+K&rft.aulast=Yokotani&rft.aufirst=N&rft.date=1993-07-01&rft.volume=2&rft.issue=7&rft.spage=1037&rft.isbn=&rft.btitle=&rft.title=Human+molecular+genetics&rft.issn=09646906&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-10-04 N1 - Date created - 1993-10-04 N1 - Date revised - 2017-01-13 N1 - Gene symbol - DPPX N1 - Genetic sequence - M96859; GENBANK; M96860 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Heterogeneity in the concerted evolution process of a tandem satellite array in meadow mice (Microtus). AN - 75913635; 8360918 AB - The evolutionary history of a 160-bp tandem satellite array, originally described from Microtus chrotorrhinus and called MSAT-160, was examined in related species of arvicolid rodents by sequence analyses, quantitative dot blotting, and Southern blotting. Results indicate that MSAT-160 is present in 12 of the 20 species and subspecies of Microtus assayed, but not in species belonging to any of the eight other genera examined. DNA from each species containing MSAT-160 was digested with 12 restriction endonucleases and restriction patterns were obtained reflecting the variable extent of homogenization of any given variant in different species. For example, with MboI digestion, M. chrotorrhinus produced a type A ladder pattern where most monomers contain the restriction site, M. ochrogaster generated a type B pattern where most monomers lack the site, and M. agrestis yielded a pattern intermediate between the A and B types. Further, dot blotting revealed copy-number differences between species. These findings indicate that changes in the periodic structure and amount of satellite DNA have occurred since these species last shared a common ancestor. In addition, various species-specific patterns were documented, illustrating that mechanisms other than genome-wide homogenization, such as stochastic mutation, out-of-register crossing over, deletion, and random amplification also play a role in structuring tandem arrays. Stochastic mutation and homogenization rates in satellite DNA, levels of species diversity, and magnitudes of chromosomal divergence differ significantly in Microtus, Mus and Ctenomys, the three rodent lineages examined. JF - Journal of molecular evolution AU - Modi, W S AD - Biological Carcinogenesis Development Program, Program Resources Inc./DynCorp, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702-1201. Y1 - 1993/07// PY - 1993 DA - July 1993 SP - 48 EP - 56 VL - 37 IS - 1 SN - 0022-2844, 0022-2844 KW - DNA, Satellite KW - 0 KW - Index Medicus KW - Animals KW - Base Sequence KW - Sequence Homology, Nucleic Acid KW - Blotting, Southern KW - Molecular Sequence Data KW - Rodentia -- genetics KW - Species Specificity KW - Cell Line KW - DNA, Satellite -- genetics KW - Biological Evolution KW - Arvicolinae -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75913635?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+evolution&rft.atitle=Heterogeneity+in+the+concerted+evolution+process+of+a+tandem+satellite+array+in+meadow+mice+%28Microtus%29.&rft.au=Modi%2C+W+S&rft.aulast=Modi&rft.aufirst=W&rft.date=1993-07-01&rft.volume=37&rft.issue=1&rft.spage=48&rft.isbn=&rft.btitle=&rft.title=Journal+of+molecular+evolution&rft.issn=00222844&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-09-24 N1 - Date created - 1993-09-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A dose escalation study to determine the toxicity and maximally tolerated dose of foscarnet. AN - 75907261; 8357555 AB - To determine the maximum tolerated dose of intravenous foscarnet (trisodium phosphonoformate hexahydrate); and to examine antiviral activity at plasma levels shown to inhibit HIV-1. Dose escalation study in three male subjects with AIDS who received foscarnet by continuous intravenous infusion at a dose of 200 mg/kg per day, after a 20 mg/kg loading dose. The dose was increased until a plasma level > 150 micrograms/ml was attained. Foscarnet was discontinued due to progressive renal insufficiency in all three patients (days 11, 19, and 21). Renal function normalized in all three, and no adverse sequelae due to foscarnet were observed at 1 year of follow-up. A seizure was observed in one patient on day 19. Maximum daily doses of foscarnet achieved were 395 mg/kg, 389 mg/kg, and 523 mg/kg. No changes in serum Ca2+, Mg2+, or PO4- were observed. Renal effects and toxicity of foscarnet in evolving renal insufficiency is self-limiting and reversible when the drug is discontinued. Incremental increases in dose can result in rapid rises in the plasma level with renal failure and may be compounded by concomitant medications and underlying illnesses. JF - AIDS (London, England) AU - Seidel, E A AU - Koenig, S AU - Polis, M A AD - Laboratory of Immunoregulation, NIAID, NIH, Bethesda, MD 20892. Y1 - 1993/07// PY - 1993 DA - July 1993 SP - 941 EP - 945 VL - 7 IS - 7 SN - 0269-9370, 0269-9370 KW - Foscarnet KW - 364P9RVW4X KW - Creatinine KW - AYI8EX34EU KW - Index Medicus KW - AIDS/HIV KW - Seizures -- complications KW - Infusions, Intravenous KW - Dose-Response Relationship, Drug KW - Humans KW - Adult KW - Middle Aged KW - Renal Insufficiency -- complications KW - Creatinine -- blood KW - Male KW - Acquired Immunodeficiency Syndrome -- complications KW - Foscarnet -- toxicity KW - Foscarnet -- administration & dosage KW - Acquired Immunodeficiency Syndrome -- drug therapy KW - HIV-1 -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75907261?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+dose+escalation+study+to+determine+the+toxicity+and+maximally+tolerated+dose+of+foscarnet.&rft.au=Seidel%2C+E+A%3BKoenig%2C+S%3BPolis%2C+M+A&rft.aulast=Seidel&rft.aufirst=E&rft.date=1993-07-01&rft.volume=7&rft.issue=7&rft.spage=941&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 - 1993-09-27 N1 - Date created - 1993-09-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Managing occupational exposures to HIV-1 in the healthcare workplace. AN - 75902475; 8354872 JF - Infection control and hospital epidemiology AU - Fahey, B J AU - Beekmann, S E AU - Schmitt, J M AU - Fedio, J M AU - Henderson, D K AD - Hospital Epidemiology Service, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/07// PY - 1993 DA - July 1993 SP - 405 EP - 412 VL - 14 IS - 7 SN - 0899-823X, 0899-823X KW - Index Medicus KW - Nursing KW - AIDS/HIV KW - Coitus -- psychology KW - Risk Factors KW - Humans KW - Pregnancy Complications, Infectious KW - First Aid KW - Counseling KW - Occupational Health Services KW - Male KW - Female KW - Pregnancy KW - Occupational Exposure -- prevention & control KW - Personnel, Hospital -- psychology KW - Occupational Diseases -- drug therapy KW - Acquired Immunodeficiency Syndrome -- transmission KW - Occupational Diseases -- etiology KW - Acquired Immunodeficiency Syndrome -- drug therapy KW - HIV-1 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75902475?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+control+and+hospital+epidemiology&rft.atitle=Managing+occupational+exposures+to+HIV-1+in+the+healthcare+workplace.&rft.au=Fahey%2C+B+J%3BBeekmann%2C+S+E%3BSchmitt%2C+J+M%3BFedio%2C+J+M%3BHenderson%2C+D+K&rft.aulast=Fahey&rft.aufirst=B&rft.date=1993-07-01&rft.volume=14&rft.issue=7&rft.spage=405&rft.isbn=&rft.btitle=&rft.title=Infection+control+and+hospital+epidemiology&rft.issn=0899823X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-09-23 N1 - Date created - 1993-09-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Estimating historical exposure to silica among mine and pottery workers in the People's Republic of China. AN - 75896354; 8394648 AB - A quantitative retrospective exposure assessment method was developed for use in a nested case-control study of lung cancer among mine and pottery workers exposed to silica dust in the People's Republic of China. Exposure assessment was carried out in 20 mines (10 tungsten, 6 iron/copper, and 4 tin) and nine pottery factories. A job title dictionary was developed and used in both the collection of historical exposure information and work histories of 1,668 (316 cases and 1,352 controls) study subjects. Several data abstraction forms were developed to collect historical and current exposure information and employees' work histories, starting in 1950. A retrospective exposure matrix was developed on the basis of facility/job title/calendar year combinations using available historical exposure information and current exposure profiles. Information on the amount of respirable, thoracic, and free silica content in total dust was used in estimating exposure to silica. Starting in 1950, 6,805 historical estimates had been carried out for 14 calendar-year periods. We estimated the average total dust concentration to be 9 mg/M3, with a range from 28 mg/M3 in earlier years to 3 mg/M3 in recent years. Several exposure indices [such as cumulative dust, average dust, cumulative respirable (< 5 mu in particle size) and thoracic (< 10 mu in particle size) silica dust, average respirable and thoracic silica dust, exposure-weighted duration, and the highest/longest exposure] were calculated for individuals by merging work history and historical exposure matrix for each study subject. We developed these various measures of exposure to allow investigators to compare and contrast different indices of historical exposure to silica. JF - American journal of industrial medicine AU - Dosemeci, M AU - Chen, J Q AU - Hearl, F AU - Chen, R G AU - McCawley, M AU - Wu, Z AU - McLaughlin, J K AU - Peng, K L AU - Chen, A L AU - Rexing, S H AD - Epidemiology and Biostatistics Program, National Cancer Institute, Bethesda, MD. Y1 - 1993/07// PY - 1993 DA - July 1993 SP - 55 EP - 66 VL - 24 IS - 1 SN - 0271-3586, 0271-3586 KW - Dust KW - 0 KW - Silicon Dioxide KW - 7631-86-9 KW - Index Medicus KW - Lung Neoplasms -- epidemiology KW - Humans KW - China -- epidemiology KW - Retrospective Studies KW - Case-Control Studies KW - Occupational Diseases -- epidemiology KW - Models, Statistical KW - Lung Neoplasms -- chemically induced KW - Occupational Diseases -- chemically induced KW - Occupational Exposure -- statistics & numerical data KW - Mining -- statistics & numerical data KW - Silicon Dioxide -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75896354?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+industrial+medicine&rft.atitle=Estimating+historical+exposure+to+silica+among+mine+and+pottery+workers+in+the+People%27s+Republic+of+China.&rft.au=Dosemeci%2C+M%3BChen%2C+J+Q%3BHearl%2C+F%3BChen%2C+R+G%3BMcCawley%2C+M%3BWu%2C+Z%3BMcLaughlin%2C+J+K%3BPeng%2C+K+L%3BChen%2C+A+L%3BRexing%2C+S+H&rft.aulast=Dosemeci&rft.aufirst=M&rft.date=1993-07-01&rft.volume=24&rft.issue=1&rft.spage=55&rft.isbn=&rft.btitle=&rft.title=American+journal+of+industrial+medicine&rft.issn=02713586&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-09-14 N1 - Date created - 1993-09-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Occupational risks for primary liver cancer in Shanghai, China. AN - 75891436; 8352295 AB - Using occupational data for over 3,400 primary liver cancer cases diagnosed between 1980 and 1984 reported to the Shanghai Cancer Registry, and employment information from the 1982 census for the Shanghai population, standardized incidence ratios were computed to generate leads to occupational risks of liver cancer. Among men, a statistically significant excess number of cases was observed for chemical processors, textile workers, wood workers, blacksmiths and machine-tool operators, and material handlers and dock workers. Increased incidence of liver cancer also was observed among female transport equipment operators. These findings indicate that a number of similar occupations are associated with increased risk of primary liver cancer in western countries and China. Although causal inferences cannot be drawn from these data, our study adds to the limited evidence of the potential role of occupational exposures in liver carcinogenesis. JF - American journal of industrial medicine AU - Chow, W H AU - McLaughlin, J K AU - Zheng, W AU - Blot, W J AU - Gao, Y T AD - Division of Cancer Etiology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/07// PY - 1993 DA - July 1993 SP - 93 EP - 100 VL - 24 IS - 1 SN - 0271-3586, 0271-3586 KW - Index Medicus KW - Risk Factors KW - Humans KW - China -- epidemiology KW - Adult KW - Incidence KW - Male KW - Female KW - Occupational Diseases -- etiology KW - Occupations -- statistics & numerical data KW - Occupational Diseases -- epidemiology KW - Liver Neoplasms -- epidemiology KW - Liver Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75891436?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+industrial+medicine&rft.atitle=Occupational+risks+for+primary+liver+cancer+in+Shanghai%2C+China.&rft.au=Chow%2C+W+H%3BMcLaughlin%2C+J+K%3BZheng%2C+W%3BBlot%2C+W+J%3BGao%2C+Y+T&rft.aulast=Chow&rft.aufirst=W&rft.date=1993-07-01&rft.volume=24&rft.issue=1&rft.spage=93&rft.isbn=&rft.btitle=&rft.title=American+journal+of+industrial+medicine&rft.issn=02713586&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-09-14 N1 - Date created - 1993-09-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Contribution of occupation and diet to white blood cell polycyclic aromatic hydrocarbon-DNA adducts in wildland firefighters. AN - 75886115; 8348057 AB - Wildland (forest) firefighters are exposed to a wide range of carcinogenic polycyclic aromatic hydrocarbons (PAH) in forest fire smoke. PAH undergo metabolic activation and can subsequently bind to DNA. In this study, we investigated the association between occupational and dietary PAH exposures and the formation of WBC PAH-DNA adducts in a population of wildland firefighters. An enzyme-linked immunosorbent assay using an antiserum elicited against benzo(a)pyrene-modified DNA was used to measure PAH-DNA adducts in WBC obtained from 47 California firefighters at two time points, early and late in the 1988 forest fire season. PAH-DNA adduct levels were not associated with cumulative hours of recent firefighting activity. However, firefighters who consumed charbroiled food within the previous week had elevated PAH-DNA adduct levels, which were related to frequency of charbroiled food intake. These findings suggest that dietary sources of PAH contribute to PAH-DNA adduct levels in peripheral WBC and should be evaluated when using this assay to assess occupational and environmental PAH exposure. JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology AU - Rothman, N AU - Correa-Villaseñor, A AU - Ford, D P AU - Poirier, M C AU - Haas, R AU - Hansen, J A AU - O'Toole, T AU - Strickland, P T AD - Environmental Epidemiology Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892. PY - 1993 SP - 341 EP - 347 VL - 2 IS - 4 SN - 1055-9965, 1055-9965 KW - Polycyclic Compounds KW - 0 KW - Smoke KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Food KW - Humans KW - Retrospective Studies KW - Protein Binding KW - California KW - Prospective Studies KW - Adult KW - Cooking KW - Middle Aged KW - Adolescent KW - Time Factors KW - Female KW - Male KW - Occupational Exposure KW - Leukocytes -- metabolism KW - Fires KW - Trees KW - DNA -- metabolism KW - Polycyclic Compounds -- metabolism KW - Diet UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75886115?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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%2C+behavior%2C+and+immunity&rft.atitle=Immunocompetence+in+the+long+sleep+and+short+sleep+mouse+lines%3A+baseline+versus+primed+responses.&rft.au=Fride%2C+E%3BMcIntyre%2C+T%3BSkolnick%2C+P%3BArora%2C+P+K&rft.aulast=Fride&rft.aufirst=E&rft.date=1993-09-01&rft.volume=7&rft.issue=3&rft.spage=231&rft.isbn=&rft.btitle=&rft.title=Brain%2C+behavior%2C+and+immunity&rft.issn=08891591&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-09-16 N1 - Date created - 1993-09-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Clinical and laboratory adverse effects associated with long-term, low-dose isotretinoin: incidence and risk factors. The Isotretinoin-Basal Cell Carcinomas Study Group. AN - 75881810; 8348061 AB - Adverse effects associated with the long-term low-dose regimens of retinoids used in cancer chemoprevention studies are not well described. In order to examine the clinical and laboratory adverse effects of 3 years of intervention with isotretinoin (10 mg/day) and to assess potential risk factors for developing these, we collected adverse effect data on patients participating in a randomized, placebo-controlled trial designed to evaluate the effectiveness of isotretinoin in preventing the subsequent occurrence of new basal cell carcinoma. Our results showed a significantly higher incidence of adverse mucocutaneous effects and serum triglyceride elevations in the isotretinoin group (P < 0.001). Associated risk factors included male gender, very fair skin, and elevated pretreatment triglyceride levels. The toxicity observed, although less severe and less frequent, was similar to that seen with higher doses and should be weighed with adverse skeletal effects when considering long-term treatment of patients with moderate cancer risk. JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology AU - Tangrea, J A AU - Adrianza, E AU - Helsel, W E AU - Taylor, P R AU - Hartman, A M AU - Peck, G L AU - Edwards, B K AD - Division of Cancer Prevention and Control, National Cancer Institute, National Institutes of Health, Bethesda, Maryland. PY - 1993 SP - 375 EP - 380 VL - 2 IS - 4 SN - 1055-9965, 1055-9965 KW - Placebos KW - 0 KW - Triglycerides KW - Cholesterol KW - 97C5T2UQ7J KW - Isotretinoin KW - EH28UP18IF KW - Index Medicus KW - Triglycerides -- blood KW - Double-Blind Method KW - Humans KW - Skin -- pathology KW - Aged KW - Pain KW - Joints -- drug effects KW - Cholesterol -- blood KW - Risk Factors KW - Hypertriglyceridemia -- chemically induced KW - Adult KW - Incidence KW - Middle Aged KW - Follow-Up Studies KW - Hypercholesterolemia -- chemically induced KW - Male KW - Female KW - Muscles -- drug effects KW - Cheilitis -- chemically induced KW - Isotretinoin -- administration & dosage KW - Carcinoma, Basal Cell -- prevention & control KW - Isotretinoin -- adverse effects KW - Skin Neoplasms -- prevention & control KW - Isotretinoin -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75881810?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+epidemiology%2C+biomarkers+%26+prevention+%3A+a+publication+of+the+American+Association+for+Cancer+Research%2C+cosponsored+by+the+American+Society+of+Preventive+Oncology&rft.atitle=Clinical+and+laboratory+adverse+effects+associated+with+long-term%2C+low-dose+isotretinoin%3A+incidence+and+risk+factors.+The+Isotretinoin-Basal+Cell+Carcinomas+Study+Group.&rft.au=Tangrea%2C+J+A%3BAdrianza%2C+E%3BHelsel%2C+W+E%3BTaylor%2C+P+R%3BHartman%2C+A+M%3BPeck%2C+G+L%3BEdwards%2C+B+K&rft.aulast=Tangrea&rft.aufirst=J&rft.date=1993-07-01&rft.volume=2&rft.issue=4&rft.spage=375&rft.isbn=&rft.btitle=&rft.title=Cancer+epidemiology%2C+biomarkers+%26+prevention+%3A+a+publication+of+the+American+Association+for+Cancer+Research%2C+cosponsored+by+the+American+Society+of+Preventive+Oncology&rft.issn=10559965&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-09-16 N1 - Date created - 1993-09-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Increased sensitivity for determination of polycyclic aromatic hydrocarbon-DNA adducts in human DNA samples by dissociation-enhanced lanthanide fluoroimmunoassay (DELFIA). AN - 75877395; 8348058 AB - A competitive enzyme-linked immunosorbent assay (ELISA), the most frequently used immunoassay for the determination of polycyclic aromatic hydrocarbon-DNA adducts in human tissues, has been modified to achieve approximately a 6-fold increase in sensitivity. The new assay, a competitive dissociation-enhanced lanthanide fluoroimmunoassay (DELFIA) has utilized the same rabbit antiserum as the ELISA, antiserum elicited against DNA modified with benzo[a]pyrene. However, the alkaline phosphatase conjugate has been replaced with a biotin-europium-labeled streptavidin signal amplification system, and the release of europium into the solution forms a highly fluorescent chelate complex that is measured by time-resolved fluorometry. The DELFIA has achieved a 5- to 6-fold increase in sensitivity for measurement of DNA samples modified in vitro with benzo[a]pyrene, for cultured cells exposed to radiolabeled benzo[a]pyrene, and for human samples from occupationally exposed workers. The assay has been validated by comparison of adduct levels determined by DELFIA, ELISA, and radioactivity in DNA from mouse keratinocytes exposed to radiolabeled benzo[a]pyrene. Human lymphocyte DNA samples from 104 Hungarian aluminum plant workers were assayed by ELISA and compared to blood cell DNA samples from 69 Italian coke oven workers assayed by DELFIA. The standard curves demonstrated that the limit of detection of 4.0 adducts in 10(8) nucleotides for polycyclic aromatic hydrocarbon-DNA adducts by ELISA, using 35 micrograms of DNA/microtiter plate well, has been decreased to 1.3 adducts in 10(8) nucleotides by DELFIA, using 20 micrograms of DNA/microtiter well. If 35 micrograms of DNA were used in the DELFIA, the calculated detection limit would be 0.7 adducts in 10(8) nucleotides.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology AU - Schoket, B AU - Doty, W A AU - Vincze, I AU - Strickland, P T AU - Ferri, G M AU - Assennato, G AU - Poirier, M C AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, NIH Bethesda, Maryland 20892. PY - 1993 SP - 349 EP - 353 VL - 2 IS - 4 SN - 1055-9965, 1055-9965 KW - Bacterial Proteins KW - 0 KW - Coke KW - Metals, Rare Earth KW - Polycyclic Compounds KW - Benzo(a)pyrene KW - 3417WMA06D KW - Europium KW - 444W947O8O KW - DNA KW - 9007-49-2 KW - Streptavidin KW - 9013-20-1 KW - Aluminum KW - CPD4NFA903 KW - Deoxyguanosine KW - G9481N71RO KW - Index Medicus KW - Fluorescence KW - Humans KW - Lymphocytes -- metabolism KW - Italy KW - Hungary KW - Enzyme-Linked Immunosorbent Assay KW - Fluorometry KW - Deoxyguanosine -- analysis KW - Chemical Industry KW - Polycyclic Compounds -- analysis KW - DNA -- analysis KW - Fluoroimmunoassay -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75877395?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+epidemiology%2C+biomarkers+%26+prevention+%3A+a+publication+of+the+American+Association+for+Cancer+Research%2C+cosponsored+by+the+American+Society+of+Preventive+Oncology&rft.atitle=Increased+sensitivity+for+determination+of+polycyclic+aromatic+hydrocarbon-DNA+adducts+in+human+DNA+samples+by+dissociation-enhanced+lanthanide+fluoroimmunoassay+%28DELFIA%29.&rft.au=Schoket%2C+B%3BDoty%2C+W+A%3BVincze%2C+I%3BStrickland%2C+P+T%3BFerri%2C+G+M%3BAssennato%2C+G%3BPoirier%2C+M+C&rft.aulast=Schoket&rft.aufirst=B&rft.date=1993-07-01&rft.volume=2&rft.issue=4&rft.spage=349&rft.isbn=&rft.btitle=&rft.title=Cancer+epidemiology%2C+biomarkers+%26+prevention+%3A+a+publication+of+the+American+Association+for+Cancer+Research%2C+cosponsored+by+the+American+Society+of+Preventive+Oncology&rft.issn=10559965&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-09-16 N1 - Date created - 1993-09-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Prior medical conditions and the risk of adult leukemia in Shanghai, People's Republic of China. AN - 75877199; 8347786 AB - A population-based case-control interview study of 486 adult leukemia cases and 502 healthy controls was carried out in Shanghai, People's Republic of China during 1987-89 to evaluate the etiologic role of prior medical conditions, medications, and diagnostic X-rays. Risks were examined separately for 236 cases with acute non-lymphocytic leukemia (ANLL), 79 with chronic myeloid leukemia (CML), 81 with acute lymphocytic leukemia (ALL), and 21 with chronic lymphocytic leukemia (CLL). Little difference was found between cases and controls for prior history of diabetes, hypertension, allergic conditions, most medications, and diagnostic X-rays. A few significant associations were observed for appendectomy, tuberculosis, and for several other chronic disorders with specific leukemia cell types, but the odds ratio estimates for most of these ranged from two to three and, with the exception of the two specified above, were based generally on five or fewer exposed controls. In contrast to an association with childhood leukemia in Shanghai, prior use of chloramphenicol was not linked with ANLL or other forms of adult leukemia. Further research is needed to clarify the relation of specific medical conditions and exposures with particular subtypes of leukemia, and to examine reasons for the low incidence of CLL in China and other Asian populations. JF - Cancer causes & control : CCC AU - Zheng, W AU - Linet, M S AU - Shu, X O AU - Pan, R P AU - Gao, Y T AU - Fraumeni, J F AD - Epidemiology and Biostatistics Program, National Cancer Institute, Bethesda, MD. Y1 - 1993/07// PY - 1993 DA - July 1993 SP - 361 EP - 368 VL - 4 IS - 4 SN - 0957-5243, 0957-5243 KW - Salicylates KW - 0 KW - Index Medicus KW - Age Factors KW - Leukemia, Lymphocytic, Chronic, B-Cell -- epidemiology KW - Humans KW - Hyperthyroidism -- epidemiology KW - Aged KW - Tuberculosis -- epidemiology KW - Population Surveillance KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma -- epidemiology KW - Salicylates -- adverse effects KW - Risk Factors KW - Leukemia, Myeloid, Acute -- epidemiology KW - Appendectomy -- statistics & numerical data KW - China -- epidemiology KW - Adult KW - Case-Control Studies KW - Middle Aged KW - Leukemia, Myelogenous, Chronic, BCR-ABL Positive -- epidemiology KW - Adolescent KW - Male KW - Female KW - Disease KW - Leukemia -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75877199?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+causes+%26+control+%3A+CCC&rft.atitle=Prior+medical+conditions+and+the+risk+of+adult+leukemia+in+Shanghai%2C+People%27s+Republic+of+China.&rft.au=Zheng%2C+W%3BLinet%2C+M+S%3BShu%2C+X+O%3BPan%2C+R+P%3BGao%2C+Y+T%3BFraumeni%2C+J+F&rft.aulast=Zheng&rft.aufirst=W&rft.date=1993-07-01&rft.volume=4&rft.issue=4&rft.spage=361&rft.isbn=&rft.btitle=&rft.title=Cancer+causes+%26+control+%3A+CCC&rft.issn=09575243&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-09-16 N1 - Date created - 1993-09-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Retroviral mediated expression of human cytochrome P450 2A6 in C3H/10T1/2 cells confers transformability by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). AN - 75869299; 8330360 AB - In order to develop more efficient in vitro systems for the study of pro-mutagenic or pro-carcinogenic chemicals, we have produced transgenic C3H/10T1/2 cell lines expressing human cytochrome P450 (CYP) 2A6. A retroviral vector containing the cDNA was packaged in psi-2 cells, and used to infect C3H/10T1/2 cells. From 100 G418-resistant clones initially isolated, three cell lines were chosen for further study based upon their morphologies, growth rates and CYP2A6-dependent coumarin 7-hydroxylase activities. Infected clone 10T1/2-04, like the 10T1/2 cells, had no detectable CYP2A6 enzyme activity, while clones 10T1/2-10 and 10T1/2-29 had microsomal CYP2A6 enzyme activities within the range found in human liver microsomes. CYP2A6 protein levels were in agreement with the observed enzyme activities. Southern blots revealed that cells from clone 10T1/2-04 contained a vector lacking the CYP2A6 cDNA, while cells from clones 10T1/2-10 and 10T1/2-29 contained multiple full-length inserts. Southern analysis also indicated the presence of an endogenous CYP2A6 ortholog in the four cell lines. All cell lines exhibited about equal sensitivity to induction of cytotoxicity and conversion to ouabain resistance by the direct acting mutagen N-methyl-N'-nitro-N-nitrosoguanidine. The four lines were also about equally sensitive to transformation by benzo[a]pyrene, a chemical requiring metabolic activation. However, only clones 10T1/2-10 and 10T1/2-29, which express CYP2A6 activity, were mutated and morphologically transformed by the tobacco specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. JF - Carcinogenesis AU - Tiano, H F AU - Hosokawa, M AU - Chulada, P C AU - Smith, P B AU - Wang, R L AU - Gonzalez, F J AU - Crespi, C L AU - Langenbach, R AD - National Institute of Environmental Health Sciences, Laboratory of Environmental Carcinogenesis and Mutagenesis, Research Triangle Park, NC 27709. Y1 - 1993/07// PY - 1993 DA - July 1993 SP - 1421 EP - 1427 VL - 14 IS - 7 SN - 0143-3334, 0143-3334 KW - Nitrosamines KW - 0 KW - 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone KW - 7S395EDO61 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Mixed Function Oxygenases KW - EC 1.- KW - Aryl Hydrocarbon Hydroxylases KW - EC 1.14.14.1 KW - CYP2A6 protein, human KW - Cytochrome P-450 CYP2A6 KW - Index Medicus KW - Animals KW - Blotting, Western KW - Cell Survival -- drug effects KW - Blotting, Southern KW - Biotransformation KW - Humans KW - Genetic Vectors KW - Mice, Inbred C3H KW - Mice KW - Cell Line KW - Cloning, Molecular KW - Nitrosamines -- toxicity KW - Mixed Function Oxygenases -- metabolism KW - Cytochrome P-450 Enzyme System -- genetics KW - Nitrosamines -- metabolism KW - Cytochrome P-450 Enzyme System -- metabolism KW - Nitrosamines -- pharmacokinetics KW - Retroviridae -- genetics KW - Cell Transformation, Neoplastic -- genetics KW - Mixed Function Oxygenases -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75869299?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Retroviral+mediated+expression+of+human+cytochrome+P450+2A6+in+C3H%2F10T1%2F2+cells+confers+transformability+by+4-%28methylnitrosamino%29-1-%283-pyridyl%29-1-butanone+%28NNK%29.&rft.au=Tiano%2C+H+F%3BHosokawa%2C+M%3BChulada%2C+P+C%3BSmith%2C+P+B%3BWang%2C+R+L%3BGonzalez%2C+F+J%3BCrespi%2C+C+L%3BLangenbach%2C+R&rft.aulast=Tiano&rft.aufirst=H&rft.date=1993-07-01&rft.volume=14&rft.issue=7&rft.spage=1421&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-08-18 N1 - Date created - 1993-08-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Electron spin resonance evidence for free radical generation in copper-treated vitamin E- and selenium-deficient rats: in vivo spin-trapping investigation. AN - 75866436; 8393522 AB - The ESR spin-trapping technique has been used to investigate free radical generation in copper-challenged rats deficient in vitamin E and/or selenium. Radical adduct excreted in the bile was detected only from copper-challenged rats deficient in both vitamin E and selenium. The phenyl-N-t-butylnitrone radical adduct has hyperfine coupling constants of aN = 15.36 G and a beta H = 2.50 G and arises from the trapping of a radical formed from an endogenous molecular species. The induction of this radical species in vivo may be important in the increased toxicity of copper in rats deficient in both vitamin E and selenium. These findings support the proposal that dietary selenium and vitamin E can protect against lipid peroxidation and copper toxicity. The results obtained suggest that the presence of only one of these nutrients in the diet is enough to prevent the formation of this radical adduct at ESR-detectable levels, and they provide the most direct ESR evidence yet obtained for the involvement of in vivo lipid peroxidation in the toxicity of copper. JF - Molecular pharmacology AU - Kadiiska, M B AU - Hanna, P M AU - Jordan, S J AU - Mason, R P AD - National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709. Y1 - 1993/07// PY - 1993 DA - July 1993 SP - 222 EP - 227 VL - 44 IS - 1 SN - 0026-895X, 0026-895X KW - Free Radicals KW - 0 KW - Copper KW - 789U1901C5 KW - Glutathione Peroxidase KW - EC 1.11.1.9 KW - Selenium KW - H6241UJ22B KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Liver -- enzymology KW - Glutathione Peroxidase -- metabolism KW - Liver -- drug effects KW - Electron Spin Resonance Spectroscopy KW - Lipid Peroxidation -- drug effects KW - Models, Chemical KW - Male KW - Selenium -- deficiency KW - Vitamin E Deficiency -- metabolism KW - Copper -- pharmacology KW - Free Radicals -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75866436?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Electron+spin+resonance+evidence+for+free+radical+generation+in+copper-treated+vitamin+E-+and+selenium-deficient+rats%3A+in+vivo+spin-trapping+investigation.&rft.au=Kadiiska%2C+M+B%3BHanna%2C+P+M%3BJordan%2C+S+J%3BMason%2C+R+P&rft.aulast=Kadiiska&rft.aufirst=M&rft.date=1993-07-01&rft.volume=44&rft.issue=1&rft.spage=222&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 - 1993-08-27 N1 - Date created - 1993-08-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Neutrophil-specific granule deficiency includes eosinophils. AN - 75865544; 8324226 AB - Neutrophil-specific granule deficiency is a disorder of leukocyte maturation associated with decreased levels of mRNA for a distinct subset of granule proteins. Our work indicates that this disorder, previously thought to be limited to the neutrophil lineage, can also include eosinophils. Immunofluorescence staining led to the discovery of a small but distinct population of peripheral white blood cells containing eosinophil peroxidase (EPO). Unlike normal eosinophils, these EPO+ cells do not have large, eosin-staining cytoplasmic granules, and are indistinguishable from granule-deficient neutrophils by light microscopy. The EPO+ cell lineage did resemble the normal eosinophil lineage in its ability to respond dramatically to granulocyte-macrophage colony-stimulating factor (GM-CSF); the size of the EPO+ peripheral cell population increased approximately 70-fold over baseline in response to GM-CSF administration. The EPO+ cells contained eosinophil Charcot-Leyden crystal protein, but were deficient in three eosinophil-specific granule proteins; neither eosinophil cationic protein, eosinophil-derived neurotoxin, nor major basic protein could be detected in these EPO+ cells, despite the presence of mRNA transcripts for each of the three absent proteins. JF - Blood AU - Rosenberg, H F AU - Gallin, J I AD - Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/07/01/ PY - 1993 DA - 1993 Jul 01 SP - 268 EP - 273 VL - 82 IS - 1 SN - 0006-4971, 0006-4971 KW - ECP KW - EDN KW - MPB KW - Blood Proteins KW - 0 KW - Eosinophil Granule Proteins KW - Neurotoxins KW - Oligodeoxyribonucleotides KW - RNA, Messenger KW - Peroxidases KW - EC 1.11.1.- KW - Eosinophil-Derived Neurotoxin KW - EC 3.1.- KW - Ribonucleases KW - Abridged Index Medicus KW - Index Medicus KW - Neurotoxins -- metabolism KW - Humans KW - Gene Expression KW - RNA, Messenger -- genetics KW - Base Sequence KW - Genes KW - Oligodeoxyribonucleotides -- chemistry KW - Molecular Sequence Data KW - Blood Proteins -- metabolism KW - Fluorescent Antibody Technique KW - Peroxidases -- metabolism KW - Hematologic Diseases -- genetics KW - Cytoplasmic Granules -- ultrastructure KW - Eosinophils -- metabolism KW - Hematologic Diseases -- metabolism KW - Cytoplasmic Granules -- metabolism KW - Eosinophils -- ultrastructure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75865544?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Neutrophil-specific+granule+deficiency+includes+eosinophils.&rft.au=Rosenberg%2C+H+F%3BGallin%2C+J+I&rft.aulast=Rosenberg&rft.aufirst=H&rft.date=1993-07-01&rft.volume=82&rft.issue=1&rft.spage=268&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-08-11 N1 - Date created - 1993-08-11 N1 - Date revised - 2017-01-13 N1 - Gene symbol - ECP; EDN; MPB N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Comparison of the toxicity of citral in F344 rats and B6C3F1 mice when administrated by microencapsulation in feed or by corn-oil gavage. AN - 75865188; 8340024 AB - A study of the potential effects of microencapsulation on the toxicity of citral was conducted in 14-day continuous feeding studies with both sexes of F344 rats and B6C3F1 mice. Toxicity by the feeding route was compared with that from bolus doses of the neat chemical in corn oil administrated by gavage. Both sexes of rats and mice were given diet containing 0, 0.63, 1.25, 2.5, 5 and 10% citral microcapsules. These feed formulations were equivalent to daily doses of 0, 142, 285, 570, 1140 and 2280 mg citral/kg body weight for rats and 0, 534, 1068, 2137, 4275 and 8550 mg citral/kg body weight for mice. The daily gavage doses were 0, 570, 1140 and 2280 mg citral/kg body weight for both sexes of rats, and 0, 534, 1068 and 2137 mg citral/kg body weight for both sexes of mice. Citral microcapsules administered in the diet did not cause mortality in mice or rats. Toxicity was confined to decreases in body weight at the 10% concentration in mice, at the 5 and 10% concentrations in rats, and decreases in absolute weights of the liver, kidney and spleen at the 10% concentration in rats. The only histopathological change observed was minimal to mild hyperplasia and/or squamous metaplasia of the respiratory epithelium in the anterior portion of the nasal passages of rats fed 5 or 10% citral microcapsules. By contrast, citral gavage caused mortality in five out of five male and female mice at 2137 mg/kg body weight, and in two out of five male mice at 1068 mg/kg body weight. There were dose-related increases in absolute liver weights of male and female mice. Cytoplasmic vacuolization of hepatocytes occurred in all female mice gavaged with 1068 and 2137 mg citral/kg body weight, and in male mice from the 2137 mg/kg dose group. Necrosis, ulceration and/or acute inflammation of the forestomach occurred in the high-dose mice of both sexes. Inflammation and/or hyperplasia of the forestomach occurred in about half of the male and female mice dosed with 1068 mg citral/kg. Citral gavage at doses that were equivalent to up to 10% in the diet (2280 mg/kg body weight) did not cause toxicity in rats, except for minimal hyperplasia of the squamous epithelium of the forestomach in high-dose males.(ABSTRACT TRUNCATED AT 400 WORDS) JF - Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association AU - Dieter, M P AU - Goehl, T J AU - Jameson, C W AU - Elwell, M R AU - Hildebrandt, P K AU - Yuan, J H AD - National Institutes of Health, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1993/07// PY - 1993 DA - July 1993 SP - 463 EP - 474 VL - 31 IS - 7 SN - 0278-6915, 0278-6915 KW - Monoterpenes KW - 0 KW - Terpenes KW - Vitamin A KW - 11103-57-4 KW - Corn Oil KW - 8001-30-7 KW - citral KW - T7EU0O9VPP KW - Index Medicus KW - Administration, Oral KW - Eating -- drug effects KW - Animals KW - Drug Compounding KW - Dose-Response Relationship, Drug KW - Vitamin A -- antagonists & inhibitors KW - Mice KW - Drug Administration Routes KW - Rats KW - Mice, Inbred Strains KW - Rats, Inbred F344 KW - Animal Feed KW - Body Weight -- drug effects KW - Toxicology -- methods KW - Species Specificity KW - Female KW - Male KW - Terpenes -- toxicity KW - Terpenes -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75865188?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Comparison+of+the+toxicity+of+citral+in+F344+rats+and+B6C3F1+mice+when+administrated+by+microencapsulation+in+feed+or+by+corn-oil+gavage.&rft.au=Dieter%2C+M+P%3BGoehl%2C+T+J%3BJameson%2C+C+W%3BElwell%2C+M+R%3BHildebrandt%2C+P+K%3BYuan%2C+J+H&rft.aulast=Dieter&rft.aufirst=M&rft.date=1993-07-01&rft.volume=31&rft.issue=7&rft.spage=463&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 - 1993-08-30 N1 - Date created - 1993-08-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Population characteristics of DNA fingerprints in humpback whales (Megaptera novaeangliae). AN - 75861502; 8340617 AB - Humpback whales exhibit a remarkable social organization that is characterized by seasonal long-distance migration (> 10,000 km/year) between summer feeding grounds in high latitudes and winter calving and breeding grounds in tropical or near-tropical waters. All populations are currently considered endangered as a result of intensive commercial exploitation during the last 200 years. Using three hypervariable minisatellite DNA probes (33.15, 3'HVR, and M13) originally developed for studies of human genetic variation, we examined genetic variation within and among three regional subpopulations of humpback whales from the North Pacific and one from the North Atlantic oceans. Analysis of DNA extracted from skin tissues collected by biopsy darting from free-ranging whales revealed considerable variation in each subpopulation. The extent of this variation argues against a recent history of inbreeding among humpback whales as a result of nineteenth- and twentieth-century hunting. A canonical variate analysis suggested a relationship between scaled genetic distance, based on similarities of DNA fingerprints, and geographic distance (i.e., longitude of regional subpopulation). Significant categorical differences were found between the two oceanic populations using a multivariate analysis of variance (MANOVA) with a modification of the Mantel nonparametric permutation test. The relationship between DNA fingerprint similarities and geographic distance suggests that nuclear gene flow between regional subpopulations within the North Pacific is restricted by relatively low rates of migratory interchange between breeding grounds or assortative mating on common wintering grounds. JF - The Journal of heredity AU - Baker, C S AU - Gilbert, D A AU - Weinrich, M T AU - Lambertsen, R AU - Calambokidis, J AU - McArdle, B AU - Chambers, G K AU - O'Brien, S J AD - Laboratory of Viral Carcinogenesis, National Cancer Institute, Frederick, MD 21701-1013. PY - 1993 SP - 281 EP - 290 VL - 84 IS - 4 SN - 0022-1503, 0022-1503 KW - DNA Probes KW - 0 KW - DNA, Satellite KW - Index Medicus KW - Animals KW - Electrophoresis, Agar Gel KW - Genetic Variation KW - Whales -- genetics KW - DNA Fingerprinting UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75861502?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+heredity&rft.atitle=Population+characteristics+of+DNA+fingerprints+in+humpback+whales+%28Megaptera+novaeangliae%29.&rft.au=Baker%2C+C+S%3BGilbert%2C+D+A%3BWeinrich%2C+M+T%3BLambertsen%2C+R%3BCalambokidis%2C+J%3BMcArdle%2C+B%3BChambers%2C+G+K%3BO%27Brien%2C+S+J&rft.aulast=Baker&rft.aufirst=C&rft.date=1993-07-01&rft.volume=84&rft.issue=4&rft.spage=281&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+heredity&rft.issn=00221503&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-09-02 N1 - Date created - 1993-09-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Trimethyltin-induced c-fos expression: adolescent vs neonatal rat hippocampus. AN - 75860361; 8337705 AB - In the adult animal, the immediate early genes such as c-fos and c-jun, and other activity-dependent genes such as ornithine decarboxylase (ODC) are induced within minutes to hours in response to perturbations to the cellular environment. We have examined the induction of these genes following acute exposure to trimethyltin (TMT) using Northern blot analysis. The induction of these genes within the hippocampus and the cerebellum was examined half an hour following acute exposure to TMT (4 mg/kg, sc). In the neonatal (PND 4) rat hippocampus, the basal expression of c-fos, c-jun, and ODC appeared to be unaltered following TMT exposure. However, in the adolescent (PND 35) rat, TMT exposure produced a dramatic induction of c-fos mRNA in the hippocampus within half an hour, while beta-actin expression remained constant. No TMT-induced changes in the expression of c-fos were seen in the cerebellum of adolescent animals. Furthermore, expression of c-jun mRNA was not altered in either the mature hippocampus or the cerebellum half an hour following TMT exposure. These results suggest that c-fos may be involved in the response of the brain to TMT in an age-dependent and region-specific manner. JF - Toxicology and applied pharmacology AU - Zawia, N H AU - Harry, G J AD - Systems Toxicity Branch, NIEHS, Research Triangle Park, North Carolina 27709. Y1 - 1993/07// PY - 1993 DA - July 1993 SP - 99 EP - 102 VL - 121 IS - 1 SN - 0041-008X, 0041-008X KW - c-fos KW - c-jun KW - RNA, Messenger KW - 0 KW - Trimethyltin Compounds KW - trimethyltin KW - 1631-73-8 KW - Ornithine Decarboxylase KW - EC 4.1.1.17 KW - Index Medicus KW - Rats KW - Animals, Newborn KW - Animals KW - Aging -- metabolism KW - Blotting, Northern KW - RNA, Messenger -- metabolism KW - Cerebellum -- drug effects KW - Injections, Subcutaneous KW - Enzyme Induction KW - Female KW - Cerebellum -- metabolism KW - Ornithine Decarboxylase -- genetics KW - Hippocampus -- metabolism KW - Trimethyltin Compounds -- administration & dosage KW - Genes, fos KW - Gene Expression Regulation -- drug effects KW - Ornithine Decarboxylase -- biosynthesis KW - Trimethyltin Compounds -- toxicity KW - Hippocampus -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75860361?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Trimethyltin-induced+c-fos+expression%3A+adolescent+vs+neonatal+rat+hippocampus.&rft.au=Zawia%2C+N+H%3BHarry%2C+G+J&rft.aulast=Zawia&rft.aufirst=N&rft.date=1993-07-01&rft.volume=121&rft.issue=1&rft.spage=99&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 - 1993-08-20 N1 - Date created - 1993-08-20 N1 - Date revised - 2017-01-13 N1 - Gene symbol - c-fos; c-jun N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chemically induced skin carcinogenesis in a transgenic mouse line (TG.AC) carrying a v-Ha-ras gene. AN - 75847672; 8330346 AB - A transgenic mouse line (TG.AC) created in the FVB/N strain, carries a v-Ha-ras gene fused to a zeta-globin promoter gene. These trangenic mice have the properties of genetically initiated skin and have been shown to be sensitive to 12-O-tetradecanoylphorbol-13-acetate (TPA), a well-described promoter of skin papillomas in the two-stage mouse skin tumorigenesis model. It was of interest to determine whether the TG.AC mouse strain was also responsive to other known promoters. Groups of heterozygous or homozygous TG.AC mice were treated topically, 2x/week, for up to 20 weeks with benzoyl peroxide (BPO), 2-butanol peroxide (2-BUP), phenol (PH), acetic acid (AA), TPA and acetone (ACN), the vehicle control. Skin papillomas were induced in all groups treated with TPA, BPO and 2-BUP. Papillomas were observed in some treatment groups as early as 3 weeks. The relative activity of the promoters was TPA > 2-BUP > BPO > PH = AA = ACN. No papillomas were observed in any of the uninitiated FVB/N mice treated in a similar manner and which served as treatment control groups. Studies to determine the sensitivity of TG.AC mice to TPA, indicated that a total dose of 25-30 micrograms of TPA administered in 3 or 10 applications, was sufficient to induce an average incidence of 11-15 papillomas per mouse. The papilloma incidence continued to increase and was maintained up to 15 weeks after TPA treatment was terminated. The short latency period and high incidence of papilloma induction indicate that TG.AC mice have a high sensitivity to known skin promoters. The TG.AC line should prove to be a sensitive model for identifying putative tumor promoters or complete carcinogens. JF - Carcinogenesis AU - Spalding, J W AU - Momma, J AU - Elwell, M R AU - Tennant, R W AD - Laboratory of Experimental Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1993/07// PY - 1993 DA - July 1993 SP - 1335 EP - 1341 VL - 14 IS - 7 SN - 0143-3334, 0143-3334 KW - v-Ha-ras KW - Acetates KW - 0 KW - Butanols KW - Carcinogens KW - Phenols KW - Phenol KW - 339NCG44TV KW - 2-butanol peroxide KW - 37364-67-3 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Acetic Acid KW - Q40Q9N063P KW - Benzoyl Peroxide KW - W9WZN9A0GM KW - Index Medicus KW - Animals KW - Homozygote KW - Dose-Response Relationship, Drug KW - Mice KW - Mice, Transgenic KW - Promoter Regions, Genetic KW - Heterozygote KW - Skin Neoplasms -- genetics KW - Genes, ras KW - Skin Neoplasms -- chemically induced KW - Papilloma -- genetics KW - Papilloma -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75847672?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Chemically+induced+skin+carcinogenesis+in+a+transgenic+mouse+line+%28TG.AC%29+carrying+a+v-Ha-ras+gene.&rft.au=Spalding%2C+J+W%3BMomma%2C+J%3BElwell%2C+M+R%3BTennant%2C+R+W&rft.aulast=Spalding&rft.aufirst=J&rft.date=1993-07-01&rft.volume=14&rft.issue=7&rft.spage=1335&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-08-18 N1 - Date created - 1993-08-18 N1 - Date revised - 2017-01-13 N1 - Gene symbol - v-Ha-ras N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Infiltrating angiolipoma of skeletal muscle. Transplacental induction in nonhuman primates by N-nitrosoethylurea. AN - 75846388; 8331894 AB - In humans, relatively little is known on the association of prenatal exposure to cancer-causing agents and the development of specific tumors later in life as a consequence. Therefore, the effects on the offspring of carcinogen exposure during gestation and the development of tumors later in life were studied in nonhuman primates. Pregnancy was confirmed in Erythrocebus patas (patas) and Macaca mulatta (rhesus) by palpation at 27 to 40 days of gestation. Pregnant animals were treated once weekly intravenously from that time with N-nitrosoethylurea according to different dosing regimens for 6 to 19 weeks with 0.05 to 0.2 mmol/kg/injection. A common lesion developing in only the offspring of mothers treated early in pregnancy was identical with the human condition referred to as intramuscular angioma, hemangioma, or infiltrating angiolipoma of skeletal muscle. In the rhesus, one of 7 animals, and in the patas, 18 of 78 monkeys developed these processes (10 to 40% per group). The lesions typically arose within, infiltrated and displaced skeletal muscle. They occurred most commonly in the lower extremities, followed by the upper extremities and the head; they recurred in three cases of incomplete resection but did not metastasize. The tumors were seen mainly in young adults of both sexes (latency range: 4 to 76 months) and consisted of vessels of variable caliber, and to varying degrees, mature adipose and connective tissue, undifferentiated mesenchymal cells, and lymphoid cell aggregates. Ultrastructurally, the endothelium possessed numerous Weibel-Palade bodies and showed strong immunoreactivity for von Willebrand factor by immunohistochemistry and immunoelectron microscopy. The present investigation suggests a classification of these lesions as infiltrating angiolipoma of skeletal muscle originating from a pluripotent mesenchymal stem cell, caused by exposure to carcinogens during early pregnancy. The great clinical and morphologic similarity of this condition with that observed in humans suggests that it may likewise be caused by exposure to an agent during pregnancy. JF - Laboratory investigation; a journal of technical methods and pathology AU - Rehm, S AU - Palmer, A E AU - Harbaugh, S W AU - Rice, J M AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute, National Institutes of Health, Frederick, Maryland. Y1 - 1993/07// PY - 1993 DA - July 1993 SP - 111 EP - 120 VL - 69 IS - 1 SN - 0023-6837, 0023-6837 KW - Ethylnitrosourea KW - P8M1T4190R KW - Index Medicus KW - Animals KW - Microscopy, Electron KW - Macaca mulatta KW - Erythrocebus patas KW - Microscopy, Immunoelectron KW - Immunohistochemistry KW - Male KW - Female KW - Pregnancy KW - Muscular Diseases -- pathology KW - Muscular Diseases -- metabolism KW - Hemangioma -- pathology KW - Muscular Diseases -- chemically induced KW - Hemangioma -- chemically induced KW - Lipoma -- pathology KW - Hemangioma -- metabolism KW - Lipoma -- metabolism KW - Lipoma -- chemically induced KW - Prenatal Exposure Delayed Effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75846388?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Laboratory+investigation%3B+a+journal+of+technical+methods+and+pathology&rft.atitle=Infiltrating+angiolipoma+of+skeletal+muscle.+Transplacental+induction+in+nonhuman+primates+by+N-nitrosoethylurea.&rft.au=Fu%2C+Y+M%3BMesri%2C+E+A%3BYu%2C+Z+X%3BKreitman%2C+R+J%3BPastan%2C+I%3BEpstein%2C+S+E&rft.aulast=Fu&rft.aufirst=Y&rft.date=1993-09-01&rft.volume=27&rft.issue=9&rft.spage=1691&rft.isbn=&rft.btitle=&rft.title=Cardiovascular+research&rft.issn=00086363&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-08-16 N1 - Date created - 1993-08-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Loss of expression of transforming growth factor beta in skin and skin tumors is associated with hyperproliferation and a high risk for malignant conversion. AN - 75840809; 7687059 AB - Mouse skin carcinomas arise from a small subpopulation of benign papillomas with an increased risk of malignant conversion. These papillomas arise with limited stimulation by tumor promoters, appear rapidly, and do not regress, suggesting that they differ in growth properties from the majority of benign tumors. The transforming growth factor beta (TGF-beta) proteins are expressed in the epidermis and are growth inhibitors for mouse keratinocytes in vitro; altered TGF-beta expression could influence the growth properties of high-risk papillomas. Normal epidermis, tumor promoter-treated epidermis, and skin papillomas at low risk for malignant conversion express TGF-beta 1 in the basal cell compartment and TGF-beta 2 in the suprabasal strata. In low-risk tumors, 90% of the proliferating cells are confined to the basal compartment. In contrast, the majority of high-risk papillomas are devoid of both TGF-beta 1 and TGF-beta 2 as soon as they arise; these tumors have up to 40% of the proliferating cells in the suprabasal layers. Squamous cell carcinomas are also devoid of TGF-beta, suggesting that they arise from the TGF-beta-deficient high-risk papillomas. In some high-risk papillomas, TGF-beta 1 loss can occur first and correlates with basal cell hyperproliferation, while TGF-beta 2 loss correlates with suprabasal hyperproliferation. Similarly, TGF-beta 1-null transgenic mice, which express wild-type levels of TGF-beta 2 in epidermis but no TGF-beta 1 in the basal layer, have a hyperproliferative basal cell layer without suprabasal proliferation. In tumors, loss of TGF-beta is controlled at the posttranscriptional level and is associated with expression of keratin 13, a documented marker of malignant progression. These results show that TGF-beta expression and function are compartmentalized in epidermis and epidermal tumors and that loss of TGF-beta is an early, biologically relevant risk factor for malignant progression. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Glick, A B AU - Kulkarni, A B AU - Tennenbaum, T AU - Hennings, H AU - Flanders, K C AU - O'Reilly, M AU - Sporn, M B AU - Karlsson, S AU - Yuspa, S H AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/07/01/ PY - 1993 DA - 1993 Jul 01 SP - 6076 EP - 6080 VL - 90 IS - 13 SN - 0027-8424, 0027-8424 KW - Transforming Growth Factor beta KW - 0 KW - Keratins KW - 68238-35-7 KW - Index Medicus KW - Animals KW - Carcinoma, Squamous Cell -- etiology KW - Papilloma -- pathology KW - Mice KW - Keratins -- analysis KW - Mice, Transgenic KW - Risk KW - Base Sequence KW - Papilloma -- etiology KW - Carcinoma, Squamous Cell -- pathology KW - Molecular Sequence Data KW - Papilloma -- chemistry KW - Carcinoma, Squamous Cell -- chemistry KW - Female KW - Cell Division KW - Transforming Growth Factor beta -- analysis KW - Skin Neoplasms -- etiology KW - Epidermis -- cytology KW - Skin Neoplasms -- pathology KW - Skin Neoplasms -- chemistry KW - Epidermis -- chemistry KW - Cell Transformation, Neoplastic UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75840809?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Loss+of+expression+of+transforming+growth+factor+beta+in+skin+and+skin+tumors+is+associated+with+hyperproliferation+and+a+high+risk+for+malignant+conversion.&rft.au=Glick%2C+A+B%3BKulkarni%2C+A+B%3BTennenbaum%2C+T%3BHennings%2C+H%3BFlanders%2C+K+C%3BO%27Reilly%2C+M%3BSporn%2C+M+B%3BKarlsson%2C+S%3BYuspa%2C+S+H&rft.aulast=Glick&rft.aufirst=A&rft.date=1993-07-01&rft.volume=90&rft.issue=13&rft.spage=6076&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 - 1993-08-06 N1 - Date created - 1993-08-06 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Development. 1990 Jul;109(3):585-95 [2401212] Growth Factors. 1990;3(1):45-52 [2383401] J Cell Physiol. 1991 Jul;148(1):157-73 [1907288] Carcinogenesis. 1991 Nov;12(11):2063-7 [1718620] Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9613-7 [1946376] J Cell Biol. 1992 Jan;116(1):187-96 [1730743] Proc Natl Acad Sci U S A. 1993 Jan 15;90(2):770-4 [8421714] Carcinogenesis. 1983;4(4):369-74 [6839411] Nature. 1983 May 5-11;303(5912):72-4 [6843661] Nature. 1983 Jul 7-13;304(5921):67-9 [6866091] Nature. 1984 Feb 16-22;307(5952):658-60 [6694757] Carcinogenesis. 1985 Nov;6(11):1607-10 [2414025] Cancer Res. 1986 Apr;46(4 Pt 2):2068-71 [2418960] Methods Enzymol. 1986;124:497-510 [3754925] Proc Natl Acad Sci U S A. 1992 Jun 15;89(12):5408-12 [1608949] Cancer Res. 1992 Jul 15;52(14):4042-5 [1319836] J Biol Chem. 1992 Jul 5;267(19):13702-7 [1618868] Cell Growth Differ. 1992 Feb;3(2):81-91 [1504019] Carcinogenesis. 1992 Dec;13(12):2367-73 [1473246] Environ Health Perspect. 1986 Sep;68:69-74 [3780634] Proc Natl Acad Sci U S A. 1987 Apr;84(7):2029-32 [3104907] J Cell Biol. 1987 Aug;105(2):965-75 [2887577] J Cell Biol. 1987 Dec;105(6 Pt 2):2861-76 [3320058] Nature. 1988 Jan 28;331(6154):363-5 [3422343] Cancer Res. 1988 Jun 1;48(11):3245-52 [2452688] Int J Cancer. 1989 May 15;43(5):915-21 [2714898] Mol Carcinog. 1988;1(3):171-9 [2471536] Mol Carcinog. 1989;2(1):22-6 [2499343] Mol Carcinog. 1988;1(2):96-108 [3076454] Cancer Res. 1990 Feb 1;50(3):653-7 [2105160] Proc Natl Acad Sci U S A. 1990 Jan;87(2):643-7 [2153961] Mol Endocrinol. 1990 Jan;4(1):46-52 [2157977] Cell. 1990 May 4;61(3):407-17 [2185890] Mol Carcinog. 1991;4(3):210-9 [2064727] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutations induced by saturated aqueous nitric oxide in the pSP189 supF gene in human Ad293 and E. coli MBM7070 cells. AN - 75838879; 8330336 AB - Nitric oxide is an important bioregulatory agent that may also be an endogenous and exogenous human mutagen. In order to study mutations generated following exposure of a shuttle vector-borne target gene to nitric oxide, mutations were induced in the supF gene of the pSP189 shuttle vector by treatment with nitric oxide in aerobic buffered solution followed by replication of the plasmid in either human Ad293 or Escherichia coli MBM7070 cells. The induced mutation frequency, which increased with nitric oxide dose, was 44-fold greater than the spontaneous background in human cells and > 15-fold greater than background in the bacterial cells when a total of 100 mmol of nitric oxide was oxidatively absorbed/I of pH 7.4 buffer containing the plasmid. The majority of point mutations analysed (61 and 75% for human and E. coli cells respectively) were AT-->GC transitions with GC-->AT transitions (29 and 23%) being the next most prevalent. The overall frequencies of the various point mutations seen in the supF gene were similar in the two cell types, although the distribution of hotspots showed differences. The results are consistent with a mutational mechanism initiated by deamination of DNA bases. JF - Carcinogenesis AU - Routledge, M N AU - Wink, D A AU - Keefer, L K AU - Dipple, A AD - Chemistry of Carcinogenesis Laboratory, National Cancer Institute, Frederick Cancer Research and Development Center, MD 21702. Y1 - 1993/07// PY - 1993 DA - July 1993 SP - 1251 EP - 1254 VL - 14 IS - 7 SN - 0143-3334, 0143-3334 KW - supF KW - DNA, Bacterial KW - 0 KW - Mutagens KW - Water KW - 059QF0KO0R KW - Nitric Oxide KW - 31C4KY9ESH KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Base Sequence KW - Cells, Cultured KW - Humans KW - Water -- chemistry KW - Molecular Sequence Data KW - Plasmids KW - DNA, Bacterial -- drug effects KW - DNA Replication -- drug effects KW - DNA -- drug effects KW - Nitric Oxide -- toxicity KW - Point Mutation KW - Escherichia coli -- drug effects KW - Mutagens -- toxicity KW - Escherichia coli -- genetics KW - Genes, Bacterial -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75838879?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Mutations+induced+by+saturated+aqueous+nitric+oxide+in+the+pSP189+supF+gene+in+human+Ad293+and+E.+coli+MBM7070+cells.&rft.au=Routledge%2C+M+N%3BWink%2C+D+A%3BKeefer%2C+L+K%3BDipple%2C+A&rft.aulast=Routledge&rft.aufirst=M&rft.date=1993-07-01&rft.volume=14&rft.issue=7&rft.spage=1251&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-08-18 N1 - Date created - 1993-08-18 N1 - Date revised - 2017-01-13 N1 - Gene symbol - supF N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - 32P-postlabeling analysis of IQ, MeIQx and PhIP adducts formed in vitro in DNA and polynucleotides and found in vivo in hepatic DNA from IQ-, MeIQx- and PhIP-treated monkeys. AN - 75838668; 8330355 AB - The 32P-postlabeling method was used to examine the adducts in DNA, polynucleotides, and mononucleotides reacted in vitro with the N-hydroxy and N-acetoxy derivatives of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3, 8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) or 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Adduct profiles were compared to those found in vivo in liver of cynomolgus monkeys fed IQ, MeIQx or PhIP. The N-acetoxy derivatives of IQ, MeIQx and PhIP (generated in situ from the corresponding N-hydroxylamine in the presence of acetic anhydride) each formed three principal adducts in DNA. Adduct 1 of IQ, MeIQx and PhIP was chromatographically identical to the 32P-labeled bis(phosphate) derivative of N-(deoxyguanosin-8-yl)-IQ, N-(deoxyguanosin-8-yl)-MeIQx, and N-(deoxyguanosin-8-yl)-PhIP respectively, and this adduct comprised approximately 65% of total adduct levels found in DNA in vitro. The C8-guanine adduct and the two minor adducts were also found in poly(dG-dC). poly(dG-dC), suggesting that the two minor adducts of IQ, MeIQx and PhIP are also formed on the guanine base. The N-acetoxy derivatives of IQ, MeIQx, and to a much lesser extent PhIP, also formed adducts with adenine-containing polynucleotides including poly(dA), poly(dA).poly(dT) and poly(dA-dT).poly(dA-dT), but these adenine adducts were chromatographically different from those found in DNA. The three guanine adducts of N-acetoxy-IQ, -MeIQx and -PhIP found in vitro in DNA and in guanine-containing polynucleotides were also found in the liver of monkeys fed IQ, MeIQx or PhIP respectively, indicating that metabolic activation via N-hydroxylation and esterification occurred in vivo in monkeys. With each compound, the C8-guanine adduct was the predominant adduct found in vivo. The results indicate similarities among IQ, MeIQx and PhIP in the DNA adducts formed in vitro and in vivo and substantiate the use of the 32P-postlabeling method for comparative adduct studies. JF - Carcinogenesis AU - Snyderwine, E G AU - Davis, C D AU - Nouso, K AU - Roller, P P AU - Schut, H A AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, Bethesda, MD. Y1 - 1993/07// PY - 1993 DA - July 1993 SP - 1389 EP - 1395 VL - 14 IS - 7 SN - 0143-3334, 0143-3334 KW - Imidazoles KW - 0 KW - Mutagens KW - Phosphorus Radioisotopes KW - Polynucleotides KW - Quinolines KW - Quinoxalines KW - 2-amino-3-methylimidazo(4,5-f)quinoline KW - 30GL3D3T0G KW - 2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline KW - 77500-04-0 KW - DNA KW - 9007-49-2 KW - 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine KW - 909C6UN66T KW - Index Medicus KW - Quinolines -- toxicity KW - Animals KW - Imidazoles -- toxicity KW - DNA Damage KW - Quinoxalines -- analysis KW - Quinoxalines -- toxicity KW - Imidazoles -- analysis KW - Autoradiography KW - Quinolines -- analysis KW - Haplorhini KW - Chromatography, High Pressure Liquid KW - Polynucleotides -- chemistry KW - Mutagens -- analysis KW - Liver -- drug effects KW - Mutagens -- toxicity KW - Liver -- metabolism KW - DNA -- chemistry KW - DNA -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75838668?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=32P-postlabeling+analysis+of+IQ%2C+MeIQx+and+PhIP+adducts+formed+in+vitro+in+DNA+and+polynucleotides+and+found+in+vivo+in+hepatic+DNA+from+IQ-%2C+MeIQx-+and+PhIP-treated+monkeys.&rft.au=Snyderwine%2C+E+G%3BDavis%2C+C+D%3BNouso%2C+K%3BRoller%2C+P+P%3BSchut%2C+H+A&rft.aulast=Snyderwine&rft.aufirst=E&rft.date=1993-07-01&rft.volume=14&rft.issue=7&rft.spage=1389&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-08-18 N1 - Date created - 1993-08-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - MK-801 impairs recognition memory in rhesus monkeys: comparison with cholinergic drugs. AN - 75836789; 8331575 AB - Both N-methyl-D-aspartate (NMDA) and cholinergic receptors are thought to participate in processes of learning and memory. The effects of the noncompetitive NMDA antagonist ((+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine) MK-801 on recognition memory in rhesus monkeys performing a computer-automated version of delayed nonmatching-to-sample DNMS were compared to those of the cholinergic compounds physostigmine and scopolamine. In the sample phase of the test, 20 symbols were presented sequentially every 30 sec on a color monitor fitted with a touch-sensitive screen. These symbols were then presented again in the same order as before, but each symbol was now paired with a different novel symbol. A monkey was rewarded with a food pellet if it touched the symbol in the sample phase and the previously unseen symbol in the choice phase. Physostigmine (3.2, 10 and 32 micrograms/kg), scopolamine (3.2, 10, 17.8 and 32 micrograms/kg) or MK-801 (3.2, 10 and 32 micrograms/kg) was injected i.m. 20, 20 and 30 min before testing, respectively. The highest doses of both MK-801 and scopolamine significantly impaired performance. In addition, scopolamine, but not MK-801, prolonged response latency, whereas MK-801, but not scopolamine, increased response bias. Physostigmine produced a small but significant increase in correct responses at the intermediate dose, but not at the highest dose. These results suggest that both the glutamatergic and the cholinergic systems participate in visual recognition memory in monkeys, though probably by different mechanisms. JF - The Journal of pharmacology and experimental therapeutics AU - Ogura, H AU - Aigner, T G AD - Laboratory of Neuropsychology, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland. Y1 - 1993/07// PY - 1993 DA - July 1993 SP - 60 EP - 64 VL - 266 IS - 1 SN - 0022-3565, 0022-3565 KW - Scopolamine Hydrobromide KW - 451IFR0GXB KW - Dizocilpine Maleate KW - 6LR8C1B66Q KW - Physostigmine KW - 9U1VM840SP KW - Index Medicus KW - Animals KW - Memory Disorders -- chemically induced KW - Dose-Response Relationship, Drug KW - Macaca mulatta KW - Male KW - Learning Disorders -- chemically induced KW - Scopolamine Hydrobromide -- pharmacology KW - Memory -- drug effects KW - Physostigmine -- pharmacology KW - Learning -- drug effects KW - Dizocilpine Maleate -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75836789?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=MK-801+impairs+recognition+memory+in+rhesus+monkeys%3A+comparison+with+cholinergic+drugs.&rft.au=Ogura%2C+H%3BAigner%2C+T+G&rft.aulast=Ogura&rft.aufirst=H&rft.date=1993-07-01&rft.volume=266&rft.issue=1&rft.spage=60&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 - 1993-08-19 N1 - Date created - 1993-08-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Leukemia, lymphoma, and multiple myeloma after pelvic radiotherapy for benign disease. AN - 75836442; 8327655 AB - The relationship between exposure to sparsely ionizing radiation and mortality due to cancers of hematopoietic and lymphopoietic tissues was studied among 12,955 women treated for benign gynecological disorders at any of 17 hospitals in New England or New York State and followed for an average of 25 years; 9770 women were treated by radiation (intracavitary 226Ra, external-beam X rays), while 3185 were treated by other methods, including curettage, surgery, and hormones. The average age at treatment was 46.5 years, and the mean dose to active bone marrow among irradiated women was 119 cGy. Forty deaths due to acute, myelocytic, or monocytic leukemia were observed among irradiated women. This number was 70% higher than expected based on U.S. mortality rates [standardized mortality ratio (SMR) = 1.7; 90% confidence interval (CI) 1.3-2.3]. A deficit was recorded among nonirradiated women, based on three observed deaths (SMR = 0.5; 90% CI 0.1-1.2). A well-defined gradient in the SMR with dose among exposed women was not detected. The SMR was highest within 5 years after irradiation but remained elevated even after 30 years. The temporal pattern differed by subtype of leukemia: excess mortality due to chronic myelocytic leukemia occurred almost exclusively within the first 15 years, whereas the SMR for acute leukemia, though also elevated, varied little over time. Cancers of lymphoreticular tissue occurred more often than expected based on U.S. mortality rates, but not appreciably differently for irradiated and nonirradiated women. There was little or no evidence of effects attributable to radiotherapy for chronic lymphocytic leukemia [relative risk (RR) = 1.1; 90% CI 0.5-3.0], Hodgkin's disease (RR = 0.9; 90% CI 0.3-3.2), non-Hodgkin's lymphoma (RR = 0.9; 90% CI 0.6-1.6), or multiple myeloma (RR = 0.6; 90% CI 0.3-1.4). These results corroborate previous findings indicating that acute and myelocytic leukemias are the most prominent malignancies after exposure to sparsely ionizing radiation, occurring in excess shortly after irradiation, and that lymphomas are either not caused by radiation or are induced only rarely. JF - Radiation research AU - Inskip, P D AU - Kleinerman, R A AU - Stovall, M AU - Cookfair, D L AU - Hadjimichael, O AU - Moloney, W C AU - Monson, R R AU - Thompson, W D AU - Wactawski-Wende, J AU - Wagoner, J K AD - Radiation Epidemiology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/07// PY - 1993 DA - July 1993 SP - 108 EP - 124 VL - 135 IS - 1 SN - 0033-7587, 0033-7587 KW - Index Medicus KW - Space life sciences KW - Radiotherapy Dosage KW - Humans KW - Middle Aged KW - Hematology KW - Follow-Up Studies KW - Bone Marrow -- radiation effects KW - Female KW - Cause of Death KW - Lymphoma -- etiology KW - Leukemia, Radiation-Induced -- blood KW - Neoplasms, Radiation-Induced KW - Radiotherapy -- methods KW - Radiotherapy -- adverse effects KW - Genital Diseases, Female -- radiotherapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75836442?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Leukemia%2C+lymphoma%2C+and+multiple+myeloma+after+pelvic+radiotherapy+for+benign+disease.&rft.au=Inskip%2C+P+D%3BKleinerman%2C+R+A%3BStovall%2C+M%3BCookfair%2C+D+L%3BHadjimichael%2C+O%3BMoloney%2C+W+C%3BMonson%2C+R+R%3BThompson%2C+W+D%3BWactawski-Wende%2C+J%3BWagoner%2C+J+K&rft.aulast=Inskip&rft.aufirst=P&rft.date=1993-07-01&rft.volume=135&rft.issue=1&rft.spage=108&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 - 1993-08-11 N1 - Date created - 1993-08-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regulation of hair follicle development: an in vitro model for hair follicle invasion of dermis and associated connective tissue remodeling. AN - 75836306; 8326151 AB - During embryonic development presumptive hair follicle cells of epithelial and mesenchymal origin are determined in defined body locations. This is followed by rapid proliferation of epithelial cells and associated penetration into the dermis in response to as yet undetermined signals. A collagen matrix culture system, which maintains the three-dimensional relationships of hair follicle cells to each other, was developed to study the regulation of the enlargement of immature hair follicles and the accompanying remodeling of the dermis. In studies with a heterogeneous dermis-derived preparation of murine hair follicles, ranging in size from the earliest down-growing budding cell mass to hair-forming follicles, we had previously shown that cell proliferation was stimulated by cholera toxin and epidermal growth factor, but only the epidermal growth factor-stimulated proliferation was accompanied by digestion of the collagen matrix due to release of collagenolytic enzymes. Further studies revealed that transforming growth factor-alpha also stimulated hair follicle cell proliferation and collagenase release. However, although transforming growth factor-beta inhibited the transforming growth factor-alpha-stimulated proliferation, it enhanced the release and activation of collagenases and other gelatin-degrading enzymes detectable by gelatin zymography. Stimulation of collagenolytic activity depended on the three-dimensional hair follicle structure and did not occur in monolayer cultures of hair follicle cells. Comparison of hair follicle buds with more developed dermis-derived hair follicles, plated at the same cell density (based on DNA content), suggested that a greater fraction of cells in the bud-stage follicle responded to the growth factors by release of collagenases. Possibly only the cells in the advancing portion of growing hair follicles that are closest to the dermal papilla cell cluster produce the collagenases in response to growth factors. To examine the participation of dermal papilla cells in collagenase release and activation, several immortalized rat whisker dermal papilla cell lines were co-cultured with mouse hair follicle buds. Co-culture resulted in a marked enlargement of follicles as well as activation of the 92-kDa type IV collagenase, produced by hair follicle buds, that correlated with ability of the dermal papilla cells to stimulate hair formation in grafts of hair follicle buds on nude mice. Dermal papilla cells cultured alone produced the 72-kDa type IV collagenase, which was also activated during co-culture with hair follicle buds. Thus, two activities, both relevant for hair follicle development, namely, cell proliferation and release and activation of collagenases, have been stimulated in immature hair follicle buds by either growth-factor supplementation or interaction with dermal papilla cells.(ABSTRACT TRUNCATED AT 400 WORDS) JF - The Journal of investigative dermatology AU - Yuspa, S H AU - Wang, Q AU - Weinberg, W C AU - Goodman, L AU - Ledbetter, S AU - Dooley, T AU - Lichti, U AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, MD 20892. Y1 - 1993/07// PY - 1993 DA - July 1993 SP - 27S EP - 32S VL - 101 IS - 1 Suppl SN - 0022-202X, 0022-202X KW - Growth Substances KW - 0 KW - Collagenases KW - EC 3.4.24.- KW - Index Medicus KW - Animals KW - Cells, Cultured KW - Growth Substances -- pharmacology KW - Epidermis -- cytology KW - Enzyme Activation -- drug effects KW - Mice KW - Mice, Inbred BALB C KW - 3T3 Cells -- enzymology KW - Collagenases -- metabolism KW - Hair -- growth & development KW - Connective Tissue -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75836306?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+investigative+dermatology&rft.atitle=Regulation+of+hair+follicle+development%3A+an+in+vitro+model+for+hair+follicle+invasion+of+dermis+and+associated+connective+tissue+remodeling.&rft.au=Yuspa%2C+S+H%3BWang%2C+Q%3BWeinberg%2C+W+C%3BGoodman%2C+L%3BLedbetter%2C+S%3BDooley%2C+T%3BLichti%2C+U&rft.aulast=Yuspa&rft.aufirst=S&rft.date=1993-07-01&rft.volume=101&rft.issue=1+Suppl&rft.spage=27S&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+investigative+dermatology&rft.issn=0022202X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-08-11 N1 - Date created - 1993-08-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chrysotile asbestos upregulates gene expression and production of alpha-receptors for platelet-derived growth factor (PDGF-AA) on rat lung fibroblasts. AN - 75833234; 8392089 AB - PDGF isoforms have been postulated to serve as mediators of fibroblast proliferation and chemotaxis during lung fibrogenesis induced by asbestos inhalation. We have studied the interaction of chrysotile asbestos fibers with rat lung fibroblasts (RLF) in vitro and the consequent changes in PDGF receptor mRNA expression, PDGF binding, and mitogenic activity of PDGF isoforms. Northern blot analysis revealed that mRNA for the PDGF-receptor alpha subtype (PDGF-R alpha) on RLF was upregulated after a 24-h exposure to asbestos in culture (0.5-15 micrograms fibers/cm2). [125I]PDGF-BB receptor assays showed that normal RLF possess mainly PDGF-R beta and a paucity of PDGF-R alpha. In agreement with the Northern data, saturation binding of [125I]PDGF-BB to RLF exposed to asbestos demonstrated an approximately 40% increase in binding sites accompanied by a twofold decrease in receptor affinity. Treating asbestos-exposed RLF with PDGF-AA, which binds only PDGF-R alpha, blocked the PDGF binding sites that were upregulated by fiber exposure. PDGF-AA had increased mitogenic potency for fiber-exposed RLF, but PDGF-BB was a less potent mitogen for these RLF. Nonfibrogenic carbonyl iron spheres induced similar changes in PDGF growth responses. These data show that inorganic particulates alter the PDGF-R alpha population on RLF without significant change in PDGF-R beta. JF - The Journal of clinical investigation AU - Bonner, J C AU - Goodell, A L AU - Coin, P G AU - Brody, A R AD - Laboratory of Pulmonary Pathobiology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1993/07// PY - 1993 DA - July 1993 SP - 425 EP - 430 VL - 92 IS - 1 SN - 0021-9738, 0021-9738 KW - Asbestos, Serpentine KW - 0 KW - Platelet-Derived Growth Factor KW - RNA, Messenger KW - Asbestos KW - 1332-21-4 KW - Receptors, Platelet-Derived Growth Factor KW - EC 2.7.10.1 KW - Abridged Index Medicus KW - Index Medicus KW - Rats KW - Gene Expression -- drug effects KW - Animals KW - Cells, Cultured KW - In Vitro Techniques KW - Cell Division -- drug effects KW - Up-Regulation KW - RNA, Messenger -- genetics KW - Fibroblasts KW - Receptors, Platelet-Derived Growth Factor -- metabolism KW - Receptors, Platelet-Derived Growth Factor -- classification KW - Platelet-Derived Growth Factor -- metabolism KW - Lung -- cytology KW - Asbestos -- pharmacology KW - Receptors, Platelet-Derived Growth Factor -- genetics KW - Platelet-Derived Growth Factor -- classification KW - Lung -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75833234?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Chrysotile+asbestos+upregulates+gene+expression+and+production+of+alpha-receptors+for+platelet-derived+growth+factor+%28PDGF-AA%29+on+rat+lung+fibroblasts.&rft.au=Bonner%2C+J+C%3BGoodell%2C+A+L%3BCoin%2C+P+G%3BBrody%2C+A+R&rft.aulast=Bonner&rft.aufirst=J&rft.date=1993-07-01&rft.volume=92&rft.issue=1&rft.spage=425&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 - 1993-08-12 N1 - Date created - 1993-08-12 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Am J Pathol. 1988 Apr;131(1):156-70 [2833103] J Biol Chem. 1992 Sep 5;267(25):18032-9 [1325456] Am J Med. 1981 Mar;70(3):542-68 [7011012] J Cell Biol. 1982 Feb;92(2):584-8 [7061598] N Engl J Med. 1982 Jun 17;306(24):1446-55 [7043267] Am J Pathol. 1982 Oct;109(1):107-14 [7124904] J Cell Physiol. 1982 Nov;113(2):261-6 [6184376] Proc Natl Acad Sci U S A. 1983 Apr;80(7):1919-23 [6300879] Cell. 1985 Nov;43(1):277-86 [2416458] N Engl J Med. 1986 Feb 20;314(8):488-500 [3511384] Cell. 1986 Jul 18;46(2):155-69 [3013421] N Engl J Med. 1987 Jul 23;317(4):202-9 [3600711] Anal Biochem. 1987 Apr;162(1):156-9 [2440339] J Cell Biol. 1988 Feb;106(2):403-13 [2828383] Exp Lung Res. 1988;14(1):51-66 [2830106] FASEB J. 1988 Apr;2(7):2272-7 [3280379] Science. 1988 Jun 10;240(4858):1529-31 [2836952] EMBO J. 1988 May;7(5):1387-93 [2842148] Science. 1989 Jan 20;243(4889):393-6 [2783498] Am J Pathol. 1989 Jan;134(1):133-40 [2913821] J Biol Chem. 1989 May 15;264(14):8120-5 [2542264] J Biol Chem. 1989 May 25;264(15):8771-8 [2542288] J Biol Chem. 1989 May 25;264(15):8905-12 [2542295] Proc Natl Acad Sci U S A. 1989 Jul;86(13):4917-21 [2544881] J Cell Physiol. 1989 Aug;140(2):295-304 [2745564] J Clin Invest. 1990 Mar;85(3):916-20 [2155930] Am J Pathol. 1990 Mar;136(3):695-705 [2156434] J Clin Invest. 1990 Jun;85(6):2023-7 [2347924] J Biol Chem. 1990 Jun 25;265(18):10238-43 [2162342] Proc Natl Acad Sci U S A. 1990 Oct;87(19):7385-9 [2170975] Cell. 1990 Nov 2;63(3):515-24 [2171777] Am J Respir Cell Mol Biol. 1990 Dec;3(6):595-602 [1701306] J Biol Chem. 1991 Jun 5;266(16):10143-7 [1709926] Carcinogenesis. 1991 Aug;12(8):1499-502 [1650293] Am J Respir Cell Mol Biol. 1991 Dec;5(6):539-47 [1958381] J Exp Med. 1992 May 1;175(5):1227-34 [1314885] Proc Natl Acad Sci U S A. 1988 Apr;85(8):2810-4 [3282240] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In vivo regulation of murine hair growth: insights from grafting defined cell populations onto nude mice. AN - 75830570; 8326145 AB - The nude mouse graft model for testing the hair-forming ability of selected cell populations has considerable potential for providing insights into factors that are important for hair follicle development and proper hair formation. We have developed a minimal component system consisting of immature hair follicle buds from newborn pigmented C57BL/6 mice and adenovirus E1A-immortalized rat vibrissa dermal papilla cells. Hair follicle buds contribute to formation of hairless skin when grafted alone or with Swiss 3T3 cells, but produce densely haired skin when grafted with a fresh dermal cell preparation. The fresh dermal cell preparation represents the single cell fraction after hair follicles have been removed from a collagenase digest of newborn mouse dermis. It provides dermal papilla cells, fibroblasts, and possibly other important growth factor-producing cell types. Rat vibrissa dermal papilla cells supported dense hair growth at early passage in culture but progressively lost this potential during repeated passage in culture. Of 19 E1A-immortalized, clonally derived rat vibrissa dermal papilla cell lines, the four most positive clones supported hair growth to the extent of approximately 200 to 300 hairs per 1-2 cm2 graft area. The remaining clones were moderately positive (five clones), weakly positive (three clones), or negative (seven clones). Swiss 3T3 cells prevented contraction of the graft area but did not appear to affect the number of hairs in the graft site produced by dermal papilla cells plus hair follicle buds alone. The relatively low hair density (estimated 1-5% of normal) resulting from grafts of hair follicle buds with the most positive of the immortalized dermal papilla cell clones compared to fresh dermal cells suggests that optimal reconstitution of hair growth requires some function of dermal papilla cells partially lost during the immortalization process and possibly the contribution of other cell types present in the fresh dermal cell preparation, which is not supplied by the Swiss 3T3 cells. The current graft system, comprising hair follicle buds and immortalized dermal papilla cell clones, provides an assay for positive or negative influences on hair growth exerted by added selected cell types, growth factors, or other substances. Characterization of the phenotype of the dermal papilla cell lines, which differ in their ability to support hair growth when grafted with hair follicle buds, may provide insight into specific dermal papilla cell properties important for their function in this system. JF - The Journal of investigative dermatology AU - Lichti, U AU - Weinberg, W C AU - Goodman, L AU - Ledbetter, S AU - Dooley, T AU - Morgan, D AU - Yuspa, S H AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, NIH, Bethesda, MD 20892. Y1 - 1993/07// PY - 1993 DA - July 1993 SP - 124S EP - 129S VL - 101 IS - 1 Suppl SN - 0022-202X, 0022-202X KW - Index Medicus KW - Evaluation Studies as Topic KW - Animals KW - Cells, Cultured KW - Skin Transplantation -- physiology KW - Mice, Nude KW - Mice KW - Mice, Inbred BALB C KW - Hair -- growth & development KW - Skin -- cytology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75830570?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+investigative+dermatology&rft.atitle=In+vivo+regulation+of+murine+hair+growth%3A+insights+from+grafting+defined+cell+populations+onto+nude+mice.&rft.au=Lichti%2C+U%3BWeinberg%2C+W+C%3BGoodman%2C+L%3BLedbetter%2C+S%3BDooley%2C+T%3BMorgan%2C+D%3BYuspa%2C+S+H&rft.aulast=Lichti&rft.aufirst=U&rft.date=1993-07-01&rft.volume=101&rft.issue=1+Suppl&rft.spage=124S&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+investigative+dermatology&rft.issn=0022202X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-08-11 N1 - Date created - 1993-08-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interleukin 4 suppresses interleukin 2 and interferon gamma production by naive T cells stimulated by accessory cell-dependent receptor engagement. AN - 75830334; 8100998 AB - Interleukin 2 (IL-2) and interferon gamma (IFN-gamma) production by CD4+ T cells and IFN-gamma production by CD8+ T cells from naive mice in response to soluble anti-CD3 and antigen-presenting cells (APCs) were strikingly inhibited by culture in the presence of IL-4. IL-4 decreased IL-2 and IFN-gamma mRNA levels after 15-24 hr but gave relatively little decrease in these mRNAs at 6-12 hr after stimulation with soluble anti-CD3. A 16-hr preculture of T cells with anti-CD3, APCs, and IL-4 was sufficient to inhibit subsequent production of IL-2 and IFN-gamma in response to restimulation in the absence of IL-4. Furthermore, IL-4 treatment of T cells purified 24 hr after stimulation inhibited their capacity to subsequently produce IL-2 in response to anti-CD3 and APCs, indicating that T cells were targets of IL-4-mediated inhibition. IL-4 blocked acute IL-2 production in response to a cytochrome c peptide of T cells derived from transgenic mice expressing T-cell receptors specific for cytochrome c but it did not block IL-2 production by such cells after they had been primed in vitro. Nor did IL-4 inhibit production of IFN-gamma by cloned T cells in response to antigen and APCs or production of IL-2 and IFN-gamma by naive T cells in response to phorbol ester and calcium ionophore. These results indicate that IL-4 strikingly inhibits IL-2 and IFN-gamma production by naive T cells in response to accessory cell-dependent, receptor-mediated stimulation (i.e., soluble anti-CD3 and APCs or antigen and APCs) but does not inhibit accessory cell-independent stimulation of naive T cells or accessory cell-dependent receptor-mediated stimulation of recently primed T cells or cloned T-cell lines. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Tanaka, T AU - Hu-Li, J AU - Seder, R A AU - Fazekas de St Groth, B AU - Paul, W E AD - Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/07/01/ PY - 1993 DA - 1993 Jul 01 SP - 5914 EP - 5918 VL - 90 IS - 13 SN - 0027-8424, 0027-8424 KW - Interleukin-2 KW - 0 KW - Interleukin-4 KW - 207137-56-2 KW - Ionomycin KW - 56092-81-0 KW - Interferon-gamma KW - 82115-62-6 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - CD4-Positive T-Lymphocytes -- metabolism KW - Cells, Cultured KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Mice KW - Ionomycin -- pharmacology KW - Mice, Inbred BALB C KW - CD4-Positive T-Lymphocytes -- drug effects KW - Female KW - Lymphocyte Activation KW - T-Lymphocytes -- metabolism KW - Antigen-Presenting Cells -- physiology KW - Interleukin-4 -- pharmacology KW - Interleukin-2 -- biosynthesis KW - Interferon-gamma -- biosynthesis KW - T-Lymphocytes -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75830334?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Interleukin+4+suppresses+interleukin+2+and+interferon+gamma+production+by+naive+T+cells+stimulated+by+accessory+cell-dependent+receptor+engagement.&rft.au=Tanaka%2C+T%3BHu-Li%2C+J%3BSeder%2C+R+A%3BFazekas+de+St+Groth%2C+B%3BPaul%2C+W+E&rft.aulast=Tanaka&rft.aufirst=T&rft.date=1993-07-01&rft.volume=90&rft.issue=13&rft.spage=5914&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 - 1993-08-06 N1 - Date created - 1993-08-06 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Immunol Rev. 1979;47:63-90 [398327] J Immunol. 1993 Mar 15;150(6):2112-20 [7680682] Immunol Rev. 1982;69:5-23 [6984001] Nature. 1985 Mar 7-13;314(6006):98-100 [3919312] Nature. 1985 May 23-29;315(6017):333-6 [2582266] J Exp Med. 1985 Nov 1;162(5):1695-708 [3877141] Proc Natl Acad Sci U S A. 1987 Mar;84(5):1374-8 [2950524] J Immunol Methods. 1987 Nov 23;104(1-2):137-42 [3119723] J Exp Med. 1987 Nov 1;166(5):1229-44 [2960769] J Exp Med. 1987 Dec 1;166(6):1774-87 [2960773] Immunol Rev. 1988 Feb;102:77-105 [2966763] J Immunol Methods. 1989 Jan 17;116(2):151-8 [2642947] J Immunol. 1989 Feb 1;142(3):800-7 [2783601] Eur J Immunol. 1989 Apr;19(4):617-23 [2567241] J Exp Med. 1989 Nov 1;170(5):1751-6 [2530302] J Exp Med. 1990 Jan 1;171(1):115-27 [2104918] J Exp Med. 1990 Sep 1;172(3):921-9 [2117636] J Immunol. 1990 Dec 1;145(11):3796-806 [2147202] J Immunol. 1991 Jun 1;146(11):3831-9 [1827817] J Immunol. 1991 Jun 15;146(12):4209-14 [1674955] J Immunol. 1992 Feb 15;148(4):1182-7 [1531351] J Immunol. 1992 Mar 15;148(6):1652-6 [1347305] J Exp Med. 1992 Jul 1;176(1):19-25 [1535368] Proc Natl Acad Sci U S A. 1992 Jul 1;89(13):6065-9 [1385868] J Exp Med. 1992 Oct 1;176(4):1091-8 [1328464] J Exp Med. 1980 Aug 1;152(2):280-95 [6156984] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evidence that the SKI antiviral system of Saccharomyces cerevisiae acts by blocking expression of viral mRNA. AN - 75822622; 8321235 AB - The SKI2 gene is part of a host system that represses the copy number of the L-A double-stranded RNA (dsRNA) virus and its satellites M and X dsRNA, of the L-BC dsRNA virus, and of the single-stranded replicon 20S RNA. We show that SKI2 encodes a 145-kDa protein with motifs characteristic of helicases and nucleolar proteins and is essential only in cells carrying M dsRNA. Unexpectedly, Ski2p does not repress M1 dsRNA copy number when M1 is supported by aN L-A cDNA clone; nonetheless, it did lower the levels of M1 dsRNA-encoded toxin produced. Since toxin secretion from cDNA clones of M1 is unaffected by Ski2p, these data suggest that Ski2p acts by specifically blocking translation of viral mRNAs, perhaps recognizing the absence of cap or poly(A). In support of this idea, we find that Ski2p represses production of beta-galactosidase from RNA polymerase I [no cap and no poly(A)] transcripts but not from RNA polymerase II (capped) transcripts. JF - Molecular and cellular biology AU - Widner, W R AU - Wickner, R B AD - Section on Genetics of Simple Eukaryotes, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892. Y1 - 1993/07// PY - 1993 DA - July 1993 SP - 4331 EP - 4341 VL - 13 IS - 7 SN - 0270-7306, 0270-7306 KW - SKI2 KW - Antiviral Agents KW - 0 KW - DNA, Fungal KW - Fungal Proteins KW - Multienzyme Complexes KW - Nuclear Proteins KW - RNA, Double-Stranded KW - RNA, Messenger KW - RNA, Viral KW - SKI2 protein, S cerevisiae KW - Saccharomyces cerevisiae Proteins KW - RNA Polymerase II KW - EC 2.7.7.- KW - RNA Polymerase I KW - EC 2.7.7.6 KW - beta-Galactosidase KW - EC 3.2.1.23 KW - Index Medicus KW - RNA Polymerase I -- metabolism KW - Multienzyme Complexes -- metabolism KW - RNA Polymerase II -- metabolism KW - Gene Expression Regulation, Viral KW - Amino Acid Sequence KW - RNA, Double-Stranded -- antagonists & inhibitors KW - Cloning, Molecular KW - RNA, Messenger -- antagonists & inhibitors KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Promoter Regions, Genetic KW - Restriction Mapping KW - beta-Galactosidase -- antagonists & inhibitors KW - Molecular Sequence Data KW - beta-Galactosidase -- genetics KW - Nuclear Proteins -- metabolism KW - Saccharomyces cerevisiae -- genetics KW - Fungal Proteins -- metabolism KW - RNA, Viral -- antagonists & inhibitors KW - Genes, Fungal KW - Saccharomyces cerevisiae -- growth & development KW - Fungal Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75822622?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Evidence+that+the+SKI+antiviral+system+of+Saccharomyces+cerevisiae+acts+by+blocking+expression+of+viral+mRNA.&rft.au=Widner%2C+W+R%3BWickner%2C+R+B&rft.aulast=Widner&rft.aufirst=W&rft.date=1993-07-01&rft.volume=13&rft.issue=7&rft.spage=4331&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 - 1993-07-30 N1 - Date created - 1993-07-30 N1 - Date revised - 2017-01-13 N1 - Gene symbol - SKI2 N1 - Genetic sequence - L13469; GENBANK N1 - SuppNotes - Cited By: Yeast. 1993 Jan;9(1):43-51 [8442386] Yeast. 1992 Dec;8(12):1007-14 [1284101] Mol Cell Biol. 1984 Apr;4(4):761-70 [6371496] Cell. 1984 Dec;39(3 Pt 2):663-73 [6096018] Proc Natl Acad Sci U S A. 1985 Jan;82(2):488-92 [3881765] Virology. 1986 Apr 15;150(1):299-303 [3006342] Mol Cell Biol. 1985 Nov;5(11):2913-23 [3018486] Proc Natl Acad Sci U S A. 1986 Oct;83(20):7826-30 [3463999] Mol Cell Biol. 1986 Feb;6(2):674-87 [3023862] Gene. 1986;45(3):299-310 [3026915] Virology. 1987 Mar;157(1):252-6 [3029964] Gene. 1987;52(2-3):225-33 [3038686] Mol Cell Biol. 1987 Aug;7(8):2947-55 [2823109] Genetics. 1987 Nov;117(3):399-408 [3319767] Methods Enzymol. 1987;155:156-65 [3323819] J Virol. 1988 Apr;62(4):1278-85 [3279233] Methods Cell Biol. 1975;11:221-33 [1102849] Nucleic Acids Res. 1976 Oct;3(10):2427-36 [792814] J Biol Chem. 1977 Dec 25;252(24):9010-7 [336627] Proc Natl Acad Sci U S A. 1978 Sep;75(9):4224-8 [360211] J Bacteriol. 1978 Dec;136(3):1002-7 [363683] Cell. 1978 Dec;15(4):1439-46 [215328] Nucleic Acids Res. 1979 Jan;6(1):27-39 [106368] J Mol Biol. 1979 Jan 25;127(3):297-308 [372542] J Virol. 1993 May;67(5):2764-71 [8474174] Yeast. 1993 Mar;9(3):251-66 [8488726] Mol Cell Biol. 1984 Jan;4(1):92-100 [6366515] Cell. 1980 Feb;19(2):403-14 [6986991] Proc Natl Acad Sci U S A. 1980 Jan;77(1):527-30 [6987655] J Bacteriol. 1980 Jul;143(1):463-70 [6995444] Cell. 1980 Aug;21(1):217-26 [6996833] J Bacteriol. 1983 Jan;153(1):163-8 [6336730] Nucleic Acids Res. 1983 Feb 25;11(4):1077-97 [6338480] Methods Enzymol. 1983;101:181-91 [6310321] Mol Cell Biol. 1984 Jan;4(1):101-9 [6199660] Mol Cell Biol. 1984 Jan;4(1):181-7 [6366509] Gene. 1987;60(2-3):237-43 [3327750] Nature. 1988 May 5;333(6168):22-3 [3362205] J Mol Biol. 1988 Apr 20;200(4):627-38 [3137346] Cell. 1988 Nov 18;55(4):663-71 [2460245] Genetics. 1988 Sep;120(1):95-108 [2851484] J Biol Chem. 1989 Apr 25;264(12):6716-23 [2651431] Mol Cell Biol. 1989 Mar;9(3):1243-54 [2657388] Dev Biol. 1989 Jul;134(1):246-57 [2567251] Genetics. 1989 May;122(1):19-27 [2659436] Yeast. 1989 May-Jun;5(3):149-58 [2660461] Nucleic Acids Res. 1989 Jun 26;17(12):4713-30 [2546125] EMBO J. 1989 Dec 20;8(13):4015-24 [2686980] Curr Genet. 1989 Sep;16(3):139-43 [2557163] J Biol Chem. 1990 Feb 5;265(4):2209-15 [2298745] Experientia. 1990 Feb 15;46(2):193-200 [2406163] Proc Natl Acad Sci U S A. 1990 Oct;87(19):7628-32 [1699230] J Mol Biol. 1990 Oct 5;215(3):403-10 [2231712] J Virol. 1991 Jan;65(1):155-61 [1985195] Proc Natl Acad Sci U S A. 1991 Jan 1;88(1):174-8 [1986362] J Biol Chem. 1991 Jul 5;266(19):12772-8 [2061340] J Biol Chem. 1991 Jul 5;266(19):12779-83 [1648104] Nucleic Acids Res. 1991 Sep 25;19(18):4949-53 [1656383] EMBO J. 1992 Feb;11(2):673-82 [1531632] Proc Natl Acad Sci U S A. 1992 Mar 15;89(6):2185-9 [1549580] DNA Seq. 1992;2(4):203-10 [1352711] EMBO J. 1992 Jul;11(7):2655-64 [1628625] Mol Cell Biol. 1992 Aug;12(8):3390-8 [1630453] J Biol Chem. 1992 Aug 15;267(23):16252-8 [1644811] Mol Cell Biol. 1992 Sep;12(9):3865-71 [1508189] Nature. 1992 Oct 22;359(6397):746-9 [1436038] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Induction of cellular p53 activity by DNA-damaging agents and growth arrest. AN - 75811602; 8321226 AB - The tumor suppressor p53 can function as a sequence-specific transcription factor and is required for activation by ionizing radiation (IR) of one or more downstream effector genes, such as the human GADD45 gene. One important consequence of IR that is probably mediated by these downstream effector genes is activation of the p53-mediated G1 cell cycle checkpoint. While the induction of reporter constructs containing p53-binding sites has already been demonstrated with p53 expression vectors, we have now demonstrated the direct activation of such a construct after treatment of the human RKO line, which has a normal p53 phenotype, with various types of DNA-damaging agents and also after growth arrest produced by medium depletion (starvation). IR, UV radiation, and methylmethane sulfonate were found to induce p53 activity when a stably integrated reporter construct containing functional p53-binding sites was used and also in mobility shift assays with a p53-binding site from the GADD45 gene, and IR-inducible gene previously associated with growth arrest. The same cell treatments that induced this p53 activity also caused an increase in cellular p53 protein levels. The response in cells lacking normal p53 or in RKO cells expressing a dominant negative mutant p53 was markedly reduced. Interestingly, the spectrum of effective inducing agents for the above-described experiments was similar to that which induces GADD45 either in cells with a normal p53 status or, with the exception of IR, in cells lacking normal p53. These results indicate a role for p53 in the IR pathway, which is completely p53 dependent, and in other genotoxic stress responses, in which p53 has a cooperative effect but is not required. JF - Molecular and cellular biology AU - Zhan, Q AU - Carrier, F AU - Fornace, A J AD - Laboratory of Molecular Pharmacology, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1993/07// PY - 1993 DA - July 1993 SP - 4242 EP - 4250 VL - 13 IS - 7 SN - 0270-7306, 0270-7306 KW - GADD45 KW - Mutagens KW - 0 KW - Tumor Suppressor Protein p53 KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Animals KW - Ultraviolet Rays KW - Humans KW - Cell Division -- drug effects KW - Transcription, Genetic KW - Binding Sites KW - Cloning, Molecular KW - Base Sequence KW - Chickens KW - Promoter Regions, Genetic KW - Tumor Cells, Cultured KW - Molecular Sequence Data KW - Suppression, Genetic KW - Signal Transduction KW - Cell Division -- radiation effects KW - DNA Damage KW - Mutagens -- pharmacology KW - Tumor Suppressor Protein p53 -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75811602?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Induction+of+cellular+p53+activity+by+DNA-damaging+agents+and+growth+arrest.&rft.au=Zhan%2C+Q%3BCarrier%2C+F%3BFornace%2C+A+J&rft.aulast=Zhan&rft.aufirst=Q&rft.date=1993-07-01&rft.volume=13&rft.issue=7&rft.spage=4242&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 - 1993-07-30 N1 - Date created - 1993-07-30 N1 - Date revised - 2017-01-13 N1 - Gene symbol - GADD45 N1 - SuppNotes - Cited By: Mol Cell Biol. 1982 Sep;2(9):1044-51 [6960240] Nat Genet. 1992 Apr;1(1):45-9 [1301998] Nucleic Acids Res. 1983 Mar 11;11(5):1475-89 [6828386] Mol Cell Biol. 1984 Sep;4(9):1689-94 [6092932] Virology. 1987 Mar;157(1):211-9 [3029959] Mol Cell Biol. 1987 Aug;7(8):2745-52 [3670292] Cancer Res. 1989 Apr 1;49(7):1687-92 [2466559] J Biol Chem. 1989 Jun 5;264(16):9539-46 [2722849] Lab Invest. 1989 Aug;61(2):143-61 [2666742] Mol Cell Biol. 1989 Oct;9(10):4196-203 [2573827] Proc Natl Acad Sci U S A. 1989 Dec;86(24):10104-7 [2602359] Science. 1990 Aug 24;249(4971):912-5 [2144057] J Biol Chem. 1990 Sep 5;265(25):15211-8 [1697587] Mol Cell Biol. 1991 Feb;11(2):1009-16 [1990262] New Biol. 1990 Aug;2(8):712-8 [2282368] J Natl Cancer Inst. 1991 Apr 3;83(7):480-4 [2005631] New Biol. 1991 Sep;3(9):825-33 [1931825] Cancer Res. 1991 Dec 1;51(23 Pt 1):6304-11 [1933891] Virology. 1992 Jan;186(1):133-47 [1727595] Mol Cell Biol. 1992 Apr;12(4):1856-63 [1312672] Mol Cell Biol. 1992 Jun;12(6):2866-71 [1588974] Science. 1992 May 8;256(5058):827-30 [1589764] J Virol. 1992 Aug;66(8):4757-62 [1352831] Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7491-5 [1323840] Cell. 1992 Aug 21;70(4):523-6 [1505019] Cell. 1992 Nov 13;71(4):587-97 [1423616] Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):12028-32 [1465435] Cell. 1992 Dec 24;71(7):1081-91 [1473146] Science. 1993 Jan 1;259(5091):84-7 [8418500] Ann N Y Acad Sci. 1992 Nov 21;663:139-53 [1482047] Proc Natl Acad Sci U S A. 1993 May 1;90(9):3988-92 [8387205] Erratum In: Mol Cell Biol 1993 Sep;13(9):5928 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Antisera specific for carcinogen-DNA adducts and carcinogen-modified DNA: applications for detection of xenobiotics in biological samples. AN - 75810768; 7686263 AB - The development of immunoassays and immunoaffinity chromatography methods for determination of carcinogen-DNA adducts and carcinogen-modified DNA samples rests upon eliciting and characterizing polyclonal and monoclonal antisera against these haptens. The use of such antisera has widespread application in investigating chronic carcinogen administration in animal models and in monitoring human tissues for evidence of carcinogen exposure. Radioimmunoassays and enzyme-linked immunosorbent assays developed with carcinogen-DNA adduct antisera are exceedingly sensitive, measuring 1 adduct in 10(8) nucleotides. Not only can DNA damage be quantified directly by immunoassay, but the antisera have also been used to isolate DNA adducts of a particular chemical class by immunoaffinity chromatography before application of more chemically-specific end-points. Both of these methodological approaches have made seminal contributions to the newly-emerging field of molecular epidemiology. This chapter will focus on methods for preparing immunogens, the establishment of immunoassays, characterization of antisera and specific problems encountered with biological samples in addition, the use of immunoaffinity chromatography for preparative concentration of DNA adducts of a particular class will be included. JF - Mutation research AU - Poirier, M C AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, NIH, Bethesda, MD 20892. Y1 - 1993/07// PY - 1993 DA - July 1993 SP - 31 EP - 38 VL - 288 IS - 1 SN - 0027-5107, 0027-5107 KW - Antibodies, Antinuclear KW - 0 KW - Antibodies, Monoclonal KW - Carcinogens KW - Carrier Proteins KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Chromatography, Affinity KW - Animals KW - Carrier Proteins -- immunology KW - Humans KW - Enzyme-Linked Immunosorbent Assay KW - Radioimmunoassay -- methods KW - DNA Damage KW - DNA -- analysis KW - DNA -- immunology KW - Carcinogens -- analysis KW - Environmental Monitoring -- methods KW - DNA -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75810768?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Antisera+specific+for+carcinogen-DNA+adducts+and+carcinogen-modified+DNA%3A+applications+for+detection+of+xenobiotics+in+biological+samples.&rft.au=Poirier%2C+M+C&rft.aulast=Poirier&rft.aufirst=M&rft.date=1993-07-01&rft.volume=288&rft.issue=1&rft.spage=31&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 - 1993-07-26 N1 - Date created - 1993-07-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pharmacokinetics of the 9-amino and 10,11-methylenedioxy derivatives of camptothecin in mice. AN - 75809818; 8319213 AB - Although 20(S)-camptothecin (CA) exhibited potent cytotoxicity against a broad spectrum of tumor models, clinical trials with the sodium salt of its opened lactone ring form were discontinued due to highly variable and severe toxicity. Recently, the 9-amino (AC) and 10,11-methylenedioxy (MC) derivatives of CA were selected for preclinical evaluation by the National Cancer Institute. In the present investigation, the pharmacokinetic behavior of CA, its sodium salt CA, AC, and MC in mice was characterized using specific liquid chromatographic assays which permitted determination of the intact lactone and opened ring carboxylate forms of these compounds. CA disposition was triexponential with a prolonged terminal phase that had a 24.6-h half-life (t1/2,z) that comprised only 14.6% of the area under the concentration-time profile. The relative magnitudes of the total body apparent volume of distribution (Vz) and terminal phase rate constant suggest that the high observed total plasma clearance (CL, 104 ml/min/kg) may be associated with extensive accumulation in peripheral tissue regions from which the drug is slowly released. In comparison, the terminal disposition phase of MC accounted for 49.7% of the area under the curve profile. It also had a shorter t1/2,z (15.2 h) and appreciably greater CL (526 ml/min/kg) and Vz (694 liters/kg). This suggested that the degree of binding to tissues relative to plasma proteins was enhanced by the methylenedioxy moiety. In contrast, the 9-amino substituent profoundly diminished the apparent extent of tissue distribution, as indicated by the magnitude of Vz (7.7 liters/kg), effecting an enhanced rate of elimination (t1/2,z, 1.4 h). Comparison of the CL of CA and its two derivatives provided an inaccurate indication of drug elimination due to the influence of their unusually large Vz values. For these compounds, the relative ease of elimination from the body was best represented by mean residence times, which were 0.55, 7.24, and 11.2 h for AC, CA, and MC, respectively. Intact lactone plasma levels achieved after dosing with the lactone form of CA and its 9-amino and 10,11-methylenedioxy derivatives exceeded the far less active carboxylate at all times. In summary, these studies indicate that considerable alterations in pharmacokinetic behavior result from structural modification of the A ring of CA. JF - Cancer research AU - Supko, J G AU - Malspeis, L AD - Laboratory of Pharmaceutical Chemistry, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1993/07/01/ PY - 1993 DA - 1993 Jul 01 SP - 3062 EP - 3069 VL - 53 IS - 13 SN - 0008-5472, 0008-5472 KW - 10,11-methylenedioxy-20-camptothecin KW - 104155-89-7 KW - 9-aminocamptothecin KW - 5MB77ICE2Q KW - Camptothecin KW - XT3Z54Z28A KW - Index Medicus KW - Animals KW - Mice KW - Tissue Distribution KW - Mice, Inbred BALB C KW - Male KW - Structure-Activity Relationship KW - Mice, Inbred DBA KW - Camptothecin -- pharmacokinetics KW - Camptothecin -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75809818?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Pharmacokinetics+of+the+9-amino+and+10%2C11-methylenedioxy+derivatives+of+camptothecin+in+mice.&rft.au=Supko%2C+J+G%3BMalspeis%2C+L&rft.aulast=Supko&rft.aufirst=J&rft.date=1993-07-01&rft.volume=53&rft.issue=13&rft.spage=3062&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 - 1993-07-30 N1 - Date created - 1993-07-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Physical methods for the detection of carcinogen-DNA adducts in humans. AN - 75805796; 7686262 AB - This report has attempted to summarize the principles, advantages, limitations and the source of data derived in the use of physical detection techniques for DNA-adduct measurement in human biomonitoring. Each method, although inherently chemically-specific, has advantages and limitations depending on the adduct type under study. These methods have a niche that is at least consistent with corroborative technology, and are being applied to dosimetry problems in the field. JF - Mutation research AU - Weston, A AD - Molecular Epidemiology Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/07// PY - 1993 DA - July 1993 SP - 19 EP - 29 VL - 288 IS - 1 SN - 0027-5107, 0027-5107 KW - Carcinogens KW - 0 KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Spectrometry, Fluorescence -- methods KW - Humans KW - Mass Spectrometry -- methods KW - Spectrophotometry, Atomic KW - Conductometry KW - Chromatography, Gas -- methods KW - Carcinogens -- metabolism KW - DNA Damage KW - DNA Mutational Analysis -- methods KW - DNA -- metabolism KW - DNA -- analysis KW - Carcinogens -- analysis KW - Environmental Monitoring -- methods KW - DNA -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75805796?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Physical+methods+for+the+detection+of+carcinogen-DNA+adducts+in+humans.&rft.au=Weston%2C+A&rft.aulast=Weston&rft.aufirst=A&rft.date=1993-07-01&rft.volume=288&rft.issue=1&rft.spage=19&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 - 1993-07-26 N1 - Date created - 1993-07-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of omega-conotoxin GVIA-sensitive Ca2+ entry in angiotensin II-stimulated [3H]phorbol 12,13-dibutyrate binding in bovine adrenal medullary cells. AN - 75800292; 8515289 AB - The relative contributions of Ca2+ influx and intracellular Ca2+ mobilization were examined for angiotensin II-stimulated [3H]phorbol 12,13-dibutyrate binding, which reflects the level of activated protein kinase C in bovine chromaffin cells. Angiotensin II receptors activate phospholipase C in chromaffin cells, leading to a short-lived mobilization of intracellular Ca2+. Angiotensin II-stimulated [3H]phorbol 12,13-dibutyrate binding was largely blocked in Ca(2+)-free buffer and by pretreatment with the Ca(2+)-channel blocker omega-conotoxin GVIA. The [3H]phorbol 12,13-dibutyrate binding response to [Sar1]angiotensin II also appeared to be voltage sensitive, as no additivity was observed with the response to the depolarizing agent 4-aminopyridine (3 mM). Threshold sensitivities of the extra- and intracellular Ca(2+)-mobilizing pathways to angiotensin II were similar, and all examined effects of angiotensin II in these cells were apparently mediated by losartan-sensitive (AT1-like) receptors. The dependence of angiotensin II-stimulated [3H]phorbol 12,13-dibutyrate binding on extracellular Ca2+ entry, in contrast to stimulation by other phospholipase C-linked receptor agonists (bradykinin and methacholine), suggests that angiotensin II preferentially stimulates protein kinase C translocation to the plasma membrane, rather than to internal membranes, in bovine adrenal medullary cells. JF - Journal of neurochemistry AU - McMillian, M K AU - Hudson, P M AU - Suh, H H AU - Ye, H AU - Tuominen, R K AU - Hong, J S AD - Laboratory of Molecular and Integrative Neuroscience, National Institute of Environmental Health Sciences, National Institute of Health, Research Triangle Park, North Carolina 27709. Y1 - 1993/07// PY - 1993 DA - July 1993 SP - 93 EP - 99 VL - 61 IS - 1 SN - 0022-3042, 0022-3042 KW - Peptides, Cyclic KW - 0 KW - Tritium KW - 10028-17-8 KW - Angiotensin II KW - 11128-99-7 KW - Phorbol 12,13-Dibutyrate KW - 37558-16-0 KW - angiotensin II, Sar(1)- KW - 59680-38-5 KW - omega-Conotoxin GVIA KW - 92078-76-7 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Osmolar Concentration KW - Animals KW - Cattle KW - Differential Threshold KW - Cells, Cultured KW - Membrane Potentials KW - Calcium -- metabolism KW - Angiotensin II -- analogs & derivatives KW - Angiotensin II -- metabolism KW - Phorbol 12,13-Dibutyrate -- metabolism KW - Adrenal Medulla -- physiology KW - Adrenal Medulla -- cytology KW - Adrenal Medulla -- metabolism KW - Peptides, Cyclic -- pharmacology KW - Angiotensin II -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75800292?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Role+of+omega-conotoxin+GVIA-sensitive+Ca2%2B+entry+in+angiotensin+II-stimulated+%5B3H%5Dphorbol+12%2C13-dibutyrate+binding+in+bovine+adrenal+medullary+cells.&rft.au=McMillian%2C+M+K%3BHudson%2C+P+M%3BSuh%2C+H+H%3BYe%2C+H%3BTuominen%2C+R+K%3BHong%2C+J+S&rft.aulast=McMillian&rft.aufirst=M&rft.date=1993-07-01&rft.volume=61&rft.issue=1&rft.spage=93&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 - 1993-07-22 N1 - Date created - 1993-07-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Analysis of a segment of the human glial fibrillary acidic protein gene that directs astrocyte-specific transcription. AN - 75799131; 8515262 AB - To understand astrocyte-specific transcription, we have been studying the human gfa gene. This gene encodes glial fibrillary acidic protein (GFAP), an intermediate filament protein expressed primarily in astrocytes. A survey of the gfa 5' flanking region showed it to contain several segments that contribute to expression of a chloramphenicol acetyltransferase reporter gene in transfected cells. The most active of these was the 124-bp B region, which spans bp -1612 to -1489. We have now used site-directed mutagenesis to analyze this region in greater detail, and show that the B region itself contains several important elements. The most crucial of these is a consensus AP-1 sequence, the binding site for the Fos and Jun families of transcription factors. The presence of members of both these families in the glial fibrillary acidic protein-expressing U251 cell line used for our transfection studies was verified by gel mobility-shift experiments. This is the first demonstration of the functioning of a specific transcription factor site for astrocytes, and provides a focus for future studies of glial fibrillary acidic protein regulation during development and reactive gliosis. JF - Journal of neurochemistry AU - Masood, K AU - Besnard, F AU - Su, Y AU - Brenner, M AD - Laboratory of Molecular Biology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/07// PY - 1993 DA - July 1993 SP - 160 EP - 166 VL - 61 IS - 1 SN - 0022-3042, 0022-3042 KW - Glial Fibrillary Acidic Protein KW - 0 KW - Oligonucleotide Probes KW - Proto-Oncogene Proteins c-fos KW - Proto-Oncogene Proteins c-jun KW - Index Medicus KW - Base Sequence KW - Proto-Oncogene Proteins c-fos -- metabolism KW - Oligonucleotide Probes -- genetics KW - Humans KW - Molecular Sequence Data KW - Proto-Oncogene Proteins c-jun -- metabolism KW - Consensus Sequence KW - Binding Sites KW - Genes KW - Astrocytes -- physiology KW - Transcription, Genetic KW - Glial Fibrillary Acidic Protein -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75799131?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Analysis+of+a+segment+of+the+human+glial+fibrillary+acidic+protein+gene+that+directs+astrocyte-specific+transcription.&rft.au=Masood%2C+K%3BBesnard%2C+F%3BSu%2C+Y%3BBrenner%2C+M&rft.aulast=Masood&rft.aufirst=K&rft.date=1993-07-01&rft.volume=61&rft.issue=1&rft.spage=160&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 - 1993-07-22 N1 - Date created - 1993-07-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A phase II evaluation of thiotepa in pediatric central nervous system malignancies. AN - 75789680; 8508417 AB - Both thiotepa and its active metabolite, tepa, efficiently cross the blood-brain barrier. After intravenous administration, the cerebrospinal fluid concentrations achieved are nearly identical to those in plasma. This provides a strong rationale for testing this agent against brain tumors. Sixty pediatric patients with recurrent primary brain tumors were treated on a multiinstitutional Phase II study of intravenous thiotepa at a dose of 65 mg/m2 administered every 3 weeks. This dose is the result of a prior pediatric Phase I trial and is significantly higher than those previously recommended. Three of 13 assessable patients with medulloblastoma had partial responses lasting 22, 25, and 54 weeks. Although no objective responses were observed in 16 assessable patients with malignant gliomas and 14 with brain stem gliomas, 5 of 16 and 4 of 14 patients in these respective strata had prolonged periods of stable disease (SD) lasting from 12 to more than 33 weeks. Nine assessable patients with ependymoma had no objective response, but two had SD, both for more than 33 weeks. Myelosuppression was the principle toxic effect encountered and appeared to be more severe in patients who had received prior craniospinal radiation therapy or nitrosourea therapy. By conventional Phase II criteria, thiotepa appears to have activity in medulloblastoma. Based on several patients with prolonged SD, it also may possess some limited activity in brain stem and malignant gliomas. The steep in vitro dose-response curve of thiotepa and the long durations of response or SD observed with the dose reported here suggest that moderate-dose to high-dose thiotepa with cytokine support or autologous bone marrow rescue may be associated with an improved response rate to this agent. JF - Cancer AU - Heideman, R L AU - Packer, R J AU - Reaman, G H AU - Allen, J C AU - Lange, B AU - Horowitz, M E AU - Steinberg, S M AU - Gillespie, A AU - Kovnar, E H AU - Balis, F M AD - Pediatric Branch, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1993/07/01/ PY - 1993 DA - 1993 Jul 01 SP - 271 EP - 275 VL - 72 IS - 1 SN - 0008-543X, 0008-543X KW - Thiotepa KW - 905Z5W3GKH KW - Abridged Index Medicus KW - Index Medicus KW - Drug Administration Schedule KW - Ependymoma -- drug therapy KW - Medulloblastoma -- drug therapy KW - Humans KW - Child KW - Child, Preschool KW - Infant KW - Cerebellar Neoplasms -- drug therapy KW - Glioma -- drug therapy KW - Adult KW - Adolescent KW - Female KW - Male KW - Brain Neoplasms -- drug therapy KW - Neoplasm Recurrence, Local -- drug therapy KW - Thiotepa -- administration & dosage KW - Thiotepa -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75789680?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+phase+II+evaluation+of+thiotepa+in+pediatric+central+nervous+system+malignancies.&rft.au=Heideman%2C+R+L%3BPacker%2C+R+J%3BReaman%2C+G+H%3BAllen%2C+J+C%3BLange%2C+B%3BHorowitz%2C+M+E%3BSteinberg%2C+S+M%3BGillespie%2C+A%3BKovnar%2C+E+H%3BBalis%2C+F+M&rft.aulast=Heideman&rft.aufirst=R&rft.date=1993-07-01&rft.volume=72&rft.issue=1&rft.spage=271&rft.isbn=&rft.btitle=&rft.title=Cancer&rft.issn=0008543X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-07-13 N1 - Date created - 1993-07-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Albendazole in human loiasis: results of a double-blind, placebo-controlled trial. AN - 75783556; 8515109 AB - To assess the filaricidal activity and clinical safety of albendazole in human loiasis, a double-blind, placebo-controlled study was conducted in an endemic area in Benin, Africa. Twenty-three men with microfilaremia (100-30,000/mL) were randomly assigned to receive albendazole (200 mg; n = 11) or placebo (n = 12) twice daily for 21 days; 1 patient from each group withdrew from the study. There were no clinical adverse effects and no observed hepatotoxicity, renal toxicity, or hematologic abnormalities attributable to the drug. In the albendazole group, microfilarial levels began to decrease at day 14 after treatment and by 6 months had fallen to a geometric mean of 20% of pretreatment levels (vs. 84.8% in the placebo group). Blood eosinophil levels and anti-filarial IgG and IgG4 also fell significantly in response to albendazole. Taken together, these data suggest that albendazole has a primary (possibly embryotoxic) effect on the adult parasite, resulting in a slow decrease in microfilaremia. JF - The Journal of infectious diseases AU - Klion, A D AU - Massougbodji, A AU - Horton, J AU - Ekoué, S AU - Lanmasso, T AU - Ahouissou, N L AU - Nutman, T B AD - Laboratory of Parasitic Diseases, National Institutes of Health, Bethesda, Maryland. Y1 - 1993/07// PY - 1993 DA - July 1993 SP - 202 EP - 206 VL - 168 IS - 1 SN - 0022-1899, 0022-1899 KW - Albendazole KW - F4216019LN KW - Abridged Index Medicus KW - Index Medicus KW - Double-Blind Method KW - Humans KW - Africa, Western KW - Adult KW - Aged KW - Middle Aged KW - Adolescent KW - Male KW - Female KW - Albendazole -- adverse effects KW - Loiasis -- drug therapy KW - Albendazole -- pharmacokinetics KW - Albendazole -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75783556?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Albendazole+in+human+loiasis%3A+results+of+a+double-blind%2C+placebo-controlled+trial.&rft.au=Klion%2C+A+D%3BMassougbodji%2C+A%3BHorton%2C+J%3BEkou%C3%A9%2C+S%3BLanmasso%2C+T%3BAhouissou%2C+N+L%3BNutman%2C+T+B&rft.aulast=Klion&rft.aufirst=A&rft.date=1993-07-01&rft.volume=168&rft.issue=1&rft.spage=202&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 - 1993-07-20 N1 - Date created - 1993-07-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Susceptibility and resistance to J3V1 retrovirus-induced murine plasmacytomagenesis in reconstituted severe combined immunodeficient mice. AN - 75772029; 7685514 AB - To date much is known about the genetics of susceptibility and resistance to plasmacytoma induction in mice, however little is known about the cellular aspects of these phenotypes. The complexity of plasmacytomagenesis allows for susceptibility and resistance to reflect differences in B cells, T cells, accessory cells and/or stromal elements contributing to the disease process. Alternatively, these phenotypes may result from differential abilities to affect events critical to plasmacytomagenesis, such as myc deregulation. To address these possibilities, the v-myc-raf-containing retrovirus, J3V1, was used to induce plasmacytomas (PCTs) in severe combined immunodeficient (SCID) mice reconstituted with susceptible (Balb/c) and/or resistant (DBA/2) cells. The results demonstrate that Balb/c bone marrow (BM)-reconstituted SCID mice yielded PCTs of donor origin, while DBA/2 BM-reconstituted mice did not. Mice reconstituted with both DBA/2 BM and Balb/c peripheral lymphocytes, as well as those reconstituted with Balb/c peripheral lymphocytes alone, also yielded only Balb/c PCTs. These results indicate that: (1) a microenvironment supportive of plasmacytomagenesis is insufficient to allow PCT development among resistant cells; (2) DBA/2 BM-derived cells do not suppress plasmacytomagenesis by target cell elimination or microenvironment destruction; (3) resistance is not solely attributable to the inability of DBA/2 B cells to deregulate myc; and (4) potential PCT targets reside in a number of lymphoid tissues. Taken together, these results demonstrate that a major aspect of resistance/susceptibility to plasmacytomagenesis is dictated by the genotype of the target B cell. JF - Oncogene AU - Hilbert, D M AU - Pumphrey, J G AU - Troppmair, J AU - Rapp, U R AU - Rudikoff, S AD - Laboratory of Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/07// PY - 1993 DA - July 1993 SP - 1993 EP - 2000 VL - 8 IS - 7 SN - 0950-9232, 0950-9232 KW - Antigens, CD KW - 0 KW - Antigens, CD5 KW - Terpenes KW - pristane KW - 26HZV48DT1 KW - Index Medicus KW - Animals KW - Antigens, CD -- analysis KW - Disease Susceptibility KW - Genes, myc KW - B-Lymphocytes -- immunology KW - Mice KW - Mice, Inbred BALB C KW - Mice, Inbred DBA KW - Terpenes -- pharmacology KW - Mice, SCID KW - Species Specificity KW - Female KW - Plasmacytoma -- genetics KW - Plasmacytoma -- immunology KW - Retroviridae -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75772029?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Susceptibility+and+resistance+to+J3V1+retrovirus-induced+murine+plasmacytomagenesis+in+reconstituted+severe+combined+immunodeficient+mice.&rft.au=Hilbert%2C+D+M%3BPumphrey%2C+J+G%3BTroppmair%2C+J%3BRapp%2C+U+R%3BRudikoff%2C+S&rft.aulast=Hilbert&rft.aufirst=D&rft.date=1993-07-01&rft.volume=8&rft.issue=7&rft.spage=1993&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-07-09 N1 - Date created - 1993-07-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Human immunodeficiency virus type 1 Vpu protein induces degradation of CD4 in vitro: the cytoplasmic domain of CD4 contributes to Vpu sensitivity. AN - 75771964; 8510209 AB - CD4 is an integral membrane glycoprotein which functions as the human immunodeficiency virus (HIV) receptor for infection of human host cells. We have recently demonstrated that Vpu, an HIV type 1 (HIV-1) encoded integral membrane phosphoprotein, induces rapid degradation of CD4 in the endoplasmic reticulum. In this report, we describe an in vitro model system that allowed us to define important parameters for Vpu-dependent CD4 degradation. The rate of CD4 decay in rabbit reticulocyte lysate was approximately one-third of that observed previously in tissue culture experiments in the presence of Vpu (40 versus 12 min) and required no other HIV-1 encoded proteins. Degradation was contingent on the presence of microsomal membranes in the assay and the coexpression of Vpu and CD4 in the same membrane compartment. By using the in vitro degradation assay, the effects of specific mutations in CD4, including C-terminal truncations and glycosylation mutants, were analyzed. The results of these experiments indicate that Vpu has the capacity to induce degradation of glycosylated as well as nonglycosylated membrane-associated CD4. Truncation of 13 C-terminal amino acids of CD4 did not affect the ability of Vpu to induce its degradation. However, the removal of 32 amino acids from the C-terminus of CD4 completely abolished sensitivity to Vpu. This suggests that Vpu targets specific sequences in the cytoplasmic domain of CD4 to induce its degradation. We also analyzed the effects of mutations in Vpu on its biological activity in the in vitro CD4 degradation assay. The results of these experiments suggest that sequences critical for this function of Vpu are located in its hydrophilic C-terminal domain. JF - Journal of virology AU - Chen, M Y AU - Maldarelli, F AU - Karczewski, M K AU - Willey, R L AU - Strebel, K AD - Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892. Y1 - 1993/07// PY - 1993 DA - July 1993 SP - 3877 EP - 3884 VL - 67 IS - 7 SN - 0022-538X, 0022-538X KW - Antigens, CD4 KW - 0 KW - Human Immunodeficiency Virus Proteins KW - Oligodeoxyribonucleotides KW - Recombinant Proteins KW - Viral Regulatory and Accessory Proteins KW - vpu protein, Human immunodeficiency virus 1 KW - Hexosaminidases KW - EC 3.2.1.- KW - Index Medicus KW - AIDS/HIV KW - Protein Biosynthesis KW - Animals KW - Solubility KW - Transcription, Genetic KW - Rabbits KW - Amino Acid Sequence KW - Glycosylation KW - Structure-Activity Relationship KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Recombinant Proteins -- metabolism KW - Cytoplasm -- metabolism KW - Hexosaminidases -- pharmacology KW - Microsomes -- metabolism KW - Oligodeoxyribonucleotides -- chemistry KW - In Vitro Techniques KW - Molecular Sequence Data KW - HIV-1 -- metabolism KW - Viral Regulatory and Accessory Proteins -- metabolism KW - Antigens, CD4 -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75771964?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Human+immunodeficiency+virus+type+1+Vpu+protein+induces+degradation+of+CD4+in+vitro%3A+the+cytoplasmic+domain+of+CD4+contributes+to+Vpu+sensitivity.&rft.au=Chen%2C+M+Y%3BMaldarelli%2C+F%3BKarczewski%2C+M+K%3BWilley%2C+R+L%3BStrebel%2C+K&rft.aulast=Chen&rft.aufirst=M&rft.date=1993-07-01&rft.volume=67&rft.issue=7&rft.spage=3877&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 - 1993-07-12 N1 - Date created - 1993-07-12 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Methods Enzymol. 1983;96:84-93 [6656655] Proc Natl Acad Sci U S A. 1977 Aug;74(8):3278-82 [198778] J Virol. 1986 Aug;59(2):284-91 [3016298] Cell. 1986 Nov 7;47(3):333-48 [3094962] Science. 1986 Nov 28;234(4780):1123-7 [3095925] Science. 1988 Sep 2;241(4870):1221-3 [3261888] Proc Natl Acad Sci U S A. 1989 Jul;86(13):5163-7 [2472639] J Virol. 1989 Sep;63(9):3784-91 [2788224] J Virol. 1990 Feb;64(2):621-9 [2404139] Nature. 1990 May 24;345(6273):356-9 [2188136] Cell. 1990 Aug 24;62(4):611-4 [2201450] J Virol. 1990 Nov;64(11):5448-56 [2214021] J Virol. 1990 Nov;64(11):5585-93 [2214026] J Virol. 1990 Dec;64(12):6297-304 [2243395] Cell. 1990 Dec 21;63(6):1129-36 [2175676] Virology. 1991 Feb;180(2):617-24 [1989386] J Biol Chem. 1991 Mar 5;266(7):4500-7 [1825655] Proc Natl Acad Sci U S A. 1991 Mar 1;88(5):1918-22 [2000396] J Biol Chem. 1991 Jun 5;266(16):10658-65 [1674746] J Virol. 1991 Dec;65(12):6387-96 [1942241] J Virol. 1992 Jan;66(1):226-34 [1727486] Curr Opin Cell Biol. 1991 Aug;3(4):592-600 [1772654] J Biol Chem. 1992 Feb 15;267(5):3268-73 [1737783] Eur J Biochem. 1992 Mar 1;204(2):875-83 [1541298] Cell. 1992 May 1;69(3):517-28 [1374685] J Virol. 1992 Dec;66(12):7193-200 [1433512] Cell. 1985 Aug;42(1):93-104 [2990730] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The PU.1/Spi-1 proto-oncogene is a transcriptional regulator of a lentivirus promoter. AN - 75771577; 8389910 AB - The enhancer unit present in the retrovirus equine infectious anemia virus (EIAV) was previously shown to contain binding sites for proteins belonging to MDBP, PEA2, AP-1, and ets families. The EIAV ets motif matches the consensus sequence for both PEA3- and PU.1-binding sites. Here, we show by gel shift analysis that PU.1, present in nuclear extracts from monocyte and B-lymphocyte cell lines, binds to oligonucleotides containing the EIAV ets element. HeLa cells transiently transfected with a PU.1 expression plasmid expressed nuclear factors that formed complexes indistinguishable from those seen with monocyte extracts. Antibodies to PU.1 protein either supershifted or abolished formation of these complexes, depending on the PU.1 epitopes recognized. The binding of PU.1 to the EIAV ets motif in vitro correlated with transcriptional activity of the EIAV promoter in transfected monocyte cell lines. In HeLa cells, the product of PU.1 cDNA bound to the EIAV ets motif and activated transcription from the EIAV promoter. The PU.1-binding site was the primary determinant of EIAV promoter activity in cell lines that express PU.1. Nucleotide determinants of PU.1 binding and a consensus PU.1 binding sequence were defined in gel shift assays using a panel of mutated oligonucleotides. To our knowledge, this is the first report of a retroviral promoter controlled by PU.1. JF - Journal of virology AU - Carvalho, M AU - Derse, D AD - Laboratory of Viral Carcinogenesis, National Cancer Institute, Frederick, Maryland 21702-1201. Y1 - 1993/07// PY - 1993 DA - July 1993 SP - 3885 EP - 3890 VL - 67 IS - 7 SN - 0022-538X, 0022-538X KW - AP-1 KW - PEA2 KW - ets KW - DNA-Binding Proteins KW - 0 KW - Proto-Oncogene Proteins KW - RNA, Messenger KW - Retroviridae Proteins, Oncogenic KW - Transcription Factors KW - v-Spi-1 protein, Friend spleen focus-forming virus KW - Index Medicus KW - Base Sequence KW - Multigene Family KW - Humans KW - Enhancer Elements, Genetic KW - In Vitro Techniques KW - Molecular Sequence Data KW - Transcription, Genetic KW - RNA, Messenger -- genetics KW - Proto-Oncogenes KW - Proto-Oncogene Proteins -- physiology KW - Cell Line KW - Binding Sites KW - Transcription Factors -- physiology KW - Promoter Regions, Genetic KW - Gene Expression Regulation, Viral KW - Infectious Anemia Virus, Equine -- genetics KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75771577?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+PU.1%2FSpi-1+proto-oncogene+is+a+transcriptional+regulator+of+a+lentivirus+promoter.&rft.au=Carvalho%2C+M%3BDerse%2C+D&rft.aulast=Carvalho&rft.aufirst=M&rft.date=1993-07-01&rft.volume=67&rft.issue=7&rft.spage=3885&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 - 1993-07-12 N1 - Date created - 1993-07-12 N1 - Date revised - 2017-01-13 N1 - Gene symbol - AP-1; PEA2; ets N1 - SuppNotes - Cited By: Cell Growth Differ. 1992 May;3(5):327-34 [1633115] Mol Cell Biol. 1992 Jul;12(7):2967-75 [1620109] J Virol. 1993 Apr;67(4):2064-74 [8383228] Mol Cell Biol. 1982 Sep;2(9):1044-51 [6960240] Nucleic Acids Res. 1983 Mar 11;11(5):1475-89 [6828386] Rev Infect Dis. 1985 Jan-Feb;7(1):83-8 [2984759] Proc Natl Acad Sci U S A. 1986 Nov;83(22):8550-4 [3022296] Nature. 1988 Jan 21;331(6153):277-80 [2827041] J Virol. 1988 Sep;62(9):3522-6 [2841502] J Virol. 1989 Jan;63(1):398-402 [2535740] Mol Cell Biol. 1989 Apr;9(4):1804-9 [2725524] EMBO J. 1989 Nov;8(11):3371-8 [2555163] Cell. 1990 Apr 6;61(1):113-24 [2180582] J Virol. 1990 Apr;64(4):1616-24 [2157047] Oncogene. 1990 May;5(5):663-8 [1693183] EMBO J. 1990 Jul;9(7):2241-6 [2162765] J Virol. 1991 Jul;65(7):3468-74 [1645778] Genes Dev. 1991 Jun;5(6):908-18 [2044959] J Virol. 1991 Oct;65(10):5391-400 [1654447] Mol Cell Biol. 1992 Jan;12(1):368-78 [1729611] Mol Cell Biol. 1992 Mar;12(3):1043-53 [1545787] J Exp Med. 1992 May 1;175(5):1391-9 [1569404] Genes Dev. 1992 Jun;6(6):965-74 [1592263] J Virol. 1992 Oct;66(10):5906-13 [1382143] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Aberrant expression of high mobility group chromosomal protein 14 affects cellular differentiation. AN - 75793539; 8514795 AB - High mobility group (HMG) 14 is a ubiquitous chromosomal protein that binds specifically to nucleosomal DNA and may be involved in a process that confers distinct properties to the chromatin structure of transcriptionally active genes. To explore the involvement of this protein in regulation of gene expression, we studied the effect of aberrant expression of HMG-14 protein on cellular differentiation. We produced stably transfected C2C12 mouse myoblasts expressing the human HMG-14 protein under the control of the mouse mammary tumor virus promoter. Transformed colonies retained their potential do differentiate into myotubes. Induction of human HMG-14 expression by dexamethasone inhibited the myogenic process. Revertant colonies, which lost the ability to express human HMG-14, regained the ability to differentiate into myotubes. Inhibition of myoblast differentiation by aberrantly expressed HMG-14 correlated with down-regulation of myogenic determination factors. The results suggest that proper cellular differentiation requires regulated expression of HMG-14 protein and are consistent with the possibility that this protein may be involved in gene regulation. JF - The Journal of biological chemistry AU - Pash, J M AU - Alfonso, P J AU - Bustin, M AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/06/25/ PY - 1993 DA - 1993 Jun 25 SP - 13632 EP - 13638 VL - 268 IS - 18 SN - 0021-9258, 0021-9258 KW - Biomarkers KW - 0 KW - High Mobility Group Proteins KW - RNA, Messenger KW - Dexamethasone KW - 7S5I7G3JQL KW - Index Medicus KW - Muscles -- cytology KW - Animals KW - Gene Expression Regulation -- physiology KW - RNA, Messenger -- metabolism KW - Transfection KW - Cells, Cultured KW - Humans KW - Dexamethasone -- pharmacology KW - RNA, Messenger -- drug effects KW - Muscles -- metabolism KW - Mice KW - High Mobility Group Proteins -- physiology KW - High Mobility Group Proteins -- biosynthesis KW - Cell Differentiation -- physiology KW - Cell Differentiation -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75793539?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Aberrant+expression+of+high+mobility+group+chromosomal+protein+14+affects+cellular+differentiation.&rft.au=Pash%2C+J+M%3BAlfonso%2C+P+J%3BBustin%2C+M&rft.aulast=Pash&rft.aufirst=J&rft.date=1993-06-25&rft.volume=268&rft.issue=18&rft.spage=13632&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 - 1993-07-22 N1 - Date created - 1993-07-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pseudomonas exotoxin and recombinant immunotoxins derived from it. AN - 75936509; 8363279 AB - Pseudomonas exotoxin (PE) is a bacterial toxin that kills mammalian cells by gaining entry to the cytosol and inactivating protein synthesis. The toxin binds and enters cells via the alpha 2-macroglobulin receptors. Within cells, the toxin is processed in several steps to produce an enzymatically active 37-kDa C-terminal fragment which translocates to the cytosol and ADP-ribosylates elongation factor 2. Because PE is a very potent toxin, derivatives of it have been produced which, when joined to various binding ligands, are capable of killing specific target cells. It is hoped that this strategy will lead to the development of effective therapeutic agents for the treatment of human diseases such as cancer, AIDS, and various immunologic disorders. JF - Annals of the New York Academy of Sciences AU - Fitzgerald, D AU - Pastan, I AD - Laboratory of Molecular Biology, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1993/06/23/ PY - 1993 DA - 1993 Jun 23 SP - 740 EP - 745 VL - 685 SN - 0077-8923, 0077-8923 KW - Bacterial Toxins KW - 0 KW - Exotoxins KW - Immunotoxins KW - Recombinant Fusion Proteins KW - Virulence Factors KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - toxA protein, Pseudomonas aeruginosa KW - EC 2.4.2.31 KW - Index Medicus KW - Animals KW - Humans KW - Exotoxins -- pharmacology KW - Recombinant Fusion Proteins -- pharmacology KW - Bacterial Toxins -- pharmacology KW - Pseudomonas aeruginosa KW - Immunotoxins -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75936509?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Pseudomonas+exotoxin+and+recombinant+immunotoxins+derived+from+it.&rft.au=Fitzgerald%2C+D%3BPastan%2C+I&rft.aulast=Fitzgerald&rft.aufirst=D&rft.date=1993-06-23&rft.volume=685&rft.issue=&rft.spage=740&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 - 1993-09-24 N1 - Date created - 1993-09-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Immune dysfunction related to drug-metabolizing enzymes. AN - 75931727; 8395782 JF - Annals of the New York Academy of Sciences AU - Albright, J F AD - Division of Allergy, Immunology and Transplantation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/06/23/ PY - 1993 DA - 1993 Jun 23 SP - 620 EP - 623 VL - 685 SN - 0077-8923, 0077-8923 KW - Pharmaceutical Preparations KW - 0 KW - Polychlorinated Dibenzodioxins KW - Receptors, Aryl Hydrocarbon KW - Receptors, Drug KW - Index Medicus KW - Animals KW - Mice, Inbred C57BL KW - Mice KW - Receptors, Drug -- physiology KW - Mice, Inbred DBA KW - Pharmaceutical Preparations -- metabolism KW - Immune System -- drug effects KW - Polychlorinated Dibenzodioxins -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75931727?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Immune+dysfunction+related+to+drug-metabolizing+enzymes.&rft.au=Albright%2C+J+F&rft.aulast=Albright&rft.aufirst=J&rft.date=1993-06-23&rft.volume=685&rft.issue=&rft.spage=620&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 - 1993-09-24 N1 - Date created - 1993-09-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The interleukin-2 receptor: a target for immunotherapy. AN - 75931688; 8363269 JF - Annals of the New York Academy of Sciences AU - Waldmann, T A AU - Goldman, C AU - Top, L AU - Grant, A AU - Burton, J AU - Bamford, R AU - Roessler, E AU - Horak, I AU - Zaknoen, S AU - Kasten-Sportes, C AD - Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/06/23/ PY - 1993 DA - 1993 Jun 23 SP - 603 EP - 610 VL - 685 SN - 0077-8923, 0077-8923 KW - Antibodies, Monoclonal KW - 0 KW - Immunotoxins KW - Receptors, Interleukin-2 KW - Index Medicus KW - AIDS/HIV KW - HTLV-I Infections -- therapy KW - Animals KW - Leukemia, T-Cell -- therapy KW - Humans KW - Immunotoxins -- therapeutic use KW - HTLV-I Infections -- immunology KW - Leukemia, T-Cell -- immunology KW - Neoplasms -- immunology KW - Antibodies, Monoclonal -- therapeutic use KW - Receptors, Interleukin-2 -- physiology KW - Receptors, Interleukin-2 -- analysis KW - Immunotherapy KW - Receptors, Interleukin-2 -- chemistry KW - Receptors, Interleukin-2 -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75931688?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+interleukin-2+receptor%3A+a+target+for+immunotherapy.&rft.au=Waldmann%2C+T+A%3BGoldman%2C+C%3BTop%2C+L%3BGrant%2C+A%3BBurton%2C+J%3BBamford%2C+R%3BRoessler%2C+E%3BHorak%2C+I%3BZaknoen%2C+S%3BKasten-Sportes%2C+C&rft.aulast=Waldmann&rft.aufirst=T&rft.date=1993-06-23&rft.volume=685&rft.issue=&rft.spage=603&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 - 1993-09-24 N1 - Date created - 1993-09-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evaluation of 'cypenhymustine', a new anticancer compound, in murine tumour models. AN - 75851488; 8330289 AB - 'Cypenhymustine', 3-[2-[bis(2'-chloroethyl)-amino] ethyl]-5,5- tetramethylenehydantoin, has been synthesised as a potential analog of spiromustine (NSC 172112). The LD50 value was determined in Swiss male mice and found to be 65.0 mg/kg by single i.p. injection. In in vivo screening experiments, three parameters, namely, ascites cell count, ascites fluid measurement and increase in life span (ILS) of drug-treated over control Swiss mice were studied in three murine ascites tumours namely Ehrlich ascites carcinoma (EAC), sarcoma-180 (S-180) and Dalton's lymphoma (DL). Cypenhymustine exhibited a very high percentage of inhibition of both the ascites cell and fluid in these models and also displayed excellent reproducible ILS activity (ILS values of 151 in EAC, 157 in S-180 and 181 in DL at the optimum dose of 3 mg/kg for days 1-7 treatment following tumour transplant on day 0) having a 'curative' effect (1-2 animals: 6 having > 60 days survival rate). The chemical alkylating activity has been compared with spiromustine and another antitumour agent namely nor-HN2. JF - Cancer letters AU - Sanyal, U AU - Bhattacharya, S AU - Sadhu, U AU - Dutta, S AU - Das, H AU - Ghosh, M AD - Department of Chemotherapy, Chittaranjan National Cancer Institute, Calcutta, India. Y1 - 1993/06/15/ PY - 1993 DA - 1993 Jun 15 SP - 1 EP - 6 VL - 70 IS - 1-2 SN - 0304-3835, 0304-3835 KW - Antineoplastic Agents KW - 0 KW - Hydantoins KW - Nitrogen Mustard Compounds KW - cypenhymustine KW - 150380-35-1 KW - Index Medicus KW - Mice, Inbred Strains KW - Drug Screening Assays, Antitumor KW - Animals KW - Dose-Response Relationship, Drug KW - Sarcoma 180 -- drug therapy KW - Carcinoma, Ehrlich Tumor -- drug therapy KW - Lethal Dose 50 KW - Lymphoma -- drug therapy KW - Mice KW - Male KW - Hydantoins -- chemical synthesis KW - Nitrogen Mustard Compounds -- therapeutic use KW - Hydantoins -- therapeutic use KW - Nitrogen Mustard Compounds -- chemical synthesis KW - Antineoplastic Agents -- chemical synthesis KW - Antineoplastic Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75851488?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+letters&rft.atitle=Evaluation+of+%27cypenhymustine%27%2C+a+new+anticancer+compound%2C+in+murine+tumour+models.&rft.au=Sanyal%2C+U%3BBhattacharya%2C+S%3BSadhu%2C+U%3BDutta%2C+S%3BDas%2C+H%3BGhosh%2C+M&rft.aulast=Sanyal&rft.aufirst=U&rft.date=1993-06-15&rft.volume=70&rft.issue=1-2&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Cancer+letters&rft.issn=03043835&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-08-17 N1 - Date created - 1993-08-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Variation in colorectal cancer incidence in the United States by subsite of origin. AN - 75796585; 8508350 AB - Colorectal cancer incidence rates vary widely internationally, by race and gender, and have changed over time. Investigation of the patterns by subsite within the colorectum may suggest clues of possible etiologic significance for further study. Using population-based data on more than 120,000 cases diagnosed 1976-1987 in the United States Surveillance, Epidemiology, and End Results program, colorectal cancer incidence was evaluated by subsite of origin. Little racial variation was evident for cecum and ascending colon cancers; rates were higher among blacks than whites for transverse and descending colon cancers but lower for sigmoid, rectosigmoid, and rectal cancers. Rates generally increased over time for most colon sites, especially sigmoid colon among white men, but declined slightly for rectal cancer among whites. The sex ratio increased among whites monotonically from 1.12 for cecum to 1.71 for rectal cancers. The distal colon cancer excess among men was most notable at older ages, contrasting with slightly higher rates among women at younger ages. Geographic differences were particularly notable for transverse and rectosigmoid colon cancers. It may be fruitful for future studies to evaluate factors affecting colorectal carcinogenesis by subsite of origin. JF - Cancer AU - Devesa, S S AU - Chow, W H AD - Division of Cancer Etiology, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1993/06/15/ PY - 1993 DA - 1993 Jun 15 SP - 3819 EP - 3826 VL - 71 IS - 12 SN - 0008-543X, 0008-543X KW - Abridged Index Medicus KW - Index Medicus KW - New Mexico -- epidemiology KW - Age Factors KW - Sex Factors KW - Humans KW - Utah -- epidemiology KW - African Americans KW - Aged KW - Sigmoid Neoplasms -- epidemiology KW - Aged, 80 and over KW - Cecal Neoplasms -- epidemiology KW - European Continental Ancestry Group KW - Adult KW - Connecticut -- epidemiology KW - Incidence KW - Middle Aged KW - United States -- epidemiology KW - Male KW - Female KW - Iowa -- epidemiology KW - Colonic Neoplasms -- epidemiology KW - Rectal Neoplasms -- pathology KW - Rectal Neoplasms -- epidemiology KW - Colonic Neoplasms -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75796585?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Variation+in+colorectal+cancer+incidence+in+the+United+States+by+subsite+of+origin.&rft.au=Devesa%2C+S+S%3BChow%2C+W+H&rft.aulast=Devesa&rft.aufirst=S&rft.date=1993-06-15&rft.volume=71&rft.issue=12&rft.spage=3819&rft.isbn=&rft.btitle=&rft.title=Cancer&rft.issn=0008543X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-07-09 N1 - Date created - 1993-07-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A brief history of opiates, opioid peptides, and opioid receptors. AN - 75794049; 8390660 JF - Proceedings of the National Academy of Sciences of the United States of America AU - Brownstein, M J AD - Laboratory of Cell Biology, National Institute of Mental Health, Bethesda, MD 20892. Y1 - 1993/06/15/ PY - 1993 DA - 1993 Jun 15 SP - 5391 EP - 5393 VL - 90 IS - 12 SN - 0027-8424, 0027-8424 KW - Endorphins KW - 0 KW - Narcotics KW - Receptors, Opioid KW - Opium KW - 8008-60-4 KW - Index Medicus KW - History of medicine KW - Opium -- history KW - History, 20th Century KW - Humans KW - Molecular Sequence Data KW - History, Ancient KW - History, 19th Century KW - Amino Acid Sequence KW - History, Medieval KW - Receptors, Opioid -- history KW - Receptors, Opioid -- metabolism KW - Endorphins -- metabolism KW - Narcotics -- therapeutic use KW - Narcotics -- adverse effects KW - Endorphins -- history KW - Narcotics -- history UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75794049?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+brief+history+of+opiates%2C+opioid+peptides%2C+and+opioid+receptors.&rft.au=Brownstein%2C+M+J&rft.aulast=Brownstein&rft.aufirst=M&rft.date=1993-06-15&rft.volume=90&rft.issue=12&rft.spage=5391&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 - 1993-07-22 N1 - Date created - 1993-07-22 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1971 Aug;68(8):1742-7 [5288759] Science. 1992 Dec 18;258(5090):1952-5 [1335167] Proc Natl Acad Sci U S A. 1973 Jul;70(7):1947-9 [4516196] Nature. 1973 Oct 26;245(5426):447-50 [4127185] Res Commun Chem Pathol Pharmacol. 1973 Nov;6(3):1052-62 [4760880] Acta Pharmacol Toxicol (Copenh). 1973;33(5):377-84 [4801083] Annu Rev Pharmacol. 1975;15:29-47 [238462] Nature. 1975 Dec 18;258(5536):577-80 [1207728] Nature. 1976 Apr 29;260(5554):793-5 [1264258] J Pharmacol Exp Ther. 1976 Jun;197(3):517-32 [945347] Nature. 1977 Jun 9;267(5611):495-9 [195217] Nature. 1979 Mar 29;278(5703):423-7 [221818] Hoppe Seylers Z Physiol Chem. 1979 Sep;360(9):1211-6 [511110] Proc Natl Acad Sci U S A. 1981 Nov;78(11):7219-23 [6118870] Nature. 1982 Jan 21;295(5846):202-6 [6276759] Nature. 1982 Jul 15;298(5871):245-9 [6123953] J Biol Chem. 1983 Feb 10;258(3):1435-8 [6130091] Proc Natl Acad Sci U S A. 1986 Dec;83(24):9832-6 [2432604] Proc Natl Acad Sci U S A. 1987 Aug;84(15):5487-91 [2440052] J Pharmacol Exp Ther. 1987 Aug;242(2):583-7 [3497260] Proc Natl Acad Sci U S A. 1989 Jul;86(13):5188-92 [2544892] Annu Rev Pharmacol Toxicol. 1990;30:123-47 [2160790] Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):12048-52 [1334555] Science. 1973 Mar 9;179(4077):1011-4 [4687585] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Directed mutagenesis and barnase-barstar recognition. AN - 75784308; 8507637 AB - Directed mutagenesis has been applied to the cloned genes of barnase and barstar, the extracellular ribonuclease of Bacillus amyloliquefaciens and its intracellular inhibitor, to locate residues involved in the mutual recognition of these two proteins. Arg59 and His102 of barnase and Asp35 and Asp39 of barstar have been so identified. With both Cys40 and Cys82 mutated to alanines, barstar is still produced in high yield and is functional both in vitro and in vivo. Methods devised for determining relative and absolute dissociation coefficients for various combinations of mutant and wild-type proteins have allowed us to determine a dissociation coefficient for the complex of wild-type barnase and barstar of about 10(-13) M, with off and on rate constants of 10(-5) s-1 and 10(8) M-1 s-1, respectively. JF - Biochemistry AU - Hartley, R W AD - Laboratory of Cellular and Developmental Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/06/15/ PY - 1993 DA - 1993 Jun 15 SP - 5978 EP - 5984 VL - 32 IS - 23 SN - 0006-2960, 0006-2960 KW - Bacterial Proteins KW - 0 KW - Recombinant Proteins KW - barstar protein, Bacillus amyloliquefaciens KW - 37328-61-3 KW - Ribonucleases KW - EC 3.1.- KW - Bacillus amyloliquefaciens ribonuclease KW - EC 3.1.4.- KW - Index Medicus KW - Base Sequence KW - Kinetics KW - Protein Denaturation KW - Molecular Sequence Data KW - Models, Chemical KW - Recombinant Proteins -- chemistry KW - Protein Binding KW - Structure-Activity Relationship KW - Mutagenesis, Site-Directed KW - Bacterial Proteins -- genetics KW - Ribonucleases -- antagonists & inhibitors KW - Bacterial Proteins -- chemistry KW - Bacterial Proteins -- metabolism KW - Ribonucleases -- genetics KW - Ribonucleases -- chemistry KW - Ribonucleases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75784308?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Directed+mutagenesis+and+barnase-barstar+recognition.&rft.au=Hartley%2C+R+W&rft.aulast=Hartley&rft.aufirst=R&rft.date=1993-06-15&rft.volume=32&rft.issue=23&rft.spage=5978&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-07-09 N1 - Date created - 1993-07-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - An insert of seven amino acids confers functional differences between smooth muscle myosins from the intestines and vasculature. AN - 75771227; 8509418 AB - The molecular mechanisms underlying the heterogeneity in contractile properties observed among smooth muscle tissues are unknown. We examined whether part of this diversity might be intrinsic to myosin by comparing structural and enzymatic properties of myosins from two physiologically diverse tissues. Using the reverse transcriptase polymerase chain reaction, we compared avian intestinal smooth muscle and vascular smooth muscle myosin heavy chain (MHC) mRNA. We found that intestinal, but not vascular, MHC mRNA contains an insert of 21 nucleotides, encoding 7 amino acids, in a region near the ATP binding site in the myosin head. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of purified myosin revealed that the relative mobilities of the previously described intestinal MHC isoforms SM1 (204 kDa) and SM2 (200 kDa) were slower than the corresponding vascular SM1 and SM2 isoforms. Furthermore, antibodies raised against a synthetic peptide corresponding to the deduced amino acid sequence of the intestinal insert strongly recognized intestinal SM1 and SM2 but only weakly recognized the vascular isoforms. The presence of the insert in intestinal myosin correlated with a higher velocity of movement of actin filaments in vitro and a higher actin-activated Mg(2+)-ATPase activity, compared with vascular myosin. Other than the MHC insert, one other structural difference distinguished intestinal and vascular myosins: two isoforms of the 17-kDa myosin light chain were found in vascular myosin, whereas a single isoform was found in intestinal myosin. Exchange of the intestinal myosin light chains onto the vascular MHC did not alter its activity in the in vitro motility assay, suggesting that the 7-amino acid MHC insert is responsible for the different enzymatic activities of vascular and intestinal myosins. JF - The Journal of biological chemistry AU - Kelley, C A AU - Takahashi, M AU - Yu, J H AU - Adelstein, R S AD - Laboratory of Molecular Cardiology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/06/15/ PY - 1993 DA - 1993 Jun 15 SP - 12848 EP - 12854 VL - 268 IS - 17 SN - 0021-9258, 0021-9258 KW - Oligodeoxyribonucleotides KW - 0 KW - RNA, Messenger KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - Ca(2+) Mg(2+)-ATPase KW - EC 3.6.1.- KW - Myosins KW - EC 3.6.4.1 KW - Index Medicus KW - Animals KW - Turkeys KW - Gizzard, Avian -- metabolism KW - Amino Acid Sequence KW - Organ Specificity KW - Binding Sites KW - Polymerase Chain Reaction KW - Base Sequence KW - Chickens KW - RNA, Messenger -- metabolism KW - Adenosine Triphosphate -- metabolism KW - Molecular Sequence Data KW - Aorta -- embryology KW - Mutagenesis, Insertional KW - Myosins -- metabolism KW - Myosins -- biosynthesis KW - Myosins -- genetics KW - Muscle, Smooth, Vascular -- metabolism KW - Ca(2+) Mg(2+)-ATPase -- metabolism KW - Muscle, Smooth -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75771227?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=An+insert+of+seven+amino+acids+confers+functional+differences+between+smooth+muscle+myosins+from+the+intestines+and+vasculature.&rft.au=Kelley%2C+C+A%3BTakahashi%2C+M%3BYu%2C+J+H%3BAdelstein%2C+R+S&rft.aulast=Kelley&rft.aufirst=C&rft.date=1993-06-15&rft.volume=268&rft.issue=17&rft.spage=12848&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 - 1993-07-13 N1 - Date created - 1993-07-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Functional redundancy of the DE-1 and alpha A-CRYBP1 regulatory sites of the mouse alpha A-crystallin promoter. AN - 75840653; 8332460 AB - Previous studies have implicated the DE-1 (-111/-106) and alpha A-CRYBP1 (-66/-57) sites for activity of the mouse alpha A-crystallin promoter in transiently transfected lens cells. Here we have used the bacterial chloramphenicol acetyltransferase (CAT) reporter gene to test the functional importance of the putative DE-1 and alpha A-CRYBP1 regulatory elements by site-specific and deletion mutagenesis in stably transformed alpha TN4-1 lens cells and in transgenic mice. FVB/N and C57BL/6 x SJL F2 hybrid transgenic mice were assayed for CAT activity in the lens, heart, lung, kidney, spleen, liver, cerebrum, and muscle. F0, F1, and F2 mice from multiple lines carrying single mutations of the DE-1 or alpha A-CRYBP1 sites showed high levels of CAT activity in the lens, but not in any of the non-lens tissues. By contrast, despite activity of the wild-type promoter, none of the mutant promoter/CAT constructs were active in the transiently transfected and stably transformed lens cells. The mice carrying transgenes with either site-specific mutations in both the DE-1 and alpha A-CRYBP1 sites or a deletion of the entire DE-1 and part of the alpha A-CRYBP1 site (-60/+46) fused to the CAT gene did not exhibit CAT activity above background in any of the tissues examined, including the lens. Our results thus indicate that the DE-1 and alpha A-CRYBP1 sites are functionally redundant in transgenic mice. Moreover, the present data coupled with previous transfection and transgenic mouse experiments suggest that this functional redundancy is confined to lens expression within the mouse and is not evident in transiently transfected and stably transformed lens cells, making the cultured lens cells sensitive indicators of functional elements of crystallin genes. JF - Nucleic acids research AU - Sax, C M AU - Ilagan, J G AU - Piatigorsky, J AD - Laboratory of Molecular and Developmental Biology, NEI, NIH, Bethesda, MD 20892. Y1 - 1993/06/11/ PY - 1993 DA - 1993 Jun 11 SP - 2633 EP - 2640 VL - 21 IS - 11 SN - 0305-1048, 0305-1048 KW - Crystallins KW - 0 KW - Oligodeoxyribonucleotides KW - Recombinant Proteins KW - DNA KW - 9007-49-2 KW - Chloramphenicol O-Acetyltransferase KW - EC 2.3.1.28 KW - beta-Galactosidase KW - EC 3.2.1.23 KW - Index Medicus KW - Animals KW - Organ Specificity KW - Mice KW - Mice, Transgenic KW - Mutagenesis KW - Mutagenesis, Site-Directed KW - Polymerase Chain Reaction KW - DNA -- isolation & purification KW - Mice, Inbred Strains KW - Base Sequence KW - Chickens KW - beta-Galactosidase -- metabolism KW - Transfection KW - Recombinant Proteins -- metabolism KW - DNA -- genetics KW - Molecular Sequence Data KW - beta-Galactosidase -- genetics KW - TATA Box KW - Female KW - Male KW - Sequence Deletion KW - Regulatory Sequences, Nucleic Acid KW - Chloramphenicol O-Acetyltransferase -- genetics KW - Promoter Regions, Genetic KW - Lens, Crystalline -- metabolism KW - Crystallins -- genetics KW - Chloramphenicol O-Acetyltransferase -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75840653?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nucleic+acids+research&rft.atitle=Functional+redundancy+of+the+DE-1+and+alpha+A-CRYBP1+regulatory+sites+of+the+mouse+alpha+A-crystallin+promoter.&rft.au=Sax%2C+C+M%3BIlagan%2C+J+G%3BPiatigorsky%2C+J&rft.aulast=Sax&rft.aufirst=C&rft.date=1993-06-11&rft.volume=21&rft.issue=11&rft.spage=2633&rft.isbn=&rft.btitle=&rft.title=Nucleic+acids+research&rft.issn=03051048&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-08-13 N1 - Date created - 1993-08-13 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Dev Biol. 1990 May;139(1):56-64 [2328840] Mol Cell Biol. 1990 Apr;10(4):1406-14 [2108316] Cell. 1990 Sep 7;62(5):841-3 [2203533] Mol Cell Biol. 1990 Dec;10(12):6813-6 [2247086] Biochim Biophys Acta. 1991 Oct 25;1080(2):173-80 [1932094] J Mol Evol. 1991 Dec;33(6):495-505 [1779432] Development. 1991 Oct;113(2):539-50 [1782865] Nucleic Acids Res. 1992 Jul 25;20(14):3701-12 [1641336] Mol Cell Biol. 1992 Sep;12(9):3978-90 [1508198] J Mol Evol. 1992 Oct;35(4):337-45 [1404419] J Biol Chem. 1992 Nov 15;267(32):23337-41 [1429679] Curr Eye Res. 1990 Jan;9(1):31-7 [2178867] J Biol Chem. 1988 Oct 25;263(30):15666-72 [3170605] Annu Rev Biochem. 1988;57:479-504 [3052280] Virology. 1973 Apr;52(2):456-67 [4705382] Proc Natl Acad Sci U S A. 1980 Dec;77(12):7380-4 [6261253] J Mol Biol. 1981 Jul 25;150(1):1-14 [6271971] Mol Cell Biol. 1982 Sep;2(9):1044-51 [6960240] Proc Natl Acad Sci U S A. 1983 Sep;80(17):5198-202 [6310564] Proc Natl Acad Sci U S A. 1985 Apr;82(8):2334-8 [3857584] Proc Natl Acad Sci U S A. 1985 Jul;82(13):4438-42 [3892534] Proc Natl Acad Sci U S A. 1985 Dec;82(23):7815-9 [3865198] J Mol Evol. 1986;24(1-2):121-9 [3104612] Differentiation. 1986;33(2):168-74 [3569698] Mol Cell Biol. 1987 May;7(5):1807-14 [3474517] Biochem Biophys Res Commun. 1989 Jan 16;158(1):319-25 [2912453] Mol Cell Biol. 1989 Mar;9(3):1083-91 [2725488] Genes Dev. 1989 May;3(5):687-96 [2744460] Cell. 1989 Jul 28;58(2):227-9 [2665943] J Biol Chem. 1989 Nov 25;264(33):19837-44 [2584197] Dev Biol. 1990 Jan;137(1):68-76 [2295367] Genes Dev. 1990 Jan;4(1):29-42 [2106471] Mol Cell Biol. 1990 Jul;10(7):3700-8 [1694016] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - GABAergic cells and signals appear together in the early post-mitotic period of telencephalic and striatal development. AN - 75902341; 8394789 AB - Single cell suspensions derived from embryonic telencephala taken from embryos of gestational day 13 (E13) as well as rat striatal tissue from E14, 15 and 17 were prepared by tissue digestion with papain. Cell suspensions were analyzed by flow cytometry or plated onto poly-D-lysine-coated culture dishes for either nuclear staining or immunocytochemistry. Experiments on functional Na+ channels and GABAA receptor expression were carried out using a fluorescence-activated cell sorter (FACS) and a negatively charged fluorescent indicator dye (oxonol). FACS analysis of embryonic cell suspensions at E13-17 consistently revealed one major subpopulation accounting for 85-90% of the events and one minor subpopulation (10-15% of the total). When sorted, the major subpopulation consisted of phase-bright cells of 5-7 microns diameter some of which had neurites. The minor population consisted of phase-dark cells and resealed membranes of 0.5-4 microns diameter as well as debris. Almost all the cells obtained in the high FALS (forward-angle light scatter) subpopulation at E17 expressed 200-kDa neurofilament and tetanus toxin antigens while the small diameter cells seldom expressed tetanus toxin and particles never did. A small number of GABA-containing neurons were detected in the telencephalon at E13 (3%) and in the developing striatum at E14 (6%). All of the GABA-containing neurons expressed neurofilament. In the embryonic rat striatum, nanomolar concentrations of muscimol (GABAA agonist) induced depolarizing responses. A small number of cells in the high FALS subpopulation were responsive to muscimol starting at embryonic day 14, and the number of responsive cells increased at E15.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Brain research. Developmental brain research AU - Fiszman, M L AU - Behar, T AU - Lange, G D AU - Smith, S V AU - Novotny, E A AU - Barker, J L AD - Laboratory of Neurophysiology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/06/08/ PY - 1993 DA - 1993 Jun 08 SP - 243 EP - 251 VL - 73 IS - 2 SN - 0165-3806, 0165-3806 KW - Fluorescent Dyes KW - 0 KW - Isoxazoles KW - Neuromuscular Depolarizing Agents KW - Sodium Channels KW - oxonol dyes (isoxazole) KW - Muscimol KW - 2763-96-4 KW - gamma-Aminobutyric Acid KW - 56-12-2 KW - Acridine Orange KW - F30N4O6XVV KW - Index Medicus KW - Animals KW - Intermediate Filaments -- metabolism KW - Sodium Channels -- physiology KW - Neuromuscular Depolarizing Agents -- pharmacology KW - Pregnancy KW - Rats KW - Phenotype KW - Rats, Sprague-Dawley KW - Flow Cytometry KW - Immunohistochemistry KW - Muscimol -- pharmacology KW - Female KW - Signal Transduction -- physiology KW - Corpus Striatum -- cytology KW - Telencephalon -- embryology KW - gamma-Aminobutyric Acid -- physiology KW - Telencephalon -- cytology KW - Mitosis -- physiology KW - Corpus Striatum -- embryology KW - Telencephalon -- enzymology KW - Corpus Striatum -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75902341?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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.+Developmental+brain+research&rft.atitle=GABAergic+cells+and+signals+appear+together+in+the+early+post-mitotic+period+of+telencephalic+and+striatal+development.&rft.au=Fiszman%2C+M+L%3BBehar%2C+T%3BLange%2C+G+D%3BSmith%2C+S+V%3BNovotny%2C+E+A%3BBarker%2C+J+L&rft.aulast=Fiszman&rft.aufirst=M&rft.date=1993-06-08&rft.volume=73&rft.issue=2&rft.spage=243&rft.isbn=&rft.btitle=&rft.title=Brain+research.+Developmental+brain+research&rft.issn=01653806&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-09-22 N1 - Date created - 1993-09-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Excitatory amino acid regulation of the enkephalin phenotype in mouse embryonic spinal cord cultures. AN - 75902096; 8353931 AB - Expression of the preproenkephalin gene in developing spinal cord-dorsal root ganglia (SC-DRG) cultures was determined by Northern analysis following treatments with different agonists and antagonists of the glutamate receptor. Cultures (10-12 days old) were treated with various concentrations (10(-7)-10(-3) M) of N-methyl-D-aspartate (NMDA), quisqualate, kainic acid (KA), 2-amino-5-phosphonovaleric acid (APV) and 5-methyl-10,11-dihydro-5H-dibenzo[a, d]cyclohepten-5,10-imine maleate (MK801) either with or without blocking spontaneous electrical activity with 1 microM tetrodotoxin (TTX). In electrically active cultures, treatments with NMDA and KA increased preproenkephalin transcripts (mRNAppENK), showing maximum effects at 1 microM (4-fold and 2-fold, respectively), while treatments with quisqualate and MK801 caused concentration-dependent down-regulation in mRNAppENK. The most effective concentrations of NMDA (1 microM) and quisqualate (10 microM) altered mRNAppENK levels within 4 h of treatment and peaked after 24 h for NMDA and 48 h for quisqualate treatment. Co-treatment with APV completely blocked the NMDA-induced rise of mRNAppENK. During electrical blockade, none of the concentrations of NMDA tested showed any effect on enkephalin expression, neither could NMDA pre-treatment prevent the TTX-induced down-regulation of mRNAppENK. Our results indicate that the activity-dependent establishment of the enkephalin phenotype is modulated through the selective activation of the NMDA-glutamate receptor. JF - Brain research. Developmental brain research AU - Summers, R W AU - Wu, X R AU - Fitzgerald, S C AU - Brenneman, D E AU - von Agoston, D AD - Laboratory of Developmental Neurobiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/06/08/ PY - 1993 DA - 1993 Jun 08 SP - 185 EP - 192 VL - 73 IS - 2 SN - 0165-3806, 0165-3806 KW - Amino Acids KW - 0 KW - Enkephalins KW - Ligands KW - Protein Precursors KW - RNA, Messenger KW - Receptors, Glutamate KW - Tetrodotoxin KW - 4368-28-9 KW - N-Methylaspartate KW - 6384-92-5 KW - preproenkephalin KW - 93443-35-7 KW - Index Medicus KW - Animals KW - Blotting, Northern KW - Receptors, Glutamate -- drug effects KW - Receptors, Glutamate -- metabolism KW - Protein Precursors -- genetics KW - Mice KW - Electric Stimulation KW - RNA, Messenger -- biosynthesis KW - Pregnancy KW - Phenotype KW - Ganglia, Spinal -- cytology KW - RNA, Messenger -- metabolism KW - N-Methylaspartate -- pharmacology KW - Cells, Cultured KW - Protein Precursors -- biosynthesis KW - Mice, Inbred C57BL KW - N-Methylaspartate -- antagonists & inhibitors KW - Ganglia, Spinal -- drug effects KW - Tetrodotoxin -- pharmacology KW - Down-Regulation -- drug effects KW - Female KW - Enkephalins -- genetics KW - Enkephalins -- biosynthesis KW - Spinal Cord -- metabolism KW - Enkephalins -- metabolism KW - Spinal Cord -- embryology KW - Amino Acids -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75902096?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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.+Developmental+brain+research&rft.atitle=Excitatory+amino+acid+regulation+of+the+enkephalin+phenotype+in+mouse+embryonic+spinal+cord+cultures.&rft.au=Summers%2C+R+W%3BWu%2C+X+R%3BFitzgerald%2C+S+C%3BBrenneman%2C+D+E%3Bvon+Agoston%2C+D&rft.aulast=Summers&rft.aufirst=R&rft.date=1993-06-08&rft.volume=73&rft.issue=2&rft.spage=185&rft.isbn=&rft.btitle=&rft.title=Brain+research.+Developmental+brain+research&rft.issn=01653806&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-09-22 N1 - Date created - 1993-09-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Brefeldin A blocks the response of cultured cells to cholera toxin. Implications for intracellular trafficking in toxin action. AN - 75766440; 8389369 AB - Cholera toxin (CT) consists of a pentameric B subunit which binds to ganglioside GM1 on the cell surface and an A subunit which activates adenylylcyclase. The latter process involves the reduction of A to the A1 peptide which ADP-ribosylates the stimulatory G protein, Gs of adenylylcyclase. There is a distinct lag phase between toxin binding and activation of adenylylcyclase. Little is known about the events during this lag including where A1 is generated and how it gains access to Gs on the cytoplasmic side of the plasma membrane. We explored the effects of several inhibitors of intracellular trafficking on the response of human SK-N-MC neurotumor and Caco-2 intestinal tumor cells to CT. Whereas chloroquine or monensin had little or no effect on CT stimulation of cyclic AMP accumulation, brefeldin A (BFA) totally inhibited the response to CT in a time- and dose-dependent and reversible manner. BFA was effective when added at the same time as CT and had an IC50 of 30 ng/ml. BFA did not alter cell surface GM1 as cells treated with BFA for 30 min bound as much 125I-CT as control cells. Furthermore, BFA inhibited CT stimulation of GM1-treated rat glioma C6 cells. BFA treatment did not affect beta-adrenergic agonist stimulation of cyclic AMP. In addition, adenylylcyclase was activated by A1 peptide and NAD+ to the same extent in membranes from control and BFA-treated cells, or when BFA was added directly to the assay. Whereas control cells generated small amounts of A1 from bound CT with time, no A1 was detected in BFA-treated cells. BFA treatment did not prevent the internalization of CT but did inhibit its degradation. BFA is known to disrupt the organization of the Golgi complex, resulting in inhibition of protein transport from the endoplasmic reticulum and redistribution of Golgi enzymes to the endoplasmic reticulum. BFA also prevents the formation of non-clathrin-coated vesicles from Golgi membranes and thus vesicular transport between Golgi cisternae. We confirmed that BFA caused the morphological disruption of the Golgi apparatus in Caco-2 cells. The data support a role for a functional Golgi apparatus with its associated vesicular routing in CT action. JF - The Journal of biological chemistry AU - Orlandi, P A AU - Curran, P K AU - Fishman, P H AD - Membrane Biochemistry Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/06/05/ PY - 1993 DA - 1993 Jun 05 SP - 12010 EP - 12016 VL - 268 IS - 16 SN - 0021-9258, 0021-9258 KW - Cyclopentanes KW - 0 KW - Mycotoxins KW - Brefeldin A KW - 20350-15-6 KW - Chloroquine KW - 886U3H6UFF KW - Cholera Toxin KW - 9012-63-9 KW - Monensin KW - 906O0YJ6ZP KW - Cyclic AMP KW - E0399OZS9N KW - Adenylyl Cyclases KW - EC 4.6.1.1 KW - Isoproterenol KW - L628TT009W KW - Index Medicus KW - Animals KW - Mycotoxins -- pharmacology KW - Enzyme Activation KW - Golgi Apparatus -- drug effects KW - Humans KW - Monensin -- pharmacology KW - Isoproterenol -- pharmacology KW - Biological Transport -- drug effects KW - Rats KW - Tumor Cells, Cultured KW - Chloroquine -- pharmacology KW - Kinetics KW - Golgi Apparatus -- ultrastructure KW - Glioma KW - Adenocarcinoma KW - Time Factors KW - Colonic Neoplasms KW - Cell Line KW - Cyclopentanes -- pharmacology KW - Cyclic AMP -- metabolism KW - Cholera Toxin -- pharmacology KW - Adenylyl Cyclases -- metabolism KW - Cholera Toxin -- antagonists & inhibitors KW - Cholera Toxin -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75766440?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Brefeldin+A+blocks+the+response+of+cultured+cells+to+cholera+toxin.+Implications+for+intracellular+trafficking+in+toxin+action.&rft.au=Orlandi%2C+P+A%3BCurran%2C+P+K%3BFishman%2C+P+H&rft.aulast=Orlandi&rft.aufirst=P&rft.date=1993-06-05&rft.volume=268&rft.issue=16&rft.spage=12010&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 - 1993-07-07 N1 - Date created - 1993-07-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Differential effects of chronic dopamine D1 and D2 receptor agonists on rotational behavior and dopamine receptor binding. AN - 75924537; 8102970 AB - The effects of chronic continuous and intermittent administration of the dopamine D1 receptor agonist SKF 38393 or the D2 receptor agonist quinpirole on rotational behavior and dopamine receptor binding were examined in rats with a unilateral 6-hydroxydopamine lesion of the nigrostriatal pathway. Continuous and intermittent SKF 38393 both decreased the rotational response to subsequent challenge with SKF 38393. Intermittent SKF 38393 increased quinpirole rotation, while continuous SKF 38393 had no effect. Continuous administration of quinpirole did not affect rotation elicited by either SKF 38393 or quinpirole. Intermittent quinpirole, however, increased both SKF 38393- and quinpirole-induced rotation. Autoradiographic techniques were used to measure D1 receptor binding in striatum and substantia nigra pars reticulata and D2 receptor binding in striatum and nucleus accumbens. Intermittent SKF 38393 reduced D1 receptor Bmax and increased D1 Kd in the striatum, while both continuous and intermittent treatment with the D1 agonist decreased D1 binding in the substantia nigra pars reticulata. Intermittent quinpirole decreased D1 receptor Kd in striatum, and continuous quinpirole reduced D1 binding slightly in substantia nigra pars reticulata. Striatal D2 receptor binding was unaffected by treatment with either SKF 38393 or quinpirole. Intermittent SKF 38393 and continuous quinpirole both reversed the lesioned-induced elevation in D2 binding in the nucleus accumbens, while intermittent quinpirole decreased D2 binding in the accumbens on both the intact and denervated sides. Thus, the effects of chronic treatment with D1 and D2 agonists on behavioral responses to D1 and D2 receptor stimulation differed considerably and were dependent on the treatment regimen employed.(ABSTRACT TRUNCATED AT 250 WORDS) JF - European journal of pharmacology AU - Engber, T M AU - Marin, C AU - Susel, Z AU - Chase, T N AD - Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/06/04/ PY - 1993 DA - 1993 Jun 04 SP - 385 EP - 393 VL - 236 IS - 3 SN - 0014-2999, 0014-2999 KW - Dopamine Agents KW - 0 KW - Ergolines KW - Receptors, Dopamine D1 KW - Receptors, Dopamine D2 KW - Quinpirole KW - 20OP60125T KW - 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine KW - 67287-49-4 KW - Oxidopamine KW - 8HW4YBZ748 KW - Index Medicus KW - Animals KW - Substantia Nigra -- injuries KW - Corpus Striatum -- metabolism KW - Autoradiography KW - Denervation KW - Binding Sites KW - Substantia Nigra -- metabolism KW - Rats KW - Rats, Sprague-Dawley KW - Oxidopamine -- toxicity KW - Nucleus Accumbens -- metabolism KW - Male KW - Ergolines -- administration & dosage KW - Ergolines -- pharmacology KW - Dopamine Agents -- pharmacology KW - Receptors, Dopamine D2 -- drug effects KW - Receptors, Dopamine D1 -- drug effects KW - Motor Activity -- drug effects KW - 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine -- pharmacology KW - 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine -- administration & dosage KW - Receptors, Dopamine D1 -- metabolism KW - Receptors, Dopamine D2 -- metabolism KW - Dopamine Agents -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75924537?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+pharmacology&rft.atitle=Differential+effects+of+chronic+dopamine+D1+and+D2+receptor+agonists+on+rotational+behavior+and+dopamine+receptor+binding.&rft.au=Engber%2C+T+M%3BMarin%2C+C%3BSusel%2C+Z%3BChase%2C+T+N&rft.aulast=Engber&rft.aufirst=T&rft.date=1993-06-04&rft.volume=236&rft.issue=3&rft.spage=385&rft.isbn=&rft.btitle=&rft.title=European+journal+of+pharmacology&rft.issn=00142999&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-09-30 N1 - Date created - 1993-09-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - NMDA receptor-mediated glutamate toxicity of cultured cerebellar, cortical and mesencephalic neurons: neuroprotective properties of amantadine and memantine. AN - 75894671; 8102306 AB - Effects of amantadine and memantine on NMDA receptor-mediated glutamate toxicity were studied in cultured cerebellar, cortical and mesencephalic neurons. Both drugs protected cerebellar and cortical neurons against glutamate toxicity, memantine being consistently more effective than amantadine but less effective than MK-801. Glutamate toxicity of dopaminergic neurons in mesencephalic cultures was only mildly attenuated by memantine but was also only incompletely blocked by MK-801. These findings suggest that adamantanamines act by inhibiting NMDA receptor-mediated excitatory neurotransmission. However, since non-NMDA receptors appear to be principal mediators of glutamate toxicity of dopaminergic mesencephalic neurons, adamantanamines may fail to protect the nigrostriatal neurons which specifically degenerate in Parkinson's disease. JF - Brain research AU - Weller, M AU - Finiels-Marlier, F AU - Paul, S M AD - Section on Molecular Pharmacology, National Institute of Mental Health, Bethesda, MD 20892. Y1 - 1993/06/04/ PY - 1993 DA - 1993 Jun 04 SP - 143 EP - 148 VL - 613 IS - 1 SN - 0006-8993, 0006-8993 KW - Excitatory Amino Acid Antagonists KW - 0 KW - Glutamates KW - Receptors, N-Methyl-D-Aspartate KW - Glutamic Acid KW - 3KX376GY7L KW - Dizocilpine Maleate KW - 6LR8C1B66Q KW - Amantadine KW - BF4C9Z1J53 KW - Memantine KW - W8O17SJF3T KW - Index Medicus KW - Rats KW - Mesencephalon -- drug effects KW - Animals KW - Rats, Sprague-Dawley KW - Cerebral Cortex -- drug effects KW - Cell Survival -- drug effects KW - Cells, Cultured KW - Cerebellum -- drug effects KW - Dizocilpine Maleate -- pharmacology KW - Receptors, N-Methyl-D-Aspartate -- physiology KW - Neurons -- drug effects KW - Memantine -- pharmacology KW - Glutamates -- toxicity KW - Amantadine -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75894671?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=NMDA+receptor-mediated+glutamate+toxicity+of+cultured+cerebellar%2C+cortical+and+mesencephalic+neurons%3A+neuroprotective+properties+of+amantadine+and+memantine.&rft.au=Weller%2C+M%3BFiniels-Marlier%2C+F%3BPaul%2C+S+M&rft.aulast=Weller&rft.aufirst=M&rft.date=1993-06-04&rft.volume=613&rft.issue=1&rft.spage=143&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 - 1993-09-15 N1 - Date created - 1993-09-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Restoration of interferon alpha potentiation of a recombinant ricin A chain immunotoxin following cytoreduction of xenografts of advanced ovarian tumors. AN - 75741059; 8492319 AB - We have demonstrated that, in the human ovarian carcinoma cell line (OVCAR-3), recombinant human interferon alpha (rHuIFN-alpha) potentiated in vitro inhibition of protein synthesis by immunotoxins. The antitumor activity of intracavitary immunotoxin administered to nude mice 5 days after tumor cell injection was enhanced by a nontherapeutic dose of rHuIFN-alpha, as evidenced by increased survival time. Our purpose was to determine the outcome of treatment with immunotoxin and rHuIFN-alpha in xenografts of more advanced tumors. At 10 or 15 days after tumor cell injection, nude mice with peritoneal OVCAR-3 xenografts were treated intraperitoneally with immunotoxin or with 454A12 monoclonal antibody (MAb) recombinant ricin A chain (rRA), alone or combined with a nontherapeutic dose of rHuIFN-alpha. The immunotoxin was composed of rRA covalently bound to an anti-CD71 (transferrin receptor) MAb. In other experiments, mice were treated intraperitoneally with cyclophosphamide and cisplatin to reduce tumor size on days 20 and 27 after tumor cell inoculation and then, beginning on day 40, with immunotoxin alone or combined with rHuIFN-alpha. Initiation of treatment 10 days after OVCAR-3 transplantation significantly increased median survival from 41 to 89 days (10% survivors on day 120) with 454A12 MAb rRA alone and to more than 120 days (70% survivors) with 454A12 MAb rRA combined with rHuIFN-alpha (P < .0001). The increase in survival time between tumor-bearing mice treated with immunotoxin combined with rHuIFN-alpha and those treated with immunotoxin alone was statistically significant (P = .017). In contrast, the 15-day transplant tumors were not curable with immunotoxin therapy (survival, 72 days; 0% survivors) and were refractory to rHuIFN-alpha potentiation (survival, 75 days; 0% survivors). After the second course of chemotherapy to reduce the size of the advanced tumors (day 40), during the ascites cell count nadir, initiation of treatment with 454A12 MAb rRA alone or combined with rHuIFN-alpha resulted in significantly different survival times of 129 and 162 days, respectively (P = .0037). Pathologic examination of surviving mice treated with chemotherapy and 454A12 MAb rRA alone or in combination with rHuIFN-alpha revealed that one (17%) of six mice and 11 (65%) of 17 were tumor free, respectively. The synergy between immunotoxins and IFN-alpha is dependent on tumor burden. These agents are less effective against large tumor burdens (i.e., advanced stage disease), but their beneficial effects re-emerge after cytoreduction by combination chemotherapy. The ideal setting for testing the efficacy of intracavitary immunotoxin combined with rHuIFN-alpha after front-line chemotherapy is in patients with residual tumor refractory to additional chemotherapy or in those with toxic effects that prevent delivery of effective doses. JF - Journal of the National Cancer Institute AU - Pearson, J W AU - Fogler, W E AU - Volker, K AU - Riggs, C W AU - Gruys, E AU - Groves, E S AU - Wiltrout, R H AU - Longo, D L AD - Biological Response Modifiers Program, National Cancer Institute (NCI), NCI-Frederick Cancer Research and Development Center FCRDC, Md 21702-1201. Y1 - 1993/06/02/ PY - 1993 DA - 1993 Jun 02 SP - 907 EP - 912 VL - 85 IS - 11 SN - 0027-8874, 0027-8874 KW - Antibodies, Monoclonal KW - 0 KW - Immunotoxins KW - Interferon Type I KW - Recombinant Proteins KW - Ricin KW - 9009-86-3 KW - Index Medicus KW - Neoplasm Transplantation KW - Animals KW - Humans KW - Mice, Nude KW - Mice KW - Drug Synergism KW - Female KW - Antibodies, Monoclonal -- therapeutic use KW - Ricin -- therapeutic use KW - Ovarian Neoplasms -- pathology KW - Interferon Type I -- therapeutic use KW - Immunotoxins -- therapeutic use KW - Ovarian Neoplasms -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75741059?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+National+Cancer+Institute&rft.atitle=Restoration+of+interferon+alpha+potentiation+of+a+recombinant+ricin+A+chain+immunotoxin+following+cytoreduction+of+xenografts+of+advanced+ovarian+tumors.&rft.au=Pearson%2C+J+W%3BFogler%2C+W+E%3BVolker%2C+K%3BRiggs%2C+C+W%3BGruys%2C+E%3BGroves%2C+E+S%3BWiltrout%2C+R+H%3BLongo%2C+D+L&rft.aulast=Pearson&rft.aufirst=J&rft.date=1993-06-02&rft.volume=85&rft.issue=11&rft.spage=907&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+National+Cancer+Institute&rft.issn=00278874&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-06-16 N1 - Date created - 1993-06-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Neuropsychiatric effects of anabolic steroids in male normal volunteers. AN - 75734884; 8492402 AB - To evaluate the acute effects of anabolic steroids on mood and behavior in male normal volunteers. A 2-week, double-blind (subject and rater), fixed-order, placebo-controlled crossover trial of methyltestosterone. An inpatient research unit at the National Institutes of Health. A volunteer sample of 20 men who were medication free, free of medical and psychiatric illness, not involved in athletic training, and had no prior history of anabolic steroid use. A sequential trial for 3 days each of the following four drug conditions: placebo baseline, low-dose methyltestosterone (40 mg/d), high-dose methyltestosterone (240 mg/d), and placebo withdrawal. Mood and behavioral ratings were completed during each drug condition and included both subjective and objective measures. Significant (P < .05) albeit subtle increases in symptom scores were observed during high-dose methyltestosterone administration compared with baseline in positive mood (euphoria, energy, and sexual arousal), negative mood (irritability, mood swings, violent feelings, and hostility), and cognitive impairment (distractibility, forgetfulness, and confusion). An acute manic episode was observed in one of the 20 subjects, representing a 5% incidence, even under these conservative conditions. An additional subject became hypomanic. Baseline characteristics including family psychiatric history or previous drug abuse did not predict symptom changes. This is the first placebo-controlled prospective study demonstrating the adverse and activating mood and behavioral effects of anabolic steroids. JF - JAMA AU - Su, T P AU - Pagliaro, M AU - Schmidt, P J AU - Pickar, D AU - Wolkowitz, O AU - Rubinow, D R AD - Section on Behavioral Endocrinology, National Institute of Mental Health/NIH, Bethesda, MD 20892. Y1 - 1993/06/02/ PY - 1993 DA - 1993 Jun 02 SP - 2760 EP - 2764 VL - 269 IS - 21 SN - 0098-7484, 0098-7484 KW - Anabolic Agents KW - 0 KW - Methyltestosterone KW - V9EFU16ZIF KW - Abridged Index Medicus KW - Index Medicus KW - Prospective Studies KW - Double-Blind Method KW - Humans KW - Adult KW - Anabolic Agents -- metabolism KW - Adolescent KW - Male KW - Psychological Tests KW - Anabolic Agents -- adverse effects KW - Behavior -- drug effects KW - Affect -- drug effects KW - Cognition -- drug effects KW - Methyltestosterone -- metabolism KW - Methyltestosterone -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75734884?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=JAMA&rft.atitle=Neuropsychiatric+effects+of+anabolic+steroids+in+male+normal+volunteers.&rft.au=Su%2C+T+P%3BPagliaro%2C+M%3BSchmidt%2C+P+J%3BPickar%2C+D%3BWolkowitz%2C+O%3BRubinow%2C+D+R&rft.aulast=Su&rft.aufirst=T&rft.date=1993-06-02&rft.volume=269&rft.issue=21&rft.spage=2760&rft.isbn=&rft.btitle=&rft.title=JAMA&rft.issn=00987484&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-06-17 N1 - Date created - 1993-06-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cancer in developing countries: opportunity and challenge. AN - 75730715; 8492315 AB - Epidemiologic observations indicate that environment and lifestyle are the major determinants of the geographical patterns of cancer. The developing countries, which account for 75% of the world's population, have lower incidence rates of cancer compared with the industrialized nations but bear more than half the global cancer burden. Demographic trends resulting from economic progress (decreasing incidence of infectious diseases, population growth, aging, and urbanization), coupled with increased tobacco consumption and dietary changes, indicate that developing countries will bear a continually increasing proportion of the world's cancer burden and its accompanying demand for the provision of costly treatment programs. Yet the developing countries command only 5% of the world's economic resources, and health care programs are already fully extended and frequently inadequate. Thus, cancer control in the developing countries, including preemptive prevention of the anticipated increases in cancers presently more common in the industrialized nations (e.g., lung, breast, and colon), should include much greater emphasis on cancer prevention than is presently the case. But there is another perspective. The developing countries, with their dramatic contrasts in lifestyles and environments and equally diverse patterns of cancer, provide an unparalleled, and often neglected, opportunity for studies directed toward understanding the mechanisms of environmental carcinogenesis. Such an understanding should eventually lead to the development of novel intervention approaches. Unfortunately, cancer research is much more difficult to conduct in the developing countries because of the lack of population-based registries, poor communication and transportation systems, and deficiencies in infrastructure, financial support, and the training of health professionals. These difficulties could be overcome, to the benefit of all, if the extent of collaboration in cancer research between the developing and industrialized nations were to be greatly expanded. JF - Journal of the National Cancer Institute AU - Magrath, I AU - Litvak, J AD - Clinical Oncology Program, National Cancer Institute, Bethesda, Md. 20892. Y1 - 1993/06/02/ PY - 1993 DA - 1993 Jun 02 SP - 862 EP - 874 VL - 85 IS - 11 SN - 0027-8874, 0027-8874 KW - Index Medicus KW - Humans KW - Incidence KW - Developing Countries -- statistics & numerical data KW - International Cooperation KW - Neoplasms -- epidemiology KW - Neoplasms -- prevention & control KW - Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75730715?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+National+Cancer+Institute&rft.atitle=Cancer+in+developing+countries%3A+opportunity+and+challenge.&rft.au=Magrath%2C+I%3BLitvak%2C+J&rft.aulast=Magrath&rft.aufirst=I&rft.date=1993-06-02&rft.volume=85&rft.issue=11&rft.spage=862&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+National+Cancer+Institute&rft.issn=00278874&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-06-16 N1 - Date created - 1993-06-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Fully automated segmentation of cerebrospinal fluid in computed tomography. AN - 75975705; 8378487 AB - A method is presented for automated delineation and measurement of cerebrospinal fluid (CSF) regions in computed tomographic (CT) sections. Regions of skull and scalp are removed by using a linear discriminant analysis approach. Beam-hardening artifact is reduced by subtracting from each section the average radial intensity profile, characterized by a polynomial function. Remaining intensity gradients are suppressed by implementing CSF segmentation with a local thresholding technique based on maximum-entropy principles. CSF fractions from 12 regions of interest (ROIs) were measured in 10 patients with alcoholic Korsakoff syndrome and 9 normal volunteers. The same ROIs were also assessed by an interactive segmentation method, which enabled the operator to compensate for beam-hardening distortions by selecting suitable threshold values for each ROI. Both methods identified the same ROIs as displaying statistically significant differences between the two subject groups. However, interactive segmentation underestimated sulcal CSF by 20-70%, which was confirmed by applying both methods to CT scans of an anthropomorphic phantom. Hence, in contrast to interactive thresholding, unsupervised segmentation relies on firmly fixed criteria that reduce the influence of beam-hardening distortions and provide more objective results. JF - Psychiatry research AU - Ruttimann, U E AU - Joyce, E M AU - Rio, D E AU - Eckardt, M J AD - Laboratory of Clinical Studies, National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, MD 20892. Y1 - 1993/06// PY - 1993 DA - June 1993 SP - 101 EP - 119 VL - 50 IS - 2 SN - 0165-1781, 0165-1781 KW - Index Medicus KW - Artifacts KW - Humans KW - Aged KW - Middle Aged KW - Cerebral Ventriculography KW - Technology, Radiologic KW - Male KW - Tomography, X-Ray Computed -- methods KW - Tomography, X-Ray Computed -- statistics & numerical data KW - Cerebrospinal Fluid -- diagnostic imaging KW - Alcohol Amnestic Disorder -- diagnostic imaging KW - Brain -- diagnostic imaging KW - Tomography, X-Ray Computed -- instrumentation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75975705?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psychiatry+research&rft.atitle=Fully+automated+segmentation+of+cerebrospinal+fluid+in+computed+tomography.&rft.au=Ruttimann%2C+U+E%3BJoyce%2C+E+M%3BRio%2C+D+E%3BEckardt%2C+M+J&rft.aulast=Ruttimann&rft.aufirst=U&rft.date=1993-06-01&rft.volume=50&rft.issue=2&rft.spage=101&rft.isbn=&rft.btitle=&rft.title=Psychiatry+research&rft.issn=01651781&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-10-15 N1 - Date created - 1993-10-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Higher levels of nicotine in arterial than in venous blood after cigarette smoking. AN - 75971483; 8370337 AB - We examined differences between arterial and venous concentrations of nicotine in human subjects. Shortly after smoking a cigarette, levels of nicotine in arterial plasma were more than double those in venous plasma. The time course of the rise in arterial nicotine levels and the magnitude of the arteriovenous difference varied considerably among subjects. For some subjects, arterial nicotine concentrations after one cigarette were similar to venous concentrations typically observed after 20 cigarettes and were nearly 10 times greater than venous concentrations. Our findings have implications for understanding the high degree of addictiveness and cardiovascular toxicity of smoked forms of drugs. JF - Drug and alcohol dependence AU - Henningfield, J E AU - Stapleton, J M AU - Benowitz, N L AU - Grayson, R F AU - London, E D AD - Addiction Research Center, National Institute on Drug Abuse, Balitmore, MD 21224. Y1 - 1993/06// PY - 1993 DA - June 1993 SP - 23 EP - 29 VL - 33 IS - 1 SN - 0376-8716, 0376-8716 KW - Nicotine KW - 6M3C89ZY6R KW - Index Medicus KW - Veins KW - Humans KW - Arteries KW - Metabolic Clearance Rate -- physiology KW - Adult KW - Male KW - Smoking -- blood KW - Nicotine -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75971483?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Drug+and+alcohol+dependence&rft.atitle=Higher+levels+of+nicotine+in+arterial+than+in+venous+blood+after+cigarette+smoking.&rft.au=Henningfield%2C+J+E%3BStapleton%2C+J+M%3BBenowitz%2C+N+L%3BGrayson%2C+R+F%3BLondon%2C+E+D&rft.aulast=Henningfield&rft.aufirst=J&rft.date=1993-06-01&rft.volume=33&rft.issue=1&rft.spage=23&rft.isbn=&rft.btitle=&rft.title=Drug+and+alcohol+dependence&rft.issn=03768716&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-10-14 N1 - Date created - 1993-10-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Comorbid psychopathy is not associated with increased D2 dopamine receptor TaqI A or B gene marker frequencies in incarcerated substance abusers. AN - 75939542; 8104042 JF - Biological psychiatry AU - Smith, S S AU - Newman, J P AU - Evans, A AU - Pickens, R AU - Wydeven, J AU - Uhl, G R AU - Newlin, D B AD - National Institute on Drug Abuse, Addiction Research Center, Baltimore, MD. PY - 1993 SP - 845 EP - 848 VL - 33 IS - 11-12 SN - 0006-3223, 0006-3223 KW - Genetic Markers KW - 0 KW - Receptors, Dopamine D2 KW - DNA KW - 9007-49-2 KW - Deoxyribonucleases, Type II Site-Specific KW - EC 3.1.21.4 KW - TCGA-specific type II deoxyribonucleases KW - Index Medicus KW - Genetic Linkage KW - Analysis of Variance KW - Psychiatric Status Rating Scales KW - Gene Frequency KW - Polymorphism, Restriction Fragment Length KW - Humans KW - Adult KW - DNA -- analysis KW - Prisoners KW - Male KW - Personality Disorders -- genetics KW - Substance-Related Disorders -- complications KW - Receptors, Dopamine D2 -- genetics KW - Personality Disorders -- psychology KW - Substance-Related Disorders -- psychology KW - Personality Disorders -- complications KW - Substance-Related Disorders -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75939542?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biological+psychiatry&rft.atitle=Comorbid+psychopathy+is+not+associated+with+increased+D2+dopamine+receptor+TaqI+A+or+B+gene+marker+frequencies+in+incarcerated+substance+abusers.&rft.au=Smith%2C+S+S%3BNewman%2C+J+P%3BEvans%2C+A%3BPickens%2C+R%3BWydeven%2C+J%3BUhl%2C+G+R%3BNewlin%2C+D+B&rft.aulast=Smith&rft.aufirst=S&rft.date=1993-06-01&rft.volume=33&rft.issue=11-12&rft.spage=845&rft.isbn=&rft.btitle=&rft.title=Biological+psychiatry&rft.issn=00063223&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-10-21 N1 - Date created - 1993-10-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Glucocorticoids synergize with tumor necrosis factor alpha in the induction of HIV expression from a chronically infected promonocytic cell line. AN - 75906717; 8347399 AB - In this study we have investigated the effects of glucocorticoids (GCs) on the expression of human immunodeficiency virus (HIV) in a chronically infected promonocytic cell line, U1. Although no increase in virus production was observed in U1 cells stimulated with physiological concentrations of GC alone, costimulation with dexamethasone plus tumor necrosis factor alpha (TNF-alpha) synergistically enhanced TNF-alpha-dependent HIV expression. Molecular analysis demonstrated that GCs plus TNF-alpha resulted in an accumulation of steady state HIV RNA secondary to either an increase in transcription or an increase in message stability. These findings may be of physiological relevance because GCs are used in the treatment of certain disorders associated with HIV infection and TNF-alpha levels have been reported to be elevated in the plasma and cerebrospinal fluid of certain HIV-infected individuals. JF - AIDS research and human retroviruses AU - Bressler, P AU - Poli, G AU - Justement, J S AU - Biswas, P AU - Fauci, A S AD - Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/06// PY - 1993 DA - June 1993 SP - 547 EP - 551 VL - 9 IS - 6 SN - 0889-2229, 0889-2229 KW - HIV Antigens KW - 0 KW - RNA, Messenger KW - Tumor Necrosis Factor-alpha KW - Dexamethasone KW - 7S5I7G3JQL KW - Index Medicus KW - AIDS/HIV KW - Virus Replication -- drug effects KW - HIV Antigens -- biosynthesis KW - Transcription, Genetic KW - Monocytes -- microbiology KW - Stem Cells -- microbiology KW - Drug Synergism KW - RNA, Messenger -- biosynthesis KW - Cell Line KW - HIV -- growth & development KW - HIV -- drug effects KW - Dexamethasone -- pharmacology KW - Tumor Necrosis Factor-alpha -- pharmacology KW - Gene Expression Regulation, Viral -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75906717?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Glucocorticoids+synergize+with+tumor+necrosis+factor+alpha+in+the+induction+of+HIV+expression+from+a+chronically+infected+promonocytic+cell+line.&rft.au=Bressler%2C+P%3BPoli%2C+G%3BJustement%2C+J+S%3BBiswas%2C+P%3BFauci%2C+A+S&rft.aulast=Bressler&rft.aufirst=P&rft.date=1993-06-01&rft.volume=9&rft.issue=6&rft.spage=547&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 - 1993-09-10 N1 - Date created - 1993-09-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Immunotherapy and neuropsychiatric toxicity. Nursing clinical management consideration. AN - 75879078; 8348526 AB - Ensuring the safety of patients who receive immunotherapy is an essential element of nursing care. Communicating changes in mental status to the medical team is important feedback for modifying or discontinuing the cycle of immunotherapy. These observations are even more crucial if neuropsychiatric toxicity (NPT) has been exhibited in a previous cycle of treatment. If nurses are aware of associative factors of NPT they can be more alert for emerging cognitive dysfunction. Early intervention will also mean the nurse will take additional measures to ensure patient safety, such as suggesting possible pharmacological alternatives and closer observation, and encouraging family members to help with orientation. The nurse can further assist by helping alleviate the patient's or family's feelings of helplessness by assuring them that the NPT will begin to subside once treatment has been terminated. JF - Cancer nursing AU - Sparber, A G AU - Biller-Sparber, K AD - National Institutes of Health, Clinical Center, Bethesda, MD. Y1 - 1993/06// PY - 1993 DA - June 1993 SP - 188 EP - 192 VL - 16 IS - 3 SN - 0162-220X, 0162-220X KW - Immunologic Factors KW - 0 KW - Interleukin-2 KW - Index Medicus KW - Nursing KW - Humans KW - Middle Aged KW - Male KW - Family -- psychology KW - Confusion -- psychology KW - Interleukin-2 -- adverse effects KW - Akathisia, Drug-Induced -- nursing KW - Substance-Related Disorders -- nursing KW - Substance-Related Disorders -- etiology KW - Akathisia, Drug-Induced -- psychology KW - Akathisia, Drug-Induced -- etiology KW - Substance-Related Disorders -- psychology KW - Confusion -- nursing KW - Confusion -- chemically induced KW - Immunologic Factors -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75879078?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+nursing&rft.atitle=Immunotherapy+and+neuropsychiatric+toxicity.+Nursing+clinical+management+consideration.&rft.au=Sparber%2C+A+G%3BBiller-Sparber%2C+K&rft.aulast=Sparber&rft.aufirst=A&rft.date=1993-06-01&rft.volume=16&rft.issue=3&rft.spage=188&rft.isbn=&rft.btitle=&rft.title=Cancer+nursing&rft.issn=0162220X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-09-10 N1 - Date created - 1993-09-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Suspended judgment. The 1953 clinical trial of diethylstilbestrol during pregnancy: could it have stopped DES use? AN - 75861820; 8339548 JF - Controlled clinical trials AU - Berendes, H W AU - Lee, Y J AD - Division of Epidemiology, Statistics and Prevention Research, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/06// PY - 1993 DA - June 1993 SP - 179 EP - 182 VL - 14 IS - 3 SN - 0197-2456, 0197-2456 KW - Diethylstilbestrol KW - 731DCA35BT KW - Index Medicus KW - History of medicine KW - United States KW - History, 20th Century KW - Adenocarcinoma -- chemically induced KW - Vaginal Neoplasms -- chemically induced KW - Humans KW - Drug Monitoring -- history KW - Vaginal Neoplasms -- history KW - United States Food and Drug Administration -- history KW - Adenocarcinoma -- history KW - Female KW - Pregnancy KW - Diethylstilbestrol -- adverse effects KW - Clinical Trials as Topic -- history KW - Clinical Trials as Topic -- standards KW - Diethylstilbestrol -- history KW - Prenatal Exposure Delayed Effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75861820?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Controlled+clinical+trials&rft.atitle=Suspended+judgment.+The+1953+clinical+trial+of+diethylstilbestrol+during+pregnancy%3A+could+it+have+stopped+DES+use%3F&rft.au=Berendes%2C+H+W%3BLee%2C+Y+J&rft.aulast=Berendes&rft.aufirst=H&rft.date=1993-06-01&rft.volume=14&rft.issue=3&rft.spage=179&rft.isbn=&rft.btitle=&rft.title=Controlled+clinical+trials&rft.issn=01972456&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-09-02 N1 - Date created - 1993-09-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Thromboxane and prostacyclin differentially regulate murine extracellular matrix gene expression. AN - 75812841; 8315934 AB - Alterations in the arachidonic acid metabolites thromboxane and prostacyclin are known to contribute to hemodynamic changes observed in certain models of acute and chronic renal failure. We have previously shown that thromboxane may have an important role in mediating glomerulosclerosis by stimulating the expression of certain extracellular matrix proteins. In the present study, we compared the effects of thromboxane and prostacyclin on the expression of genes encoding basement membrane proteins using a murine teratocarcinoma cell line, that when differentiated to an endodermal phenotype synthesizes abundant extracellular matrix. Incubation of these cells with stable analogs of thromboxane and prostacyclin for four hours resulted in changes in basement membrane gene expression. Thromboxane increased steady-state mRNA levels for all three laminin chains, type IV collagen, and fibronectin, but decreased the level of mRNA for heparan sulfate proteoglycan. In contrast, incubation with carbo-prostacyclin, a stable analog of prostacyclin, decreased the steady-state mRNA level for the laminin A and B1 chains, type IV collagen and fibronectin, and increased the mRNA level for heparan sulfate proteoglycan and laminin B2. Carbo-prostacyclin did not affect cellular proliferation or thymidine incorporation. These results indicate that eicosanoids directly modulate matrix gene expression independently of hemodynamic influence, and independently of effects mediated by platelets, or mitogenesis. Furthermore, these findings suggest that the alterations in renal eicosanoid metabolism may directly participate in the pathogenesis of glomerulosclerosis and thus provide a rationale for therapy directed toward the specific inhibition of thromboxane in the treatment of progressive glomerular sclerosis. JF - Kidney international AU - Bruggeman, L A AU - Pellicoro, J A AU - Horigan, E A AU - Klotman, P E AD - Molecular Medicine Section, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland. Y1 - 1993/06// PY - 1993 DA - June 1993 SP - 1219 EP - 1225 VL - 43 IS - 6 SN - 0085-2538, 0085-2538 KW - Extracellular Matrix Proteins KW - 0 KW - Fibronectins KW - Heparan Sulfate Proteoglycans KW - Laminin KW - Proteoglycans KW - RNA, Messenger KW - Thromboxane A2 KW - 57576-52-0 KW - Collagen KW - 9007-34-5 KW - Heparitin Sulfate KW - 9050-30-0 KW - Epoprostenol KW - DCR9Z582X0 KW - Index Medicus KW - Collagen -- genetics KW - Animals KW - Proteoglycans -- genetics KW - Tumor Cells, Cultured KW - Laminin -- genetics KW - RNA, Messenger -- analysis KW - Mice KW - Fibronectins -- genetics KW - Heparitin Sulfate -- genetics KW - Epoprostenol -- pharmacology KW - Extracellular Matrix Proteins -- genetics KW - Gene Expression Regulation -- drug effects KW - Thromboxane A2 -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75812841?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Kidney+international&rft.atitle=Thromboxane+and+prostacyclin+differentially+regulate+murine+extracellular+matrix+gene+expression.&rft.au=Bruggeman%2C+L+A%3BPellicoro%2C+J+A%3BHorigan%2C+E+A%3BKlotman%2C+P+E&rft.aulast=Bruggeman&rft.aufirst=L&rft.date=1993-06-01&rft.volume=43&rft.issue=6&rft.spage=1219&rft.isbn=&rft.btitle=&rft.title=Kidney+international&rft.issn=00852538&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-07-27 N1 - Date created - 1993-07-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of 3-methylcholanthrene induction on the distribution and DNA adduction of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) in F344 rats. AN - 75791207; 8514213 AB - 3-Methylcholanthrene (3MC) is a potent inducer of the cytochrome P450IA family of enzymes that catalyses the metabolic activation of the food mutagen/carcinogen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ). We have examined the effect of pretreatment with 3MC on the distribution and DNA adduct formation of IQ in male Fischer F344 rats. 3 hr after a single dose of [14C]IQ (10 mg/kg body weight, by gavage), the level of radioactivity in extrahepatic tissues was 30-70% less in 3MC-pretreated rats than in vehicle control rats. Although the level of radioactivity in the liver did not change after 3MC pretreatment, IQ-DNA adduct levels, measured by the 32P-postlabelling method, were 60% lower in the livers of 3MC-pretreated rats than those of control rats, and 83-97% lower in extrahepatic tissues such as the kidneys, colon, small intestine, bladder, heart and lung. IQ-DNA adducts in the testes and brain were found in control rats but were not detected in 3MC-pretreated rats. The rate of removal of IQ-DNA adducts from the livers of control and 3MC-pretreated animals was the same from 3 to 48 hr. At 48 hr, the adduct level in 3MC-pretreated rats remained lower than that seen in the control rats. The data suggest that 3MC induction of the P450IA family of cytochromes in vivo results in an increased rate of IQ detoxification. JF - Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association AU - Snyderwine, E G AU - Nouso, K AU - Schut, H A AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, Bethesda, MD 20892. Y1 - 1993/06// PY - 1993 DA - June 1993 SP - 415 EP - 423 VL - 31 IS - 6 SN - 0278-6915, 0278-6915 KW - Carcinogens KW - 0 KW - Mutagens KW - Quinolines KW - 2-amino-3-methylimidazo(4,5-f)quinoline KW - 30GL3D3T0G KW - Methylcholanthrene KW - 56-49-5 KW - DNA KW - 9007-49-2 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Oxidoreductases KW - EC 1.- KW - Cytochrome P-450 CYP1A1 KW - EC 1.14.14.1 KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Enzyme Induction -- drug effects KW - Tissue Distribution KW - Male KW - Quinolines -- toxicity KW - Methylcholanthrene -- pharmacology KW - DNA -- metabolism KW - Carcinogens -- pharmacokinetics KW - Carcinogens -- toxicity KW - Mutagens -- toxicity KW - Cytochrome P-450 Enzyme System -- biosynthesis KW - Mutagens -- pharmacokinetics KW - Quinolines -- pharmacokinetics KW - Oxidoreductases -- biosynthesis KW - DNA -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75791207?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Effect+of+3-methylcholanthrene+induction+on+the+distribution+and+DNA+adduction+of+2-amino-3-methylimidazo%5B4%2C5-f%5Dquinoline+%28IQ%29+in+F344+rats.&rft.au=Snyderwine%2C+E+G%3BNouso%2C+K%3BSchut%2C+H+A&rft.aulast=Snyderwine&rft.aufirst=E&rft.date=1993-06-01&rft.volume=31&rft.issue=6&rft.spage=415&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 - 1993-07-20 N1 - Date created - 1993-07-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Immunohistochemical localization of transforming growth factor-beta 1 in rats with experimental silicosis, alveolar type II hyperplasia, and lung cancer. AN - 75783349; 8389528 AB - Immunohistochemical localization of transforming growth factor-beta 1 (TGF-beta 1) was studied in the lungs of rats given crystalline silica or ferric oxide by single intratracheal instillation. Ferric oxide elicited no progressive granulomatous reaction, no epithelial hyperplasia, and no lung tumors; no demonstrable reactivity to TGF-beta 1 was observed. Silica induced a granulomatous reaction with progressive fibrosis, adjacent alveolar type II hyperplasia, and alveolar carcinomas. Rabbit polyclonal antibodies to synthetic peptides corresponding to the first 30 amino acids of mature TGF-beta 1, anti-LC (1-30), and anti-CC (1-30) were used for the localization of intracellular and extracellular TGF-beta 1. An antibody to a peptide corresponding to amino acids 266-278 of the TGF-beta 1 precursor sequence, anti-Pre (266-278), was used to detect the TGF-beta precursor and the latency-associated peptide. Intracellular mature TGF-beta (anti-LC) was demonstrated in fibroblasts and macrophages located at the periphery of silicotic granulomas and in fibroblasts adjacent to hyperplastic type II cells. Extracellular mature TGF-beta 1 was localized in the connective tissue matrix of the granulomas and in the stroma of both hyperplastic type II cells and well-differentiated adenocarcinomas. Immunoreactivity to anti-Pre was localized, intracellularly, in hyperplastic alveolar type II cells and their proliferative lesions adjacent to granulomas, in adenomas, but not in adenocarcinomas. The hyperplastic type II cells appear to be the sites of production and secretion of TGF-beta 1, which may regulate their own growth and differentiation and mediate the production of extracellular TGF-beta 1-associated matrix. The lack of reactivity to TGF-beta 1 precursor in the adenocarcinomas is consistent with the loss of normal cellular differentiation and function. TGF-beta 1 appears to have a pathogenetic role in silica-induced mesenchymal and epithelial lesions. The role of TGF-beta 1 and other cytokines in silica-induced carcinogenesis requires further investigation. JF - The American journal of pathology AU - Williams, A O AU - Flanders, K C AU - Saffiotti, U AD - Laboratory of Experimental Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/06// PY - 1993 DA - June 1993 SP - 1831 EP - 1840 VL - 142 IS - 6 SN - 0002-9440, 0002-9440 KW - Ferric Compounds KW - 0 KW - Protein Precursors KW - Transforming Growth Factor beta KW - ferric oxide KW - 1K09F3G675 KW - Silicon Dioxide KW - 7631-86-9 KW - Abridged Index Medicus KW - Index Medicus KW - Rats KW - Hyperplasia -- pathology KW - Animals KW - Rats, Inbred F344 KW - Protein Precursors -- metabolism KW - Hyperplasia -- etiology KW - Hyperplasia -- metabolism KW - Disease Models, Animal KW - Male KW - Female KW - Silicosis -- metabolism KW - Pulmonary Alveoli -- pathology KW - Adenocarcinoma -- metabolism KW - Silicosis -- pathology KW - Lung -- chemistry KW - Lung -- metabolism KW - Lung -- pathology KW - Adenocarcinoma -- pathology KW - Transforming Growth Factor beta -- analysis KW - Adenoma -- metabolism KW - Lung Neoplasms -- etiology KW - Transforming Growth Factor beta -- physiology KW - Adenocarcinoma -- etiology KW - Adenoma -- etiology KW - Adenoma -- pathology KW - Transforming Growth Factor beta -- metabolism KW - Silicosis -- etiology KW - Lung Neoplasms -- metabolism KW - Lung Neoplasms -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75783349?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+of+pathology&rft.atitle=Immunohistochemical+localization+of+transforming+growth+factor-beta+1+in+rats+with+experimental+silicosis%2C+alveolar+type+II+hyperplasia%2C+and+lung+cancer.&rft.au=Williams%2C+A+O%3BFlanders%2C+K+C%3BSaffiotti%2C+U&rft.aulast=Williams&rft.aufirst=A&rft.date=1993-06-01&rft.volume=142&rft.issue=6&rft.spage=1831&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+pathology&rft.issn=00029440&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-07-08 N1 - Date created - 1993-07-08 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Am J Respir Cell Mol Biol. 1991 May;4(5):455-62 [2021482] N Engl J Med. 1991 Apr 4;324(14):933-40 [1900574] Hum Pathol. 1992 Jan;23(1):13-20 [1544664] Microbiol Immunol. 1986;30(11):1189-98 [3027514] Br J Cancer. 1980 Jun;41(6):908-17 [6252921] Fed Proc. 1983 Jun;42(9):2621-6 [6303865] Cancer Res. 1984 May;44(5):2170-80 [6324999] J Clin Invest. 1984 May;73(5):1462-72 [6325504] J Leukoc Biol. 1986 Feb;39(2):123-32 [3001212] J Biol Chem. 1986 Mar 25;261(9):4337-45 [3456347] Proc Natl Acad Sci U S A. 1986 Jun;83(12):4167-71 [2424019] Cancer Res. 1986 Sep;46(9):4665-71 [3089593] Exp Cell Res. 1986 Dec;167(2):539-49 [3464447] Am J Ind Med. 1987;11(1):93-107 [3028139] Lab Invest. 1987 Nov;57(5):546-54 [2824924] J Cell Biol. 1987 Dec;105(6 Pt 2):2861-76 [3320058] Biochem J. 1987 Nov 1;247(3):597-604 [3501287] Proc Natl Acad Sci U S A. 1988 Mar;85(5):1539-43 [3422749] Nature. 1988 Mar 17;332(6161):217-9 [2831460] J Biol Chem. 1988 Jun 5;263(16):7646-54 [3163692] J Pharmacol Exp Ther. 1988 Aug;246(2):765-71 [2457084] Br J Cancer. 1988 Jun;57(6):594-600 [3044431] Recent Prog Horm Res. 1988;44:157-97 [3064207] J Cell Biol. 1989 Feb;108(2):653-60 [2465297] Am J Ind Med. 1989;15(3):343-6 [2539015] J Clin Invest. 1989 May;83(5):1661-6 [2708527] J Mol Cell Cardiol. 1989 Feb;21 Suppl 1:151-9 [2733025] Proc Natl Acad Sci U S A. 1989 Jun;86(12):4544-8 [2734305] J Cell Biol. 1989 Jun;108(6):2477-82 [2500447] J Exp Med. 1989 Sep 1;170(3):727-37 [2475572] Postgrad Med J. 1988;64 Suppl 4:26-34 [3076931] J Clin Invest. 1989 Dec;84(6):1836-42 [2480367] Nature. 1990 Mar 15;344(6263):245-7 [2156165] Am J Respir Cell Mol Biol. 1990 Apr;2(4):381-90 [2157474] Ann N Y Acad Sci. 1990;580:225-32 [2186691] J Cell Biol. 1990 Aug;111(2):757-63 [1696270] Am J Respir Cell Mol Biol. 1991 Aug;5(2):155-62 [1892646] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Expression of hepatocyte growth factor and c-met genes during hepatic differentiation and liver development in the rat. AN - 75783323; 8506951 AB - Hepatocyte growth factor (HGF) is a potent mitogen for mature hepatocytes in vitro. The receptor for HGF has recently been characterized as the product of the proto-oncogene c-met. We have examined the possible involvement of HGF in hepatic growth and differentiation in the rat. The experimental systems used were acetylaminofluorene treatment combined with partial hepatectomy to induce proliferation and differentiation of oval cells in adult liver and the pre- and postnatal liver. In the acetylaminofluorene model, Northern blot analysis showed that level of HGF transcripts increased one day after partial hepatectomy, reached a peak by day 6, were maintained at that level until day 13, and then declined, reaching normal level at 20 days. The expression of c-met also increased gradually, reached a peak around 9 to 13 days after partial hepatectomy, at which time oval cell proliferation was most prominent. In the developing liver, an elevated level of HGF transcripts was found between 4 and 21 days after birth. The expression of c-met also slightly increased at the same time. In situ hybridization showed that the transcripts for HGF were localized in desmin-positive Ito cells, whereas the transcripts for c-met were strongly expressed by oval cells. We have shown earlier that Ito cells and oval cells proliferate simultaneously and exist in close proximity in the acetylaminofluorene model and that Ito cells are a primary source of growth factors such as transforming growth factor-alpha and acidic fibroblast growth factors. The data presented here suggest that HGF is, in combination with other growth factors, involved in the proliferation and differentiation of oval cells via a paracrine mechanism. JF - The American journal of pathology AU - Hu, Z AU - Evarts, R P AU - Fujio, K AU - Marsden, E R AU - Thorgeirsson, S S AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-0037. Y1 - 1993/06// PY - 1993 DA - June 1993 SP - 1823 EP - 1830 VL - 142 IS - 6 SN - 0002-9440, 0002-9440 KW - Proto-Oncogene Proteins KW - 0 KW - Hepatocyte Growth Factor KW - 67256-21-7 KW - 2-Acetylaminofluorene KW - 9M98QLJ2DL KW - Proto-Oncogene Proteins c-met KW - EC 2.7.10.1 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Blotting, Northern KW - Cell Division -- drug effects KW - Transcription, Genetic KW - Rats KW - In Situ Hybridization KW - Rats, Inbred F344 KW - 2-Acetylaminofluorene -- pharmacology KW - Hepatectomy KW - Cell Differentiation -- drug effects KW - Time Factors KW - Immunohistochemistry KW - Male KW - Hepatocyte Growth Factor -- analysis KW - Hepatocyte Growth Factor -- physiology KW - Liver -- cytology KW - Gene Expression -- genetics KW - Proto-Oncogene Proteins -- analysis KW - Proto-Oncogenes -- genetics KW - Hepatocyte Growth Factor -- genetics KW - Proto-Oncogene Proteins -- metabolism KW - Liver -- metabolism KW - Proto-Oncogene Proteins -- genetics KW - Liver -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75783323?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+of+pathology&rft.atitle=Expression+of+hepatocyte+growth+factor+and+c-met+genes+during+hepatic+differentiation+and+liver+development+in+the+rat.&rft.au=Hu%2C+Z%3BEvarts%2C+R+P%3BFujio%2C+K%3BMarsden%2C+E+R%3BThorgeirsson%2C+S+S&rft.aulast=Hu&rft.aufirst=Z&rft.date=1993-06-01&rft.volume=142&rft.issue=6&rft.spage=1823&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+pathology&rft.issn=00029440&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-07-08 N1 - Date created - 1993-07-08 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nature. 1989 May 11;339(6220):155-6 [2541345] Proc Natl Acad Sci U S A. 1989 Oct;86(19):7432-6 [2477840] Nature. 1989 Nov 23;342(6248):440-3 [2531289] Mol Carcinog. 1989;2(6):345-54 [2619882] Proc Natl Acad Sci U S A. 1990 Apr;87(8):3200-4 [2139229] Curr Opin Cell Biol. 1990 Feb;2(1):121-30 [2183836] J Clin Invest. 1990 Jun;85(6):1833-43 [1693377] Cancer Res. 1990 Jul 1;50(13):3811-5 [1693878] Ann N Y Acad Sci. 1990;593:231-42 [2165377] Biochem Biophys Res Commun. 1990 Nov 30;173(1):42-7 [2147853] Biochem Biophys Res Commun. 1991 Jan 15;174(1):331-7 [1846541] Science. 1991 Feb 15;251(4995):802-4 [1846706] Biochem Biophys Res Commun. 1991 Jan 31;174(2):831-8 [1704229] Hepatology. 1991 Apr;13(4):743-50 [1826282] Biochem Biophys Res Commun. 1991 Apr 15;176(1):45-51 [1708252] Oncogene. 1991 Apr;6(4):501-4 [1827664] Biochem Biophys Res Commun. 1991 May 31;177(1):330-5 [1828341] Biochem Biophys Res Commun. 1991 May 31;177(1):559-65 [1828343] Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):7001-5 [1831266] Hepatology. 1991 Sep;14(3):488-94 [1831438] Mol Cell Biol. 1991 Sep;11(9):4405-14 [1875930] Exp Cell Res. 1991 Sep;196(1):114-20 [1879464] EMBO J. 1991 Oct;10(10):2867-78 [1655405] FEBS Lett. 1991 Sep 23;290(1-2):9-12 [1915898] Biochem Biophys Res Commun. 1991 Oct 31;180(2):765-73 [1835386] Cell. 1991 Nov 29;67(5):901-8 [1835669] Hepatology. 1992 Jan;15(1):149-55 [1530787] Mol Carcinog. 1992;5(1):25-31 [1543539] Biochem Biophys Res Commun. 1992 Mar 16;183(2):739-42 [1532309] Crit Rev Oncog. 1992;3(1-2):27-54 [1312869] Lab Invest. 1992 Oct;67(4):427-33 [1279268] Br J Cancer. 1979 Nov;40(5):782-90 [41564] Cancer Res. 1984 Oct;44(10):4414-9 [6235912] Biochem Biophys Res Commun. 1984 Aug 16;122(3):1450-9 [6477569] J Cell Sci. 1985 Aug;77:209-23 [3841349] Cancer Res. 1987 Oct 15;47(20):5469-75 [2443240] Carcinogenesis. 1987 Nov;8(11):1737-40 [3664968] Proc Natl Acad Sci U S A. 1989 Mar;86(5):1558-62 [2922399] Cancer Res. 1989 Mar 15;49(6):1541-7 [2466557] Blood. 1989 May 15;73(7):1794-800 [2469500] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of a binding site for the human immunodeficiency virus type 1 nucleocapsid protein. AN - 75773355; 8506369 AB - The nucleocapsid (NC) protein NCp7 of human immunodeficiency virus type 1 (HIV-1) is important for encapsidation of the virus genome, RNA dimerization, and primer tRNA annealing in vitro. Here we present evidence from gel mobility-shift experiments indicating that NCp7 binds specifically to an RNA sequence. Two complexes were identified in native gels. The more slowly migrating complex contained two RNA molecules and one peptide, while the more rapidly migrating one is composed of one RNA and one peptide. Further, mutational analysis of the RNA shows that the predicted stem and loop structure of stem-loop 1 plays a critical role. Our results show that NCp7 binds to a unique RNA structure within the psi region; in addition, this structure is necessary for RNA dimerization. We propose that NCp7 binds to the RNA via a direct interaction of one zinc-binding motif to stem-loop 1 followed by binding of the other zinc-binding motif to stem-loop 1, stem-loop 2, or the linker region of the second RNA molecule, forming a bridge between the two RNAs. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Sakaguchi, K AU - Zambrano, N AU - Baldwin, E T AU - Shapiro, B A AU - Erickson, J W AU - Omichinski, J G AU - Clore, G M AU - Gronenborn, A M AU - Appella, E AD - Laboratory of Cell Biology, National Cancer Institute, Bethesda, MD 20892. Y1 - 1993/06/01/ PY - 1993 DA - 1993 Jun 01 SP - 5219 EP - 5223 VL - 90 IS - 11 SN - 0027-8424, 0027-8424 KW - gag KW - Cross-Linking Reagents KW - 0 KW - Peptide Fragments KW - RNA, Viral KW - Viral Core Proteins KW - Bromodeoxyuridine KW - G34N38R2N1 KW - Index Medicus KW - AIDS/HIV KW - Peptide Fragments -- metabolism KW - Ultraviolet Rays KW - Nucleic Acid Conformation KW - Binding Sites KW - Mutagenesis KW - Peptide Fragments -- chemical synthesis KW - Zinc Fingers -- physiology KW - Base Sequence KW - Zinc Fingers -- genetics KW - Molecular Sequence Data KW - Protein Folding KW - Genes, gag KW - Sequence Deletion KW - HIV-1 -- metabolism KW - HIV-1 -- genetics KW - Capsid -- genetics KW - RNA, Viral -- chemistry KW - Viral Core Proteins -- genetics KW - Capsid -- metabolism KW - RNA, Viral -- genetics KW - Viral Core Proteins -- metabolism KW - RNA, Viral -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75773355?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Identification+of+a+binding+site+for+the+human+immunodeficiency+virus+type+1+nucleocapsid+protein.&rft.au=Sakaguchi%2C+K%3BZambrano%2C+N%3BBaldwin%2C+E+T%3BShapiro%2C+B+A%3BErickson%2C+J+W%3BOmichinski%2C+J+G%3BClore%2C+G+M%3BGronenborn%2C+A+M%3BAppella%2C+E&rft.aulast=Sakaguchi&rft.aufirst=K&rft.date=1993-06-01&rft.volume=90&rft.issue=11&rft.spage=5219&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 - 1993-07-07 N1 - Date created - 1993-07-07 N1 - Date revised - 2017-01-13 N1 - Gene symbol - gag N1 - SuppNotes - Cited By: Nucleic Acids Res. 1990 Dec 25;18(24):7287-92 [2259624] J Mol Biol. 1990 Dec 5;216(3):689-99 [2124274] Int J Pept Protein Res. 1990 Dec;36(6):551-8 [1708745] J Virol. 1992 Feb;66(2):632-40 [1309906] J Virol. 1992 Jul;66(7):4144-53 [1602537] Proc Natl Acad Sci U S A. 1992 Jul 15;89(14):6472-6 [1631144] Pept Res. 1988 Nov-Dec;1(2):74-80 [2856555] J Virol. 1981 Jan;37(1):109-16 [6260966] J Biol Chem. 1981 Aug 25;256(16):8400-6 [6267042] J Virol. 1985 May;54(2):401-7 [3989912] Anal Biochem. 1987 Nov 1;166(2):368-79 [2449095] EMBO J. 1988 Jun;7(6):1777-83 [2458920] Science. 1989 Apr 7;244(4900):48-52 [2468181] Proc Natl Acad Sci U S A. 1989 Oct;86(20):7706-10 [2479010] J Virol. 1990 Jan;64(1):450-2 [2152832] J Virol. 1990 Feb;64(2):774-83 [2153242] Methods Enzymol. 1989;180:51-62 [2482430] Biochemistry. 1990 Jan 16;29(2):329-40 [2105740] J Mol Biol. 1990 Jan 20;211(2):447-63 [2407856] J Virol. 1990 Jul;64(7):3207-11 [2191147] Comput Appl Biosci. 1990 Oct;6(4):309-18 [1701685] J Biol Chem. 1991 Apr 15;266(11):7306-11 [2016331] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Oxidative stress and thiol modification induced by chronic administration of haloperidol. AN - 75773018; 8509999 AB - Haloperidol, a widely used neuroleptic, acts through blockade of dopamine receptors leading to increased turnover of dopamine. Increased turnover of dopamine could lead to excessive production of hydrogen peroxide and, thus, generate oxidative stress. The effect of chronic administration of haloperidol on glutathione (GSH)-protein thiol homeostasis and lipid peroxidation was examined in rat brain regions. The oxidized GSH levels increased significantly, though not substantially, in cortex (CT, 15%), striatum (ST, 28%) and midbrain (MB, 27%). Maximal decreases in GSH levels were noted in CT (23%), ST (28%) and MB (20%) after 1 month of haloperidol administration. The GSH levels recovered thereafter, and after 6 months of haloperidol treatment, the GSH levels were not significantly different from control in ST and MB. The depleted GSH was recovered essentially as protein-GSH mixed disulfide with a concomitant decrease in the protein thiol concentration in all the three regions of the brain. The increase in oxidized GSH concentration represented only 1.8, 2.0 and 3.5% of the depleted GSH in the CT, ST and MB after 1 month of haloperidol administration. The concentration of thiobarbituric acid-reactive products increased significantly up to 3 months of haloperidol treatment, but at the end of 6 months, the levels were substantially decreased. The present study demonstrates that haloperidol administration for 1 month results in significant oxidative stress in CT, ST and MB regions of the brain, as demonstrated by alterations in GSH-protein thiol homeostasis and increased lipid peroxidation products. However, after prolonged administration of haloperidol for 6 months, the GSH-protein thiol homeostasis is restored to a large extent, concomitant with the decrease in the concentration of lipid peroxidation products. Administration of haloperidol leads to development of tolerance (supersensitivity of the dopamine autoreceptors) to neuroleptics, which is associated with decreased turnover of dopamine; this may result in overcoming the oxidative stress generated initially due to increased dopamine turnover. JF - The Journal of pharmacology and experimental therapeutics AU - Shivakumar, B R AU - Ravindranath, V AD - Department of Neurochemistry, National Institute of Mental Health and Neuro Sciences, Bangalore, India. Y1 - 1993/06// PY - 1993 DA - June 1993 SP - 1137 EP - 1141 VL - 265 IS - 3 SN - 0022-3565, 0022-3565 KW - Sulfhydryl Compounds KW - 0 KW - Malondialdehyde KW - 4Y8F71G49Q KW - Glutathione KW - GAN16C9B8O KW - Haloperidol KW - J6292F8L3D KW - Index Medicus KW - Rats KW - Oxidation-Reduction KW - Malondialdehyde -- metabolism KW - Animals KW - Rats, Sprague-Dawley KW - Sulfhydryl Compounds -- metabolism KW - Brain -- drug effects KW - Brain -- metabolism KW - Homeostasis -- drug effects KW - Haloperidol -- adverse effects KW - Glutathione -- metabolism KW - Haloperidol -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75773018?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Oxidative+stress+and+thiol+modification+induced+by+chronic+administration+of+haloperidol.&rft.au=Shivakumar%2C+B+R%3BRavindranath%2C+V&rft.aulast=Shivakumar&rft.aufirst=B&rft.date=1993-06-01&rft.volume=265&rft.issue=3&rft.spage=1137&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 - 1993-07-14 N1 - Date created - 1993-07-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutagenesis of EIAV TAT reveals structural features essential for transcriptional activation and TAR element recognition. AN - 75772969; 8389074 AB - Certain members of the lentivirus subfamily of retroviruses encode unique transcriptional activator (Tat) proteins that modify the transcription complex after binding to the 5' end of nascent viral mRNA. The Tat proteins are modular, containing RNA-binding and activation domains that can be exchanged between different Tat proteins or replaced with heterologous protein fragments. While there is considerable sequence conservation among the divergent Tat proteins, there are also some structural differences that might be informative. For example, a cluster of basic amino acids in HIV-1 Tat is sufficient for RNA binding in vivo and in vitro. The homologous region of EIAV Tat is necessary but not sufficient for recognition of its cognate cis-acting RNA element; the entire C-terminal 26 amino acids of EIAV Tat, including the basic patch, are required. To better understand the structure-function relationships in EIAV Tat, we have generated a battery of expression plasmids encoding insertion, deletion, and missense mutations in the carboxy-terminal region of the tat gene. The plasmids were tested for their ability to trans-activate the EIAV promoter or to trans-inhibit a heterologous Tat protein. A mutation of a glutamine to an arginine in the cluster of basic residues generated a potent trans-dominant inhibitor of both EIAV and HIV-1 Tat, indicating that the mutation abolished RNA binding but did not alter the activation domain. Mutations at the extreme C-terminus of EIAV Tat impaired both RNA binding and activation domain functions, suggesting effects on secondary or tertiary structure. JF - Virology AU - Derse, D AU - Newbold, S H AD - Laboratory of Viral Carcinogenesis, NCI-Frederick Cancer Research and Development Center, Maryland 21702-1201. Y1 - 1993/06// PY - 1993 DA - June 1993 SP - 530 EP - 536 VL - 194 IS - 2 SN - 0042-6822, 0042-6822 KW - Gene Products, tat KW - 0 KW - RNA-Binding Proteins KW - Recombinant Fusion Proteins KW - tat Gene Products, Human Immunodeficiency Virus KW - Index Medicus KW - AIDS/HIV KW - HIV-1 -- genetics KW - DNA Mutational Analysis KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Sequence Homology, Amino Acid KW - Precipitin Tests KW - Transcriptional Activation KW - Structure-Activity Relationship KW - Mutagenesis KW - Promoter Regions, Genetic KW - RNA-Binding Proteins -- genetics KW - Gene Expression Regulation, Viral KW - RNA-Binding Proteins -- immunology KW - Infectious Anemia Virus, Equine -- genetics KW - Transcription, Genetic KW - Gene Products, tat -- immunology KW - Gene Products, tat -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75772969?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Virology&rft.atitle=Mutagenesis+of+EIAV+TAT+reveals+structural+features+essential+for+transcriptional+activation+and+TAR+element+recognition.&rft.au=Derse%2C+D%3BNewbold%2C+S+H&rft.aulast=Derse&rft.aufirst=D&rft.date=1993-06-01&rft.volume=194&rft.issue=2&rft.spage=530&rft.isbn=&rft.btitle=&rft.title=Virology&rft.issn=00426822&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-06-25 N1 - Date created - 1993-06-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - 2B and 2C mutations are essential but mutations throughout the genome of HAV contribute to adaptation to cell culture. AN - 75771337; 8389072 AB - Chimeric viruses constructed from various portions of two infectious cDNA clones representing the genomes of the wild-type and cell culture-adapted mutants of the HM-175 strain of hepatitis A virus were compared for their ability to replicate in cultures of fetal rhesus kidney cells. Mutations located in either the 5' or 3' third of the genome could markedly enhance growth in vitro but only when they were combined with mutations in the P2 region within either the 2B or the 2C gene. Therefore, mutations in 2B and 2C are essential for cell culture adaptation but mutations elsewhere in the genome also contribute significantly to the enhanced growth rate. JF - Virology AU - Emerson, S U AU - Huang, Y K AU - Purcell, R H AD - Hepatitis Viruses Section, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/06// PY - 1993 DA - June 1993 SP - 475 EP - 480 VL - 194 IS - 2 SN - 0042-6822, 0042-6822 KW - 2B KW - 2C KW - Capsid Proteins KW - 0 KW - DNA, Recombinant KW - DNA, Viral KW - Viral Nonstructural Proteins KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Animals KW - Transfection KW - Cells, Cultured KW - Capsid -- genetics KW - Macaca mulatta KW - DNA, Viral -- genetics KW - Adaptation, Biological KW - Cloning, Molecular KW - Viral Nonstructural Proteins -- genetics KW - Hepatovirus -- growth & development KW - Mutation -- genetics KW - Genome, Viral KW - Hepatovirus -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75771337?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Virology&rft.atitle=2B+and+2C+mutations+are+essential+but+mutations+throughout+the+genome+of+HAV+contribute+to+adaptation+to+cell+culture.&rft.au=Emerson%2C+S+U%3BHuang%2C+Y+K%3BPurcell%2C+R+H&rft.aulast=Emerson&rft.aufirst=S&rft.date=1993-06-01&rft.volume=194&rft.issue=2&rft.spage=475&rft.isbn=&rft.btitle=&rft.title=Virology&rft.issn=00426822&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-06-25 N1 - Date created - 1993-06-25 N1 - Date revised - 2017-01-13 N1 - Gene symbol - 2B; 2C N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regulation of gonadotropin-releasing hormone by protein kinase-A and -C in immortalized hypothalamic neurons. AN - 75770896; 8504741 AB - As major signal transduction cascades, the protein kinase-A and -C (PKA and PKC) pathways have been implicated in the regulation of GnRH synthesis and secretion in the hypothalamus. We have investigated the roles of these pathways in the regulation of GnRH transcription, mRNA levels, propeptide processing, and secretion in GT1-7 cells, a mouse hypothalamic GnRH neuronal cell line. Forskolin, which activates adenylate cyclase to raise cAMP levels, had no effect on GnRH mRNA levels at 10 microM, but induced c-fos mRNA at 30 min. An activator of PKC, 12-O-tetradecanoylphorbol-13-acetate (TPA; 100 nM), also induced c-fos at 30 min, but produced a progressive decline in GnRH mRNA, resulting in a 70% decrease by 16 h. Coadministration of 10 nM TPA and 20 microM of a PKC inhibitor, NPC 15437 [2,6-diamino-N-([1-(1-oxotridecyl)2-piperidinyl]methyl)hexanami de], prevented c-fos induction, but did not antagonize GnRH repression. Instead, the inhibitor itself reduced GnRH mRNA levels by 56% at 16 h (with no effect on c-fos mRNA). Thus, since extended exposure to TPA can down-regulate PKC, suppression of GnRH mRNA by TPA may be due to decreased PKC activity, indicating a role for PKC in the maintenance of the GnRH gene expression (a role that is unlikely to involve c-fos). In transient transfections, the transcriptional activity from 3 kilobases of GnRH 5'-flanking sequence was repressed 2-fold by either 100 nM TPA or 20 microM NPC 15437 at 24 h, demonstrating that suppression of GnRH mRNA is at least, in part, at the level of transcription. In contrast, both TPA (100 nM) and forskolin (10 microM) stimulated secretion. Enhancement of GnRH secretion by TPA was robust and rapid (2.5 min), while the response to forskolin was relatively delayed (2 h). Over a 24-h period, unstimulated cells released primarily unprocessed prohormone, whereas forskolin and TPA stimulated the secretion of processed products. These data indicate that PKC and PKA may influence propeptide processing and/or the route of GnRH secretion. These data demonstrate that the PKA and PKC pathways regulate GnRH at the multiple levels of transcription, pro-GnRH processing, and GnRH secretion. JF - Endocrinology AU - Wetsel, W C AU - Eraly, S A AU - Whyte, D B AU - Mellon, P L AD - Laboratory of Molecular and Integrative Neuroscience, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1993/06// PY - 1993 DA - June 1993 SP - 2360 EP - 2370 VL - 132 IS - 6 SN - 0013-7227, 0013-7227 KW - Oligonucleotide Probes KW - 0 KW - Piperidines KW - Protein Precursors KW - RNA, Messenger KW - progonadoliberin I KW - NPC 15437 KW - 136449-85-9 KW - Colforsin KW - 1F7A44V6OU KW - Gonadotropin-Releasing Hormone KW - 33515-09-2 KW - Protein Kinases KW - EC 2.7.- KW - Protein Kinase C KW - EC 2.7.11.13 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Abridged Index Medicus KW - Index Medicus KW - Piperidines -- pharmacology KW - Protein Processing, Post-Translational -- drug effects KW - Animals KW - Colforsin -- pharmacology KW - Base Sequence KW - Transcription, Genetic -- drug effects KW - Protein Precursors -- metabolism KW - Oligonucleotide Probes -- genetics KW - RNA, Messenger -- metabolism KW - Molecular Sequence Data KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Cell Line, Transformed KW - Gonadotropin-Releasing Hormone -- metabolism KW - Protein Kinase C -- antagonists & inhibitors KW - Protein Kinases -- physiology KW - Neurons -- metabolism KW - Neurons -- drug effects KW - Hypothalamus -- metabolism KW - Neurons -- cytology KW - Hypothalamus -- cytology KW - Protein Kinase C -- physiology KW - Gonadotropin-Releasing Hormone -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75770896?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Regulation+of+gonadotropin-releasing+hormone+by+protein+kinase-A+and+-C+in+immortalized+hypothalamic+neurons.&rft.au=Wetsel%2C+W+C%3BEraly%2C+S+A%3BWhyte%2C+D+B%3BMellon%2C+P+L&rft.aulast=Wetsel&rft.aufirst=W&rft.date=1993-06-01&rft.volume=132&rft.issue=6&rft.spage=2360&rft.isbn=&rft.btitle=&rft.title=Endocrinology&rft.issn=00137227&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-07-02 N1 - Date created - 1993-07-02 N1 - Date revised - 2017-01-24 N1 - Last updated - 2017-01-25 ER - TY - JOUR T1 - A recombinant form of Pseudomonas exotoxin A containing transforming growth factor alpha near its carboxyl terminus for the treatment of bladder cancer. AN - 75766364; 8501821 AB - The epidermal growth factor receptor (EGFR) is overexpressed on the superficial layers of malignant urothelium and is suspected of playing a role in tumor progression. TP40 is a chimeric protein composed of transforming growth factor-alpha (TGF alpha) fused to a modified form of Pseudomonas exotoxin A (PE) that is selectively cytotoxic to EGFR-bearing cells and is currently undergoing clinical study for the intravesical therapy of bladder cancer. We constructed a recombinant toxin PE35/TGF alpha-KDEL as an improved agent for the local therapy of EGFR-bearing bladder cancer. PE35/TGF alpha-KDEL does not require intracellular proteolysis to generate a carboxyl-terminal fragment capable of reaching the target cell cytosol and contains a modified carboxyl-terminal sequence KDEL, that increases toxin activity. These features make PE35/TGF alpha-KDEL from 10- to 700-fold more potent than TP40 on four human bladder cancer cell lines. PE35/TGF alpha-KDEL may be a useful agent for treatment of EGFR-bearing cancers. JF - The Journal of urology AU - Theuer, C P AU - FitzGerald, D J AU - Pastan, I AD - Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/06// PY - 1993 DA - June 1993 SP - 1626 EP - 1632 VL - 149 IS - 6 SN - 0022-5347, 0022-5347 KW - Bacterial Toxins KW - 0 KW - Exotoxins KW - Immunotoxins KW - Recombinant Fusion Proteins KW - Recombinant Proteins KW - Transforming Growth Factor alpha KW - Virulence Factors KW - transforming growth factor(alpha)-Pseudomonas exotoxin A (35) KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - toxA protein, Pseudomonas aeruginosa KW - EC 2.4.2.31 KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - Abridged Index Medicus KW - Index Medicus KW - Receptor, Epidermal Growth Factor -- drug effects KW - Drug Screening Assays, Antitumor KW - Humans KW - In Vitro Techniques KW - Pseudomonas aeruginosa KW - Drug Design KW - Recombinant Proteins -- therapeutic use KW - Transforming Growth Factor alpha -- therapeutic use KW - Urinary Bladder Neoplasms -- chemistry KW - Bacterial Toxins -- therapeutic use KW - Urinary Bladder Neoplasms -- therapy KW - Immunotoxins -- therapeutic use KW - Exotoxins -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75766364?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+urology&rft.atitle=A+recombinant+form+of+Pseudomonas+exotoxin+A+containing+transforming+growth+factor+alpha+near+its+carboxyl+terminus+for+the+treatment+of+bladder+cancer.&rft.au=Theuer%2C+C+P%3BFitzGerald%2C+D+J%3BPastan%2C+I&rft.aulast=Theuer&rft.aufirst=C&rft.date=1993-06-01&rft.volume=149&rft.issue=6&rft.spage=1626&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+urology&rft.issn=00225347&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-06-29 N1 - Date created - 1993-06-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mechanisms of nitric oxide-mediated neurotoxicity in primary brain cultures. AN - 75756910; 7684776 AB - In addition to mediating several physiological functions, nitric oxide (NO) has been implicated in the cytotoxicities observed following activation of macrophages or excess stimulation of neurons by glutamate. We extend our previous observations of glutamate-stimulated, NO-mediated neurotoxicity in primary cultures of rat fetal cortical, striatal, and hippocampal neurons. Neurotoxicity elicited by either NMDA or sodium nitroprusside (SNP) exhibits a similar concentration-effect relationship and time course. The concentration-effect curve of NMDA-induced neurotoxicity is shifted to the right in the presence of nitro-L-arginine and farther to the right in arginine-free media. The rank order of potency of several NO synthase (NOS) inhibitors in preventing neurotoxicity is the same as the rank order of these compounds in inhibiting NOS, and this inhibition is stereospecific. NMDA neurotoxicity is also prevented by flavoprotein inhibitors and calmodulin inhibitors, fitting with the roles of flavoproteins and calmodulin as NOS regulators. 8-Bromo-cGMP and guanylyl cyclase inhibitors do not affect neurotoxicity, while superoxide dismutase attenuates neurotoxicity. NOS neurons appear to be the source of neurotoxic NO in culture, as lesions of these neurons with 20 microM quisqualate diminish subsequent NMDA neurotoxicity. Moreover, NMDA neurotoxicity develops over time in culture coincident with the expression of NOS. Immunohistochemical localization of NOS in cultures and intact brain demonstrates widespread distribution of the cell processes suggesting that NOS neurons contact the majority of cortical neurons and so could mediate widespread neurotoxicity. JF - The Journal of neuroscience : the official journal of the Society for Neuroscience AU - Dawson, V L AU - Dawson, T M AU - Bartley, D A AU - Uhl, G R AU - Snyder, S H AD - National Institute on Drug Abuse, Addiction Research Center, Laboratory of Molecular Neurobiology, Baltimore, Maryland 21224. Y1 - 1993/06// PY - 1993 DA - June 1993 SP - 2651 EP - 2661 VL - 13 IS - 6 SN - 0270-6474, 0270-6474 KW - Neurotoxins KW - 0 KW - Superoxides KW - 11062-77-4 KW - Nitric Oxide KW - 31C4KY9ESH KW - N-Methylaspartate KW - 6384-92-5 KW - Nitric Oxide Synthase KW - EC 1.14.13.39 KW - Amino Acid Oxidoreductases KW - EC 1.4.- KW - Cyclic GMP KW - H2D2X058MU KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Rats KW - Animals KW - Superoxides -- pharmacology KW - Amino Acid Oxidoreductases -- metabolism KW - N-Methylaspartate -- pharmacology KW - Cells, Cultured KW - Amino Acid Oxidoreductases -- antagonists & inhibitors KW - Cyclic GMP -- physiology KW - Calcium -- physiology KW - Neurons -- enzymology KW - Brain -- cytology KW - Brain -- drug effects KW - Nitric Oxide -- metabolism KW - Neurotoxins -- pharmacology KW - Brain -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75756910?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mechanisms+of+nitric+oxide-mediated+neurotoxicity+in+primary+brain+cultures.&rft.au=Dawson%2C+V+L%3BDawson%2C+T+M%3BBartley%2C+D+A%3BUhl%2C+G+R%3BSnyder%2C+S+H&rft.aulast=Dawson&rft.aufirst=V&rft.date=1993-06-01&rft.volume=13&rft.issue=6&rft.spage=2651&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+neuroscience+%3A+the+official+journal+of+the+Society+for+Neuroscience&rft.issn=02706474&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-06-28 N1 - Date created - 1993-06-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Parameters affecting the development of non-Hodgkin's lymphoma in patients with severe human immunodeficiency virus infection receiving antiretroviral therapy. AN - 75754273; 8099121 AB - To investigate the occurrence of non-Hodgkin's lymphoma (NHL) in human immunodeficiency virus (HIV)-infected patients receiving long-term antiretroviral therapy and factors associated with the development of these lymphomas. The charts of 55 patients with advanced HIV infection receiving zidovudine (formerly known as azidothymidine [AZT])-based therapy and 61 patients receiving dideoxyinosine (ddI) were examined for the occurrence of NHL. Stored samples from the AZT-based treatment cohort were examined retrospectively for parameters predictive of the subsequent development of lymphoma. Eight of 55 patients receiving AZT-based therapy developed NHL, yielding an estimated probability of 12% (95% confidence interval [CI], 4.7% to 27.1%) after 24 months, and 29.2% (95% CI, 15.2% to 48.7%) after 36 months. Four of 61 patients receiving ddI developed NHL, yielding a 6.2% (95% CI, 2.1% to 17%) estimated probability after 24 months, and 9.5% (95% CI, 3.6% to 22.8%) after 36 months. The difference between these cohorts was not significant (two-tailed P [P2] = .13). Patients with less than 50 CD4 cells/microL developed NHL at a significantly higher rate (P2 = .0085). This was particularly true for patients who presented with primary CNS lymphoma (PCNSL). For patients receiving AZT-based therapy, pretreatment serum interleukin-6 (IL-6) levels were somewhat higher in those who subsequently developed NHL than in those who did not (P2 = .048). HIV-infected patients with profound immunodeficiency, especially those with less than 50 CD4 cells/microL, are at substantial risk of developing NHL and particularly PCNSL. Additional studies are needed to define the role of other factors such as IL-6 in the pathogenesis of these opportunistic tumors. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Pluda, J M AU - Venzon, D J AU - Tosato, G AU - Lietzau, J AU - Wyvill, K AU - Nelson, D L AU - Jaffe, E S AU - Karp, J E AU - Broder, S AU - Yarchoan, R AD - Medicine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/06// PY - 1993 DA - June 1993 SP - 1099 EP - 1107 VL - 11 IS - 6 SN - 0732-183X, 0732-183X KW - Interleukin-6 KW - 0 KW - Zidovudine KW - 4B9XT59T7S KW - Didanosine KW - K3GDH6OH08 KW - Index Medicus KW - AIDS/HIV KW - Interleukin-6 -- blood KW - Risk Factors KW - Humans KW - Leukocyte Count KW - CD4-Positive T-Lymphocytes KW - Zidovudine -- therapeutic use KW - Didanosine -- therapeutic use KW - Lymphoma, AIDS-Related -- immunology KW - Zidovudine -- adverse effects KW - HIV Infections -- complications KW - HIV Infections -- immunology KW - HIV Infections -- drug therapy KW - Lymphoma, Non-Hodgkin -- etiology KW - Didanosine -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75754273?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Parameters+affecting+the+development+of+non-Hodgkin%27s+lymphoma+in+patients+with+severe+human+immunodeficiency+virus+infection+receiving+antiretroviral+therapy.&rft.au=Pluda%2C+J+M%3BVenzon%2C+D+J%3BTosato%2C+G%3BLietzau%2C+J%3BWyvill%2C+K%3BNelson%2C+D+L%3BJaffe%2C+E+S%3BKarp%2C+J+E%3BBroder%2C+S%3BYarchoan%2C+R&rft.aulast=Pluda&rft.aufirst=J&rft.date=1993-06-01&rft.volume=11&rft.issue=6&rft.spage=1099&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 - 1993-06-29 N1 - Date created - 1993-06-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - cDNA cloning, chromosomal mapping, and functional characterization of the human peroxisome proliferator activated receptor. AN - 75752033; 7684926 AB - The human peroxisome proliferator activated receptor (hPPAR) was cloned from a human liver cDNA library. The cDNA exhibited 85% and 91% DNA and deduced amino acid sequence identity with mouse PPAR (mPPAR), respectively. The hPPAR gene was mapped on human chromosome 22 slightly telomeric to a linkage group of six genes and genetic markers that are located in the general region 22q12-q13.1. Cotransfection assays of mouse Hepa 1 cells were used to roughly compare the ability of hPPAR- and mPPAR-expressed cDNAs to trans-activate the acyl CoA oxidase (ACO) PPAR response element located 5' upstream to the minimal thymidine kinase promoter driving the expression of the chloramphenicol acetyl transferase (CAT) reporter gene. Both receptors elicited a response with the prototypical peroxisome proliferators nafenopin, clofibrate, and WY-14,643. Moreover, using cotransfection assays in which the CAT reporter plasmid contained the CYP4 A6 gene response element rather than the ACO element, it was shown that hPPAR is capable of very efficiently trans-activating a second PPAR response element. These results indicate that the PPAR is present in humans in a form that is functional and can trans-activate response elements derived from two different genes, the rat ACO and the rabbit CYP4A6. JF - Biochemistry AU - Sher, T AU - Yi, H F AU - McBride, O W AU - Gonzalez, F J AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1993/06/01/ PY - 1993 DA - 1993 Jun 01 SP - 5598 EP - 5604 VL - 32 IS - 21 SN - 0006-2960, 0006-2960 KW - Oligodeoxyribonucleotides KW - 0 KW - Pyrimidines KW - Receptors, Cell Surface KW - Receptors, Cytoplasmic and Nuclear KW - Transcription Factors KW - Nafenopin KW - 093W78U96W KW - pirinixic acid KW - 86C4MRT55A KW - DNA KW - 9007-49-2 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Mixed Function Oxygenases KW - EC 1.- KW - Oxidoreductases KW - Cytochrome P-450 CYP4A KW - EC 1.14.15.3 KW - Acyl-CoA Oxidase KW - EC 1.3.3.6 KW - Chloramphenicol O-Acetyltransferase KW - EC 2.3.1.28 KW - Thymidine Kinase KW - EC 2.7.1.21 KW - Deoxyribonuclease HpaII KW - EC 3.1.21.- KW - Deoxyribonucleases, Type II Site-Specific KW - EC 3.1.21.4 KW - TCGA-specific type II deoxyribonucleases KW - Clofibrate KW - HPN91K7FU3 KW - Index Medicus KW - Genetic Linkage KW - Animals KW - Humans KW - Chromosome Mapping KW - Rats KW - Promoter Regions, Genetic KW - Lod Score KW - Molecular Sequence Data KW - Microbodies -- ultrastructure KW - Microbodies -- drug effects KW - Microbodies -- metabolism KW - Gene Library KW - Cytochrome P-450 Enzyme System -- genetics KW - Nafenopin -- pharmacology KW - Pyrimidines -- pharmacology KW - Rabbits KW - Amino Acid Sequence KW - Mice KW - Chloramphenicol O-Acetyltransferase -- metabolism KW - Transcription Factors -- genetics KW - Cloning, Molecular KW - Clofibrate -- pharmacology KW - Polymerase Chain Reaction KW - Chloramphenicol O-Acetyltransferase -- genetics KW - Base Sequence KW - Oxidoreductases -- genetics KW - Thymidine Kinase -- genetics KW - Mixed Function Oxygenases -- genetics KW - Chromosomes, Human, Pair 22 KW - Polymorphism, Restriction Fragment Length KW - DNA -- genetics KW - Receptors, Cell Surface -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75752033?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=cDNA+cloning%2C+chromosomal+mapping%2C+and+functional+characterization+of+the+human+peroxisome+proliferator+activated+receptor.&rft.au=Sher%2C+T%3BYi%2C+H+F%3BMcBride%2C+O+W%3BGonzalez%2C+F+J&rft.aulast=Sher&rft.aufirst=T&rft.date=1993-06-01&rft.volume=32&rft.issue=21&rft.spage=5598&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-07-06 N1 - Date created - 1993-07-06 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - S60099; GENBANK; L16878; L02932; L16873; L11867; L11866; L11865; L16876; L16875; L16874 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dissociation of progeny vaccinia virus from the cell membrane is regulated by a viral envelope glycoprotein: effect of a point mutation in the lectin homology domain of the A34R gene. AN - 75751129; 8497053 AB - Vaccinia virus strains vary considerably in the amounts of extracellular enveloped virus (EEV) that they release from infected cells. The IHD-J strain produces up to 40 times more EEV than does the related WR strain and consequently generates elongated comet-shaped virus plaques instead of sharply defined round ones in susceptible monolayer cells under liquid medium. The difference in EEV formation is due to the retention of enveloped WR virions on the cell surface (R. Blasco and B. Moss, J. Virol. 66:4170-4179, 1992). By using WR and IHD-J DNA fragments for marker transfer and analyzing the progeny virus by the comet formation assay, we determined that gene A34R and at least one other gene regulate the release of cell-associated virions. Replacement of the A34R gene of WR with the corresponding gene from IHD-J increased the amount of EEV produced by 10-fold and conferred the ability to form distinctive comet-shaped plaques. Gene A34R encodes an EEV-specific glycoprotein with homology to C-type animal lectins (S.A. Duncan and G.L. Smith, J. Virol. 66:1610-1621, 1992). The nucleotide sequences of the A34R genes of WR and IHD-J strains differed in six positions, of which four were silent. One of the codon mutations (Lys-151-->Glu), which is located in the putative carbohydrate recognition domain, was sufficient to transfer a comet-forming phenotype to WR virus. These data indicate that the A34R-encoded glycoprotein is involved, through its lectin homology domain, in the retention of progeny virus on the surface of parental cells and raise the possibility that the protein also has a role in virus attachment to uninfected cells. JF - Journal of virology AU - Blasco, R AU - Sisler, J R AU - Moss, B AD - Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892. Y1 - 1993/06// PY - 1993 DA - June 1993 SP - 3319 EP - 3325 VL - 67 IS - 6 SN - 0022-538X, 0022-538X KW - A34R KW - A34R protein, Vaccina virus KW - 0 KW - Glycoproteins KW - Viral Envelope Proteins KW - Index Medicus KW - Phenotype KW - Mutagenesis, Site-Directed KW - Animals KW - Base Sequence KW - Viral Plaque Assay KW - DNA Mutational Analysis KW - Molecular Sequence Data KW - Biological Transport KW - Cosmids KW - Sequence Analysis, DNA KW - Chromosome Mapping KW - Vaccinia virus -- genetics KW - Genes, Viral -- genetics KW - Vaccinia virus -- growth & development KW - Point Mutation KW - Cell Membrane -- metabolism KW - Glycoproteins -- genetics KW - Viral Envelope Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75751129?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Dissociation+of+progeny+vaccinia+virus+from+the+cell+membrane+is+regulated+by+a+viral+envelope+glycoprotein%3A+effect+of+a+point+mutation+in+the+lectin+homology+domain+of+the+A34R+gene.&rft.au=Blasco%2C+R%3BSisler%2C+J+R%3BMoss%2C+B&rft.aulast=Blasco&rft.aufirst=R&rft.date=1993-06-01&rft.volume=67&rft.issue=6&rft.spage=3319&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 - 1993-06-21 N1 - Date created - 1993-06-21 N1 - Date revised - 2017-01-13 N1 - Gene symbol - A34R N1 - SuppNotes - Cited By: Virology. 1971 Dec;46(3):507-32 [4944855] J Gen Virol. 1991 Jun;72 ( Pt 6):1349-76 [2045793] Virology. 1976 Aug;73(1):43-58 [960564] J Virol. 1978 Jul;27(1):28-37 [691112] J Virol. 1991 Nov;65(11):5910-20 [1920620] Virology. 1992 Mar;187(1):251-60 [1736527] J Virol. 1992 Mar;66(3):1610-21 [1738204] Virology. 1992 Jun;188(2):801-10 [1585649] J Virol. 1992 Jul;66(7):4170-9 [1602540] J Gen Virol. 1992 Nov;73 ( Pt 11):2887-902 [1331292] J Virol. 1992 Dec;66(12):7217-24 [1433514] Nature. 1992 Nov 12;360(6400):127-34 [1436090] J Virol. 1979 Jul;31(1):147-55 [501796] J Virol. 1979 Nov;32(2):614-22 [501802] J Gen Virol. 1980 Sep;50(1):89-100 [7441216] J Virol. 1981 Sep;39(3):903-13 [7288920] J Virol. 1982 Jul;43(1):136-49 [6286993] J Gen Virol. 1985 Mar;66 ( Pt 3):643-6 [3973566] Virology. 1986 Apr 30;150(2):451-62 [3008418] J Virol. 1986 Jun;58(3):757-64 [3701927] Virology. 1986 Nov;155(1):97-105 [3465088] J Virol. 1987 Jun;61(6):1765-71 [3033308] J Biol Chem. 1988 Jul 15;263(20):9557-60 [3290208] Nucleic Acids Res. 1990 Sep 25;18(18):5347-51 [2216706] Virology. 1990 Nov;179(1):247-66, 517-63 [2219722] J Virol. 1991 Jul;65(7):3435-42 [2041074] Prog Med Virol. 1973;16:86-108 [4356899] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pharmacokinetics of piroxantrone in a phase I trial of piroxantrone and granulocyte-colony stimulating factor. AN - 75746091; 7684320 AB - Piroxantrone is an anthrapyrazole derivative with broad antitumor activity in vitro. In previous phase I trials, the dose-limiting toxicity of this agent was myelosuppression. Therefore, a phase I and pharmacokinetic study of a 1-h infusion of piroxantrone in combination with granulocyte-colony stimulating factor was conducted. In this article, we report the results of the pharmacokinetic analysis. Thirty-seven patients were studied over a dosage range of 150 to 555 mg/m2. The plasma elimination of piroxantrone was biexponential with a mean (+/- SD) t1/2 alpha of 3.2 +/- 2.7 min and a mean (+/- SD) t1/2 beta of 82 +/- 92 min. Clearance was 840 +/- 230 ml/min/m2. A limited sampling strategy was developed to allow the estimation of total drug exposure (area under the plasma concentration-time curve) from the plasma piroxantrone concentrations at 30, 60, and 120 min after the start of the infusion. The pharmacokinetic behavior of a presumed piroxantrone metabolite not previously described in plasma was also characterized. Based on in vitro cytotoxicity studies with partially purified extract of this compound, we do not believe that it contributes to the antitumor effects of piroxantrone at the concentrations observed in plasma. Finally, piroxantrone elimination was linear over the nearly 4-fold dose range studied, indicating that when dose adjustments are made, systemic drug exposure will remain predictable. JF - Cancer research AU - Berg, S L AU - Savarese, D M AU - Balis, F M AU - Denicoff, A M AU - Hillig, M AU - O'Shaughnessy, J A AU - Poplack, D G AU - Cowan, K H AD - Pediatric Branch, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1993/06/01/ PY - 1993 DA - 1993 Jun 01 SP - 2587 EP - 2590 VL - 53 IS - 11 SN - 0008-5472, 0008-5472 KW - Anthraquinones KW - 0 KW - Antineoplastic Agents KW - Pyrazoles KW - Granulocyte Colony-Stimulating Factor KW - 143011-72-7 KW - piroxantrone KW - YL4TY9WH22 KW - Index Medicus KW - Humans KW - Adult KW - Pyrazoles -- administration & dosage KW - Neoplasms -- drug therapy KW - Pyrazoles -- urine KW - Antineoplastic Agents -- administration & dosage KW - Antineoplastic Agents -- pharmacokinetics KW - Anthraquinones -- administration & dosage KW - Anthraquinones -- pharmacokinetics KW - Granulocyte Colony-Stimulating Factor -- administration & dosage KW - Antineoplastic Agents -- blood KW - Anthraquinones -- urine KW - Anthraquinones -- blood KW - Antineoplastic Agents -- urine KW - Pyrazoles -- blood KW - Pyrazoles -- pharmacokinetics KW - Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75746091?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Pharmacokinetics+of+piroxantrone+in+a+phase+I+trial+of+piroxantrone+and+granulocyte-colony+stimulating+factor.&rft.au=Berg%2C+S+L%3BSavarese%2C+D+M%3BBalis%2C+F+M%3BDenicoff%2C+A+M%3BHillig%2C+M%3BO%27Shaughnessy%2C+J+A%3BPoplack%2C+D+G%3BCowan%2C+K+H&rft.aulast=Berg&rft.aufirst=S&rft.date=1993-06-01&rft.volume=53&rft.issue=11&rft.spage=2587&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 - 1993-06-21 N1 - Date created - 1993-06-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Fine-structure analysis of the P7 plasmid partition site. AN - 75745969; 8501048 AB - The par region of bacteriophage P7 is responsible for active partition of the P7 plasmid prophage into daughter cells. The cis-acting partition site was defined precisely as a 75-bp sequence that was necessary and sufficient to promote correct segregation of an unstable vector plasmid when the two P7 partition proteins, ParA and ParB, were supplied in trans. Roughly the same region was necessary to exert partition-mediated incompatibility. The minimal site contains an integration host factor (IHF) protein binding site bracketed by regions containing heptamer repeat sequences that individually bind ParB. An additional sequence forms the left boundary of the site. Site-directed mutations in the latter sequence, as well as the IHF motif and the rightmost ParB box, blocked site function. Although the P7 site shares 55% sequence identity with its counterpart in bacteriophage P1, functional interactions between the partition sites and the Par proteins of the two plasmids were entirely species specific in vivo. The P1 sequence has similar IHF and ParB binding motifs, but the left boundary sequence differs radically and may define a point of species-specific contact with the Par proteins. No evidence was found for the existence of a functional P7 analog of the P1 parS core, a small subregion of the P1 site that, in isolation, acts as an enfeebled partition site with modified incompatibility properties. JF - Journal of bacteriology AU - Hayes, F AU - Davis, M A AU - Austin, S J AD - Laboratory of Chromosome Biology, ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Maryland 21702. Y1 - 1993/06// PY - 1993 DA - June 1993 SP - 3443 EP - 3451 VL - 175 IS - 11 SN - 0021-9193, 0021-9193 KW - parA KW - parB KW - Bacterial Proteins KW - 0 KW - chromosome partition proteins, bacterial KW - Index Medicus KW - Virus Replication KW - Mutagenesis, Site-Directed KW - Base Sequence KW - DNA Mutational Analysis KW - Molecular Sequence Data KW - Bacterial Proteins -- genetics KW - Plasmids -- genetics KW - Proviruses -- genetics KW - Coliphages -- growth & development KW - Coliphages -- genetics KW - Proviruses -- growth & development UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75745969?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+bacteriology&rft.atitle=Fine-structure+analysis+of+the+P7+plasmid+partition+site.&rft.au=Hayes%2C+F%3BDavis%2C+M+A%3BAustin%2C+S+J&rft.aulast=Hayes&rft.aufirst=F&rft.date=1993-06-01&rft.volume=175&rft.issue=11&rft.spage=3443&rft.isbn=&rft.btitle=&rft.title=Journal+of+bacteriology&rft.issn=00219193&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-07-01 N1 - Date created - 1993-07-01 N1 - Date revised - 2017-01-13 N1 - Gene symbol - parA; parB N1 - SuppNotes - Cited By: J Mol Biol. 1968 Apr 14;33(1):327-9 [4869227] Biotechniques. 1991 Mar;10(3):319, 326-8 [2064770] Proc Natl Acad Sci U S A. 1976 Jun;73(6):1959-63 [132662] Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7 [271968] Gene. 1977;2(2):95-113 [344137] Nucleic Acids Res. 1978 Sep;5(9):3157-70 [212715] Plasmid. 1978 Sep;1(4):421-34 [372974] Cell. 1981 Sep;25(3):729-36 [7026049] J Bacteriol. 1982 Oct;152(1):63-71 [6749822] J Mol Biol. 1983 Sep 15;169(2):353-72 [6312056] J Mol Biol. 1983 Sep 15;169(2):373-87 [6225875] Gene. 1984 Nov;31(1-3):165-71 [6098521] J Mol Biol. 1985 Sep 20;185(2):261-72 [3903163] J Mol Biol. 1986 Nov 20;192(2):275-85 [3560217] Proc Natl Acad Sci U S A. 1987 Dec;84(23):8544-7 [3317415] Plasmid. 1987 Jul;18(1):93-8 [2827210] Proc Natl Acad Sci U S A. 1988 Sep;85(18):6657-61 [2842786] J Biol Chem. 1991 Aug 5;266(22):14328-37 [1860842] J Gen Microbiol. 1992 Jan;138(1):1-16 [1556544] Mol Microbiol. 1992 May;6(9):1141-7 [1534133] Biotechniques. 1992 Jun;12(6):830-2 [1379442] J Bacteriol. 1992 Aug;174(16):5190-5 [1322881] Annu Rev Biochem. 1992;61:283-306 [1497312] Plasmid. 1988 Mar;19(2):103-12 [3420178] EMBO J. 1988 Jun;7(6):1881-8 [3049080] Proc Natl Acad Sci U S A. 1989 Apr;86(7):2172-5 [2648393] Cell. 1989 Jun 2;57(5):869-80 [2541927] J Mol Biol. 1989 Oct 5;209(3):393-406 [2585492] Annu Rev Genet. 1989;23:37-69 [2694936] EMBO J. 1990 Apr;9(4):991-8 [2182325] Mol Microbiol. 1990 Sep;4(9):1455-63 [2149583] J Bacteriol. 1991 Jun;173(12):3630-4 [2050624] J Mol Biol. 1969 May 14;41(3):459-72 [4896022] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Kinetics of serum and cellular interleukin-5 in posttreatment eosinophilia of patients with lymphatic filariasis. AN - 75744893; 8501330 AB - Peripheral blood eosinophil counts and serum levels and in vitro production of eosinophilopoietic cytokines were assessed before and at frequent intervals after diethylcarbamazine treatment of Bancroftian filariasis. Eosinophil counts peaked at day 7 after the start of treatment (359% +/- 118% of pretreatment levels) and declined to pretreatment levels by day 17. Serum interleukin (IL)-5, undetectable in 14 of 15 patients before treatment, rose sharply but transiently, with peak levels (32 +/- 7 pg/mL) 2 days after diethylcarbamazine treatment. Granulocyte-macrophage colony-stimulating factor and IL-3 were not detectable in serum at any time. In vitro mitogen-induced IL-5 levels decreased significantly in 7 of 9 patients 3 days after treatment when serum IL-5 was at near-peak levels. By day 10 IL-5 values increased in 8 of 9 patients compared with treatment values (P < .02). These data define the temporal relation between serum IL-5 levels and the subsequent development of eosinophilia and suggest that lymphocytes are the source of IL-5. JF - The Journal of infectious diseases AU - Limaye, A P AU - Ottesen, E A AU - Kumaraswami, V AU - Abrams, J S AU - Regunathan, J AU - Vijayasekaran, V AU - Jayaraman, K AU - Nutman, T B AD - Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/06// PY - 1993 DA - June 1993 SP - 1396 EP - 1400 VL - 167 IS - 6 SN - 0022-1899, 0022-1899 KW - Interleukin-5 KW - 0 KW - Ionomycin KW - 56092-81-0 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Diethylcarbamazine KW - V867Q8X3ZD KW - Abridged Index Medicus KW - Index Medicus KW - Kinetics KW - Humans KW - Adult KW - Eosinophils -- metabolism KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Ionomycin -- pharmacology KW - Adolescent KW - Diethylcarbamazine -- therapeutic use KW - Male KW - Interleukin-5 -- metabolism KW - Elephantiasis, Filarial -- immunology KW - Interleukin-5 -- blood KW - Eosinophilia -- immunology KW - Elephantiasis, Filarial -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75744893?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Kinetics+of+serum+and+cellular+interleukin-5+in+posttreatment+eosinophilia+of+patients+with+lymphatic+filariasis.&rft.au=Limaye%2C+A+P%3BOttesen%2C+E+A%3BKumaraswami%2C+V%3BAbrams%2C+J+S%3BRegunathan%2C+J%3BVijayasekaran%2C+V%3BJayaraman%2C+K%3BNutman%2C+T+B&rft.aulast=Limaye&rft.aufirst=A&rft.date=1993-06-01&rft.volume=167&rft.issue=6&rft.spage=1396&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 - 1993-06-29 N1 - Date created - 1993-06-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Topical application of T-2 toxin inhibits the contact hypersensitivity response in BALB/c mice. AN - 75744606; 8496607 AB - T-2 toxin, a trichothecene mycotoxin, has previously been shown to alter immune functions and promote skin tumors. We demonstrate that topically applied T-2 toxin reduces the ear swelling response to oxazolone challenge in BALB/c mice. For this reduction in ear swelling to occur, toxin application must be at, or within, 1 h after challenge. Dose-response studies showed a 44% reduction in ear swelling with 30 ng of T-2 toxin as compared with a similar reduction with 300 ng of dexamethasone. T-2 toxin did not affect Ag transport from the challenge site to the draining lymph nodes as measured by FITC transport. However, T-2 toxin significantly reduced both MHC class II (Ia) expression and Ag presentation at the same concentrations. Because T-2 toxin, a known protein synthesis inhibitor, was found to inhibit protein synthesis in epidermal cell cultures as measured by [3H]-leucine incorporation, cycloheximide was also examined. Cycloheximide reduced both oxazolone-induced ear swelling and Ag presentation in a similar manner to T-2 toxin. One mechanism of action for T-2 toxin in reducing the contact hypersensitivity response is via inhibition of protein synthesis and effective Ag presentation by epidermal Langerhans cells. This may involve alterations in Ia Ag expression, although a role for class II in the induction phase of the contact hypersensitivity response has not been established definitively. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Blaylock, B L AU - Kouchi, Y AU - Comment, C E AU - Pollock, P L AU - Luster, M I AD - Environmental Immunology Section, National Institute of Environmental Health Sciences/NIH, Research Triangle Park, NC 27709. Y1 - 1993/06/01/ PY - 1993 DA - 1993 Jun 01 SP - 5135 EP - 5143 VL - 150 IS - 11 SN - 0022-1767, 0022-1767 KW - Histocompatibility Antigens Class II KW - 0 KW - Protein Synthesis Inhibitors KW - Oxazolone KW - 15646-46-5 KW - Cycloheximide KW - 98600C0908 KW - T-2 Toxin KW - I3FL5NM3MO KW - Abridged Index Medicus KW - Index Medicus KW - Protein Biosynthesis KW - Animals KW - Langerhans Cells -- drug effects KW - Oxazolone -- toxicity KW - Cell Movement -- immunology KW - Mice KW - Histocompatibility Antigens Class II -- analysis KW - Langerhans Cells -- metabolism KW - Mice, Inbred BALB C KW - Langerhans Cells -- immunology KW - Protein Synthesis Inhibitors -- toxicity KW - Biological Transport -- immunology KW - Cells, Cultured KW - Cycloheximide -- pharmacology KW - Kinetics KW - Administration, Topical KW - Female KW - Dermatitis, Allergic Contact -- immunology KW - Dermatitis, Allergic Contact -- prevention & control KW - T-2 Toxin -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75744606?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Topical+application+of+T-2+toxin+inhibits+the+contact+hypersensitivity+response+in+BALB%2Fc+mice.&rft.au=Blaylock%2C+B+L%3BKouchi%2C+Y%3BComment%2C+C+E%3BPollock%2C+P+L%3BLuster%2C+M+I&rft.aulast=Blaylock&rft.aufirst=B&rft.date=1993-06-01&rft.volume=150&rft.issue=11&rft.spage=5135&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 - 1993-06-22 N1 - Date created - 1993-06-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Growth regulation of primary rat tracheal epithelial cell cultures by endogenous transforming growth factor-beta s. AN - 75741714; 8491788 AB - Primary rat tracheal epithelial (RTE) cell cultures have previously been shown to secrete transforming growth factor-beta (TGF beta) and to be growth inhibited by exogenous TGF beta. The purpose of the present studies was to determine whether the endogenous TGF beta(s) were regulating the growth of RTE cell cultures and, if so, which isoforms were involved. Neutralizing antibodies specific to TGF beta 1 and TGF beta 2 were added to cultures, and their effects on several growth parameters were measured. Addition of antibodies to early cultures (day 1), resulted in 1.8- and 3-fold increases in colony formation and cell number, respectively, above control IgG-treated cultures. Antibody dose-response experiments revealed that TGF beta 2 was the predominant isoform inhibiting early RTE cell growth. The antibody treatments resulted in similar stimulation of early growth at low and high seeding densities, suggesting that the endogenous TGF beta s were acting locally. Anti-TGF beta 1 treatment of cultures at various stages of growth resulted in 1.2-1.7-fold increases in DNA synthesis above controls, whereas anti-TGF beta 2 treatment resulted in increased DNA synthesis only in early and late cultures (1.7- and 2.5-fold, respectively), but not during midlogarithmic growth. Continuous treatment with a combination of both antibodies resulted in increased growth and decreased exfoliation in early cultures, but had no effect on the slow down of growth in late cultures. Thus endogenous TGF beta s inhibited primarily early growth and contributed to, but did not appear to be responsible for, plateau of growth in late stage cultures. Antibody treatment of secondary cultures resulted in 4-70-fold increases in colony formation, depending on the age of the primary cultures when replated, indicating that endogenous production of both TGF beta 1 and TGF beta 2 greatly inhibits the subculturability of primary RTE cells. Other experiments suggested that cholera toxin enhances RTE cell growth in part by counteracting the inhibitory effects of endogenous TGF beta s. JF - Journal of cellular physiology AU - Rundhaug, J E AU - Nettesheim, P AD - Laboratory of Pulmonary Pathobiology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1993/06// PY - 1993 DA - June 1993 SP - 483 EP - 493 VL - 155 IS - 3 SN - 0021-9541, 0021-9541 KW - Antibodies KW - 0 KW - Transforming Growth Factor beta KW - DNA KW - 9007-49-2 KW - Cholera Toxin KW - 9012-63-9 KW - Index Medicus KW - Animals KW - Cell Count KW - Cholera Toxin -- pharmacology KW - DNA -- biosynthesis KW - Rats KW - Rats, Inbred F344 KW - Epithelial Cells KW - Cells, Cultured KW - Cell Death KW - Epithelium -- metabolism KW - Male KW - Cell Division KW - Transforming Growth Factor beta -- biosynthesis KW - Transforming Growth Factor beta -- pharmacology KW - Trachea -- metabolism KW - Trachea -- cytology KW - Transforming Growth Factor beta -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75741714?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+cellular+physiology&rft.atitle=Growth+regulation+of+primary+rat+tracheal+epithelial+cell+cultures+by+endogenous+transforming+growth+factor-beta+s.&rft.au=Rundhaug%2C+J+E%3BNettesheim%2C+P&rft.aulast=Rundhaug&rft.aufirst=J&rft.date=1993-06-01&rft.volume=155&rft.issue=3&rft.spage=483&rft.isbn=&rft.btitle=&rft.title=Journal+of+cellular+physiology&rft.issn=00219541&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-06-17 N1 - Date created - 1993-06-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutation of the serine 15 phosphorylation site of human p53 reduces the ability of p53 to inhibit cell cycle progression. AN - 75737894; 8502477 AB - Overexpression of wild-type p53 prevents cells from entering the S phase of the cell cycle. The amino-terminal transactivation region of p53 is phosphorylated by several protein kinases, including DNA-PK, a nuclear serine/threonine protein kinase that in vitro requires DNA for activity. DNA-PK was recently shown to phosphorylate serines 15 and 37 of human p53 (Lees-Miller et al., 1992. Mol. Cell. Biol., 12, 5041-5049). To prevent phosphorylation at these sites, mutants were constructed that changed the codons for serine 15 or serine 37 to alanine codons. Expression of p53-Ala-37 in stably transformed T98G cells blocked progression of the cells into S phase as well as did the expression of wild-type p53. In contrast, p53-Ala-15 was partially defective in blocking cell cycle progression. Several cell clones transformed with the mutant p53-Ala-15 gene expressed normal levels of p53 mRNA but accumulated little or no detectable p53 protein. However, by using a transient expression system driven by a strong cytomegalovirus promoter, we showed that the inability of p53-Ala-15 to fully block cell cycle progression was not due to inadequate levels of expression or to a failure of the mutant protein to accumulate in the nucleus. These results suggest that phosphorylation of Ser-15 may affect p53 function. JF - Oncogene AU - Fiscella, M AU - Ullrich, S J AU - Zambrano, N AU - Shields, M T AU - Lin, D AU - Lees-Miller, S P AU - Anderson, C W AU - Mercer, W E AU - Appella, E AD - Laboratory of Cell Biology, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/06// PY - 1993 DA - June 1993 SP - 1519 EP - 1528 VL - 8 IS - 6 SN - 0950-9232, 0950-9232 KW - p53 KW - Antibodies, Monoclonal KW - 0 KW - Oligodeoxyribonucleotides KW - Peptides KW - RNA, Messenger KW - Tumor Suppressor Protein p53 KW - Serine KW - 452VLY9402 KW - Protein Kinases KW - EC 2.7.- KW - Index Medicus KW - Peptides -- chemical synthesis KW - Immunoblotting KW - Blotting, Northern KW - Humans KW - Peptides -- immunology KW - Amino Acid Sequence KW - Mutagenesis, Site-Directed KW - Protein Kinases -- metabolism KW - Polymerase Chain Reaction KW - Base Sequence KW - RNA, Messenger -- metabolism KW - Phosphorylation KW - Transfection KW - Kinetics KW - Molecular Sequence Data KW - Cell Line KW - Tumor Suppressor Protein p53 -- analysis KW - Genes, p53 KW - Cell Cycle -- physiology KW - Tumor Suppressor Protein p53 -- genetics KW - Tumor Suppressor Protein p53 -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75737894?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mutation+of+the+serine+15+phosphorylation+site+of+human+p53+reduces+the+ability+of+p53+to+inhibit+cell+cycle+progression.&rft.au=Fiscella%2C+M%3BUllrich%2C+S+J%3BZambrano%2C+N%3BShields%2C+M+T%3BLin%2C+D%3BLees-Miller%2C+S+P%3BAnderson%2C+C+W%3BMercer%2C+W+E%3BAppella%2C+E&rft.aulast=Fiscella&rft.aufirst=M&rft.date=1993-06-01&rft.volume=8&rft.issue=6&rft.spage=1519&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-06-29 N1 - Date created - 1993-06-29 N1 - Date revised - 2017-01-13 N1 - Gene symbol - p53 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Heat shock proteins DnaJ, DnaK, and GrpE stimulate P1 plasmid replication by promoting initiator binding to the origin. AN - 75736808; 8501058 AB - Binding of the P1-encoded protein RepA to the origin of P1 plasmid replication is essential for initiation of DNA replication and for autoregulatory repression of the repA promoter. Previous studies have shown defects in both initiation and repression in hosts lacking heat shock proteins DnaJ, DnaK, and GrpE and have suggested that these proteins play a role in the RepA-DNA binding required for initiation and repression. In this study, using in vivo dimethyl sulfate footprinting, we have confirmed the roles of the three heat shock proteins in promoting RepA binding to the origin. The defects in both activities could be suppressed by increasing the concentration of wild-type RepA over the physiological level. We also isolated RepA mutants that were effective initiators and repressors without requiring the heat shock proteins. These data suggest that the heat shock proteins facilitate both repression and initiation by promoting only the DNA-binding activity of RepA. In a similar plasmid, F, initiator mutants that confer heat shock protein independence for replication were also found, but they were defective for repression. We propose that the initiator binding involved in repression and the initiator binding involved in initiation are similar in P1 but different in F. JF - Journal of bacteriology AU - Sozhamannan, S AU - Chattoraj, D K AD - Laboratory of Biochemistry, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1993/06// PY - 1993 DA - June 1993 SP - 3546 EP - 3555 VL - 175 IS - 11 SN - 0021-9193, 0021-9193 KW - Bacterial Proteins KW - 0 KW - DNA-Binding Proteins KW - DnaJ protein, E coli KW - Escherichia coli Proteins KW - GrpE protein, Bacteria KW - HSP40 Heat-Shock Proteins KW - HSP70 Heat-Shock Proteins KW - Heat-Shock Proteins KW - Proteins KW - Trans-Activators KW - replication initiator protein KW - dnaK protein, E coli KW - EC 3.6.1.- KW - DNA Helicases KW - EC 3.6.4.- KW - Index Medicus KW - Polymerase Chain Reaction KW - Base Sequence KW - Transformation, Genetic KW - Molecular Sequence Data KW - Promoter Regions, Genetic -- genetics KW - Sequence Analysis, DNA KW - Mutagenesis KW - Bacterial Proteins -- genetics KW - Bacterial Proteins -- pharmacology KW - Plasmids -- genetics KW - Bacterial Proteins -- metabolism KW - Bacteriophage P1 -- growth & development KW - Heat-Shock Proteins -- pharmacology KW - Virus Replication -- drug effects KW - Bacteriophage P1 -- genetics KW - DNA Replication UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75736808?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+bacteriology&rft.atitle=Heat+shock+proteins+DnaJ%2C+DnaK%2C+and+GrpE+stimulate+P1+plasmid+replication+by+promoting+initiator+binding+to+the+origin.&rft.au=Sozhamannan%2C+S%3BChattoraj%2C+D+K&rft.aulast=Sozhamannan&rft.aufirst=S&rft.date=1993-06-01&rft.volume=175&rft.issue=11&rft.spage=3546&rft.isbn=&rft.btitle=&rft.title=Journal+of+bacteriology&rft.issn=00219193&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-07-01 N1 - Date created - 1993-07-01 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Mol Biol. 1973 May 5;76(1):45-60 [4578100] EMBO J. 1990 Dec;9(12):4027-36 [2249663] J Bacteriol. 1979 May;138(2):339-44 [374384] Genetics. 1979 Oct;93(2):321-43 [395024] Mol Gen Genet. 1982;187(3):375-83 [6294468] J Mol Biol. 1984 Mar 5;173(3):307-24 [6699914] Gene. 1984 Sep;29(3):303-13 [6237955] Proc Natl Acad Sci U S A. 1985 May;82(9):2588-92 [3857601] J Biol Chem. 1986 Mar 15;261(8):3548-55 [3949778] Mol Gen Genet. 1986 May;203(2):208-13 [3526090] Cell. 1986 Sep 26;46(7):959-61 [2944601] J Mol Biol. 1986 Nov 20;192(2):275-85 [3560217] Proc Natl Acad Sci U S A. 1987 Jun;84(11):3668-72 [3035546] Gene. 1987;53(1):85-96 [3596251] J Bacteriol. 1987 Aug;169(8):3737-42 [3611028] Proc Natl Acad Sci U S A. 1987 Dec;84(24):8849-53 [2447584] Cell. 1988 Feb 26;52(4):551-7 [3277720] J Bacteriol. 1988 Aug;170(8):3554-60 [3403509] Annu Rev Genet. 1988;22:631-77 [2853609] J Bacteriol. 1989 May;171(5):2337-46 [2651398] J Bacteriol. 1989 May;171(5):2748-55 [2651417] Microbiol Rev. 1989 Mar;53(1):1-24 [2540407] J Biol Chem. 1989 Jun 25;264(18):10699-708 [2525129] J Biol Chem. 1989 Jun 25;264(18):10709-18 [2543679] J Biol Chem. 1989 Jun 25;264(18):10719-25 [2525130] EMBO J. 1989 May;8(5):1601-8 [2527744] Mol Gen Genet. 1989 Aug;218(2):183-9 [2674651] J Bacteriol. 1989 Nov;171(11):6025-9 [2681150] J Bacteriol. 1989 Nov;171(11):6030-8 [2681151] Gene. 1989 Dec 21;85(1):15-23 [2533576] J Bacteriol. 1990 Apr;172(4):2055-64 [2180916] New Biol. 1990 Sep;2(9):812-7 [2279033] J Bacteriol. 1991 Feb;173(3):1064-72 [1991708] J Bacteriol. 1991 Feb;173(3):1268-78 [1991720] Nature. 1991 Mar 14;350(6314):165-7 [2005967] Mol Microbiol. 1991 Mar;5(3):529-34 [2046546] Trends Biochem Sci. 1991 Apr;16(4):159-63 [1877092] Proc Natl Acad Sci U S A. 1991 Sep 15;88(18):7903-7 [1896443] Mol Microbiol. 1991 Dec;5(12):3015-23 [1809840] Biotechnology (N Y). 1992 Mar;10(3):301-4 [1369475] J Biol Chem. 1992 Jun 5;267(16):11520-4 [1597479] J Bacteriol. 1992 Sep;174(17):5597-603 [1512194] Proc Natl Acad Sci U S A. 1992 Oct 1;89(19):8923-7 [1409587] Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10345-9 [1438220] Proc Natl Acad Sci U S A. 1990 Apr;87(7):2690-4 [2181445] Mol Gen Genet. 1990 Jan;220(2):277-82 [2183004] Nature. 1990 Apr 26;344(6269):882-4 [2109835] Cell. 1990 Jun 15;61(6):1013-20 [2140957] J Biol Chem. 1990 Jul 25;265(21):12111-4 [2197269] J Bacteriol. 1990 Aug;172(8):4386-91 [2165477] J Bacteriol. 1990 Aug;172(8):4441-7 [2198259] Cell. 1990 Sep 7;62(5):939-44 [2203539] J Biol Chem. 1990 Nov 5;265(31):19244-8 [2229074] J Mol Biol. 1976 Jul 5;104(3):541-55 [781293] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Salvage trial of trimetrexate-leucovorin for the treatment of cerebral toxoplasmosis in patients with AIDS. AN - 75735742; 8501335 AB - The clinical efficacy of trimetrexate, a dihydrofolate reductase inhibitor with potent in vitro antitoxoplasma activity, was assessed in 9 sulfonamide-intolerant patients with AIDS and biopsy-proven cerebral toxoplasmosis. The 9 patients were treated for 28-149 days with trimetrexate (30-280 mg/m2/day) plus leucovorin (20-90 mg/m2 every 6 h). Radiographic responses were documented in 8 patients, and clinical responses in 5 patients. Despite continued therapy, all patients deteriorated clinically and radiographically within 13-109 days of their initial improvement. Trimetrexate at very high doses for extended periods was not associated with serious toxicity. Trimetrexate alone had dramatic but transient activity in sulfonamide-intolerant patients and thus is not adequate as single-agent therapy for AIDS-associated toxoplasmosis. JF - The Journal of infectious diseases AU - Masur, H AU - Polis, M A AU - Tuazon, C U AU - Ogata-Arakaki, D AU - Kovacs, J A AU - Katz, D AU - Hilt, D AU - Simmons, T AU - Feuerstein, I AU - Lundgren, B AD - National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/06// PY - 1993 DA - June 1993 SP - 1422 EP - 1426 VL - 167 IS - 6 SN - 0022-1899, 0022-1899 KW - Leucovorin KW - Q573I9DVLP KW - Trimetrexate KW - UPN4ITI8T4 KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Drug Evaluation KW - Humans KW - Adult KW - Tomography, X-Ray Computed KW - Adolescent KW - Male KW - Female KW - Acquired Immunodeficiency Syndrome -- complications KW - Toxoplasmosis, Cerebral -- drug therapy KW - Toxoplasmosis, Cerebral -- complications KW - Trimetrexate -- therapeutic use KW - Toxoplasmosis, Cerebral -- diagnostic imaging KW - Leucovorin -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75735742?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Salvage+trial+of+trimetrexate-leucovorin+for+the+treatment+of+cerebral+toxoplasmosis+in+patients+with+AIDS.&rft.au=Masur%2C+H%3BPolis%2C+M+A%3BTuazon%2C+C+U%3BOgata-Arakaki%2C+D%3BKovacs%2C+J+A%3BKatz%2C+D%3BHilt%2C+D%3BSimmons%2C+T%3BFeuerstein%2C+I%3BLundgren%2C+B&rft.aulast=Masur&rft.aufirst=H&rft.date=1993-06-01&rft.volume=167&rft.issue=6&rft.spage=1422&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 - 1993-06-29 N1 - Date created - 1993-06-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Child-care debate - transformed or distorted? AN - 39047130; 1253926 JF - American psychologist Y1 - 1993/06// PY - 1993 DA - Jun 1993 SP - 692 VL - 48 IS - 6 SN - 0003-066X, 0003-066X KW - Sociology KW - Child care UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39047130?accountid=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=American+psychologist&rft.atitle=Child-care+debate+-+transformed+or+distorted%3F&rft.au=&rft.aulast=&rft.aufirst=&rft.date=1993-06-01&rft.volume=48&rft.issue=6&rft.spage=692&rft.isbn=&rft.btitle=&rft.title=American+psychologist&rft.issn=0003066X&rft_id=info:doi/ LA - English DB - International Bibliography of the Social Sciences (IBSS) N1 - Date revised - 2013-06-12 N1 - Last updated - 2013-09-16 N1 - SubjectsTermNotLitGenreText - 2192 ER - TY - JOUR T1 - State-dependent radial elasticity of attached cross-bridges in single skinned fibres of rabbit psoas muscle. AN - 1647020020; 21249423 AB - 1. In a single skinned fibre of rabbit psoas muscle, upon attachment of cross bridges to actin in the presence of ADP or pyrophosphate (PPi), the separation between the contractile filaments, as determined by equatorial X-ray diffraction, is found to decrease, suggesting that force is generated in the radial direction. 2. The single muscle fibres were subjected to compression by 0-8% of dextran T500. The changes in lattice spacings by dextran compression were compared with changes induced by cross-bridge attachment to actin. Based on this comparison, the magnitude and the direction of the radial force generated by the attached cross-bridges were estimated. The radial cross-bridge force varied with filament separation, and the magnitude of the radial cross-bridge force reached as high as the maximal axial force produced during isometric contraction. 3. One key parameter of the radial elasticity, i.e. the equilibrium spacing where the radial force is zero, was found to depend on the ligand bound to the myosin head. In the presence of ADP, the equilibrium spacing was 36 nm. In the presence of MgPPi the equilibrium spacing shifted to 35 nm and Ca2+ had little effect on the equilibrium spacing. 4. The equilibrium spacing was independent of the fraction of cross-bridges attached to actin. The fraction of cross-bridges attached in rigor was modulated from 100% to close to 0% by adding up to 10 mM of ATP gamma S in the rigor solution. The lattice spacing remained at 38 nm, the equilibrium spacing for nucleotide-free cross-bridges at mu = 170 mM. 5. Radial force generated by cross-bridges in rigor at large lattice spacings (38 nm < or = d10 < or = 46 nm) appeared to vary linearly with lattice spacing. 6. The titration of ATP gamma S to fibres in rigor provided a correlation between the radial stiffness of the nucleotide-free cross-bridges and the equatorial intensities. The relation between the equatorial intensity ratio I11/I10 and radial stiffness appeared to be approximately linear. 7. The fibres under different conditions showed a wide range of radial stiffness, which was not proportional to the apparent axial stiffness of the fibre. If the apparent axial stiffness is a measure of the fraction of cross-bridges bound to actin, it follows that the radial elastic constant is state dependent; or vice versa.(ABSTRACT TRUNCATED AT 400 WORDS) JF - Journal of Physiology (London) AU - Xu, S AU - Brenner, B AU - Yu, L C AD - National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/06/01/ PY - 1993 DA - 1993 Jun 01 SP - 749 EP - 765 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 465 IS - 1 SN - 0022-3751, 0022-3751 KW - Physical Education Index KW - X-Ray KW - Biochemistry KW - Animal subjects KW - Muscles KW - Isometrics KW - Balance KW - PE 090:Sports Medicine & Exercise Sport Science UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1647020020?accountid=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+Physiology+%28London%29&rft.atitle=State-dependent+radial+elasticity+of+attached+cross-bridges+in+single+skinned+fibres+of+rabbit+psoas+muscle.&rft.au=Xu%2C+S%3BBrenner%2C+B%3BYu%2C+L+C&rft.aulast=Xu&rft.aufirst=S&rft.date=1993-06-01&rft.volume=465&rft.issue=1&rft.spage=749&rft.isbn=&rft.btitle=&rft.title=Journal+of+Physiology+%28London%29&rft.issn=00223751&rft_id=info:doi/10.1113%2Fjphysiol.1993.sp019704 LA - English DB - Physical Education Index N1 - Date revised - 2015-01-01 N1 - Document feature - figure 0 N1 - Last updated - 2015-11-16 N1 - SubjectsTermNotLitGenreText - X-Ray; Biochemistry; Animal subjects; Muscles; Isometrics; Balance DO - http://dx.doi.org/10.1113/jphysiol.1993.sp019704 ER - TY - JOUR T1 - Nonpromoting 12-deoxyphorbol 13-esters inhibit phorbol 12-myristate 13-acetate induced tumor promotion in CD-1 mouse skin AN - 15971245; 4064023 AB - Prostratin and 12-deoxyphorbol 13-phenylacetate (dPP) form a new class of protein kinase C activators of unique biological activity. Although they bind to and activate protein kinase C, in mouse skin they either fail to induce typical phorbol ester (PMA) effects (e.g., hyperplasia) or induce only partial response (e.g., inflammation). Furthermore, pretreatment with these agents inhibits a range of PMA induced effects (acute and chronic hyperplasia, inflammation, etc.) These observations suggested that prostratin and dPP would function as inhibitors of phorbol ester tumor promotion. Here we verify that prediction. We report that both compounds reduced both the average number of papillomas and the tumor incidence in a tumor promotion schedule in CD-1 mouse skin, in which each PMA application was preceded by 12-deoxyphorbol 13-monoester pretreatment. The highest dose of prostratin used (2.56 mu mol or 1 mg/pretreatment) caused a 96% (23-fold) reduction in the average number of papillomas with a decrease of tumor incidence from 97 to 40%. The highest dose of dPP used (21.4 nmol or 10 mu g/pretreatment) induced an 86% (7-fold) reduction in the average number of papillomas with a 53% reduction of tumor incidence from 100 to 47%. The inhibitory effect was dose dependent. The dose causing 50% inhibition was 11 nmol/pretreatment for prostratin and 0.8 nmol/pretreatment for dPP. Maximal inhibition of tumor promotion was accompanied by a block of epidermal hyperplasia; however, significant inhibition of tumor induction was observed at doses without any apparent effect on the PMA induced hyperplasia (DBO). JF - Cancer Research AU - Szallasi, Z AU - Krsmanovic, L AU - Blumberg, P M AD - Molecular Mechanisms of Tumor Promotion Section, Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, NIH, Bethesda, MD 20892, USA Y1 - 1993/06// PY - 1993 DA - Jun 1993 SP - 2507 EP - 2512 VL - 53 IS - 11 SN - 0008-5472, 0008-5472 KW - 12-deoxyphorbol 13-esters KW - phorbol 12-myristate 13-acetate KW - mice KW - TPA KW - Toxicology Abstracts KW - tumors KW - skin KW - X 24172:Plants UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15971245?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Research&rft.atitle=Nonpromoting+12-deoxyphorbol+13-esters+inhibit+phorbol+12-myristate+13-acetate+induced+tumor+promotion+in+CD-1+mouse+skin&rft.au=Szallasi%2C+Z%3BKrsmanovic%2C+L%3BBlumberg%2C+P+M&rft.aulast=Szallasi&rft.aufirst=Z&rft.date=1993-06-01&rft.volume=53&rft.issue=11&rft.spage=2507&rft.isbn=&rft.btitle=&rft.title=Cancer+Research&rft.issn=00085472&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; skin ER - TY - JOUR T1 - Child-Care Debate: Transformed or Distorted? AN - 1289903466 JF - American Psychologist Y1 - 1993/06/01/ PY - 1993 DA - 1993 Jun 01 SP - 692 CY - Arlington, Va. PB - American Psychological Association VL - 48 IS - 6 SN - 0003-066X KW - Psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1289903466?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Apio&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Psychologist&rft.atitle=Child-Care+Debate%3A+Transformed+or+Distorted%3F&rft.au=&rft.aulast=&rft.aufirst=&rft.date=1993-06-01&rft.volume=48&rft.issue=6&rft.spage=692&rft.isbn=&rft.btitle=&rft.title=American+Psychologist&rft.issn=0003066X&rft_id=info:doi/ DB - Periodicals Index Online N1 - Last updated - 2013-02-21 ER - TY - JOUR T1 - Trophic factor production by reactive astrocytes in injured brain. AN - 75785218; 8099771 JF - Annals of the New York Academy of Sciences AU - Schwartz, J P AU - Sheng, J G AU - Mitsuo, K AU - Shirabe, S AU - Nishiyama, N AD - Clinical Neuroscience Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/05/28/ PY - 1993 DA - 1993 May 28 SP - 226 EP - 234 VL - 679 SN - 0077-8923, 0077-8923 KW - Biomarkers KW - 0 KW - Enkephalins KW - Glial Fibrillary Acidic Protein KW - Nerve Growth Factors KW - Neuropeptides KW - Neurotoxins KW - Protein Precursors KW - RNA, Messenger KW - proenkephalin KW - Somatostatin KW - 51110-01-1 KW - Enkephalin, Methionine KW - 58569-55-4 KW - Oxidopamine KW - 8HW4YBZ748 KW - Index Medicus KW - Enkephalin, Methionine -- analysis KW - Aging -- metabolism KW - Animals KW - Fetus KW - Mice KW - Somatostatin -- biosynthesis KW - Cerebellum -- metabolism KW - Rats KW - Rats, Sprague-Dawley KW - Enkephalins -- biosynthesis KW - RNA, Messenger -- metabolism KW - Cerebellum -- growth & development KW - Oxidopamine -- toxicity KW - Cells, Cultured KW - Protein Precursors -- biosynthesis KW - MPTP Poisoning KW - Mice, Inbred C57BL KW - Enkephalin, Methionine -- metabolism KW - Male KW - Nerve Growth Factors -- biosynthesis KW - Glial Fibrillary Acidic Protein -- metabolism KW - Glial Fibrillary Acidic Protein -- analysis KW - Neuropeptides -- biosynthesis KW - Neurotoxins -- toxicity KW - Astrocytes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75785218?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Trophic+factor+production+by+reactive+astrocytes+in+injured+brain.&rft.au=Schwartz%2C+J+P%3BSheng%2C+J+G%3BMitsuo%2C+K%3BShirabe%2C+S%3BNishiyama%2C+N&rft.aulast=Schwartz&rft.aufirst=J&rft.date=1993-05-28&rft.volume=679&rft.issue=&rft.spage=226&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 - 1993-07-15 N1 - Date created - 1993-07-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nutrient and food group intake by tobacco use status: the 1987 National Health Interview Survey. AN - 75784323; 8512257 JF - Annals of the New York Academy of Sciences AU - Subar, A F AU - Harlan, L C AD - Applied Research Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/05/28/ PY - 1993 DA - 1993 May 28 SP - 310 EP - 21; discussion 321-2 VL - 686 SN - 0077-8923, 0077-8923 KW - Index Medicus KW - United States KW - Regression Analysis KW - Sex Factors KW - Humans KW - Adult KW - Aged KW - Nutrition Surveys KW - Middle Aged KW - Male KW - Female KW - Plants, Toxic KW - Smoking KW - Diet -- trends KW - Diet -- statistics & numerical data KW - Tobacco, Smokeless UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75784323?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Nutrient+and+food+group+intake+by+tobacco+use+status%3A+the+1987+National+Health+Interview+Survey.&rft.au=Subar%2C+A+F%3BHarlan%2C+L+C&rft.aulast=Subar&rft.aufirst=A&rft.date=1993-05-28&rft.volume=686&rft.issue=&rft.spage=310&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 - 1993-07-15 N1 - Date created - 1993-07-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The goldfish as a drug discovery vehicle for Parkinson's disease and other neurodegenerative disorders. AN - 75782545; 8512193 JF - Annals of the New York Academy of Sciences AU - Pollard, H B AU - Adeyemo, M AU - Dhariwal, K AU - Levine, M AU - Caohuy, H AU - Markey, S AU - Markey, C J AU - Youdim, M B AD - Laboratory of Cell Biology and Genetics, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/05/28/ PY - 1993 DA - 1993 May 28 SP - 317 EP - 320 VL - 679 SN - 0077-8923, 0077-8923 KW - Neurotoxins KW - 0 KW - Index Medicus KW - Rats KW - Animals KW - Humans KW - Disease Models, Animal KW - Mice KW - Primates KW - Parkinson Disease, Secondary -- chemically induced KW - MPTP Poisoning KW - Alzheimer Disease -- drug therapy KW - Goldfish KW - Alzheimer Disease -- chemically induced KW - Neurotoxins -- toxicity KW - Parkinson Disease, Secondary -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75782545?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+goldfish+as+a+drug+discovery+vehicle+for+Parkinson%27s+disease+and+other+neurodegenerative+disorders.&rft.au=Pollard%2C+H+B%3BAdeyemo%2C+M%3BDhariwal%2C+K%3BLevine%2C+M%3BCaohuy%2C+H%3BMarkey%2C+S%3BMarkey%2C+C+J%3BYoudim%2C+M+B&rft.aulast=Pollard&rft.aufirst=H&rft.date=1993-05-28&rft.volume=679&rft.issue=&rft.spage=317&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 - 1993-07-15 N1 - Date created - 1993-07-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Induction of a neuroprotective state in cerebellar granule cells following activation of N-methyl-D-aspartate receptors. AN - 75781704; 8099772 JF - Annals of the New York Academy of Sciences AU - Marini, A M AU - Paul, S M AD - Section on Molecular Pharmacology, National Institutes of Health, National Institute of Mental Health, Bethesda, Maryland 20892. Y1 - 1993/05/28/ PY - 1993 DA - 1993 May 28 SP - 253 EP - 259 VL - 679 SN - 0077-8923, 0077-8923 KW - Glutamates KW - 0 KW - Neurotoxins KW - Pyridinium Compounds KW - Receptors, N-Methyl-D-Aspartate KW - Dactinomycin KW - 1CC1JFE158 KW - Glutamic Acid KW - 3KX376GY7L KW - 1-(4-methoxyphenyl)pyridinium KW - 42850-10-2 KW - N-Methylaspartate KW - 6384-92-5 KW - Dizocilpine Maleate KW - 6LR8C1B66Q KW - Cycloheximide KW - 98600C0908 KW - Index Medicus KW - Dactinomycin -- pharmacology KW - Animals KW - Cell Survival -- drug effects KW - Cells, Cultured KW - Cycloheximide -- pharmacology KW - Dizocilpine Maleate -- pharmacology KW - Pyridinium Compounds -- antagonists & inhibitors KW - Neurons -- metabolism KW - Pyridinium Compounds -- toxicity KW - Neurons -- drug effects KW - Cerebellum -- pathology KW - Receptors, N-Methyl-D-Aspartate -- metabolism KW - Neurotoxins -- toxicity KW - Cerebellum -- metabolism KW - Neurons -- pathology KW - Receptors, N-Methyl-D-Aspartate -- drug effects KW - Glutamates -- pharmacology KW - N-Methylaspartate -- pharmacology KW - Cerebellum -- drug effects KW - N-Methylaspartate -- toxicity KW - Glutamates -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75781704?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Induction+of+a+neuroprotective+state+in+cerebellar+granule+cells+following+activation+of+N-methyl-D-aspartate+receptors.&rft.au=Marini%2C+A+M%3BPaul%2C+S+M&rft.aulast=Marini&rft.aufirst=A&rft.date=1993-05-28&rft.volume=679&rft.issue=&rft.spage=253&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 - 1993-07-15 N1 - Date created - 1993-07-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Preliminary observations on the in vitro toxicity of N-butylbenzenesulfonamide: a newly discovered neurotoxin. AN - 75771604; 8512189 JF - Annals of the New York Academy of Sciences AU - Nerurkar, V R AU - Wakayama, I AU - Rowe, T AU - Yanagihara, R AU - Garruto, R M AD - Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/05/28/ PY - 1993 DA - 1993 May 28 SP - 280 EP - 287 VL - 679 SN - 0077-8923, 0077-8923 KW - Biomarkers KW - 0 KW - Neurotoxins KW - Plasticizers KW - Sulfonamides KW - Tritium KW - 10028-17-8 KW - N-butylbenzenesulfonamide KW - 3622-84-2 KW - L-Lactate Dehydrogenase KW - EC 1.1.1.27 KW - Thymidine KW - VC2W18DGKR KW - Index Medicus KW - Thymidine -- metabolism KW - Rats KW - Animals KW - Tumor Cells, Cultured KW - L-Lactate Dehydrogenase -- analysis KW - Kinetics KW - Cell Division -- drug effects KW - Glioma KW - Cell Death -- drug effects KW - Plasticizers -- toxicity KW - DNA Replication -- drug effects KW - Cell Line KW - Sulfonamides -- toxicity KW - Neurotoxins -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75771604?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Preliminary+observations+on+the+in+vitro+toxicity+of+N-butylbenzenesulfonamide%3A+a+newly+discovered+neurotoxin.&rft.au=Nerurkar%2C+V+R%3BWakayama%2C+I%3BRowe%2C+T%3BYanagihara%2C+R%3BGarruto%2C+R+M&rft.aulast=Nerurkar&rft.aufirst=V&rft.date=1993-05-28&rft.volume=679&rft.issue=&rft.spage=280&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 - 1993-07-15 N1 - Date created - 1993-07-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Synergistic antiproliferative effects of interleukin-1 alpha and doxorubicin against the human ovarian carcinoma cell line (NIH:OVCAR-3). AN - 75781769; 8512591 AB - Interleukin-1 alpha (IL-1 alpha) exerts antiproliferative effects on a human ovarian carcinoma cell line, NIH:OVCAR-3, which is resistant to clinically relevant concentrations of doxorubicin (DOX) and other chemotherapeutic agents. This action of IL-1 alpha depends on the presence of type I (80 kDa) receptors, although no quantitative relationship has been established between receptor occupancy and inhibition of cell growth. When NIH:OVCAR-3 cells were exposed to IL-1 alpha and DOX in combination, a mutual potentiation of the antiproliferative effects of the two agents was observed. This synergistic effect was not due to IL-1 receptor expression up-regulation by DOX, and receptor-dependent internalization of the cytokine was also unaffected. The involvement of IL-1 receptors is supported by the observation that synergism between the two agents was diminished (but not abolished) in the presence of a specific IL-1 receptor antagonist at concentrations blocking more than 75% of IL-1 alpha binding. DOX was found to significantly increase IL-1 alpha accumulation by NIH:OVCAR-3 cells after long-term (48 hr) exposure to the cytokine at 37 degrees, which might be due to increased nonspecific fluid phase uptake or to interference with cytokine degradation and/or release processes. The potent synergy of IL-1 alpha and DOX against ovarian carcinoma cells in vitro suggests that this drug combination may be effective against this disease in the clinic. JF - Biochemical pharmacology AU - Monti, E AU - Mimnaugh, E G AU - Sinha, B K AD - Biochemical and Molecular Pharmacology Section, National Cancer Institute, NIH, Bethesda, MD 20892. Y1 - 1993/05/25/ PY - 1993 DA - 1993 May 25 SP - 2099 EP - 2107 VL - 45 IS - 10 SN - 0006-2952, 0006-2952 KW - Interleukin-1 KW - 0 KW - Iodine Radioisotopes KW - Receptors, Interleukin-1 KW - Doxorubicin KW - 80168379AG KW - Index Medicus KW - Drug Interactions KW - Interleukin-1 -- administration & dosage KW - Tumor Cells, Cultured -- drug effects KW - Humans KW - Cell Division -- drug effects KW - Intracellular Fluid -- metabolism KW - Doxorubicin -- administration & dosage KW - Protein Binding KW - Receptors, Interleukin-1 -- drug effects KW - Up-Regulation -- physiology KW - Interleukin-1 -- metabolism KW - Doxorubicin -- pharmacology KW - Interleukin-1 -- pharmacokinetics KW - Up-Regulation -- drug effects KW - Receptors, Interleukin-1 -- metabolism KW - Receptors, Interleukin-1 -- physiology KW - Drug Synergism KW - Female KW - Ovarian Neoplasms -- metabolism KW - Ovarian Neoplasms -- pathology KW - Antineoplastic Combined Chemotherapy Protocols -- pharmacology KW - Ovarian Neoplasms -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75781769?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+pharmacology&rft.atitle=Synergistic+antiproliferative+effects+of+interleukin-1+alpha+and+doxorubicin+against+the+human+ovarian+carcinoma+cell+line+%28NIH%3AOVCAR-3%29.&rft.au=Monti%2C+E%3BMimnaugh%2C+E+G%3BSinha%2C+B+K&rft.aulast=Monti&rft.aufirst=E&rft.date=1993-05-25&rft.volume=45&rft.issue=10&rft.spage=2099&rft.isbn=&rft.btitle=&rft.title=Biochemical+pharmacology&rft.issn=00062952&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-07-09 N1 - Date created - 1993-07-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The human papillomavirus E7 protein as a transforming and transactivating factor. AN - 75768444; 8389201 AB - The HPV proteins encoded by the early viral genes, including E6 and E7, are thought to subvert the normal regulatory pathways of infected cells to accommodate viral replication. Mechanistically some of this is accomplished by protein-protein interactions between viral proteins and a number of key cellular regulatory proteins that include tumor suppressor gene products. By undermining cellular regulatory pathways the HPV oncogenes cause hyperproliferation and the perturbation of normal cellular differentiation pathways. Although expression of the high-risk HPV-encoded E6 and E7 oncoproteins may be important prerequisites for cellular transformation, it is very likely that additional cellular changes are necessary for carcinogenic progression. The elucidation of the role of the early HPV genes in the initiation and/or maintenance of carcinogenic progression will continue to be a fascinating area of investigation and may reveal new opportunities for antiviral therapy and antitumor intervention. JF - Biochimica et biophysica acta AU - Münger, K AU - Phelps, W C AD - Laboratory of Tumor Virus Biology, National Cancer Institute, Bethesda, MD 20892. Y1 - 1993/05/25/ PY - 1993 DA - 1993 May 25 SP - 111 EP - 123 VL - 1155 IS - 1 SN - 0006-3002, 0006-3002 KW - Oncogene Proteins, Viral KW - 0 KW - Papillomavirus E7 Proteins KW - oncogene protein E7, Human papillomavirus type 16 KW - Index Medicus KW - Animals KW - Genes, Retinoblastoma KW - Humans KW - Molecular Sequence Data KW - Uterine Cervical Neoplasms -- genetics KW - Amino Acid Sequence KW - Female KW - Oncogene Proteins, Viral -- chemistry KW - Papillomaviridae KW - Transcriptional Activation KW - Oncogene Proteins, Viral -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75768444?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochimica+et+biophysica+acta&rft.atitle=The+human+papillomavirus+E7+protein+as+a+transforming+and+transactivating+factor.&rft.au=M%C3%BCnger%2C+K%3BPhelps%2C+W+C&rft.aulast=M%C3%BCnger&rft.aufirst=K&rft.date=1993-05-25&rft.volume=1155&rft.issue=1&rft.spage=111&rft.isbn=&rft.btitle=&rft.title=Biochimica+et+biophysica+acta&rft.issn=00063002&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-07-07 N1 - Date created - 1993-07-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Assessment of the carcinogenic potential of chlorinated water: experimental studies of chlorine, chloramine, and trihalomethanes. AN - 75717628; 8487327 AB - Water chlorination has been one of the major disease prevention treatments of this century. While epidemiologic studies suggest an association between cancer in humans and consumption of chlorination byproducts in drinking water, these studies have not been adequate to draw definite conclusions about the carcinogenic potential of the individual byproducts. The purpose of this study was to investigate the carcinogenic potential of chlorinated or chloraminated drinking water and of four organic trihalomethane byproducts of chlorination (chloroform, bromodichloromethane, chlorodibromomethane, and bromoform) in rats and mice. Bromodichloromethane, chlorodibromomethane, bromoform, chlorine, or chloramine was administered to both sexes of F344/N rats and (C57BL/6 x C3H)F1 mice (hereafter called B6C3F1 mice). Chloroform was given to both sexes of Osborne-Mendel rats and B6C3F1 mice. Chlorine or chloramine was administered daily in the drinking water for 2 years at doses ranging from 0.05 to 0.3 mmol/kg per day. The trihalomethanes were administered by gavage in corn oil at doses ranging from 0.15 to 4.0 mmol/kg per day for 2 years, with the exception of chloroform, which was given for 78 weeks. The trihalomethanes were carcinogenic in the liver, kidney, and/or intestine of rodents. There was equivocal evidence for carcinogenicity in female rats that received chlorinated or chloraminated drinking water; this evidence was based on a marginal increase in the incidence of mononuclear cell leukemia. Rodents were generally exposed to lower doses of chlorine and chloramine than to the trihalomethanes, but the doses in these studies were the maximum that the animals would consume in the drinking water. The highest doses used in the chlorine and chloramine studies were equivalent to a daily gavage dose of bromodichloromethane that induced neoplasms of the large intestine in rats. In contrast to the results with the trihalomethanes, administration of chlorine or chloramine did not cause a clear carcinogenic response in rats or mice after long-term exposure. These results suggest that organic byproducts of chlorination are the chemicals of greatest concern in assessment of the carcinogenic potential of chlorinated drinking water. JF - Journal of the National Cancer Institute AU - Dunnick, J K AU - Melnick, R L AD - National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, N.C. 27709. Y1 - 1993/05/19/ PY - 1993 DA - 1993 May 19 SP - 817 EP - 822 VL - 85 IS - 10 SN - 0027-8874, 0027-8874 KW - Chloramines KW - 0 KW - Chlorofluorocarbons, Methane KW - Chlorine KW - 4R7X1O2820 KW - chloramine KW - KW8K411A1P KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Liver -- drug effects KW - Kidney Neoplasms -- chemically induced KW - Dose-Response Relationship, Drug KW - Mice, Inbred C57BL KW - Mice, Inbred C3H KW - Intestinal Neoplasms -- chemically induced KW - Liver Neoplasms, Experimental -- chemically induced KW - Mice KW - Male KW - Female KW - Chlorine -- toxicity KW - Chloramines -- toxicity KW - Water Supply -- standards KW - Neoplasms, Experimental -- chemically induced KW - Chlorofluorocarbons, Methane -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75717628?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+National+Cancer+Institute&rft.atitle=Assessment+of+the+carcinogenic+potential+of+chlorinated+water%3A+experimental+studies+of+chlorine%2C+chloramine%2C+and+trihalomethanes.&rft.au=Dunnick%2C+J+K%3BMelnick%2C+R+L&rft.aulast=Dunnick&rft.aufirst=J&rft.date=1993-05-19&rft.volume=85&rft.issue=10&rft.spage=817&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+National+Cancer+Institute&rft.issn=00278874&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-06-10 N1 - Date created - 1993-06-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pitfalls inherent in retrospective time-to-event studies: the example of time to pregnancy. AN - 75826062; 8327803 AB - Retrospective studies of time from initiation of risk (for example, transfusion of HIV-infected blood) to the occurrence of an endpoint of interest are useful in epidemiology. One example is studies of time to pregnancy, which have evaluated exposures that may affect human fertility. One can reconstruct the non-contracepting interval required for each woman's most recent pregnancy and then treat the data as if the couples had been studied prospectively. As we illustrate, however, failure-time models can be dangerously misleading when there have been trends over calendar time in exposures under study. We propose an ad hoc method for evaluating possible effects on fertility despite this bias, by making use of external data on trends in the exposure over time. This approach applies a prospective model and generates an empirical p-value, based on comparing the data-based estimated exposure coefficient with its null distribution estimated by simulation. A second method maximizes a conditional likelihood, and we show that this is equivalent to logistically modelling the relative odds for the subject's exposure as related to the reported time she required to achieve pregnancy. JF - Statistics in medicine AU - Weinberg, C R AU - Baird, D D AU - Rowland, A S AD - Statistics and Biomathematics Branch, National Institute of Environmental Health Sciences, NC 27709. Y1 - 1993/05/15/ PY - 1993 DA - 1993 May 15 SP - 867 EP - 879 VL - 12 IS - 9 SN - 0277-6715, 0277-6715 KW - Nitrous Oxide KW - K50XQU1029 KW - Index Medicus KW - Nitrous Oxide -- adverse effects KW - Cross-Sectional Studies KW - Infertility, Female -- epidemiology KW - Humans KW - Retrospective Studies KW - Occupational Exposure -- adverse effects KW - Dental Assistants -- statistics & numerical data KW - Bias (Epidemiology) KW - California -- epidemiology KW - Female KW - Infertility, Female -- chemically induced KW - Models, Statistical KW - Pregnancy -- statistics & numerical data UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75826062?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Statistics+in+medicine&rft.atitle=Pitfalls+inherent+in+retrospective+time-to-event+studies%3A+the+example+of+time+to+pregnancy.&rft.au=Weinberg%2C+C+R%3BBaird%2C+D+D%3BRowland%2C+A+S&rft.aulast=Weinberg&rft.aufirst=C&rft.date=1993-05-15&rft.volume=12&rft.issue=9&rft.spage=867&rft.isbn=&rft.btitle=&rft.title=Statistics+in+medicine&rft.issn=02776715&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-08-06 N1 - Date created - 1993-08-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Birth weight and perinatal mortality: the effect of maternal smoking. AN - 75807958; 8317439 AB - Infants born to mothers who smoke are a few hundred grams smaller, on average, than the infants of nonsmokers. This effect on fetal growth is regarded as evidence of the reproductive toxicity of cigarette smoking. In this paper, data from nearly 260,000 births in the state of Missouri (1980-1984) were analyzed using a method based on adjustment to relative birth weight. Two additional effects of smoking are demonstrated with this analysis; i.e., smokers are at higher risk of delivering very small preterm infants, and their infants have higher perinatal mortality at every relative birth weight. The latter is not apparent on an absolute birth weight scale and thus is not generally recognized. A supplementary analysis of births at high altitude is carried out to suggest that effects on fetal growth (whether from smoking or other factors) can occur independently of effects on mortality. JF - American journal of epidemiology AU - Wilcox, A J AD - Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1993/05/15/ PY - 1993 DA - 1993 May 15 SP - 1098 EP - 1104 VL - 137 IS - 10 SN - 0002-9262, 0002-9262 KW - Index Medicus KW - Altitude KW - Humans KW - Infant, Newborn KW - Infant, Premature KW - United States -- epidemiology KW - Colorado -- epidemiology KW - Female KW - Pregnancy KW - Embryonic and Fetal Development -- drug effects KW - Birth Weight KW - Smoking -- adverse effects KW - Infant Mortality KW - Prenatal Exposure Delayed Effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75807958?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+epidemiology&rft.atitle=Birth+weight+and+perinatal+mortality%3A+the+effect+of+maternal+smoking.&rft.au=Wilcox%2C+A+J&rft.aulast=Wilcox&rft.aufirst=A&rft.date=1993-05-15&rft.volume=137&rft.issue=10&rft.spage=1098&rft.isbn=&rft.btitle=&rft.title=American+journal+of+epidemiology&rft.issn=00029262&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-07-26 N1 - Date created - 1993-07-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Stability, clearance, and disposition of intraventricularly administered oligodeoxynucleotides: implications for therapeutic application within the central nervous system. AN - 75784065; 8506315 AB - We report experiments in the rat demonstrating the feasibility of intraventricular administration of oligodeoxynucleotides (ODNs) as a regional treatment approach to disorders within the central nervous system (CNS). Although we find little intrinsic nuclease activity in cerebrospinal fluid (CSF), phosphodiester ODNs are rapidly degraded by brain-associated alpha-exonuclease activity. Phosphorothioate ODNs, however, appear resistant to degradation in the CNS and, after intraventricular administration, we find they are cleared in a manner consistent with CSF bulk flow. Continuous infusion of ODN at 1.5 nmol/hr by miniosmotic pump can maintain micromolar concentrations of intact phosphorothioate ODN in CSF for at least 1 week without obvious neurologic or systemic toxicity. After infusion, extensive brain penetration and marked cellular uptake, especially by astrocytic cells, is demonstrated. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Whitesell, L AU - Geselowitz, D AU - Chavany, C AU - Fahmy, B AU - Walbridge, S AU - Alger, J R AU - Neckers, L M AD - Tumor Cell Biology Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/05/15/ PY - 1993 DA - 1993 May 15 SP - 4665 EP - 4669 VL - 90 IS - 10 SN - 0027-8424, 0027-8424 KW - Oligodeoxyribonucleotides KW - 0 KW - Thionucleotides KW - Index Medicus KW - Rats KW - Microscopy, Fluorescence KW - Animals KW - Rats, Sprague-Dawley KW - Base Sequence KW - Molecular Sequence Data KW - Tissue Distribution KW - Thionucleotides -- chemistry KW - Female KW - Injections, Intraventricular KW - Oligodeoxyribonucleotides -- pharmacokinetics KW - Oligodeoxyribonucleotides -- chemistry KW - Oligodeoxyribonucleotides -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75784065?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Stability%2C+clearance%2C+and+disposition+of+intraventricularly+administered+oligodeoxynucleotides%3A+implications+for+therapeutic+application+within+the+central+nervous+system.&rft.au=Whitesell%2C+L%3BGeselowitz%2C+D%3BChavany%2C+C%3BFahmy%2C+B%3BWalbridge%2C+S%3BAlger%2C+J+R%3BNeckers%2C+L+M&rft.aulast=Whitesell&rft.aufirst=L&rft.date=1993-05-15&rft.volume=90&rft.issue=10&rft.spage=4665&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 - 1993-07-02 N1 - Date created - 1993-07-02 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Brain Res. 1973 Mar 30;52:323-32 [4739806] Differentiation. 1983;25(2):193-203 [6198232] J Neurochem. 1985 Aug;45(2):508-13 [2409231] Nature. 1992 Sep 3;359(6390):67-70 [1522889] Crit Rev Oncog. 1992;3(1-2):175-231 [1312868] Antisense Res Dev. 1991 Winter;1(4):343-50 [1821655] Proc Natl Acad Sci U S A. 1991 Sep 1;88(17):7595-9 [1881900] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Oxygen toxicity in a polyamine-depleted spe2 delta mutant of Saccharomyces cerevisiae. AN - 75781978; 8506320 AB - When a mutant of Saccharomyces cerevisiae (spe2 delta) that cannot make spermidine or spermine was incubated in a polyamine-deficient medium in oxygen, there was a rapid cessation of cell growth and associated cell death. In contrast, when the mutant cells were incubated in the polyamine-deficient medium in air or anaerobically, the culture stopped growing more gradually, and there was no significant loss of cell viability. We also found that the polyamine-deficient cells grown in air, but not those grown anaerobically, showed a permanent loss of functional mitochondria ("respiratory competency"), as evidenced by their inability to grow on glycerol as the sole carbon source. These data support the postulation that polyamines act, in part, by protecting cell components from damage resulting from oxidation. However, since the mutant cells still required spermidine or spermine for growth when incubated under strictly anaerobic conditions, polyamines must also have other essential functions. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Balasundaram, D AU - Tabor, C W AU - Tabor, H AD - Section on Pharmacology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/05/15/ PY - 1993 DA - 1993 May 15 SP - 4693 EP - 4697 VL - 90 IS - 10 SN - 0027-8424, 0027-8424 KW - SOD1 KW - SPE2 KW - Polyamines KW - 0 KW - Superoxide Dismutase KW - EC 1.15.1.1 KW - Adenosylmethionine Decarboxylase KW - EC 4.1.1.50 KW - Oxygen KW - S88TT14065 KW - Index Medicus KW - Space life sciences KW - Phenotype KW - Superoxide Dismutase -- metabolism KW - Mitochondria -- metabolism KW - Anaerobiosis KW - Adenosylmethionine Decarboxylase -- physiology KW - Saccharomyces cerevisiae -- physiology KW - Oxygen -- toxicity KW - Polyamines -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75781978?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Oxygen+toxicity+in+a+polyamine-depleted+spe2+delta+mutant+of+Saccharomyces+cerevisiae.&rft.au=Balasundaram%2C+D%3BTabor%2C+C+W%3BTabor%2C+H&rft.aulast=Balasundaram&rft.aufirst=D&rft.date=1993-05-15&rft.volume=90&rft.issue=10&rft.spage=4693&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 - 1993-07-02 N1 - Date created - 1993-07-02 N1 - Date revised - 2017-01-13 N1 - Gene symbol - SOD1; SPE2 N1 - SuppNotes - Cited By: Comp Biochem Physiol B. 1989;93(3):647-51 [2758801] J Bacteriol. 1980 Jun;142(3):791-9 [6991493] Proc Natl Acad Sci U S A. 1990 Apr;87(7):2851-5 [2181453] Arch Biochem Biophys. 1990 May 1;278(2):386-91 [2139316] J Biol Chem. 1990 Dec 25;265(36):22321-8 [2266128] Proc Natl Acad Sci U S A. 1991 Jul 1;88(13):5872-6 [2062864] J Bacteriol. 1991 Sep;173(18):5918-20 [1885557] Eur J Biochem. 1981 May;116(1):1-6 [7018900] J Bacteriol. 1983 Jan;153(1):163-8 [6336730] CRC Crit Rev Biochem. 1983;14(1):47-92 [6340956] Annu Rev Biochem. 1984;53:749-90 [6206782] Microbiol Rev. 1985 Mar;49(1):81-99 [3157043] Biochem Biophys Res Commun. 1985 Jul 31;130(2):533-9 [2992473] Proc Natl Acad Sci U S A. 1986 Jun;83(11):3820-4 [3520557] Biochem J. 1988 Jan 1;249(1):33-6 [3124824] Proc Natl Acad Sci U S A. 1988 Jul;85(13):4789-93 [3290902] Yeast. 1986 Sep;2(3):163-7 [3333305] J Biol Chem. 1989 May 15;264(14):7761-4 [2542241] Microbiol Rev. 1992 Jun;56(2):280-90 [1620066] Proc Natl Acad Sci U S A. 1992 Dec 1;89(23):11426-7 [1454830] Proc Natl Acad Sci U S A. 1992 Dec 1;89(23):11428-30 [1454831] Yeast. 1992 Dec;8(12):1033-41 [1293883] J Mol Biol. 1970 Sep 14;52(2):323-35 [5485912] J Biol Chem. 1978 Mar 25;253(6):1838-45 [204632] J Bacteriol. 1978 Apr;134(1):208-13 [348678] J Bacteriol. 1978 Apr;134(1):214-20 [348679] Biochem J. 1989 May 15;260(1):1-10 [2673211] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Generation of free radicals in reactions of Ni(II)-thiol complexes with molecular oxygen and model lipid hydroperoxides. AN - 75763630; 8388916 AB - The generation of free radicals from reactions of nickel(II)-thiol complexes with molecular oxygen and model lipid hydroperoxides was investigated by electron spin resonance (ESR) utilizing 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) as a spin trap. Incubation of nickel(II) [Ni(II)] with cysteine in an aerobic environment generated hydroxyl (.OH) radical, which then reacted with cysteine to generate a carbon-centered alkyl (.R) radical. Radical generation was inhibited under a nitrogen atmosphere. Model lipid hydroperoxides, cumene hydroperoxide, and t-butyl hydroperoxide enhanced the yield of these radicals and also generated an alkoxyl (.OR) radical. Radical yield decreased by approximately half under a nitrogen atmosphere. Although histidine did not cause radical formation in the reaction between Ni(II) and cumene hydroperoxide under aerobic conditions, the addition of histidine to a mixture containing Ni(II), cysteine, and cumene hydroperoxide under the same experimental conditions increased the yield of .R radical but lowered the yield of .OR and .OH radical adducts. It thus appears that histidine caused the .OH attack to be more site-specific. Similar results were obtained utilizing t-butyl hydroperoxide. Penicillamine or N-acetylcysteine yielded similar results except that under aerobic conditions, reaction between Ni(II) and N-acetylcysteine without hydroperoxide did not generate a significant concentration of free radicals. Under the same experimental conditions, cystine did not generate any detectable free radicals, suggesting an important role of the -SH group in Ni(II)-mediated free radical generation. The results indicate that free radical generation from the reaction of Ni(II)-thiol complexes and molecular oxygen, and/or lipid hydroperoxides, may play an important role in the mechanism(s) of Ni(II) toxicity and carcinogenesis. JF - Journal of inorganic biochemistry AU - Shi, X AU - Dalal, N S AU - Kasprzak, K S AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland 21702. Y1 - 1993/05/15/ PY - 1993 DA - 1993 May 15 SP - 211 EP - 225 VL - 50 IS - 3 SN - 0162-0134, 0162-0134 KW - Benzene Derivatives KW - 0 KW - Free Radicals KW - Lipid Peroxides KW - Peroxides KW - Sulfhydryl Compounds KW - Histidine KW - 4QD397987E KW - Nickel KW - 7OV03QG267 KW - tert-Butylhydroperoxide KW - 955VYL842B KW - Penicillamine KW - GNN1DV99GX KW - Cysteine KW - K848JZ4886 KW - cumene hydroperoxide KW - PG7JD54X4I KW - Oxygen KW - S88TT14065 KW - Acetylcysteine KW - WYQ7N0BPYC KW - Index Medicus KW - Cysteine -- metabolism KW - Peroxides -- metabolism KW - Electron Spin Resonance Spectroscopy KW - Benzene Derivatives -- metabolism KW - Acetylcysteine -- metabolism KW - Penicillamine -- metabolism KW - Histidine -- pharmacology KW - Sulfhydryl Compounds -- metabolism KW - Oxygen -- metabolism KW - Nickel -- metabolism KW - Lipid Peroxides -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75763630?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+inorganic+biochemistry&rft.atitle=Generation+of+free+radicals+in+reactions+of+Ni%28II%29-thiol+complexes+with+molecular+oxygen+and+model+lipid+hydroperoxides.&rft.au=Shi%2C+X%3BDalal%2C+N+S%3BKasprzak%2C+K+S&rft.aulast=Shi&rft.aufirst=X&rft.date=1993-05-15&rft.volume=50&rft.issue=3&rft.spage=211&rft.isbn=&rft.btitle=&rft.title=Journal+of+inorganic+biochemistry&rft.issn=01620134&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-06-29 N1 - Date created - 1993-06-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Retinoid status controls the appearance of reserve cells and keratin expression in mouse cervical epithelium. AN - 75722629; 7683571 AB - We describe an animal model to induce the histogenesis of squamous metaplasia of the cervical columnar epithelium, a condition usually preceding cervical neoplasia. This model is based on dietary retinoid depletion in female mice. Control sibling mice fed the same diet but with all-trans-retinoic acid (at 3 micrograms/g diet) showed the normal endocervical epithelial and glandular columnar morphology, typical of a simple epithelium without subcolumnar reserve cells. The stratified squamous ectocervical epithelium of these mice fed all-trans retinoic acid showed intense immunohistochemical staining in basal and suprabasal cells with mono-specific antibodies against keratins K5, K14, K6, K13, and, suprabasally, with antibodies specific for K1 and K10. At the squamocolumnar junction, the adjacent columnar epithelium (termed "suprajunctional") did not show staining for K5, K14, K6, K13, K1, and K10 but specifically stained for keratin K8, typical of simple epithelia and absent from the adjacent ectocervical squamous stratified lining (termed "subjunctional"), in striking contrast. Sections of the squamocolumnar junction from mice kept on the vitamin A-deficient diet for 10 weeks showed suprajunctional isolated patches of reserve cells, proximal and distal to the junction. These cells were detected prior to any symptoms of vitamin A deficiency, such as loss of body weight or respiratory discomfort. The subcolumnar reserve cells induced by vitamin A deficiency displayed positive staining for K5 and K14. As deficiency became severe, the reserve cells occupied the entirety of the suprajunctional basement membrane. This epithelium eventually became stratified and squamous metaplastic, the squamocolumnar junction was no longer discernible, and the entire endocervical epithelium and the endometrial glands lost K8 positivity, while acquiring K5, K14, K6, K13, K1, and K10 keratins typical of the ectocervix under normal conditions of vitamin A nutriture. Vitamin A deficiency also altered keratin expression and localization in squamous subjunctional epithelium. In situ hybridization studies for K1 and K5 mRNA showed their major site of expression at the basal (K5) and immediately suprabasal (K1) cell layers. The localization of both K5 and K1 proteins in these same cell layers, and above, is consistent with transcriptional regulation of these keratins. Early vitamin A deficiency caused the appearance of single subcolumnar reserve cells expressing K5 mRNA. After these cells grew into a squamous focus, K1 mRNA became expressed suprabasally. We conclude that retinoid status plays a key role in maintaining differentiative characteristics of the cervical and glandular epithelia and, as such, may be a modulating factor in the development of cervical cancer. JF - Cancer research AU - Darwiche, N AU - Celli, G AU - Sly, L AU - Lancillotti, F AU - De Luca, L M AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, NIH, Bethesda, Maryland 20892. Y1 - 1993/05/15/ PY - 1993 DA - 1993 May 15 SP - 2287 EP - 2299 VL - 53 IS - 10 Suppl SN - 0008-5472, 0008-5472 KW - RNA, Messenger KW - 0 KW - Retinoids KW - Tretinoin KW - 5688UTC01R KW - Keratins KW - 68238-35-7 KW - Index Medicus KW - Animals KW - Carcinoma, Squamous Cell -- etiology KW - Disease Models, Animal KW - Mice, Nude KW - Mice KW - Vitamin A Deficiency -- pathology KW - RNA, Messenger -- genetics KW - Mice, Inbred BALB C KW - Metaplasia -- etiology KW - Phenotype KW - In Situ Hybridization KW - Carcinoma, Squamous Cell -- pathology KW - Metaplasia -- pathology KW - Diet KW - Epithelium -- pathology KW - Vitamin A Deficiency -- complications KW - Immunohistochemistry KW - Female KW - Uterine Cervical Neoplasms -- etiology KW - Keratins -- genetics KW - Cervix Uteri -- pathology KW - Cervix Uteri -- drug effects KW - Tretinoin -- pharmacology KW - Cervix Uteri -- physiology KW - Retinoids -- metabolism KW - Keratins -- physiology KW - Precancerous Conditions -- etiology KW - Uterine Cervical Neoplasms -- pathology KW - Precancerous Conditions -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75722629?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Retinoid+status+controls+the+appearance+of+reserve+cells+and+keratin+expression+in+mouse+cervical+epithelium.&rft.au=Darwiche%2C+N%3BCelli%2C+G%3BSly%2C+L%3BLancillotti%2C+F%3BDe+Luca%2C+L+M&rft.aulast=Darwiche&rft.aufirst=N&rft.date=1993-05-15&rft.volume=53&rft.issue=10+Suppl&rft.spage=2287&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 - 1993-06-10 N1 - Date created - 1993-06-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A masked, randomized, dose-response study between cyclosporine A and G in the treatment of sight-threatening uveitis of noninfectious origin. AN - 75718999; 8488909 AB - Thirty-two patients with sight-threatening uveitis and a decrease in visual acuity requiring systemic therapy were randomly assigned to either cyclosporine A or G in a dose-escalation study. Groups received from 2.5 mg/kg of body weight/day to 10 mg/kg of body weight/day of either drug along with low-dose prednisone. More patients taking cyclosporine G had improved visual acuity and a decrease in macular edema, which occurred more rapidly than in the other group, even at the lower doses tested. No difference in renal function was noted between groups at any doses tested. Four patients receiving cyclosporine G had hepatic alterations, but only one required cessation of the drug. The study indicates the potential usefulness of cyclosporine G, particularly at lower doses (4 mg/kg of body weight/day), which could lower the potential for serious renal complications. JF - American journal of ophthalmology AU - Nussenblatt, R B AU - de Smet, M D AU - Rubin, B AU - Freidlin, V AU - Whitcup, S M AU - Davis, J AU - Herman, D AU - Bloom, J N AU - Sran, P K AU - Whitcher, S AD - Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/05/15/ PY - 1993 DA - 1993 May 15 SP - 583 EP - 591 VL - 115 IS - 5 SN - 0002-9394, 0002-9394 KW - Cyclosporins KW - 0 KW - Immunosuppressive Agents KW - cyclosporin G KW - 74436-00-3 KW - Cyclosporine KW - 83HN0GTJ6D KW - Prednisone KW - VB0R961HZT KW - Abridged Index Medicus KW - Index Medicus KW - Double-Blind Method KW - Dose-Response Relationship, Drug KW - Humans KW - Visual Acuity -- drug effects KW - Adult KW - Prednisone -- administration & dosage KW - Male KW - Female KW - Cyclosporins -- adverse effects KW - Cyclosporine -- administration & dosage KW - Cyclosporine -- adverse effects KW - Vision Disorders -- etiology KW - Vision Disorders -- prevention & control KW - Uveitis -- complications KW - Uveitis -- physiopathology KW - Cyclosporins -- administration & dosage KW - Uveitis -- drug therapy KW - Immunosuppressive Agents -- adverse effects KW - Immunosuppressive Agents -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75718999?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+ophthalmology&rft.atitle=A+masked%2C+randomized%2C+dose-response+study+between+cyclosporine+A+and+G+in+the+treatment+of+sight-threatening+uveitis+of+noninfectious+origin.&rft.au=Nussenblatt%2C+R+B%3Bde+Smet%2C+M+D%3BRubin%2C+B%3BFreidlin%2C+V%3BWhitcup%2C+S+M%3BDavis%2C+J%3BHerman%2C+D%3BBloom%2C+J+N%3BSran%2C+P+K%3BWhitcher%2C+S&rft.aulast=Nussenblatt&rft.aufirst=R&rft.date=1993-05-15&rft.volume=115&rft.issue=5&rft.spage=583&rft.isbn=&rft.btitle=&rft.title=American+journal+of+ophthalmology&rft.issn=00029394&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-06-08 N1 - Date created - 1993-06-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A cytotoxic ribonuclease. Study of the mechanism of onconase cytotoxicity. AN - 75715251; 8486718 AB - Onconase, or P-30, is a protein initially purified from extracts of Rana pipiens oocytes and early embryos based upon its anticancer activity both in vitro and in vivo. It is a basic single-chain protein with an apparent molecular mass of 12,000 daltons and is homologous to RNase A. In cultured 9L glioma cells, onconase inhibits protein synthesis with an IC50 of about 10(-7) M. The inhibition of protein synthesis correlates with cell death determined by clonogenic assays. 125I-Labeled onconase binds to specific sites on cultured 9L glioma cells. Scatchard analysis of the binding data shows that onconase appears to bind to cells with two different affinities, one with a Kd of 6.2 x 10(-8) and another of 2.5 x 10(-7) M. Each cell could bind about 3 x 10(5) molecules of onconase at each of the two affinity sites. The low affinity Kd is similar to the IC50 for onconase toxicity. Onconase also demonstrates a saturability of cytotoxicity at a concentration that would saturate the low affinity binding site. Incubation at 4 degrees C increased the binding of onconase to cells relative to 37 degrees C binding and also increased the sensitivity of cells to onconase toxicity, indicating that receptor binding may be an initial step in cell toxicity. Onconase cytotoxicity can be blocked by metabolic inhibitors, NaN3 and 2-deoxyglucose, and cytotoxicity is potentiated 10-fold by monensin. Ribonuclease activity appears necessary for onconase toxicity because alkylated onconase, which only retains 2% of the ribonuclease activity, was at least 100-fold less potent in inhibiting protein synthesis in cells. Onconase inhibition of protein synthesis in 9L cells coincides with the degradation of cellular 28 S and 18 S rRNA. In contrast to RNase A, onconase is resistant to two RNase inhibitors, placental ribonuclease inhibitor and Inhibit-Ace. Northern hybridization with placental ribonuclease inhibitor cDNA probe indicates that 9L glioma cells contain endogenous placental ribonuclease inhibitor mRNA. Based on these results, we propose that onconase toxicity results from onconase binding to cell surface receptors, internalization to the cell cytosol where it degrades ribosomal RNA, inhibiting protein synthesis and causing cell death. JF - The Journal of biological chemistry AU - Wu, Y AU - Mikulski, S M AU - Ardelt, W AU - Rybak, S M AU - Youle, R J AD - Biochemistry Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/05/15/ PY - 1993 DA - 1993 May 15 SP - 10686 EP - 10693 VL - 268 IS - 14 SN - 0021-9258, 0021-9258 KW - Antineoplastic Agents KW - 0 KW - Cyclopentanes KW - Egg Proteins KW - Neoplasm Proteins KW - Placental Hormones KW - Protein Synthesis Inhibitors KW - RNA, Messenger KW - placental ribonuclease inhibitor KW - 120178-77-0 KW - Brefeldin A KW - 20350-15-6 KW - Ribonucleases KW - EC 3.1.- KW - Ribonuclease, Pancreatic KW - EC 3.1.27.5 KW - Leucine KW - GMW67QNF9C KW - ranpirnase KW - ZE15FIT23E KW - Index Medicus KW - Rana pipiens KW - Animals KW - Neoplasm Proteins -- biosynthesis KW - Blotting, Northern KW - Dose-Response Relationship, Drug KW - Ribonuclease, Pancreatic -- toxicity KW - RNA, Messenger -- genetics KW - Autoradiography KW - Embryo, Nonmammalian KW - Ribonuclease, Pancreatic -- metabolism KW - Placental Hormones -- biosynthesis KW - Cyclopentanes -- pharmacology KW - Tumor Cells, Cultured KW - RNA, Messenger -- metabolism KW - Kinetics KW - Leucine -- metabolism KW - Oocytes KW - Glioma KW - Tumor Stem Cell Assay KW - Ribonucleases -- toxicity KW - Ribonucleases -- antagonists & inhibitors KW - Protein Synthesis Inhibitors -- pharmacology KW - Cell Survival -- drug effects KW - Antineoplastic Agents -- metabolism KW - Antineoplastic Agents -- toxicity KW - Egg Proteins -- metabolism KW - Egg Proteins -- toxicity KW - Ribonucleases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75715251?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+cytotoxic+ribonuclease.+Study+of+the+mechanism+of+onconase+cytotoxicity.&rft.au=Wu%2C+Y%3BMikulski%2C+S+M%3BArdelt%2C+W%3BRybak%2C+S+M%3BYoule%2C+R+J&rft.aulast=Wu&rft.aufirst=Y&rft.date=1993-05-15&rft.volume=268&rft.issue=14&rft.spage=10686&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 - 1993-06-08 N1 - Date created - 1993-06-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Multiple myeloma. New approaches to therapy. AN - 75699286; 7683062 JF - JAMA AU - Dunbar, C E AU - Nienhuis, A W AD - Hematology Branch, National Heart, Lung, and Blood Institute, Bethesda, Md, National Institutes of Health 20892. Y1 - 1993/05/12/ PY - 1993 DA - 1993 May 12 SP - 2412 EP - 2416 VL - 269 IS - 18 SN - 0098-7484, 0098-7484 KW - Genetic Markers KW - 0 KW - Interferon-alpha KW - Interleukin-6 KW - Granulocyte Colony-Stimulating Factor KW - 143011-72-7 KW - Cyclophosphamide KW - 8N3DW7272P KW - Melphalan KW - Q41OR9510P KW - Fluorouracil KW - U3P01618RT KW - Abridged Index Medicus KW - Index Medicus KW - Interferon-alpha -- therapeutic use KW - Granulocyte Colony-Stimulating Factor -- therapeutic use KW - Interleukin-6 -- secretion KW - Combined Modality Therapy KW - Humans KW - Transplantation, Autologous KW - Fluorouracil -- therapeutic use KW - Whole-Body Irradiation KW - Cyclophosphamide -- therapeutic use KW - Genetic Therapy -- methods KW - Middle Aged KW - Melphalan -- therapeutic use KW - Research KW - Bone Marrow Transplantation KW - Female KW - Multiple Myeloma -- genetics KW - Multiple Myeloma -- therapy KW - Multiple Myeloma -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75699286?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=proceeding&rft.jtitle=JAMA&rft.atitle=Multiple+myeloma.+New+approaches+to+therapy.&rft.au=Dunbar%2C+C+E%3BNienhuis%2C+A+W&rft.aulast=Dunbar&rft.aufirst=C&rft.date=1993-05-12&rft.volume=269&rft.issue=18&rft.spage=2412&rft.isbn=&rft.btitle=&rft.title=JAMA&rft.issn=00987484&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-05-25 N1 - Date created - 1993-05-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Prediction of alternative RNA secondary structures based on fluctuating thermodynamic parameters. AN - 19797125; 8739496 AB - In this paper we present a new method for predicting a set of RNA secondary structures that are thermodynamically favored in RNA folding simulations. This method uses a large number of 'simulated energy rules' (SER) generated by perturbing the free energy parameters derived experimentally within the range of the experimental errors. The structure with the lowest free energy is computed for each SER. Structural comparisons are used to avoid multiple generation of similar structures. Computed structures are evaluated using the energy distribution of the lowest free energy structures derived in the simulation. Predicted be graphically displayed with their occurring frequencies in the simulation by dot-plot representations. On average, about 90% of phylogenetic helixes in the known models of tRNA, Group I self-splicing intron, and Escherichia coli 16 S rRNA, were predicted using the method. JF - Nucleic Acids Research AU - Le, S Y AU - Chen, J H AU - Maizel, J V AD - Laboratory of Mathematical Biology, National Cancer Institute, NIH, Frederick, MD 21702. Y1 - 1993/05/11/ PY - 1993 DA - 1993 May 11 SP - 2173 EP - 2178 PB - Oxford University Press, Oxford Journals, Great Clarendon Street VL - 21 IS - 9 SN - 0305-1048, 0305-1048 KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - Protein structure KW - Phylogeny KW - rRNA KW - Thermodynamics KW - tRNA KW - Secondary structure KW - Escherichia coli KW - Introns KW - Free energy KW - Models KW - J 02310:Genetics & Taxonomy KW - N 14810:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19797125?accountid=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=Nucleic+Acids+Research&rft.atitle=Prediction+of+alternative+RNA+secondary+structures+based+on+fluctuating+thermodynamic+parameters.&rft.au=Le%2C+S+Y%3BChen%2C+J+H%3BMaizel%2C+J+V&rft.aulast=Le&rft.aufirst=S&rft.date=1993-05-11&rft.volume=21&rft.issue=9&rft.spage=2173&rft.isbn=&rft.btitle=&rft.title=Nucleic+Acids+Research&rft.issn=03051048&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2008-12-01 N1 - Last updated - 2015-03-27 N1 - SubjectsTermNotLitGenreText - Phylogeny; Protein structure; rRNA; Thermodynamics; tRNA; Secondary structure; Introns; Free energy; Models; Escherichia coli ER - TY - JOUR T1 - A method to increase the cumulative cleavage efficiency of ribozymes: thermal cycling. AN - 19713290; 8733210 AB - Images JF - Nucleic Acids Research AU - Dropulic, B AU - Lin, N H AU - Jeang, K T AD - Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/05/11/ PY - 1993 DA - 1993 May 11 SP - 2273 EP - 2274 PB - Oxford University Press, Oxford Journals, Great Clarendon Street VL - 21 IS - 9 SN - 0305-1048, 0305-1048 KW - Biotechnology and Bioengineering Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - Ribozymes KW - W 30940:Products KW - N 14810:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19713290?accountid=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=Nucleic+Acids+Research&rft.atitle=A+method+to+increase+the+cumulative+cleavage+efficiency+of+ribozymes%3A+thermal+cycling.&rft.au=Dropulic%2C+B%3BLin%2C+N+H%3BJeang%2C+K+T&rft.aulast=Dropulic&rft.aufirst=B&rft.date=1993-05-11&rft.volume=21&rft.issue=9&rft.spage=2273&rft.isbn=&rft.btitle=&rft.title=Nucleic+Acids+Research&rft.issn=03051048&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2008-12-01 N1 - Last updated - 2015-03-27 N1 - SubjectsTermNotLitGenreText - Ribozymes ER - TY - JOUR T1 - Activation of ADP-ribosylation factor by Golgi membranes. Evidence for a brefeldin A- and protease-sensitive activating factor on Golgi membranes. AN - 75730021; 8486645 AB - Recent evidence has implicated ADP-ribosylation factor (ARF) proteins as critical regulators of the protein secretory pathway, particularly in the endoplasmic reticulum-Golgi pathway. We have examined whether Golgi membranes contain activators of ARF and the consequences of ARF activation and acylation on its membrane association. Two means were used to assess ARF activation. First, guanosine 5'-3-O-(thio)triphosphate (GTP gamma S) binding to protein was found to be greater when ARF and Golgi were incubated together than when either was incubated alone. These data suggested that ARF GTP gamma S was formed. This was confirmed by showing that the GTP gamma S-bound protein functioned as a cofactor for cholera toxin-stimulated ADP-ribosylation of Gs alpha, a reaction for which activated ARF is a necessary cofactor. Trypsin treatment of Golgi, an inhibitory ARF peptide, and brefeldin A each inhibited Golgi-mediated activation by approximately 70%, demonstrating that a specific protein interaction is required for the majority of the ARF activation. This ARF-activating protein is a strong candidate for the molecular target for brefeldin A. The ubiquitous nature of ARF proteins and their importance in both the exocytic and endocytic pathways may explain the effects of brefeldin A on both exocytic and endocytic membrane traffic in animal cells. A protease-insensitive activation of ARF by Golgi could also be demonstrated and was the dominant activity observed in submicromolar concentrations of magnesium. We believe this to be the lipid-mediated process described previously for purified ARF proteins. ARF activation resulted in tight association of ARF with phospholipid vesicles. Vesicle association required amino-terminal myristoylation of ARF whereas activation did not. These studies indicate that the brefeldin A-sensitive ARF-activating protein and other factors that determine the level of activation of ARF in animal cells are fundamental regulators of membrane traffic in animal cells. JF - The Journal of biological chemistry AU - Randazzo, P A AU - Yang, Y C AU - Rulka, C AU - Kahn, R A AD - Section of Regulatory Mechanisms, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/05/05/ PY - 1993 DA - 1993 May 05 SP - 9555 EP - 9563 VL - 268 IS - 13 SN - 0021-9258, 0021-9258 KW - Carrier Proteins KW - 0 KW - Cyclopentanes KW - Myristic Acids KW - Peptides KW - Recombinant Proteins KW - Myristic Acid KW - 0I3V7S25AW KW - NAD KW - 0U46U6E8UK KW - Guanosine Diphosphate KW - 146-91-8 KW - Brefeldin A KW - 20350-15-6 KW - Guanosine 5'-O-(3-Thiotriphosphate) KW - 37589-80-3 KW - Guanosine Triphosphate KW - 86-01-1 KW - Cholera Toxin KW - 9012-63-9 KW - Endopeptidases KW - EC 3.4.- KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - ADP-Ribosylation Factors KW - EC 3.6.5.2 KW - Dimyristoylphosphatidylcholine KW - U86ZGC74V5 KW - Index Medicus KW - Peptides -- chemical synthesis KW - Animals KW - Guanosine Diphosphate -- metabolism KW - Humans KW - Cholera Toxin -- pharmacology KW - Brain -- metabolism KW - Guanosine Triphosphate -- metabolism KW - Rats KW - NAD -- metabolism KW - Recombinant Proteins -- metabolism KW - Molecular Sequence Data KW - CHO Cells KW - Dimyristoylphosphatidylcholine -- metabolism KW - Centrifugation, Density Gradient KW - Endoplasmic Reticulum -- metabolism KW - Carrier Proteins -- metabolism KW - Amino Acid Sequence KW - Myristic Acids -- metabolism KW - Cyclopentanes -- pharmacology KW - Cattle KW - Kinetics KW - Guanosine 5'-O-(3-Thiotriphosphate) -- metabolism KW - Cricetinae KW - GTP-Binding Proteins -- metabolism KW - GTP-Binding Proteins -- isolation & purification KW - Endopeptidases -- metabolism KW - Liver -- metabolism KW - Golgi Apparatus -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75730021?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Activation+of+ADP-ribosylation+factor+by+Golgi+membranes.+Evidence+for+a+brefeldin+A-+and+protease-sensitive+activating+factor+on+Golgi+membranes.&rft.au=Randazzo%2C+P+A%3BYang%2C+Y+C%3BRulka%2C+C%3BKahn%2C+R+A&rft.aulast=Randazzo&rft.aufirst=P&rft.date=1993-05-05&rft.volume=268&rft.issue=13&rft.spage=9555&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 - 1993-06-04 N1 - Date created - 1993-06-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of the fusion peptide sequence in initial stages of influenza hemagglutinin-induced cell fusion. AN - 75726655; 8387488 AB - The fusion activity of influenza hemagglutinin (HA) and of HA proteins altered in the amino terminus of HA2 (fusion peptide) by site-directed mutagenesis (Gething, M.-J., Doms, R. W., York, D., and White, J. (1986) J. Cell Biol. 102, 11-23) was analyzed following expression in CV-1 cells using SV40-HA recombinant virus vectors. Fusion was monitored by the redistribution of lipid and cytoplasmic dyes between fluorescently labeled erythrocytes and HA-expressing CV-1 cells using spectrofluorometry and fluorescence microscopy. The kinetics of lipid redistribution after lowering the pH showed the same pattern for wild type HA and nonlethal mutants, although there were shifts in the pH threshold. The time for commitment to the fusogenic state and the temperature dependence of the processes leading to HA-mediated fusion were also the same for wild type and nonlethal mutants. However, striking differences were observed between wild type HA and the nonlethal mutants in their ability to induce pH-dependent redistribution from erythrocytes to HA-expressing cells of large molecular weight (M(r) > 10,000) fluorescently labeled dextran molecules. The data indicate that the kinetic processes which are measurable in the time range of seconds are insensitive to the structure of the fusion peptide. Surprisingly, however, the fusion peptide plays an important role in later processes related to pore widening which eventually results in delivery of the nucleocapsid into the cell. JF - The Journal of biological chemistry AU - Schoch, C AU - Blumenthal, R AD - Section on Membrane Structure and Function, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/05/05/ PY - 1993 DA - 1993 May 05 SP - 9267 EP - 9274 VL - 268 IS - 13 SN - 0021-9258, 0021-9258 KW - Hemagglutinin Glycoproteins, Influenza Virus KW - 0 KW - Hemagglutinins, Viral KW - Viral Envelope Proteins KW - Index Medicus KW - Animals KW - Simian virus 40 -- genetics KW - Humans KW - Hydrogen-Ion Concentration KW - Amino Acid Sequence KW - Mutagenesis, Site-Directed KW - Kinetics KW - Cercopithecus aethiops KW - Kidney KW - Molecular Sequence Data KW - Viral Envelope Proteins -- metabolism KW - Cell Line KW - Erythrocyte Membrane -- metabolism KW - Hemagglutinins, Viral -- metabolism KW - Cell Fusion KW - Hemagglutinins, Viral -- genetics KW - Erythrocytes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75726655?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Role+of+the+fusion+peptide+sequence+in+initial+stages+of+influenza+hemagglutinin-induced+cell+fusion.&rft.au=Schoch%2C+C%3BBlumenthal%2C+R&rft.aulast=Schoch&rft.aufirst=C&rft.date=1993-05-05&rft.volume=268&rft.issue=13&rft.spage=9267&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 - 1993-06-04 N1 - Date created - 1993-06-04 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - J02127; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutational analysis of the Golgi retention signal of bovine beta-1,4-galactosyltransferase. AN - 75726494; 8387508 AB - To examine the role of the NH2-terminal region of the 402-residue-long beta-1,4-galactosyltransferase (beta-1,4-GT), a series of mutants and chimeric cDNA were constructed by polymerase chain reaction and transiently expressed in COS-7 cells, the enzyme activities were measured, and the protein was localized in the cells by subcellular fractionation or indirect immunofluorescence microscopy. We showed earlier that the deletion of the amino-terminal cytoplasmic tail and transmembrane domain from GT abolishes the stable expression of this protein in mammalian cells (Masibay, A.S., Boeggeman, E., and Qasba, P.K. (1992) Mol. Biol. Rep. 16, 99-104). Further deletion analyses of the amino-terminal region show that the first 21 amino acids of beta-1,4-GT are not essential for the stable production of the protein and are consistently localized in the Golgi apparatus. In addition, analysis of hybrid constructs showed that residues 1-25 of alpha-1,3-galactosyltransferase can functionally replace the beta-1,4-GT amino-terminal domain (residues 1-43). This fusion protein also showed Golgi localization. On the other hand, the alpha-2,6-sialyltransferase/beta-1,4-GT fusion protein (alpha-2,6-ST/beta-1,4-GT) needed additional COOH-terminal sequences flanking the transmembrane domain of the alpha-2,6-ST for stability and Golgi localization. Substitution of Arg-24, Leu-25, Leu-26, and His-33 of the beta-1,4-GT transmembrane by Ile (pLFM) or substitution of Tyr by Ile at positions 40 and 41 coupled with the insertion of 4 Ile residues at position 43 (pLB) released the mutant proteins from the Golgi and was detected on the cell surface. Our results show that (a) the transmembrane domains of beta-1,4-GT, alpha-1,3-galactosyltransferase, and alpha-2,6-ST, along with its stem region, all play a role in Golgi targeting and participate in a common mechanism that allows the protein to be processed properly and not be degraded in vivo; (b) increasing the length of the transmembrane domain overrides the Golgi retention signal and directs the enzyme to the plasma membrane; and (c) the length of the hydrophobic region of the transmembrane domain of beta-1,4-GT is an important parameter but is not sufficient by itself for Golgi retention. JF - The Journal of biological chemistry AU - Masibay, A S AU - Balaji, P V AU - Boeggeman, E E AU - Qasba, P K AD - Laboratory of Mathematical Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/05/05/ PY - 1993 DA - 1993 May 05 SP - 9908 EP - 9916 VL - 268 IS - 13 SN - 0021-9258, 0021-9258 KW - DNA, Recombinant KW - 0 KW - Oligodeoxyribonucleotides KW - Protein Sorting Signals KW - Recombinant Proteins KW - N-Acetyllactosamine Synthase KW - EC 2.4.1.90 KW - Sodium-Potassium-Exchanging ATPase KW - EC 3.6.3.9 KW - Index Medicus KW - Animals KW - Immunoblotting KW - Cell Membrane -- enzymology KW - Amino Acid Sequence KW - Mutagenesis KW - Base Sequence KW - Cattle KW - Sodium-Potassium-Exchanging ATPase -- metabolism KW - DNA, Recombinant -- metabolism KW - Transfection KW - Recombinant Proteins -- metabolism KW - Molecular Sequence Data KW - Recombinant Proteins -- analysis KW - Cell Line KW - Sequence Deletion KW - Protein Conformation KW - Protein Sorting Signals -- metabolism KW - N-Acetyllactosamine Synthase -- genetics KW - N-Acetyllactosamine Synthase -- analysis KW - N-Acetyllactosamine Synthase -- metabolism KW - Golgi Apparatus -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75726494?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mutational+analysis+of+the+Golgi+retention+signal+of+bovine+beta-1%2C4-galactosyltransferase.&rft.au=Masibay%2C+A+S%3BBalaji%2C+P+V%3BBoeggeman%2C+E+E%3BQasba%2C+P+K&rft.aulast=Masibay&rft.aufirst=A&rft.date=1993-05-05&rft.volume=268&rft.issue=13&rft.spage=9908&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 - 1993-06-04 N1 - Date created - 1993-06-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Binding of mutants of human insulin-like growth factor II to insulin-like growth factor binding proteins 1-6. AN - 75721283; 7683646 AB - A family of six specific insulin-like growth factor binding proteins (IGFBPs) modulates the biological actions of the insulin-like growth factors, IGF-I and IGF-II. In the present study, we determined the binding affinity of purified human IGFBPs 1-6 for recombinant human IGF-II mutants whose binding to IGF-I, IGF-II/mannose 6-phosphate, and insulin receptors was previously reported (Sakano, K., Enjoh, T., Numata, F., Fujiwara, H., Marumoto, Y., Higashihashi, N., Sato, Y., Perdue, J. F., and Fujita-Yamaguchi, Y. (1991) J. Biol. Chem. 266, 20626-20635). Of the regions studied, the most important determinants of IGF-II binding to the IGFBPs were A-domain residues 48-50 and B-domain residue 26. Substitution of residues 48-50 with the analogous residues from human insulin (Thr-Ser-Ile) reduced binding to IGFBP-1, -5, and -6 more than 50-fold and to IGFBP-4 by 15-50-fold; binding to IGFBP-2 and -3 was reduced 6-12-fold. The same substitution markedly reduced binding to the IGF-II/mannose 6-phosphate receptor but not to IGF-I or insulin receptors. Although substitution of residues 54 and 55 with the analogous residues from IGF-I (Arg-Arg) abolished binding to the IGF-II/mannose 6-phosphate receptor, binding to IGFBPs was not substantially affected. Substitution of Phe26 with Ser or Leu, which decreased binding to the IGF-I and insulin receptors, reduced binding to IGFBP-1 and -6 up to 80-fold, but had lesser effects on the other IGFBPs. [Leu27]IGF-II and [Leu43]IGF-II, which had a more markedly reduced affinity for the IGF-I and insulin receptors than did [Ser26]IGF-II, were bound by the IGFBPs with relatively unchanged affinity compared with IGF-II. Thus, the determinants of IGF-II binding to IGFBPs partially overlap those for the IGF-II/mannose 6-phosphate receptor and overlap those for the IGF-I receptor to a lesser extent. IGFBP-1 and IGFBP-6 are most sensitive to changes in IGF-II structure, although IGFBP-1 binds IGF-I and IGF-II with equal affinity, whereas IGFBP-6 has a marked preferential binding affinity for IGF-II. IGF-II mutants with selective impairment in recognition by specific IGFBPs or receptors will provide a useful tool for dissecting the role of the different IGF binding macromolecules in the mediation of IGF-II actions. JF - The Journal of biological chemistry AU - Bach, L A AU - Hsieh, S AU - Sakano, K AU - Fujiwara, H AU - Perdue, J F AU - Rechler, M M AD - Growth and Development Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/05/05/ PY - 1993 DA - 1993 May 05 SP - 9246 EP - 9254 VL - 268 IS - 13 SN - 0021-9258, 0021-9258 KW - Carrier Proteins KW - 0 KW - Insulin-Like Growth Factor Binding Protein 1 KW - Insulin-Like Growth Factor Binding Protein 2 KW - Insulin-Like Growth Factor Binding Protein 4 KW - Insulin-Like Growth Factor Binding Protein 5 KW - Insulin-Like Growth Factor Binding Protein 6 KW - Insulin-Like Growth Factor Binding Proteins KW - Recombinant Proteins KW - Insulin-Like Growth Factor I KW - 67763-96-6 KW - Insulin-Like Growth Factor II KW - 67763-97-7 KW - Index Medicus KW - Animals KW - Humans KW - Liver -- metabolism KW - Insulin-Like Growth Factor I -- metabolism KW - Amino Acid Sequence KW - Pregnancy KW - Rats KW - Mutagenesis, Site-Directed KW - Recombinant Proteins -- isolation & purification KW - Amniotic Fluid -- metabolism KW - Recombinant Proteins -- metabolism KW - Kinetics KW - Binding, Competitive KW - Molecular Sequence Data KW - Sequence Homology, Amino Acid KW - Female KW - Sequence Deletion KW - Carrier Proteins -- metabolism KW - Carrier Proteins -- cerebrospinal fluid KW - Insulin-Like Growth Factor II -- genetics KW - Insulin-Like Growth Factor II -- metabolism KW - Carrier Proteins -- isolation & purification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75721283?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Binding+of+mutants+of+human+insulin-like+growth+factor+II+to+insulin-like+growth+factor+binding+proteins+1-6.&rft.au=Bach%2C+L+A%3BHsieh%2C+S%3BSakano%2C+K%3BFujiwara%2C+H%3BPerdue%2C+J+F%3BRechler%2C+M+M&rft.aulast=Bach&rft.aufirst=L&rft.date=1993-05-05&rft.volume=268&rft.issue=13&rft.spage=9246&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 - 1993-06-04 N1 - Date created - 1993-06-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A controlled trial of HA-1A in a canine model of gram-negative septic shock. AN - 75671326; 8474201 AB - To investigate the therapeutic efficacy and microbiological and physiological effects of a human IgM monoclonal antibody (HA-1A) directed against the lipid A component of endotoxin in a canine model of sepsis that simulates the cardiovascular abnormalities of human septic shock. Blinded, placebo-controlled 28-day trial. Purpose-bred beagles were implanted with an intraperitoneal clot infected with Escherichia coli O111:B4. At clot placement, animals received HA-1A (10 mg.kg-1), control human IgM antibody (10 mg.kg-1), or control human serum albumin intravenously. All animals were given antibiotic and fluid therapy. Survival and microbiological and physiological events. Only two (15%) of 13 animals in the HA-1A group, compared with eight (57%) of 14 control animals (combined control human IgM antibody and control human serum albumin groups) (P = .05), survived 28 days. At 24 hours, the HA-1A group had lower mean arterial pressure (P = .04) and cardiac index (P = .004) and higher lactate levels (P = .05) compared with the combined-controls group. In addition, these parameters in the HA-1A group were significantly more predictive of death. The HA-1A and combined-controls groups had similar significant increases in the level of endotoxemia and bacteremia. Studies of toxic effects showed no harmful effects of control human IgM antibody in infected animals or HA-1A in non-infected animals. In a canine model of E coli sepsis, HA-1A did not alter levels of bacteremia or endotoxemia and actually decreased survival. If these data are relevant to human septic shock, HA-1A therapy should be limited until the conditions under which this monoclonal antibody has beneficial or deleterious effects are more completely defined. JF - JAMA AU - Quezado, Z M AU - Natanson, C AU - Alling, D W AU - Banks, S M AU - Koev, C A AU - Elin, R J AU - Hosseini, J M AU - Bacher, J D AU - Danner, R L AU - Hoffman, W D AD - Department of Critical Care Medicine, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/05/05/ PY - 1993 DA - 1993 May 05 SP - 2221 EP - 2227 VL - 269 IS - 17 SN - 0098-7484, 0098-7484 KW - Antibodies, Monoclonal KW - 0 KW - Endotoxins KW - Immunoglobulin M KW - Serum Albumin KW - nebacumab KW - 138330-99-1 KW - Abridged Index Medicus KW - Index Medicus KW - Serum Albumin -- pharmacology KW - Immunoglobulin M -- pharmacology KW - Animals KW - Humans KW - Escherichia coli Infections -- drug therapy KW - Dogs KW - Disease Models, Animal KW - Male KW - Female KW - Survival Analysis KW - Gram-Negative Bacterial Infections -- mortality KW - Shock, Septic -- immunology KW - Shock, Septic -- drug therapy KW - Gram-Negative Bacterial Infections -- immunology KW - Gram-Negative Bacterial Infections -- drug therapy KW - Endotoxins -- immunology KW - Antibodies, Monoclonal -- pharmacology KW - Shock, Septic -- mortality KW - Antibodies, Monoclonal -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75671326?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=JAMA&rft.atitle=A+controlled+trial+of+HA-1A+in+a+canine+model+of+gram-negative+septic+shock.&rft.au=Quezado%2C+Z+M%3BNatanson%2C+C%3BAlling%2C+D+W%3BBanks%2C+S+M%3BKoev%2C+C+A%3BElin%2C+R+J%3BHosseini%2C+J+M%3BBacher%2C+J+D%3BDanner%2C+R+L%3BHoffman%2C+W+D&rft.aulast=Quezado&rft.aufirst=Z&rft.date=1993-05-05&rft.volume=269&rft.issue=17&rft.spage=2221&rft.isbn=&rft.btitle=&rft.title=JAMA&rft.issn=00987484&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-05-20 N1 - Date created - 1993-05-20 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: JAMA. 1993 May 5;269(17):2266-7 [8474207] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cognitive and behavioral profile of the oculocerebrorenal syndrome of Lowe. AN - 85274336; pmid-8488875 AB - BACKGROUND: The oculocerebrorenal syndrome of Lowe (OCRL) is an X-linked disorder characterized by congenital cataracts, cognitive impairment, and renal tubular dysfunction. Significant behavioral difficulties have been reported, but no formal study of intelligence or behavior has been described. METHODS: We surveyed IQ and behavior using archival data and standardized instruments in 47 affected males. RESULTS: Mean IQ was in the moderate mental retardation range (40 or = 70). The OCRL population was comparable to a normative population with mental retardation in language, communication, and socialization skills, but lower in independent living skills than means of either populations of individuals with mental retardation or visual impairment. Maladaptive behaviors, particularly stubbornness, temper tantrums, and stereotypic behaviors, were very frequent (> 80%). CONCLUSIONS: The diagnosis of OCRL is compatible with normal intelligence. Maladaptive behaviors significantly interfere with adaptive functions. These behaviors appear to define a characteristic behavioral phenotype in OCRL. JF - American Journal of Medical Genetics AU - Kenworthy, L AU - Park, T AU - Charnas, L R AD - Human Genetics Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892. PY - 1993 SP - 297 EP - 303 VL - 46 IS - 3 SN - 0148-7299, 0148-7299 KW - Mental Retardation KW - Intelligence KW - Support, U.S. Gov't, P.H.S. KW - Human KW - Adult KW - Stereotyped Behavior KW - Oculocerebrorenal Syndrome KW - Child KW - Aggression KW - Adolescent KW - Male KW - Rage KW - Mental Disorders UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85274336?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Journal+of+Medical+Genetics&rft.atitle=Cognitive+and+behavioral+profile+of+the+oculocerebrorenal+syndrome+of+Lowe.&rft.au=Kenworthy%2C+L%3BPark%2C+T%3BCharnas%2C+L+R&rft.aulast=Kenworthy&rft.aufirst=L&rft.date=1993-05-01&rft.volume=46&rft.issue=3&rft.spage=297&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Medical+Genetics&rft.issn=01487299&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Expression of AMPA-selective glutamate receptor subunits in morphologically defined neurons of the mammalian cochlear nucleus. AN - 85241299; pmid-7683046 AB - Glutamate and related amino acids mediate fast excitatory neurotransmission in the vertebrate CNS via ligand-gated cationic channels in the neuronal membrane. These channels are composed of different subunits that assemble into a functional receptor/channel complex. Although studies have shown that these subunits are differentially expressed in neurons, few studies have quantitatively addressed the cell-specific expression of glutamate subunits in relation to known glutamatergic pathways. In the vertebrate auditory system, glutamate is the proposed neurotransmitter of the auditory nerve and parallel fiber pathways. In situ hybridization histochemistry was used to localize AMPA-selective glutamate receptor subunit mRNAs in seven cell types of the rat cochlear nucleus. GluR1-GluR4 AMPA-selective subunits were all expressed in cochlear nucleus neurons; however, the subunits expressed in identified cells varied with the cell type. Granule cells, previously not known to receive glutamatergic input, expressed GluR2 and GluR4 subunits. Cartwheel and stellate interneurons in the dorsal cochlear nucleus, which receive parallel fiber input, expressed all four subunits. Neurons receiving synaptic input from the auditory nerve, including globular, round, spherical, and fusiform cells, expressed GluR2, GluR3, and GluR4 subunits. Furthermore, a subpopulation of round cells in the ventral cochlear nucleus, and fusiform cells in the dorsal cochlear nucleus, expressed the GluR3 subunit at greatly reduced levels compared to neighboring cells. The results confirm the auditory nerve and parallel fiber pathways as glutamatergic and identify a third synaptic population, projecting to granule cells, which is likely glutamatergic. The data suggest that the composition of GluR1-GluR4 subunits on neurons in the cochlear nucleus may be related to presynaptic input; moreover, heterogeneous patterns of expression of the GluR3 subunit, in addition, suggest that variability in mRNA levels within one population of morphologically defined cells is present. JF - The Journal of Neuroscience AU - Hunter, C AU - Petralia, R S AU - Vu T AU - Wenthold, R J AD - Section on Neurotransmitter Receptor Biology, NIDCD, National Institutes of Health, Bethesda, Maryland 20892. PY - 1993 SP - 1932 EP - 1946 VL - 13 IS - 5 SN - 0270-6474, 0270-6474 KW - Rats KW - RNA, Messenger KW - Granulocytes KW - In Situ Hybridization KW - Auditory Pathways KW - Neurons KW - alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid KW - Receptors, Glutamate KW - Animal KW - Cochlear Nerve KW - Ibotenic Acid KW - Tissue Distribution KW - Silver UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85241299?accountid=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=Expression+of+AMPA-selective+glutamate+receptor+subunits+in+morphologically+defined+neurons+of+the+mammalian+cochlear+nucleus.&rft.au=Hunter%2C+C%3BPetralia%2C+R+S%3BVu+T%3BWenthold%2C+R+J&rft.aulast=Hunter&rft.aufirst=C&rft.date=1993-05-01&rft.volume=13&rft.issue=5&rft.spage=1932&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 - Cerebrospinal fluid pharmacokinetics and toxicology of intraventricular and intrathecal arabinosyl-5-azacytosine (fazarabine, NSC 281272) in the nonhuman primate. AN - 76144203; 7505267 AB - Arabinosyl-5-azacytosine (AAC), a new nucleoside antimetabolite, is broadly active in preclinical tumor screening evaluations. To assess the potential for intrathecal use of this drug, we studied the toxicity and pharmacokinetics of intrathecal and intraventricular administration in nonhuman primates. Four adult male rhesus monkeys were given single 10 mg intrathecal (n = 1) or intraventricular (n = 3) doses of AAC to determine its acute toxicity and pharmacokinetic parameters. An additional 3 animals were given four weekly 10 mg intrathecal doses to assess the systemic and neurologic toxicity associated with chronic administration. Disappearance from the cerebrospinal fluid (CSF) was biexponential, and CSF clearance was 0.2 ml/min, which exceeds the rate of CSF bulk flow by 5-fold. The peak CSF concentration and area under the concentration x time curve achieved with the intraventricular administration of 10 mg were one hundred, and fifty fold greater, respectively, than those achieved after an intravenous dose of 200 mg/kg (1500-2400 mg) in prior experiments. No clinically evident neurotoxicity was observed in either the single or the weekly x 4 dose groups. A slight, transient CSF pleocytosis and increased CSF protein was observed. Systemic toxicity was limited to one animal in the weekly x 4 dose group who demonstrated a mild and transient decrease in his peripheral leukocyte count unassociated with a change in his hematocrit or platelet count. These studies in nonhuman primates demonstrate a clear pharmacokinetic advantage for intrathecal vs systemic administration of AAC. This is demonstrated by a 50-fold greater CSF drug exposure with an intrathecal or intraventricular dose 1/200th of that which can be given systemically.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Investigational new drugs AU - Heideman, R L AU - McCully, C AU - Balis, F M AU - Poplack, D G AD - Pediatric Branch, National Cancer Institute, Bethesda, Maryland 20892. PY - 1993 SP - 135 EP - 140 VL - 11 IS - 2-3 SN - 0167-6997, 0167-6997 KW - Antineoplastic Agents KW - 0 KW - fazarabine KW - 5V71D8JOKK KW - Azacitidine KW - M801H13NRU KW - Index Medicus KW - Animals KW - Injections, Spinal KW - Macaca mulatta KW - Male KW - Injections, Intraventricular KW - Azacitidine -- pharmacokinetics KW - Antineoplastic Agents -- cerebrospinal fluid KW - Azacitidine -- cerebrospinal fluid KW - Azacitidine -- toxicity KW - Antineoplastic Agents -- pharmacokinetics KW - Antineoplastic Agents -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76144203?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Investigational+new+drugs&rft.atitle=Cerebrospinal+fluid+pharmacokinetics+and+toxicology+of+intraventricular+and+intrathecal+arabinosyl-5-azacytosine+%28fazarabine%2C+NSC+281272%29+in+the+nonhuman+primate.&rft.au=Heideman%2C+R+L%3BMcCully%2C+C%3BBalis%2C+F+M%3BPoplack%2C+D+G&rft.aulast=Heideman&rft.aufirst=R&rft.date=1993-05-01&rft.volume=11&rft.issue=2-3&rft.spage=135&rft.isbn=&rft.btitle=&rft.title=Investigational+new+drugs&rft.issn=01676997&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-01-24 N1 - Date created - 1994-01-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Multiple effects of spermine on N-methyl-D-aspartic acid receptor responses of rat cultured hippocampal neurones. AN - 76046679; 8229795 AB - 1. The modulation by polyamines of responses to N-methyl-D-aspartic acid (NMDA) was studied using a rapid perfusion system and whole-cell voltage-clamp recording from rat hippocampal neurons in dissociated culture. 2. Concentration jump responses to 100 microM NMDA in the presence of 10 microM glycine revealed potentiation by 3 mM spermine at a membrane potential of +60 mV, but depression at -120 mV; the degree of potentiation at +60 mV was variable from cell to cell while marked depression at -120 mV was observed in all cells. The depression of responses to NMDA by spermine was highly voltage dependent (z delta = 1.17) with an apparent equilibrium dissociation constant for block at 0 mV of 27 mM. 3. Analysis of spermine dose-potentiation curves for responses recorded at +60 mV in the presence of 10 microM glycine revealed a half-maximal effect at 125 microM. Under the same conditions, but at -60 mV, analysis of spermine-evoked depression was performed for cells with less than 5% potentiation at +60 mV, and revealed half-maximal inhibition at 344 microM. 4. Dose-response analysis for the glycine-sensitive activation of NMDA receptors at +60 mV revealed a 3.5-fold increase in apparent affinity for glycine in the presence of 1 mM spermine. This increase in affinity for glycine was accompanied by a 3.3-fold decrease in the rate of development of glycine-sensitive desensitization, and a 2.4-fold decrease in the rate of dissociation of glycine from NMDA receptors, while the rate constant for dissociation of NMDA was not reduced. 5. In the presence of non-saturating concentrations of glycine, spermine-induced potentiation at +60 mV developed with two exponential components: a slow glycine-sensitive component, the amplitude and time constant of which decreased with increasing glycine concentration (30 nM glycine, amplitude = 80.2 +/- 5.1%, tau = 780 +/- 79 ms; 3 microM glycine, amplitude = 22.6 +/- 7.1%, tau = 45 +/- 13 ms), and a faster component (tau < 20 ms at all concentrations of glycine), the amplitude of which varied from cell to cell, and which became larger with increase in concentration of glycine. When responses to the application of spermine were measured in the presence 10 microM L-alanine instead of 100 nM glycine, the slow component of potentiation was absent.(ABSTRACT TRUNCATED AT 400 WORDS) JF - The Journal of physiology AU - Benveniste, M AU - Mayer, M L AD - Laboratory of Cellular and Molecular Neurophysiology, NICHD, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/05// PY - 1993 DA - May 1993 SP - 131 EP - 163 VL - 464 SN - 0022-3751, 0022-3751 KW - Receptors, N-Methyl-D-Aspartate KW - 0 KW - Spermine KW - 2FZ7Y3VOQX KW - N-Methylaspartate KW - 6384-92-5 KW - Glycine KW - TE7660XO1C KW - Index Medicus KW - Rats KW - Animals KW - N-Methylaspartate -- pharmacology KW - Glycine -- pharmacology KW - Dose-Response Relationship, Drug KW - Cells, Cultured KW - Kinetics KW - Glycine -- metabolism KW - N-Methylaspartate -- antagonists & inhibitors KW - Membrane Potentials KW - Drug Synergism KW - Neurons -- metabolism KW - Spermine -- pharmacology KW - Receptors, N-Methyl-D-Aspartate -- drug effects KW - Hippocampus -- metabolism KW - Hippocampus -- cytology KW - Neurons -- physiology KW - Receptors, N-Methyl-D-Aspartate -- metabolism KW - Hippocampus -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76046679?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+physiology&rft.atitle=Multiple+effects+of+spermine+on+N-methyl-D-aspartic+acid+receptor+responses+of+rat+cultured+hippocampal+neurones.&rft.au=Benveniste%2C+M%3BMayer%2C+M+L&rft.aulast=Benveniste&rft.aufirst=M&rft.date=1993-05-01&rft.volume=464&rft.issue=&rft.spage=131&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+physiology&rft.issn=00223751&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-11-26 N1 - Date created - 1993-11-26 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Neuron. 1992 Feb;8(2):343-52 [1531415] Science. 1992 Jan 24;255(5043):470-2 [1346477] Mol Pharmacol. 1992 Apr;41(4):727-35 [1373801] Science. 1992 May 22;256(5060):1217-21 [1350383] Proc Natl Acad Sci U S A. 1992 Oct 1;89(19):9359-63 [1409641] J Physiol. 1992 May;450:643-72 [1359126] J Physiol. 1990 Sep;428:313-31 [2172523] J Gen Physiol. 1973 Jun;61(6):687-708 [4541078] Pflugers Arch. 1981 Aug;391(2):85-100 [6270629] J Physiol. 1983 Jun;339:663-78 [6310093] Nature. 1984 Feb 2-8;307(5950):462-5 [6320006] Nature. 1984 May 17-23;309(5965):261-3 [6325946] Biophys J. 1986 Mar;49(3):607-18 [2421791] J Physiol. 1987 Dec;394:501-27 [2451020] J Physiol. 1988 May;399:247-66 [2457089] Science. 1988 Aug 12;241(4867):835-7 [2841759] J Neurochem. 1988 Sep;51(3):830-6 [2457653] J Physiol. 1988 Jan;395:131-59 [2457675] Neurosci Lett. 1988 Jul 8;89(3):313-8 [2458553] Nature. 1989 Mar 30;338(6214):425-7 [2538755] Science. 1989 Mar 24;243(4898):1611-3 [2467381] Mol Pharmacol. 1989 Oct;36(4):575-81 [2554112] Mol Pharmacol. 1989 Nov;36(5):758-65 [2555674] Mol Pharmacol. 1989 Dec;36(6):836-9 [2557533] J Neurosci. 1990 Jan;10(1):1-10 [1688928] Neuron. 1990 May;4(5):725-31 [2160836] J Physiol. 1990 Mar;422:203-25 [1972190] J Neurophysiol. 1990 Jun;63(6):1373-84 [1972740] Synapse. 1990;5(4):294-8 [1972818] Eur J Pharmacol. 1990 Apr 25;179(3):477-8 [1694770] J Physiol. 1989 Aug;415:329-50 [2561788] Nature. 1990 Aug 9;346(6284):565-7 [1974037] Neuron. 1990 Aug;5(2):199-208 [2166545] Trends Pharmacol Sci. 1990 Jul;11(7):290-6 [2167544] J Physiol. 1990 Sep;428:333-57 [2146385] Mol Pharmacol. 1990 Oct;38(4):554-61 [2172769] J Pharmacol Exp Ther. 1990 Dec;255(3):1001-7 [2148185] Proc Natl Acad Sci U S A. 1990 Dec;87(24):9971-4 [1702227] Life Sci. 1991;48(6):469-98 [1825128] Neurosci Lett. 1990 Nov 27;120(1):17-20 [2149877] Biophys J. 1991 Mar;59(3):560-73 [1710938] J Neurochem. 1991 Sep;57(3):811-8 [1830614] Neuron. 1991 Oct;7(4):605-13 [1681832] Mol Pharmacol. 1992 Jan;41(1):83-8 [1370709] J Neurosci. 1992 Feb;12(2):635-43 [1346806] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Studies of binding and internalization of human recombinant monocyte chemotactic and activating factor (MCAF) by monocytic cells. AN - 76036060; 8218939 AB - Recombinant human monocyte chemotactic and activating factor (MCAF) was iodinated and specific binding sites for this cytokine were detected on human peripheral blood monocytes, the monocytic leukemia cell line THP-1, and on PMA-differentiated HL60 and U937 cell lines. The binding sites were specific for MCAF since other polypeptide cytokines and the chemotactic peptide formyl-methionyl-leucyl-phenylalanine (fMLP) failed to compete for 125I-rhMCAF binding. Steady-state binding experiments at 4 degrees C revealed the presence of 13,000 and 18,000 receptor sites/cell on monocytes and THP-1 cells with Kd values of 22.5 nM and 25.7 nM, respectively. Compared to a human natural MCAF, rhMCAF was less potent in inducing maximal monocyte migration. Human natural MCAF similarly competed more efficiently for 125I-rhMCAF binding than unlabelled rhMCAF. The ligand-receptor association was highly temperature-dependent, with maximal ligand uptake at 37 degrees C accompanied by internalization of the ligand-receptor complexes. The internalized 125I-MCAF was progressively degraded and released into the culture medium starting at 30 min. Lysosomotropic ammonium chloride could inhibit the degradation of this ligand suggesting the involvement of lysosomal enzymes in the proteolytic digestion. Incubation with cycloheximide did not block the rapid reappearance of MCAF receptors within 20 min on the cell surface indicative of receptor recycling rather than new protein synthesis. These data indicate that monocytic cells express specific receptors for rhMCAF which can be dynamically regulated by MCAF. JF - Cytokine AU - Wang, J M AU - Hishinuma, A AU - Oppenheim, J J AU - Matsushima, K AD - Laboratory of Molecular Immunoregulation, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland 21702. Y1 - 1993/05// PY - 1993 DA - May 1993 SP - 264 EP - 275 VL - 5 IS - 3 SN - 1043-4666, 1043-4666 KW - Chemokine CCL2 KW - 0 KW - Chemotactic Factors KW - Cytokines KW - Receptors, CCR2 KW - Receptors, Chemokine KW - Receptors, Cytokine KW - Recombinant Proteins KW - Cycloheximide KW - 98600C0908 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Leukemia, Monocytic, Acute KW - Tumor Cells, Cultured KW - Recombinant Proteins -- metabolism KW - Kinetics KW - Humans KW - Cycloheximide -- pharmacology KW - In Vitro Techniques KW - Biological Transport KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Cell Line KW - Neutrophils -- metabolism KW - Receptors, Cytokine -- biosynthesis KW - Monocytes -- metabolism KW - Cytokines -- metabolism KW - Chemotactic Factors -- metabolism KW - Receptors, Cytokine -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76036060?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cytokine&rft.atitle=Studies+of+binding+and+internalization+of+human+recombinant+monocyte+chemotactic+and+activating+factor+%28MCAF%29+by+monocytic+cells.&rft.au=Wang%2C+J+M%3BHishinuma%2C+A%3BOppenheim%2C+J+J%3BMatsushima%2C+K&rft.aulast=Wang&rft.aufirst=J&rft.date=1993-05-01&rft.volume=5&rft.issue=3&rft.spage=264&rft.isbn=&rft.btitle=&rft.title=Cytokine&rft.issn=10434666&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-12-15 N1 - Date created - 1993-12-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Liver carcinogenesis is not a predicted outcome of chemically induced hepatocyte proliferation. AN - 75944606; 8367884 AB - Cell proliferation has long been recognized as a basic component of multistage carcinogenesis. Based largely on the finding that certain nongenotoxic chemical carcinogens induce cell proliferation in the same organ that develops tumors after long-term exposure, some suggest that the increased rates of cell division account for the carcinogenicity of these chemicals. This paper examines relationships between chemically induced liver toxicity, cell proliferation, and liver carcinogenesis; major factors include consistency, transient vs. sustained dose-response correspondence, and scientific plausibility. For a presumed mechanism to be valid, a sustained proliferative response is critical, largely because transient increases in hepatocyte proliferation are not sufficient to induce cancer or promote liver tumor development. A consistent association between liver toxicity and carcinogenicity has not been established. Our evaluation of studies on purported relationships between chemically induced cell proliferation and liver carcinogenesis shows: 1) that inconsistencies in sex and species specificity exist, 2) that a large percentage of proliferative responses are transient, 3) that inconsistencies in response to various hepatic peroxisome proliferators are common, and 4) that dose-response and duration relationships have not been sufficiently examined. Studies of proliferative responses of putative preneoplastic cells in the liver indicate that these cells divide faster than normal hepatocytes and also have higher death rates. Chemicals that induce cell proliferation in preneoplastic foci do not always provide a persistent increase in replication rates, even with continuous exposure. A selective growth advantage to preneoplastic cells in the liver may be provided either by an enhancement of the replication rates of these cells compared to the surrounding normal hepatocytes, by inhibition of cell loss, or by inhibition of the growth rate of normal cells. More work is needed to understand how chemical carcinogens and noncarcinogens affect cell division and cell loss of normal hepatocytes and of preneoplastic cells; measurements of hepatocyte proliferation alone are not sufficient to elucidate mechanisms of liver tumor development or to predict liver carcinogenesis. Because of our limited knowledge of the complex molecular changes occurring during liver cancer, it would be inappropriate and far too premature to amend scientific risk assessment procedures for nongenotoxic chemical carcinogens based on oversimplified or incompletely tested speculations. JF - Toxicology and industrial health AU - Melnick, R L AU - Huff, J AD - National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709. PY - 1993 SP - 415 EP - 438 VL - 9 IS - 3 SN - 0748-2337, 0748-2337 KW - Carcinogens KW - 0 KW - Hydrocarbons, Halogenated KW - Index Medicus KW - Rats KW - Animals KW - Hydrocarbons, Halogenated -- toxicity KW - Cell Transformation, Neoplastic -- pathology KW - Dose-Response Relationship, Drug KW - Chemical and Drug Induced Liver Injury KW - Cell Transformation, Neoplastic -- chemically induced KW - Cell Division -- drug effects KW - Carcinogenicity Tests KW - Mice KW - Male KW - Female KW - Liver -- drug effects KW - Liver Diseases -- pathology KW - Liver Neoplasms -- chemically induced KW - Carcinogens -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75944606?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+industrial+health&rft.atitle=Liver+carcinogenesis+is+not+a+predicted+outcome+of+chemically+induced+hepatocyte+proliferation.&rft.au=Melnick%2C+R+L%3BHuff%2C+J&rft.aulast=Melnick&rft.aufirst=R&rft.date=1993-05-01&rft.volume=9&rft.issue=3&rft.spage=415&rft.isbn=&rft.btitle=&rft.title=Toxicology+and+industrial+health&rft.issn=07482337&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-10-01 N1 - Date created - 1993-10-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Oxidative DNA damage by crystalline silica. AN - 75881151; 8394268 AB - Using a simple DNA strand breakage assay, we detected the production of oxidant species, probably hydroxyl free radicals, in buffered suspensions of crystalline silica at pH 7.4. DNA damage was affected by the presence of oxygen and was accelerated by superoxide dismutase and by hydrogen peroxide. Deferoxamine blocked damage by hydrogen peroxide and silica but accelerated DNA damage by silica alone and by superoxide dismutase and silica. DNA damage was blocked by catalase and by the scavenging agents dimethyl sulfoxide and sodium benzoate. Chemical etching of crystalline silica to remove impurities by treatment of the surface with hydrofluoric acid resulted in markedly diminished DNA damaging ability. Even preparations of crystalline silica previously characterized as highly pure contained trace iron impurities in amounts significant enough to produce oxygen free radicals in aqueous suspension. Both superoxide and Fenton reaction oxidants were produced. We conclude that silica is able to mediate DNA strand breakage in vitro and that this DNA damage may be an important factor in silica toxicity. JF - Free radical biology & medicine AU - Daniel, L N AU - Mao, Y AU - Saffiotti, U AD - Laboratory of Experimental Pathology, National Cancer Institute, Bethesda, MD 20892-0041. Y1 - 1993/05// PY - 1993 DA - May 1993 SP - 463 EP - 472 VL - 14 IS - 5 SN - 0891-5849, 0891-5849 KW - Silicon Dioxide KW - 7631-86-9 KW - Hydrogen Peroxide KW - BBX060AN9V KW - Catalase KW - EC 1.11.1.6 KW - Superoxide Dismutase KW - EC 1.15.1.1 KW - Deoxyribonuclease HindIII KW - EC 3.1.21.- KW - Deferoxamine KW - J06Y7MXW4D KW - Oxygen KW - S88TT14065 KW - Index Medicus KW - Oxidation-Reduction KW - Crystallization KW - Oxygen Consumption -- drug effects KW - Superoxide Dismutase -- pharmacology KW - Deferoxamine -- pharmacology KW - Oxygen -- pharmacology KW - Hydrogen Peroxide -- pharmacology KW - Catalase -- pharmacology KW - Silicon Dioxide -- pharmacology KW - DNA Damage -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75881151?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Free+radical+biology+%26+medicine&rft.atitle=Oxidative+DNA+damage+by+crystalline+silica.&rft.au=Daniel%2C+L+N%3BMao%2C+Y%3BSaffiotti%2C+U&rft.aulast=Daniel&rft.aufirst=L&rft.date=1993-05-01&rft.volume=14&rft.issue=5&rft.spage=463&rft.isbn=&rft.btitle=&rft.title=Free+radical+biology+%26+medicine&rft.issn=08915849&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-09-10 N1 - Date created - 1993-09-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Palpebral amelanotic melanomas in F344 rats. AN - 75854128; 8333109 AB - Spontaneous amelanotic melanomas in the eyelids of F344 rats were found in one of 1/926 (0.11%) male and 5/925 (0.54%) female F344 rats that were used as control and treated animals in five different carcinogenicity studies conducted by the National Toxicology Program (Research Triangle Park, NC). These melanomas were grossly recognized as single, tan or white, well-circumscribed masses of the right or left eyelid. These melanomas primarily occurred in the dermis of the skin of the eyelids and consisted of poorly differentiated spindle cells characteristically arranged in interlacing fascicles. Rarely, epithelioid tumor cells were also observed, and these tumor cells showed a negative histochemical reaction for melanin. The epidermis and dermal-epidermal junction were usually uninvolved. The diagnosis of amelanotic melanoma could only be established by electron microscopic examination. The most striking ultrastructural feature of the tumor cells was a large number of intracytoplasmic premelanosomes (stage II melanosomes without melanin), which nearly filled the cytoplasm of most tumor cells. Giant premelanosomes and melanophagosomes were also seen. The tumor cells did not possess the ultrastructural features characteristics of Schwann cells (thin, long cell processes and pericytoplasmic basal laminae). The histologic and ultrastructural features of these palpebral tumors were similar to those of cutaneous amelanotic melanomas of the pinna in F344 rats. JF - Veterinary pathology AU - Yoshitomi, K AU - Boorman, G A AD - Experimental Pathology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC. Y1 - 1993/05// PY - 1993 DA - May 1993 SP - 280 EP - 286 VL - 30 IS - 3 SN - 0300-9858, 0300-9858 KW - Index Medicus KW - Rats KW - Animals KW - Carcinogenicity Tests KW - Microscopy, Electron KW - Male KW - Female KW - Rats, Inbred F344 KW - Eyelid Neoplasms -- pathology KW - Melanoma -- pathology KW - Melanoma -- chemically induced KW - Eyelid Neoplasms -- chemically induced KW - Melanocytes -- ultrastructure KW - Rodent Diseases -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75854128?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Veterinary+pathology&rft.atitle=Palpebral+amelanotic+melanomas+in+F344+rats.&rft.au=Yoshitomi%2C+K%3BBoorman%2C+G+A&rft.aulast=Yoshitomi&rft.aufirst=K&rft.date=1993-05-01&rft.volume=30&rft.issue=3&rft.spage=280&rft.isbn=&rft.btitle=&rft.title=Veterinary+pathology&rft.issn=03009858&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-08-16 N1 - Date created - 1993-08-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Proconvulsant action of diethyldithiocarbamate in stimulation of the perforant path. AN - 75851788; 8393131 AB - The ability of diethyldithiocarbamate (DEDTC) to prolong electrical afterdischarge (AD) and lower the threshold for behavioral seizures elicited by stimulation of the perforant path (PPS) was examined. DEDTC was given in doses of 25, 50, and 100 mg/kg, IP. The effects of DEDTC on the threshold for wet dog shakes (WDS) and the number of WDS elicited by PPS were inconsistent. It had no effect on the duration of AD accompanied with WDS. However, DEDTC, at both 50 and 100 mg/kg, significantly lowered the threshold for rearing accompanied with forelimb clonus. At 100 mg/kg, it also prolonged the duration of AD occurring with these seizures. The effects of DEDTC were transitory and coincided with the time course for its ability to chelate the mossy fiber intravesicular pool of zinc (i.e., that which is released by activation of dentate granule cells). It is suggested that release of zinc from the mossy fibers may serve to protect the hippocampus from paroxysmal seizure activity. JF - Neurotoxicology and teratology AU - Mitchell, C L AU - Barnes, M I AD - Laboratory of Molecular and Integrative Neuroscience, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. PY - 1993 SP - 165 EP - 171 VL - 15 IS - 3 SN - 0892-0362, 0892-0362 KW - Chelating Agents KW - 0 KW - Convulsants KW - Ditiocarb KW - 99Z2744345 KW - Zinc KW - J41CSQ7QDS KW - Index Medicus KW - Seizures -- chemically induced KW - Animals KW - Dose-Response Relationship, Drug KW - Neural Pathways -- physiology KW - Zinc -- blood KW - Seizures -- prevention & control KW - Histocytochemistry KW - Neural Pathways -- drug effects KW - Hippocampus -- drug effects KW - Rats KW - Chelating Agents -- pharmacology KW - Rats, Inbred F344 KW - Zinc -- physiology KW - Male KW - Hippocampus -- anatomy & histology KW - Ditiocarb -- toxicity KW - Behavior, Animal -- drug effects KW - Convulsants -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75851788?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurotoxicology+and+teratology&rft.atitle=Proconvulsant+action+of+diethyldithiocarbamate+in+stimulation+of+the+perforant+path.&rft.au=Mitchell%2C+C+L%3BBarnes%2C+M+I&rft.aulast=Mitchell&rft.aufirst=C&rft.date=1993-05-01&rft.volume=15&rft.issue=3&rft.spage=165&rft.isbn=&rft.btitle=&rft.title=Neurotoxicology+and+teratology&rft.issn=08920362&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-08-23 N1 - Date created - 1993-08-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Trends in cirrhosis morbidity and mortality: United States, 1979-1988. AN - 75848700; 8337600 JF - Seminars in liver disease AU - Dufour, M C AU - Stinson, F S AU - Caces, M F AD - Division of Biometry and Epidemiology, National Institute on Alcohol Abuse and Alcoholism, Rockville, Maryland 20857. Y1 - 1993/05// PY - 1993 DA - May 1993 SP - 109 EP - 125 VL - 13 IS - 2 SN - 0272-8087, 0272-8087 KW - Index Medicus KW - Humans KW - Death Certificates KW - Adult KW - Incidence KW - Aged KW - Middle Aged KW - Hospitalization -- statistics & numerical data KW - Adolescent KW - United States -- epidemiology KW - Morbidity KW - Male KW - Female KW - Prevalence KW - Liver Cirrhosis -- epidemiology KW - Liver Cirrhosis, Alcoholic -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75848700?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+liver+disease&rft.atitle=Trends+in+cirrhosis+morbidity+and+mortality%3A+United+States%2C+1979-1988.&rft.au=Dufour%2C+M+C%3BStinson%2C+F+S%3BCaces%2C+M+F&rft.aulast=Dufour&rft.aufirst=M&rft.date=1993-05-01&rft.volume=13&rft.issue=2&rft.spage=109&rft.isbn=&rft.btitle=&rft.title=Seminars+in+liver+disease&rft.issn=02728087&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-08-26 N1 - Date created - 1993-08-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chronic inhibition of monoamine oxidase type A increases noradrenaline release in rat frontal cortex. AN - 75833094; 8391652 AB - Chronic but not acute treatment of rats with MAO inhibitors, as with other antidepressant drugs, has been shown to down-regulate the number of cerebro-cortical beta-adrenoceptors. In order to establish whether this effect is associated with an increase in cortical noradrenaline release, rats were treated for 1, 3 or 21 days with clorgyline (2 mg/kg i.p. single injection; 1 mg/kg i.p. repeated injections), and the frontal cortex was then perfused by microdialysis in the awake animal. Control animals were injected with saline. The concentration of noradrenaline in the microdialysate increased only slightly after 1 or 3 days of clorgyline treatment but increased fourfold over control levels after 21 days treatment. Yohimbine (20 mumol/l) added to the perfusing solution caused a similar degree of enhancement in microdialysate noradrenaline concentration in all groups of rats. Tetrodotoxin (10 mumol/l) reduced noradrenaline concentration to low levels in all groups of animals, but noradrenaline was still detectable in the microdialysate in rats treated with clorgyline for 21 days. Concentrations of the deaminated metabolites dihydroxyphenylacetic acid, dihydroxyphenylglycol and methoxy-hydroxyphenylglycol were lowest after the 21 day clorgyline treatment. Determination of enzyme activity ex vivo showed that MAO-A was inhibited more than 95% by all clorgyline treatments with less than 10% inhibition of MAO-B. The results indicate that cerebrocortical noradrenaline release increases gradually during chronic MAO inhibition. This may be the result of more complete inhibition of the enzyme with time, not detectable by the ex vivo assay, but shown by the progressive reduction in metabolite levels.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Naunyn-Schmiedeberg's archives of pharmacology AU - Finberg, J P AU - Pacak, K AU - Kopin, I J AU - Goldstein, D S AD - Clinical Neurochemistry Section, N.I.N.D.S., N.I.H., Bethesda, MD 20892. Y1 - 1993/05// PY - 1993 DA - May 1993 SP - 500 EP - 505 VL - 347 IS - 5 SN - 0028-1298, 0028-1298 KW - Monoamine Oxidase Inhibitors KW - 0 KW - Receptors, Adrenergic, alpha KW - Yohimbine KW - 2Y49VWD90Q KW - Tetrodotoxin KW - 4368-28-9 KW - Monoamine Oxidase KW - EC 1.4.3.4 KW - Clorgyline KW - LYJ16FZU9Q KW - Norepinephrine KW - X4W3ENH1CV KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Dialysis KW - Clorgyline -- administration & dosage KW - Yohimbine -- pharmacology KW - Receptors, Adrenergic, alpha -- metabolism KW - Tetrodotoxin -- pharmacology KW - Monoamine Oxidase -- metabolism KW - Male KW - Frontal Lobe -- drug effects KW - Norepinephrine -- metabolism KW - Frontal Lobe -- enzymology KW - Monoamine Oxidase Inhibitors -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75833094?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Naunyn-Schmiedeberg%27s+archives+of+pharmacology&rft.atitle=Chronic+inhibition+of+monoamine+oxidase+type+A+increases+noradrenaline+release+in+rat+frontal+cortex.&rft.au=Finberg%2C+J+P%3BPacak%2C+K%3BKopin%2C+I+J%3BGoldstein%2C+D+S&rft.aulast=Finberg&rft.aufirst=J&rft.date=1993-05-01&rft.volume=347&rft.issue=5&rft.spage=500&rft.isbn=&rft.btitle=&rft.title=Naunyn-Schmiedeberg%27s+archives+of+pharmacology&rft.issn=00281298&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-08-05 N1 - Date created - 1993-08-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Psychometric instruments to assist in alcoholism treatment planning. AN - 75809000; 8315703 AB - The clinical practice of alcoholism treatment can be enhanced by the judicious use of standardized psychometric instruments to characterize clients during the course of treatment. Knowledge of key behavioral, personality, and alcohol-specific factors will increase the clinician's ability to select the most appropriate treatment option, or, even if treatment options are limited, at least to develop a treatment plant with the patient's unique needs in mind. Monitoring of progress towards treatment goals can also be facilitated by the use of selected assessment tools. Seven examples of well-validated instruments are discussed, with suggestions on how data derived from them may be applied in the treatment planning process. JF - Journal of substance abuse treatment AU - Allen, J P AU - Mattson, M E AD - National Institute on Alcohol Abuse and Alcoholism, Rockville, Maryland 20857. PY - 1993 SP - 289 EP - 296 VL - 10 IS - 3 SN - 0740-5472, 0740-5472 KW - Index Medicus KW - Motivation KW - Personality Inventory -- statistics & numerical data KW - Combined Modality Therapy KW - Humans KW - Alcohol Drinking -- psychology KW - Psychometrics KW - Alcoholism -- rehabilitation KW - Personality Assessment -- statistics & numerical data KW - Patient Care Planning KW - Alcoholism -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75809000?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+substance+abuse+treatment&rft.atitle=Psychometric+instruments+to+assist+in+alcoholism+treatment+planning.&rft.au=Allen%2C+J+P%3BMattson%2C+M+E&rft.aulast=Allen&rft.aufirst=J&rft.date=1993-05-01&rft.volume=10&rft.issue=3&rft.spage=289&rft.isbn=&rft.btitle=&rft.title=Journal+of+substance+abuse+treatment&rft.issn=07405472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-07-29 N1 - Date created - 1993-07-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Generation of free radicals from model lipid hydroperoxides and H2O2 by Co(II) in the presence of cysteinyl and histidyl chelators. AN - 75806328; 8318649 AB - Electron spin resonance spin trapping was utilized to investigate the generation of free radicals from cumene hydroperoxide (cumene-OOH), tert-butyl hydroperoxide (tert-butyl-OOH), and H2O2 at pH 7.2 by Co(II) in the presence of cysteinyl and histidyl chelating agents. The spin trap used was 5,5-dimethyl-1-pyrroline N-oxide. Incubation of Co(II) with cumene-OOH or tert-butyl-OOH did not generate any detectable amounts of free radicals. However, in the presence of glutathione, cysteine, penicillamine, or N-acetylcysteine, Co(II) generated cumene-OOH-derived carbon-centered radicals, cumene alkoxyl radicals, and hydroxyl (.OH) radicals. Oxidized glutathione and cystine used instead of reduced glutathione or cysteine did not generate any free radical, indicating an important role of the -SH group in radical generation. While the addition of diethylenetriaminepentaacetic acid (DTPA) prevented radical generation, deferoxamine had only a slightly inhibitory effect. Similar results to those obtained using cumene-OOH were obtained utilizing tert-butyl-OOH in place of cumene-OOH. The yields of free radicals were in the order of glutathione > cysteine > penicillamine > N-acetylcysteine. Incubation of Co(II) with cumene-OOH ort-butyl-OOH in the presence of the histidyl oligopeptide Gly-Gly-His also generated lipid hydroperoxide-derived free radicals, with the yield being comparable to that obtained using thiols. In contrast, histidine, anserine, homocarnosine, or carnosine did not cause any free radical generation from Co(II) and lipid hydroperoxides. Incubation of Co(II) with H2)2 produced only a small amount of .OH radicals.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Chemical research in toxicology AU - Shi, X AU - Dalal, N S AU - Kasprzak, K S AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland 21702. PY - 1993 SP - 277 EP - 283 VL - 6 IS - 3 SN - 0893-228X, 0893-228X KW - Butanols KW - 0 KW - Chelating Agents KW - Free Radicals KW - Lipid Peroxides KW - Peptide Fragments KW - homocarnosine KW - 3650-73-5 KW - Cobalt KW - 3G0H8C9362 KW - Histidine KW - 4QD397987E KW - Carnosine KW - 8HO6PVN24W KW - Hydrogen Peroxide KW - BBX060AN9V KW - Glutathione KW - GAN16C9B8O KW - Penicillamine KW - GNN1DV99GX KW - Anserine KW - HDQ4N37UGV KW - Cysteine KW - K848JZ4886 KW - tert-Butyl Alcohol KW - MD83SFE959 KW - Glycine KW - TE7660XO1C KW - Acetylcysteine KW - WYQ7N0BPYC KW - Index Medicus KW - Acetylcysteine -- chemistry KW - Peptide Fragments -- chemistry KW - Carnosine -- analogs & derivatives KW - Glycine -- pharmacology KW - Peptide Fragments -- pharmacology KW - Carnosine -- pharmacology KW - Penicillamine -- chemistry KW - Glutathione -- chemistry KW - Free Radicals -- chemistry KW - Anserine -- pharmacology KW - Free Radicals -- metabolism KW - Butanols -- chemistry KW - Cobalt -- toxicity KW - Cysteine -- pharmacology KW - Chelating Agents -- pharmacology KW - Cobalt -- chemistry KW - Lipid Peroxides -- chemistry KW - Lipid Peroxides -- metabolism KW - Hydrogen Peroxide -- chemistry KW - Histidine -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75806328?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemical+research+in+toxicology&rft.atitle=Generation+of+free+radicals+from+model+lipid+hydroperoxides+and+H2O2+by+Co%28II%29+in+the+presence+of+cysteinyl+and+histidyl+chelators.&rft.au=Shi%2C+X%3BDalal%2C+N+S%3BKasprzak%2C+K+S&rft.aulast=Shi&rft.aufirst=X&rft.date=1993-05-01&rft.volume=6&rft.issue=3&rft.spage=277&rft.isbn=&rft.btitle=&rft.title=Chemical+research+in+toxicology&rft.issn=0893228X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-08-03 N1 - Date created - 1993-08-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Paternal lineage of alcoholism, cohort effects, and alcoholism criteria. AN - 75798496; 8518712 AB - Adoption studies have led to the suggestion that there may be two distinct subgroups of alcoholics with differing genetic contributions. Among 249 male alcoholics we used discriminant analysis to relate the features of type 1 and type 2 alcoholism to the presence or absence of a family history of alcoholism in male paternal relatives. We found that guilt and binging, features usually attributed to type 1 (milieu-limited) alcoholism, were in fact more prevalent in the family history positive group. An additional cohort analysis found cohort-related variations in type 1/type 2 characteristics. The possible implications of these findings are discussed. JF - Addiction (Abingdon, England) AU - De Jong, J A AU - Roy, A AD - Laboratory of Clinical Studies, DICBR, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland. Y1 - 1993/05// PY - 1993 DA - May 1993 SP - 623 EP - 629 VL - 88 IS - 5 SN - 0965-2140, 0965-2140 KW - Index Medicus KW - Risk Factors KW - Models, Genetic KW - Humans KW - Cohort Studies KW - Adult KW - Alcohol Drinking -- psychology KW - Middle Aged KW - Follow-Up Studies KW - Alcohol Drinking -- genetics KW - Male KW - Child of Impaired Parents -- psychology KW - Alcoholism -- classification KW - Alcoholism -- genetics KW - Alcoholism -- psychology KW - Social Environment UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75798496?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Paternal+lineage+of+alcoholism%2C+cohort+effects%2C+and+alcoholism+criteria.&rft.au=De+Jong%2C+J+A%3BRoy%2C+A&rft.aulast=De+Jong&rft.aufirst=J&rft.date=1993-05-01&rft.volume=88&rft.issue=5&rft.spage=623&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 - 1993-07-28 N1 - Date created - 1993-07-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Improved protein detection with a polyvinylidene fluoride transfer membrane for two-dimensional gel electrophoresis. AN - 75789847; 7685610 JF - BioTechniques AU - Patterson, R M AU - Witcher, L L AU - He, C AU - Selkirk, J K AU - Merrick, B A AD - National Institute of Environmental Health Sciences, Laboratory of Molecular Carcinogenesis, Research Triangle Park, NC 27709. Y1 - 1993/05// PY - 1993 DA - May 1993 SP - 752 EP - 753 VL - 14 IS - 5 SN - 0736-6205, 0736-6205 KW - Membranes, Artificial KW - 0 KW - Polyvinyls KW - Proteins KW - polyvinylidene fluoride KW - 24937-79-9 KW - Index Medicus KW - Animals KW - Fibroblasts -- chemistry KW - Mice KW - Staining and Labeling KW - Biotechnology KW - Electrophoresis, Gel, Two-Dimensional -- methods KW - Proteins -- isolation & purification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75789847?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=BioTechniques&rft.atitle=Improved+protein+detection+with+a+polyvinylidene+fluoride+transfer+membrane+for+two-dimensional+gel+electrophoresis.&rft.au=Patterson%2C+R+M%3BWitcher%2C+L+L%3BHe%2C+C%3BSelkirk%2C+J+K%3BMerrick%2C+B+A&rft.aulast=Patterson&rft.aufirst=R&rft.date=1993-05-01&rft.volume=14&rft.issue=5&rft.spage=752&rft.isbn=&rft.btitle=&rft.title=BioTechniques&rft.issn=07366205&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-07-20 N1 - Date created - 1993-07-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - D1 and D2 dopamine receptor-mediated mechanisms and behavioral supersensitivity. AN - 75782351; 8516358 AB - The contribution of D1 and D2 dopamine (DA) receptor mechanisms to the behavioral supersensitivity and receptor upregulation induced by chronic DA antagonist administration were compared. Rats received either the selective D1 DA receptor antagonist SCH23390, the selective D2 DA receptor antagonist raclopride, their combination, or haloperidol, a predominantly D2 antagonist, for 21 days. Equivalent cataleptogenic doses of all drugs and drug combinations were employed. Tolerance to the cataleptic response was observed only in the haloperidol-treated group. Apomorphine-induced stereotypies were significantly enhanced in SCH23390-, raclopride-, and haloperidol-treated rats. In contrast, coadministration of both SCH23390 and raclopride had no effect on apomorphine-induced stereotypy. These findings suggest that neuroleptics blocking in equal proportion D1 and D2 receptor sites might be less likely to induce tardive dyskinesia and drug tolerance than those acting selectively on one or the other of these receptor subtypes. JF - Pharmacology, biochemistry, and behavior AU - Marin, C AU - Parashos, S A AU - Kapitzoglou-Logothetis, V AU - Peppe, A AU - Chase, T N AD - Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892. Y1 - 1993/05// PY - 1993 DA - May 1993 SP - 195 EP - 200 VL - 45 IS - 1 SN - 0091-3057, 0091-3057 KW - Benzazepines KW - 0 KW - Dopamine D2 Receptor Antagonists KW - Receptors, Dopamine D1 KW - Salicylamides KW - Raclopride KW - 430K3SOZ7G KW - Haloperidol KW - J6292F8L3D KW - Apomorphine KW - N21FAR7B4S KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Catalepsy -- chemically induced KW - Benzazepines -- pharmacology KW - Apomorphine -- pharmacology KW - Up-Regulation -- drug effects KW - Haloperidol -- pharmacology KW - Salicylamides -- pharmacology KW - Stereotyped Behavior -- drug effects KW - Male KW - Behavior, Animal -- drug effects KW - Receptors, Dopamine D1 -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75782351?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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%2C+biochemistry%2C+and+behavior&rft.atitle=D1+and+D2+dopamine+receptor-mediated+mechanisms+and+behavioral+supersensitivity.&rft.au=Marin%2C+C%3BParashos%2C+S+A%3BKapitzoglou-Logothetis%2C+V%3BPeppe%2C+A%3BChase%2C+T+N&rft.aulast=Marin&rft.aufirst=C&rft.date=1993-05-01&rft.volume=45&rft.issue=1&rft.spage=195&rft.isbn=&rft.btitle=&rft.title=Pharmacology%2C+biochemistry%2C+and+behavior&rft.issn=00913057&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-07-19 N1 - Date created - 1993-07-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Biosynthesis of dopamine and serotonin in the rat brain after repeated cocaine injections: a microdissection mapping study. AN - 75779490; 8511717 AB - The purpose of the present study was to examine the effects of chronic cocaine on dopamine (DA) and serotonin (5-HT) synthesis in several rat brain regions implicated in drug reinforcement. Male rats were treated twice daily with cocaine (15 mg/kg, ip) or saline for 1 week. After 42 hr of abstinence, rats were challenged with either cocaine (15 mg/kg, ip) or saline, followed by the aromatic L-amino acid decarboxylase inhibitor 3-hydroxybenzylhydrazine (NSD-1015; 100 mg/kg, ip). Animals were decapitated 30 min after NSD-1015 and discrete brain regions were microdisected from 300 microns frozen sections. Postmortem tissue levels of 3,4-dihydroxyphenylalanine (DOPA) and 5-hyroxytryptophan (5-HTP) were quantified by HPLC with electrochemical detection and used to estimate biosynthesis of DA and 5-HT, respectively. In chronic saline-treated rats, cocaine dramatically suppressed DA and 5-HT synthesis in all forebrain regions examined, including: medial prefrontal cortex, nucleus accumbens, caudate nucleus, olfactory tubercle, and basolateral amygdala. The degree of inhibition ranged from 35-65% and was more pronounced in 5-HT neurons compared to DA neurons in the same tissue sample. In general, chronic cocaine did not significantly alter basal levels of DOPA or 5-HTP; a notable exception was lateral hypothalamus, where chronic cocaine reduced basal DA synthesis to 75% of control. After repeated cocaine injections, the synthesis-inhibiting effect of a challenge injection of cocaine was attenuated in many brain areas. These data suggest that whereas acute cocaine decreases DA and 5-HT synthesis in forebrain, chronic cocaine is not neurotoxic to DA and 5-HT neurons. In addition, the mechanism(s) mediating cocaine-induced suppression of monoamine synthesis may become desensitized by chronic exposure to the drug. JF - Synapse (New York, N.Y.) AU - Baumann, M H AU - Raley, T J AU - Partilla, J S AU - Rothman, R B AD - Clinical Psychopharmacology Section, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 21224. Y1 - 1993/05// PY - 1993 DA - May 1993 SP - 40 EP - 50 VL - 14 IS - 1 SN - 0887-4476, 0887-4476 KW - Serotonin KW - 333DO1RDJY KW - Dihydroxyphenylalanine KW - 63-84-3 KW - 5-Hydroxytryptophan KW - C1LJO185Q9 KW - Cocaine KW - I5Y540LHVR KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Rats KW - Electrochemistry -- methods KW - Animals KW - Rats, Sprague-Dawley KW - Dihydroxyphenylalanine -- metabolism KW - 5-Hydroxytryptophan -- metabolism KW - Injections KW - Male KW - Dissection KW - Chromatography, High Pressure Liquid KW - Serotonin -- biosynthesis KW - Dopamine -- biosynthesis KW - Brain -- metabolism KW - Cocaine -- pharmacology KW - Cocaine -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75779490?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Biosynthesis+of+dopamine+and+serotonin+in+the+rat+brain+after+repeated+cocaine+injections%3A+a+microdissection+mapping+study.&rft.au=Baumann%2C+M+H%3BRaley%2C+T+J%3BPartilla%2C+J+S%3BRothman%2C+R+B&rft.aulast=Baumann&rft.aufirst=M&rft.date=1993-05-01&rft.volume=14&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 - 1993-07-15 N1 - Date created - 1993-07-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A mechanistic model of effects of dioxin on gene expression in the rat liver. AN - 75779124; 8511776 AB - Improved methods for estimating the shape of the response curve for effects of exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) are needed in order to evaluate possible adverse health effects of TCDD. A mathematical model has been constructed to describe TCDD-mediated alterations in hepatic proteins in the rat. In this model it was assumed that TCDD mediates increases in the liver concentration of transforming growth factor-alpha (TGF-alpha) by a mechanism which requires the aryl hydrocarbon (Ah) receptor. TGF-alpha subsequently binds to the epidermal growth factor (EGF) receptor, a process which is known to cause internalization of this receptor in hepatocytes. This action is thought to be an early event in the generation of a mitogenic signal. Because TCDD decreases binding of EGF in the livers of intact female rats but not in ovariectomized rats, this effect was further assumed to be dependent on estrogen action. The model postulates Ah receptor-dependent effects on the concentration of cytochrome P450 1A2 (CYP1A2), which is involved in the metabolism of estradiol, and on the concentration of the estrogen receptor. The model also incorporates information on induction of cytochrome P450 1A1 (CYP1A1) by TCDD. The biochemical response curves for all these proteins were hyperbolic (Hill exponents in the equations for their expression were found to be 1), indicating a proportional relationship between target tissue dose and protein concentration at low administered doses of TCDD. The model successfully reproduced the observed tissue distribution of TCDD, the concentrations of CYP1A1 and CYP1A2, and the effects of TCDD on the Ah, estrogen, and EGF receptors over a wide dose range. JF - Toxicology and applied pharmacology AU - Kohn, M C AU - Lucier, G W AU - Clark, G C AU - Sewall, C AU - Tritscher, A M AU - Portier, C J AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1993/05// PY - 1993 DA - May 1993 SP - 138 EP - 154 VL - 120 IS - 1 SN - 0041-008X, 0041-008X KW - Estrogens KW - 0 KW - Polychlorinated Dibenzodioxins KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - Index Medicus KW - Receptor, Epidermal Growth Factor -- drug effects KW - Rats KW - Animals KW - Estrogens -- metabolism KW - Dose-Response Relationship, Drug KW - Cell Division -- drug effects KW - Cytochrome P-450 Enzyme System -- metabolism KW - Tissue Distribution KW - Female KW - Gene Expression -- drug effects KW - Polychlorinated Dibenzodioxins -- pharmacokinetics KW - Liver -- drug effects KW - Polychlorinated Dibenzodioxins -- toxicity KW - Models, Biological UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75779124?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+mechanistic+model+of+effects+of+dioxin+on+gene+expression+in+the+rat+liver.&rft.au=Kohn%2C+M+C%3BLucier%2C+G+W%3BClark%2C+G+C%3BSewall%2C+C%3BTritscher%2C+A+M%3BPortier%2C+C+J&rft.aulast=Kohn&rft.aufirst=M&rft.date=1993-05-01&rft.volume=120&rft.issue=1&rft.spage=138&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 - 1993-07-09 N1 - Date created - 1993-07-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Quantification of axotomy-induced alteration of neuropeptide mRNAs in dorsal root ganglion neurons with special reference to neuropeptide Y mRNA and the effects of neonatal capsaicin treatment. AN - 75772334; 7685398 AB - Alteration in mRNA expression in dorsal root ganglia (DRG) neurons encoding 5 neuropeptides was quantitatively compared in normal rats and in those neonatally treated with capsaicin, a selective neurotoxin which destroys a subpopulation of DRG neurons with unmyelinated axons. Adult rats received a unilateral transection of the sciatic nerve and were killed 7 days later. Oligonucleotide probes specific for the genes encoding neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), galanin (GAL), somatostatin (SOM), and calcitonin gene-related peptide (CGRP) were used for in situ hybridization and RNA blot analysis. Following the nerve cut, RNA blot analysis demonstrated a dramatic induction of NPY, VIP, and GAL mRNA levels from the undetectable constitutive level of expression. Conversely, CGRP and SOM mRNAs, which are constitutively expressed, were reduced 55% and 70%, respectively, following the nerve cut. A unimodal size distribution for neurons expressing NPY mRNA was determined, with a mean cross-sectional area of 1700 microns2 representing 24.4% of DRG neurons ipsilateral to the nerve cut. Neurons expressing VIP mRNA were mainly small sized, with a cross-sectional area of approximately 700 microns2, while those expressing GAL mRNA were both small (approximately 700 microns2) and medium (approximately 1,300 microns2) sized. The percentages of neurons expressing VIP or GAL mRNA were 19.9% and 33.7%, respectively. In neonatal capsaicin-treated rats, there was a 10% reduction in neurons expressing NPY mRNA, a 37% reduction for VIP, and a 27% for GAL mRNA compared to vehicle-treated rats after nerve cut. Capsaicin-sensitive neurons comprised 37% of CGRP neurons and 83% of SOM neurons. These observations suggest that NPY is primarily induced in myelinated primary afferent neurons, while VIP and GAL mRNA induction occurs in a mixed population, a sizeable percentage of which has unmyelinated axons. Additionally, SOM mRNA expression is associated mainly with unmyelinated primary afferents. JF - Journal of neuroscience research AU - Noguchi, K AU - De León, M AU - Nahin, R L AU - Senba, E AU - Ruda, M A AD - Neurobiology and Anesthesiology Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/05/01/ PY - 1993 DA - 1993 May 01 SP - 54 EP - 66 VL - 35 IS - 1 SN - 0360-4012, 0360-4012 KW - Neuropeptide Y KW - 0 KW - Neuropeptides KW - Oligonucleotide Probes KW - Peptides KW - RNA, Messenger KW - Sulfur Radioisotopes KW - Vasoactive Intestinal Peptide KW - 37221-79-7 KW - Somatostatin KW - 51110-01-1 KW - Calcitonin Gene-Related Peptide KW - 83652-28-2 KW - Galanin KW - 88813-36-9 KW - Capsaicin KW - S07O44R1ZM KW - Index Medicus KW - Vasoactive Intestinal Peptide -- biosynthesis KW - Gene Expression -- drug effects KW - Somatostatin -- genetics KW - Animals KW - Calcitonin Gene-Related Peptide -- genetics KW - Peptide Biosynthesis KW - Autoradiography KW - Somatostatin -- biosynthesis KW - Neuropeptide Y -- genetics KW - Rats KW - Neuropeptide Y -- biosynthesis KW - Animals, Newborn KW - Rats, Sprague-Dawley KW - In Situ Hybridization KW - Calcitonin Gene-Related Peptide -- biosynthesis KW - Peptides -- genetics KW - Vasoactive Intestinal Peptide -- genetics KW - Male KW - Ganglia, Spinal -- cytology KW - Neurons -- metabolism KW - RNA, Messenger -- metabolism KW - Neurons -- drug effects KW - Ganglia, Spinal -- metabolism KW - Neurons -- cytology KW - Sciatic Nerve -- physiology KW - Neuropeptides -- biosynthesis KW - Ganglia, Spinal -- drug effects KW - Neuropeptides -- genetics KW - Capsaicin -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75772334?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Quantification+of+axotomy-induced+alteration+of+neuropeptide+mRNAs+in+dorsal+root+ganglion+neurons+with+special+reference+to+neuropeptide+Y+mRNA+and+the+effects+of+neonatal+capsaicin+treatment.&rft.au=Noguchi%2C+K%3BDe+Le%C3%B3n%2C+M%3BNahin%2C+R+L%3BSenba%2C+E%3BRuda%2C+M+A&rft.aulast=Noguchi&rft.aufirst=K&rft.date=1993-05-01&rft.volume=35&rft.issue=1&rft.spage=54&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 - 1993-07-15 N1 - Date created - 1993-07-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cancer and other causes of death among male and female farmers from twenty-three states. AN - 75771679; 8506851 AB - Occupation and industry codes on death certificates from 23 states for 1984-1988 were used to evaluate mortality risks among white and nonwhite, male and female farmers. Proportionate mortality and proportionate cancer mortality ratios were calculated using deaths among nonfarmers from the same states to generate expected numbers. Among farmers there were 119,648 deaths among white men, 2,400 among white women, 11,446 among nonwhite men, and 2,066 among nonwhite women. Deficits occurred in all race-sex groups for infective and parasitic diseases, all cancer combined, lung cancer, liver cancer, diseases of the nervous system, multiple sclerosis, hypertension, and emphysema. As reported in other studies, white male farmers had excesses of cancer of the lymphatic and hematopoietic system, lip, eye, brain, and prostate. Excesses of cancers of the pancreas, kidney, bone, and thyroid were new findings. Regional patterns were evident, particularly among white men. Significant excesses for accidents, vascular lesions of the central nervous system (CNS), and cancers of the prostate tended to occur in most geographic regions, while excesses for mechanical suffocation, non-Hodgkin's lymphoma, and cancers of the lip, brain, and the lymphatic and hematopoietic system were limited to the Central states. Increases among nonwhite men were similar to those in white men for some causes of death (vascular lesions of the CNS and cancers of the pancreas and prostate), but were absent for others (lymphatic and hematopoietic system, lip, eye, kidney, and brain). Women (white and nonwhite) had excesses for vascular lesions of the CNS, disease of the genitourinary system (white women only), and cancers of the stomach and cervix (nonwhite women only). Cancer of the buccal cavity and pharynx was slightly elevated among women, and white women had nonsignificant excesses of multiple myeloma and leukemia. Excesses for leukemia and non-Hodgkin's lymphoma occurred among white men and women, but not among nonwhites. Excesses for several types of accidental deaths were seen among all race-sex groups. JF - American journal of industrial medicine AU - Blair, A AU - Dosemeci, M AU - Heineman, E F AD - Occupational Studies Section, National Cancer Institute, Bethesda, MD 20892. Y1 - 1993/05// PY - 1993 DA - May 1993 SP - 729 EP - 742 VL - 23 IS - 5 SN - 0271-3586, 0271-3586 KW - Index Medicus KW - Humans KW - Continental Population Groups KW - United States -- epidemiology KW - Male KW - Female KW - Cause of Death KW - Agricultural Workers' Diseases -- mortality KW - Agricultural Workers' Diseases -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75771679?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+industrial+medicine&rft.atitle=Cancer+and+other+causes+of+death+among+male+and+female+farmers+from+twenty-three+states.&rft.au=Blair%2C+A%3BDosemeci%2C+M%3BHeineman%2C+E+F&rft.aulast=Blair&rft.aufirst=A&rft.date=1993-05-01&rft.volume=23&rft.issue=5&rft.spage=729&rft.isbn=&rft.btitle=&rft.title=American+journal+of+industrial+medicine&rft.issn=02713586&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-07-07 N1 - Date created - 1993-07-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - p53 mutations in human immortalized epithelial cell lines. AN - 75769231; 8504475 AB - Although rodent cells have been immortalized following transfection with a mutant p53 gene, the role of p53 in the immortalization of human cells is unknown. Therefore, human epithelial cell lines were examined for p53 mutations in exons 4-9 which include the evolutionarily conserved regions. A spontaneously immortalized skin keratinocyte cell line, HaCat, and three ras-transfected clones, have a p53 mutational spectrum that is typical of ultraviolet light induced mutations. A normal finite lifespan cell strain (184) and two benzo[a]pyrene immortalized mammary epithelial cell lines derived from 184 (184A1 and 184B5) contain wild type p53 sequences in exons 4-9, although elevated levels of nuclear p53 indicate an alteration in the stability of the normally transient protein. Wild type p53 was found in human bronchial, esophageal and hepatic epithelial cells immortalized by SV40 T antigen gene and human renal epithelial cells immortalized by adenovirus 5. BEAS-2B, an SV40 T antigen immortalized bronchial epithelial cell line and two subclones, have a germline polymorphism at codon 47. Inactivation of p53 by mechanisms such as mutation or complexing with proteins of DNA tumor viruses appears to be important in the immortalization of human epithelial cells. JF - Carcinogenesis AU - Lehman, T A AU - Modali, R AU - Boukamp, P AU - Stanek, J AU - Bennett, W P AU - Welsh, J A AU - Metcalf, R A AU - Stampfer, M R AU - Fusenig, N AU - Rogan, E M AD - Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, MD 20892. Y1 - 1993/05// PY - 1993 DA - May 1993 SP - 833 EP - 839 VL - 14 IS - 5 SN - 0143-3334, 0143-3334 KW - p53 KW - ras KW - Oligodeoxyribonucleotides KW - 0 KW - Tumor Suppressor Protein p53 KW - Benzo(a)pyrene KW - 3417WMA06D KW - Index Medicus KW - Benzo(a)pyrene -- pharmacology KW - Tumor Suppressor Protein p53 -- biosynthesis KW - Exons KW - Humans KW - Breast KW - Respiratory System KW - Epithelium -- drug effects KW - Genes, ras KW - Polymerase Chain Reaction KW - Tumor Suppressor Protein p53 -- analysis KW - Base Sequence KW - Molecular Sequence Data KW - Kidney KW - Introns KW - Epithelium -- metabolism KW - Cell Line, Transformed KW - Immunohistochemistry KW - Cell Transformation, Neoplastic KW - Female KW - Genes, p53 KW - Mutation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75769231?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=p53+mutations+in+human+immortalized+epithelial+cell+lines.&rft.au=Lehman%2C+T+A%3BModali%2C+R%3BBoukamp%2C+P%3BStanek%2C+J%3BBennett%2C+W+P%3BWelsh%2C+J+A%3BMetcalf%2C+R+A%3BStampfer%2C+M+R%3BFusenig%2C+N%3BRogan%2C+E+M&rft.aulast=Lehman&rft.aufirst=T&rft.date=1993-05-01&rft.volume=14&rft.issue=5&rft.spage=833&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-07-06 N1 - Date created - 1993-07-06 N1 - Date revised - 2017-01-13 N1 - Gene symbol - p53; ras N1 - SuppNotes - Erratum In: Carcinogenesis 1993 Jul;14(7):1491 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inhalation exposure to a hepatocarcinogenic concentration of methylene chloride does not induce sustained replicative DNA synthesis in hepatocytes of female B6C3F1 mice. AN - 75768087; 8099314 AB - We have used methylene chloride as a model to study cellular and molecular processes responsible for liver tumor induction by chlorinated hydrocarbons. Because of current interest in the role of enhanced cell proliferation in tumor induction, measurement of S-phase hepatocytes was incorporated into recently conducted toxicity and carcinogenicity studies. In prechronic studies, female B6C3F1 mice were exposed to 0, 1000, 2000 or 8000 p.p.m. methylene chloride by inhalation, 5 days per week, for up to 4 weeks followed by a 1 and 2 week recovery period. Mice exposed to concentrations of 2000, 4000 or 8000 p.p.m. methylene chloride had sustained increased liver weight commencing after 1 week of exposure and returning to normal after the 1 or 2 week recovery period. The increased liver weight was attributed to hepatocellular hypertrophy secondary to intracellular glycogen accumulation. Tritiated thymidine was administered by osmotic minipumps to label S-phase hepatocytes over a 6 day period. At most intervals examined there was decreased hepatocyte labeling in mice exposed to methylene chloride. However, there was a transitory increased number of S-phase hepatocytes observed at the 2 week interval in the 1000, 4000 and 8000 p.p.m. methylene chloride groups. In a chronic study, female mice were exposed to 2000 p.p.m. methylene chloride for up to two years. Following labeling with BRDU using 6 day minipumps, a statistically significant decrease in S-phase hepatocytes was observed after 13 weeks of methylene chloride exposure. A minor increased labeling index (LI) observed at 52 weeks was not considered to be a methylene chloride treatment-related effect. Retrospective immunohistochemical staining for proliferating cell nuclear antigen (PCNA) in liver sections containing foci of cellular alteration allowed demonstration of S-phase hepatocytes in these clonally expanded preneoplastic lesions. While foci frequently had higher LI's than surrounding normal hepatocytes, there was no difference in the mean LI of foci from methylene chloride-treated mice versus foci occurring spontaneously in control mice. The absence of a sustained increase in S-phase hepatocytes in female B6C3F1 mice suggests that enhanced cell proliferation is not a major mechanistic factor associated with the observed hepatocarcinogenicity of methylene chloride. JF - Carcinogenesis AU - Foley, J F AU - Tuck, P D AU - Ton, T V AU - Frost, M AU - Kari, F AU - Anderson, M W AU - Maronpot, R R AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1993/05// PY - 1993 DA - May 1993 SP - 811 EP - 817 VL - 14 IS - 5 SN - 0143-3334, 0143-3334 KW - Antigens, Neoplasm KW - 0 KW - Carcinogens KW - Liver Glycogen KW - Nuclear Proteins KW - Proliferating Cell Nuclear Antigen KW - Methylene Chloride KW - 588X2YUY0A KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Animals KW - Mitotic Index -- drug effects KW - Antigens, Neoplasm -- analysis KW - Cell Division -- drug effects KW - Mice KW - Nuclear Proteins -- analysis KW - Mice, Inbred Strains KW - Hypertrophy KW - Liver Glycogen -- metabolism KW - Administration, Inhalation KW - Cell Cycle -- drug effects KW - Female KW - Liver -- pathology KW - Carcinogens -- administration & dosage KW - Methylene Chloride -- toxicity KW - Liver -- drug effects KW - Carcinogens -- toxicity KW - Liver -- metabolism KW - Methylene Chloride -- administration & dosage KW - DNA -- biosynthesis KW - DNA Replication -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75768087?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Inhalation+exposure+to+a+hepatocarcinogenic+concentration+of+methylene+chloride+does+not+induce+sustained+replicative+DNA+synthesis+in+hepatocytes+of+female+B6C3F1+mice.&rft.au=Foley%2C+J+F%3BTuck%2C+P+D%3BTon%2C+T+V%3BFrost%2C+M%3BKari%2C+F%3BAnderson%2C+M+W%3BMaronpot%2C+R+R&rft.aulast=Foley&rft.aufirst=J&rft.date=1993-05-01&rft.volume=14&rft.issue=5&rft.spage=811&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-07-06 N1 - Date created - 1993-07-06 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Carcinogenesis. 1993 May;14(5):787-8 [8504469] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characterization of p53 mutations in methylene chloride-induced lung tumors from B6C3F1 mice. AN - 75767114; 8504472 AB - Mutations of the p53 tumor suppressor gene are the most common defined genetic alterations seen in a wide variety of human cancers. In contrast, little is known about the importance of the p53 gene in chemically induced tumors of rodents, which are widely used as models for the evaluation of human health risks. In this study we examined 54 methylene chloride-induced and seven spontaneously arising lung tumors from female B6C3F1 mice for losses of heterozygosity (LOH) at markers near the p53 gene on chromosome 11. LOH was detected in seven methylene chloride-induced lung carcinomas by Southern analysis of a restriction fragment length polymorphism and PCR analysis of five simple sequence length polymorphisms. In each case allele loss was observed at all six markers; thus, these chromosomal alterations were likely to have resulted from mitotic nondisjunction. In contrast, LOH was not detected in 20 liver tumors from methylene chloride-treated mice at the Acrb locus, which is tightly linked to the p53 gene on chromosome 11. In addition single strand conformation polymorphism analysis was performed to screen for mutations in the most conserved regions of the p53 gene (exons 5 to 8). Consequently, potential mutations identified by direct sequencing, were only detected in four of the seven tumor samples with LOH, but not in any of the remaining lung tumors. Overexpression of the p53 protein by immunohistochemical staining was detected only in the four tumors that contained p53 point mutations and in a focal area of another tumor. Finally, using a simple sequence length polymorphism within the retinoblastoma tumor suppressor gene, LOH on mouse chromosome 14 was also detected in three lung carcinomas and one liver tumor. Inactivation of p53 and possibly the retinoblastoma tumor suppressor gene appear to be infrequent events in lung and liver tumors from methylene chloride treated mice. JF - Carcinogenesis AU - Hegi, M E AU - Söderkvist, P AU - Foley, J F AU - Schoonhoven, R AU - Swenberg, J A AU - Kari, F AU - Maronpot, R AU - Anderson, M W AU - Wiseman, R W AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC 27709. Y1 - 1993/05// PY - 1993 DA - May 1993 SP - 803 EP - 810 VL - 14 IS - 5 SN - 0143-3334, 0143-3334 KW - Acrb KW - Csfgm KW - Hpg KW - Krt-1 KW - Myla KW - p53 KW - Carcinogens KW - 0 KW - DNA, Neoplasm KW - Genetic Markers KW - Oligodeoxyribonucleotides KW - Tumor Suppressor Protein p53 KW - Methylene Chloride KW - 588X2YUY0A KW - Index Medicus KW - Animals KW - Polymorphism, Genetic KW - Exons KW - Mice KW - DNA, Neoplasm -- isolation & purification KW - Chromosome Mapping KW - Mice, Inbred Strains KW - Tumor Suppressor Protein p53 -- analysis KW - Base Sequence KW - Heterozygote KW - Molecular Sequence Data KW - DNA, Neoplasm -- genetics KW - Immunohistochemistry KW - Female KW - Methylene Chloride -- toxicity KW - Genes, p53 KW - Carcinogens -- toxicity KW - Lung Neoplasms -- genetics KW - Lung Neoplasms -- chemically induced KW - Mutagenesis KW - Lung Neoplasms -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75767114?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Characterization+of+p53+mutations+in+methylene+chloride-induced+lung+tumors+from+B6C3F1+mice.&rft.au=Hegi%2C+M+E%3BS%C3%B6derkvist%2C+P%3BFoley%2C+J+F%3BSchoonhoven%2C+R%3BSwenberg%2C+J+A%3BKari%2C+F%3BMaronpot%2C+R%3BAnderson%2C+M+W%3BWiseman%2C+R+W&rft.aulast=Hegi&rft.aufirst=M&rft.date=1993-05-01&rft.volume=14&rft.issue=5&rft.spage=803&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-07-06 N1 - Date created - 1993-07-06 N1 - Date revised - 2017-01-13 N1 - Gene symbol - Acrb; Csfgm; Hpg; Krt-1; Myla; p53 N1 - SuppNotes - Comment In: Carcinogenesis. 1993 May;14(5):787-8 [8504469] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Detection of metabolites of polycyclic aromatic hydrocarbons in human urine. AN - 75767084; 8504465 AB - A non-invasive assay has been developed for the recovery of r-7,t-8,t-9,c-10-tetrahydroxy-7,8,9,10-tetrahydrobenzo[alpha]-pyrene (BP-7,10/8,9-tetrol) from human urine. This tetrol is excreted as a metabolite of benzo[alpha]pyrene (BP) in a process catalyzed by cytochrome P450 enzymes and epoxide hydrolases. Urine was hydrolysed to release activated benzo[alpha]-pyrene-diol-epoxides covalently bound to macromolecular species or conjugated tetrols. The relatively non-polar organic molecules from urine hydrolysates were collected on octadecasilane chromatography columns (Sep-Paks). Materials eluted in solvent (80% CH3OH), were further purified on immunoaffinity columns with antibodies raised against anti-N2-[10(7,8,9-trihydroxy-7,8,9,10-tetrahydrobenzo [alpha]pyrenyl)]-guanosine. HPLC was then used to isolate BP-7,10/8,9-tetrol, which was quantitated by synchronous fluorescence spectroscopy (SFS). This assay detected 0.24-3.12 pmol BP-7,10/8,9-tetrol per ml urine (limit of detection 0.01 pmol/ml, given 10 ml urine), in four study subjects. Reproducibility was assessed by adding tritium labeled BP-7,10/8,9-tetrol (1500 fmol) to a urine sample previously identified to contain the tetrol at levels below the limit of detection of the fluorescence assay; a recovery of > 30% of the added radioactivity was achieved (510 +/- 64 fmol, mean +/- SD, n = 3). Because HPLC alone was not sufficient to isolate materials for quantitation by SFS directly from human urine, immunoaffinity chromatography was found to be a necessary preparatory step in BP-7,10/8,9-tetrol isolation. These data demonstrate the presence of tetrahydrotetrol metabolites of BP in human urine and suggest that measurement of BP-7,10/8,9-tetrol and other polycyclic aromatic hydrocarbon-tetrols may prove to be valuable dosimeters of human internal exposure to polycyclic aromatic hydrocarbons. JF - Carcinogenesis AU - Weston, A AU - Bowman, E D AU - Carr, P AU - Rothman, N AU - Strickland, P T AD - Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/05// PY - 1993 DA - May 1993 SP - 1053 EP - 1055 VL - 14 IS - 5 SN - 0143-3334, 0143-3334 KW - Benzopyrenes KW - 0 KW - Tritium KW - 10028-17-8 KW - Benzo(a)pyrene KW - 3417WMA06D KW - 7,8,9,10-tetrahydroxytetrahydrobenzo(a)pyrene KW - 59957-91-4 KW - Index Medicus KW - Reference Values KW - Spectrometry, Fluorescence -- methods KW - Lung Neoplasms -- urine KW - Biotransformation KW - Humans KW - Benzopyrenes -- analysis KW - Benzo(a)pyrene -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75767084?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Detection+of+metabolites+of+polycyclic+aromatic+hydrocarbons+in+human+urine.&rft.au=Weston%2C+A%3BBowman%2C+E+D%3BCarr%2C+P%3BRothman%2C+N%3BStrickland%2C+P+T&rft.aulast=Weston&rft.aufirst=A&rft.date=1993-05-01&rft.volume=14&rft.issue=5&rft.spage=1053&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-07-06 N1 - Date created - 1993-07-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Deficient gene specific repair of cisplatin-induced lesions in Xeroderma pigmentosum and Fanconi's anemia cell lines. AN - 75761168; 8504485 AB - Cisplatin is a chemotherapeutic agent known to cause DNA damage. The cytotoxicity of this drug is believed to result from the formation of DNA intrastrand adducts (IA) and DNA interstrand crosslinks (ICL). While there are many studies on DNA repair of cisplatin damage at the overall level of the genome in various human cell lines, there is little information on the gene-specific repair. In this report, we have measured the formation and repair of cisplatin induced DNA adducts in the dihydrofolate reductase (DHFR) and ribosomal RNA (rRNA) genes in three cell lines: normal human fibroblasts, Fanconi's anemia complementation group A (FAA) and Xeroderma pigmentosum complementation group A (XPA). It is generally thought that XPA cells lack nucleotide excision repair and that FAA cells are deficient in the repair of DNA ICL. We find that normal human fibroblast cells repair 84% of the ICL in the DHFR gene after 24 h, whereas XPA and FAA cell lines only repaired 32 and 50% of the ICL respectively. Furthermore, 69% of the cisplatin IA in the DHFR gene were repaired in 24 h in normal human fibroblasts compared to 22% for XPA and 24% for FAA cells. The repair of the rRNA gene was less efficient than in the DHFR gene, but the relative pattern between the different cell lines was similar to that of the DHFR gene. We thus find that FAA cells are deficient not only in the gene specific repair of cisplatin ICL, but also in the gene specific repair of the more common cisplatin IA. XPA cells are normally thought to be without any nucleotide excision repair capacity, but our data could support a slight ICL unhooking activity. JF - Carcinogenesis AU - Zhen, W AU - Evans, M K AU - Haggerty, C M AU - Bohr, V A AD - Laboratory of Molecular Pharmacology, National Cancer Institute, NIH, Bethesda, MD 20892. Y1 - 1993/05// PY - 1993 DA - May 1993 SP - 919 EP - 924 VL - 14 IS - 5 SN - 0143-3334, 0143-3334 KW - DHFR KW - DNA, Ribosomal KW - 0 KW - DNA KW - 9007-49-2 KW - Tetrahydrofolate Dehydrogenase KW - EC 1.5.1.3 KW - Cisplatin KW - Q20Q21Q62J KW - Index Medicus KW - Fibroblasts -- drug effects KW - Kinetics KW - Humans KW - Genetic Complementation Test KW - DNA, Ribosomal -- drug effects KW - Time Factors KW - Fibroblasts -- metabolism KW - DNA, Ribosomal -- genetics KW - Chromosome Mapping KW - Cell Line KW - Tetrahydrofolate Dehydrogenase -- genetics KW - DNA Repair KW - DNA Damage KW - Cisplatin -- toxicity KW - DNA -- genetics KW - Xeroderma Pigmentosum -- genetics KW - Fanconi Anemia -- genetics KW - DNA -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75761168?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Deficient+gene+specific+repair+of+cisplatin-induced+lesions+in+Xeroderma+pigmentosum+and+Fanconi%27s+anemia+cell+lines.&rft.au=Zhen%2C+W%3BEvans%2C+M+K%3BHaggerty%2C+C+M%3BBohr%2C+V+A&rft.aulast=Zhen&rft.aufirst=W&rft.date=1993-05-01&rft.volume=14&rft.issue=5&rft.spage=919&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-07-06 N1 - Date created - 1993-07-06 N1 - Date revised - 2017-01-13 N1 - Gene symbol - DHFR N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of varying exposure regimens on methylene chloride-induced lung and liver tumors in female B6C3F1 mice. AN - 75761084; 8504473 AB - Methylene chloride is a high production chemical used in a variety of applications resulting in estimated occupational and consumer exposures of at least one million people per day. Results of previously reported chronic evaluations of inhaled methylene chloride indicated that it caused mammary tumors in Fischer 344 rats and neoplasia in the lungs and liver of B6C3F1 mice. Mechanism(s) for methylene chloride-induced carcinogenesis have not been adequately elucidated. In this paper we describe the histologic evaluation of animals at a number of intermittent times for the purposes of assessing the progressive development of liver and lung neoplasia. Additionally, a series of stop-exposure treatments was conducted to evaluate the role of different methylene chloride exposure durations on the induction of hepatic and pulmonary neoplasia in female mice. Inhalation exposure to 2000 p.p.m. methylene chloride for 6 h per day, 5 days per week, for 104 weeks resulted in an 8-fold increase in the incidence of exposed animals having a lung adenoma or carcinoma (63 versus 7.5%; P < 0.01) and a 13-fold increase in the total number of pulmonary adenomas and carcinomas per animal at risk (0.97 versus 0.075; P < 0.01). This exposure also caused a 2.5-fold increase in the incidence of mice having liver tumors (69 versus 27%; P < 0.01) and a 3-fold increase in the total number of hepatic adenomas and carcinomas per animal at risk (1.34 versus 0.46; P < 0.01). Methylene chloride exposure hastened the first appearance of lung tumors (by 1 year) compared to that observed in control animals; chemical-induced and spontaneous liver tumors first occurred simultaneously. A shorter exposure duration was sufficient to attain maximal numbers of lung tumors than that needed for a maximal liver tumor burden. Lung tumor multiplicity was substantially increased by having additional time after cessation of the chemical treatment. This contrasts with the findings in liver, where additional post-exposure latency time did not effect tumor multiplicity compared to that of mice evaluated immediately after cessation of exposure. The incidence of lung alveolar hyperplasia in methylene chloride exposed animals was very low, even in tumor-bearing animals and the hyperplasias were not seen until at least 13 weeks after appearance of adenomas and carcinomas. Thus, the genesis of methylene chloride induced lung tumors in B6C3F1 mice is not preceded by overt cytotoxicity, enhanced cell proliferation nor observed hyperplasia.(ABSTRACT TRUNCATED AT 400 WORDS) JF - Carcinogenesis AU - Kari, F W AU - Foley, J F AU - Seilkop, S K AU - Maronpot, R R AU - Anderson, M W AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1993/05// PY - 1993 DA - May 1993 SP - 819 EP - 826 VL - 14 IS - 5 SN - 0143-3334, 0143-3334 KW - Carcinogens KW - 0 KW - Methylene Chloride KW - 588X2YUY0A KW - Index Medicus KW - Mice, Inbred Strains KW - Animals KW - Hyperplasia KW - Drug Administration Schedule KW - Carcinoma -- pathology KW - Adenoma -- chemically induced KW - Mice KW - Adenoma -- pathology KW - Time Factors KW - Female KW - Carcinoma -- chemically induced KW - Liver Neoplasms -- pathology KW - Liver -- pathology KW - Carcinogens -- administration & dosage KW - Methylene Chloride -- toxicity KW - Liver -- drug effects KW - Lung -- drug effects KW - Liver Neoplasms -- chemically induced KW - Carcinogens -- toxicity KW - Methylene Chloride -- administration & dosage KW - Lung Neoplasms -- chemically induced KW - Lung -- pathology KW - Lung Neoplasms -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75761084?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Effect+of+varying+exposure+regimens+on+methylene+chloride-induced+lung+and+liver+tumors+in+female+B6C3F1+mice.&rft.au=Kari%2C+F+W%3BFoley%2C+J+F%3BSeilkop%2C+S+K%3BMaronpot%2C+R+R%3BAnderson%2C+M+W&rft.aulast=Kari&rft.aufirst=F&rft.date=1993-05-01&rft.volume=14&rft.issue=5&rft.spage=819&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-07-06 N1 - Date created - 1993-07-06 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Carcinogenesis. 1993 May;14(5):787-8 [8504469] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ras proto-oncogene activation in liver and lung tumors from B6C3F1 mice exposed chronically to methylene chloride. AN - 75761036; 8504471 AB - Methylene chloride has been the subject of recent toxicological and carcinogenesis studies because of significant human exposure and widespread use in industrial processing, food preparation and agriculture. In this study, liver and lung tumors, induced in female B6C3F1 mice by inhalation of 2000 p.p.m. methylene chloride (6 h/day, 5 days/week continuous exposure), were examined for the presence of activated ras proto-oncogenes. DNA was isolated from 49 spontaneous and 50 methylene chloride-induced liver tumors and screened by oligonucleotide hybridization of PCR amplified H-ras gene fragments for codon 61 mutations. In the chemically induced tumors, 38 mutations were detected, 16 C to A transversions in base 1, 16 A to G transitions in base 2 and 6 A to T transversions in base 2. This mutation profile was similar to that identified for the H-ras gene in the spontaneous liver tumors and suggests that methylene chloride acts in liver by promoting cells with spontaneous lesions. Tumors in which H-ras codon 61 mutations were not detected were examined for the presence of transforming genes by the nude mouse tumorigenicity assay. Except for activated K-ras genes detected in DNA from two methylene chloride induced tumors and one spontaneous tumor, no other transforming genes were identified. DNA from 54 lung tumors was screened by direct sequencing of PCR amplified DNA fragments of the K-ras gene for first and second exon mutations, and 12 mutations were identified, 5 in exon one and 7 in exon 2. The low number of spontaneous tumors available in this study limits the interpretation of the data, and thus the frequency and spectrum of K-ras activation in the methylene chloride induced tumors was not significantly different from that in the seven spontaneous tumors analyzed. Since K-ras activation was not detected in 80% of the tumors, the nude mouse tumorigenicity assay was used to examine the lung tumors for the presence of other transforming genes. At present no transforming genes other than ras genes were identified in either liver or lung tumors. JF - Carcinogenesis AU - Devereux, T R AU - Foley, J F AU - Maronpot, R R AU - Kari, F AU - Anderson, M W AD - Laboratory of Molecular Toxicology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1993/05// PY - 1993 DA - May 1993 SP - 795 EP - 801 VL - 14 IS - 5 SN - 0143-3334, 0143-3334 KW - H-ras KW - K-ras KW - ras KW - Carcinogens KW - 0 KW - Codon KW - DNA, Neoplasm KW - Oligodeoxyribonucleotides KW - Methylene Chloride KW - 588X2YUY0A KW - Index Medicus KW - 3T3 Cells KW - Animals KW - Polymorphism, Genetic KW - Exons KW - Mice, Nude KW - Mice KW - DNA, Neoplasm -- isolation & purification KW - Chromosome Mapping KW - Polymerase Chain Reaction KW - Mice, Inbred Strains KW - Base Sequence KW - Blotting, Southern KW - Adenoma -- chemically induced KW - Molecular Sequence Data KW - DNA, Neoplasm -- genetics KW - Adenoma -- genetics KW - Female KW - Carcinoma -- chemically induced KW - Carcinoma -- genetics KW - Genes, ras KW - Methylene Chloride -- toxicity KW - Point Mutation KW - Liver Neoplasms -- chemically induced KW - Carcinogens -- toxicity KW - Lung Neoplasms -- genetics KW - Lung Neoplasms -- chemically induced KW - Gene Expression Regulation, Neoplastic -- drug effects KW - Liver Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75761036?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Ras+proto-oncogene+activation+in+liver+and+lung+tumors+from+B6C3F1+mice+exposed+chronically+to+methylene+chloride.&rft.au=Devereux%2C+T+R%3BFoley%2C+J+F%3BMaronpot%2C+R+R%3BKari%2C+F%3BAnderson%2C+M+W&rft.aulast=Devereux&rft.aufirst=T&rft.date=1993-05-01&rft.volume=14&rft.issue=5&rft.spage=795&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-07-06 N1 - Date created - 1993-07-06 N1 - Date revised - 2017-01-13 N1 - Gene symbol - H-ras; K-ras; ras N1 - SuppNotes - Comment In: Carcinogenesis. 1993 May;14(5):787-8 [8504469] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Relative performance of the MAST, VAST, and CAGE versus DSM-III-R criteria for alcohol dependence. AN - 75759551; 8501469 AB - A number of instruments have been developed to screen for alcoholism. With the advent of DSM-III and lay administered psychiatric diagnostic instruments, a test of the performance of these screens relative to diagnostic instruments is critical. In this paper, we document the relative effectiveness in a general medical clinic of the Michigan Alcoholism Screening Test (MAST), the Veterans Alcoholism Screening Test (VAST), and the CAGE questions in comparison to the DSM-III-R criteria for alcohol dependence as measured in the Composite International Diagnostic Interview (CIDI). All of the screens performed at acceptable levels, but the MAST and VAST tended to have higher performance characteristics. At the recommended cut points, they had higher sensitivity for lifetime alcohol dependence (VAST 95.1%, MAST 90.2%, CAGE 78.0%) as well as higher specificity (VAST 80.3%, MAST 81.7%, CAGE 76.1%). For present alcohol dependence only, at the recommended cut points the MAST and CAGE had sensitivity of 100% but specificity of 62.0 and 61.0% respectively. The VAST had sensitivity of 83.3% and specificity of 89.0%. We conclude that all three perform well relative to DSM-III-R criteria. JF - Journal of clinical epidemiology AU - Magruder-Habib, K AU - Stevens, H A AU - Alling, W C AD - National Institute of Mental Health, Rockville, MD 20857. Y1 - 1993/05// PY - 1993 DA - May 1993 SP - 435 EP - 441 VL - 46 IS - 5 SN - 0895-4356, 0895-4356 KW - Index Medicus KW - Sensitivity and Specificity KW - Psychiatric Status Rating Scales KW - Humans KW - Surveys and Questionnaires KW - Predictive Value of Tests KW - Middle Aged KW - Mass Screening -- methods KW - Male KW - Prevalence KW - Alcoholism -- diagnosis KW - Psychological Tests -- statistics & numerical data KW - Alcoholism -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75759551?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+epidemiology&rft.atitle=Relative+performance+of+the+MAST%2C+VAST%2C+and+CAGE+versus+DSM-III-R+criteria+for+alcohol+dependence.&rft.au=Magruder-Habib%2C+K%3BStevens%2C+H+A%3BAlling%2C+W+C&rft.aulast=Magruder-Habib&rft.aufirst=K&rft.date=1993-05-01&rft.volume=46&rft.issue=5&rft.spage=435&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+epidemiology&rft.issn=08954356&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-07-01 N1 - Date created - 1993-07-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hepatic stem cells. AN - 75745511; 8494039 JF - The American journal of pathology AU - Thorgeirsson, S S AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute. National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/05// PY - 1993 DA - May 1993 SP - 1331 EP - 1333 VL - 142 IS - 5 SN - 0002-9440, 0002-9440 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Humans KW - Cell Differentiation KW - Liver Neoplasms -- etiology KW - Cell Line KW - Liver -- cytology KW - Stem Cells -- cytology KW - Stem Cells -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75745511?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+of+pathology&rft.atitle=Hepatic+stem+cells.&rft.au=Thorgeirsson%2C+S+S&rft.aulast=Thorgeirsson&rft.aufirst=S&rft.date=1993-05-01&rft.volume=142&rft.issue=5&rft.spage=1331&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+pathology&rft.issn=00029440&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-06-14 N1 - Date created - 1993-06-14 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Biochem Cell Biol. 1986 Aug;64(8):788-802 [2429680] Lab Invest. 1985 Apr;52(4):354-62 [2858600] Cancer Res. 1985 Feb;45(2):673-81 [2578305] Cancer Res. 1984 Dec;44(12 Pt 1):5463-74 [6388826] Am J Pathol. 1983 Jan;110(1):70-4 [6185004] Cancer Res. 1984 Jan;44(1):332-8 [6690044] Exp Cell Res. 1984 Sep;154(1):38-52 [6468534] Ann N Y Acad Sci. 1980;349:165-82 [6784634] Ann N Y Acad Sci. 1980;349:138-52 [6939360] Carcinogenesis. 1987 Nov;8(11):1737-40 [3664968] In Vitro Cell Dev Biol. 1987 May;23(5):339-48 [3294781] Am J Pathol. 1987 Apr;127(1):168-81 [3031986] Gastroenterology. 1987 Dec;93(6):1414-9 [3315827] J Pathol Bacteriol. 1958 Oct;76(2):441-9 [13588479] Hepatology. 1992 Dec;16(6):1327-33 [1280243] Am J Physiol. 1992 Aug;263(2 Pt 1):G139-48 [1325126] Hepatology. 1991 Jul;14(1):144-9 [2066062] Proc Natl Acad Sci U S A. 1991 Feb 15;88(4):1217-21 [1899924] Lab Invest. 1990 Jul;63(1):4-20 [2197504] Pathobiology. 1990;58(2):65-77 [2193646] Cancer Res. 1988 Jan 15;48(2):368-78 [2446746] Mol Carcinog. 1988;1(3):189-95 [3074814] Prog Clin Biol Res. 1990;331:325-34 [2315345] Biochem Pharmacol. 1990 Jun 15;39(12):1837-46 [2191651] Cancer Res. 1990 Jul 1;50(13):3811-5 [1693878] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Induction of multidrug resistance gene expression during cholestasis in rats and nonhuman primates. AN - 75736053; 8098315 AB - P-glycoprotein, an energy-dependent plasma membrane drug-efflux pump capable of reducing the intracellular concentration of a variety of hydrophobic xenobiotics, is encoded by mdr1, a member of the multidrug-resistant (mdr) gene family. The physiological function of this protein is unknown. Because of its location on the bile canalicular domain of the hepatocyte, we and others have hypothesized that P-glycoprotein may have a physiological role as a biliary transporter of xenobiotics and endobiotics and that its expression may therefore be altered in cholestasis. Both obstructive and alpha-naphthylisothiocyanate-induced cholestasis increased mdr1a and 1b gene expression in rat liver. Hepatic P-glycoprotein levels were also increased, and the protein remained localized at the biliary hepatocyte domain. Induction of mdr1a and mdr1b gene expression in rat liver was accomplished by means of increased transcription. alpha-Naphthylisothiocyanate-induced cholestasis in cynomolgus monkeys increased hepatic expression of both the mdr1 and 2 genes. To investigate the possible role of P-glycoprotein as a biliary efflux transporter, biliary excretion of vinblastine, a representative substrate of P-glycoprotein, was studied in rats. Increased hepatic mdr messenger RNA and P-glycoprotein levels, mediated by the xenobiotic inducer 2-acetylaminofluorene, resulted in a significant increase in biliary excretion of vinblastine, which was antagonized by the P-glycoprotein inhibitor verapamil. These findings suggest that P-glycoprotein functions as a biliary efflux pump for xenobiotics and, possibly, for unidentified physiological inducers that may mediate increased transcription of the mdr gene observed during cholestasis. JF - Hepatology (Baltimore, Md.) AU - Schrenk, D AU - Gant, T W AU - Preisegger, K H AU - Silverman, J A AU - Marino, P A AU - Thorgeirsson, S S AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/05// PY - 1993 DA - May 1993 SP - 854 EP - 860 VL - 17 IS - 5 SN - 0270-9139, 0270-9139 KW - mdr KW - Carrier Proteins KW - 0 KW - Membrane Glycoproteins KW - P-Glycoprotein KW - Vinblastine KW - 5V9KLZ54CY KW - Index Medicus KW - Rats KW - Animals KW - Vinblastine -- metabolism KW - Rats, Inbred F344 KW - Blotting, Western KW - Macaca fascicularis KW - Blotting, Northern KW - Bile -- metabolism KW - Immunohistochemistry KW - Male KW - Female KW - Drug Resistance -- genetics KW - Membrane Glycoproteins -- physiology KW - Carrier Proteins -- genetics KW - Carrier Proteins -- physiology KW - Gene Expression Regulation KW - Cholestasis -- genetics KW - Membrane Glycoproteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75736053?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Induction+of+multidrug+resistance+gene+expression+during+cholestasis+in+rats+and+nonhuman+primates.&rft.au=Schrenk%2C+D%3BGant%2C+T+W%3BPreisegger%2C+K+H%3BSilverman%2C+J+A%3BMarino%2C+P+A%3BThorgeirsson%2C+S+S&rft.aulast=Schrenk&rft.aufirst=D&rft.date=1993-05-01&rft.volume=17&rft.issue=5&rft.spage=854&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 - 1993-06-15 N1 - Date created - 1993-06-15 N1 - Date revised - 2017-01-13 N1 - Gene symbol - mdr N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Comparison of lead bioavailability in F344 rats fed lead acetate, lead oxide, lead sulfide, or lead ore concentrate from Skagway, Alaska. AN - 75729992; 8492331 AB - An animal model using rats was developed to initiate investigations on the bioavailability of different sources of environmental lead. Lead must be absorbed and transported to target organs like brain, liver, kidney, and bone, before susceptible cells can be harmed. The bioavailability and therefore the toxicity of lead are dependent upon the route of exposure, dose, chemical structure, solubility, particle size, matrix incorporation, and other physiological and physicochemical factors. In the present study male F344 rats were fed < or = 38 microns size particles of lead sulfide, lead oxide, lead acetate, and a lead ore concentrate from Skagway, Alaska, mixed into the diet at doses of 0, 10, 30, and 100 ppm as lead for 30 d. No mortality or overt symptoms of lead toxicity were observed during the course of the study. Maximum blood lead concentrations attained in the 100 ppm groups were approximately 80 micrograms/dl in rats fed lead acetate and lead oxide, and were approximately 10 micrograms/dl in those fed lead sulfide and lead ore concentrate. Maximum bone lead levels in rats fed soluble lead oxide and lead acetate were much higher (approximately 200 micrograms/g) than those seen in rats fed the less soluble lead sulfide and lead ore (approximately 10 micrograms); kidney lead concentrations were also about 10-fold greater in rats fed the more soluble compared to the less soluble lead compounds. However, strong correlations between dose and tissue lead concentrations were observed in rats fed each of the four different lead compounds. Kidney lesions graded as minimal occurred in 7/10 rats fed 30 ppm and in 10/10 rats fed 100 ppm lead acetate, but not at lower doses or from other lead compounds. Similarly, urinary aminolevulinic acid excretion, a biomarker for lead toxicity, was increased in rats fed 100 ppm lead acetate or lead oxide, but was unaffected at lower doses or by the less soluble lead compounds. Although the histological and biochemical responses to lead toxicity were restricted to the more soluble lead compounds in this study, lead from Skagway lead ore concentrate and lead sulfide was also bioavailable, and accumulated in proportion to dose in vulnerable target organs such as bone and kidney. Longer-term studies with different mining materials are being conducted to determine if tissue lead continues to increase, and whether the levels attained are toxic. Data from such studies can be used to compare the toxicity and bioavailability of lead from different sources in the environment. JF - Journal of toxicology and environmental health AU - Dieter, M P AU - Matthews, H B AU - Jeffcoat, R A AU - Moseman, R F AD - National Institute of Environmental Health Sciences, Research Triangle Institute, NC 27709. Y1 - 1993/05// PY - 1993 DA - May 1993 SP - 79 EP - 93 VL - 39 IS - 1 SN - 0098-4108, 0098-4108 KW - Organometallic Compounds KW - 0 KW - Oxides KW - Sulfides KW - lead sulfide KW - 2425D15SYM KW - Lead KW - 2P299V784P KW - lead oxide KW - 4IN6FN8492 KW - lead acetate KW - RX077P88RY KW - Index Medicus KW - Rats KW - Administration, Oral KW - Animals KW - Rats, Inbred F344 KW - Kidney Tubules -- pathology KW - Bone and Bones -- chemistry KW - Kidney Tubules -- drug effects KW - Environmental Exposure KW - Intestinal Absorption KW - Alaska KW - Tissue Distribution KW - Male KW - Biological Availability KW - Oxides -- pharmacokinetics KW - Organometallic Compounds -- toxicity KW - Oxides -- toxicity KW - Lead -- blood KW - Organometallic Compounds -- pharmacokinetics KW - Sulfides -- pharmacokinetics KW - Lead -- toxicity KW - Oxides -- blood KW - Sulfides -- blood KW - Organometallic Compounds -- blood KW - Sulfides -- toxicity KW - Mining KW - Lead -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75729992?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+toxicology+and+environmental+health&rft.atitle=Comparison+of+lead+bioavailability+in+F344+rats+fed+lead+acetate%2C+lead+oxide%2C+lead+sulfide%2C+or+lead+ore+concentrate+from+Skagway%2C+Alaska.&rft.au=Dieter%2C+M+P%3BMatthews%2C+H+B%3BJeffcoat%2C+R+A%3BMoseman%2C+R+F&rft.aulast=Dieter&rft.aufirst=M&rft.date=1993-05-01&rft.volume=39&rft.issue=1&rft.spage=79&rft.isbn=&rft.btitle=&rft.title=Journal+of+toxicology+and+environmental+health&rft.issn=00984108&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-06-17 N1 - Date created - 1993-06-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Selective growth arrest and phenotypic reversion of prostate cancer cells in vitro by nontoxic pharmacological concentrations of phenylacetate. AN - 75723973; 8486788 AB - Differentiation therapy may provide an alternative for treatment of cancers that do not respond to cytotoxic chemotherapy or hormonal manipulations. This hypothesis led us to evaluate the effect of a nontoxic differentiation inducer, sodium phenylacetate (NaPA), on hormone-refractory prostate cancer, the second most common cause of cancer deaths in men. NaPA treatment of androgen-independent PC3 and DU145 prostate cell lines, like that of hormone-responsive LNCaP cultures, resulted in dose-dependent inhibition of cell proliferation. Similar treatments were not significantly inhibitory to replicating normal endothelial cells and skin fibroblasts. In addition to the selective cytostatic effect, NaPA induced reversion of the prostatic cells to a nonmalignant phenotype, evidenced by their reduced invasiveness and loss of tumorigenicity in athymic mice. Phenotypic reversion was accompanied by alterations in gene expression, including selective reduction in tumor growth factor-beta 2 mRNA levels and increased amounts of class I major histocompatibility complex HLA transcripts. Furthermore, there was a decrease in tumor-associated proteolysis mediated by urokinase plasminogen activator, a molecular marker of disease progression in humans. When tumor cells were treated with NaPA together with suramin, a drug with demonstrable activity in patients, there was complete abrogation of cell growth under conditions in which each treatment alone produced only a partial effect. The in vitro antineoplastic activity was observed with drug concentrations that have been achieved in humans with no significant toxicities, suggesting that PA, used alone or in combination with other antitumor agents, warrants evaluation in the treatment of advanced prostatic cancer. JF - The Journal of clinical investigation AU - Samid, D AU - Shack, S AU - Myers, C E AD - Clinical Pharmacology Branch, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1993/05// PY - 1993 DA - May 1993 SP - 2288 EP - 2295 VL - 91 IS - 5 SN - 0021-9738, 0021-9738 KW - HLA-A3 Antigen KW - 0 KW - Phenylacetates KW - RNA, Neoplasm KW - Transforming Growth Factor beta KW - Glutamine KW - 0RH81L854J KW - Suramin KW - 6032D45BEM KW - phenylacetic acid KW - ER5I1W795A KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - HLA-A3 Antigen -- genetics KW - Humans KW - Mice KW - Mice, Nude KW - RNA, Neoplasm -- genetics KW - Suramin -- pharmacology KW - DNA Replication -- drug effects KW - Phenotype KW - Neoplasm Transplantation KW - Glutamine -- pharmacology KW - RNA, Neoplasm -- isolation & purification KW - Tumor Cells, Cultured KW - Cell Survival -- drug effects KW - Neoplasm Invasiveness -- pathology KW - Transplantation, Heterologous KW - Transforming Growth Factor beta -- genetics KW - Female KW - Male KW - Prostatic Neoplasms -- pathology KW - Phenylacetates -- pharmacology KW - Cell Division -- drug effects KW - Prostatic Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75723973?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Selective+growth+arrest+and+phenotypic+reversion+of+prostate+cancer+cells+in+vitro+by+nontoxic+pharmacological+concentrations+of+phenylacetate.&rft.au=Samid%2C+D%3BShack%2C+S%3BMyers%2C+C+E&rft.aulast=Samid&rft.aufirst=D&rft.date=1993-05-01&rft.volume=91&rft.issue=5&rft.spage=2288&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 - 1993-06-04 N1 - Date created - 1993-06-04 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cancer Res. 1981 Apr;41(4):1324-8 [7214322] J Urol. 1989 Jul;142(1):193-8 [2659823] Br J Cancer. 1989 Sep;60(3):397-400 [2506920] Am Heart J. 1990 Sep;120(3):757-61; discussion 769-72 [2117846] Cancer Res. 1990 Nov 1;50(21):6827-9 [2119883] N Engl J Med. 1991 Jan 24;324(4):236-45 [1985245] J Urol. 1991 Feb;145(2):393-8 [1824865] Prog Clin Biol Res. 1990;359:155-64; discussion 177-80 [2284289] Cancer Res. 1991 May 1;51(9):2498-505 [2015610] Cancer Metastasis Rev. 1990 Dec;9(4):353-67 [2129023] In Vitro Cell Dev Biol. 1991 Apr;27A(4):327-36 [1856158] Cell Regul. 1991 Mar;2(3):241-9 [1859854] Semin Cancer Biol. 1990 Apr;1(2):117-26 [2151734] Cancer Commun. 1991 Aug;3(8):255-64 [1653586] Cancer Res. 1991 Sep 15;51(18):4948-54 [1654207] Cancer Res. 1991 Dec 15;51(24):6629-35 [1742736] Cancer Res. 1992 Apr 1;52(7):1988-92 [1372534] Cancer Res. 1992 Apr 15;52(8):2138-42 [1559217] J Neurosurg. 1992 May;76(5):799-804 [1373442] Leukemia. 1992;6 Suppl 2:24-7 [1349662] J Clin Oncol. 1992 Jun;10(6):881-9 [1375283] N Engl J Med. 1992 Aug 20;327(8):569-70 [1378939] Blood. 1992 Sep 15;80(6):1576-81 [1381630] Nature. 1970 Sep 12;227(5263):1136-7 [4915990] Proc R Soc Lond B Biol Sci. 1972 Jul 25;182(1066):25-35 [4403084] Can J Microbiol. 1972 Aug;18(8):1257-61 [5052893] J Bacteriol. 1976 Oct;128(1):182-91 [10273] Int J Cancer. 1978 Mar 15;21(3):274-81 [631930] Natl Cancer Inst Monogr. 1978 Dec;(49):17-21 [571045] Cancer Treat Rep. 1981;65 Suppl 4:61-5 [7346158] Arch Biochem Biophys. 1983 Apr 1;222(1):259-65 [6838224] Cancer Res. 1983 Aug;43(8):3466-92 [6305486] Cancer Metastasis Rev. 1983;2(1):5-23 [6616442] Cancer Res. 1984 Jan;44(1):311-8 [6197164] Cancer Treat Rep. 1984 Jan;68(1):199-205 [6692427] N Engl J Med. 1984 Jun 21;310(25):1630-4 [6427608] J Immunol. 1985 Oct;135(4):2835-41 [2993417] Invasion Metastasis. 1985;5(6):344-55 [4066206] Proc Natl Acad Sci U S A. 1986 Jun;83(12):4167-71 [2424019] Pediatr Res. 1986 Nov;20(11):1117-21 [3099249] Pharmacol Ther. 1985;30(3):277-86 [2433702] Cancer Res. 1987 Jun 15;47(12):3239-45 [2438036] Mol Cell Biol. 1987 Jun;7(6):2196-200 [2439904] Cancer Res. 1988 Jan 15;48(2):291-6 [3121170] Proc Natl Acad Sci U S A. 1988 Jan;85(1):79-82 [3277172] Biochem Int. 1988 Feb;16(2):339-47 [3365266] J Biol Chem. 1988 Sep 15;263(26):12805-8 [2843499] J Urol. 1988 Dec;140(6):1466-9 [3193516] Eur Urol. 1988;15(3-4):256-8 [3145889] Prog Clin Biol Res. 1980;37:115-32 [7384082] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transmission-blocking activity of a chitinase inhibitor and activation of malarial parasite chitinase by mosquito protease. AN - 75719941; 8483942 AB - During development in the mosquito midgut, malarial parasites must traverse a chitin-containing peritrophic matrix (PM) that forms around the food bolus. Previously Huber et al. [Huber, M., Cabib, E. & Miller, L. H. (1991) Proc. Natl. Acad. Sci. USA 88, 2807-2810] reported that the parasite secretes a protein with chitinase activity, and they suggested that parasite chitinase (EC 3.2.1.14) plays an important role in the parasite's egress from the blood meal. We found that allosamidin, a specific inhibitor of chitinase, completely blocked oocyst development in vivo and thus blocked malaria parasite transmission. Addition of exogenous chitinase to the blood meal prevented the PM from forming and reversed the transmission-blocking activity of allosamidin. Using exogenous chitinase, we also found that the PM does not limit the number of parasites that develop into oocysts, suggesting that the parasite produces sufficient quantities of chitinase to penetrate this potential barrier. In addition, we found that treatment of parasite chitinase with a diisopropyl fluorophosphate-sensitive trypsinlike protease from the mosquito midgut or endoproteinase Lys-C increased its enzymatic activity. These results suggest that malaria parasite has evolved an intricate mechanism to adapt to the PM and the protease-rich environment of the mosquito midgut. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Shahabuddin, M AU - Toyoshima, T AU - Aikawa, M AU - Kaslow, D C AD - Molecular Vaccine Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/05/01/ PY - 1993 DA - 1993 May 01 SP - 4266 EP - 4270 VL - 90 IS - 9 SN - 0027-8424, 0027-8424 KW - Insecticides KW - 0 KW - Trisaccharides KW - allosamidin KW - 103782-08-7 KW - Chitinases KW - EC 3.2.1.14 KW - Endopeptidases KW - EC 3.4.- KW - Acetylglucosamine KW - V956696549 KW - Index Medicus KW - Animals KW - Chickens KW - Enzyme Activation KW - Kinetics KW - Streptomyces griseus -- enzymology KW - Aedes -- physiology KW - Trisaccharides -- pharmacology KW - Aedes -- drug effects KW - Plasmodium gallinaceum -- physiology KW - Acetylglucosamine -- pharmacology KW - Anopheles -- enzymology KW - Plasmodium gallinaceum -- enzymology KW - Endopeptidases -- metabolism KW - Aedes -- enzymology KW - Chitinases -- metabolism KW - Plasmodium gallinaceum -- drug effects KW - Insecticides -- pharmacology KW - Plasmodium falciparum -- drug effects KW - Plasmodium falciparum -- physiology KW - Acetylglucosamine -- analogs & derivatives KW - Chitinases -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75719941?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Transmission-blocking+activity+of+a+chitinase+inhibitor+and+activation+of+malarial+parasite+chitinase+by+mosquito+protease.&rft.au=Shahabuddin%2C+M%3BToyoshima%2C+T%3BAikawa%2C+M%3BKaslow%2C+D+C&rft.aulast=Shahabuddin&rft.aufirst=M&rft.date=1993-05-01&rft.volume=90&rft.issue=9&rft.spage=4266&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 - 1993-06-01 N1 - Date created - 1993-06-01 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Annu Rev Entomol. 1977;22:219-40 [319739] Nature. 1981 Nov 26;294(5839):364-6 [7031476] J Immunol. 1983 Nov;131(5):2557-62 [6631012] Cell Tissue Res. 1986;245(1):19-27 [3524850] J Parasitol. 1986 Oct;72(5):723-7 [3806321] Acta Trop. 1965;22:148-54 [14319772] Biochim Biophys Acta. 1991 Jan 23;1073(1):177-82 [1991132] Exp Parasitol. 1991 Feb;72(2):145-56 [2009919] Proc Natl Acad Sci U S A. 1991 Apr 1;88(7):2807-10 [2011589] Proc Biol Sci. 1991 Aug 22;245(1313):121-6 [1682935] Science. 1992 Jan 24;255(5043):448-50 [1734521] Mol Biochem Parasitol. 1988 Jun;29(2-3):223-5 [3412376] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The spatial distribution of immunotoxins in solid tumors: assessment by quantitative autoradiography. AN - 75718914; 8481911 AB - The spatial distribution of i.v. administered immunotoxins in s.c. human rhabdomyosarcoma RD2 xenografts was studied. The toxin and immunotoxins were: (a) diphtheria toxin (DT); (b) a binding-deficient form of DT (CRM107) linked to a monoclonal IgG1 antibody (454A12) directed against the human transferrin receptor (454A12-107); (c) the binding-deficient form of DT linked to the Fab' fragment of 454A12 (Fab'-107); and (d) the binding-deficient form of DT coupled to MOPC21, a monoclonal IgG1 with no significant binding to RD2 cells. DT and the immunotoxins were radiolabeled with 125I and injected via the tail vein into tumor-bearing athymic mice (median tumor weight, 0.25 g). Tumors were removed 2, 6, and 24 h after injection of DT or immunotoxin. Film images of 20-microns frozen sections were digitized by video microscopy, and gray levels were converted to tissue concentrations based upon the film response to radioactivity standards and the specific activity of the radiolabeled toxins. Images of the tumors were characterized quantitatively by the kurtosis and the area above threshold; the kurtosis is a measure of the spatial heterogeneity of the radiolabeled immunotoxins, and the area above threshold is defined here as the fractional tumor area that reaches or exceeds 1.5% of the initial plasma concentration. The spatial distribution of DT in the tumors was extremely uniform, characterized by low kurtosis values. In contrast, the autoradiograms of 454A12-107 were punctate in appearance and were characterized by very high kurtosis values. Fab'-107, which has approximately one-half the molecular weight of the intact immunotoxin and binds only monovalently, also produced punctate images with kurtosis values similar to those for 454A12-107. The nonbinding immunotoxin distributed somewhat less uniformly than DT but much more homogeneously than either of the binding immunotoxins. DT, 454A12-107, and Fab'-107 have similar affinities for their respective receptors, but the concentration of binding sites for DT on RD2 cells (<3,000 receptors/cell) is much lower than the concentration of transferrin receptor (60,000 receptors/cell). Thus, the heterogeneous distribution of 454A12-107 and Fab'-107 probably reflects retarded penetration due to binding to the tumor cells. The area above threshold was greatest for DT and lowest for 454A12-107; the fragment and nonbinding immunotoxins had intermediate values. The lower area above threshold for the nonbinding immunotoxin as compared with DT may be due to the considerably large molecular weight and hence the lower capillary permeability and diffusion coefficient of the immunotoxin.(ABSTRACT TRUNCATED AT 400 WORDS) JF - Cancer research AU - Sung, C AU - Dedrick, R L AU - Hall, W A AU - Johnson, P A AU - Youle, R J AD - Biomedical Engineering and Instrumentation Program, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, Maryland 20892. Y1 - 1993/05/01/ PY - 1993 DA - 1993 May 01 SP - 2092 EP - 2099 VL - 53 IS - 9 SN - 0008-5472, 0008-5472 KW - Diphtheria Toxin KW - 0 KW - Immunotoxins KW - Index Medicus KW - Animals KW - Tumor Cells, Cultured KW - Humans KW - In Vitro Techniques KW - Diphtheria Toxin -- metabolism KW - Mice, Nude KW - Mice KW - Tissue Distribution KW - Female KW - Sarcoma, Experimental -- metabolism KW - Immunotoxins -- metabolism KW - Autoradiography -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75718914?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+spatial+distribution+of+immunotoxins+in+solid+tumors%3A+assessment+by+quantitative+autoradiography.&rft.au=Sung%2C+C%3BDedrick%2C+R+L%3BHall%2C+W+A%3BJohnson%2C+P+A%3BYoule%2C+R+J&rft.aulast=Sung&rft.aufirst=C&rft.date=1993-05-01&rft.volume=53&rft.issue=9&rft.spage=2092&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 - 1993-06-01 N1 - Date created - 1993-06-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Differences in the antibody response to human immunodeficiency virus-1 envelope glycoprotein (gp160) in infected laboratory workers and vaccinees. AN - 75716764; 7683694 AB - Studies of the immune response to the human immunodeficiency virus (HIV) have been hampered by the antigenic diversity of the HIV envelope protein. In an effort to predict the efficacy of vaccination we have compared the systemic anti-envelope antibody response in seronegative volunteers immunized with recombinant gp160 (either in vaccinia or as soluble protein produced in baculovirus) derived from the HTLV-IIIB strain of HIV-1 and in two laboratory workers accidentally infected with the same strain. 11 of 14 vaccinees responded to immunization by producing anti-gp160 of similar titer and the same isotype as that seen in the laboratory workers. Four vaccinees also had antibody to the principal neutralizing domain (V3 loop) that was comparable in titer with that seen in the laboratory workers, but the fine specificity of anti-V3 antibody was qualitatively different in the two groups. Antibody that can block the interaction between CD4 and gp120 was present at comparable levels in three vaccines and the lab workers. Neutralizing antibody titers were markedly lower in the vaccinees than in the laboratory workers. In seven of the vaccinees, an immunodominant epitope was at amino acid 720-740. Analyses of monoclonal antibodies to this region indicate that they do not neutralize, bind to infected cells, nor function as immunotoxins. Although the anti-gp160 antibody response was of similar magnitude in both infected and vaccinated individuals, there were important qualitative differences. JF - The Journal of clinical investigation AU - Pincus, S H AU - Messer, K G AU - Schwartz, D H AU - Lewis, G K AU - Graham, B S AU - Blattner, W A AU - Fisher, G AD - Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840. Y1 - 1993/05// PY - 1993 DA - May 1993 SP - 1987 EP - 1996 VL - 91 IS - 5 SN - 0021-9738, 0021-9738 KW - AIDS Vaccines KW - 0 KW - Antibodies, Monoclonal KW - Antibodies, Viral KW - Antigens, CD4 KW - Epitopes KW - Gene Products, env KW - HIV Envelope Protein gp120 KW - HIV Envelope Protein gp160 KW - Immunoglobulin G KW - Peptides KW - Protein Precursors KW - Vaccines, Synthetic KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Reference Values KW - Antibodies, Monoclonal -- metabolism KW - Humans KW - Peptides -- immunology KW - Amino Acid Sequence KW - HIV Envelope Protein gp120 -- metabolism KW - Immunoglobulin G -- immunology KW - Antigens, CD4 -- metabolism KW - Antibodies, Viral -- blood KW - Immunoglobulin G -- blood KW - Epitopes -- analysis KW - Neutralization Tests KW - Molecular Sequence Data KW - Enzyme-Linked Immunosorbent Assay KW - Cell Line KW - HIV-1 -- immunology KW - Protein Precursors -- immunology KW - AIDS Vaccines -- immunology KW - Vaccines, Synthetic -- immunology KW - Protein Precursors -- genetics KW - Medical Laboratory Personnel KW - Gene Products, env -- immunology KW - Antibody Formation KW - HIV Seropositivity -- immunology KW - HIV Seropositivity -- blood KW - Gene Products, env -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75716764?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Differences+in+the+antibody+response+to+human+immunodeficiency+virus-1+envelope+glycoprotein+%28gp160%29+in+infected+laboratory+workers+and+vaccinees.&rft.au=Pincus%2C+S+H%3BMesser%2C+K+G%3BSchwartz%2C+D+H%3BLewis%2C+G+K%3BGraham%2C+B+S%3BBlattner%2C+W+A%3BFisher%2C+G&rft.aulast=Pincus&rft.aufirst=S&rft.date=1993-05-01&rft.volume=91&rft.issue=5&rft.spage=1987&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 - 1993-06-04 N1 - Date created - 1993-06-04 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1989 Sep;86(17):6768-72 [2771954] Science. 1988 Jan 1;239(4835):68-71 [3336776] Science. 1988 Feb 26;239(4843):1021-3 [2830667] Proc Natl Acad Sci U S A. 1988 Mar;85(6):1932-6 [2450351] Proc Natl Acad Sci U S A. 1988 May;85(9):3198-202 [2452447] Virology. 1988 Jul;165(1):209-15 [2838959] Proc Natl Acad Sci U S A. 1988 Jul;85(14):5200-4 [2455898] Proc Natl Acad Sci U S A. 1988 Sep;85(18):6944-8 [3413127] J Virol. 1988 Oct;62(10):3779-88 [3047430] Nature. 1989 Jun 1;339(6223):385-8, 340 [2542797] Nature. 1989 Aug 10;340(6233):431-2 [2787895] J Virol. 1989 Sep;63(9):3579-85 [2474670] Ann Intern Med. 1991 Jan 15;114(2):119-27 [1984386] Proc Natl Acad Sci U S A. 1991 Jan 15;88(2):542-6 [1988952] Science. 1990 Dec 14;250(4987):1590-3 [1703322] Lancet. 1991 Mar 9;337(8741):567-72 [1671940] N Engl J Med. 1991 Jun 13;324(24):1677-84 [1674589] N Engl J Med. 1991 Jun 13;324(24):1733-5 [2034251] J Immunol. 1991 Jun 15;146(12):4315-24 [1710247] J Immunol. 1991 Jun 15;146(12):4325-32 [1710248] Science. 1991 Jul 5;253(5015):71-4 [1905842] Biotechniques. 1991 Mar;10(3):336-42 [2064772] J Virol. 1991 Sep;65(9):4832-8 [1714520] Immunol Today. 1991 Jul;12(7):211-3 [1716107] J Virol. 1991 Nov;65(11):5983-90 [1717712] Science. 1991 Oct 4;254(5028):105-8 [1718036] Science. 1991 Nov 1;254(5032):647 [1948042] Proc Natl Acad Sci U S A. 1992 Jan 15;89(2):461-5 [1370580] Nature. 1992 Feb 20;355(6362):728-30 [1741059] Science. 1992 Jun 19;256(5064):1687-90 [1609280] J Infect Dis. 1992 Aug;166(2):244-52 [1353102] Immunol Rev. 1980;49:79-91 [6154642] Science. 1986 Mar 28;231(4745):1556-9 [3006246] J Virol. 1986 Aug;59(2):284-91 [3016298] EMBO J. 1986 Nov;5(11):3065-71 [3466790] J Clin Microbiol. 1987 May;25(5):845-8 [2438302] Cell. 1987 Sep 11;50(6):975-85 [2441877] J Immunol Methods. 1987 Sep 24;102(2):259-74 [2443575] Nature. 1990 Jun 14;345(6276):622-5 [2190095] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Radiation-associated lung cancer: a comparison of the histology of lung cancers in uranium miners and survivors of the atomic bombings of Hiroshima and Nagasaki. AN - 75716335; 8387679 AB - A binational panel of Japanese and American pulmonary pathologists reviewed tissue slides of lung cancer cases diagnosed among Japanese A-bomb survivors and American uranium miners and classified the cases according to histological subtype. Blind reviews were completed on slides from 92 uranium miners and 108 A-bomb survivors, without knowledge of population, sex, age, smoking history, or level of radiation exposure. Consensus diagnoses were obtained with respect to principal subtype, including squamous-cell cancer, small-cell cancer, adenocarcinoma, and less frequent subtypes. The results were analyzed in terms of population, radiation dose, and smoking history. As expected, the proportion of squamous-cell cancer was positively related to smoking history in both populations. The relative frequencies of small-cell cancer and adenocarcinoma were very different in the two populations, but this difference was accounted for adequately by differences in radiation dose or, more specifically, dose-based relative risk estimates based on published data. Radiation-induced cancers appeared more likely to be of the small-cell subtype, and less likely to be adenocarcinomas, in both populations. The data appeared to require no additional explanation in terms of radiation quality (alpha particles vs gamma rays), uniform or local irradiation, inhaled vs external radiation source, or other population difference. JF - Radiation research AU - Land, C E AU - Shimosato, Y AU - Saccomanno, G AU - Tokuoka, S AU - Auerbach, O AU - Tateishi, R AU - Greenberg, S D AU - Nambu, S AU - Carter, D AU - Akiba, S AD - National Cancer Institute, Bethesda, Maryland. Y1 - 1993/05// PY - 1993 DA - May 1993 SP - 234 EP - 243 VL - 134 IS - 2 SN - 0033-7587, 0033-7587 KW - Uranium KW - 4OC371KSTK KW - Index Medicus KW - Space life sciences KW - Carcinoma, Squamous Cell -- etiology KW - Carcinoma, Small Cell -- etiology KW - Carcinoma, Squamous Cell -- epidemiology KW - Carcinoma, Small Cell -- epidemiology KW - Humans KW - Aged KW - Japan -- epidemiology KW - Smoking KW - Adenocarcinoma -- epidemiology KW - Adenocarcinoma -- etiology KW - Middle Aged KW - United States -- epidemiology KW - Female KW - Male KW - Occupational Exposure KW - Lung Neoplasms -- etiology KW - Lung Neoplasms -- epidemiology KW - Neoplasms, Radiation-Induced -- etiology KW - Neoplasms, Radiation-Induced -- pathology KW - Nuclear Warfare KW - Neoplasms, Radiation-Induced -- epidemiology KW - Mining KW - Lung Neoplasms -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75716335?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Radiation-associated+lung+cancer%3A+a+comparison+of+the+histology+of+lung+cancers+in+uranium+miners+and+survivors+of+the+atomic+bombings+of+Hiroshima+and+Nagasaki.&rft.au=Land%2C+C+E%3BShimosato%2C+Y%3BSaccomanno%2C+G%3BTokuoka%2C+S%3BAuerbach%2C+O%3BTateishi%2C+R%3BGreenberg%2C+S+D%3BNambu%2C+S%3BCarter%2C+D%3BAkiba%2C+S&rft.aulast=Land&rft.aufirst=C&rft.date=1993-05-01&rft.volume=134&rft.issue=2&rft.spage=234&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 - 1993-06-10 N1 - Date created - 1993-06-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Recombination sequence-binding protein in thymocytes undergoing T-cell receptor gene rearrangement. AN - 75710347; 8483928 AB - Rearrangement of T-cell antigen receptor and immunoglobulin genes occurs in immature lymphoid cells by an unknown mechanism. To identify components of the rearrangement machinery, we isolated a population of murine thymocytes enriched for rearranging pre-T cells. In the nuclear fraction of these cells, we detected a protein that specifically bound the recombination sequences that flank T-cell receptor and immunoglobulin genes and are required for their rearrangement. This protein recognized both heptamer and nonamer motifs of the recombination sequence, separated by either 12 or 23 bp. The protein complexed with the recombination sequence oligonucleotide had an apparent molecular mass of 30 kDa. The binding characteristics of the protein and its presence in rearranging thymocytes and cell lines suggest that it could serve as the recognition unit of a recombinase complex. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Muegge, K AU - West, M AU - Durum, S K AD - Biological Carcinogenesis and Development Program, Program Resources, Inc.,/Dyncorp, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702-1201. Y1 - 1993/05/01/ PY - 1993 DA - 1993 May 01 SP - 4151 EP - 4155 VL - 90 IS - 9 SN - 0027-8424, 0027-8424 KW - DNA-Binding Proteins KW - 0 KW - Nuclear Proteins KW - Oligodeoxyribonucleotides KW - Receptors, Antigen, T-Cell, alpha-beta KW - Index Medicus KW - Animals KW - Nuclear Proteins -- isolation & purification KW - Cell Nucleus -- metabolism KW - Thymus Gland -- metabolism KW - Mice KW - Thymus Gland -- immunology KW - Mice, Inbred Strains KW - Base Sequence KW - T-Lymphocyte Subsets -- immunology KW - Mice, Inbred C57BL KW - Molecular Sequence Data KW - Substrate Specificity KW - Cell Line, Transformed KW - DNA-Binding Proteins -- isolation & purification KW - Nuclear Proteins -- metabolism KW - Time Factors KW - Radiation Chimera KW - DNA-Binding Proteins -- metabolism KW - Gene Rearrangement, T-Lymphocyte -- radiation effects KW - Recombination, Genetic KW - T-Lymphocytes -- radiation effects KW - Receptors, Antigen, T-Cell, alpha-beta -- genetics KW - T-Lymphocytes -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75710347?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Recombination+sequence-binding+protein+in+thymocytes+undergoing+T-cell+receptor+gene+rearrangement.&rft.au=Muegge%2C+K%3BWest%2C+M%3BDurum%2C+S+K&rft.aulast=Muegge&rft.aufirst=K&rft.date=1993-05-01&rft.volume=90&rft.issue=9&rft.spage=4151&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 - 1993-06-01 N1 - Date created - 1993-06-01 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Genes Dev. 1989 Jul;3(7):1053-61 [2777075] Genes Dev. 1987 Oct;1(8):751-61 [3428598] Cell. 1989 Nov 17;59(4):585-8 [2684413] Nature. 1989 Dec 21-28;342(6252):934-7 [2556644] Genes Dev. 1989 Nov;3(11):1801-13 [2606349] Science. 1990 Jun 22;248(4962):1517-23 [2360047] Cancer Cells. 1990 Jan;2(1):1-8 [2201335] J Immunogenet. 1990 Feb-Apr;17(1-2):67-75 [2212701] Nature. 1990 Oct 4;347(6292):479-82 [2215662] Annu Rev Immunol. 1991;9:323-50 [1910681] EMBO J. 1991 Oct;10(10):3025-32 [1915277] J Biol Chem. 1991 Dec 5;266(34):23334-40 [1744127] Eur J Immunol. 1992 Feb;22(2):505-10 [1537384] Cell. 1992 Mar 6;68(5):855-67 [1547487] Cell. 1992 Mar 6;68(5):869-77 [1547488] Cell. 1992 May 1;69(3):529-37 [1316241] Cell. 1984 Feb;36(2):357-69 [6537904] Proc Natl Acad Sci U S A. 1987 Oct;84(20):7019-23 [3118358] Science. 1987 Nov 20;238(4830):1134-8 [3120312] Science. 1989 Oct 13;246(4927):249-51 [2799385] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The N-methyl-D-aspartate antagonist MK-801 fails to protect dopaminergic neurons from 1-methyl-4-phenylpyridinium toxicity in vitro. AN - 75684862; 8473912 AB - Recent reports suggest that NMDA receptor antagonists when administered in vivo can protect dopaminergic neurons from the toxic actions of MPP+. In the present study the possible neuro-protective effects against MPP+ toxicity of the noncompetitive NMDA receptor antagonist MK-801 was studied in primary cultures of fetal rat mesencephalic dopamine neurons. MK-801 failed to protect dopaminergic neurons from MPP+ toxicity at concentrations that completely block NMDA-induced toxicity of these same neurons. In contrast to work carried out in cerebellar granule cells, MPP+ toxicity of mesencephalic dopamine neurons was unaffected by preexposure to subtoxic concentrations of either NMDA or cycloheximide. Our findings suggest that the toxic effects of MPP+ on dopaminergic neurons are not mediated through a direct interaction with the NMDA subtype of glutamate receptor. JF - Journal of neurochemistry AU - Finiels-Marlier, F AU - Marini, A M AU - Williams, P AU - Paul, S M AD - Section on Molecular Pharmacology, National Institute of Mental Health, Bethesda, Maryland 20892. Y1 - 1993/05// PY - 1993 DA - May 1993 SP - 1968 EP - 1971 VL - 60 IS - 5 SN - 0022-3042, 0022-3042 KW - N-Methylaspartate KW - 6384-92-5 KW - Dizocilpine Maleate KW - 6LR8C1B66Q KW - Cycloheximide KW - 98600C0908 KW - 1-Methyl-4-phenylpyridinium KW - R865A5OY8J KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Mesencephalon -- drug effects KW - Animals KW - Cells, Cultured KW - Cycloheximide -- pharmacology KW - Mesencephalon -- cytology KW - Neurons -- metabolism KW - N-Methylaspartate -- pharmacology KW - Neurons -- drug effects KW - N-Methylaspartate -- antagonists & inhibitors KW - Dopamine -- metabolism KW - Dizocilpine Maleate -- pharmacology KW - 1-Methyl-4-phenylpyridinium -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75684862?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+N-methyl-D-aspartate+antagonist+MK-801+fails+to+protect+dopaminergic+neurons+from+1-methyl-4-phenylpyridinium+toxicity+in+vitro.&rft.au=Finiels-Marlier%2C+F%3BMarini%2C+A+M%3BWilliams%2C+P%3BPaul%2C+S+M&rft.aulast=Finiels-Marlier&rft.aufirst=F&rft.date=1993-05-01&rft.volume=60&rft.issue=5&rft.spage=1968&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 - 1993-05-18 N1 - Date created - 1993-05-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Functional and molecular characterization of tumor-infiltrating lymphocytes transduced with tumor necrosis factor-alpha cDNA for the gene therapy of cancer in humans. AN - 75675601; 8473752 AB - TNF is effective in causing the regression of selected murine tumors when administered at high concentrations. Therapeutic levels in humans cannot be obtained systemically, however, because of dose-limiting toxicity. The development of immunotherapy with IL-2 and tumor-infiltrating lymphocytes (TIL), which can accumulate at tumor sites in some patients, and of efficient retroviral techniques for gene transfer into eukaryotic cells has allowed new therapeutic approaches using TNF. We have retrovirally transduced human TIL with the gene for TNF in an attempt to deliver high concentrations of TNF to the tumor site without dose-limiting systemic toxicity. Successful gene insertion was confirmed by Southern hybridization in 16 of 16 transduced and selected TIL cultures from 15 different patients, with an estimated 28 to 93% transduced cells within each culture. Transduced selected TIL cultures produced greater amounts of TNF, compared with nontransduced controls, in 11 of 16 cultures evaluated. However, overall production of TNF was > 30-fold lower, compared with a transduced and highly selected tumor cell line control (MEL-TNF). In addition, steady state levels of vector-derived transcript in nine of 10 transduced selected TIL cultures were < 14% of the amount seen in the MEL-TNF control line. In an attempt to increase TNF production, TIL were transduced with a mutated form of TNF containing the IFN-gamma signal peptide in place of the transmembranous region, to enhance secretion into the endoplasmic reticulum. By using this vector, TNF production increased by an average of fivefold. These studies demonstrate that TIL can be genetically modified to express and secrete a protein for use in targeted cancer therapy but that partial expression blockades exist that prevent maximal cytokine production by introduced genes in TIL. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Hwu, P AU - Yannelli, J AU - Kriegler, M AU - Anderson, W F AU - Perez, C AU - Chiang, Y AU - Schwarz, S AU - Cowherd, R AU - Delgado, C AU - Mulé, J AD - Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/05/01/ PY - 1993 DA - 1993 May 01 SP - 4104 EP - 4115 VL - 150 IS - 9 SN - 0022-1767, 0022-1767 KW - Tumor Necrosis Factor-alpha KW - 0 KW - DNA KW - 9007-49-2 KW - Abridged Index Medicus KW - Index Medicus KW - Tumor Cells, Cultured KW - Humans KW - Genetic Vectors KW - Transcription, Genetic KW - Repetitive Sequences, Nucleic Acid KW - Lymphocytes, Tumor-Infiltrating -- physiology KW - Transfection KW - DNA -- genetics KW - Tumor Necrosis Factor-alpha -- biosynthesis KW - Genetic Therapy KW - Neoplasms -- therapy KW - Tumor Necrosis Factor-alpha -- genetics KW - Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75675601?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Functional+and+molecular+characterization+of+tumor-infiltrating+lymphocytes+transduced+with+tumor+necrosis+factor-alpha+cDNA+for+the+gene+therapy+of+cancer+in+humans.&rft.au=Hwu%2C+P%3BYannelli%2C+J%3BKriegler%2C+M%3BAnderson%2C+W+F%3BPerez%2C+C%3BChiang%2C+Y%3BSchwarz%2C+S%3BCowherd%2C+R%3BDelgado%2C+C%3BMul%C3%A9%2C+J&rft.aulast=Hwu&rft.aufirst=P&rft.date=1993-05-01&rft.volume=150&rft.issue=9&rft.spage=4104&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 - 1993-05-20 N1 - Date created - 1993-05-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The RRE of human immunodeficiency virus type 1 contributes to cell-type-specific viral tropism. AN - 75675510; 8474177 AB - As part of a general program investigating the mechanism of the Rev axis of human immunodeficiency virus type 1 (HIV-1) autoregulation, a series of proviral HIV-1 mutants which differ from the parental HXB2 strain at selected positions within the RRE were constructed. All of the mutations were designed to perturb the RRE by introducing local helix disruptions without altering the coding potential of the overlapping envelope open reading frame. Viral replication in various cell types was monitored by a cell supernatant reverse transcriptase assay and Northern (RNA blot) analysis. All proviral RRE mutants displayed at least some impairment in replication. However, the relative impairment varied drastically among the various cell types tested. This suggests that the RRE may contribute to cell-type-specific viral tropism. JF - Journal of virology AU - Dayton, E T AU - Konings, D A AU - Lim, S Y AU - Hsu, R K AU - Butini, L AU - Pantaleo, G AU - Dayton, A I AD - National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892. Y1 - 1993/05// PY - 1993 DA - May 1993 SP - 2871 EP - 2878 VL - 67 IS - 5 SN - 0022-538X, 0022-538X KW - Gene Products, rev KW - 0 KW - RNA, Viral KW - rev Gene Products, Human Immunodeficiency Virus KW - Index Medicus KW - AIDS/HIV KW - Virus Replication KW - Lymphocyte Activation KW - Base Sequence KW - Gene Products, rev -- metabolism KW - Sequence Alignment KW - Molecular Sequence Data KW - Databases, Factual KW - Cell Line -- microbiology KW - Virion -- isolation & purification KW - Nucleic Acid Conformation KW - Mutagenesis KW - HIV-1 -- genetics KW - HIV-1 -- pathogenicity KW - Proviruses -- genetics KW - HIV-1 -- growth & development KW - RNA, Viral -- genetics KW - Proviruses -- pathogenicity KW - Acquired Immunodeficiency Syndrome -- microbiology KW - Proviruses -- growth & development UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75675510?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&rft.genre=dissertations+%26+theses&rft.jtitle=&rft.atitle=&rft.au=Gratien%2C+Christopher&rft.aulast=Gratien&rft.aufirst=Christopher&rft.date=2015-01-01&rft.volume=&rft.issue=&rft.spage=&rft.isbn=9781339057934&rft.btitle=&rft.title=The+mountains+are+ours+Ecology+and+settlement+in+late+Ottoman+and+early+Republican+Cilicia%2C+1856-1956&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-05-17 N1 - Date created - 1993-05-17 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nature. 1984 Dec 20-1985 Jan 2;312(5996):763-7 [6096719] J Virol. 1992 Apr;66(4):2588-93 [1548785] Proc Natl Acad Sci U S A. 1985 Jul;82(13):4539-43 [2989831] J Immunol. 1985 Nov;135(5):3151-62 [2995487] Science. 1986 Mar 28;231(4745):1549-53 [3006244] Cell. 1986 Mar 28;44(6):941-7 [2420471] Nature. 1987 Aug 20-26;328(6132):728-30 [2441266] Science. 1987 Aug 21;237(4817):888-93 [3497453] Nature. 1989 Mar 16;338(6212):254-7 [2784194] Science. 1989 Apr 7;244(4900):48-52 [2468181] Science. 1989 Dec 22;246(4937):1625-9 [2688093] Nucleic Acids Res. 1990 Mar 25;18(6):1613-23 [2326200] J Immunol. 1990 Jun 15;144(12):4628-32 [1972163] J Virol. 1990 Sep;64(9):4390-8 [2384920] Nature. 1990 Nov 1;348(6296):69-73 [2172833] J Virol. 1990 Dec;64(12):5966-75 [2243382] EMBO J. 1990 Dec;9(12):4155-60 [2249669] Nature. 1991 Jan 10;349(6305):167-9 [1986308] J Virol. 1991 Feb;65(2):1041-5 [1987367] J Virol. 1991 Mar;65(3):1414-9 [1995951] J Exp Med. 1991 Mar 1;173(3):589-97 [1705278] Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3097-101 [2014229] Biochim Biophys Acta. 1991 Apr 16;1072(1):63-80 [2018779] Genes Dev. 1991 May;5(5):808-19 [1827422] Cell. 1991 May 17;65(4):651-62 [2032289] Science. 1991 Jul 5;253(5015):71-4 [1905842] J Virol. 1991 Aug;65(8):4350-8 [2072454] J Virol. 1991 Nov;65(11):5765-73 [1920615] J Virol. 1991 Dec;65(12):6931-41 [1658383] Annu Rev Microbiol. 1991;45:219-50 [1741615] J Virol. 1992 Feb;66(2):1139-51 [1731093] J Virol. 1992 Apr;66(4):2577-82 [1548783] Nature. 1984 Dec 20-1985 Jan 2;312(5996):767-8 [6083454] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Picolinic acid, a catabolite of L-tryptophan, is a costimulus for the induction of reactive nitrogen intermediate production in murine macrophages. AN - 75666806; 8473748 AB - In this study we investigated the effects of picolinic acid, a catabolite of L-tryptophan, on the production of L-arginine-derived reactive nitrogen intermediates in the murine macrophage cell line ANA-1. ANA-1 macrophages did not produce nitrite (NO2-) constitutively, but accumulated detectable levels of NO2- on exposure to IFN-gamma. Picolinic acid, although ineffective by itself, augmented IFN-gamma-induced NO2- production. The activity of picolinic acid was evident at 1 mM and reached its maximum at 4 mM. Picolinic acid also augmented the IFN-gamma-dependent expression of TNF-alpha mRNA, but did not appreciably affect the secretion of the TNF-alpha protein. Neutralizing concentrations of anti-TNF mAb completely abrogated IFN-gamma- and IFN-gamma plus rTNF-alpha-induced NO2- production in ANA-1 macrophages, but only decreased by approximately 50% the synergistic interaction between IFN-gamma and picolinic acid. Although IL-4 inhibited the expression of IFN-gamma plus picolinic acid-induced TNF-alpha mRNA and protein, it only partially suppressed picolinic acid-dependent NO2- production. Therefore, picolinic acid may affect NO2- production via both TNF-alpha-dependent and TNF-alpha-independent pathways. Overall, this study suggests that amino acid catabolites may be important for the activation and the expression of effector functions by murine macrophages, and provides the first evidence of a possible connection between tryptophan and arginine metabolism. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Melillo, G AU - Cox, G W AU - Radzioch, D AU - Varesio, L AD - Laboratory of Molecular Immunoregulation, National Cancer Institute-Frederick Cancer Research and Development Center, NIH, MD 21702-1201. Y1 - 1993/05/01/ PY - 1993 DA - 1993 May 01 SP - 4031 EP - 4040 VL - 150 IS - 9 SN - 0022-1767, 0022-1767 KW - Nitrites KW - 0 KW - Picolinic Acids KW - RNA, Messenger KW - Tumor Necrosis Factor-alpha KW - Interleukin-4 KW - 207137-56-2 KW - omega-N-Methylarginine KW - 27JT06E6GR KW - Interferon-gamma KW - 82115-62-6 KW - Tryptophan KW - 8DUH1N11BX KW - Arginine KW - 94ZLA3W45F KW - picolinic acid KW - QZV2W997JQ KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Interleukin-4 -- pharmacology KW - RNA, Messenger -- analysis KW - Interferon-gamma -- pharmacology KW - Tumor Necrosis Factor-alpha -- physiology KW - Mice KW - Tumor Necrosis Factor-alpha -- genetics KW - Arginine -- pharmacology KW - Macrophage Activation -- drug effects KW - Mice, Inbred C57BL KW - Drug Synergism KW - Arginine -- analogs & derivatives KW - Cell Line KW - Nitrites -- metabolism KW - Tryptophan -- metabolism KW - Macrophages -- drug effects KW - Picolinic Acids -- pharmacology KW - Macrophages -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75666806?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Picolinic+acid%2C+a+catabolite+of+L-tryptophan%2C+is+a+costimulus+for+the+induction+of+reactive+nitrogen+intermediate+production+in+murine+macrophages.&rft.au=Melillo%2C+G%3BCox%2C+G+W%3BRadzioch%2C+D%3BVaresio%2C+L&rft.aulast=Melillo&rft.aufirst=G&rft.date=1993-05-01&rft.volume=150&rft.issue=9&rft.spage=4031&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 - 1993-05-20 N1 - Date created - 1993-05-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Fertility and pregnancy after treatment for cancer during childhood or adolescence AN - 1434023382; 18537369 AB - Because most children and adolescents with cancer now survive, issues regarding the late effects of therapy, including fertility and the health of offspring, are increasingly important. This article summarizes the literature regarding issues related to fertility in survivors of cancer, including actual fertility, gonadal function, menarche, menopause, and birth defects and cancer in the offspring. Radiation therapy to the gonads and alkylating agent chemotherapy, either alone or in combination, impair actual fertility in survivors of childhood and adolescent cancer. Males are particularly affected by alkylating agents, and females who have had radiation therapy to the abdomen have decreased fertility and an increased risk of adverse pregnancy outcomes. Consequently, these women should be followed up as high-risk obstetrical patients. Offspring of survivors of cancer appear to have little risk of childhood cancer or birth defects. Thus, in most instances, survivors of cancer should not be discouraged from having children and can expect a good outcome of pregnancy. This article concludes with advice to survivors and clinicians who counsel survivors. JF - Cancer AU - Nicholson, HStacy AU - Byrne, Julianne AD - Clinical Epidemiology Branch, EPN 400, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/05// PY - 1993 DA - May 1993 SP - 3392 EP - 3399 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 71 IS - S10 SN - 0008-543X, 0008-543X KW - Risk Abstracts KW - Radiation therapy KW - Health risks KW - Fertility KW - Congenital defects KW - Offspring KW - Children KW - Cancer KW - Adolescents KW - Pregnancy KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1434023382?accountid=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&rft.atitle=Fertility+and+pregnancy+after+treatment+for+cancer+during+childhood+or+adolescence&rft.au=Nicholson%2C+HStacy%3BByrne%2C+Julianne&rft.aulast=Nicholson&rft.aufirst=HStacy&rft.date=1993-05-01&rft.volume=71&rft.issue=S10&rft.spage=3392&rft.isbn=&rft.btitle=&rft.title=Cancer&rft.issn=0008543X&rft_id=info:doi/10.1002%2F1097-0142%2819930515%2971%3A10%2B3.0.CO%3B+2-F LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2013-09-01 N1 - Last updated - 2013-10-04 N1 - SubjectsTermNotLitGenreText - Radiation therapy; Health risks; Fertility; Congenital defects; Offspring; Children; Adolescents; Cancer; Pregnancy DO - http://dx.doi.org/10.1002/1097-0142(19930515)71:10+<3392::AID-CNCR2820711743>3.0.CO; ER - TY - JOUR T1 - Phosphorylation of HIV-1 gag proteins by protein kinase C. AN - 75685009; 8473314 AB - We have demonstrated that the 17-kDa N-terminal matrix protein (p17gag) of HIV-1 Pr55gag is a substrate for protein kinase C (PKC). Phosphorylation of p17gag and Pr55gag was studied in vivo by infecting COS-7 cells with a recombinant vaccinia virus containing the HIV-1 gag-pol gene. Basal gag protein phosphorylation was inhibited up to 75% with the PKC inhibitor, H-7, and stimulated 3-4-fold with phorbol 12-myristate 13-acetate. In experiments using MCF-7 cell lines, p17gag and Pr55gag were dramatically phosphorylated only in clones with high PKC activity. Bacterially expressed and purified non-myristoylated and N-myristoylated p17gag were efficiently phosphorylated in a Ca2+ and phosphatidylserine-dependent manner by purified PKC. The N-myristoylated p17gag exhibited an apparent Km = 4 microM for PKC phosphorylation. Both in vitro and in vivo phosphorylated p17gag yielded identical V8 protease digestion phosphopeptide maps, indicating identical PKC phosphorylation sites. Phosphoamino acid analysis of the in vitro phosphorylated p17gag revealed only phosphoserine. These data are consistent with the identification of a highly conserved consensus PKC phosphorylation site motif in the HIV-1 gag protein at Ser111 and suggests that PKC phosphorylation plays an important role in gag protein function. JF - The Journal of biological chemistry AU - Burnette, B AU - Yu, G AU - Felsted, R L AD - Laboratory of Biological Chemistry, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/04/25/ PY - 1993 DA - 1993 Apr 25 SP - 8698 EP - 8703 VL - 268 IS - 12 SN - 0021-9258, 0021-9258 KW - Gene Products, gag KW - 0 KW - HIV Antigens KW - Protein Precursors KW - Viral Proteins KW - gag Gene Products, Human Immunodeficiency Virus KW - p17 protein, Human Immunodeficiency Virus Type 1 KW - p55 gag precursor protein, Human immunodeficiency virus 1 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - AIDS/HIV KW - Protein Precursors -- metabolism KW - Tumor Cells, Cultured KW - Phosphorylation KW - Peptide Mapping KW - Tetradecanoylphorbol Acetate -- pharmacology KW - HIV Antigens -- metabolism KW - Protein Kinase C -- metabolism KW - HIV-1 -- metabolism KW - Gene Products, gag -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75685009?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Phosphorylation+of+HIV-1+gag+proteins+by+protein+kinase+C.&rft.au=Burnette%2C+B%3BYu%2C+G%3BFelsted%2C+R+L&rft.aulast=Burnette&rft.aufirst=B&rft.date=1993-04-25&rft.volume=268&rft.issue=12&rft.spage=8698&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 - 1993-05-14 N1 - Date created - 1993-05-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Lysine 87 in the beta subunit of tryptophan synthase that forms an internal aldimine with pyridoxal phosphate serves critical roles in transimination, catalysis, and product release. AN - 75684156; 8473317 AB - This study provides valuable insights into the functions of the lysine residue that forms an internal aldimine with pyridoxal phosphate in the beta subunit of tryptophan synthase from Salmonella typhimurium. Our spectroscopic and kinetic studies demonstrate that a mutant alpha 2 beta 2 complex having beta subunit lysine 87 replaced by threonine forms external aldimines with several amino acids including L-serine, beta-chloro-1-alanine, L-tryptophan, and D-tryptophan. Because the rates of aldimine formation are very slow, we conclude that one role of lysine 87 in the wild type enzyme is to facilitate formation of external aldimines by transimination. Lysine 87 is an essential catalytic residue because the mutant alpha 2 beta 2 complex has no measurable activity in reactions catalyzed by the beta subunit and does not convert external aldimines to products. The mutant enzyme carries out two slow partial beta-elimination reactions: the conversion of beta-chloro-L-alanine and L-serine to enzyme-bound aminoacrylate. The reaction with L-serine is catalyzed by ammonia, which partially replaces the deleted epsilon-amino group. Lysine 87 is important for substrate and product release because L-serine, L-tryptophan, and aminoacrylate dissociate very slowly from the mutant alpha 2 beta 2 complex. Our ability to prepare very stable derivatives of the mutant alpha 2 beta 2 complex containing tightly bound aldimines with a substrate, a product, or a reaction intermediate provides valuable materials for ongoing x-ray crystallographic investigations and future kinetic analyses of the allosteric activation of the alpha subunit by beta subunit ligands. JF - The Journal of biological chemistry AU - Lu, Z AU - Nagata, S AU - McPhie, P AU - Miles, E W AD - Laboratory of Biochemical Pharmacology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/04/25/ PY - 1993 DA - 1993 Apr 25 SP - 8727 EP - 8734 VL - 268 IS - 12 SN - 0021-9258, 0021-9258 KW - Imines KW - 0 KW - Pyridoxal Phosphate KW - 5V5IOJ8338 KW - Tryptophan Synthase KW - EC 4.2.1.20 KW - Lysine KW - K3Z4F929H6 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Imines -- chemistry KW - Spectrum Analysis KW - Isomerism KW - Circular Dichroism KW - Imines -- metabolism KW - Salmonella typhimurium -- enzymology KW - Catalysis KW - Tryptophan Synthase -- metabolism KW - Tryptophan Synthase -- chemistry KW - Pyridoxal Phosphate -- chemistry KW - Tryptophan Synthase -- genetics KW - Pyridoxal Phosphate -- metabolism KW - Lysine -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75684156?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Lysine+87+in+the+beta+subunit+of+tryptophan+synthase+that+forms+an+internal+aldimine+with+pyridoxal+phosphate+serves+critical+roles+in+transimination%2C+catalysis%2C+and+product+release.&rft.au=Lu%2C+Z%3BNagata%2C+S%3BMcPhie%2C+P%3BMiles%2C+E+W&rft.aulast=Lu&rft.aufirst=Z&rft.date=1993-04-25&rft.volume=268&rft.issue=12&rft.spage=8727&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 - 1993-05-14 N1 - Date created - 1993-05-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Correlations between chemically related site-specific carcinogenic effects in long-term studies in rats and mice. AN - 75807609; 8513764 AB - We examined a database of 379 long-term carcinogenicity studies in rats and mice to evaluate sex and species correlations in site-specific carcinogenic responses. Within a species, most target sites showed a strong correlation between males and females. For example, chemicals producing forestomach or liver tumors in males were likely to produce these same types of tumors in females. There was also a significant correlation between species for certain site-specific carcinogenic effects, most notably tumors of the forestomach, liver, and thyroid gland. In contrast, adrenal pheochromocytoma, preputial/clitoral gland neoplasms, and lung tumors showed no significant interspecies correlation. Many chemicals produced a syndrome of carcinogenic effects involving tumors of the skin, Zymbal gland, preputial/clitoral gland, mammary gland, and/or oral cavity. Regarding different target sites, there appeared to be a correlation between thyroid and liver tumors both within and between species. Further, all chemicals producing mesotheliomas in male rats also produced mammary gland neoplasms in female rats. In contrast, kidney and urinary bladder tumors showed no significant association with any other tumor type in rats or mice. If a chemical produced a site-specific carcinogenic effect in female rats or mice, there was approximately a 65% probability that the chemical would also be carcinogenic at that same site in males. The interspecies correlation was somewhat lower: approximately 36% of the site-specific carcinogenic effects observed in one species (rats or mice) were also observed in the other species.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Environmental health perspectives AU - Haseman, J K AU - Lockhart, A M AD - Statistics and Biomathematics Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1993/04/22/ PY - 1993 DA - 1993 Apr 22 SP - 50 EP - 54 VL - 101 IS - 1 SN - 0091-6765, 0091-6765 KW - Carcinogens KW - 0 KW - Index Medicus KW - Rats KW - Mammary Neoplasms, Experimental -- chemically induced KW - Animals KW - Stomach Neoplasms -- chemically induced KW - Sex Characteristics KW - Databases, Factual KW - Carcinogenicity Tests KW - Liver Neoplasms, Experimental -- chemically induced KW - Mice KW - Species Specificity KW - Male KW - Female KW - Neoplasms -- chemically induced KW - Carcinogens -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75807609?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Correlations+between+chemically+related+site-specific+carcinogenic+effects+in+long-term+studies+in+rats+and+mice.&rft.au=Haseman%2C+J+K%3BLockhart%2C+A+M&rft.aulast=Haseman&rft.aufirst=J&rft.date=1993-04-22&rft.volume=101&rft.issue=1&rft.spage=50&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 - 1993-07-19 N1 - Date created - 1993-07-19 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Annu Rev Pharmacol Toxicol. 1991;31:621-52 [2064387] Cancer Lett. 1987 Oct 30;37(2):125-32 [3677049] Environ Health Perspect. 1987 Oct;74:229-35 [3691430] Mutat Res. 1988 Jan;204(1):17-115 [3277047] Environ Health Perspect. 1991 Jun;93:247-70 [1773796] Environ Health Perspect. 1991 Jun;93:233-46 [1773795] Regul Toxicol Pharmacol. 1992 Oct;16(2):177-88 [1438997] Environ Health Perspect. 1989 May;81:211-9 [2759059] Fundam Appl Toxicol. 1992 Aug;19(2):207-13 [1516777] Regul Toxicol Pharmacol. 1986 Jun;6(2):155-70 [3726178] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Receptor mechanisms and dose-response models for the effects of dioxins. AN - 75796207; 8390353 AB - There is increasing evidence that receptor-mediated events impact one or more stages responsible for tumor development in experimental animals and humans. Although many chemicals and endogenous hormones require receptor interactions as a necessary event in their carcinogenic activity, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and its structural analogs are the most visible examples of receptor-mediated carcinogens. TCDD, or dioxin as it is frequently called, interacts with the Ah receptor (AhR), which functions in a manner analogous to receptors for steroids. TCDD produces a wide spectrum of biochemical and toxic responses in in vitro and in vivo systems, and the Ah receptor is generally considered necessary for most if not all of these responses. Risk assessments for dioxin made by the United States and other countries throughout the world have been based on its carcinogenecity in experimental animals. Recently, epidemiology studies have indicated that TCDD is a human carcinogen at high doses. Because TCDD appears to be acting like a potent and persistent hormone agonist, it appears reasonable to incorporate mechanistic information on receptor-mediated events in risk assessments for TCDD. This information may be obtained from steroid receptor action and from molecular data on the Ah receptor. In this paper, we evaluate the scientific foundation on which mechanistic models for estimating dioxin's risks should be based. These models need to recognize the mechanisms possible for the diversity of biological responses that are initiated by a single receptor interacting with a single ligand. The U.S. EPA is currently reevaluating dioxin's risks by examining the possibility of developing biologically based models.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Environmental health perspectives AU - Lucier, G W AU - Portier, C J AU - Gallo, M A AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1993/04/22/ PY - 1993 DA - 1993 Apr 22 SP - 36 EP - 44 VL - 101 IS - 1 SN - 0091-6765, 0091-6765 KW - CYP1A1 KW - Dioxins KW - 0 KW - Receptors, Aryl Hydrocarbon KW - Receptors, Drug KW - Index Medicus KW - Rats KW - Animals KW - Guinea Pigs KW - Dose-Response Relationship, Drug KW - Risk Factors KW - Humans KW - Male KW - Female KW - Cell Transformation, Neoplastic -- genetics KW - Dioxins -- metabolism KW - Receptors, Drug -- metabolism KW - Neoplasms -- chemically induced KW - Dioxins -- toxicity KW - Models, Biological UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75796207?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Receptor+mechanisms+and+dose-response+models+for+the+effects+of+dioxins.&rft.au=Lucier%2C+G+W%3BPortier%2C+C+J%3BGallo%2C+M+A&rft.aulast=Lucier&rft.aufirst=G&rft.date=1993-04-22&rft.volume=101&rft.issue=1&rft.spage=36&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 - 1993-07-19 N1 - Date created - 1993-07-19 N1 - Date revised - 2017-01-13 N1 - Gene symbol - CYP1A1 N1 - SuppNotes - Cited By: Environ Health Perspect. 1987 Dec;76:125-31 [3447890] J Biol Chem. 1976 Aug 25;251(16):4936-46 [956169] Fed Proc. 1980 Jan;39(1):73-5 [7351247] Cancer Res. 1980 Oct;40(10):3616-20 [6108157] Nature. 1982 Nov 18;300(5889):271-3 [7144882] Environ Health Perspect. 1985 Feb;59:121-8 [2985378] Science. 1987 May 22;236(4804):933-41 [3554512] Environ Health Perspect. 1987 Dec;76:57-63 [3447904] J Biol Chem. 1988 Sep 25;263(27):13802-5 [2843537] Am J Ind Med. 1989;16(4):455-74 [2558567] Annu Rev Pharmacol Toxicol. 1990;30:251-77 [2188570] N Engl J Med. 1991 Jan 24;324(4):212-8 [1985242] Biochemistry. 1991 Mar 19;30(11):2909-16 [1848780] Cancer Res. 1991 Mar 1;51(5):1391-7 [1671757] Science. 1991 Apr 5;252(5002):9 [2011755] Science. 1991 May 17;252(5008):954-8 [1852076] Cell Biol Toxicol. 1991 Jan;7(1):67-94 [2054688] Science. 1991 Oct 18;254(5030):377 [1656528] Science. 1991 Oct 18;254(5030):415-8 [1925598] FASEB J. 1991 Dec;5(15):3092-9 [1743440] Science. 1992 Feb 21;255(5047):979-83 [1312255] Risk Anal. 1991 Dec;11(4):565-8 [1664119] Biochem Biophys Res Commun. 1992 Apr 15;184(1):246-53 [1314586] Cancer Res. 1992 Jun 15;52(12):3436-42 [1596902] Cancer Res. 1992 Jun 15;52(12):3478-82 [1596905] Carcinogenesis. 1992 Aug;13(8):1389-95 [1354083] Proc Natl Acad Sci U S A. 1992 Sep 1;89(17):8185-9 [1325649] Nucleic Acids Res. 1993 Jan 11;21(1):119-25 [8382788] Environ Health Perspect. 1992 Nov;98:125-32 [1336723] Fundam Appl Toxicol. 1993 Jan;20(1):48-56 [8381755] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Prospective randomized trial of high-dose interleukin-2 alone or in conjunction with lymphokine-activated killer cells for the treatment of patients with advanced cancer. AN - 75673918; 8468720 AB - Treatment using interleukin-2 (IL-2) alone or in conjunction with lymphokine-activated killer (LAK) cells has been shown to mediate disease regression in selected patients with advanced cancer. This prospective randomized trial was designed to determine whether the administration of LAK cells in conjunction with high-dose IL-2 alters response and survival rates, compared with those for IL-2 alone, in patients with advanced cancer. The 181 patients who had metastatic cancer that had failed to respond to standard therapy or who had disease for which no effective therapy existed received treatment with high-dose IL-2 alone or with LAK cells plus IL-2. Both treatment groups were to receive the same dose of IL-2 administered according to the same schedule. IL-2 doses were omitted depending on the tolerance of the patient. Of the 181 patients, 97 had renal cell cancer and 54 had melanoma. Median potential follow-up was 63.2 months. There were 10 complete responses among the 85 assessable patients who received IL-2 plus LAK cells, compared with four among the 79 who received IL-2 alone. There were 14 and 12 partial responses, respectively. Complete response continues in seven patients at 50-66 months. The 36-month actuarial survival with IL-2 plus LAK cells was 31%, compared with 17% with IL-2 alone (two-sided P value [P2] = .089). A trend toward improved survival was seen for patients with melanoma who received IL-2 plus LAK cells, compared with those who received IL-2 alone (24-month survival: 32% versus 15%; 48-month survival: 18% versus 4%; P2 = .064 [corrected]). None of 26 patients with melanoma who received IL-2 alone are alive; five of 28 who received IL-2 plus LAK cells are alive, and three continue in complete response. No difference in survival was seen in patients with renal cell cancer in the two treatment groups. There were six treatment-related deaths (3.3%); three were due to myocardial infarction. Other toxic effects resolved by discontinuation of IL-2. Many toxic effects were related to increased vascular permeability induced by IL-2. Some patients with metastatic cancer have prolonged remission when they are treated with high-dose IL-2 alone or in conjunction with LAK cells. Our results suggest a trend toward increased survival when IL-2 is given with LAK cells in patients with melanoma, but no trend was observed for patients with renal cell cancer. As these studies continue, efforts are underway to develop improved immunotherapies using tumor-infiltrating lymphocytes (TIL) and gene-modified TIL. JF - Journal of the National Cancer Institute AU - Rosenberg, S A AU - Lotze, M T AU - Yang, J C AU - Topalian, S L AU - Chang, A E AU - Schwartzentruber, D J AU - Aebersold, P AU - Leitman, S AU - Linehan, W M AU - Seipp, C A AD - Division of Cancer Treatment, National Cancer Institute, Bethesda, Md 20892. Y1 - 1993/04/21/ PY - 1993 DA - 1993 Apr 21 SP - 622 EP - 632 VL - 85 IS - 8 SN - 0027-8874, 0027-8874 KW - Interleukin-2 KW - 0 KW - Index Medicus KW - Leukapheresis KW - Prospective Studies KW - Combined Modality Therapy KW - Humans KW - Adult KW - Treatment Outcome KW - Aged KW - Middle Aged KW - Child KW - Adolescent KW - Male KW - Female KW - Survival Analysis KW - Interleukin-2 -- adverse effects KW - Interleukin-2 -- administration & dosage KW - Neoplasms -- pathology KW - Interleukin-2 -- therapeutic use KW - Neoplasms -- therapy KW - Killer Cells, Lymphokine-Activated -- transplantation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75673918?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+National+Cancer+Institute&rft.atitle=Prospective+randomized+trial+of+high-dose+interleukin-2+alone+or+in+conjunction+with+lymphokine-activated+killer+cells+for+the+treatment+of+patients+with+advanced+cancer.&rft.au=Rosenberg%2C+S+A%3BLotze%2C+M+T%3BYang%2C+J+C%3BTopalian%2C+S+L%3BChang%2C+A+E%3BSchwartzentruber%2C+D+J%3BAebersold%2C+P%3BLeitman%2C+S%3BLinehan%2C+W+M%3BSeipp%2C+C+A&rft.aulast=Rosenberg&rft.aufirst=S&rft.date=1993-04-21&rft.volume=85&rft.issue=8&rft.spage=622&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+National+Cancer+Institute&rft.issn=00278874&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-05-07 N1 - Date created - 1993-05-07 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: J Natl Cancer Inst 1993 Jul 7;85(13):1091 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of high-protein diet on pyrimidine synthesis and response to PALA in mouse tissues. AN - 75661101; 8468725 AB - High-protein diets have been found to protect mice from the lethal effects of cytotoxic pyrimidine analogues and to reduce the toxicity of the antipyrimidine fluorouracil (5-FU), but the biochemical explanation for these effects is not known. PALA potentiates the chemotherapeutic efficacy of 5-FU, and each of the two agents can produce dose-limiting intestinal toxic effects. We have shown that intraperitoneal infusion of ammonium chloride stimulates intestinal de novo pyrimidine synthesis. This stimulation with excess ammonia, which can also result from high-protein intake, is dependent on the presence of carbamoyl phosphate synthetase I, an enzyme in the liver and intestine but not in most tumors. These findings suggest that a high-protein diet can stimulate pyrimidine synthesis in the liver and intestine but leave it unchanged in tumor tissue. The purpose of this study was to determine whether varying dietary protein causes pharmacologically relevant and preferential changes in de novo pyrimidine synthesis. Mice were fed diets containing 18%, 35%, or 50% casein. Dietary effects on de novo pyrimidine synthesis were measured in the intestine, liver, and B16 mouse melanoma in mice treated with PALA and in untreated mice. De novo synthesis was measured by infusion of [15N]alanine into intact animals, determination of 15N incorporation into uracil by use of gas chromatography-mass spectrometry, and calculation of the fraction of the uracil nucleotide pool formed by de novo synthesis. In mice on a 50% casein diet (high protein), de novo pyrimidine synthesis increased substantially in the liver and intestine, compared with synthesis in mice receiving 18% casein. Increase in pyrimidine synthesis in B16 tumor tissue was negligible. The high-protein diet protected the intestine and liver from depletion of uracil nucleotide pools by PALA, and toxicity in tumor-free animals was reduced, as determined by mortality after PALA treatment. Sensitivity of the B16 tumor to the biochemical and cytotoxic effects of PALA was not diminished. We propose that the basis for these effects of a high-protein diet is the generation of excess carbamoyl phosphate in tissues containing carbamoyl phosphate synthetase I. This carbamoyl phosphate can stimulate de novo pyrimidine synthesis and compete with drugs that interact with enzymes of the de novo pathway, thereby selectively protecting the liver and intestine. These data provide a biochemical explanation for reported effects of high-protein diet on toxicity of antipyrimidines like 5-FU. Studies are underway to determine if stimulation of pyrimidine synthesis by excess ammonia improves therapy with 5-FU alone or combined with PALA. JF - Journal of the National Cancer Institute AU - Zaharevitz, D W AU - Grubb, M F AU - Hyman, R AU - Chisena, C AU - Cysyk, R L AD - Laboratory of Medicinal Chemistry, National Cancer Institute, Bethesda, Md 20892. Y1 - 1993/04/21/ PY - 1993 DA - 1993 Apr 21 SP - 662 EP - 666 VL - 85 IS - 8 SN - 0027-8874, 0027-8874 KW - Antimetabolites, Antineoplastic KW - 0 KW - Dietary Proteins KW - Pyrimidines KW - Aspartic Acid KW - 30KYC7MIAI KW - sparfosic acid KW - 78QVZ7RG8L KW - Phosphonoacetic Acid KW - N919E46723 KW - Index Medicus KW - Animals KW - Melanoma, Experimental -- metabolism KW - Intestines -- drug effects KW - Liver -- drug effects KW - Mice, Inbred C57BL KW - Liver -- metabolism KW - Mice KW - Intestines -- metabolism KW - Mice, Inbred BALB C KW - Male KW - Mice, Inbred DBA KW - Aspartic Acid -- pharmacology KW - Dietary Proteins -- administration & dosage KW - Aspartic Acid -- analogs & derivatives KW - Phosphonoacetic Acid -- analogs & derivatives KW - Phosphonoacetic Acid -- pharmacology KW - Pyrimidines -- biosynthesis KW - Antimetabolites, Antineoplastic -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75661101?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+National+Cancer+Institute&rft.atitle=Effect+of+high-protein+diet+on+pyrimidine+synthesis+and+response+to+PALA+in+mouse+tissues.&rft.au=Zaharevitz%2C+D+W%3BGrubb%2C+M+F%3BHyman%2C+R%3BChisena%2C+C%3BCysyk%2C+R+L&rft.aulast=Zaharevitz&rft.aufirst=D&rft.date=1993-04-21&rft.volume=85&rft.issue=8&rft.spage=662&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+National+Cancer+Institute&rft.issn=00278874&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-05-07 N1 - Date created - 1993-05-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Differential effects of activation of protein kinase C and cyclic-AMP-dependent protein kinase on sodium-dependent phosphate uptake in NIH 3T3 cells. AN - 75682506; 8471634 AB - Activation of protein kinase C (PKC) by phorbol ester (PMA), or by diacylglycerol analogue (OAG) treatment of NIH 3T3 cells resulted in the rapid (within 2-5 min) stimulation (approx. 2-fold) of sodium-dependent phosphate (Pi) transport. Conversely, preincubation of these cells with forskolin and cholera toxin, or incubation with 8-bromo-cAMP, to activate cAMP-dependent protein kinase (PKA), resulted in a decrease in Na+/Pi transport. Activation of either PKC or PKA did not change the Vmax of Pi uptake. However, activation of PKC did result in an increase, while activation of PKA caused a decrease, in the affinity for Pi. These results indicate that there is differential regulation of Na+/Pi uptake in NIH 3T3 cells by activators of PKC (stimulated) and PKA (inhibited) as a consequence of changes in the affinity of the transporter for Pi. JF - Biochimica et biophysica acta AU - Oláh, Z AU - Lehel, C AU - Anderson, W B AD - Laboratory of Cellular Oncology, National Cancer Institute, National Institutes of Health, Bethesda 20892. Y1 - 1993/04/16/ PY - 1993 DA - 1993 Apr 16 SP - 333 EP - 338 VL - 1176 IS - 3 SN - 0006-3002, 0006-3002 KW - Carrier Proteins KW - 0 KW - Phosphate-Binding Proteins KW - Phosphates KW - Protein Kinase Inhibitors KW - Colforsin KW - 1F7A44V6OU KW - 8-Bromo Cyclic Adenosine Monophosphate KW - 23583-48-4 KW - Cholera Toxin KW - 9012-63-9 KW - Sodium KW - 9NEZ333N27 KW - Protein Kinases KW - EC 2.7.- KW - Protein Kinase C KW - EC 2.7.11.13 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - Carrier Proteins -- metabolism KW - 3T3 Cells -- drug effects KW - Cholera Toxin -- pharmacology KW - Mice KW - 8-Bromo Cyclic Adenosine Monophosphate -- pharmacology KW - Models, Biological KW - Colforsin -- pharmacology KW - Kinetics KW - 3T3 Cells -- metabolism KW - Enzyme Activation -- drug effects KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Time Factors KW - Signal Transduction KW - Protein Kinase C -- metabolism KW - Phosphates -- metabolism KW - Protein Kinases -- metabolism KW - Sodium -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75682506?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochimica+et+biophysica+acta&rft.atitle=Differential+effects+of+activation+of+protein+kinase+C+and+cyclic-AMP-dependent+protein+kinase+on+sodium-dependent+phosphate+uptake+in+NIH+3T3+cells.&rft.au=Ol%C3%A1h%2C+Z%3BLehel%2C+C%3BAnderson%2C+W+B&rft.aulast=Ol%C3%A1h&rft.aufirst=Z&rft.date=1993-04-16&rft.volume=1176&rft.issue=3&rft.spage=333&rft.isbn=&rft.btitle=&rft.title=Biochimica+et+biophysica+acta&rft.issn=00063002&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-05-18 N1 - Date created - 1993-05-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regulation of eukaryotic translation initiation factor expression during T-cell activation. AN - 75672348; 8471627 AB - Primary T-cells are metabolically quiescent, with little DNA, RNA or protein synthesis. Upon mitogenic stimulation the rate of protein synthesis increases 10-fold. We have studied the role of eIF-2 and eIF-4 alpha (eIF-4E) expression in the mechanism of translational activation. During this period, the levels of eIF-2 alpha and eIF-4 alpha mRNA increase some 50-fold. Similar to the increase in ribosomes and mRNA, the number of eIF-2 alpha, eIF-2 beta, and eIF-4 alpha molecules per cell also increase 2-3-fold. This suggests that in addition to an increase in the pool size of translational components, an additional mechanism exists which results in an increased efficiency of factor utilization. We have looked at initiation factor phosphorylation. We find that eIF-2 alpha does not undergo significant changes in its phosphorylation state nor is there a change in the efficiency of eIF-2 utilization. However, there is a rapid increase in the phosphorylation state of eIF-4 alpha which correlates with the rapid increase in translational activity. It thus appears there are 2 distinct components responsible for the translational activation of quiescent T-cells during mitogenic stimulation. The first is the phosphorylation of eIF-4 alpha, with a concomitant increase in the efficiency of eIF-4 alpha utilization. The second is an increase in the pool sizes of eIF-2 and eIF-4 alpha. JF - Biochimica et biophysica acta AU - Boal, T R AU - Chiorini, J A AU - Cohen, R B AU - Miyamoto, S AU - Frederickson, R M AU - Sonenberg, N AU - Safer, B AD - Molecular Hematology Branch, NHLBI, NIH, Bethesda, MD 20892. Y1 - 1993/04/16/ PY - 1993 DA - 1993 Apr 16 SP - 257 EP - 264 VL - 1176 IS - 3 SN - 0006-3002, 0006-3002 KW - Eukaryotic Initiation Factor-2 KW - 0 KW - Peptide Initiation Factors KW - Phytohemagglutinins KW - RNA, Messenger KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Protein Biosynthesis KW - Phosphorylation KW - Humans KW - RNA, Messenger -- analysis KW - Eukaryotic Initiation Factor-2 -- genetics KW - Gene Expression Regulation KW - T-Lymphocytes -- metabolism KW - Peptide Initiation Factors -- genetics KW - Lymphocyte Activation -- genetics KW - Peptide Initiation Factors -- biosynthesis KW - T-Lymphocytes -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75672348?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochimica+et+biophysica+acta&rft.atitle=Regulation+of+eukaryotic+translation+initiation+factor+expression+during+T-cell+activation.&rft.au=Boal%2C+T+R%3BChiorini%2C+J+A%3BCohen%2C+R+B%3BMiyamoto%2C+S%3BFrederickson%2C+R+M%3BSonenberg%2C+N%3BSafer%2C+B&rft.aulast=Boal&rft.aufirst=T&rft.date=1993-04-16&rft.volume=1176&rft.issue=3&rft.spage=257&rft.isbn=&rft.btitle=&rft.title=Biochimica+et+biophysica+acta&rft.issn=00063002&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-05-18 N1 - Date created - 1993-05-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Site-directed mutagenesis of mouse steroid 7 alpha-hydroxylase (cytochrome P-450(7) alpha): role of residue-209 in determining steroid-cytochrome P-450 interaction. AN - 75718274; 8484736 AB - We have cloned a cDNA encoding mouse steroid 7 alpha-hydroxylase P450(7) alpha (cytochrome P-450(7) alpha) and expressed it in Saccharomyces cerevisiae. Mouse P450(7) alpha is 70% identical in its amino acid sequence with the mouse steroid 15 alpha-hydroxylase P450(15) alpha (2A4). The Leu at position 209 of P450(15) alpha is the most important residue to determine the steroid hydroxylase activity of the P450 [Lindberg and Negishi (1989) Nature (London) 339, 632-634]. The P450(7) alpha contains Asn at the position corresponding to the Leu-209 of P450(15) alpha, although both P450s hydroxylate testosterone. The CO-reduced P450(7) alpha complex is unstable, so that it is quickly converted into the inactive P420, whereas the P450(15) alpha is very stable. The P450(7) alpha, however, is stabilized either by addition of testosterone or by a mutation of Asn-209 to Leu. The mutant P450(7) alpha displays a 17-fold lower Vmax. value than the wild-type enzyme. Unexpectedly, it also has 3-fold lower Km and Kd values. Residue 209 in P450(7) alpha, therefore, appears to be located at a critical site of the haem-substrate-binding pocket. Corticosterone inhibits the testosterone 7 alpha-hydroxylase activity of the wild-type P450(7) alpha, whereas it does not inhibit the mutant P450(7) alpha. Conversely, the P450(15) alpha activity becomes inhibited by corticosterone upon the replacement of Leu-209 by Asn. In addition, this mutation increases the corticosterone 15 alpha-hydroxylase activity of P450(15) alpha at least 20-fold. Whereas the inhibition by corticosterone depends on the presence of Asn at position 209, deoxycorticosterone inhibits the activities of the P450s regardless of the type of residue at 209. The results indicate, therefore, that the identity of residue 209 determines the affinity as well as specificity of steroid binding to both P450(7) alpha and P450(15) alpha. JF - The Biochemical journal AU - Iwasaki, M AU - Lindberg, R L AU - Juvonen, R O AU - Negishi, M AD - Pharmacogenetics Section, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709. Y1 - 1993/04/15/ PY - 1993 DA - 1993 Apr 15 SP - 569 EP - 573 VL - 291 ( Pt 2) SN - 0264-6021, 0264-6021 KW - Coumarins KW - 0 KW - Hydroxyprogesterones KW - 11-hydroxyprogesterone KW - 312-90-3 KW - Desoxycorticosterone KW - 40GP35YQ49 KW - Progesterone KW - 4G7DS2Q64Y KW - Asparagine KW - 7006-34-0 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - coumarin KW - A4VZ22K1WT KW - Steroid Hydroxylases KW - EC 1.14.- KW - Aryl Hydrocarbon Hydroxylases KW - EC 1.14.14.1 KW - steroid hormone 7-alpha-hydroxylase KW - testosterone 7-alpha-hydroxylase, hamster KW - Leucine KW - GMW67QNF9C KW - Corticosterone KW - W980KJ009P KW - Index Medicus KW - Animals KW - Progesterone -- pharmacology KW - Amino Acid Sequence KW - Mice KW - Structure-Activity Relationship KW - Binding Sites KW - Base Sequence KW - Coumarins -- pharmacology KW - Molecular Sequence Data KW - Desoxycorticosterone -- pharmacology KW - Spectrophotometry KW - Corticosterone -- pharmacology KW - Mice, Inbred AKR KW - Hydroxyprogesterones -- pharmacology KW - Mutagenesis, Site-Directed KW - Cytochrome P-450 Enzyme System -- genetics KW - Cytochrome P-450 Enzyme System -- chemistry KW - Steroid Hydroxylases -- metabolism KW - Steroid Hydroxylases -- chemistry KW - Cytochrome P-450 Enzyme System -- metabolism KW - Steroid Hydroxylases -- genetics KW - Steroid Hydroxylases -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75718274?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Biochemical+journal&rft.atitle=Site-directed+mutagenesis+of+mouse+steroid+7+alpha-hydroxylase+%28cytochrome+P-450%287%29+alpha%29%3A+role+of+residue-209+in+determining+steroid-cytochrome+P-450+interaction.&rft.au=Iwasaki%2C+M%3BLindberg%2C+R+L%3BJuvonen%2C+R+O%3BNegishi%2C+M&rft.aulast=Iwasaki&rft.aufirst=M&rft.date=1993-04-15&rft.volume=291+%28+Pt+2%29&rft.issue=&rft.spage=569&rft.isbn=&rft.btitle=&rft.title=The+Biochemical+journal&rft.issn=02646021&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-06-01 N1 - Date created - 1993-06-01 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - L06463; GENBANK; D17642; X68677; X70243; D17801; D17800; D17802; D17798; D17799; D17797 N1 - SuppNotes - Cited By: DNA. 1985 Jun;4(3):203-10 [3159557] J Biol Chem. 1964 Jul;239:2370-8 [14209971] J Biol Chem. 1988 Dec 5;263(34):17995-8002 [3192524] Biochem Pharmacol. 1988 Dec 15;37(24):4778-80 [3202910] J Biol Chem. 1989 Jan 5;264(1):21-6 [2535839] Biochem Biophys Res Commun. 1989 Feb 15;158(3):717-22 [2493247] J Biol Chem. 1989 Apr 15;264(11):6465-71 [2703500] Biochemistry. 1989 Jan 24;28(2):656-60 [2713336] Nature. 1989 Jun 22;339(6226):632-4 [2733794] Biochemistry. 1989 May 16;28(10):4169-72 [2765478] Biochemistry. 1989 Aug 22;28(17):6848-57 [2819037] J Biol Chem. 1990 Oct 5;265(28):17197-201 [1976628] DNA Cell Biol. 1991 Jan-Feb;10(1):1-14 [1991046] J Biol Chem. 1991 Feb 25;266(6):3380-2 [1995602] J Biol Chem. 1991 Apr 5;266(10):6215-20 [1706711] Anal Biochem. 1976 May 7;72:248-54 [942051] Methods Enzymol. 1978;52:258-79 [209288] J Mol Biol. 1980 Oct 25;143(2):161-78 [6260957] Proc Natl Acad Sci U S A. 1983 Jul;80(13):3963-5 [6575390] Anal Biochem. 1984 Feb;136(2):390-6 [6426342] J Biol Chem. 1991 Jun 25;266(18):11939-46 [2050688] J Biol Chem. 1991 Sep 5;266(25):16431-5 [1885576] J Biol Chem. 1992 Jan 5;267(1):83-90 [1730627] Methods Enzymol. 1991;206:11-30 [1784202] J Biol Chem. 1993 Jan 15;268(2):759-62 [8419350] J Biol Chem. 1988 Mar 25;263(9):4166-71 [3346244] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Domains of the integrase protein of human immunodeficiency virus type 1 responsible for polynucleotidyl transfer and zinc binding. AN - 75692645; 8386373 AB - The integrase protein of human immunodeficiency virus type 1 carries out a set of polynucleotidyl transfer reactions that result in the covalent attachment of the retroviral cDNA to host DNA. We have analyzed the activities of a set of deletion derivatives of the integrase protein. The analysis reveals that a central domain of only 137 amino acids is sufficient in vitro to catalyze a subset of the reactions carried out by the complete protein. This polypeptide contains an amino acid sequence motif, Asp-Xaa39-58-Asp-Xaa35-Glu (DX39-58DX35E, where X and the subscript indicate the intervening amino acids between the invariant acidic residues), that is found in the integrases of retroviruses and retrotransposons and also the transposase proteins of some bacterial transposable elements. We also find that the integrase protein can bind Zn2+, and the histidine and cysteine residues of another conserved motif (HX3-7HX23-32CX2C) are required for efficient Zn2+ binding. The activities displayed by deletion mutants suggest to us possible functions for the various parts of integrase. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Bushman, F D AU - Engelman, A AU - Palmer, I AU - Wingfield, P AU - Craigie, R AD - Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/04/15/ PY - 1993 DA - 1993 Apr 15 SP - 3428 EP - 3432 VL - 90 IS - 8 SN - 0027-8424, 0027-8424 KW - Peptide Fragments KW - 0 KW - Recombinant Proteins KW - DNA Nucleotidyltransferases KW - EC 2.7.7.- KW - Integrases KW - Nucleotidyltransferases KW - Transposases KW - Zinc KW - J41CSQ7QDS KW - Index Medicus KW - AIDS/HIV KW - Peptide Fragments -- metabolism KW - Peptide Fragments -- isolation & purification KW - Escherichia coli -- genetics KW - Amino Acid Sequence KW - Binding Sites KW - Cloning, Molecular KW - Mutagenesis KW - Recombinant Proteins -- isolation & purification KW - Recombinant Proteins -- metabolism KW - Restriction Mapping KW - Molecular Sequence Data KW - Sequence Deletion KW - Nucleotidyltransferases -- metabolism KW - HIV-1 -- genetics KW - Zinc -- metabolism KW - DNA Nucleotidyltransferases -- isolation & purification KW - DNA Nucleotidyltransferases -- genetics KW - HIV-1 -- enzymology KW - DNA Nucleotidyltransferases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75692645?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Domains+of+the+integrase+protein+of+human+immunodeficiency+virus+type+1+responsible+for+polynucleotidyl+transfer+and+zinc+binding.&rft.au=Bushman%2C+F+D%3BEngelman%2C+A%3BPalmer%2C+I%3BWingfield%2C+P%3BCraigie%2C+R&rft.aulast=Bushman&rft.aufirst=F&rft.date=1993-04-15&rft.volume=90&rft.issue=8&rft.spage=3428&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 - 1993-05-17 N1 - Date created - 1993-05-17 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cell. 1985 Jul;41(3):867-76 [2988793] Proc Natl Acad Sci U S A. 1992 Oct 15;89(20):9598-602 [1409671] Gene. 1987;56(1):125-35 [3315856] EMBO J. 1987 Oct;6(10):3163-9 [2826132] Proc Natl Acad Sci U S A. 1988 Jun;85(12):4195-9 [3260031] Cell. 1988 Aug 12;54(4):497-504 [3401925] J Virol. 1989 Mar;63(3):1404-7 [2536841] Proc Natl Acad Sci U S A. 1989 Apr;86(8):2525-9 [2539592] Q Rev Biol. 1989 Mar;64(1):1-30 [2469098] Cell. 1989 Oct 20;59(2):373-83 [2553269] J Virol. 1989 Dec;63(12):5319-27 [2555556] Cell. 1990 Jan 12;60(1):3-4 [2403842] Genes Dev. 1990 Mar;4(3):324-30 [2159935] J Mol Biol. 1990 Jun 20;213(4):583-91 [2162963] J Bacteriol. 1990 Jul;172(7):4090-9 [2163395] Annu Rev Biophys Biophys Chem. 1990;19:405-21 [2114117] Proc Natl Acad Sci U S A. 1990 Jul;87(13):5119-23 [2164223] Cell. 1990 Aug 24;62(4):829-37 [2167180] Curr Top Microbiol Immunol. 1990;157:19-48 [2203610] Cell. 1990 Oct 5;63(1):87-95 [2170022] J Virol. 1990 Nov;64(11):5656-9 [2214031] Mol Microbiol. 1990 Jun;4(6):961-75 [2170815] Science. 1990 Sep 28;249(4976):1555-8 [2171144] Proc Natl Acad Sci U S A. 1991 Feb 15;88(4):1339-43 [1847518] Mol Microbiol. 1990 Oct;4(10):1771-7 [1963920] Nucleic Acids Res. 1991 Feb 25;19(4):851-60 [1850126] Cell. 1991 May 31;65(5):805-16 [1645619] J Virol. 1991 Sep;65(9):4636-44 [1870194] Cell. 1991 Dec 20;67(6):1211-21 [1760846] Nucleic Acids Res. 1991 Dec 25;19(24):6691-8 [1662361] Science. 1992 Feb 7;255(5045):723-6 [1738845] Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3458-62 [1533044] Mol Cell Biol. 1992 May;12(5):2331-8 [1314954] J Biol Chem. 1992 May 15;267(14):9639-44 [1577801] Virology. 1992 Jun;188(2):459-68 [1585629] J Biol Chem. 1992 Aug 15;267(23):16037-40 [1322888] J Biol Chem. 1992 Oct 25;267(30):21273-6 [1383220] J Virol. 1992 Nov;66(11):6361-9 [1404595] Proc Natl Acad Sci U S A. 1986 Oct;83(20):7648-52 [2429313] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Induction of neoplastic progression in Syrian hamster embryo cells treated with protein phosphatase inhibitors. AN - 75677451; 8385570 AB - In these studies, Syrian hamster embryo cells (SHE), which were isolated at different stages of neoplastic progression, were used to test the ability of the protein phosphatase inhibitors, okadaic acid and sodium orthovanadate (Na3VO4) to induce neoplastic progression. We observed that these chemicals can induce transition of the cells from one stage to the other at different points in the multistep process of neoplastic transformation. Three steps in this multistep process were studied: escape from cellular senescence, loss of a tumor suppressor gene function in immortal cells, and aquisition of anchorage-independent growth. Treatment of normal, primary SHE cells with okadaic acid or Na3VO4 allowed the cells to escape senescence and become immortal at a low frequency. The induction of immortality was associated with nonrandom chromosome changes, including trisomy 8 and 11 and monosomy 13 and Xq. The transition of preneoplastic cells to more advanced stages was also studied in immortal, nontumorigenic cells that either have retained (supB+) or have lost (supB-) the ability to suppress tumorigenicity of a transformed cell line in cell hybrids. SupB+ and supB- cells do not normally grow in agar, but supB- cells will grow in agar if additional growth factors are added. However, upon addition of protein phosphatase inhibitors, supB+ cells exhibited the supB- phenotype; for example, colony formation of supB+ cells was observed in agar supplemented with growth factors and protein phosphatase inhibitors. Following treatment, selection of these colonies showed that 89% of these cells heritably acquired the phenotype of cells that have lost the suppressor gene function (supB-). SupB- cells were also treated with protein phosphatase inhibitors in soft agar in the presence of additional growth factors. While the frequency of colonies in agar supplemented with growth factors in agar was not greatly enhanced, approximately 50% of the colonies acquired the ability to grow in agar autonomously without the supplemented growth factors, similar to tumorigenic cells. These studies suggest that Na3VO4 and okadaic acid induce progression of cells through various stages in this multistep system. JF - Cancer research AU - Afshari, C A AU - Kodama, S AU - Bivins, H M AU - Willard, T B AU - Fujiki, H AU - Barrett, J C AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina 27709. Y1 - 1993/04/15/ PY - 1993 DA - 1993 Apr 15 SP - 1777 EP - 1782 VL - 53 IS - 8 SN - 0008-5472, 0008-5472 KW - Ethers, Cyclic KW - 0 KW - Okadaic Acid KW - 1W21G5Q4N2 KW - Vanadates KW - 3WHH0066W5 KW - Phosphoprotein Phosphatases KW - EC 3.1.3.16 KW - Index Medicus KW - Phenotype KW - Karyotyping KW - Animals KW - Dose-Response Relationship, Drug KW - Cells, Cultured KW - Mutation KW - Embryo, Mammalian KW - Cricetinae KW - Cell Division KW - Phosphoprotein Phosphatases -- antagonists & inhibitors KW - Ethers, Cyclic -- toxicity KW - Vanadates -- toxicity KW - Cell Transformation, Neoplastic -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75677451?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Induction+of+neoplastic+progression+in+Syrian+hamster+embryo+cells+treated+with+protein+phosphatase+inhibitors.&rft.au=Afshari%2C+C+A%3BKodama%2C+S%3BBivins%2C+H+M%3BWillard%2C+T+B%3BFujiki%2C+H%3BBarrett%2C+J+C&rft.aulast=Afshari&rft.aufirst=C&rft.date=1993-04-15&rft.volume=53&rft.issue=8&rft.spage=1777&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 - 1993-05-11 N1 - Date created - 1993-05-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Human immunodeficiency virus type 1 coat protein neurotoxicity mediated by nitric oxide in primary cortical cultures. AN - 75672887; 8097316 AB - The human immunodeficiency virus type 1 coat protein, gp120, kills neurons in primary cortical cultures at low picomolar concentrations. The toxicity requires external glutamate and calcium and is blocked by glutamate receptor antagonists. Nitric oxide (NO) contributes to gp120 toxicity, since nitroarginine, an inhibitor of NO synthase, prevents toxicity as does deletion of arginine from the incubation medium and hemoglobin, which binds NO. Superoxide dismutase also attenuates toxicity, implying a role for superoxide anions. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Dawson, V L AU - Dawson, T M AU - Uhl, G R AU - Snyder, S H AD - National Institute on Drug Abuse, Addiction Research Center, Baltimore, MD 21224. Y1 - 1993/04/15/ PY - 1993 DA - 1993 Apr 15 SP - 3256 EP - 3259 VL - 90 IS - 8 SN - 0027-8424, 0027-8424 KW - Excitatory Amino Acid Antagonists KW - 0 KW - Glutamates KW - HIV Envelope Protein gp120 KW - Hemoglobins KW - Inositol Phosphates KW - Neurotoxins KW - Quinoxalines KW - Nitroarginine KW - 2149-70-4 KW - Nitric Oxide KW - 31C4KY9ESH KW - Glutamic Acid KW - 3KX376GY7L KW - FG 9041 KW - 62T278S1MX KW - Dizocilpine Maleate KW - 6LR8C1B66Q KW - Arginine KW - 94ZLA3W45F KW - Dantrolene KW - F64QU97QCR KW - Cyclic GMP KW - H2D2X058MU KW - Nifedipine KW - I9ZF7L6G2L KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - AIDS/HIV KW - Animals KW - Fetus KW - Dantrolene -- pharmacology KW - Inositol Phosphates -- metabolism KW - Calcium -- pharmacology KW - Hemoglobins -- pharmacology KW - Cell Death -- drug effects KW - Dizocilpine Maleate -- pharmacology KW - Rats KW - Nifedipine -- pharmacology KW - Cyclic GMP -- metabolism KW - Hemoglobins -- metabolism KW - Cell Survival -- drug effects KW - Cells, Cultured KW - Glutamates -- pharmacology KW - Models, Neurological KW - Quinoxalines -- pharmacology KW - Cerebral Cortex -- cytology KW - Neurons -- metabolism KW - Cerebral Cortex -- metabolism KW - Neurons -- drug effects KW - Neurons -- cytology KW - Nitric Oxide -- metabolism KW - HIV Envelope Protein gp120 -- toxicity KW - Neurotoxins -- toxicity KW - HIV-1 KW - Arginine -- analogs & derivatives KW - Arginine -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75672887?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Human+immunodeficiency+virus+type+1+coat+protein+neurotoxicity+mediated+by+nitric+oxide+in+primary+cortical+cultures.&rft.au=Dawson%2C+V+L%3BDawson%2C+T+M%3BUhl%2C+G+R%3BSnyder%2C+S+H&rft.aulast=Dawson&rft.aufirst=V&rft.date=1993-04-15&rft.volume=90&rft.issue=8&rft.spage=3256&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 - 1993-05-17 N1 - Date created - 1993-05-17 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Brain Res. 1978 Jun 30;149(2):279-93 [27283] J Biol Chem. 1992 Jun 5;267(16):10976-81 [1375933] Ann Neurol. 1986 Jun;19(6):517-24 [3729308] Ann Neurol. 1986 Jun;19(6):525-35 [3014994] Science. 1986 Sep 5;233(4768):1089-93 [3016903] Ann Neurol. 1986 Sep;20(3):289-95 [3532930] N Engl J Med. 1987 Dec 24;317(26):1643-7 [3479685] Science. 1988 Feb 5;239(4840):586-92 [3277272] J Neurosci. 1988 Jun;8(6):2153-63 [3385492] Nature. 1988 Oct 13;335(6191):639-42 [2845276] Proc Natl Acad Sci U S A. 1989 Jan;86(2):621-5 [2536171] Neurosci Lett. 1992 Feb 3;135(2):227-30 [1625799] Science. 1992 Jul 24;257(5069):494-6 [1353273] J Neurochem. 1992 Sep;59(3):897-905 [1379633] FASEB J. 1992 Sep;6(12):3051-64 [1381691] Neuroreport. 1992 Jun;3(6):530-2 [1382661] J Immunol. 1992 Oct 15;149(8):2736-41 [1383325] Ann Neurol. 1992 Sep;32(3):297-311 [1384420] Neuroreport. 1992 Oct;3(10):913-5 [1421098] Neuroreport. 1992 Jul;3(7):645-8 [1384768] Mol Pharmacol. 1992 Oct;42(4):619-26 [1331753] Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10945-9 [1279698] Brain Res. 1992 Oct 30;594(2):189-96 [1450945] Biochem J. 1989 Mar 1;258(2):621-4 [2706006] Proc Natl Acad Sci U S A. 1990 Feb;87(4):1620-4 [2154753] Science. 1990 Apr 20;248(4953):364-7 [2326646] J Neurochem. 1990 Jul;55(1):114-21 [2162373] Science. 1990 Aug 3;249(4968):549-53 [2200125] J Exp Med. 1992 Dec 1;176(6):1703-18 [1460427] Brain Res. 1992 Dec 11;598(1-2):196-202 [1486480] Proc Natl Acad Sci U S A. 1990 Nov;87(21):8607-11 [1978327] Science. 1990 Dec 14;250(4987):1593-6 [2148832] J Biol Chem. 1991 Mar 5;266(7):4244-50 [1847917] Trends Neurosci. 1991 Feb;14(2):60-7 [1708538] Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):6368-71 [1648740] Neuron. 1991 Jul;7(1):111-8 [1676893] Ion Channels. 1988;1:213-49 [2856492] Ann Neurol. 1991 Jun;29(6):651-7 [1909852] Arch Biochem Biophys. 1991 Aug 1;288(2):481-7 [1654835] Ann Neurol. 1991 Jul;30(1):110-4 [1656845] Eur J Pharmacol. 1991 Nov 12;204(3):339-40 [1773832] Nature. 1992 Feb 20;355(6362):722-5 [1371330] Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):2590-4 [1372982] Trends Neurosci. 1992 Mar;15(3):75-9 [1373919] J Pharmacol Exp Ther. 1985 Mar;232(3):708-16 [2983068] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dating the genetic bottleneck of the African cheetah. AN - 75670294; 8475057 AB - The cheetah is unusual among fields in exhibiting near genetic uniformity at a variety of loci previously screened to measure population genetic diversity. It has been hypothesized that a demographic crash or population bottleneck in the recent history of the species is causal to the observed monomorphic profiles for nuclear coding loci. The timing of a bottleneck is difficult to assess, but certain aspects of the cheetah's natural history suggest it may have occurred near the end of the last ice age (late Pleistocene, approximately 10,000 years ago), when a remarkable extinction of large vertebrates occurred on several continents. To further define the timing of such a bottleneck, the character of genetic diversity for two rapidly evolving DNA sequences, mitochondrial DNA and hypervariable minisatellite loci, was examined. Moderate levels of genetic diversity were observed for both of these indices in surveys of two cheetah subspecies, one from South Africa and one from East Africa. Back calculation from the extent of accumulation of DNA diversity based on observed mutation rates for VNTR (variable number of tandem repeats) loci and mitochondrial DNA supports a hypothesis of an ancient Pleistocene bottleneck that rendered the cheetah depauperate in genetic variation for nuclear coding loci but would allow sufficient time for partial reconstitution of more rapidly evolving genomic DNA segments. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Menotti-Raymond, M AU - O'Brien, S J AD - Biological Carcinogenesis and Development Program, National Cancer Institute, Frederick, MD 21702. Y1 - 1993/04/15/ PY - 1993 DA - 1993 Apr 15 SP - 3172 EP - 3176 VL - 90 IS - 8 SN - 0027-8424, 0027-8424 KW - DNA, Mitochondrial KW - 0 KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Phylogeny KW - Animals KW - Restriction Mapping KW - DNA Fingerprinting KW - South Africa KW - Namibia KW - DNA, Mitochondrial -- genetics KW - Genetic Variation KW - Acinonyx -- genetics KW - DNA -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75670294?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Dating+the+genetic+bottleneck+of+the+African+cheetah.&rft.au=Menotti-Raymond%2C+M%3BO%27Brien%2C+S+J&rft.aulast=Menotti-Raymond&rft.aufirst=M&rft.date=1993-04-15&rft.volume=90&rft.issue=8&rft.spage=3172&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 - 1993-05-17 N1 - Date created - 1993-05-17 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Genetics. 1981 Jan;97(1):145-63 [6266912] Mol Biol Evol. 1992 Jul;9(4):729-43 [1630309] Science. 1985 Mar 22;227(4693):1428-34 [2983425] Proc Natl Acad Sci U S A. 1987 Jan;84(2):508-11 [3467370] Biol Reprod. 1987 Mar;36(2):351-60 [3580457] Nature. 1988 Mar 17;332(6161):278-81 [3347271] Microb Pathog. 1987 Apr;2(4):269-82 [3507555] Hum Genet. 1989 Dec;84(1):75-8 [2558069] Proc Natl Acad Sci U S A. 1990 Jan;87(2):836-40 [1967831] Proc Natl Acad Sci U S A. 1990 Mar;87(5):1772-6 [1968637] Nature. 1990 Mar 15;344(6263):238-40 [1969116] Proc Natl Acad Sci U S A. 1990 Apr;87(7):2496-500 [2320570] Genomics. 1990 Mar;6(3):461-74 [1970327] Nature. 1990 Apr 19;344(6268):764-7 [1970419] Am J Hum Genet. 1990 Sep;47(3):499-514 [1975479] Am J Hum Genet. 1991 May;48(5):824-40 [2018036] Hum Genet. 1991 Sep;87(5):632-3 [1916768] J Hered. 1991 Sep-Oct;82(5):378-86 [1940281] Annu Rev Genet. 1991;25:45-69 [1667462] Proc Natl Acad Sci U S A. 1984 Apr;81(7):1991-5 [6326095] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Muscarinic receptor-mediated tyrosine phosphorylation of phospholipase C-gamma. An alternative mechanism for cholinergic-induced phosphoinositide breakdown. AN - 75668616; 7681827 AB - In Chinese hamster ovary cells transfected with m5 muscarinic receptors, carbachol stimulates both calcium influx and calcium release from intracellular stores. The marine toxin maitotoxin (MTX) elicits a similar response on calcium influx. Carbachol- and MTX-induced calcium influx can be inhibited by the proposed blockers of receptor-operated calcium channels (ROCC), CAI and SK&F 96365. Both carbachol and MTX induce a significant increase in total protein tyrosine phosphorylation, which is dependent on extracellular calcium and can be inhibited by CAI and SK&F 96365. Phospholipase C-gamma was identified as one of the substrates subject to calcium-dependent tyrosine phosphorylation following carbachol or MTX stimulation. Carbachol-induced [3H]inositol trisphosphate formation was partially inhibited by an inhibitor of tyrosine kinases, by removal of extracellular calcium, and by the inhibitor of receptor-operated calcium channels CAI suggesting that phosphorylation of phospholipase C-gamma plays a role in the muscarinic activation of phosphoinositide breakdown. Such an effect of carbachol is reminiscent of effects observed with peptide growth factors and represents a novel alternative signaling pathway for a muscarinic G protein-coupled receptor. JF - The Journal of biological chemistry AU - Gusovsky, F AU - Lueders, J E AU - Kohn, E C AU - Felder, C C AD - Laboratory of Bioorganic Chemistry, National Institute of Digestive Diseases and Kidney, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/04/15/ PY - 1993 DA - 1993 Apr 15 SP - 7768 EP - 7772 VL - 268 IS - 11 SN - 0021-9258, 0021-9258 KW - Calcium Channel Blockers KW - 0 KW - Isoenzymes KW - Marine Toxins KW - Oxocins KW - Phosphatidylinositols KW - Receptors, Muscarinic KW - Phosphotyrosine KW - 21820-51-9 KW - Tyrosine KW - 42HK56048U KW - Carbachol KW - 8Y164V895Y KW - maitotoxin KW - 9P59GES78D KW - Type C Phospholipases KW - EC 3.1.4.- KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Marine Toxins -- pharmacology KW - Animals KW - Phosphorylation KW - Calcium Channel Blockers -- pharmacology KW - Transfection KW - Kinetics KW - CHO Cells KW - Cricetinae KW - Calcium -- metabolism KW - Receptors, Muscarinic -- genetics KW - Phosphatidylinositols -- metabolism KW - Tyrosine -- analogs & derivatives KW - Carbachol -- pharmacology KW - Isoenzymes -- metabolism KW - Tyrosine -- analysis KW - Type C Phospholipases -- metabolism KW - Receptors, Muscarinic -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75668616?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Muscarinic+receptor-mediated+tyrosine+phosphorylation+of+phospholipase+C-gamma.+An+alternative+mechanism+for+cholinergic-induced+phosphoinositide+breakdown.&rft.au=Gusovsky%2C+F%3BLueders%2C+J+E%3BKohn%2C+E+C%3BFelder%2C+C+C&rft.aulast=Gusovsky&rft.aufirst=F&rft.date=1993-04-15&rft.volume=268&rft.issue=11&rft.spage=7768&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 - 1993-05-06 N1 - Date created - 1993-05-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transgenic mouse model for synergistic effects of nuclear oncogenes and growth factors in tumorigenesis: interaction of c-myc and transforming growth factor alpha in hepatic oncogenesis. AN - 75653923; 8467484 AB - Double transgenic mice bearing fusion genes consisting of mouse albumin enhancer/promoter-mouse c-myc complementary DNA and mouse metallothionein 1 promoter-human transforming growth factor alpha complementary DNA were generated to investigate the interaction of these genes in hepatic oncogenesis and to provide a general paradigm for characterizing the interaction of nuclear oncogenes and growth factors in tumorigenesis. Coexpression of c-myc and transforming growth factor alpha as transgenes in the mouse liver resulted in a tremendous acceleration of neoplastic development in this organ as compared to expression of either of these transgenes alone. The two distinct cellular reactions that occurred in the liver of the double transgenic mice prior to the appearance of liver tumors were dysplastic and apoptotic changes in the existing hepatocytes followed by emergence of multiple focal lesions composed of both hyperplastic and dysplastic cell populations. These observations suggest that the interaction of c-myc and transforming growth factor alpha, and possibly other combinations of nuclear oncogenes and growth factors, during development of hepatic neoplasia contributes to the selection and expansion of the preneoplastic cell populations which consequently increases the probability of malignant conversion. JF - Cancer research AU - Murakami, H AU - Sanderson, N D AU - Nagy, P AU - Marino, P A AU - Merlino, G AU - Thorgeirsson, S S AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, NIH, Bethesda, Maryland 20892. Y1 - 1993/04/15/ PY - 1993 DA - 1993 Apr 15 SP - 1719 EP - 1723 VL - 53 IS - 8 SN - 0008-5472, 0008-5472 KW - c-myc KW - Transforming Growth Factor alpha KW - 0 KW - Zinc KW - J41CSQ7QDS KW - Index Medicus KW - Animals KW - Zinc -- pharmacology KW - Cell Nucleus -- metabolism KW - Gene Expression KW - Disease Models, Animal KW - Mice KW - Mice, Transgenic KW - Male KW - Cell Transformation, Neoplastic -- genetics KW - Liver Neoplasms, Experimental -- genetics KW - Cocarcinogenesis KW - Transforming Growth Factor alpha -- genetics KW - Genes, myc UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75653923?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Transgenic+mouse+model+for+synergistic+effects+of+nuclear+oncogenes+and+growth+factors+in+tumorigenesis%3A+interaction+of+c-myc+and+transforming+growth+factor+alpha+in+hepatic+oncogenesis.&rft.au=Murakami%2C+H%3BSanderson%2C+N+D%3BNagy%2C+P%3BMarino%2C+P+A%3BMerlino%2C+G%3BThorgeirsson%2C+S+S&rft.aulast=Murakami&rft.aufirst=H&rft.date=1993-04-15&rft.volume=53&rft.issue=8&rft.spage=1719&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 - 1993-05-11 N1 - Date created - 1993-05-11 N1 - Date revised - 2017-01-13 N1 - Gene symbol - c-myc N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - G2 delay induced by nitrogen mustard in human cells affects cyclin A/cdk2 and cyclin B1/cdc2-kinase complexes differently. AN - 75636249; 8463339 AB - We investigated the temporal regulation of cyclin A- and B1-dependent kinases in human lymphoma cells treated with nitrogen mustard (HN2) and pentoxifylline, to determine whether the activity of these complexes correlated with cell cycle arrest induced by DNA damage. Cells were synchronized in G1/S, treated with HN2, and then postincubated with pentoxifylline. HN2-induced a protracted delay in G2 phase. This delay correlated with suppression of cyclin B1- and cdc2-kinase activities, and stabilization of hyperphosphorylated-cdc2 in the presence of similar cyclin B1 levels to those found in mitosis. HN2 had no discernible effect on the S phase activity of cyclin A- or cdk2-immune complexes. Entry of control cells into mitosis correlated with destruction of cyclin A, disappearance of cyclin A-bound cdk2 and decreased cdk2 kinase activity. G2 delay induced by HN2 was associated with stabilization of cyclin A, increased abundance of cyclin A-bound cdk2, and increased cdk2 activity. Cyclin A was also associated with cdc2, which, contrary to complexes containing cdk2, were only activated upon entry into mitosis. Pentoxifylline abrogated cell cycle arrest induced by aphidicolin and HN2 in human lymphoma cells. Pentoxifylline also reverted the activity of cyclin A- and B1-kinases in HN2-treated cells to approximately that observed in controls. Our findings suggest that delayed entry into mitosis following DNA damage correlates with suppression of cyclin B1/cdc2 and cyclin A/cdc2 complexes, while maintaining cyclin A/cdc2 complexes in an active state. Furthermore, we found that pentoxifylline disrupts the signal transduction pathway that regulates these complexes when damaged DNA is present, resulting in abrogation of cell cycle arrest. JF - The Journal of biological chemistry AU - O'Connor, P M AU - Ferris, D K AU - Pagano, M AU - Draetta, G AU - Pines, J AU - Hunter, T AU - Longo, D L AU - Kohn, K W AD - Laboratory of Molecular Pharmacology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/04/15/ PY - 1993 DA - 1993 Apr 15 SP - 8298 EP - 8308 VL - 268 IS - 11 SN - 0021-9258, 0021-9258 KW - Antigen-Antibody Complex KW - 0 KW - Cyclins KW - Aphidicolin KW - 38966-21-1 KW - Mechlorethamine KW - 50D9XSG0VR KW - Protein Kinases KW - EC 2.7.- KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - CDC2 Protein Kinase KW - EC 2.7.11.22 KW - CDC2-CDC28 Kinases KW - CDK2 protein, human KW - Cyclin-Dependent Kinase 2 KW - Cyclin-Dependent Kinases KW - Pentoxifylline KW - SD6QCT3TSU KW - Index Medicus KW - Aphidicolin -- pharmacology KW - Pentoxifylline -- pharmacology KW - Tumor Cells, Cultured KW - Mitotic Index -- drug effects KW - Kinetics KW - Humans KW - Flow Cytometry KW - Time Factors KW - Protein Binding KW - Lymphoma KW - Protein Kinases -- metabolism KW - Protein Kinases -- isolation & purification KW - G2 Phase -- drug effects KW - CDC2 Protein Kinase -- isolation & purification KW - CDC2 Protein Kinase -- metabolism KW - Cyclins -- isolation & purification KW - Cyclins -- metabolism KW - Mechlorethamine -- pharmacology KW - Cell Cycle -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75636249?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=G2+delay+induced+by+nitrogen+mustard+in+human+cells+affects+cyclin+A%2Fcdk2+and+cyclin+B1%2Fcdc2-kinase+complexes+differently.&rft.au=O%27Connor%2C+P+M%3BFerris%2C+D+K%3BPagano%2C+M%3BDraetta%2C+G%3BPines%2C+J%3BHunter%2C+T%3BLongo%2C+D+L%3BKohn%2C+K+W&rft.aulast=O%27Connor&rft.aufirst=P&rft.date=1993-04-15&rft.volume=268&rft.issue=11&rft.spage=8298&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 - 1993-05-06 N1 - Date created - 1993-05-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cross-talk between m1 muscarinic acetylcholine and beta 2-adrenergic receptors. cAMP and the third intracellular loop of m1 muscarinic receptors confer heterologous regulation. AN - 75635987; 8385129 AB - Genes encoding the m1 muscarinic (m1 mAChR) and beta 2-adrenergic receptors (beta 2AR) were stably co-expressed into Chinese hamster ovary (CHO) cells to study receptor regulation and cross-talk. Persistent activation of the beta 2AR/adenylate cyclase pathway by isoproterenol leads to heterologous desensitization, internalization, and down-regulation of the m1 mAChR which is comparable, but smaller in magnitude, with that seen with persistent activation of the m1 mAChR by carbachol. This heterologous effect was mimicked by dibutyryl cAMP and forskolin and antagonized by the protein kinase A (PKA) inhibitor H-8. A potential consensus sequence for phosphorylation by PKA (Lys351-Arg-Lys-Thr354) exists on the third intracellular loop of the m1 mAChR, suggesting that receptor phosphorylation by PKA may be involved in heterologous regulation. The loss of m1 mAChRs induced by carbachol was not reversed by H-8, indicating that homologous regulation is not dependent on PKA. Recent evidence suggests that muscarinic agonist-mediated internalization of the m1 mAChR involves the third intracellular loop (i3) (Maeda, S., Lameh, J., Mallet, W. G., Philip, M., Ramachandran, J., and Sadee, W. (1990) FEBS Lett. 269, 386-388). Three deletion mutant receptors were constructed in which the majority, or small regions, of i3 were eliminated but the membrane proximal portions of the loop were left intact. Each of the mutants was co-expressed with the beta 2AR in CHO cells. A small region in i3 was identified which is crucial for carbachol- and isoproterenol-promoted internalization and down-regulation. This region contains a series of 6 serine residues within an 8-amino acid stretch. A similar domain has been identified in the carboxyl tail of the beta 2AR and has been proposed to participate in receptor internalization (Hausdorff, W. P., Campbell, P. T., Ostrowski, J., Yu, S. S., Caron, M. G., and Lefkowitz, R. J. (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 2979-2983). JF - The Journal of biological chemistry AU - Lee, N H AU - Fraser, C M AD - Section on Molecular Neurobiology, National Institute on Alcohol Abuse and Alcoholism, Rockville, Maryland 20852. Y1 - 1993/04/15/ PY - 1993 DA - 1993 Apr 15 SP - 7949 EP - 7957 VL - 268 IS - 11 SN - 0021-9258, 0021-9258 KW - Isoquinolines KW - 0 KW - Oligodeoxyribonucleotides KW - Phosphatidylinositols KW - Protein Kinase Inhibitors KW - Receptors, Adrenergic, beta KW - Receptors, Muscarinic KW - Colforsin KW - 1F7A44V6OU KW - Bucladesine KW - 63X7MBT2LQ KW - Quinuclidinyl Benzilate KW - 6581-06-2 KW - N-(2-(methylamino)ethyl)-5-isoquinolinesulfonamide KW - 84478-11-5 KW - Carbachol KW - 8Y164V895Y KW - Cyclic AMP KW - E0399OZS9N KW - Adenylyl Cyclases KW - EC 4.6.1.1 KW - Isoproterenol KW - L628TT009W KW - Index Medicus KW - Phosphatidylinositols -- metabolism KW - Animals KW - Protein Structure, Secondary KW - Bucladesine -- pharmacology KW - Isoproterenol -- pharmacology KW - Mutagenesis KW - Carbachol -- metabolism KW - Isoquinolines -- pharmacology KW - Base Sequence KW - Colforsin -- pharmacology KW - Quinuclidinyl Benzilate -- metabolism KW - Transfection KW - Molecular Sequence Data KW - CHO Cells KW - Down-Regulation -- drug effects KW - Carbachol -- pharmacology KW - Sequence Deletion KW - Cricetinae KW - Receptors, Muscarinic -- genetics KW - Receptors, Adrenergic, beta -- metabolism KW - Receptors, Adrenergic, beta -- genetics KW - Cyclic AMP -- metabolism KW - Adenylyl Cyclases -- metabolism KW - Receptors, Muscarinic -- chemistry KW - Receptors, Muscarinic -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75635987?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cross-talk+between+m1+muscarinic+acetylcholine+and+beta+2-adrenergic+receptors.+cAMP+and+the+third+intracellular+loop+of+m1+muscarinic+receptors+confer+heterologous+regulation.&rft.au=Lee%2C+N+H%3BFraser%2C+C+M&rft.aulast=Lee&rft.aufirst=N&rft.date=1993-04-15&rft.volume=268&rft.issue=11&rft.spage=7949&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 - 1993-05-06 N1 - Date created - 1993-05-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Prevention of relapse of histoplasmosis with itraconazole in patients with the acquired immunodeficiency syndrome. AN - 75634887; 8383934 AB - To assess the efficacy and safety of itraconazole in preventing relapse of histoplasmosis after induction therapy with amphotericin B in patients with the acquired immunodeficiency syndrome (AIDS) and disseminated histoplasmosis. A prospective, multicenter, open-label clinical trial, with follow-up for at least 52 weeks. Tertiary care hospitals participating in a clinical investigation sponsored by the National Institutes of Allergy and Infectious Diseases (AIDS Clinical Trial Group and Mycoses Study Group). Forty-two patients with AIDS who had successfully completed induction therapy for disseminated histoplasmosis amphotericin B, at least 15 mg/kg body weight given over 4 to 12 weeks. Itraconazole, 200 mg given orally twice daily. Response to therapy, specifically prevention of histoplasmosis relapse, was the main outcome measure. Secondary end points were survival and the effect of therapy on Histoplasma capsulatum variety capsulatum antigen levels in urine and serum. Plasma itraconazole concentrations were measured to document drug absorption and compliance with therapy. The median follow-up was 109 weeks, and median survival was 98 weeks. Two relapses occurred (5%; 95% CI, 0.5% to 16%), one in a patient withdrawn from the study 18 weeks earlier and one in a patient who did not comply with the study therapy. Patients with elevated antigen levels at study entry showed clearance of antigen from urine and serum; urine specimens became negative in 43% of patients (CI, 26% to 59%), and serum specimens became negative in 75% of patients (CI, 56% to 94%). Only one patient discontinued treatment because of itraconazole toxicity (hypokalemia). Itraconazole, 200 mg twice daily, is safe and effective in preventing relapse of disseminated histoplasmosis in patients with AIDS. Antigen clearance from blood and urine correlates with clinical efficacy. JF - Annals of internal medicine AU - Wheat, J AU - Hafner, R AU - Wulfsohn, M AU - Spencer, P AU - Squires, K AU - Powderly, W AU - Wong, B AU - Rinaldi, M AU - Saag, M AU - Hamill, R AU - Murphy, R AU - Connolly-Stringfield, P AU - Briggs, N AU - Owens, S AU - National Institute of Allergy and Infectious Diseases Clinical Trials and Mycoses Study Group Collaborators AD - Indiana University School of Medicine, Wishard Memorial Hospital, Indianapolis 46202-2879. ; National Institute of Allergy and Infectious Diseases Clinical Trials and Mycoses Study Group Collaborators Y1 - 1993/04/15/ PY - 1993 DA - 1993 Apr 15 SP - 610 EP - 616 VL - 118 IS - 8 SN - 0003-4819, 0003-4819 KW - Antifungal Agents KW - 0 KW - Antigens, Fungal KW - Itraconazole KW - 304NUG5GF4 KW - Amphotericin B KW - 7XU7A7DROE KW - Ketoconazole KW - R9400W927I KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Humans KW - Recurrence KW - Prospective Studies KW - Patient Compliance KW - Adult KW - Middle Aged KW - Adolescent KW - Amphotericin B -- therapeutic use KW - Antigens, Fungal -- metabolism KW - Female KW - Male KW - Histoplasma -- immunology KW - AIDS-Related Opportunistic Infections -- drug therapy KW - Antifungal Agents -- adverse effects KW - Ketoconazole -- therapeutic use KW - Ketoconazole -- analogs & derivatives KW - Ketoconazole -- adverse effects KW - Histoplasmosis -- drug therapy KW - Ketoconazole -- blood KW - Antifungal Agents -- blood KW - Antifungal Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75634887?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+internal+medicine&rft.atitle=Prevention+of+relapse+of+histoplasmosis+with+itraconazole+in+patients+with+the+acquired+immunodeficiency+syndrome.&rft.au=Wheat%2C+J%3BHafner%2C+R%3BWulfsohn%2C+M%3BSpencer%2C+P%3BSquires%2C+K%3BPowderly%2C+W%3BWong%2C+B%3BRinaldi%2C+M%3BSaag%2C+M%3BHamill%2C+R%3BMurphy%2C+R%3BConnolly-Stringfield%2C+P%3BBriggs%2C+N%3BOwens%2C+S%3BNational+Institute+of+Allergy+and+Infectious+Diseases+Clinical+Trials+and+Mycoses+Study+Group+Collaborators&rft.aulast=Wheat&rft.aufirst=J&rft.date=1993-04-15&rft.volume=118&rft.issue=8&rft.spage=610&rft.isbn=&rft.btitle=&rft.title=Annals+of+internal+medicine&rft.issn=00034819&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-04-15 N1 - Date created - 1993-04-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Protection of human endothelial cells from oxidant injury by adenovirus-mediated transfer of the human catalase cDNA. AN - 75700507; 8479912 AB - In a variety of disorders, endothelial cells are exposed to high levels of oxidants, generated within the cells and/or consequent to local inflammation. In the context of the sensitivity of endothelial cells to oxidant stress, particularly related to H2O2, we have designed a replication deficient recombinant adenovirus containing the human catalase cDNA (AdCL) to transfer the catalase cDNA to the endothelial cells, in order to augment intracellular anti-H2O2 protection. Human umbilical vein endothelial cells that were not infected or infected with control adenovirus maintained low levels of catalase mRNA. Endothelial cells infected with AdCL expressed AdCL-driven exogenous catalase mRNA, as early as 24 hr and at least for 7 days. Catalase protein levels were increased significantly over controls in cells infected with AdCL, as were catalase activity levels, with catalase activity correlated closely with levels of catalase protein. Importantly, when the endothelial cells were exposed to 500 microM H2O2, all the AdCL infected endothelial cells survived, compared to only 37% of the control cells. Thus, a recombinant adenovirus containing the human catalase cDNA is able to infect human endothelial cells in vitro and express high levels of functional intracellular catalase, protecting the cells against H2O2-mediated oxidant stress. These observations support the feasibility of the transfer of catalase cDNA to human endothelium to protect against oxidant injury. JF - Nucleic acids research AU - Erzurum, S C AU - Lemarchand, P AU - Rosenfeld, M A AU - Yoo, J H AU - Crystal, R G AD - Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/04/11/ PY - 1993 DA - 1993 Apr 11 SP - 1607 EP - 1612 VL - 21 IS - 7 SN - 0305-1048, 0305-1048 KW - RNA, Messenger KW - 0 KW - Hydrogen Peroxide KW - BBX060AN9V KW - Catalase KW - EC 1.11.1.6 KW - Index Medicus KW - Adenoviridae KW - Base Sequence KW - RNA, Messenger -- metabolism KW - Transfection KW - Cells, Cultured KW - Humans KW - Genetic Vectors KW - Molecular Sequence Data KW - Gene Expression KW - Hydrogen Peroxide -- toxicity KW - Catalase -- metabolism KW - Catalase -- biosynthesis KW - Endothelium, Vascular -- metabolism KW - Hydrogen Peroxide -- metabolism KW - Catalase -- genetics KW - Endothelium, Vascular -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75700507?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nucleic+acids+research&rft.atitle=Protection+of+human+endothelial+cells+from+oxidant+injury+by+adenovirus-mediated+transfer+of+the+human+catalase+cDNA.&rft.au=Erzurum%2C+S+C%3BLemarchand%2C+P%3BRosenfeld%2C+M+A%3BYoo%2C+J+H%3BCrystal%2C+R+G&rft.aulast=Erzurum&rft.aufirst=S&rft.date=1993-04-11&rft.volume=21&rft.issue=7&rft.spage=1607&rft.isbn=&rft.btitle=&rft.title=Nucleic+acids+research&rft.issn=03051048&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-05-25 N1 - Date created - 1993-05-25 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Am J Respir Cell Mol Biol. 1991 Apr;4(4):364-8 [1901719] Eur Respir J Suppl. 1990 Oct;11:482s-484s [2278607] Biochemistry. 1991 Sep 24;30(38):9305-13 [1654093] Pharmacol Ther. 1989;44(2):297-307 [2519346] J Clin Invest. 1992 Jan;89(1):197-202 [1370294] Cell. 1992 Jan 10;68(1):143-55 [1370653] Free Radic Biol Med. 1991;11(6):545-55 [1778501] Am J Respir Cell Mol Biol. 1992 Feb;6(2):175-82 [1540380] Circ Res. 1992 May;70(5):991-8 [1568306] Atherosclerosis. 1991 Nov;91(1-2):1-14 [1811545] Proc Natl Acad Sci U S A. 1992 Jul 15;89(14):6482-6 [1631146] Virology. 1973 Apr;52(2):456-67 [4705382] J Gen Virol. 1977 Jul;36(1):59-74 [886304] J Clin Invest. 1981 Sep;68(3):714-21 [6268662] Lab Invest. 1982 Nov;47(5):412-26 [6290784] Cell. 1982 Dec;31(3 Pt 2):543-51 [6297772] J Clin Invest. 1984 Jan;73(1):87-95 [6690485] J Immunol Methods. 1983 Dec 16;65(1-2):55-63 [6606682] J Clin Invest. 1984 Mar;73(3):706-13 [6707200] Circ Shock. 1984;12(4):229-39 [6327114] Methods Enzymol. 1984;105:121-6 [6727660] Am Rev Respir Dis. 1984 Aug;130(2):209-13 [6087699] Proc Natl Acad Sci U S A. 1984 Dec;81(23):7269-73 [6095281] N Engl J Med. 1985 Jan 17;312(3):159-63 [2981404] Nucleic Acids Res. 1986 Jul 11;14(13):5561-2 [3755526] J Lab Clin Med. 1986 Sep;108(3):190-8 [3091744] Am J Physiol. 1986 Nov;251(5 Pt 1):C671-80 [3777154] J Free Radic Biol Med. 1986;2(5-6):359-65 [3598065] Am Rev Respir Dis. 1987 Aug;136(2):483-5 [3619213] FASEB J. 1987 Nov;1(5):358-64 [2824268] J Clin Invest. 1988 Apr;81(4):1297-301 [3127425] J Biol Chem. 1988 May 15;263(14):6884-92 [3129432] J Clin Invest. 1988 May;81(5):1556-62 [3130395] J Clin Invest. 1988 Sep;82(3):1040-50 [2843565] N Engl J Med. 1989 Feb 9;320(6):365-76 [2536474] Free Radic Biol Med. 1988;5(5-6):409-19 [3076884] Biotechniques. 1988 Jul-Aug;6(7):616-29 [3078719] Free Radic Biol Med. 1990;8(2):201-9 [2185145] Science. 1991 Apr 19;252(5004):431-4 [2017680] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Report of the Cancer Therapy Evaluation Program monitoring plan for secondary acute myeloid leukemia following treatment with epipodophyllotoxins. AN - 75663389; 8455202 AB - Recent reports have documented the occurrence of treatment-related acute myeloid leukemia (AML) following therapy with epipodophyllotoxins. These reports have led to growing concern among oncologists, which could lead to premature abandonment of these agents at a time when the relationship between cumulative dose of epipodophyllotoxin and risk of treatment-related AML has not been determined. Because of the increasingly important role of epipodophyllotoxins in the treatment of several types of adult and pediatric tumors, the Cancer Therapy Evaluation Program (CTEP) of the National Cancer Institute (NCI) has developed a monitoring plan to obtain reliable estimates of the risk of treatment-related AML following epipodophyllotoxin treatment. We identified 12 NCI-supported Cooperative Group clinical trials in which patients with solid tumors are being treated with epipodophyllotoxins at different cumulative doses. One trial is using a moderate dose of teniposide (900 mg/m2), and 11 trials are using etoposide at a low dose ( or = 4000 mg/m2). Cases of treatment-related AML and treatment-related myelodysplastic syndrome (MDS) (hereafter referred to as treatment-related AML/MDS) occurring in these trials are reported to CTEP, with initial analysis for each cumulative dose group triggered by the reporting of four cases of treatment-related AML/MDS in that group. For each analysis, total patient follow-up for the group is determined and cumulative 6-year incidence rate is calculated. Three cases of treatment-related AML and one case of treatment-related MDS (with documented monosomy 7) were reported in a group of 207 patients who received etoposide at a low cumulative dose. The calculated 6-year rate of development of treatment-related AML/MDS was 3.2% (95% upper confidence interval bounded by 7.2%). The 6-year cumulative rate of treatment-related AML/MDS (3.2%) is within the range previously reported for alkylator-based regimens that did not include epipodophyllotoxins. Previous reports have suggested that higher cumulative doses of alkylators are associated with increased risk of treatment-related AML, and a critical goal of the monitoring plan is to determine whether a similar relationship exists for the epipodophyllotoxins. Estimates will be developed for leukemogenic risk for the moderate- and high-cumulative-dose groups when four cases of treatment-related AML/MDS have been identified within each group. JF - Journal of the National Cancer Institute AU - Smith, M A AU - Rubinstein, L AU - Cazenave, L AU - Ungerleider, R S AU - Maurer, H M AU - Heyn, R AU - Khan, F M AU - Gehan, E AD - Cancer Therapy Evaluation Program, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/04/07/ PY - 1993 DA - 1993 Apr 07 SP - 554 EP - 558 VL - 85 IS - 7 SN - 0027-8874, 0027-8874 KW - Etoposide KW - 6PLQ3CP4P3 KW - Podophyllotoxin KW - L36H50F353 KW - Index Medicus KW - Acute Disease KW - Humans KW - Adult KW - Clinical Trials as Topic KW - Incidence KW - Etoposide -- adverse effects KW - Child KW - Leukemia, Myeloid -- chemically induced KW - Podophyllotoxin -- adverse effects KW - Myelodysplastic Syndromes -- chemically induced KW - Neoplasms, Second Primary -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75663389?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+National+Cancer+Institute&rft.atitle=Report+of+the+Cancer+Therapy+Evaluation+Program+monitoring+plan+for+secondary+acute+myeloid+leukemia+following+treatment+with+epipodophyllotoxins.&rft.au=Smith%2C+M+A%3BRubinstein%2C+L%3BCazenave%2C+L%3BUngerleider%2C+R+S%3BMaurer%2C+H+M%3BHeyn%2C+R%3BKhan%2C+F+M%3BGehan%2C+E&rft.aulast=Smith&rft.aufirst=M&rft.date=1993-04-07&rft.volume=85&rft.issue=7&rft.spage=554&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+National+Cancer+Institute&rft.issn=00278874&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-04-16 N1 - Date created - 1993-04-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In vivo inhibition of glucocorticoid-inducible gene expression by dimethylnitrosamine in rat liver. AN - 75679948; 8097092 AB - Sprague-Dawley rats were pretreated with a single i.p. injection of either 2.25 mL/kg of phosphate-buffered saline (PBS) or 22.5 mg/kg of dimethylnitrosamine (DMN) followed 2 hr later by a single i.p. injection of either 1.35 mg/kg of dexamethasone (DEX) or the vehicle, a 50% ethanol solution, both delivered in a volume of 3 mL/kg. RNA levels of the hormone-inducible, specialized liver function genes, tyrosine aminotransferase (TAT) and glutamine synthetase (GS), were monitored 4, 5, 6, 7, 8, and 10 hr after the DEX injection. Maximal induction of both the TAT (26-fold) and GS (6-fold) RNAs occurred 6 hr after DEX administration in PBS-pretreated animals. Pretreatment with DMN caused at least a 42% inhibition of DEX-induced RNA accumulation at every time point examined, with greater than 90% inhibition occurring when the genes were maximally induced at 6 hr. This inhibition was not due to any alterations of the glucocorticoid receptors as DMN had no effect on the binding affinity or amounts of glucocorticoid receptors present in rat hepatic cytosols. These results suggest that chemical carcinogens such as DMN may affect normal gene function in vivo by inhibiting the cellular response to hormone receptors mediating differentiation-associated, specialized cell functions. JF - Biochemical pharmacology AU - Miller, M S AU - Buzard, G S AU - McDowell, A E AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702. Y1 - 1993/04/06/ PY - 1993 DA - 1993 Apr 06 SP - 1465 EP - 1470 VL - 45 IS - 7 SN - 0006-2952, 0006-2952 KW - Carcinogens KW - 0 KW - RNA, Messenger KW - Receptors, Glucocorticoid KW - Dexamethasone KW - 7S5I7G3JQL KW - Tyrosine Transaminase KW - EC 2.6.1.5 KW - Glutamate-Ammonia Ligase KW - EC 6.3.1.2 KW - Dimethylnitrosamine KW - M43H21IO8R KW - Index Medicus KW - Gene Expression -- drug effects KW - Animals KW - Receptors, Glucocorticoid -- drug effects KW - Tyrosine Transaminase -- biosynthesis KW - Tyrosine Transaminase -- genetics KW - RNA, Messenger -- analysis KW - Receptors, Glucocorticoid -- metabolism KW - Glutamate-Ammonia Ligase -- genetics KW - Rats KW - Rats, Sprague-Dawley KW - Glutamate-Ammonia Ligase -- biosynthesis KW - Enzyme Induction KW - Time Factors KW - Dimethylnitrosamine -- pharmacology KW - Carcinogens -- pharmacology KW - Liver -- enzymology KW - Carcinogens -- administration & dosage KW - Dexamethasone -- metabolism KW - Liver -- drug effects KW - Dexamethasone -- antagonists & inhibitors KW - Dimethylnitrosamine -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75679948?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+pharmacology&rft.atitle=In+vivo+inhibition+of+glucocorticoid-inducible+gene+expression+by+dimethylnitrosamine+in+rat+liver.&rft.au=Miller%2C+M+S%3BBuzard%2C+G+S%3BMcDowell%2C+A+E&rft.aulast=Miller&rft.aufirst=M&rft.date=1993-04-06&rft.volume=45&rft.issue=7&rft.spage=1465&rft.isbn=&rft.btitle=&rft.title=Biochemical+pharmacology&rft.issn=00062952&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-05-10 N1 - Date created - 1993-05-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Studies on the substrate specificity of the proteinase of equine infectious anemia virus using oligopeptide substrates. AN - 75648831; 8384879 AB - The proteinase of the equine infectious anemia virus (EIAV), a lentivirus closely related to human immunodeficiency virus (HIV), was purified from concentrated virus. The specificity of the enzyme was characterized using oligopeptides representing naturally occurring cleavage sites in the Gag and Gag-Pol polyproteins. The length of the substrate binding pocket was found to be 1-2 residues longer than that of HIV proteinases. Although the EIAV and HIV proteinases cleaved most of the peptides at the same bond, some were hydrolyzed by only the EIAV enzyme. Oligopeptides representing cleavage sites in the nucleocapsid protein were also found to be substrates of the EIAV proteinase. However, these peptides were not hydrolyzed by the HIV proteinases. While peptides representing the corresponding sequences in the first cysteine arrays of the nucleocapsid proteins of HIV-1 and HIV-2 were substrates of the proteinases, peptides representing the homologous sequences in the second Cys arrays were resistant against the proteolytic attack. A three-dimensional model of the EIAV proteinase built on the basis of homology with HIV-1 proteinase was used to interpret the differences. In addition to the oligopeptides representing cleavage sites in the Gag and Gag-Pol polyproteins, the EIAV proteinase was also able to cleave an oligopeptide mimicking a cleavage site in the transmembrane protein. Our results suggest that the specificity of lentiviral proteinases share common characteristics, although substantial differences may exist in hydrolysis of some peptides. JF - Biochemistry AU - Tözsér, J AU - Friedman, D AU - Weber, I T AU - Bláha, I AU - Oroszlan, S AD - Laboratory of Molecular Virology and Carcinogenesis, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland 21702-1201. Y1 - 1993/04/06/ PY - 1993 DA - 1993 Apr 06 SP - 3347 EP - 3353 VL - 32 IS - 13 SN - 0006-2960, 0006-2960 KW - Oligopeptides KW - 0 KW - Proteins KW - Retroviridae Proteins KW - Endopeptidases KW - EC 3.4.- KW - HIV Protease KW - EC 3.4.23.- KW - Index Medicus KW - AIDS/HIV KW - Retroviridae Proteins -- metabolism KW - Protein Processing, Post-Translational KW - Molecular Sequence Data KW - Oligopeptides -- metabolism KW - Amino Acid Sequence KW - Substrate Specificity KW - HIV Protease -- chemistry KW - Proteins -- metabolism KW - Endopeptidases -- isolation & purification KW - Infectious Anemia Virus, Equine -- enzymology KW - Endopeptidases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75648831?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Studies+on+the+substrate+specificity+of+the+proteinase+of+equine+infectious+anemia+virus+using+oligopeptide+substrates.&rft.au=T%C3%B6zs%C3%A9r%2C+J%3BFriedman%2C+D%3BWeber%2C+I+T%3BBl%C3%A1ha%2C+I%3BOroszlan%2C+S&rft.aulast=T%C3%B6zs%C3%A9r&rft.aufirst=J&rft.date=1993-04-06&rft.volume=32&rft.issue=13&rft.spage=3347&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-05-05 N1 - Date created - 1993-05-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tyrosine phosphorylation of pp125FAK by the aggregation of high affinity immunoglobulin E receptors requires cell adherence. AN - 75662936; 8463210 AB - The aggregation of the high affinity IgE receptor (Fc epsilon RI) in adherent rat basophilic leukemia (RBL-2H3) cells induces the tyrosine phosphorylation of several proteins. We examined whether focal adhesion-associated tyrosine kinase, pp125FAK, is one of these proteins. Anti-pp125FAK monoclonal antibody immunoblotted and precipitated a 115-kDa tyrosine-phosphorylated protein. In the absence of Fc epsilon RI aggregation, pp125FAK was tyrosine-phosphorylated only in adherent cells. Aggregating Fc epsilon RI in adherent cells markedly enhanced tyrosine phosphorylation of pp125FAK. This increase was detectable within 1 min of Fc epsilon RI aggregation and was maximal by 15 min. In contrast, in nonadherent cells Fc epsilon RI aggregation did not induce tyrosine phosphorylation of pp125FAK. The enhanced influx of calcium by calcium ionophore or the activation of protein kinase C by phorbol myristate acetate induced tyrosine phosphorylation of pp125FAK only in adherent cells. Thus, Fc epsilon RI-induced tyrosine phosphorylation of pp125FAK could be mediated by the activation of protein kinase C and/or the induction of calcium influx. The data indicate that cell adherence is essential for Fc epsilon RI-induced tyrosine phosphorylation of pp125FAK. JF - The Journal of biological chemistry AU - Hamawy, M M AU - Mergenhagen, S E AU - Siraganian, R P AD - Laboratory of Immunology, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/04/05/ PY - 1993 DA - 1993 Apr 05 SP - 6851 EP - 6854 VL - 268 IS - 10 SN - 0021-9258, 0021-9258 KW - Cell Adhesion Molecules KW - 0 KW - Receptors, IgE KW - Calcimycin KW - 37H9VM9WZL KW - Tyrosine KW - 42HK56048U KW - Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - Focal Adhesion Kinase 1 KW - EC 2.7.10.2 KW - Focal Adhesion Protein-Tyrosine Kinases KW - Ptk2 protein, rat KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Rats KW - Immunoblotting KW - Animals KW - Tumor Cells, Cultured KW - Phosphorylation KW - Kinetics KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Calcimycin -- pharmacology KW - Receptors, IgE -- metabolism KW - Cell Adhesion Molecules -- metabolism KW - Tyrosine -- metabolism KW - Receptor Aggregation KW - Protein-Tyrosine Kinases -- metabolism KW - Cell Adhesion UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75662936?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Tyrosine+phosphorylation+of+pp125FAK+by+the+aggregation+of+high+affinity+immunoglobulin+E+receptors+requires+cell+adherence.&rft.au=Hamawy%2C+M+M%3BMergenhagen%2C+S+E%3BSiraganian%2C+R+P&rft.aulast=Hamawy&rft.aufirst=M&rft.date=1993-04-05&rft.volume=268&rft.issue=10&rft.spage=6851&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 - 1993-05-05 N1 - Date created - 1993-05-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Toxicity of Bordetella avium beta-cystathionase toward MC3T3-E1 osteogenic cells. AN - 75659811; 8463265 AB - Bordetella avium is the etiological agent of an upper respiratory disease in birds which, symptomatically and pathologically, resembles bordetellosis in humans. Studies of the virulence of this organism revealed a novel cytotoxic protein, designated osteotoxin, that was lethal for MC3T3-E1 osteogenic cells, fetal bovine trabecular cells, UMR106-01(BSP) rat osteosarcoma cells, and embryonic bovine tracheal cells. The osteotoxin lacked dermonecrotic toxin activity, exhibited no cross-reactivity with antibody against B. avium dermonecrotic toxin, and was non-proteolytic. Osteotoxin (M(r) approximately 80,000 by gel filtration, pI 5.4) was purified to electrophoretic homogeneity from B. avium 197. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and spectrophotometric analyses showed that the native protein was a homodimer and that each of the non-covalently linked subunits (M(r) approximately 41,000) contained one molecule of pyridoxal 5'-phosphate. Microsequencing of the first 32 amino acids from the NH2 terminus allowed the synthesis of two oligonucleotide probes, which, together with polyclonal antibody to the purified protein, facilitated cloning, sequencing, and expression of the osteotoxin gene product in Escherichia coli. The open reading frame encodes a polypeptide of 396 amino acid residues (M(r) = 42,606, calculated pI 5.9), whose sequence exhibits approximately 38% identity (approximately 60% similarity) to pyridoxal 5'-phosphate-dependent beta-cystathionase(s) from E. coli, Salmonella typhimurium, and rat liver. The characteristic motif, TKYXXGHSD, associated with binding the cofactor in these enzymes is also present in osteotoxin. Physicochemical and enzymatic analyses established the coidentity of osteotoxin with beta-cystathionase. The region upstream of the beta-cystathionase (metC) gene in B. avium 197 lacked regulatory sequences ("Met boxes") described for metC in enteric species, and enzyme production was not repressed by methionine. Incubation of MC3T3-E1 osteogenic cells in medium containing L-[35S]cystine and purified beta-cystathionase resulted in 35S-labeling of the enzyme and at least one major MC3T3-E1 cell protein (M(r) approximately 50,000). cytotoxicity can be attributed to: 1) beta-cystathionase-catalyzed cleavage of L-cystine in the medium and formation of reactive sulfane-containing derivative(s), and 2) transfer of sulfane sulfur to metabolically sensitive or structurally important proteins in the osteogenic cells. JF - The Journal of biological chemistry AU - Gentry-Weeks, C R AU - Keith, J M AU - Thompson, J AD - Laboratory of Microbial Ecology, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/04/05/ PY - 1993 DA - 1993 Apr 05 SP - 7298 EP - 7314 VL - 268 IS - 10 SN - 0021-9258, 0021-9258 KW - Bacterial Toxins KW - 0 KW - DNA, Bacterial KW - Virulence Factors, Bordetella KW - dermonecrotic toxin, Bordetella KW - Transglutaminases KW - EC 2.3.2.13 KW - Lyases KW - EC 4.- KW - cystathionine beta-lyase KW - EC 4.4.1.8 KW - Index Medicus KW - Swine KW - Animals KW - Turkeys KW - Electrophoresis, Polyacrylamide Gel KW - Guinea Pigs KW - Isoelectric Point KW - Rabbits KW - Amino Acid Sequence KW - Cloning, Molecular KW - Rats KW - Base Sequence KW - Blotting, Western KW - Cattle KW - Spectrum Analysis KW - Cells, Cultured KW - Kinetics KW - Restriction Mapping KW - Cell Death KW - Molecular Sequence Data KW - Substrate Specificity KW - Sequence Homology, Amino Acid KW - Cell Line KW - Osteoblasts -- drug effects KW - Bacterial Toxins -- genetics KW - Bacterial Toxins -- antagonists & inhibitors KW - Bacterial Toxins -- isolation & purification KW - Lyases -- toxicity KW - Lyases -- genetics KW - Lyases -- antagonists & inhibitors KW - Bacterial Toxins -- toxicity KW - Bordetella -- enzymology KW - Lyases -- isolation & purification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75659811?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Toxicity+of+Bordetella+avium+beta-cystathionase+toward+MC3T3-E1+osteogenic+cells.&rft.au=Gentry-Weeks%2C+C+R%3BKeith%2C+J+M%3BThompson%2C+J&rft.aulast=Gentry-Weeks&rft.aufirst=C&rft.date=1993-04-05&rft.volume=268&rft.issue=10&rft.spage=7298&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 - 1993-05-05 N1 - Date created - 1993-05-05 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - L10425; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Using the tolerable-dose diagram in the design of phase I combination chemotherapy trials. AN - 85276125; pmid-8478673 AB - PURPOSE: Choosing maximum-tolerated doses (MTDs) of agents to be administered in combination is more complicated than choosing the MTD for a single agent. This is because there are many combinations of doses that will be tolerated. We offer guidance in targeting specific MTD combinations, and suggest trial designs to achieve these targets. METHODS: A graphical method based on a simple, previously described mathematical model is used to guide the phase I trial design. The method involves constructing a tolerable-dose diagram, which displays the toxicities that are expected to occur at various dose combinations. The data required for the method are the single-agent toxicity profiles of the agents. Designs for combinations of taxol with fluorouracil, carboplatin, doxorubicin, cyclophosphamide, and cisplatin are used to demonstrate the methods. RESULTS: For all of the drugs considered here, leukopenia is dose-limiting or nearly dose-limiting. Consequently, no major improvement in total dose-intensity is achievable by combining these drugs. If leukopenia can be eliminated or substantially reduced by use of chemoprotective agents, then a cyclophosphamide/taxol combination appears promising from a dose-intensity point of view. For other combinations, the doses must be reduced from single-agent MTD levels. In the absence of biologic information such as concentrations needed for optimal modulation, it is suggested that single-agent MTDs be reduced approximately proportionately for each drug in the combination. CONCLUSION: Tolerable-dose diagrams are useful for planning phase I trials of combinations of agents. They can suggest which combinations are promising from a dose-intensity perspective, as well as dose-escalation schemes for combinations to be pursued for dose-intensity or other considerations. JF - Journal of Clinical Oncology AU - Korn, E L AU - Simon, R AD - Biometric Research Branch, National Cancer Institute, Bethesda, MD 20892. PY - 1993 SP - 794 EP - 801 VL - 11 IS - 4 SN - 0732-183X, 0732-183X KW - Antineoplastic Agents KW - Human KW - Carboplatin KW - Cyclophosphamide KW - Doxorubicin KW - Clinical Trials, Phase I UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85276125?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Clinical+Oncology&rft.atitle=Using+the+tolerable-dose+diagram+in+the+design+of+phase+I+combination+chemotherapy+trials.&rft.au=Korn%2C+E+L%3BSimon%2C+R&rft.aulast=Korn&rft.aufirst=E&rft.date=1993-04-01&rft.volume=11&rft.issue=4&rft.spage=794&rft.isbn=&rft.btitle=&rft.title=Journal+of+Clinical+Oncology&rft.issn=0732183X&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Safety of rapid-rate transcranial magnetic stimulation in normal volunteers. AN - 85239836; pmid-7683602 AB - In 9 normal volunteers, we studied the safety of rapid-rate transcranial magnetic stimulation (rTMS) applied to different scalp positions at various frequencies and intensities. Pure tone threshold audiometry showed temporary threshold shifts in 3 subjects. In the subject stimulated at the highest intensity, rTMS induced a focal, secondarily generalized seizure despite the absence of definite risk factors for seizures. Rapid-rate TMS did not result in any important changes in the neurological examination findings, cognitive performance, electroencephalogram, electrocardiogram, and hormone levels (prolactin, adrenocorticotropic hormone, thyroid-stimulating hormone, luteinizing hormone, and follicle-stimulating hormone). In 10 additional subjects, the electromyographic activity in several contralateral muscles showed that trains of rTMS applied to the motor cortex induced a spread of cortical excitability. The spread of excitability depended on the intensity and frequency of the stimuli and probably constituted an early epileptogenic effect of rTMS. Guidelines for preventing the undesirable side effects of rTMS are offered. JF - Electroencephalography and Clinical Neurophysiology AU - Pascual-Leone, A AU - Houser, C M AU - Reese, K AU - Shotland, L I AU - Grafman, J AU - Sato, S AU - Valls-Solé J AU - Brasil-Neto, J P AU - Wassermann, E M AU - Cohen, L G AD - Human Cortical Physiology Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892. PY - 1993 SP - 120 EP - 130 VL - 89 IS - 2 SN - 0013-4694, 0013-4694 KW - Reference Values KW - Magnetics KW - Audiometry KW - Human KW - Safety KW - Electroencephalography KW - Muscles KW - Brain KW - Electromyography KW - Mental Recall KW - Memory KW - Adult KW - Middle Age KW - Gonadotropins, Pituitary KW - Neuropsychological Tests KW - Neuropeptides KW - Male KW - Female KW - Reaction Time UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85239836?accountid=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=Electroencephalography+and+Clinical+Neurophysiology&rft.atitle=Safety+of+rapid-rate+transcranial+magnetic+stimulation+in+normal+volunteers.&rft.au=Pascual-Leone%2C+A%3BHouser%2C+C+M%3BReese%2C+K%3BShotland%2C+L+I%3BGrafman%2C+J%3BSato%2C+S%3BValls-Sol%C3%A9+J%3BBrasil-Neto%2C+J+P%3BWassermann%2C+E+M%3BCohen%2C+L+G&rft.aulast=Pascual-Leone&rft.aufirst=A&rft.date=1993-04-01&rft.volume=89&rft.issue=2&rft.spage=120&rft.isbn=&rft.btitle=&rft.title=Electroencephalography+and+Clinical+Neurophysiology&rft.issn=00134694&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Court-ordered reimbursement for unproven medical technology. Circumventing technology assessment. AN - 85226122; pmid-8468767 AB - OBJECTIVE--Because we found examples where courts of law ruled against insurance carriers that had been sued for reimbursement for unproven medical procedures, we conducted a case study to determine the reasoning behind these decisions that run counter to accepted medical science. Such actions circumvent health technology assessment and could contribute to escalating health care costs and poorer quality health care. DATA SOURCES--A literature search identified 17 cases between 1980 and 1989 in which an insurance company was sued to reimburse a patient who had received an unproven or questionable health technology; 14 of these suits were decided in favor of the plaintiff, and the insurance company was ordered to pay. Discussed in this article are six of these cases, two involving Laetrile (amygdalin), two involving immunoaugmentative therapy, and two involving thermography, technologies that had previously been assessed as not safe, not effective, or inadequately evaluated. DATA SYNTHESIS AND CONCLUSIONS--The circumstances determining how the courts arrive at these "unscientific" decisions fall into three general categories: (1) for legal reasons, the insurance contract is interpreted in favor of the insured; (2) the reluctance and/or inability, legal or otherwise, of the courts to use published scientific literature; and (3) the use of adversarial "expert" witnesses with potential conflicts of interest. To address this situation, we first urge the legal and insurance industries to cooperate in improving the contract language and process in a way that would be both legally and scientifically appropriate. Second, we encourage the courts to use and foster the use of published peer-reviewed scientific material as evidence whenever possible. Third, we recommend that the courts choose their own unbiased expert witnesses to interpret scientific material. JF - JAMA AU - Ferguson, J H AU - Dubinsky, M AU - Kirsch, P J AD - Office of Medical Application of Research, National Institutes of Health, Bethesda, Md 20892. PY - 1993 SP - 2116 EP - 2121 VL - 269 IS - 16 SN - 0098-7484, 0098-7484 KW - United States KW - Contracts KW - Human KW - Immunotherapy KW - Wounds and Injuries KW - Reimbursement Mechanisms KW - Technology Assessment, Biomedical KW - Federal Government KW - Thermography KW - Neoplasms KW - Amygdalin KW - Male KW - Female KW - Complementary Therapies KW - Judicial Role UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85226122?accountid=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=JAMA&rft.atitle=Court-ordered+reimbursement+for+unproven+medical+technology.+Circumventing+technology+assessment.&rft.au=Ferguson%2C+J+H%3BDubinsky%2C+M%3BKirsch%2C+P+J&rft.aulast=Ferguson&rft.aufirst=J&rft.date=1993-04-01&rft.volume=269&rft.issue=16&rft.spage=2116&rft.isbn=&rft.btitle=&rft.title=JAMA&rft.issn=00987484&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - From the National Institute on Deafness and Other Communication Disorders. AN - 85203825; pmid-8483612 JF - Otolaryngology--Head and Neck Surgery AU - Snow, J B AD - National Institute on Deafness and other Communication Disorders, Bethesda, Maryland 20892, USA. PY - 1993 SP - 380 EP - 383 VL - 108 IS - 4 SN - 0194-5998, 0194-5998 KW - United States KW - Human KW - Deafness KW - National Institutes of Health (U.S.) KW - Communication Disorders UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85203825?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Otolaryngology--Head+and+Neck+Surgery&rft.atitle=From+the+National+Institute+on+Deafness+and+Other+Communication+Disorders.&rft.au=Snow%2C+J+B&rft.aulast=Snow&rft.aufirst=J&rft.date=1993-04-01&rft.volume=108&rft.issue=4&rft.spage=380&rft.isbn=&rft.btitle=&rft.title=Otolaryngology--Head+and+Neck+Surgery&rft.issn=01945998&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Speech production changes under fluency-evoking conditions in nonstuttering speakers. AN - 85157952; pmid-8487517 AB - Changes in airflow and intraoral pressure between baseline and four fluency-evoking conditions--choral reading (CR), metronome pacing (MET), delayed auditory feedback (DAF), and masking noise (NOISE)--were studied in 12 American English nonstuttering speakers. The duration, amplitude, and velocity of airflow and intraoral pressure development during the initial plosive and the duration and intensity of the following vowel were measured in eight target CVC words. Speech rate was computed for each sentence. Comparisons between baseline and the corresponding production in each condition revealed significant changes in peak flow, pressure rise time, peak instantaneous pressure velocity, speech rate, intensity, and vowel duration. Vowel duration increased under DAF, MET, and NOISE conditions. Peak pressure and pressure velocity decreased during CR and MET and increased during NOISE, but did not change during DAF. Subjects were consistent in the variables they modified across conditions. Changes in the aerodynamic variables were not related to intensity or rate changes. Thus, nonstuttering speakers modify intraoral pressure and flow under fluency-evoking conditions. JF - Journal of Speech and Hearing Research AU - Stager, S V AU - Ludlow, C L AD - Voice and Speech Section, VSLB, NIDCD, National Institutes of Health, Bethesda, MD 20892. PY - 1993 SP - 245 EP - 253 VL - 36 IS - 2 SN - 0022-4685, 0022-4685 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85157952?accountid=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+Speech+and+Hearing+Research&rft.atitle=Speech+production+changes+under+fluency-evoking+conditions+in+nonstuttering+speakers.&rft.au=Stager%2C+S+V%3BLudlow%2C+C+L&rft.aulast=Stager&rft.aufirst=S&rft.date=1993-04-01&rft.volume=36&rft.issue=2&rft.spage=245&rft.isbn=&rft.btitle=&rft.title=Journal+of+Speech+and+Hearing+Research&rft.issn=00224685&rft_id=info:doi/ LA - English DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Potentiation of radiation effects in plateau phase human glioma cells by combination of metabolic inhibitors. AN - 75937416; 8359829 AB - Effects of glycolytic inhibitor 2-deoxy-D-glucose (2-DG) on radiation damage were studied in a human glioma cell line (BMG-1), grown to confluence in monolayer. After irradiation (60Co-gamma-rays, 2 Gy) and incubation with low concentrations of 2-DG (0.5, 1.25 mM; 2-DG/glucose = 0.1, 0.25; 2 hr), in the absence or presence of respiratory inhibitor KCN (0.5-2 mM), cells were trypsinized and plated to assay radiation induced cytogenetic damage (micronuclei formation). The observations made were: (1) 2-DG and/or KCN treatments did not induce damage in unirradiated cells. (2) Either of these treatments did not increase radiation induced micronuclei formation. (3) Presence of 2-DG along with KCN (1,2 mM) significantly enhanced the radiation induced micronuclei formation. (4) Preliminary experiments by macrocolony assay showed that radiation induced cell death was also significantly increased by the combined treatment. These observations suggest that presence of clinically feasible, low concentrations of 2-DG (2-DG/glucose < 0.5) for short intervals of time after radiation could increase radiation damage in non-cycling, hypoxic tumour cells with impaired oxidative and increased glycolytic energy metabolism. JF - Indian journal of experimental biology AU - Kalia, V K AD - Department of Biophysics, National Institute of Mental Health & Neurosciences, Bangalore, India. Y1 - 1993/04// PY - 1993 DA - April 1993 SP - 312 EP - 315 VL - 31 IS - 4 SN - 0019-5189, 0019-5189 KW - DNA, Neoplasm KW - 0 KW - Deoxyglucose KW - 9G2MP84A8W KW - Potassium Cyanide KW - MQD255M2ZO KW - Index Medicus KW - DNA, Neoplasm -- radiation effects KW - DNA, Neoplasm -- drug effects KW - Tumor Cells, Cultured KW - Cell Survival -- drug effects KW - Humans KW - Chemotherapy, Adjuvant KW - DNA Damage -- drug effects KW - Potassium Cyanide -- therapeutic use KW - Glioma -- drug therapy KW - Deoxyglucose -- therapeutic use KW - Brain Neoplasms -- drug therapy KW - Brain Neoplasms -- radiotherapy KW - Deoxyglucose -- pharmacology KW - Potassium Cyanide -- pharmacology KW - Glioma -- radiotherapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75937416?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Indian+journal+of+experimental+biology&rft.atitle=Potentiation+of+radiation+effects+in+plateau+phase+human+glioma+cells+by+combination+of+metabolic+inhibitors.&rft.au=Kalia%2C+V+K&rft.aulast=Kalia&rft.aufirst=V&rft.date=1993-04-01&rft.volume=31&rft.issue=4&rft.spage=312&rft.isbn=&rft.btitle=&rft.title=Indian+journal+of+experimental+biology&rft.issn=00195189&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-09-28 N1 - Date created - 1993-09-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Contamination and restoration of groundwater aquifers. AN - 75907815; 8354172 AB - Humans are exposed to chemicals in contaminated groundwaters that are used as sources of drinking water. Chemicals contaminate groundwater resources as a result of waste disposal methods for toxic chemicals, overuse of agricultural chemicals, and leakage of chemicals into the subsurface from buried tanks used to hold fluid chemicals and fuels. In the process, both the solid portions of the subsurface and the groundwaters that flow through these porous structures have become contaminated. Restoring these aquifers and minimizing human exposure to the parent chemicals and their degradation products will require the identification of suitable biomarkers of human exposure; better understandings of how exposure can be related to disease outcome; better understandings of mechanisms of transport of pollutants in the heterogeneous structures of the subsurface; and field testing and evaluation of methods proposed to restore and cleanup contaminated aquifers. In this review, progress in these many different but related activities is presented. JF - Environmental health perspectives AU - Piver, W T AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1993/04// PY - 1993 DA - April 1993 SP - 237 EP - 247 VL - 100 SN - 0091-6765, 0091-6765 KW - Water Pollutants, Chemical KW - 0 KW - Index Medicus KW - Environmental Health KW - Humans KW - Porosity KW - Fresh Water -- chemistry KW - Water Pollutants, Chemical -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75907815?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Contamination+and+restoration+of+groundwater+aquifers.&rft.au=Piver%2C+W+T&rft.aulast=Piver&rft.aufirst=W&rft.date=1993-04-01&rft.volume=100&rft.issue=&rft.spage=237&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 - 1993-09-22 N1 - Date created - 1993-09-22 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Int J Cancer. 1987 Feb 15;39(2):155-61 [3804490] Am J Ind Med. 1990;18(3):303-5 [2220835] Appl Environ Microbiol. 1987 Feb;53(2):254-60 [3105454] J Occup Med. 1979 Nov;21(11):741-4 [512718] Science. 1981 Jan 9;211(4478):132-8 [7444456] Br J Cancer. 1981 Feb;43(2):169-76 [7470379] Int J Cancer. 1982 Mar 15;29(3):239-47 [7040259] Am J Epidemiol. 1982 May;115(5):720-8 [7081203] J Natl Cancer Inst. 1983 Jul;71(1):31-7 [6575207] Am J Epidemiol. 1983 Jul;118(1):72-7 [6869365] Neurotoxicology. 1983 Spring;4(1):113-29 [6192367] J Natl Cancer Inst. 1984 Jun;72(6):1233-40 [6587145] Appl Environ Microbiol. 1985 Jan;49(1):242-3 [3919642] Appl Environ Microbiol. 1985 May;49(5):1080-3 [3923927] Am J Epidemiol. 1985 Feb;121(2):225-37 [4014117] Am J Epidemiol. 1985 Mar;121(3):391-402 [4014129] Environ Health Perspect. 1985 May;60:11-28 [4029096] J Occup Med. 1985 Aug;27(8):580-4 [3897488] Arch Environ Health. 1985 Jul-Aug;40(4):211-4 [4051575] J Natl Cancer Inst. 1986 Feb;76(2):229-34 [3456061] Br J Ind Med. 1986 Feb;43(2):75-83 [3753879] Scand J Work Environ Health. 1985 Dec;11(6):397-407 [3912986] JAMA. 1986 Sep 5;256(9):1141-7 [3801091] Carcinogenesis. 1986 Sep;7(9):1519-21 [3742724] Mayo Clin Proc. 1986 Sep;61(9):706-13 [3528698] J Natl Cancer Inst. 1987 May;78(5):899-910 [3471999] Neurology. 1987 Jul;37(7):1229-31 [3037439] Br J Cancer. 1988 Apr;57(4):443 [3390384] Br J Cancer. 1988 May;57(5):516-20 [3395559] Neurotoxicology. 1988 Summer;9(2):249-71 [2462700] Br J Ind Med. 1989 Feb;46(2):143-4 [2923826] Cancer Res. 1989 Sep 1;49(17):4682-9 [2547513] Br J Ind Med. 1989 Aug;46(8):516-20 [2775671] Br J Cancer. 1989 Sep;60(3):385-8 [2789947] Appl Environ Microbiol. 1989 Sep;55(9):2144-51 [2552919] Environ Health Perspect. 1989 Nov;83:117-43 [2695322] Environ Health Perspect. 1989 Nov;83:179-90 [2695324] J Am Coll Cardiol. 1990 Nov;16(5):1304-9 [2229779] Epidemiology. 1990 Sep;1(5):349-56 [2078610] Science. 1991 May 10;252(5007):830-3 [2028258] Appl Environ Microbiol. 1991 Mar;57(3):744-50 [1903914] Toxicol Lett. 1991 Jun;57(1):101-11 [2048155] Arch Microbiol. 1991;155(3):238-48 [1904702] Chem Res Toxicol. 1991 Jul-Aug;4(4):391-407 [1912325] Chem Res Toxicol. 1991 Jul-Aug;4(4):445-53 [1912332] Environ Health Perspect. 1991 Aug;94:135-41 [1954924] Environ Health Perspect. 1991 Aug;94:189-93 [1954930] Environ Health Perspect. 1989 Nov;83:191-203 [2533555] Environ Health Perspect. 1989 Nov;83:205-14 [2533556] Environ Health Perspect. 1989 Nov;83:5-24 [2559844] Int J Epidemiol. 1989 Dec;18(4):768-74 [2621012] J Natl Cancer Inst. 1990 Apr 4;82(7):575-82 [2313734] Carcinogenesis. 1990 May;11(5):755-60 [1692265] J Am Coll Cardiol. 1990 Jul;16(1):155-64 [2358589] Cancer Res. 1990 Oct 15;50(20):6585-91 [2208120] Br J Cancer. 1987 Jan;55(1):81-4 [3814481] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetic toxicology: current status of methods of carcinogen identification. AN - 75903919; 8354178 AB - A critical aspect of the efforts to relate the results of short-term genetic toxicity tests with those from long-term rodent tests for carcinogens is the quality and consistency of the studies conducted by the National Toxicology Program. Analysis of the results in relationship to chemical structure has shown that mutagenic potential is a primary risk factor for carcinogen identification. Chemicals positive in the Salmonella assay-generally possess "structural alerts" for electrophilic interactions, are predominantly represented among chemicals producing trans-species carcinogenic effects in rodents, and among those identified as carcinogenic to humans. Current efforts are aimed at defining toxicological, structural, and mechanistic properties of nonmutagens that are carcinogenic in rodents. JF - Environmental health perspectives AU - Tennant, R W AU - Zeiger, E AD - Experimental Carcinogenesis and Mutagenesis Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1993/04// PY - 1993 DA - April 1993 SP - 307 EP - 315 VL - 100 SN - 0091-6765, 0091-6765 KW - Carcinogens KW - 0 KW - Mutagens KW - Index Medicus KW - Animals KW - Reproducibility of Results KW - Cells, Cultured KW - Carcinogenicity Tests KW - Biological Assay KW - Disease Models, Animal KW - Mice KW - Mice, Transgenic KW - Carcinogens -- toxicity KW - Mutagens -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75903919?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Genetic+toxicology%3A+current+status+of+methods+of+carcinogen+identification.&rft.au=Tennant%2C+R+W%3BZeiger%2C+E&rft.aulast=Tennant&rft.aufirst=R&rft.date=1993-04-01&rft.volume=100&rft.issue=&rft.spage=307&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 - 1993-09-22 N1 - Date created - 1993-09-22 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1973 Aug;70(8):2281-5 [4151811] Mutat Res. 1988 Jan;204(1):17-115 [3277047] Proc Natl Acad Sci U S A. 1981 Jun;78(6):3779-83 [7022455] Mutat Res. 1983 May;113(3-4):173-215 [6341825] Ann N Y Acad Sci. 1983;407:387-94 [6576681] Mutat Res. 1988 Jun;203(3):145-54 [3374512] Environ Mol Mutagen. 1988;12 Suppl 13:19-36 [3416839] Environ Mol Mutagen. 1988;12 Suppl 13:195-229 [3416840] Mutat Res. 1989 Jun;223(2):73-103 [2662004] Mutat Res. 1989 Sep;227(1):59-62 [2770777] Mutagenesis. 1990 Jan;5(1):3-14 [2184307] Mutat Res. 1990 May;241(1):95-108 [2110294] Fundam Appl Toxicol. 1990 Apr;14(3):513-22 [2111256] Cell. 1990 Jun 1;61(5):759-67 [2188735] Mutat Res. 1990 Jun-Aug;234(3-4):135-9 [2366781] Mutat Res. 1990 Jun-Aug;234(3-4):187-93 [2114536] Mutat Res. 1990 Jun-Aug;234(3-4):257-61 [2366790] Science. 1990 Aug 31;249(4972):970-1 [2136249] Mutagenesis. 1990 Jul;5(4):313-21 [2118975] Cell. 1991 Jan 25;64(2):235-48 [1988146] Mutat Res. 1991 May;257(3):209-27 [2014033] Mutat Res. 1991 May;257(3):229-306 [1707500] Environ Mol Mutagen. 1990;16 Suppl 18:1-14 [2091921] Environ Mol Mutagen. 1990;16 Suppl 18:15-31 [2091922] Cancer Res. 1991 Jun 1;51(11):2751-61 [2032214] Science. 1991 Nov 22;254(5035):1138-46 [1659741] Science. 1991 Nov 22;254(5035):1153-60 [1957167] Mol Carcinog. 1991;4(6):420-40 [1793481] Mutat Res. 1992 Feb;271(1):39-48 [1371828] Environ Health Perspect. 1991 Dec;96:47-51 [1820276] Environ Health Perspect. 1993 Apr;100:283-91 [8354176] Environ Mutagen. 1983;5(5):705-16 [6617600] Mutat Res. 1984 Feb;130(1):11-25 [6420694] Environ Mutagen. 1985;7(1):1-51 [3967632] Environ Mutagen. 1985;7(5):663-76 [3930236] Environ Mutagen. 1985;7 Suppl 5:1-248 [3905369] Environ Mutagen. 1986;8(2):183-204 [3698942] Mutat Res. 1986 Sep;168(2):69-240 [3528831] Science. 1987 May 22;236(4804):933-41 [3554512] Proc Natl Acad Sci U S A. 1980 Apr;77(4):1763-7 [6929519] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Aquatic toxicology: past, present, and prospects. AN - 75903875; 8354173 AB - Aquatic organisms have played important roles as early warning and monitoring systems for pollutant burdens in our environment. However, they have significant potential to do even more, just as they have in basic biology where preparations like the squid axon have been essential tools in establishing physiological and biochemical mechanisms. This review provides a brief summary of the history of aquatic toxicology, focusing on the nature of aquatic contaminants, the levels of contamination in our waters, and the origins of these agents. It considers the features of the aquatic environment that determine the availability of xenobiotics to aquatic life and the fate of foreign chemicals within the organism. Finally, toxic effects are considered with primary emphasis on the potential of aquatic models to facilitate identification of the underlying mechanisms of toxicity. JF - Environmental health perspectives AU - Pritchard, J B AD - Laboratory of Cellular and Molecular Pharmacology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1993/04// PY - 1993 DA - April 1993 SP - 249 EP - 257 VL - 100 SN - 0091-6765, 0091-6765 KW - Carcinogens, Environmental KW - 0 KW - Water Pollutants, Chemical KW - Index Medicus KW - Animals KW - Carcinogens, Environmental -- adverse effects KW - Water Pollutants, Chemical -- adverse effects KW - Toxicology -- trends KW - Forecasting KW - Water Pollutants, Chemical -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75903875?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Aquatic+toxicology%3A+past%2C+present%2C+and+prospects.&rft.au=Pritchard%2C+J+B&rft.aulast=Pritchard&rft.aufirst=J&rft.date=1993-04-01&rft.volume=100&rft.issue=&rft.spage=249&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 - 1993-09-22 N1 - Date created - 1993-09-22 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Environ Health Perspect. 1987 Apr;71:77-85 [3297667] Am J Physiol. 1991 Dec;261(6 Pt 2):R1329-40 [1750557] Environ Health Perspect. 1987 Apr;71:97-103 [3297669] Science. 1967 May 12;156(3776):821-4 [6022229] Fed Proc. 1967 Jul-Aug;26(4):1029-39 [6028768] Science. 1968 Oct 11;162(3850):271-3 [4877438] Nature. 1969 Aug 16;223(5207):753-4 [5802690] Sci Am. 1970 Apr;222(4):72-8 [4984790] Comp Biochem Physiol. 1968 Sep;26(3):853-64 [5758312] Comp Biochem Physiol A Comp Physiol. 1972 May 1;42(1):205-11 [4402709] Comp Gen Pharmacol. 1973 Sep;4(15):305-13 [4788472] Nature. 1976 Jan 15;259(5539):122-4 [128701] Annu Rev Pharmacol Toxicol. 1977;17:167-77 [326162] Ann N Y Acad Sci. 1978 Sep 29;298:389-408 [280189] Environ Health Perspect. 1979 Feb;28:81-8 [488052] Environ Health Perspect. 1980 Feb;34:159-62 [6993200] Am J Med. 1981 Jan;70(1):9-11 [7457493] Regul Toxicol Pharmacol. 1981 Jun;1(1):110-2 [7186150] Toxicol Appl Pharmacol. 1985 Feb;77(2):325-33 [3975903] J Appl Toxicol. 1985 Aug;5(4):261-4 [4045099] Annu Rev Physiol. 1986;48:377-88 [3010818] Cancer Res. 1986 Aug;46(8):3817-24 [3731058] Bull Environ Contam Toxicol. 1987 Jun;38(6):1037-43 [3580610] Environ Health Perspect. 1987 Apr;71:105-19 [3297653] Environ Health Perspect. 1987 Apr;71:129-37 [3297655] Environ Health Perspect. 1987 Apr;71:147-53 [3297657] Environ Health Perspect. 1987 Apr;71:155-70 [3297658] Environ Health Perspect. 1987 Apr;71:17-24 [3297659] Environ Health Perspect. 1987 Apr;71:171-86 [3297660] Environ Health Perspect. 1987 Apr;71:25-9 [2439326] Environ Health Perspect. 1987 Apr;71:31-46 [3297662] Environ Health Perspect. 1987 Apr;71:5-16 [3297664] Environ Health Perspect. 1987 Apr;71:59-68 [3297665] Am J Physiol. 1987 Dec;253(6 Pt 1):G816-22 [3425718] Carcinogenesis. 1988 Jun;9(6):1029-32 [3370748] Vet Hum Toxicol. 1986;28 Suppl 1:38-44 [3334693] Am J Physiol. 1989 Sep;257(3 Pt 2):R484-93 [2551193] Science. 1989 Oct 20;246(4928):352-8 [2678474] Environ Health Perspect. 1991 Jan;90:101-9 [2050047] Environ Health Perspect. 1991 Jan;90:111-6 [2050048] Environ Health Perspect. 1991 Jan;90:149-54 [2050053] Environ Health Perspect. 1991 Jan;90:27-33 [2050071] Environ Health Perspect. 1991 Jan;90:69-73 [1904811] Environ Health Perspect. 1991 Jan;90:7-15 [2050084] Environ Health Perspect. 1991 Jan;90:75-84 [1904812] Cancer Res. 1964 Aug;24:1194-201 [14216151] Environ Health Perspect. 1991 Jan;90:85-92 [2050085] Environ Health Perspect. 1991 Jan;90:93-100 [2050086] Annu Rev Pharmacol Toxicol. 1991;31:371-99 [2064380] Science. 1991 Aug 2;253(5019):512-3 [1857982] J Toxicol Environ Health. 1991 Aug;33(4):395-453 [1875429] Pharmacol Toxicol. 1991 Jun;68(6):424-9 [1653953] J Theor Biol. 1991 Aug 7;151(3):417-28 [1943151] Toxicol Appl Pharmacol. 1991 Sep 15;110(3):486-504 [1949016] Environ Health Perspect. 1987 Apr;71:87-95 [3297668] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Environmental toxicology of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans. AN - 75903855; 8394802 AB - Few environmental compounds have generated as much interest and controversy within the scientific community and in the lay public as polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs). Their ubiquitous presence in the environment and the risk of accidental exposure has raised concern over a possible threat of PCDDs or PCDFs to human health. The most extensively studied and potent isomer is 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD or dioxin). Dioxin is a multisite toxicant in laboratory rodents resulting in a number of tissue-, species-, and sex-dependent responses. Much has been learned about the mechanism of dioxin's effects, especially for the induction of cytochrome P-450 enzymes. Binding of PCDDs and PCDFs to a receptor protein, termed the dioxin or Ah receptor, is necessary for most biological and toxic responses. The most common toxic response used for evaluating the human health risk posed by PCDDs and PCDFs is the hepatocarcinogenic response observed primarily in rodents. Despite extensive research efforts, the effects of PCDDs and PCDFs on humans are not well characterized. However, available data indicate there is good agreement between known effects of dioxin in laboratory animals and those described in epidemiological studies for effects in humans. The sequence in events initiated by the Ah receptor interacting with dioxin-responsive genes and ending with altered patterns of differentiation and growth must be sought in order to understand tissue, species, sex, and interindividual variation in biological responses and the health risk posed by PCDDs and PCDFs. JF - Environmental health perspectives AU - Vanden Heuvel, J P AU - Lucier, G AD - Laboratory of Biochemical Risk Analysis, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1993/04// PY - 1993 DA - April 1993 SP - 189 EP - 200 VL - 100 SN - 0091-6765, 0091-6765 KW - Benzofurans KW - 0 KW - Dibenzofurans, Polychlorinated KW - Environmental Pollutants KW - Polychlorinated Dibenzodioxins KW - Receptors, Aryl Hydrocarbon KW - Receptors, Drug KW - Index Medicus KW - Ecology KW - Animals KW - Reproducibility of Results KW - Dose-Response Relationship, Drug KW - Humans KW - Disease Models, Animal KW - Receptors, Drug -- physiology KW - Polychlorinated Dibenzodioxins -- analogs & derivatives KW - Environmental Pollutants -- toxicity KW - Polychlorinated Dibenzodioxins -- adverse effects KW - Polychlorinated Dibenzodioxins -- toxicity KW - Benzofurans -- adverse effects KW - Environmental Pollutants -- adverse effects KW - Benzofurans -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75903855?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Environmental+toxicology+of+polychlorinated+dibenzo-p-dioxins+and+polychlorinated+dibenzofurans.&rft.au=Vanden+Heuvel%2C+J+P%3BLucier%2C+G&rft.aulast=Vanden+Heuvel&rft.aufirst=J&rft.date=1993-04-01&rft.volume=100&rft.issue=&rft.spage=189&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 - 1993-09-22 N1 - Date created - 1993-09-22 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Science. 1991 May 17;252(5008):954-8 [1852076] Environ Health Perspect. 1993 Mar;99:383-90 [8319655] Annu Rev Pharmacol Toxicol. 1991;31:73-100 [2064388] Cancer Res. 1973 Jul;33(7):1654-6 [4721228] Mol Pharmacol. 1973 Nov;9(6):736-47 [4762634] J Natl Cancer Inst. 1975 Dec;55(6):1453-9 [173869] J Biol Chem. 1976 Aug 25;251(16):4936-46 [956169] J Toxicol Environ Health. 1977 Oct;3(3):451-64 [926199] Toxicol Appl Pharmacol. 1978 Nov;46(2):279-303 [734660] Lancet. 1979 Feb 24;1(8113):446-7 [84301] Mol Pharmacol. 1980 Jan;17(1):86-94 [7383021] Ann Occup Hyg. 1979;22(4):411-20 [547800] Drug Chem Toxicol. 1979;2(1-2):49-60 [548255] Cancer Res. 1980 Oct;40(10):3616-20 [6108157] Eur J Biochem. 1982 Mar;123(1):209-15 [6279396] Annu Rev Pharmacol Toxicol. 1982;22:517-54 [6282188] Cancer Res. 1982 Dec;42(12):5030-7 [6291746] Nature. 1982 Nov 18;300(5889):271-3 [7144882] Biochem Biophys Res Commun. 1984 Jan 13;118(1):183-90 [6320820] Toxicol Appl Pharmacol. 1984 Apr;73(2):311-22 [6710531] Environ Health Perspect. 1985 Feb;59:121-8 [2985378] Dev Pharmacol Ther. 1980;1(2-3):137-62 [6100719] Annu Rev Pharmacol Toxicol. 1986;26:371-99 [3013079] Toxicol Appl Pharmacol. 1987 Feb;87(2):306-14 [3029898] Toxicol Appl Pharmacol. 1987 May;88(3):329-37 [3033846] Carcinogenesis. 1987 Oct;8(10):1491-9 [2888545] Environ Health Perspect. 1987 Dec;76:71-7 [2834195] Proc Natl Acad Sci U S A. 1988 Jun;85(12):4128-32 [3380784] Cancer. 1988 Aug 1;62(3):652-6 [3390800] J Biol Chem. 1988 Sep 25;263(27):13802-5 [2843537] Carcinogenesis. 1988 Nov;9(11):1935-41 [3141074] Am J Epidemiol. 1989 Jun;129(6):1187-200 [2729256] Hum Toxicol. 1989 May;8(3):173-203 [2663703] EMBO J. 1990 Jan;9(1):69-76 [2153080] Am J Ind Med. 1989;16(4):455-74 [2558567] Annu Rev Pharmacol Toxicol. 1990;30:251-77 [2188570] Neurotoxicol Teratol. 1990 May-Jun;12(3):239-48 [2115098] Toxicol Appl Pharmacol. 1990 Dec;106(3):518-28 [2260098] N Engl J Med. 1991 Jan 24;324(4):212-8 [1985242] DNA Cell Biol. 1991 Jan-Feb;10(1):1-14 [1991046] Cancer Res. 1991 Mar 1;51(5):1391-7 [1671757] Mutat Res. 1991 Apr;247(2):259-66 [2011143] Teratology. 1990 Dec;42(6):619-27 [2087682] Sci Total Environ. 1991 May 1;104(1-2):73-86 [1871591] Lancet. 1991 Oct 19;338(8773):959-64 [1681339] Science. 1991 Oct 18;254(5030):415-8 [1925598] Med Hypotheses. 1991 Aug;35(4):295-7 [1943878] Toxicol Appl Pharmacol. 1991 Dec;111(3):422-31 [1660630] Cancer Res. 1992 Jun 15;52(12):3436-42 [1596902] Environ Health Perspect. 1992 Nov;98:125-32 [1336723] Arch Toxicol. 1991;65(2):114-8 [1647757] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Carcinogenicity of 1,3-butadiene. AN - 75903365; 8354171 AB - 1,3-Butadiene, a high-production volume chemical used largely in the manufacture of synthetic rubber, is a multiple organ carcinogen in rats and mice. In inhalation studies conducted in mice by the National Toxicology Program, high rates of early lethal lymphomas occurring at exposure levels of 625 ppm or higher reduced the development and expression of later developing tumors at other sites. Use of survival-adjusted tumor rates to account for competing risk factors provided a clearer indication of the dose responses for 1,3-butadiene-induced neoplasms. An increase in lung tumors in female mice was observed at exposure concentrations as low as 6.25 ppm, the lowest concentration ever used in a long-term carcinogenicity study of this gas. Human exposures to 1,3-butadiene by workers employed at facilities that produce this chemical and at facilities that produce styrene-butadiene rubber have been measured at levels higher than those that cause cancer in animals. Furthermore, epidemiology studies have consistently revealed associations between occupational exposure to 1,3-butadiene and excess mortality due to lymphatic and hematopoietic cancers. In response to the carcinogenicity findings for 1,3-butadiene in animals and in humans, the Occupational Safety and Health Administration has proposed lowering the occupational exposure standard for this chemical from 1000 ppm to 2 ppm. Future work is needed to understand the mechanisms of tumor induction by 1,3-butadiene; however, the pursuit of this research should not delay the reduction of human exposure to this chemical. JF - Environmental health perspectives AU - Melnick, R L AU - Shackelford, C C AU - Huff, J AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1993/04// PY - 1993 DA - April 1993 SP - 227 EP - 236 VL - 100 SN - 0091-6765, 0091-6765 KW - Air Pollutants, Occupational KW - 0 KW - Butadienes KW - Carcinogens, Environmental KW - 1,3-butadiene KW - JSD5FGP5VD KW - Index Medicus KW - Rats KW - Animals KW - Dose-Response Relationship, Drug KW - Risk Factors KW - Humans KW - Mice KW - Female KW - Carcinogens, Environmental -- adverse effects KW - Butadienes -- toxicity KW - Air Pollutants, Occupational -- adverse effects KW - Butadienes -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75903365?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Carcinogenicity+of+1%2C3-butadiene.&rft.au=Melnick%2C+R+L%3BShackelford%2C+C+C%3BHuff%2C+J&rft.aulast=Melnick&rft.aufirst=R&rft.date=1993-04-01&rft.volume=100&rft.issue=&rft.spage=227&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 - 1993-09-22 N1 - Date created - 1993-09-22 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Natl Cancer Inst. 1966 Dec;37(6):825-38 [5955045] J Occup Med. 1987 Aug;29(8):675-80 [3655951] Mutat Res. 1979 Apr;66(4):367-71 [379632] Toxicol Lett. 1980 Aug;6(3):125-30 [6996220] Xenobiotica. 1982 Feb;12(2):137-44 [7090423] Scand J Work Environ Health. 1982 Dec;8(4):250-9 [7170621] J Cancer Res Clin Oncol. 1983;106(2):112-6 [6630281] Am J Ind Med. 1987;12(3):311-29 [3674024] Virology. 1987 Dec;161(2):457-62 [2825417] Arch Toxicol. 1987;61(1):7-11 [3439877] Biometrics. 1988 Jun;44(2):417-31 [3390507] Fundam Appl Toxicol. 1989 May;12(4):731-7 [2744275] Arch Toxicol Suppl. 1989;13:246-9 [2774939] Toxicol Appl Pharmacol. 1989 Oct;101(1):170-6 [2552616] Cancer Res. 1990 Aug 1;50(15):4818-23 [2196119] Environ Health Perspect. 1990 Jun;86:107-17 [2401250] Environ Health Perspect. 1990 Jun;86:11-8 [2401251] Environ Health Perspect. 1990 Jun;86:119-28 [2401252] Environ Health Perspect. 1990 Jun;86:129-34 [2401253] Environ Health Perspect. 1990 Jun;86:135-41 [2205483] Environ Health Perspect. 1990 Jun;86:49-55 [2169411] Environ Health Perspect. 1990 Jun;86:9-10 [2401277] Cancer Res. 1990 Oct 15;50(20):6592-9 [2208121] Rev Environ Contam Toxicol. 1992;124:111-44 [1732994] J Natl Cancer Inst. 1963 Jul;31:41-55 [14043038] Science. 1985 Feb 1;227(4686):548-9 [3966163] Arch Toxicol. 1984 Oct;55(4):213-8 [6517696] Arch Toxicol. 1984 Oct;55(4):219-23 [6517697] Toxicol Lett. 1986 Feb;30(2):131-6 [3705101] Arch Toxicol. 1986 Apr;58(4):235-8 [3718226] Cancer Res. 1986 Sep;46(9):4372-8 [3731095] Am Ind Hyg Assoc J. 1987 May;48(5):407-13 [3591659] Science. 1987 Sep 11;237(4820):1309-16 [3629242] Biochem Biophys Res Commun. 1978 Jan 30;80(2):298-305 [341894] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Advances in mechanisms of activation and deactivation of environmental chemicals. AN - 75902992; 8354165 AB - Environmental chemicals are both activated and detoxified by phase I and phase II enzymes. The principal enzymes involved in phase I reactions are the cytochrome P-450s. The phase II enzymes include hydrolase and the conjugative enzymes such as glucuronyltransferases, glutathione transferases, N-acetyltransferase, and sulfotransferase. Although other phase I and phase II enzymes exist, the present review is limited to these enzymes. Once thought to be a single enzyme, multiple cytochrome P-450 enzymes have been purified and characterized from many different species across the evolutionary tree. The application of molecular biology techniques to this field has identified more than 150 cytochrome P-450 genes to date. At least 20-30 cytochrome P-450 enzymes appear to exist in each mammalian species, and many polymorphisms in these enzymes are being identified. The cytochrome P-450 enzymes can now be expressed in recombinant form using cDNA expression systems. The phase II conjugative enzymes add a hydrophilic moiety such as sulfate, glucuronide, or acetate to compounds, which increases their water solubility and facilitates their excretion. However, conjugates of a number of compounds also result in more reactive electrophilic species, which appear to be the ultimate carcinogens. Many of these phase II enzymes also represent families of enzymes, and polymorphisms can affect the ability of these enzymes to metabolize chemicals. Whenever possible, we have reviewed knowledge of the human enzymes involved in particular pathways. JF - Environmental health perspectives AU - Goldstein, J A AU - Faletto, M B AD - Laboratory of Environmental Risk Analysis, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1993/04// PY - 1993 DA - April 1993 SP - 169 EP - 176 VL - 100 SN - 0091-6765, 0091-6765 KW - Environmental Pollutants KW - 0 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Index Medicus KW - Molecular Structure KW - Cell Membrane -- enzymology KW - Humans KW - Cytosol -- enzymology KW - Cytochrome P-450 Enzyme System -- metabolism KW - Environmental Pollutants -- metabolism KW - Inactivation, Metabolic KW - Environmental Pollutants -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75902992?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Advances+in+mechanisms+of+activation+and+deactivation+of+environmental+chemicals.&rft.au=Goldstein%2C+J+A%3BFaletto%2C+M+B&rft.aulast=Goldstein&rft.aufirst=J&rft.date=1993-04-01&rft.volume=100&rft.issue=&rft.spage=169&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 - 1993-09-22 N1 - Date created - 1993-09-22 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Pharmacol Rev. 1979 Dec;31(4):277-95 [399809] Science. 1965 Jan 22;147(3656):400-2 [14221486] Lancet. 1982 Oct 16;2(8303):842-5 [6126711] Nature. 1984 Nov 8-14;312(5990):169-70 [6504125] Carcinogenesis. 1985 Feb;6(2):199-201 [3971485] Carcinogenesis. 1985 Feb;6(2):219-23 [3971488] Cancer Res. 1987 Mar 1;47(5):1466-9 [3815349] Xenobiotica. 1988 Jan;18(1):29-39 [3354230] Cancer Res. 1988 Aug 15;48(16):4695-700 [3135117] Pharmacol Rev. 1988 Dec;40(4):243-88 [3072575] Cancer Res. 1989 Jun 15;49(12):3218-28 [2655891] Nature. 1989 Jun 22;339(6226):632-4 [2733794] Proc Natl Acad Sci U S A. 1989 Oct;86(20):7696-700 [2813353] Carcinogenesis. 1990 Jan;11(1):33-6 [2295125] Br J Clin Pharmacol. 1990 Jan;29(1):101-9 [2153391] Pharmacol Ther. 1990;45(2):153-239 [2405436] Cancer Res. 1990 Jun 1;50(11):3367-76 [2334931] Am J Hum Genet. 1990 Dec;47(6):994-1001 [1978565] DNA Cell Biol. 1991 Jan-Feb;10(1):1-14 [1991046] Mol Pharmacol. 1991 Feb;39(2):184-91 [1996083] Chem Res Toxicol. 1991 Jul-Aug;4(4):391-407 [1912325] Carcinogenesis. 1991 Oct;12(10):1839-45 [1934265] Pharmacol Rev. 1966 Mar;18(1):805-38 [5325210] Biochem Biophys Res Commun. 1966 Sep 8;24(5):668-74 [5970499] Pharmacol Rev. 1967 Sep;19(3):317-66 [4383307] J Biol Chem. 1968 Mar 25;243(6):1331-2 [4385007] Cancer Res. 1976 Sep;36(9 pt.1):3358-66 [788899] Chem Res Toxicol. 1991 Mar-Apr;4(2):168-79 [1664256] Arch Biochem Biophys. 1958 Jun;75(2):376-86 [13534720] Nature. 1959 Aug 1;184(Suppl 6):363-4 [13811548] J Biol Chem. 1962 Apr;237:1375-6 [14482007] Biochem Z. 1963;338:741-55 [14087340] J Biol Chem. 1964 Jul;239:2370-8 [14209971] J Biol Chem. 1964 Jul;239:2379-85 [14209972] Cancer. 1981 May 15;47(10):2327-45 [7272889] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chemical agents and the immune response. AN - 75900085; 8354170 AB - Our desire to understand the potential adverse human health effects of environmental chemical exposure has coincided with an increased understanding of the immune system and an appreciation of its complex regulatory network. This has spawned a broad interest in the area of immunotoxicology within the scientific community as well as certain concerns in the public sector regarding chemical-induced hypersensitivity and immunosuppression. The incidence of alleged human sensitization to chemicals has increased, in part, due to the fact that chemical companies are moving to larger and/or different markets. It has been estimated that 35 million Americans suffer from allergic disease, of which 2-5% are from occupational exposure. Although there is not yet a clear understanding of dose-response relationships or disease predisposition, there are many well-defined examples (isocyanates, anhydrides) of chemical sensitizers in humans and experimental animals. Evidence that chemicals suppress immune responses in humans is considerably less well established, although there is a public perception that chemicals generally cause immunosuppression. This perception has been fueled by highly publicized legal cases and scientific controversies within the academic and industrial communities. As a consequence of these public and scientific concerns, many of the regulatory agencies are developing immunotoxicity testing guidelines. At the present, however, there are limitations on adequate human methodology and data that allow the extrapolation of animal data to assess human risk. The potential for human immunosuppression remains of concern, however, because of a large database generated from animal studies that demonstrates immunosuppression as well as reports of immunosuppression in humans inadvertently (e.g., halogenated aromatic hydrocarbons) or occupationally (asbestos, benzene) exposed to xenobiotics.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Environmental health perspectives AU - Luster, M I AU - Rosenthal, G J AD - National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1993/04// PY - 1993 DA - April 1993 SP - 219 EP - 226 VL - 100 SN - 0091-6765, 0091-6765 KW - Aerosols KW - 0 KW - Biological Factors KW - Environmental Pollutants KW - Index Medicus KW - AIDS/HIV KW - Humans KW - Autoimmunity -- drug effects KW - Acquired Immunodeficiency Syndrome -- drug therapy KW - Antibody Formation -- drug effects KW - Biological Factors -- adverse effects KW - Drug-Related Side Effects and Adverse Reactions KW - Immunity -- drug effects KW - Environmental Pollutants -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75900085?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Chemical+agents+and+the+immune+response.&rft.au=Luster%2C+M+I%3BRosenthal%2C+G+J&rft.aulast=Luster&rft.aufirst=M&rft.date=1993-04-01&rft.volume=100&rft.issue=&rft.spage=219&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 - 1993-09-22 N1 - Date created - 1993-09-22 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Invest Dermatol. 1991 Jun;96(6):864-70 [1828476] J Invest Dermatol. 1959 Mar;32(3):445-50 [13641822] Cytokine. 1990 Jan;2(1):68-75 [2104215] Environ Res. 1978 Jul;16(1-3):92-100 [98327] J Immunol. 1982 May;128(5):2147-52 [6801132] Am J Clin Pathol. 1982 Apr;77(4):409-13 [7041618] Annu Rev Pharmacol Toxicol. 1986;26:547-65 [3521463] J Interferon Res. 1986 Apr;6(2):143-52 [2425014] Toxicol Ind Health. 1988 Sep;4(3):391-5 [3176044] Cell Immunol. 1988 Dec;117(2):289-302 [2973843] Int J Immunopharmacol. 1989;11(2):199-206 [2495254] Radiology. 1989 Jul;172(1):259-65 [2544923] Toxicol Appl Pharmacol. 1989 Nov;101(2):328-39 [2554533] Immunopharmacol Immunotoxicol. 1989;11(2-3):421-43 [2621324] Med Clin North Am. 1990 Mar;74(2):425-40 [2181213] Regul Toxicol Pharmacol. 1990 Feb;11(1):81-9 [2184468] Drugs. 1990 May;39(5):741-56 [2191850] Fundam Appl Toxicol. 1990 May;14(4):666-75 [2361570] J Natl Cancer Inst. 1990 Sep 5;82(17):1392-6 [2201784] J Neurol. 1990 Jul;237(4):247-50 [2391547] Toxicol Appl Pharmacol. 1990 Sep 15;105(3):492-502 [2237921] Lancet. 1991 Jan 26;337(8735):211-4 [1670850] Toxicol Appl Pharmacol. 1991 Mar 1;107(3):555-61 [2000641] Fundam Appl Toxicol. 1991 Jul;17(1):159-76 [1655546] J Immunol. 1991 Oct 1;147(7):2116-21 [1833452] Immunopharmacol Immunotoxicol. 1991;13(3):237-50 [1719060] Arch Environ Health. 1991 Sep-Oct;46(5):262-70 [1953033] J Invest Dermatol. 1991 Sep;97(3):478-82 [1678766] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Fertility, reproduction, and genetic disease: studies on the mutagenic effects of environmental agents on mammalian germ cells. AN - 75899917; 8354176 AB - Because genetically based diseases have a major impact on human health, the National Institute of Environmental Health Sciences (NIEHS) has conducted a research and testing program for more than a decade to address chemical induction of heritable genetic damage in the germ cells of mammals. Although most genetic disease results from preexisting mutations, a portion is due to the occurrence of new mutations. The supposition that exposure to mutagenic chemicals contributes to the occurrence of new mutations in the human population is strongly supported by the results from animal models. Such studies clearly demonstrate the potential of environmental chemicals to induce mutations in both somatic and reproductive cells of mammals. This NIEHS program has become a leader in the identification of genetic hazards in the environment and in the acquisition of animal model data used by regulatory agencies in assessing genetic risks to human health. JF - Environmental health perspectives AU - Shelby, M D AU - Bishop, J B AU - Mason, J M AU - Tindall, K R AD - Environmental Carcinogenesis and Mutagenesis Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1993/04// PY - 1993 DA - April 1993 SP - 283 EP - 291 VL - 100 SN - 0091-6765, 0091-6765 KW - Environmental Pollutants KW - 0 KW - Mutagens KW - Index Medicus KW - Animals KW - Mammals KW - Humans KW - Mice KW - Forecasting KW - Reproduction -- drug effects KW - Germ Cells -- drug effects KW - Genetic Diseases, Inborn -- chemically induced KW - Environmental Pollutants -- adverse effects KW - Fertility -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75899917?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Fertility%2C+reproduction%2C+and+genetic+disease%3A+studies+on+the+mutagenic+effects+of+environmental+agents+on+mammalian+germ+cells.&rft.au=Shelby%2C+M+D%3BBishop%2C+J+B%3BMason%2C+J+M%3BTindall%2C+K+R&rft.aulast=Shelby&rft.aufirst=M&rft.date=1993-04-01&rft.volume=100&rft.issue=&rft.spage=283&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 - 1993-09-22 N1 - Date created - 1993-09-22 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1989 Oct;86(20):7971-5 [2530578] Mutat Res. 1992 Jul;282(3):151-8 [1378547] Biochim Biophys Acta. 1990 Jun 1;1032(1):1-17 [2194566] Ann Hum Genet. 1967 Aug;31(1):1-20 [6056557] Mutat Res. 1975 Dec;33(2-3):239-50 [175269] Am J Med Genet. 1978;1(4):417-36 [665727] Science. 1981 May 22;212(4497):888-93 [7233180] J Med Genet. 1981 Apr;18(2):99-100 [7241541] Mutat Res. 1983 Apr;114(3):389-423 [6220220] Mutat Res. 1983 Aug;115(3):255-91 [6346080] Cell. 1983 Oct;34(3):1043-52 [6313205] Mutat Res. 1984 Nov;129(2):235-41 [6504062] Mutat Res. 1984 Dec;129(3):381-8 [6513965] Mutat Res. 1985 May-Jun;143(1-2):51-3 [2987686] Am J Med Genet. 1985 Jun;21(2):231-42 [4014310] Am J Med Genet. 1985 Jun;21(2):243-55 [4014311] Environ Mutagen. 1986;8(1):1-7 [3943495] Mutat Res. 1986 Jun;170(3):161-6 [3713725] J Biol Chem. 1986 Sep 15;261(26):12368-74 [3017971] Environ Mutagen. 1986;8(6):867-72 [3780618] Mutat Res. 1987 Jan;176(1):47-52 [3796658] Mutat Res. 1987 Feb;176(2):269-74 [3807937] Environ Mutagen. 1987;9(4):363-8 [3582296] Mutat Res. 1987 Aug;188(4):335-42 [3614250] Hum Genet. 1987 Nov;77(3):241-5 [3479387] Proc Natl Acad Sci U S A. 1988 Mar;85(6):1962-6 [3126501] Am J Hum Genet. 1988 May;42(5):677-93 [3358420] Mutat Res. 1988 May;199(1):175-81 [3362157] N Engl J Med. 1988 Jul 28;319(4):189-94 [3393170] Nature. 1988 Sep 29;335(6189):414-7 [3419517] Mutat Res. 1988 Nov;196(3):259-92 [3059177] N Engl J Med. 1989 Jan 5;320(1):19-23 [2909875] Mutat Res. 1989 Feb;210(2):313-22 [2911257] Mutat Res. 1989 Feb;210(2):337-44 [2911260] Mutat Res. 1989 May;226(1):61-4 [2716770] Proc Natl Acad Sci U S A. 1989 May;86(10):3704-8 [2726748] Mutat Res. 1989 Jun;212(2):241-52 [2499779] Mutat Res. 1990 Jun;230(2):205-17 [2374557] Environ Mol Mutagen. 1990;16(2):126-31 [2209562] Mutat Res. 1991 Jan;246(1):31-43 [1986266] Mutat Res. 1991 Feb;262(2):101-7 [2000095] Proc Natl Acad Sci U S A. 1991 Sep 15;88(18):7958-62 [1832771] Mutat Res. 1991 Sep-Oct;250(1-2):431-7 [1944356] Mutat Res. 1991 Sep-Oct;250(1-2):439-46 [1944357] Environ Mol Mutagen. 1991;18(4):303-6 [1748095] Fundam Appl Toxicol. 1992 Feb;18(2):189-92 [1601219] Mutat Res. 1992 Jun;282(2):127-33 [1377351] Mutat Res. 1990 Apr;229(2):161-72 [2320028] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Asbestos-induced lung disease. AN - 75899856; 8354168 AB - This review attempts to deal with two major questions concerning asbestos-induced lung disease: How does inhaled asbestos cause cell proliferation and fibrosis? and Will there continue to be risk from exposure to asbestos in schools and public buildings? The first is a scientific question that has spawned many interesting new experiments over the past 10 years, and there appear to be two hypothetical schemes which could explain, at least in part, the fibroproliferative effects of asbestos fibers. One supports the view that toxic oxygen radicals generated on fiber surfaces and/or intracellularly are the central mediators of disease. The second hypothesis is not mutually exclusive of the first, but, in my opinion, may be integral to it, i.e., the cellular injury induced by oxygen radicals stimulates the elaboration of multiple varieties of growth factors and cytokines that mediate the pathogenesis of asbestosis. There is increasing evidence that molecules such as platelet-derived growth factor and transforming growth factor beta, both synthesized and secreted by activated lung macrophages, are responsible, respectively, for the increased interstitial cell populations and extracellular matrix proteins that are the hallmarks of asbestos-induced fibrosis. The challenge today is to establish which combinations of the many factors released actually are playing a role in disease pathogenesis. The issue of continued risk currently is more a question of policy and perception than science because a sufficient database has not yet been established to allow full knowledge of the circumstances under which asbestos in buildings constitutes an ongoing health hazard. The litigious nature of this question does not help its resolution. In as much as public policy statements and risk assessment are not within my purview, I have focused on the state-of-the-art of asbestos as a complete carcinogen. It appears to be generally nongenotoxic, but all asbestos fiber types can induce chromosomal mutations and aneuploidy, perhaps through their ability to disrupt normal chromosome segregation. JF - Environmental health perspectives AU - Brody, A R AD - Laboratory of Pulmonary Pathobiology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1993/04// PY - 1993 DA - April 1993 SP - 21 EP - 30 VL - 100 SN - 0091-6765, 0091-6765 KW - Asbestos KW - 1332-21-4 KW - Index Medicus KW - Schools KW - Risk Factors KW - Humans KW - Cell Division -- physiology KW - Lung Diseases -- etiology KW - Pulmonary Fibrosis -- etiology KW - Environmental Exposure KW - Asbestos -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75899856?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Asbestos-induced+lung+disease.&rft.au=Brody%2C+A+R&rft.aulast=Brody&rft.aufirst=A&rft.date=1993-04-01&rft.volume=100&rft.issue=&rft.spage=21&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 - 1993-09-22 N1 - Date created - 1993-09-22 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cancer Res. 1991 Sep 15;51(18):4942-7 [1893384] Environ Res. 1992 Jun;58(1):97-116 [1317793] Am Rev Respir Dis. 1989 May;139(5):1265-73 [2540689] J Biol Chem. 1989 May 25;264(15):8771-8 [2542288] Am J Ind Med. 1989;15(5):511-6 [2741957] Br J Cancer. 1974 Mar;29(3):252-69 [4364384] Br J Exp Pathol. 1976 Oct;57(5):505-14 [1036714] Am Rev Respir Dis. 1981 Jun;123(6):670-9 [6267971] N Engl J Med. 1982 Jun 17;306(24):1446-55 [7043267] N Engl J Med. 1982 Jun 17;306(24):1480-2 [7078593] Am J Pathol. 1982 Oct;109(1):107-14 [7124904] Arch Pathol Lab Med. 1982 Oct 8;106(11):544-96 [6897166] Am J Pathol. 1983 Sep;112(3):326-37 [6311019] Lab Invest. 1983 Oct;49(4):468-75 [6312192] Am Rev Respir Dis. 1983 Oct;128(4):724-9 [6625350] Arch Biochem Biophys. 1984 Jan;228(1):373-6 [6320737] Cancer Res. 1984 May;44(5):2170-80 [6324999] Cancer Res. 1984 Nov;44(11):5017-22 [6091868] Exp Lung Res. 1984;7(2):133-47 [6098439] Carcinogenesis. 1985 Mar;6(3):473-5 [3978760] Proc Natl Acad Sci U S A. 1985 Jun;82(11):3884-8 [2987952] Inflammation. 1985 Jun;9(2):139-47 [2989174] Lab Invest. 1985 Sep;53(3):320-7 [3928965] Ann Occup Hyg. 1985;29(3):357-63 [4073703] Cell. 1985 Nov;43(1):277-86 [2416458] Cancer Genet Cytogenet. 1986 Feb 15;20(3-4):191-201 [3943062] Lab Invest. 1986 Feb;54(2):204-12 [3945053] Mutat Res. 1986 Mar;169(3):141-8 [3005853] Cancer Genet Cytogenet. 1986 Jul;22(3):225-37 [3708554] Cell. 1986 Jul 18;46(2):155-69 [3013421] Am Rev Respir Dis. 1986 Jul;134(1):128-33 [3729150] Cancer Res. 1986 Nov;46(11):5795-802 [3756923] J Clin Invest. 1987 Feb;79(2):319-26 [3543052] Cancer Res. 1987 Mar 15;47(6):1681-6 [3028612] Hereditas. 1986;105(2):233-9 [3818338] Am Rev Respir Dis. 1987 Jun;135(6):1345-52 [3592407] FASEB J. 1988 Apr;2(7):2272-7 [3280379] Am J Pathol. 1988 Apr;131(1):156-70 [2833103] Science. 1988 Jun 10;240(4858):1529-31 [2836952] J Cell Physiol. 1988 Oct;137(1):45-54 [2844836] J Clin Invest. 1988 Nov;82(5):1685-93 [3183063] Am J Pathol. 1989 Jan;134(1):133-40 [2913821] Am J Ind Med. 1988;14(6):635-41 [3232683] Environ Health Perspect. 1989 May;81:81-9 [2667990] Toxicol Appl Pharmacol. 1989 Aug;100(1):132-44 [2548304] Am Rev Respir Dis. 1989 Oct;140(4):1075-81 [2529800] Biochem J. 1989 Oct 15;263(2):539-45 [2556998] Science. 1990 Jan 19;247(4940):294-301 [2153315] Am J Respir Cell Mol Biol. 1989 Sep;1(3):231-5 [2624762] Am Rev Respir Dis. 1990 Mar;141(3):765-88 [2155556] Am J Pathol. 1990 Mar;136(3):695-705 [2156434] Am Rev Respir Dis. 1990 May;141(5 Pt 1):1266-71 [2160214] Eur J Cell Biol. 1990 Apr;51(2):327-34 [2190835] Science. 1990 Aug 31;249(4972):1007-11 [2204108] Am J Respir Cell Mol Biol. 1991 Dec;5(6):539-47 [1958381] Exp Lung Res. 1991 Nov-Dec;17(6):1011-24 [1663030] J Clin Invest. 1990 Oct;86(4):1055-64 [2170444] Proc Natl Acad Sci U S A. 1990 Oct;87(19):7385-9 [2170975] Chest. 1991 Jan;99(1):191-8 [1984952] CMAJ. 1991 Mar 1;144(5):554-6 [1998901] In Vitro Cell Dev Biol. 1990 Dec;26(12):1135-43 [1706697] Am J Respir Cell Mol Biol. 1991 May;4(5):397-407 [1850605] Toxicol Ind Health. 1990 Dec;6(6):629-36 [2097821] Environ Res. 1991 Jun;55(1):97-106 [1855494] Comment In: Environ Health Perspect. 1993 Dec;101(7):564-5 [8143579] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mechanisms of multistep carcinogenesis and carcinogen risk assessment. AN - 75899078; 8354184 AB - Many different types of chemical exposures can increase the incidence of tumors in animals and humans, but usually a long period of time is required before the carcinogenic risk of an exposure is manifested. Both of these observations can be explained by a multistep/multigene model of carcinogenesis. In this model, a normal cell evolves into a cancer cell as the result of heritable changes in multiple, independent genes. The two-stage model of initiation and promotion for chemical carcinogenesis has provided a paradigm by which chemicals can act by qualitatively different mechanisms, but the process of carcinogenesis is now recognized as more complex than simply initiation and promotion. Even a three-stage model of initiation, promotion, and progression, which can be operationally defined, is not adequate to describe the carcinogenic process. The number of genes altered in a cancer cell compared to a normal cell is not known; recent evidence suggests that 3-10 genetic events are involved in common adult malignancies in humans. Two distinct classes of genes, protooncogenes and tumor-suppressor genes, are involved in the cancer process. Multiple oncogenes may be activated in a tumor, while multiple tumor-suppressor genes may be inactivated. Identification of the genes involved in carcinogenesis and elucidation of the mechanisms of their activation or inactivation allows a better understanding of how chemical carcinogens influence the process of neoplastic evolution. The findings of multiple genetic changes (including point mutations, chromosomal translocations, deletions, gene amplification, and numerical chromosome changes) in activated protooncogenes and inactivated tumor-suppressor genes provide experimental support for Boveri's somatic mutation theory of carcinogenesis. In addition to mutagenic mechanisms, chemicals may heritably alter cells by epigenetic mechanisms and enhance the clonal expansion of altered cells. Most chemical carcinogens operate via a combination of mechanisms, and even their primary mechanism of action may vary depending on the target tissues. The classification of chemicals by mechanism of action or by nongenotoxic or genotoxic activity has certain inherent difficulties because no classification of chemicals is exhaustive or definitive. JF - Environmental health perspectives AU - Barrett, J C AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1993/04// PY - 1993 DA - April 1993 SP - 9 EP - 20 VL - 100 SN - 0091-6765, 0091-6765 KW - Estrogens KW - 0 KW - Asbestos KW - 1332-21-4 KW - Index Medicus KW - Animals KW - Risk Factors KW - Humans KW - Cell Division -- drug effects KW - Asbestos -- adverse effects KW - Estrogens -- adverse effects KW - Mutagenesis KW - Neoplasms -- chemically induced KW - Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75899078?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mechanisms+of+multistep+carcinogenesis+and+carcinogen+risk+assessment.&rft.au=Barrett%2C+J+C&rft.aulast=Barrett&rft.aufirst=J&rft.date=1993-04-01&rft.volume=100&rft.issue=&rft.spage=9&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 - 1993-09-22 N1 - Date created - 1993-09-22 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Science. 1989 Apr 14;244(4901):207-11 [2565047] Carcinogenesis. 1989 May;10(5):847-50 [2565171] IARC Sci Publ. 1989;(90):54-73 [2663719] Environ Health Perspect. 1989 May;81:81-9 [2667990] Environ Health Perspect. 1989 May;81:91-4 [2667992] Cancer Res. 1989 Oct 15;49(20):5489-96 [2676144] Environ Health Perspect. 1989 Jul;82:125-63 [2676495] J Natl Cancer Inst. 1989 Dec 6;81(23):1780-6 [2685334] Science. 1990 Feb 9;247(4943):707-10 [2300822] Pharmacol Ther. 1990;46(3):469-86 [2188272] Cell. 1990 Jun 1;61(5):759-67 [2188735] Mutat Res. 1990 Jun-Aug;234(3-4):257-61 [2366790] Cancer Res. 1990 Dec 1;50(23):7415-21 [2174724] Ren Fail. 1991;13(4):211-25 [1780490] Am J Ind Med. 1992;21(2):253-73 [1536158] Regul Toxicol Pharmacol. 1992 Oct;16(2):111-25 [1279759] Cancer Res. 1950 Nov;10(11):713-7 [14783769] Arch Environ Health. 1963 Dec;7:668-74 [14077213] Science. 1989 May 12;244(4905):707-12 [2470152] Cancer Res. 1989 Jul 15;49(14):3713-21 [2660980] Mutat Res. 1989 Jun;223(2):73-103 [2662004] Proc Natl Acad Sci U S A. 1989 Jul;86(13):5099-103 [2567993] Cancer Res. 1984 May;44(5):2170-80 [6324999] Science. 1984 Jun 8;224(4653):1121-4 [6719137] Environ Res. 1984 Aug;34(2):227-41 [6086305] CRC Crit Rev Toxicol. 1974 Jan;2(4):419-43 [4822436] N Engl J Med. 1975 Feb 13;292(7):334-9 [1117962] Natl Cancer Inst Monogr. 1979 May;(51):239-50 [384263] Natl Cancer Inst Monogr. 1979 May;(51):41-56 [384264] J Natl Cancer Inst. 1980 Sep;65(3):627-30 [6774154] IARC Sci Publ. 1980;(27):243-55 [6449480] Science. 1981 Jun 19;212(4501):1402-4 [6262919] Science. 1981 Oct 23;214(4519):401-7 [7291981] J Supramol Struct Cell Biochem. 1981;17(2):133-46 [7033553] Carcinogenesis. 1981;2(12):1375-9 [7326837] Cancer Res. 1982 Aug;42(8):3040-5 [6284354] Carcinogenesis. 1982;3(8):895-8 [6812976] Cancer Res. 1983 May;43(5):2034-41 [6403231] J Natl Cancer Inst. 1983 Mar;70(3):455-63 [6572736] Mol Pharmacol. 1983 Mar;23(2):278-81 [6682170] Cancer Res. 1983 Aug;43(8):3814-21 [6861146] Nature. 1983 Jul 7-13;304(5921):67-9 [6866091] Environ Health Perspect. 1983 Apr;50:309-20 [6873021] Cancer Lett. 1983 Dec;21(2):141-7 [6652618] Cancer Res. 1984 Jan;44(1):184-9 [6317168] Proc Natl Acad Sci U S A. 1984 Aug;81(15):4940-4 [6589638] Mutat Res. 1984 Aug;140(4):205-7 [6472331] Pharmacol Rev. 1984 Jun;36(2 Suppl):53S-70S [6473503] Cancer Res. 1984 Nov;44(11):5017-22 [6091868] Gan. 1984 Dec;75(12):1046-8 [6526218] Carcinogenesis. 1985 Mar;6(3):473-5 [3978760] Nature. 1985 May 30-Jun 5;315(6018):382-5 [3923365] Carcinogenesis. 1985 Jun;6(6):865-71 [4006072] Carcinogenesis. 1985 Oct;6(10):1421-6 [3840060] Carcinog Compr Surv. 1985;9:123-37 [4053069] Carcinogenesis. 1985 Nov;6(11):1607-10 [2414025] Science. 1985 Nov 15;230(4727):770-6 [2997917] Environ Mutagen. 1986;8(1):129-59 [3510860] Cancer Res. 1986 Apr;46(4 Pt 2):2088-95 [3948182] Cancer Lett. 1986 Mar;30(3):269-74 [2870794] Cancer Res. 1986 Jun;46(6):2863-5 [3084079] Cancer Genet Cytogenet. 1986 Jul;22(3):225-37 [3708554] Nature. 1986 Jul 3-9;322(6074):78-80 [3014349] Proc Natl Acad Sci U S A. 1986 Aug;83(16):5825-9 [3016723] Carcinogenesis. 1986 Nov;7(11):1845-8 [3769132] Science. 1987 Jan 9;235(4785):177-82 [3798106] Science. 1987 Jan 16;235(4786):305-11 [3541204] Proc Natl Acad Sci U S A. 1987 Apr;84(7):2029-32 [3104907] Science. 1987 Sep 11;237(4820):1309-16 [3629242] Mutat Res. 1988 Jan;204(1):3-15 [3277048] Environ Health Perspect. 1987 Dec;76:65-70 [3447905] Science. 1988 Jul 1;241(4861):79-81 [3388020] N Engl J Med. 1988 Sep 1;319(9):525-32 [2841597] Proc Natl Acad Sci U S A. 1988 Sep;85(17):6389-93 [2457913] Carcinogenesis. 1988 Nov;9(11):2045-52 [3052903] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chemicals and cancer in humans: first evidence in experimental animals. AN - 75898455; 8354167 AB - Certain human diseases have been traced to exposure to environmental and occupational chemicals. In many instances the first evidence of potential adverse effects came from experimental studies and were subsequently discovered in humans. Associations of human cancers, as a diverse group of diseases, and chemicals have been made since the middle 1700s. Since then, nearly 100 chemicals, mixtures of chemicals, or exposure circumstances are now recognized as being or strongly implicated as being carcinogenic to humans. Of the less than 1000 agents evaluated adequately for carcinogenicity in laboratory animals, a varying spectrum of data from studies on humans are available for only about 20-25%. So far, more than 60 agents are linked unequivocally as causing cancer in humans, and another 50 or so are strongly suspected of being carcinogenic to humans. Not all of these have been or can be evaluated in animals because some are industrial processes or "occupations," some are environmental and cultural risk factors, and some are mixtures of agents. For those that can be studied experimentally, the qualitative concordance between humans and animals approaches unity, and in every case there is at least one common organ site of cancer in both species. The evidence of carcinogenicity in experimental animals preceded that observed in humans for nearly 30 agents and is the subject of this paper. JF - Environmental health perspectives AU - Huff, J AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1993/04// PY - 1993 DA - April 1993 SP - 201 EP - 210 VL - 100 SN - 0091-6765, 0091-6765 KW - Carcinogens, Environmental KW - 0 KW - Index Medicus KW - Animals KW - Environmental Health KW - Humans KW - Disease Models, Animal KW - Occupational Diseases -- chemically induced KW - Carcinogens, Environmental -- adverse effects KW - Neoplasms, Experimental -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75898455?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Chemicals+and+cancer+in+humans%3A+first+evidence+in+experimental+animals.&rft.au=Huff%2C+J&rft.aulast=Huff&rft.aufirst=J&rft.date=1993-04-01&rft.volume=100&rft.issue=&rft.spage=201&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 - 1993-09-22 N1 - Date created - 1993-09-22 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Scand J Work Environ Health. 1992;18 Suppl 1:83-9 [1411384] Environ Health Perspect. 1993 Apr;100:189-200 [8394802] Environ Health Perspect. 1993 Apr;100:227-36 [8354171] Environ Health Perspect. 1993 Apr;100:39-44 [8354180] Environ Health Perspect. 1993 Apr;100:9-20 [8354184] Environ Health Perspect. 1990 Jun;86:107-17 [2401250] Environ Health Perspect. 1990 Jun;86:119-28 [2401252] Epidemiology. 1990 Sep;1(5):349-56 [2078610] Am J Public Health. 1991 Jun;81(6):791-800 [2029056] Scand J Work Environ Health. 1991 Feb;17(1):7-19 [2047810] Environ Health Perspect. 1991 Jan;90:127-32 [2050050] Cell Biol Toxicol. 1991 Jan;7(1):67-94 [2054688] Annu Rev Pharmacol Toxicol. 1991;31:621-52 [2064387] Scand J Work Environ Health. 1991 Aug;17(4):231-9 [1925434] Prog Histochem Cytochem. 1991;23(1-4):45-60 [1947167] Rev Environ Contam Toxicol. 1992;124:111-44 [1732994] Environ Health Perspect. 1991 Jun;93:247-70 [1773796] Cancer Res. 1992 Apr 15;52(8):2357-61 [1559239] Br J Ind Med. 1955 Apr;12(2):81-6 [14363586] Environ Health Perspect. 1990 Jun;86:27-36 [2401263] Cancer Res. 1990 Oct 15;50(20):6441-8 [2208102] Cancer Res. 1990 Oct 15;50(20):6592-9 [2208121] Prog Exp Tumor Res. 1969;11:222-34 [4888943] Cancer Res. 1971 May;31(5):516-22 [5582114] J Occup Med. 1974 Mar;16(3):150-1 [4856325] Med Lav. 1974 Nov-Dec;65(11-12):421-44 [4477887] Cancer Res. 1978 Apr;38(4):877-85 [346205] Environ Health Perspect. 1978 Feb;22:163-5 [648484] Annu Rev Pharmacol Toxicol. 1979;19:511-30 [378109] Environ Health Perspect. 1979 Oct;32:297-300 [120250] Ann N Y Acad Sci. 1981;363:139-44 [6942719] Environ Health Perspect. 1981 Oct;41:59-62 [6277614] J Occup Med. 1982 Oct;24(10):767-9 [7143123] Cancer Res. 1984 May;44(5):2244-50 [6370426] Ann Occup Hyg. 1984;28(3):291-305 [6508080] Int Arch Occup Environ Health. 1984;54(4):317-24 [6511101] Science. 1985 Feb 1;227(4686):548-9 [3966163] Int J Epidemiol. 1985 Mar;14(1):22-31 [3988437] Carcinogenesis. 1985 Nov;6(11):1653-65 [3902269] J Occup Med. 1985 Nov;27(11):835-40 [4067690] JAMA. 1986 Mar 28;255(12):1575-8 [3951093] JAMA. 1986 Sep 5;256(9):1141-7 [3801091] J Urol. 1986 Oct;136(4):834-6 [3020259] Carcinogenesis. 1986 Nov;7(11):1853-63 [3769134] J Natl Cancer Inst. 1987 Jan;78(1):191-3 [3467126] J Natl Cancer Inst. 1987 Feb;78(2):247-52 [3468288] Am J Ind Med. 1987;11(2):157-63 [3826078] J Occup Med. 1987 Mar;29(3):217-28 [3559766] Cancer Res. 1987 Jun 1;47(11):3012-31 [3105872] JAMA. 1987 May 1;257(17):2290 [3573228] Annu Rev Public Health. 1987;8:355-85 [3555527] Lancet. 1987 Nov 14;2(8568):1153 [2890054] J Natl Cancer Inst. 1987 Nov;79(5):911-21 [3479642] Fundam Appl Toxicol. 1987 Oct;9(3):367-79 [3319745] J Natl Cancer Inst. 1987 Dec;79(6):1269-79 [3480378] Int J Cancer. 1988 Feb 15;41(2):184-97 [3338870] Scand J Work Environ Health. 1987 Dec;13(6):493-504 [3433051] Int Arch Occup Environ Health. 1988;60(1):21-4 [3350600] Am J Public Health. 1988 May;78(5):570-1 [3354743] Ann N Y Acad Sci. 1988;534:31-8 [3291709] Ann N Y Acad Sci. 1988;534:78-83 [3291727] J Occup Med. 1988 Jun;30(6):475-6, 478, 480-1 [3392613] Cancer Metastasis Rev. 1988 Apr;7(1):5-18 [3293832] Risk Anal. 1988 Jun;8(2):205-14 [3045903] Acta Oncol. 1988;27(5):465-72 [3060154] Lancet. 1989 Apr 22;1(8643):911 [2565003] Toxicol Ind Health. 1989 Oct;5(5):699-730 [2815102] Jpn J Cancer Res. 1989 Sep;80(9):795-807 [2513295] Klin Wochenschr. 1989 Dec 4;67(23):1169-73 [2691755] Pharmacol Ther. 1990;46(3):469-86 [2188272] Am J Ind Med. 1990;17(6):683-99 [2343874] Exp Pathol. 1989;37(1-4):128-32 [2637142] Science. 1990 Aug 31;249(4972):970-1 [2136249] Scand J Work Environ Health. 1991 Aug;17(4):248-54 [1925436] J Natl Cancer Inst. 1992 May 20;84(10):764-71 [1573662] Environ Health Perspect. 1991 Dec;96:23-31 [1820269] Scand J Work Environ Health. 1992;18 Suppl 1:31-7 [1411375] Scand J Work Environ Health. 1992;18 Suppl 1:74-82 [1411383] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Developmental toxicology: status of the field and contribution of the National Toxicology Program. AN - 75880379; 8354175 AB - The NTP has conducted developmental toxicity studies on more than 50 chemicals, often in multiple species. Several chemicals caused developmental toxicity in the absence of any toxicity to the mother. Although hazard to humans is determined by the level of exposure to the chemical and its inherent toxicity, those agents that selectively disturb the development of the conceptus are of particular concern because other manifestations of toxicity would not warn the mother of overexposure. Whether the LOAEL (lowest-observed adverse effect level) for maternal toxicity was high or low did not correlate with the potential of chemicals to cause developmental toxicity. The form of developmental toxicity that determined the LOAEL most frequently was decreased body weight in mice and rats, but not rabbits, where the LOAEL was determined more often by an increase in resorptions. Several in vitro and short-term tests appear promising as screens to predict the outcome of developmental toxicity studies in mammals. However, the only screens that have undergone formal validation studies are those evaluated by the NTP. Improvements in our ability to predict risk to humans have been limited by our knowledge of the mechanisms by which agents cause developmental toxicity. Thus, future growth is dependent on a better understanding of the biological processes that regulate normal development, therein providing the necessary framework for understanding mechanisms of abnormal development. JF - Environmental health perspectives AU - Schwetz, B A AU - Harris, M W AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1993/04// PY - 1993 DA - April 1993 SP - 269 EP - 282 VL - 100 SN - 0091-6765, 0091-6765 KW - Index Medicus KW - United States KW - Maternal-Fetal Exchange KW - Animals KW - Humans KW - Data Interpretation, Statistical KW - Forecasting KW - Abnormalities, Drug-Induced -- etiology KW - Female KW - Pregnancy KW - Embryonic and Fetal Development -- drug effects KW - Toxicology -- trends UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75880379?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Developmental+toxicology%3A+status+of+the+field+and+contribution+of+the+National+Toxicology+Program.&rft.au=Schwetz%2C+B+A%3BHarris%2C+M+W&rft.aulast=Schwetz&rft.aufirst=B&rft.date=1993-04-01&rft.volume=100&rft.issue=&rft.spage=269&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 - 1993-09-22 N1 - Date created - 1993-09-22 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Toxicol Appl Pharmacol. 1985 Oct;81(1):113-27 [4049413] Neurotoxicology. 1990 Summer;11(2):189-98 [2234540] Fundam Appl Toxicol. 1987 Jan;8(1):115-26 [3556817] Fundam Appl Toxicol. 1987 May;8(4):571-82 [3609543] Fundam Appl Toxicol. 1987 Jul;9(1):173-81 [3622959] Toxicol Appl Pharmacol. 1987 Sep 15;90(2):206-16 [3629596] Rev Environ Contam Toxicol. 1988;102:1-78 [3275996] Fundam Appl Toxicol. 1988 Apr;10(3):395-412 [3371580] Teratology. 1988 Jun;37(6):539-52 [3400069] Fundam Appl Toxicol. 1991 Apr;16(3):401-13 [1855614] Fundam Appl Toxicol. 1991 May;16(4):742-8 [1884913] Environ Health Perspect. 1991 Aug;94:265-8 [1683285] Teratology. 1992 Apr;45(4):337-9 [1350114] Fundam Appl Toxicol. 1992 Feb;18(2):266-77 [1601227] Fundam Appl Toxicol. 1992 Jul;19(1):15-25 [1397797] Fundam Appl Toxicol. 1988 Nov;11(4):673-84 [3229591] Fundam Appl Toxicol. 1989 Apr;12(3):442-8 [2731659] Fundam Appl Toxicol. 1989 Nov;13(4):641-51 [2620788] Fundam Appl Toxicol. 1990 Jan;14(1):167-78 [2155147] Fundam Appl Toxicol. 1990 Apr;14(3):502-12 [2340980] Environ Health Perspect. 1990 Jun;86:79-84 [2205495] Teratology. 1990 Aug;42(2):131-6 [2171152] Fundam Appl Toxicol. 1990 Aug;15(2):350-6 [2227160] Fundam Appl Toxicol. 1986 Oct;7(3):434-43 [3781133] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - IL-1 receptor antagonist (IL-1ra) augments IL-2-induced pulmonary vascular leak. AN - 75844585; 8331927 AB - Interleukin-2 (IL-2) therapy is dose limited by a severe vascular leak with resulting systemic and pulmonary toxicity. Although recognized as a mediator of septic shock and vascular leak, the relative role of IL-1 in IL-2 toxicity is unclear. We evaluated the effect of IL-1 receptor antagonist (IL-1ra) on IL-2 lethality, pulmonary vascular leak, and treatment of pulmonary metastases in a murine model. In vivo induction of mRNA for IL-1 alpha was evaluated in liver by Northern blots after 0, 5, 8, and 11 doses of IL-2 in C3H/HEN mice. The expression index for the IL-1 alpha gene increased from 0.16 to 0.74 after 5 doses of IL-2, and further increased to 1.04 after 11 doses of IL-2. C3H/HEN mice (n = 56) were randomized to receive phosphate-buffered saline (PBS), IL-1ra high dose (HD), or IL-1ra low dose (LD) by continuous subcutaneous infusion via Alzet mini-pumps. The biologic effectiveness of the dose and administration of IL-1ra was determined by the ability to block IL-1-induced IL-6 production in vivo. Mean serum IL-6 levels 3 hr after intraperitoneal IL-1 alpha (10 micrograms/kg) were: PBS, 3730 +/- 526 (mean +/- SEM pg/ml); IL-1ra (LD), 1156 +/- 398; and IL-1ra (HD), 594 +/- 30 (P < 0.01, IL-1ra HD or LD vs PBS). Pulmonary vascular leak was measured by iv I125 albumin after 8 doses of IL-2 (100,000 U ip q 8 hr).(ABSTRACT TRUNCATED AT 250 WORDS) JF - The Journal of surgical research AU - Thom, A K AU - Fraker, D L AU - Norton, J A AD - Surgical Metabolism Section, National Cancer Institutes, National Institutes of Health, Bethesda, Maryland 20894. Y1 - 1993/04// PY - 1993 DA - April 1993 SP - 336 EP - 341 VL - 54 IS - 4 SN - 0022-4804, 0022-4804 KW - Interleukin-1 KW - 0 KW - Interleukin-2 KW - Interleukin-6 KW - RNA, Messenger KW - Receptors, Interleukin-1 KW - Index Medicus KW - Animals KW - Lung Neoplasms -- prevention & control KW - RNA, Messenger -- metabolism KW - Lung Neoplasms -- secondary KW - Interleukin-6 -- metabolism KW - Mice, Inbred C57BL KW - Mice, Inbred C3H KW - Gene Expression KW - Mice KW - Interleukin-1 -- genetics KW - Drug Synergism KW - Female KW - Interleukin-2 -- pharmacology KW - Pulmonary Circulation -- drug effects KW - Receptors, Interleukin-1 -- antagonists & inhibitors KW - Capillary Permeability -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75844585?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+surgical+research&rft.atitle=IL-1+receptor+antagonist+%28IL-1ra%29+augments+IL-2-induced+pulmonary+vascular+leak.&rft.au=Thom%2C+A+K%3BFraker%2C+D+L%3BNorton%2C+J+A&rft.aulast=Thom&rft.aufirst=A&rft.date=1993-04-01&rft.volume=54&rft.issue=4&rft.spage=336&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+surgical+research&rft.issn=00224804&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-08-16 N1 - Date created - 1993-08-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interleukin-1 receptor antibody (IL-1rab) protection and treatment against lethal endotoxemia in mice. AN - 75842433; 8331925 AB - Interleukin-1 (IL-1) is a mediator of endotoxin shock and IL-1 receptor blockade has been shown to have therapeutic efficacy against endotoxic shock and sepsis in laboratory models. The current studies were designed to characterize the efficacy of a murine monoclonal IL-1 receptor antibody (IL-1rab) against endotoxin (LPS) lethality and to investigate whether combined anticytokine therapy using the IL-1rab and a highly specific polyclonal rabbit anti-mouse TNF antibody (TNF Ab) could provide additive or synergistic efficacy against LPS lethality in C57B1/6 female mice. A single intraperitoneal (ip) dose of IL-1rab, 0.1 or 0.2 mg, significantly reduced lethality from LPS, 30 to 40 mg/kg ip, compared to nonimmune IgG, 0.1 or 0.2 mg, in control mice (P2 < 0.05). Treatment with IL-1rab was effective when administered from 6 hr before to 1 hr after LPS. After LPS, circulating levels of IL-6 were significantly lower in IL-1rab-treated mice [IL-6 (ng/ml) 2 h after LPS: IgG, 100 +/- 25, IL-1rab, 41 +/- 8; 4 h after LPS: IgG, 46 +/- 13, IL-1rab, 8 +/- 1; P2 < 0.05 and 0.03, respectively]. Northern blot analysis showed that IL-1rab markedly lowered IL-6 gene expression after LPS. Combined treatment with IL-1rab and TNF Ab did not result in any improvement in survival after LPS compared to either agent alone. These results indicate that an IL-1 receptor antibody has therapeutic efficacy against LPS and significantly decreases IL-6 production.(ABSTRACT TRUNCATED AT 250 WORDS) JF - The Journal of surgical research AU - McNamara, M J AU - Norton, J A AU - Nauta, R J AU - Alexander, H R AD - Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/04// PY - 1993 DA - April 1993 SP - 316 EP - 321 VL - 54 IS - 4 SN - 0022-4804, 0022-4804 KW - Antibodies KW - 0 KW - Cytokines KW - Endotoxins KW - Receptors, Interleukin-1 KW - Tumor Necrosis Factor-alpha KW - Index Medicus KW - Cytokines -- blood KW - Animals KW - Escherichia coli Infections -- therapy KW - Tumor Necrosis Factor-alpha -- immunology KW - Mice, Inbred C57BL KW - Escherichia coli Infections -- mortality KW - Mice KW - Escherichia coli Infections -- blood KW - Drug Synergism KW - Female KW - Receptors, Interleukin-1 -- immunology KW - Antibodies -- therapeutic use KW - Escherichia coli KW - Endotoxins -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75842433?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+surgical+research&rft.atitle=Interleukin-1+receptor+antibody+%28IL-1rab%29+protection+and+treatment+against+lethal+endotoxemia+in+mice.&rft.au=McNamara%2C+M+J%3BNorton%2C+J+A%3BNauta%2C+R+J%3BAlexander%2C+H+R&rft.aulast=McNamara&rft.aufirst=M&rft.date=1993-04-01&rft.volume=54&rft.issue=4&rft.spage=316&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+surgical+research&rft.issn=00224804&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-08-16 N1 - Date created - 1993-08-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Toxicokinetics of pentachloroanisole in F344 rats and B6C3F1 mice. AN - 75840563; 8337901 AB - 1. Toxicokinetics of pentachloroanisole (PCA) were studied in F344 rat and B6C3F1 mouse of both sexes by gavage at doses of 10, 20 and 40 mg/kg and by i.v. at 10 mg/kg. 2. PCA was rapidly demethylated to pentachlorophenol (PCP) in both rat and mouse and the resulting PCP plasma concentrations were much higher than that of parent PCA due to the much smaller apparent volume of distribution of PCP. 3. Peak plasma concentrations of PCA and PCP increased with dose in both rat and mouse. 4. Bioavailability of PCA was low in both rat and mouse and was sex independent. 5. The high plasma concentrations and relatively long biological half-life of PCP in both species after both i.v. and oral dosing with PCA indicate possible bioaccumulation of PCP upon multiple oral administrations of PCA. JF - Xenobiotica; the fate of foreign compounds in biological systems AU - Yuan, J H AU - Goehl, T J AU - Murrill, E AU - Moore, R AU - Clark, J AU - Hong, L AU - Irwin, R AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1993/04// PY - 1993 DA - April 1993 SP - 427 EP - 438 VL - 23 IS - 4 SN - 0049-8254, 0049-8254 KW - Anisoles KW - 0 KW - pentachloroanisole KW - 14D125MH3W KW - Pentachlorophenol KW - D9BSU0SE4T KW - Index Medicus KW - Animals KW - Pentachlorophenol -- pharmacokinetics KW - Injections, Intravenous KW - Sex Characteristics KW - Intubation, Gastrointestinal KW - Mice KW - Pentachlorophenol -- blood KW - Biological Availability KW - Rats KW - Mice, Inbred Strains KW - Rats, Inbred F344 KW - Half-Life KW - Female KW - Male KW - Anisoles -- pharmacokinetics KW - Anisoles -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75840563?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Xenobiotica%3B+the+fate+of+foreign+compounds+in+biological+systems&rft.atitle=Toxicokinetics+of+pentachloroanisole+in+F344+rats+and+B6C3F1+mice.&rft.au=Yuan%2C+J+H%3BGoehl%2C+T+J%3BMurrill%2C+E%3BMoore%2C+R%3BClark%2C+J%3BHong%2C+L%3BIrwin%2C+R&rft.aulast=Yuan&rft.aufirst=J&rft.date=1993-04-01&rft.volume=23&rft.issue=4&rft.spage=427&rft.isbn=&rft.btitle=&rft.title=Xenobiotica%3B+the+fate+of+foreign+compounds+in+biological+systems&rft.issn=00498254&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-08-26 N1 - Date created - 1993-08-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chlorisondamine, a non-competitive ganglionic blocker, antagonizes the cardiovascular effects of cocaine in conscious squirrel monkeys. AN - 75825502; 8100996 AB - Cocaine (0.3 mg/kg i.v.) produced prolonged pressor and tachycardiac responses in conscious squirrel monkeys. Peak pressor and tachycardiac responses following cocaine were 32.7 +/- 3.3 mm Hg and 78.8 +/- 7.4 beats/min, respectively. Pretreatment with 1 mg/kg chlorisondamine, a noncompetitive ganglionic blocker, attenuated the pressor (18.3 +/- 3.8 mm Hg) and tachycardiac (63.7 +/- 10 beats/min) effects of cocaine, while 5 mg/kg chlorisondamine completely prevented these effects of cocaine. This finding supports the conclusion that the cardiovascular effects of cocaine are centrally mediated. JF - Pharmacological research AU - Tella, S R AU - Schindler, C W AU - Goldberg, S R AD - Behavioral Pharmacology and Genetics Section, National Institute on Drug Abuse Addiction Research Center, Baltimore, MD 21224. Y1 - 1993/04// PY - 1993 DA - April 1993 SP - 233 EP - 239 VL - 27 IS - 3 SN - 1043-6618, 1043-6618 KW - Ganglionic Blockers KW - 0 KW - Hexamethonium Compounds KW - Hexamethonium KW - 3C9PSP36Z2 KW - Cocaine KW - I5Y540LHVR KW - Chlorisondamine KW - JD3M24F66I KW - Index Medicus KW - Animals KW - Heart Rate -- drug effects KW - Drug Interactions KW - Consciousness KW - Injections, Intravenous KW - Ganglionic Blockers -- pharmacology KW - Blood Pressure -- drug effects KW - Hexamethonium Compounds -- pharmacology KW - Chlorisondamine -- pharmacology KW - Saimiri -- physiology KW - Cardiovascular System -- drug effects KW - Cocaine -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75825502?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Chlorisondamine%2C+a+non-competitive+ganglionic+blocker%2C+antagonizes+the+cardiovascular+effects+of+cocaine+in+conscious+squirrel+monkeys.&rft.au=Tella%2C+S+R%3BSchindler%2C+C+W%3BGoldberg%2C+S+R&rft.aulast=Tella&rft.aufirst=S&rft.date=1993-04-01&rft.volume=27&rft.issue=3&rft.spage=233&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 - 1993-08-12 N1 - Date created - 1993-08-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Crevice-forming mutants in the rigid core of bovine pancreatic trypsin inhibitor: crystal structures of F22A, Y23A, N43G, and F45A. AN - 75798606; 8518731 AB - Crystal structures of four mutants of bovine pancreatic trypsin inhibitor (F22A, Y23A, N43G, and F45A), engineered to alter their stability properties, have been determined. The mutated residues, which are highly conserved among Kunitz-type inhibitors, are located in the rigid core of the molecule. Replacement of the partially buried bulky residues of the wild-type protein with smaller residues resulted in crevices open to the exterior of the molecule. The overall three-dimensional structure of these mutants is very similar to that of the wild-type protein and only small rearrangements are observed among the atoms lining the crevices. JF - Protein science : a publication of the Protein Society AU - Danishefsky, A T AU - Housset, D AU - Kim, K S AU - Tao, F AU - Fuchs, J AU - Woodward, C AU - Wlodawer, A AD - Macromolecular Structure Laboratory, NCI-Frederick Cancer Research and Development Center, ABL, Basic Research Program, Maryland 21702. Y1 - 1993/04// PY - 1993 DA - April 1993 SP - 577 EP - 587 VL - 2 IS - 4 SN - 0961-8368, 0961-8368 KW - Trypsin Inhibitors KW - 0 KW - Water KW - 059QF0KO0R KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Animals KW - Protein Structure, Secondary KW - Cattle KW - X-Ray Diffraction KW - Models, Molecular KW - Pancreas KW - Water -- chemistry KW - Hydrogen Bonding KW - Trypsin Inhibitors -- chemistry KW - Trypsin Inhibitors -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75798606?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Protein+science+%3A+a+publication+of+the+Protein+Society&rft.atitle=Crevice-forming+mutants+in+the+rigid+core+of+bovine+pancreatic+trypsin+inhibitor%3A+crystal+structures+of+F22A%2C+Y23A%2C+N43G%2C+and+F45A.&rft.au=Danishefsky%2C+A+T%3BHousset%2C+D%3BKim%2C+K+S%3BTao%2C+F%3BFuchs%2C+J%3BWoodward%2C+C%3BWlodawer%2C+A&rft.aulast=Danishefsky&rft.aufirst=A&rft.date=1993-04-01&rft.volume=2&rft.issue=4&rft.spage=577&rft.isbn=&rft.btitle=&rft.title=Protein+science+%3A+a+publication+of+the+Protein+Society&rft.issn=09618368&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-07-23 N1 - Date created - 1993-07-23 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Biochemistry. 1972 Aug 1;11(16):2967-77 [5041905] Protein Sci. 1993 Apr;2(4):588-96 [7686069] Eur J Biochem. 1978 Jul 17;88(1):87-95 [27364] J Mol Biol. 1982 Sep 15;160(2):343-61 [6184480] J Mol Biol. 1984 Dec 5;180(2):301-29 [6210373] J Mol Biol. 1985 Sep 20;185(2):405-19 [2414451] Methods Enzymol. 1985;115:157-71 [3841179] Methods Enzymol. 1985;115:252-70 [3841182] J Mol Biol. 1986 Aug 20;190(4):593-604 [3097327] J Mol Biol. 1987 Jan 5;193(1):145-56 [2438420] Biochemistry. 1987 Aug 11;26(16):5163-72 [2444253] J Mol Biol. 1987 Dec 5;198(3):469-80 [2448484] Nature. 1988 Feb 11;331(6156):525-7 [2893289] Nature. 1988 Feb 11;331(6156):528-30 [2893290] Nature. 1988 Feb 11;331(6156):530-2 [2893291] J Biol Chem. 1988 May 5;263(13):6001-4 [2452157] Cold Spring Harb Symp Quant Biol. 1987;52:511-9 [2456884] Nature. 1989 Mar 9;338(6211):127-32 [2465497] J Mol Biol. 1991 Aug 5;220(3):757-70 [1714504] J Mol Biol. 1991 Sep 20;221(2):669-91 [1920440] Science. 1991 Nov 15;254(5034):974-80 [1948083] Science. 1992 Jan 10;255(5041):178-83 [1553543] J Mol Biol. 1992 Apr 5;224(3):671-83 [1373774] Proc Natl Acad Sci U S A. 1992 Jun 1;89(11):5083-7 [1594616] J Mol Biol. 1992 Oct 5;227(3):757-75 [1383552] J Mol Biol. 1973 Jul 5;77(3):417-36 [4737866] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of the herbicide atrazine in the development of non-Hodgkin's lymphoma. AN - 75797933; 8316777 AB - Atrazine is the most commonly used herbicide in the United States and is a wide-spread groundwater contaminant in the Midwest. The role of atrazine in the development of human non-Hodgkin's lymphoma (NHL) was investigated in three case-referent studies conducted in four midwestern states in the United States. A total of 993 white men with NHL and 2918 population-based referents were interviewed concerning their agricultural practices. When the results of the three studies were combined, atrazine use was associated with an odds ratio of 1.4 [95% confidence interval (95% CI) 1.1-1.8, 130 cases, 249 referents) for NHL. However, adjustments for the use of 2,4-dichlorophenoxyacetic acid and organophosphate insecticides reduced the apparent association between NHL and atrazine in all but one state and reduced the associations for the long-term and frequent users in Nebraska. Detailed analyses suggested that there was little or no increase in the risk of NHL attributable to the agricultural use of atrazine. JF - Scandinavian journal of work, environment & health AU - Hoar Zahm, S AU - Weisenburger, D D AU - Cantor, K P AU - Holmes, F F AU - Blair, A AD - Environmental Epidemiology Branch, National Cancer Institute, Rockville, Maryland 20892. Y1 - 1993/04// PY - 1993 DA - April 1993 SP - 108 EP - 114 VL - 19 IS - 2 SN - 0355-3140, 0355-3140 KW - Atrazine KW - QJA9M5H4IM KW - Index Medicus KW - Risk Factors KW - Humans KW - Adult KW - Aged KW - Midwestern United States KW - Middle Aged KW - Male KW - Female KW - Agricultural Workers' Diseases -- chemically induced KW - Occupational Exposure -- adverse effects KW - Lymphoma, Non-Hodgkin -- chemically induced KW - Atrazine -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75797933?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Scandinavian+journal+of+work%2C+environment+%26+health&rft.atitle=Role+of+the+herbicide+atrazine+in+the+development+of+non-Hodgkin%27s+lymphoma.&rft.au=Hoar+Zahm%2C+S%3BWeisenburger%2C+D+D%3BCantor%2C+K+P%3BHolmes%2C+F+F%3BBlair%2C+A&rft.aulast=Hoar+Zahm&rft.aufirst=S&rft.date=1993-04-01&rft.volume=19&rft.issue=2&rft.spage=108&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 completed - 1993-07-28 N1 - Date created - 1993-07-28 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Scand J Work Environ Health. 1994 Jun;20(3):223-6 [7973496] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Leukocyte CD18 monoclonal antibody worsens endotoxemia and cardiovascular injury in canines with septic shock. AN - 75795917; 8099906 AB - We investigated the effects of a murine monoclonal antibody directed against the canine leukocyte CD11/18 adhesion complex (MAb R15.7) in a canine model of septic shock. Awake 2-yr-old purpose-bred beagles were studied 7 days before and 1, 2, 4, and 10 days after intraperitoneal placement of an Escherichia coli-infected fibrin clot. Starting 12 h before clot placement, animals received 0.5-1 mg/kg iv every 12 h (4 doses total) of either MAb R15.7 (MAb group, n = 8) or, as controls, murine serum protein (n = 8). After infected clot placement, all animals received antibiotic (ceftriaxne, 100 mg.kg-1.day-1 for 4 days). Two of eight control animals and four of eight MAb animals died (P = 0.4). During the first 8 h after clot placement, MAb animals, compared with control animals, had greater (P < 0.06) increases in serum endotoxin levels and higher (P < 0.05) neutrophil counts. Day 1 after clot placement, MAb animals, compared with control animals, had decreased (P < 0.05) central venous pressure and arterial pH and increased (P < 0.05) arterial lactate. Day 2 after clot placement, MAb animals, compared with control animals, had decreased (P < 0.05) cardiac index and mean arterial pressure. In summary, MAb R15.7, although associated with increased neutrophil counts, worsened serum endotoxemia, acidosis, and cardiovascular function in this canine model of septic shock. These data suggest that in septic shock, antibody directed against this leukocyte membrane protein complex may be harmful, possibly via impairment of normal leukocyte function. JF - Journal of applied physiology (Bethesda, Md. : 1985) AU - Eichacker, P Q AU - Hoffman, W D AU - Farese, A AU - Danner, R L AU - Suffredini, A F AU - Waisman, Y AU - Banks, S M AU - Mouginis, T AU - Wilson, L AU - Rothlein, R AD - Critical Care Medicine Department, National Institutes of Health, Bethesda 20892. Y1 - 1993/04// PY - 1993 DA - April 1993 SP - 1885 EP - 1892 VL - 74 IS - 4 SN - 8750-7587, 8750-7587 KW - Antibodies, Monoclonal KW - 0 KW - Antigens, CD KW - Antigens, CD11 KW - Antigens, CD18 KW - Endotoxins KW - Receptors, Leukocyte-Adhesion KW - Index Medicus KW - Animals KW - Acid-Base Equilibrium KW - Neutrophils KW - Antibodies, Monoclonal -- blood KW - Dogs KW - Endotoxins -- toxicity KW - Receptors, Leukocyte-Adhesion -- immunology KW - Leukocyte Count KW - Antibodies, Monoclonal -- administration & dosage KW - Toxemia -- blood KW - Shock, Septic -- complications KW - Cardiovascular System -- injuries KW - Shock, Septic -- immunology KW - Cardiovascular System -- immunology KW - Toxemia -- immunology KW - Toxemia -- complications KW - Shock, Septic -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75795917?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+applied+physiology+%28Bethesda%2C+Md.+%3A+1985%29&rft.atitle=Leukocyte+CD18+monoclonal+antibody+worsens+endotoxemia+and+cardiovascular+injury+in+canines+with+septic+shock.&rft.au=Eichacker%2C+P+Q%3BHoffman%2C+W+D%3BFarese%2C+A%3BDanner%2C+R+L%3BSuffredini%2C+A+F%3BWaisman%2C+Y%3BBanks%2C+S+M%3BMouginis%2C+T%3BWilson%2C+L%3BRothlein%2C+R&rft.aulast=Eichacker&rft.aufirst=P&rft.date=1993-04-01&rft.volume=74&rft.issue=4&rft.spage=1885&rft.isbn=&rft.btitle=&rft.title=Journal+of+applied+physiology+%28Bethesda%2C+Md.+%3A+1985%29&rft.issn=87507587&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-07-19 N1 - Date created - 1993-07-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Seasonal variation in behavioral responses to m-CPP in patients with seasonal affective disorder and controls. AN - 75782546; 8390305 AB - This paper reports the behavioral responses to m-chlorophenylpiperazine (m-CPP), a serotonin agonist, in patients with seasonal affective disorder (SAD) and controls during the summer. Results are compared with the responses of SAD patients and controls given m-CPP in the winter. Results of the winter study were reported earlier by our group. Baseline Hamilton depression ratings in SAD patients were significantly lower in the summer than in winter (p < 0.05). Additionally, in both SAD patients and controls, there were seasonal differences on the National Institute of Mental Health (NIMH) self-rating scale items: "depressed affect," "dysphoria," and "functional deficit" at baseline. The behavioral responses to m-CPP across seasons differentiated patients from normals only in the "activation/euphoria" item, on which a far greater response was seen in patients than in controls during the winter. This behavioral response may be a state marker for winter depression, as it was significantly reduced after light treatment of these patients in the winter, and in the summer. SAD patients responded differently from controls on "altered self-awareness" and "dysphoria" independently of seasons, and these responses may be considered as possible trait markers for this condition. These results provide further evidence of a possible deficiency in serotonergic transmission in seasonal affective disorder. JF - Biological psychiatry AU - Joseph-Vanderpool, J R AU - Jacobsen, F M AU - Murphy, D L AU - Hill, J L AU - Rosenthal, N E AD - Section on Environmental Psychiatry, NIMH, Bethesda, MD 20892. Y1 - 1993/04/01/ PY - 1993 DA - 1993 Apr 01 SP - 496 EP - 504 VL - 33 IS - 7 SN - 0006-3223, 0006-3223 KW - Piperazines KW - 0 KW - Receptors, Serotonin KW - Serotonin Receptor Agonists KW - Serotonin KW - 333DO1RDJY KW - 1-(3-chlorophenyl)piperazine KW - REY0CNO998 KW - Index Medicus KW - Receptors, Serotonin -- physiology KW - Euphoria -- drug effects KW - Receptors, Serotonin -- drug effects KW - Serotonin -- physiology KW - Infusions, Intravenous KW - Synaptic Transmission -- drug effects KW - Humans KW - Circadian Rhythm -- drug effects KW - Euphoria -- physiology KW - Personality Inventory KW - Synaptic Transmission -- physiology KW - Circadian Rhythm -- physiology KW - Adult KW - Middle Aged KW - Female KW - Male KW - Serotonin Receptor Agonists -- adverse effects KW - Seasonal Affective Disorder -- drug therapy KW - Seasonal Affective Disorder -- physiopathology KW - Piperazines -- therapeutic use KW - Seasons KW - Serotonin Receptor Agonists -- therapeutic use KW - Seasonal Affective Disorder -- psychology KW - Piperazines -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75782546?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biological+psychiatry&rft.atitle=Seasonal+variation+in+behavioral+responses+to+m-CPP+in+patients+with+seasonal+affective+disorder+and+controls.&rft.au=Joseph-Vanderpool%2C+J+R%3BJacobsen%2C+F+M%3BMurphy%2C+D+L%3BHill%2C+J+L%3BRosenthal%2C+N+E&rft.aulast=Joseph-Vanderpool&rft.aufirst=J&rft.date=1993-04-01&rft.volume=33&rft.issue=7&rft.spage=496&rft.isbn=&rft.btitle=&rft.title=Biological+psychiatry&rft.issn=00063223&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-07-20 N1 - Date created - 1993-07-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular genetics in Saccharomyces kluyveri: the HIS3 homolog and its use as a selectable marker gene in S. kluyveri and Saccharomyces cerevisiae. AN - 75780179; 8511965 AB - We cloned the Saccharomyces kluyveri HIS3 homolog, k-HIS3, and made a partial deletion of the gene. The k-HIS3 gene complemented a HIS3 deletion in S. cerevisiae. The DNA sequences of the open reading frames (ORFs) of the HIS3 homologs are 70% identical at the DNA level and 83% identical at the deduced amino acid level. The ORF upstream of the k-HIS3 gene is related to the PET56 gene of S. cerevisiae found upstream of the HIS3 gene of S. cerevisiae. The ORF downstream from the k-HIS3 gene is not related to the DED1 gene found downstream of the HIS3 gene in S. cerevisiae. JF - Yeast (Chichester, England) AU - Weinstock, K G AU - Strathern, J N AD - Laboratory of Eukaryotic Gene Expression, ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, MD 21702-1201. Y1 - 1993/04// PY - 1993 DA - April 1993 SP - 351 EP - 361 VL - 9 IS - 4 SN - 0749-503X, 0749-503X KW - HIS3 KW - PET56 KW - URA3 KW - Genetic Markers KW - 0 KW - Uracil KW - 56HH86ZVCT KW - Hydro-Lyases KW - EC 4.2.1.- KW - imidazoleglycerolphosphate dehydratase KW - EC 4.2.1.19 KW - Index Medicus KW - Saccharomyces cerevisiae -- genetics KW - Base Sequence KW - Uracil -- metabolism KW - Transformation, Genetic KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Sequence Analysis, DNA KW - Selection, Genetic KW - Chromosome Mapping KW - Mutagenesis KW - Cloning, Molecular KW - Genes, Fungal -- genetics KW - Saccharomyces -- genetics KW - Hydro-Lyases -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75780179?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Yeast+%28Chichester%2C+England%29&rft.atitle=Molecular+genetics+in+Saccharomyces+kluyveri%3A+the+HIS3+homolog+and+its+use+as+a+selectable+marker+gene+in+S.+kluyveri+and+Saccharomyces+cerevisiae.&rft.au=Weinstock%2C+K+G%3BStrathern%2C+J+N&rft.aulast=Weinstock&rft.aufirst=K&rft.date=1993-04-01&rft.volume=9&rft.issue=4&rft.spage=351&rft.isbn=&rft.btitle=&rft.title=Yeast+%28Chichester%2C+England%29&rft.issn=0749503X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-07-15 N1 - Date created - 1993-07-15 N1 - Date revised - 2017-01-13 N1 - Gene symbol - HIS3; PET56; URA3 N1 - Genetic sequence - Z14125; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Fast pre-potential generation in rat hippocampal CA1 pyramidal neurons. AN - 75777391; 8506028 AB - Small all-or-none pre-potentials have been shown under some conditions to underlie antidromic and orthodromic spike discharge in somatic recordings of hippocampal pyramidal neurons [Andersen P. and Lomo T. (1966) Expl Brain Res. 2, 247-260; Kandel E. R. et al. (1961) J. Neurophysiol. 24, 225-242; Schwartzkroin P. A. (1977) Brain Res. 128, 53-68; Spencer W. A. and Kandel E. R. (1961) J. Neurophysiol. 24, 272-285]. These potentials are taken to reflect spike discharge in distant regions of the cell (axonal or dendritic) [Andersen P. and Lomo T. (1966) Expl Brain Res. 2, 247-260; Kandel E. R. and Spencer W. A. (1961) Ann. N. Y. Acad. Sci. 94, 570-603; Schwartzkroin P. A. (1977) Brain Res. 128, 53-68] or electronic spike conduction across a gap junction between neighboring pyramidal cells [Dudek F. E. et al. (1983) In Basic Mechanisms of Neural Hyperexcitability, pp. 31-73]. The present study compared pre-potentials recorded at the somatic and dendritic levels and used restricted applications of tetrodotoxin to examine the relationship between pre-potentials and Na+ spike discharge. Intrasomatic and intradendritic recordings were obtained from CA1 pyramidal neurons of rat hippocampal slices maintained in vitro. Orthodromic and antidromic spike discharge was evoked by stimulation of afferent fibers in stratum radiatum and pyramidal cell axons in the alveus, respectively. Focal pressure application of tetrodotoxin in the immediate vicinity of somatic or dendritic recordings uncovered pre-potentials following blockade of antidromic spike discharge. Blockade of these pre-potentials required the diffusion of tetrodotoxin to a location remote from the recording site. Focal application of tetrodotoxin in the cell body layer reliably uncovered orthodromic pre-potentials at the soma only when stimulus intensity was raised beyond threshold for somatic spike discharge; e.g. to intensities shown to initiate spike discharge in apical dendritic locations [Turner R. W. et al. (1991) J. Neurosci. 11, 2270-2280]. These data provide evidence that propagation of a Na+ spike over the pyramidal cell axis is preceded by a depolarization in the form of a pre-potential. The uncovering of orthodromic somatic pre-potentials by tetrodotoxin during suprathreshold activation further supports the proposal [Spencer W. A. and Kandel E. R. (1961) J. Neurophysiol. 24, 272-285] that dendritic spike discharge [Turner R. W. et al. (1991) J. Neurosci. 11, 2270-2280] can underlie fast pre-potential generation in pyramidal cell somata. JF - Neuroscience AU - Turner, R W AU - Meyers, D E AU - Barker, J L AD - Laboratory of Neurophysiology, National Institutes of Health, NINCDS, Bethesda, MD. Y1 - 1993/04// PY - 1993 DA - April 1993 SP - 949 EP - 959 VL - 53 IS - 4 SN - 0306-4522, 0306-4522 KW - Tetrodotoxin KW - 4368-28-9 KW - Sodium KW - 9NEZ333N27 KW - Index Medicus KW - Animals KW - Sodium -- physiology KW - Membrane Potentials -- physiology KW - Electrophysiology KW - Electric Stimulation KW - Rats KW - Neural Conduction -- physiology KW - In Vitro Techniques KW - Rats, Wistar KW - Membrane Potentials -- drug effects KW - Tetrodotoxin -- pharmacology KW - Dendrites -- drug effects KW - Male KW - Pyramidal Tracts -- cytology KW - Hippocampus -- physiology KW - Hippocampus -- cytology KW - Neurons -- physiology KW - Pyramidal Tracts -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75777391?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuroscience&rft.atitle=Fast+pre-potential+generation+in+rat+hippocampal+CA1+pyramidal+neurons.&rft.au=Turner%2C+R+W%3BMeyers%2C+D+E%3BBarker%2C+J+L&rft.aulast=Turner&rft.aufirst=R&rft.date=1993-04-01&rft.volume=53&rft.issue=4&rft.spage=949&rft.isbn=&rft.btitle=&rft.title=Neuroscience&rft.issn=03064522&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-07-08 N1 - Date created - 1993-07-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Taste intensity performance in patients irradiated to the head and neck. AN - 75776920; 8511171 AB - Decrements in taste-detection thresholds during radiotherapy and subsequent recovery in the months after therapy are well documented. However, few studies have explored suprathreshold taste intensity perception in radiation patients. This cross-sectional study compared taste function in 15 men postradiation with a group of 23 healthy, nonirradiated male volunteers. A direct-scaling procedure was used to assess taste intensity perception of the four basic taste qualities. Patients performed nearly as well as control subjects on objective measures of suprathreshold functioning. Postradiation intensity judgments of salty (sodium chloride), sweet (sucrose), and bitter (quinine sulfate) solutions were not significantly reduced. Subtle, age-related taste impairments were identified for sour perception (citric acid) postradiotherapy. Younger patients judged citric acid to be more intense than did age-appropriate control subjects, whereas older patients judged it to be less intense. Moreover, younger patients were likely to be midly dysgeusic, whereas older patients appeared to be hypogeusic for citric acid. This study provides evidence for near normal suprathreshold taste intensity perception in patients who have received head and neck irradiation. JF - Physiology & behavior AU - Schwartz, L K AU - Weiffenbach, J M AU - Valdez, I H AU - Fox, P C AD - Clinical Investigations and Patient Care Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/04// PY - 1993 DA - April 1993 SP - 671 EP - 677 VL - 53 IS - 4 SN - 0031-9384, 0031-9384 KW - Index Medicus KW - Salivation -- radiation effects KW - Radiotherapy Dosage KW - Humans KW - Adult KW - Ageusia -- physiopathology KW - Aged KW - Middle Aged KW - Follow-Up Studies KW - Salivation -- physiology KW - Male KW - Female KW - Taste Threshold -- radiation effects KW - Hodgkin Disease -- radiotherapy KW - Lymphoma, Non-Hodgkin -- radiotherapy KW - Head and Neck Neoplasms -- radiotherapy KW - Taste Threshold -- physiology KW - Carcinoma, Squamous Cell -- radiotherapy KW - Radiation Injuries -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75776920?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Physiology+%26+behavior&rft.atitle=Taste+intensity+performance+in+patients+irradiated+to+the+head+and+neck.&rft.au=Schwartz%2C+L+K%3BWeiffenbach%2C+J+M%3BValdez%2C+I+H%3BFox%2C+P+C&rft.aulast=Schwartz&rft.aufirst=L&rft.date=1993-04-01&rft.volume=53&rft.issue=4&rft.spage=671&rft.isbn=&rft.btitle=&rft.title=Physiology+%26+behavior&rft.issn=00319384&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-07-12 N1 - Date created - 1993-07-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Styrene inhalation toxicity studies in mice. I. Hepatotoxicity in B6C3F1 mice. AN - 75769377; 8504906 AB - Studies were conducted to evaluate the toxic effects of short-term repeated styrene inhalation in B6C3F1 mice. Male and female mice were exposed to 0, 125, 250, or 500 ppm styrene, 6 hr/day, for up to 14 days. Styrene toxicity was characterized by severe centrilobular hepatic necrosis and deaths after one exposure to 500 ppm or two exposures to 250 ppm. Mortality and hepatotoxicity were not increased by additional exposures, and in surviving mice, regeneration and repair of initial hepatic injury occurred in spite of continued exposure for 14 days. A marked sex difference was observed, with male mice significantly more susceptible to styrene toxicity than females. A nonlinear dose response was observed where mortality in male and female mice was greater in the 250 ppm dose group than that in the 500 ppm dose group. Severe congestion and necrosis of the liver was present in moribund mice; hepatic congestion and serum alanine aminotransferase and sorbitol dehydrogenase were significantly greater in moribund animals. JF - Fundamental and applied toxicology : official journal of the Society of Toxicology AU - Morgan, D L AU - Mahler, J F AU - O'Connor, R W AU - Price, H C AU - Adkins, B AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1993/04// PY - 1993 DA - April 1993 SP - 325 EP - 335 VL - 20 IS - 3 SN - 0272-0590, 0272-0590 KW - Styrenes KW - 0 KW - Styrene KW - 44LJ2U959V KW - Index Medicus KW - Mice, Inbred Strains KW - Animals KW - Liver -- blood supply KW - Drug Administration Schedule KW - Liver -- drug effects KW - Dose-Response Relationship, Drug KW - Body Weight -- drug effects KW - Mice KW - Administration, Inhalation KW - Male KW - Female KW - Organ Size -- drug effects KW - Chemical and Drug Induced Liver Injury -- blood KW - Chemical and Drug Induced Liver Injury -- mortality KW - Chemical and Drug Induced Liver Injury -- pathology KW - Styrenes -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75769377?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.atitle=Styrene+inhalation+toxicity+studies+in+mice.+I.+Hepatotoxicity+in+B6C3F1+mice.&rft.au=Morgan%2C+D+L%3BMahler%2C+J+F%3BO%27Connor%2C+R+W%3BPrice%2C+H+C%3BAdkins%2C+B&rft.aulast=Morgan&rft.aufirst=D&rft.date=1993-04-01&rft.volume=20&rft.issue=3&rft.spage=325&rft.isbn=&rft.btitle=&rft.title=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.issn=02720590&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-07-08 N1 - Date created - 1993-07-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inhalation toxicity of 1,6-hexanediamine dihydrochloride in F344/N rats and B6C3F1 mice. AN - 75765226; 8504909 AB - 1,6-Hexanediamine (HDA) is a high production volume chemical which is used as an intermediate in the synthesis of paints, resins, inks, and textiles and as a corrosion inhibitor in lubricants. Two- and 13-week studies of the toxicity of the dihydrochloride salt of HDA (HDDC) were conducted in male and female Fischer 344/N rats and B6C3F1 mice using whole-body inhalation exposure. Both species were evaluated for histopathologic and reproductive effects, and rats were examined for clinical chemistry and hematologic changes. In the 2-week inhalation studies, animals were exposed to 10-800 mg HDDC/m3, 6 hr per day. All rats, all female mice, and two of five male mice in the high-exposure group died before the end of the study. Surviving mice in this group had a dose-dependent depression in body weight gain. Clinical signs were primarily related to upper respiratory tract irritation and included dyspnea and nasal discharge in both species. Treatment-related histopathologic lesions included inflammation and necrosis of the laryngeal epithelium of both species and the tracheal epithelium of mice, as well as focal inflammation and ulceration of the respiratory and olfactory nasal mucosa. In the 13-week inhalation studies, animals were exposed to HDDC at concentrations of 1.6-160 mg/m3 for 6 hr per day, 5 days per week. In addition to the base study groups, a supplemental group of rats at each exposure level was included to assess the effect of HDDC on reproduction. No treatment-related changes in organ weights or organ-to-body-weight ratios occurred in rats, and no treatment-related clinical signs or gross lesions were seen in either species. Chemical-related microscopic lesions were limited to the upper respiratory tract (larynx and nasal passages) in the two highest exposure groups and were similar in both species. These lesions included minimal to mild focal erosion, ulceration, inflammation, and hyperplasia of the laryngeal epithelium, in addition to degeneration of the olfactory and respiratory nasal epithelium. HDDC caused no significant changes in sperm morphology or vaginal cytology and no significant adverse effects on reproduction in rats or mice. Hematologic and clinical chemistry changes in rats were minor and sporadic and were not accompanied by related histologic findings. HDDC did not increase the frequency of micronucleated erythrocytes in mice.(ABSTRACT TRUNCATED AT 400 WORDS) JF - Fundamental and applied toxicology : official journal of the Society of Toxicology AU - Hébert, C D AU - Elwell, M R AU - Travlos, G S AU - Zeiger, E AU - French, J E AU - Bucher, J R AD - Experimental Toxicology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1993/04// PY - 1993 DA - April 1993 SP - 348 EP - 359 VL - 20 IS - 3 SN - 0272-0590, 0272-0590 KW - Diamines KW - 0 KW - 1,6-diaminohexane KW - ZRA5J5B2QW KW - Index Medicus KW - Vagina -- drug effects KW - Animals KW - Drug Administration Schedule KW - Reproduction -- drug effects KW - Dose-Response Relationship, Drug KW - Vagina -- pathology KW - Spermatozoa -- pathology KW - Mice KW - Rats KW - Mice, Inbred Strains KW - Rats, Inbred F344 KW - Micronucleus Tests KW - Spermatozoa -- drug effects KW - Body Weight -- drug effects KW - Administration, Inhalation KW - Female KW - Male KW - Organ Size -- drug effects KW - Diamines -- administration & dosage KW - Diamines -- blood KW - Diamines -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75765226?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.atitle=Inhalation+toxicity+of+1%2C6-hexanediamine+dihydrochloride+in+F344%2FN+rats+and+B6C3F1+mice.&rft.au=H%C3%A9bert%2C+C+D%3BElwell%2C+M+R%3BTravlos%2C+G+S%3BZeiger%2C+E%3BFrench%2C+J+E%3BBucher%2C+J+R&rft.aulast=H%C3%A9bert&rft.aufirst=C&rft.date=1993-04-01&rft.volume=20&rft.issue=3&rft.spage=348&rft.isbn=&rft.btitle=&rft.title=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.issn=02720590&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-07-08 N1 - Date created - 1993-07-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pharmacological issues in the treatment of bipolar disorder: focus on mood-stabilizing compounds. AN - 75762492; 8500079 AB - The acute and chronic pharmacotherapy of bipolar disorder requires an understanding of the pharmacology of very dissimilar compounds--the mood stabilizers (lithium, carbamazepine and valproate) and several classes of antidepressants. No definitive data are available on the primary mode of action of mood stabilizers, and those used show no single pharmacological property. On the other hand, the pharmacokinetics and dynamics of these compounds are well studied. JF - Canadian journal of psychiatry. Revue canadienne de psychiatrie AU - Potter, W Z AU - Ketter, T A AD - Section on Clinical Pharmacology, National Institute of Mental Health, Bethesda, Maryland 20892. Y1 - 1993/04// PY - 1993 DA - April 1993 SP - S51 EP - S56 VL - 38 IS - 3 Suppl 2 SN - 0706-7437, 0706-7437 KW - Anticonvulsants KW - 0 KW - Antidepressive Agents KW - Carbamazepine KW - 33CM23913M KW - Valproic Acid KW - 614OI1Z5WI KW - Index Medicus KW - Drug Interactions KW - Carbamazepine -- adverse effects KW - Carbamazepine -- pharmacokinetics KW - Humans KW - Infant, Newborn KW - Carbamazepine -- therapeutic use KW - Female KW - Pregnancy KW - Anticonvulsants -- pharmacokinetics KW - Bipolar Disorder -- blood KW - Antidepressive Agents -- pharmacokinetics KW - Bipolar Disorder -- drug therapy KW - Anticonvulsants -- adverse effects KW - Bipolar Disorder -- psychology KW - Antidepressive Agents -- therapeutic use KW - Valproic Acid -- adverse effects KW - Antidepressive Agents -- adverse effects KW - Valproic Acid -- therapeutic use KW - Anticonvulsants -- therapeutic use KW - Valproic Acid -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75762492?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Canadian+journal+of+psychiatry.+Revue+canadienne+de+psychiatrie&rft.atitle=Pharmacological+issues+in+the+treatment+of+bipolar+disorder%3A+focus+on+mood-stabilizing+compounds.&rft.au=Potter%2C+W+Z%3BKetter%2C+T+A&rft.aulast=Potter&rft.aufirst=W&rft.date=1993-04-01&rft.volume=38&rft.issue=3+Suppl+2&rft.spage=S51&rft.isbn=&rft.btitle=&rft.title=Canadian+journal+of+psychiatry.+Revue+canadienne+de+psychiatrie&rft.issn=07067437&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-07-01 N1 - Date created - 1993-07-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Epidermal growth factor receptor ligands regulate keratin 8 expression in keratinocytes, and transforming growth factor alpha mediates the induction of keratin 8 by the v-rasHa oncogene. AN - 75748447; 7684248 AB - Cytokeratins 8 and 18 (Endo A and B) are among the earliest expressed embryonic genes and the major components of the cytoskeleton in simple epithelia of the adult. Recent data indicate that these cytokeratins are aberrantly expressed in several epithelial tumor types and that expression in cultured mouse keratinocytes is linked to activation of the rasHa oncogene. Furthermore, up-regulation of K8/K18 in keratinocytes is associated with reciprocal suppression of K1. We now show that the aberrant expression of K8 and K18 and suppression of K1 in cultured keratinocytes transduced with the v-rasHa gene are mediated by a factor secreted into the culture medium. Furthermore, transforming growth factor alpha (TGF-alpha) and epidermal growth factor elicit an identical pattern of K8/K18 expression and K1 suppression in normal keratinocytes. The factor in medium from v-rasHa keratinocytes is TGF-alpha, as a specific blocking antibody for rat and mouse TGF-alpha prevents the expression of K8 and restores expression of K1. The tyrosine kinase inhibitor genistein also prevents K8 induction in v-rasHa keratinocytes and in normal keratinocytes treated with TGF-alpha- or v-rasHa-conditioned medium. However, simply stimulating proliferation of keratinocytes by cholera toxin does not result in expression of K8 or suppression of K1. Finally, tumor grafts from neoplastic epidermal cells overexpressing TGF-alpha via retroviral transduction of human TGF-alpha complementary DNA in vitro show coordinate expression of K8 and human TGF-alpha. These studies indicate that K8 expression in keratinocytes, and derivative neoplastic cells, in vivo and in vitro is regulated by epidermal growth factor receptor ligands. Since the expression of cytokines and K8/K18 in early embryogenesis is often coincident, cytokines may be the physiological mediators of K8/K18 expression in embryonic cells. JF - Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research AU - Cheng, C AU - Tennenbaum, T AU - Dempsey, P J AU - Coffey, R J AU - Yuspa, S H AU - Dlugosz, A A AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1993/04// PY - 1993 DA - April 1993 SP - 317 EP - 327 VL - 4 IS - 4 SN - 1044-9523, 1044-9523 KW - v-rasHa KW - Biological Factors KW - 0 KW - Culture Media, Conditioned KW - Transforming Growth Factor alpha KW - Transforming Growth Factor beta KW - Epidermal Growth Factor KW - 62229-50-9 KW - Keratins KW - 68238-35-7 KW - Index Medicus KW - Biological Factors -- isolation & purification KW - Animals KW - Transforming Growth Factor beta -- physiology KW - Cells, Cultured KW - Mice KW - Gene Expression Regulation KW - Mice, Inbred BALB C KW - Genes, ras KW - Transforming Growth Factor alpha -- physiology KW - Keratinocytes -- metabolism KW - Keratins -- biosynthesis KW - Epidermal Growth Factor -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75748447?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cell+growth+%26+differentiation+%3A+the+molecular+biology+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=Epidermal+growth+factor+receptor+ligands+regulate+keratin+8+expression+in+keratinocytes%2C+and+transforming+growth+factor+alpha+mediates+the+induction+of+keratin+8+by+the+v-rasHa+oncogene.&rft.au=Cheng%2C+C%3BTennenbaum%2C+T%3BDempsey%2C+P+J%3BCoffey%2C+R+J%3BYuspa%2C+S+H%3BDlugosz%2C+A+A&rft.aulast=Cheng&rft.aufirst=C&rft.date=1993-04-01&rft.volume=4&rft.issue=4&rft.spage=317&rft.isbn=&rft.btitle=&rft.title=Cell+growth+%26+differentiation+%3A+the+molecular+biology+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10449523&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-06-18 N1 - Date created - 1993-06-18 N1 - Date revised - 2017-01-13 N1 - Gene symbol - v-rasHa N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Residues in pockets B and F of HLA-B27 are critical in the presentation of an influenza A virus nucleoprotein peptide and influence the stability of peptide - MHC complexes. AN - 75742702; 8494822 AB - Six pockets, designated A through F, which extend from the peptide binding site of class I HLA molecules, have been postulated to play an important role in determining peptide binding specificity. HLA-B27 mutant molecules with single amino acid substitutions at residues 9his-->phe, 24thr-->ser, 45glu-->thr, and 67cys-->ala in pocket B; 114his-->asn in pocket D; and 116asp-->phe in pocket F have been generated and characterized for their capacity to present an influenza A nucleoprotein peptide (NP 383-391) for cytotoxic T lymphocyte recognition. We report here that substitutions in residues 45, 67, and 116 affect presentation of NP 383-391 when peptide is processed and loaded during viral infection. Using 125I-labeled NP peptide, we demonstrate that substitutions in residues 67 and 116 alter the stability of NP-HLA-B27 complexes. A substitution at position 9 of the NP peptide complements the mutation introduced at residue 116, suggesting that the NP peptide binds with its carboxy terminal amino acid in pocket F. These findings indicate that polymorphic residues within pockets B and F of HLA-B27 play a crucial role in peptide binding and stability of peptide-MHC class I complexes. Furthermore, our results suggest that substitutions at allele-specific residues within pockets B and F alter the stability of NP-HLA-B27 complexes resulting in the diminution or abrogation of NP presentation during viral infection. JF - International immunology AU - Carreno, B M AU - Winter, C C AU - Taurog, J D AU - Hansen, T H AU - Biddison, W E AD - Molecular Immunology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/04// PY - 1993 DA - April 1993 SP - 353 EP - 360 VL - 5 IS - 4 SN - 0953-8178, 0953-8178 KW - HLA-B27 Antigen KW - 0 KW - Macromolecular Substances KW - NP protein, Influenza A virus KW - Nucleoproteins KW - RNA-Binding Proteins KW - Viral Core Proteins KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Drug Stability KW - Base Sequence KW - Humans KW - DNA -- genetics KW - Adult KW - Molecular Sequence Data KW - Influenza A virus -- immunology KW - Influenza A virus -- metabolism KW - Amino Acid Sequence KW - Protein Binding KW - Binding Sites KW - Viral Core Proteins -- immunology KW - Nucleoproteins -- metabolism KW - HLA-B27 Antigen -- metabolism KW - Viral Core Proteins -- metabolism KW - HLA-B27 Antigen -- genetics KW - HLA-B27 Antigen -- chemistry KW - Nucleoproteins -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75742702?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+immunology&rft.atitle=Residues+in+pockets+B+and+F+of+HLA-B27+are+critical+in+the+presentation+of+an+influenza+A+virus+nucleoprotein+peptide+and+influence+the+stability+of+peptide+-+MHC+complexes.&rft.au=Carreno%2C+B+M%3BWinter%2C+C+C%3BTaurog%2C+J+D%3BHansen%2C+T+H%3BBiddison%2C+W+E&rft.aulast=Carreno&rft.aufirst=B&rft.date=1993-04-01&rft.volume=5&rft.issue=4&rft.spage=353&rft.isbn=&rft.btitle=&rft.title=International+immunology&rft.issn=09538178&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-06-23 N1 - Date created - 1993-06-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Environmental health science research and human risk assessment. AN - 75717620; 8484031 JF - Regulatory toxicology and pharmacology : RTP AU - Olden, K AD - Office of the Director, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709-2233. Y1 - 1993/04// PY - 1993 DA - April 1993 SP - 230 EP - 233 VL - 17 IS - 2 Pt 1 SN - 0273-2300, 0273-2300 KW - Hazardous Substances KW - 0 KW - Index Medicus KW - Risk Factors KW - Humans KW - Communication KW - Research KW - Environmental Health KW - Hazardous Substances -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75717620?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Regulatory+toxicology+and+pharmacology+%3A+RTP&rft.atitle=Environmental+health+science+research+and+human+risk+assessment.&rft.au=Olden%2C+K&rft.aulast=Olden&rft.aufirst=K&rft.date=1993-04-01&rft.volume=17&rft.issue=2+Pt+1&rft.spage=230&rft.isbn=&rft.btitle=&rft.title=Regulatory+toxicology+and+pharmacology+%3A+RTP&rft.issn=02732300&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-06-01 N1 - Date created - 1993-06-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Serum creatine phosphokinase elevations in patients with tardive dyskinesia. AN - 75707686; 8097656 AB - We describe a case of marked increases in serum creatine phosphokinase (CPK) associated with a dramatic exacerbation of tardive dyskinesia (TD). Chart review of eight additional patients with severe TD revealed three cases with mild CPK elevations. These cases suggest that TD, especially when accompanied by dystonia, may be associated with pathology of striated muscle. JF - The British journal of psychiatry : the journal of mental science AU - Egan, M F AU - Dargham, A A AU - Kirch, D G AU - Wyatt, R J AD - Neuropsychiatry Branch, NIMH Neuroscience Research Center, St Elizabeth's, Washington, DC 20032. Y1 - 1993/04// PY - 1993 DA - April 1993 SP - 551 EP - 553 VL - 162 SN - 0007-1250, 0007-1250 KW - Antipsychotic Agents KW - 0 KW - Creatine Kinase KW - EC 2.7.3.2 KW - Index Medicus KW - Humans KW - Adult KW - Neurologic Examination -- drug effects KW - Middle Aged KW - Adolescent KW - Male KW - Antipsychotic Agents -- administration & dosage KW - Schizophrenia -- enzymology KW - Creatine Kinase -- blood KW - Dyskinesia, Drug-Induced -- enzymology KW - Dyskinesia, Drug-Induced -- psychology KW - Dyskinesia, Drug-Induced -- diagnosis KW - Schizophrenic Psychology KW - Schizophrenia -- drug therapy KW - Antipsychotic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75707686?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+British+journal+of+psychiatry+%3A+the+journal+of+mental+science&rft.atitle=Serum+creatine+phosphokinase+elevations+in+patients+with+tardive+dyskinesia.&rft.au=Egan%2C+M+F%3BDargham%2C+A+A%3BKirch%2C+D+G%3BWyatt%2C+R+J&rft.aulast=Egan&rft.aufirst=M&rft.date=1993-04-01&rft.volume=162&rft.issue=&rft.spage=551&rft.isbn=&rft.btitle=&rft.title=The+British+journal+of+psychiatry+%3A+the+journal+of+mental+science&rft.issn=00071250&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-06-03 N1 - Date created - 1993-06-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular alterations in the neostriatum of human cocaine addicts. AN - 75707425; 7683144 AB - Molecular changes in the neostriatum of human subjects who died with a history of cocaine abuse were revealed in discrete cell populations by means of the techniques of in situ hybridization histochemistry and in vitro receptor binding and autoradiography. Cocaine subjects had a history of repeated cocaine use and had cocaine and/or cocaine metabolites on board at the time of death. These subjects were compared to control subjects that had both a negative history and toxicology of cocaine use. Selective alterations in mRNA levels of striatal neuropeptides were detected in cocaine subjects compared to control subjects, especially for the opioid peptides. Marked reductions in the levels of enkephalin mRNA and mu opiate receptor binding were found in the caudate and putamen, concomitant with elevations in levels of dynorphin mRNA and kappa opiate receptor binding in the putamen and caudate, respectively. Dopamine uptake site binding was reduced in the caudate and putamen of cocaine subjects. The greater magnitude of changes in the dorsolateral striatum (caudate and putamen) as opposed to the ventromedial striatum (nucleus accumbens) suggests that cocaine abuse preferentially alters the biosynthetic activity of striatal systems associated with sensorimotor functioning. Additionally, an imbalance in the activity of the two major striatal output pathways in cocaine users is implicated because peptide mRNA levels were reduced in enkephalinergic striatopallidal neurons and increased in dynorphinergic striatonigral neurons. Another imbalance, that of reductions of transmitter mRNA and receptor expression associated with euphoria (enkephalin and mu opiate receptors), together with elevations in mRNAs of transmitter systems associated with dysphoria (dynorphin and kappa opiate receptors), suggests a model of dysphoria and craving in the human cocaine addict brain. JF - Synapse (New York, N.Y.) AU - Hurd, Y L AU - Herkenham, M AD - Section on Functional Neuroanatomy, National Institute of Mental Health, Bethesda, Maryland 20892. Y1 - 1993/04// PY - 1993 DA - April 1993 SP - 357 EP - 369 VL - 13 IS - 4 SN - 0887-4476, 0887-4476 KW - Enkephalins KW - 0 KW - RNA, Messenger KW - Receptors, Dopamine KW - Receptors, Opioid, kappa KW - Receptors, Opioid, mu KW - Substance P KW - 33507-63-0 KW - Dynorphins KW - 74913-18-1 KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Receptors, Dopamine -- drug effects KW - Humans KW - Receptors, Opioid, kappa -- metabolism KW - Receptors, Opioid, kappa -- drug effects KW - Substance P -- biosynthesis KW - Receptors, Opioid, mu -- metabolism KW - Histocytochemistry KW - Autoradiography KW - RNA, Messenger -- biosynthesis KW - In Situ Hybridization KW - Enkephalins -- biosynthesis KW - Adult KW - Putamen -- metabolism KW - Nucleus Accumbens -- metabolism KW - Receptors, Opioid, mu -- drug effects KW - Middle Aged KW - Adolescent KW - Female KW - Male KW - Receptors, Dopamine -- metabolism KW - Dynorphins -- biosynthesis KW - Substance-Related Disorders -- pathology KW - Neostriatum -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75707425?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Molecular+alterations+in+the+neostriatum+of+human+cocaine+addicts.&rft.au=Hurd%2C+Y+L%3BHerkenham%2C+M&rft.aulast=Hurd&rft.aufirst=Y&rft.date=1993-04-01&rft.volume=13&rft.issue=4&rft.spage=357&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 - 1993-05-25 N1 - Date created - 1993-05-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Measurement of heroin and its metabolites by isotope-dilution electron-impact mass spectrometry. AN - 75707287; 8472364 AB - A solid-phase extraction procedure was developed for the isolation of heroin, 6-acetylmorphine, and morphine from blood, plasma, saliva, and urine with subsequent assay by gas chromatography/mass spectrometry. Aprotic solvents, mild elution conditions, and an enzyme inhibitor were used to ensure maximum analyte stability. Samples were extracted and the extract was divided into two equal portions. One portion was assayed directly for heroin; detector response was linear over a concentration range of 1.0 to 250 micrograms/L. The second part of the extract was reacted with N-methyl-bis-trifluoroacetamide and assayed for the trifluoroacetyl derivatives of 6-acetylmorphine and morphine; detector response was linear over a concentration range of 1.0 to 500 micrograms/L. The limit of sensitivity was 1.0 microgram/L for each analyte. Hydrolysis of heroin to 6-acetylmorphine during extraction and analysis was < 5%. The method can be used to corroborate heroin use and to study the pharmacological effects of heroin and its metabolites. JF - Clinical chemistry AU - Goldberger, B A AU - Darwin, W D AU - Grant, T M AU - Allen, A C AU - Caplan, Y H AU - Cone, E J AD - Addiction Research Center, National Institute on Drug Abuse, Baltimore, MD 21224. Y1 - 1993/04// PY - 1993 DA - April 1993 SP - 670 EP - 675 VL - 39 IS - 4 SN - 0009-9147, 0009-9147 KW - Morphine Derivatives KW - 0 KW - Heroin KW - 70D95007SX KW - Morphine KW - 76I7G6D29C KW - 6-O-monoacetylmorphine KW - M5E47P1ZCH KW - Index Medicus KW - Saliva -- chemistry KW - Humans KW - Indicator Dilution Techniques KW - Substance-Related Disorders -- metabolism KW - Quality Control KW - Male KW - Heroin -- analysis KW - Morphine -- urine KW - Morphine -- blood KW - Morphine -- analysis KW - Gas Chromatography-Mass Spectrometry KW - Heroin -- blood KW - Heroin -- urine KW - Body Fluids -- chemistry KW - Morphine Derivatives -- urine KW - Morphine Derivatives -- blood KW - Morphine Derivatives -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75707287?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+chemistry&rft.atitle=Measurement+of+heroin+and+its+metabolites+by+isotope-dilution+electron-impact+mass+spectrometry.&rft.au=Goldberger%2C+B+A%3BDarwin%2C+W+D%3BGrant%2C+T+M%3BAllen%2C+A+C%3BCaplan%2C+Y+H%3BCone%2C+E+J&rft.aulast=Goldberger&rft.aufirst=B&rft.date=1993-04-01&rft.volume=39&rft.issue=4&rft.spage=670&rft.isbn=&rft.btitle=&rft.title=Clinical+chemistry&rft.issn=00099147&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-05-14 N1 - Date created - 1993-05-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Substrate-specific proteases (BLT-esterase) are localized predominantly in the natural killer cells of unprimed mice. AN - 75707194; 8482926 AB - In leukocytes isolated from unprimed mice, the levels of extractable N alpha-Cbz-Lys-thiobenzylesteresterase (BLT-esterase) closely correlated with the number of natural killer (NK) cells. The spleens of mice that exhibit severe combined immunodeficiency (SCID) contained much higher levels of this enzyme than other mouse strains. Treatments that resulted in a local accumulation of NK cells (as assessed by lytic activity) produced a concomitant increase in BLT-esterase activity. However, short-term in vitro treatment of spleen cells with interferon (IFN)-alpha/beta indicated that BLT-esterase levels correlated more closely with absolute numbers of NK cells than with their lytic capacity. There was a very good correlation between the numbers of cells bearing the NK phenotype (NK-1.1+) and BLT-esterase levels. Cells positively sorted using the NK-specific antibodies NK-1.1 and LGL-1 had high enzymatic activity. The BLT-esterase levels were high in both the NK-1.1+/LGL-1- and NK-1.1+/LGL-1+ subsets. Highly purified CD4+ and CD8+ T cells and sIg+ B cells demonstrated negligible enzyme, as did populations of cells highly enriched for macrophages or neutrophils. However, it should be stressed that the inbred mice used on this study have been maintained in a pathogen-free facility. It would be anticipated that mice maintained under less stringent conditions could exhibit appreciable levels of BLT-esterase activity in their T cells. Nonetheless, BLT-esterase is present at high levels in NK cells and cannot be regarded as a T cell-specific enzyme. JF - Journal of leukocyte biology AU - Sayers, T J AU - Mason, L H AU - Pilaro, A AU - Wiltrout, T A AU - Komschlies, K AU - Munger, W L AU - Wiltrout, R H AD - Biological Carcinogenesis Development Program, PRI/DynCorp, NCI-FCRDC, Frederick, Maryland 21702-1201. Y1 - 1993/04// PY - 1993 DA - April 1993 SP - 454 EP - 461 VL - 53 IS - 4 SN - 0741-5400, 0741-5400 KW - Interferon Inducers KW - 0 KW - Interferon Type I KW - Recombinant Proteins KW - Poly I-C KW - 24939-03-5 KW - Polylysine KW - 25104-18-1 KW - poly ICLC KW - 59789-29-6 KW - Interferon-gamma KW - 82115-62-6 KW - Granzymes KW - EC 3.4.21.- KW - Serine Endopeptidases KW - Carboxymethylcellulose Sodium KW - K679OBS311 KW - Index Medicus KW - Animals KW - Liver -- enzymology KW - Interferon-gamma -- pharmacology KW - Mice, Nude KW - Mice KW - Mice, Inbred BALB C KW - Carboxymethylcellulose Sodium -- pharmacology KW - Poly I-C -- pharmacology KW - Polylysine -- pharmacology KW - Interferon Inducers -- pharmacology KW - Interferon Type I -- pharmacology KW - Liver -- drug effects KW - Kinetics KW - Lymph Nodes -- enzymology KW - T-Lymphocyte Subsets -- immunology KW - Mice, Inbred C57BL KW - Spleen -- immunology KW - Flow Cytometry KW - Substrate Specificity KW - Mice, SCID KW - Lymph Nodes -- drug effects KW - Male KW - Serine Endopeptidases -- metabolism KW - Killer Cells, Natural -- immunology KW - Killer Cells, Natural -- enzymology KW - Killer Cells, Natural -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75707194?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+leukocyte+biology&rft.atitle=Substrate-specific+proteases+%28BLT-esterase%29+are+localized+predominantly+in+the+natural+killer+cells+of+unprimed+mice.&rft.au=Sayers%2C+T+J%3BMason%2C+L+H%3BPilaro%2C+A%3BWiltrout%2C+T+A%3BKomschlies%2C+K%3BMunger%2C+W+L%3BWiltrout%2C+R+H&rft.aulast=Sayers&rft.aufirst=T&rft.date=1993-04-01&rft.volume=53&rft.issue=4&rft.spage=454&rft.isbn=&rft.btitle=&rft.title=Journal+of+leukocyte+biology&rft.issn=07415400&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-06-03 N1 - Date created - 1993-06-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Maturational changes in dermal absorption of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in Fischer 344 rats. AN - 75705095; 8480330 AB - An earlier study indicated that percutaneous absorption of a 40-nmol dose of TCDD decreased with aging in rats, suggesting that the potential for systemic exposure following dermal contact would be decreased in older age groups. In this study, maturational changes in potential for systemic exposure to TCDD following dermal application of a low dose (200 pmol) of this chemical were examined in male Fischer 344 rats. Absorption, tissue distribution, and elimination of TCDD, measured as TCDD-derived radioactivity, were examined 72 hr after dermal application of 200 pmol [3H]TCDD (111 pmol/cm2 applied over 1.8 cm2) to the interscapular region of 3-, 5-, 8-, 10-, and 36-week-old rats. The dose was applied in 60 microliters acetone and the application site was covered with a perforated metal cap; animals were held in individual metabolism cages. Dermal absorption was greatest in 3-week-old rats (approximately 129 pmol; approximately 64% of the administered dose), decreasing to approximately 80 pmol (approximately 40%) in 5-, 8-, and 10-week-old rats and to 45 pmol (approximately 22%) in 36-week-old rats. In each age group, 70 to 80% of the radioactivity remaining at the application site 72 hr after dosing could be removed with acetone swabs. Major tissue depots of radioactivity were liver and fat; skin and muscle were minor depots. Changes in distribution of absorbed TCDD-derived radioactivity reflected changes in body mass of these depots; however, tissue concentration also varied. Whole body dissection was performed on rats to determine body mass of tissue depots. Adipose tissue content (Y) increased linearly with body weight (X), Y = 0.03X + 2.1 (r2 = 0.95). Elimination of absorbed TCDD-derived radioactivity was incomplete in all age groups with larger residues being recovered in the carcass. Results indicate that TCDD is absorbed to a greater degree through skin of very young animals and that a significant decrease in potential for systemic exposure may occur during maturation and again during aging. JF - Toxicology and applied pharmacology AU - Anderson, Y B AU - Jackson, J A AU - Birnbaum, L S AD - Experimental Toxicology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1993/04// PY - 1993 DA - April 1993 SP - 214 EP - 220 VL - 119 IS - 2 SN - 0041-008X, 0041-008X KW - Polychlorinated Dibenzodioxins KW - 0 KW - Index Medicus KW - Rats KW - Aging -- physiology KW - Animals KW - Rats, Inbred F344 KW - Administration, Cutaneous KW - Tissue Distribution KW - Male KW - Polychlorinated Dibenzodioxins -- pharmacokinetics KW - Polychlorinated Dibenzodioxins -- administration & dosage KW - Polychlorinated Dibenzodioxins -- toxicity KW - Skin Absorption -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75705095?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Maturational+changes+in+dermal+absorption+of+2%2C3%2C7%2C8-tetrachlorodibenzo-p-dioxin+%28TCDD%29+in+Fischer+344+rats.&rft.au=Anderson%2C+Y+B%3BJackson%2C+J+A%3BBirnbaum%2C+L+S&rft.aulast=Anderson&rft.aufirst=Y&rft.date=1993-04-01&rft.volume=119&rft.issue=2&rft.spage=214&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 - 1993-05-25 N1 - Date created - 1993-05-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Electrophysiological characterization of rat striatal neurons in vitro following a unilateral lesion of dopamine cells. AN - 75702081; 8480280 AB - The effects of a unilateral 6 to 19-week lesion of dopamine cells on the excitability of rat striatal neurons were investigated in vitro using the intracellularly recorded membrane properties of neurons obtained ipsilateral and contralateral to 6-hydroxydopamine (6-OHDA) injection sites. Neurons ipsilateral to the lesion site and in striatal tissue depleted of dopamine exhibited resting membrane potentials and membrane resistances similar to those recorded in contralateral striatal neurons. Denervation appeared to have no appreciable effect on the proportion of neurons exhibiting various patterns of neuronal spiking (repetitive, bursting, or single spike) evoked by depolarizing current pulses. Current-voltage determinations revealed nominal rectification in the majority of neurons and marked nonlinearity consistent with inward rectification at potentials hyperpolarized and depolarized to rest in a large proportion of the remaining neurons. Neurons ipsilateral to 6-OHDA lesion sites exhibited these relationships in the same proportion as contralateral control cells. However, ipsilateral neurons with nominal rectification exhibited an average rate constant for the early onset of small hyperpolarizing membrane transients which was significantly smaller than that of controls. This finding suggests that intrinsic membrane parameters regulating the excitability of certain striatal neurons may be under the influence of dopamine or other factors closely associated with nigrostriatal nerve terminals. JF - Synapse (New York, N.Y.) AU - Twery, M J AU - Thompson, L A AU - Walters, J R AD - Cellular Physiology and Neurotransmission Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/04// PY - 1993 DA - April 1993 SP - 322 EP - 332 VL - 13 IS - 4 SN - 0887-4476, 0887-4476 KW - Oxidopamine KW - 8HW4YBZ748 KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Oxidopamine -- toxicity KW - Membrane Potentials -- physiology KW - Electrophysiology KW - Cell Membrane -- physiology KW - Male KW - Corpus Striatum -- cytology KW - Corpus Striatum -- physiology KW - Neurons -- physiology KW - Dopamine -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75702081?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Electrophysiological+characterization+of+rat+striatal+neurons+in+vitro+following+a+unilateral+lesion+of+dopamine+cells.&rft.au=Twery%2C+M+J%3BThompson%2C+L+A%3BWalters%2C+J+R&rft.aulast=Twery&rft.aufirst=M&rft.date=1993-04-01&rft.volume=13&rft.issue=4&rft.spage=322&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 - 1993-05-25 N1 - Date created - 1993-05-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Treatment of Parkinson's disease with the partial dopamine agonist EMD 49980. AN - 75699914; 8097280 AB - The motor effects of the partial dopamine agonist EMD 49980 were evaluated in parkinsonian patients under controlled conditions. EMD 49980 monotherapy resulted in a mild improvement in parkinsonian symptoms, but when co-administered with levodopa, had no significant effect on dyskinesias or on the antiparkinsonian effect of the dopamine precursor. These results suggest that EMD 49980 exerts a net weak dopamine agonist effect but fails to ameliorate levodopa-induced dyskinesias. JF - Movement disorders : official journal of the Movement Disorder Society AU - Bravi, D AU - Davis, T L AU - Mouradian, M M AU - Chase, T N AD - Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/04// PY - 1993 DA - April 1993 SP - 195 EP - 197 VL - 8 IS - 2 SN - 0885-3185, 0885-3185 KW - Dopamine Agents KW - 0 KW - Indoles KW - Pyridines KW - Receptors, Dopamine KW - roxindole KW - 43227SMS0O KW - Levodopa KW - 46627O600J KW - Index Medicus KW - Brain -- physiopathology KW - Dyskinesia, Drug-Induced -- drug therapy KW - Double-Blind Method KW - Humans KW - Brain -- drug effects KW - Adult KW - Neurologic Examination -- drug effects KW - Levodopa -- therapeutic use KW - Middle Aged KW - Dyskinesia, Drug-Induced -- physiopathology KW - Levodopa -- adverse effects KW - Male KW - Female KW - Receptors, Dopamine -- drug effects KW - Dopamine Agents -- therapeutic use KW - Receptors, Dopamine -- physiology KW - Indoles -- therapeutic use KW - Pyridines -- therapeutic use KW - Parkinson Disease -- physiopathology KW - Parkinson Disease -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75699914?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Movement+disorders+%3A+official+journal+of+the+Movement+Disorder+Society&rft.atitle=Treatment+of+Parkinson%27s+disease+with+the+partial+dopamine+agonist+EMD+49980.&rft.au=Bravi%2C+D%3BDavis%2C+T+L%3BMouradian%2C+M+M%3BChase%2C+T+N&rft.aulast=Bravi&rft.aufirst=D&rft.date=1993-04-01&rft.volume=8&rft.issue=2&rft.spage=195&rft.isbn=&rft.btitle=&rft.title=Movement+disorders+%3A+official+journal+of+the+Movement+Disorder+Society&rft.issn=08853185&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-05-18 N1 - Date created - 1993-05-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Differential effects of dietary beta-carotene on papilloma and carcinoma formation induced by an initiation-promotion protocol in SENCAR mouse skin. AN - 75693096; 8472337 AB - SENCAR mice were used to determine the effects of the provitamin A compound beta-carotene on papilloma formation and the conversion of papillomas to carcinomas in a two-stage protocol with one application of the initiator 7,12-dimethylbenz[a]anthracene (DMBA, 20 micrograms) and 20 weekly applications of the promotor 12-O-tetradecanoylphorbol-13-acetate (TPA, 2 micrograms). A purified vitamin A-free diet was supplemented with beta-carotene at four levels (0.6, 6, 60 and 600 micrograms/g of diet) for female mice and two levels (60 and 600 micrograms/g) for male mice. Dietary supplementations of beta-carotene did not result in significant changes in body weight and survival of female and male mice. However, papillomas developed more rapidly and papilloma incidence (% mice with papillomas) reached its maximum (100%) sooner in male mice fed 600 micrograms of beta-carotene/g of diet than those fed 60 micrograms/g. There were smaller differences in papilloma incidence among the dietary groups in female mice, but the papilloma incidence again reached 100% sooner in mice fed 600 micrograms of beta-carotene/g of diet. Female and male mice fed 600 micrograms of beta-carotene/g of diet had significantly higher papilloma yields (average number of papillomas/mouse) than other dietary groups and a very low percentage of these papillomas converted to carcinomas in these mice. Thus, beta-carotene at 600 micrograms/g inhibited the conversion of papillomas to carcinomas in both sexes. In addition, papilloma yields were higher in female mice and these papillomas regressed more quickly than those in the corresponding groups of male mice. In conclusion, dietary beta-carotene caused differential effects on papilloma and carcinoma yields and sex-dependent differences in papilloma formation in female and male SENCAR mice treated with DMBA and TPA in a two-stage carcinogenesis protocol. JF - Carcinogenesis AU - Chen, L C AU - Sly, L AU - Jones, C S AU - Tarone, R AU - De Luca, L M AD - Differentiation Control Section, National Cancer Institute, Bethesda, MD. Y1 - 1993/04// PY - 1993 DA - April 1993 SP - 713 EP - 717 VL - 14 IS - 4 SN - 0143-3334, 0143-3334 KW - beta Carotene KW - 01YAE03M7J KW - Carotenoids KW - 36-88-4 KW - 9,10-Dimethyl-1,2-benzanthracene KW - 57-97-6 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - Cocarcinogenesis KW - Sex Factors KW - Dose-Response Relationship, Drug KW - Mice KW - Pregnancy KW - Incidence KW - Neoplasms, Multiple Primary -- chemically induced KW - Female KW - Male KW - Skin Neoplasms -- chemically induced KW - Skin Neoplasms -- epidemiology KW - Carcinoma -- epidemiology KW - Carotenoids -- administration & dosage KW - Carotenoids -- pharmacology KW - Papilloma -- chemically induced KW - Papilloma -- epidemiology KW - Carcinoma -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75693096?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Differential+effects+of+dietary+beta-carotene+on+papilloma+and+carcinoma+formation+induced+by+an+initiation-promotion+protocol+in+SENCAR+mouse+skin.&rft.au=Chen%2C+L+C%3BSly%2C+L%3BJones%2C+C+S%3BTarone%2C+R%3BDe+Luca%2C+L+M&rft.aulast=Chen&rft.aufirst=L&rft.date=1993-04-01&rft.volume=14&rft.issue=4&rft.spage=713&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-05-17 N1 - Date created - 1993-05-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of varying the onset of exposure to DDT on its modulation of AFB1-induced hepatocarcinogenesis in the rat. AN - 75693006; 8097137 AB - We have previously reported that p,p'-dichlorodiphenyl-trichloroethane (DDT) inhibited the hepatocarcinogenicity of aflatoxin B1 (AFB1) if given to rats 1 week prior to AFB1 but could enhance the carcinogenesis when given 1 week after the completion of AFB1 treatment. However, simultaneous administration of DDT with AFB1 resulted in a slight reduction in the incidence of liver tumours. In the present experiment in which the dose of AFB1 was reduced to about half of that used previously, we observed that DDT markedly inhibited the hepatocarcinogenesis if given to animals starting at the same time with AFB1. On the other hand, giving DDT to animals starting in the middle of AFB1 treatment resulted in a significant enhancement of hepatocarcinogenesis. DDT exhibited a maximal tumour promoting effect when given either 1 or 3 weeks after completion of AFB1 treatment. It enhanced the number of animals bearing liver carcinomas as well as the number of carcinomas per animal. Determination of gamma-glutamyltranspeptidase in the serum revealed that the activity increased only in animals bearing big and/or a number of carcinomas in the livers especially in those promoted by DDT. These results therefore demonstrated that DDT will act as an inhibitor of AFB1-induced hepatocarcinogenesis if it is given to animals starting either prior to or at the same time as carcinogen. On the other hand, it will act as a tumour promoter if given to animals starting either in the middle of or after the completion of AFB1 treatment. JF - Carcinogenesis AU - Rojanapo, W AU - Kupradinun, P AU - Tepsuwan, A AU - Tanyakaset, M AD - Biochemistry and Chemical Carcinogenesis Section, National Cancer Institute, Bangkok, Thailand. Y1 - 1993/04// PY - 1993 DA - April 1993 SP - 663 EP - 667 VL - 14 IS - 4 SN - 0143-3334, 0143-3334 KW - Aflatoxin B1 KW - 9N2N2Y55MH KW - DDT KW - CIW5S16655 KW - gamma-Glutamyltransferase KW - EC 2.3.2.2 KW - Dimethyl Sulfoxide KW - YOW8V9698H KW - Index Medicus KW - Rats KW - Animals KW - Drug Administration Schedule KW - Rats, Wistar KW - gamma-Glutamyltransferase -- blood KW - Male KW - Organ Size -- drug effects KW - Liver -- pathology KW - Liver -- enzymology KW - DDT -- administration & dosage KW - Cocarcinogenesis KW - Liver Neoplasms, Experimental -- pathology KW - Liver -- drug effects KW - Liver Neoplasms, Experimental -- enzymology KW - DDT -- toxicity KW - Aflatoxin B1 -- administration & dosage KW - Liver Neoplasms, Experimental -- chemically induced KW - Aflatoxin B1 -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75693006?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Effect+of+varying+the+onset+of+exposure+to+DDT+on+its+modulation+of+AFB1-induced+hepatocarcinogenesis+in+the+rat.&rft.au=Rojanapo%2C+W%3BKupradinun%2C+P%3BTepsuwan%2C+A%3BTanyakaset%2C+M&rft.aulast=Rojanapo&rft.aufirst=W&rft.date=1993-04-01&rft.volume=14&rft.issue=4&rft.spage=663&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-05-17 N1 - Date created - 1993-05-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The role of O6-alkylguanine-DNA alkyltransferase in protecting Rat4 cells against the mutagenic effects of O6-substituted guanine residues incorporated in codon 12 of the H-ras gene. AN - 75691116; 8472320 AB - The role of rat O6-alkylguanine-DNA alkyltransferase (AGT) in modulating mutagenesis by O6-substituted guanines in the rat H-ras gene was examined. Rat4 cells were transfected with vectors carrying O6-methyl-, O6-ethyl- or O6-benzylguanine residues in place of the normal guanines at either the first, second, or both the first and second positions in codon 12 (GGA) of the H-ras coding sequence. The percentage of transformed colonies was determined for cells grown in normal medium or in medium containing O6-benzylguanine to completely deplete AGT. In parallel experiments with O6-methylguanine-containing vectors, the percentage of cellular DNA harboring codon 12 mutations was determined for normal cells and cells lacking AGT. A reasonable correspondence was observed between the percentage of mutated DNA and the percentage of transformed colonies produced in both types of cells. The results indicate that the contribution of AGT to the repair of O6-substituted guanine damage decreases as the O6 substituent is changed from methyl > ethyl > benzyl. Additionally, cellular AGT appears to repair an O6-methylguanine more readily at the first position of codon 12 than the second position. However, other repair mechanisms in these mammalian cells appear to play a major role in correcting low levels of O6-substituted guanine damage including O6-methylguanine damage. JF - Carcinogenesis AU - Bishop, R E AU - Dunn, L L AU - Pauly, G T AU - Dolan, M E AU - Moschel, R C AD - Chemistry of Carcinogenesis Laboratory, ABL-Basic Research Program, National Cancer Institute, Frederick Cancer Research and Development Center, MD 21702. Y1 - 1993/04// PY - 1993 DA - April 1993 SP - 593 EP - 598 VL - 14 IS - 4 SN - 0143-3334, 0143-3334 KW - H-ras KW - Codon KW - 0 KW - O(6)-benzylguanine KW - 01KC87F8FE KW - 6-ethylguanine KW - 51866-19-4 KW - Guanine KW - 5Z93L87A1R KW - O-(6)-methylguanine KW - 9B710FV2AE KW - Methyltransferases KW - EC 2.1.1.- KW - O(6)-Methylguanine-DNA Methyltransferase KW - EC 2.1.1.63 KW - Index Medicus KW - Base Sequence KW - Cell Transformation, Neoplastic -- pathology KW - Transfection KW - Plasmids -- genetics KW - DNA Damage KW - Cells, Cultured KW - Molecular Sequence Data KW - Cell Transformation, Neoplastic -- genetics KW - Genes, ras -- genetics KW - DNA Repair KW - Codon -- genetics KW - Codon -- chemistry KW - Methyltransferases -- physiology KW - Guanine -- analogs & derivatives KW - Mutagenesis -- genetics KW - Guanine -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75691116?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=The+role+of+O6-alkylguanine-DNA+alkyltransferase+in+protecting+Rat4+cells+against+the+mutagenic+effects+of+O6-substituted+guanine+residues+incorporated+in+codon+12+of+the+H-ras+gene.&rft.au=Bishop%2C+R+E%3BDunn%2C+L+L%3BPauly%2C+G+T%3BDolan%2C+M+E%3BMoschel%2C+R+C&rft.aulast=Bishop&rft.aufirst=R&rft.date=1993-04-01&rft.volume=14&rft.issue=4&rft.spage=593&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-05-17 N1 - Date created - 1993-05-17 N1 - Date revised - 2017-01-13 N1 - Gene symbol - H-ras N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of protein kinase C and cytokines on the function and production of cytolytic granules in alpha CD3-activated killer-cell-mediated killing of tumor cells. AN - 75687234; 8473055 AB - The effects of PMA and staurosporine (PKC depletor/antagonist) and IL-2/IL4 were used to determine the role of PKC and cytokine on alpha CD3-induced activated killer cells (CD3-AK). The present study examines their effects on the production of BLT-esterase and on the effector function of CD3-AK cells as well as the cytolytic granules. The production of BLT-esterase generally correlated with the cytolytic activity of CD3-AK cells and was reduced by PKC depletor/inhibitor but increased by IL-4. In studying the effector function of CD3-AK cells, we found that adding PMA or SSP at the effector phase inhibited the PKC-dependent slow lysis. PMA, but not SSP, also reduced fast lysis, which was shown to be a PKC-independent event. Additional experiments were performed to determine the effect of PKC on the lytic granules and to ascertain whether PMA has other effects on the effector-to-target relationship unrelated to PKC. It was found that neither PMA nor SSP affects the function of cytolytic granules, as measured by hemolytic assay against anucleated target (SRBC). These findings indicate that PKC has no direct effect on the granules. During testing against the nucleated tumor target through a novel approach using non-cytolytic surrogate killers, the lytic activity of the granules was inhibited by PMA, suggesting that exocytosis or delivery of granules to nucleated target cells may require mobilization of intracellular Ca2+ in the killer cells, and this process is inhibited by PMA. Our findings indicate that PKC and cytokines regulate the production but not the lytic activity of cytolytic granules. Nonetheless, delivery of cytolytic granules from killer cells to the nucleated tumor target appears to be a Ca(2+)-dependent event unrelated to PKC. JF - International journal of cancer AU - Wu, J AU - Shiver, J AU - Hargrove, M E AU - Ting, C C AD - Office of the Director, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/04/01/ PY - 1993 DA - 1993 Apr 01 SP - 973 EP - 977 VL - 53 IS - 6 SN - 0020-7136, 0020-7136 KW - Alkaloids KW - 0 KW - Antibodies KW - Antigens, CD3 KW - Cytokines KW - Protein Kinase C KW - EC 2.7.11.13 KW - Granzymes KW - EC 3.4.21.- KW - Serine Endopeptidases KW - Staurosporine KW - H88EPA0A3N KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - Mice KW - Cytotoxicity, Immunologic KW - Tumor Cells, Cultured KW - Serine Endopeptidases -- metabolism KW - Immunotherapy, Adoptive KW - Mice, Inbred C57BL KW - Alkaloids -- pharmacology KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Female KW - Protein Kinase C -- antagonists & inhibitors KW - Neoplasms, Experimental -- therapy KW - Antigens, CD3 -- pharmacology KW - Cytoplasmic Granules -- physiology KW - Cytokines -- physiology KW - Protein Kinase C -- physiology KW - Cytoplasmic Granules -- drug effects KW - Antibody-Dependent Cell Cytotoxicity -- physiology KW - Killer Cells, Natural -- immunology KW - Killer Cells, Natural -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75687234?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+journal+of+cancer&rft.atitle=Role+of+protein+kinase+C+and+cytokines+on+the+function+and+production+of+cytolytic+granules+in+alpha+CD3-activated+killer-cell-mediated+killing+of+tumor+cells.&rft.au=Wu%2C+J%3BShiver%2C+J%3BHargrove%2C+M+E%3BTing%2C+C+C&rft.aulast=Wu&rft.aufirst=J&rft.date=1993-04-01&rft.volume=53&rft.issue=6&rft.spage=973&rft.isbn=&rft.btitle=&rft.title=International+journal+of+cancer&rft.issn=00207136&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-05-14 N1 - Date created - 1993-05-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - 7-Alkyldeoxyguanosine adduct detection by two-step HPLC and the 32P-postlabeling assay. AN - 75686122; 8386066 AB - 7-Alkyldeoxyguanosine DNA adducts may be a marker for some N-nitroso compound exposures and subsequent human cancer risk. A sensitive and highly specific assay for the detection of 7-methyl-2'-deoxyguanosine-3'-monophosphate (7-methyldGp) and 7-ethyl-2'-deoxyguanosine-3'-monophosphate (7-ethyldGp) has been developed by combining two different HPLC purification steps with the 32P-postlabeling assay. We previously reported that ion-pair reverse-phase (IP) chromatography coupled with the 32P-postlabeling assay detects 7-methyldGp in human lung, but have found that other nucleotides and unknown adducts co-elute. Thus, weak anion exchange (AE) HPLC was added in tandem with IP HPLC prior to the 32P-postlabeling assay. 2'-Deoxyguanosine-3'-monophosphate (dGp) is incorporated into the assay as an internal standard for the assessment of enzyme labeling efficiency and adduct recovery. The methodology was validated using radiolabeled DNA and liquid scintillation counting, which accounts for adduct loss from enzymatic digestion to detection. Levels of 7-ethyldGp also were correlated with accelerator mass spectrometry. The overall adduct recovery with this method was 58% for 7-methyldGp and 98% for 7-ethyldGp. The detection limit for both assays using 100 micrograms of DNA was one adduct in 10(8) unmodified dGp. 7-MethyldGp and 7-ethyldGp levels were determined in ten human lung samples at levels of 1.4-5.4 and 0.6-3.1 adducts per 10(7) dGp respectively, and in five human lymphocyte samples at levels of 5.0-8.3 and 0.3-1.4 adducts per 10(7) dGp respectively. Combining the two HPLC purification steps and the 32P-postlabeling assay attains chemical specificity, retains sufficient quantitative sensitivity and should be useful in human biomonitoring studies. JF - Carcinogenesis AU - Kato, S AU - Petruzzelli, S AU - Bowman, E D AU - Turteltaub, K W AU - Blomeke, B AU - Weston, A AU - Shields, P G AD - Laboratory of Human Carcinogenesis, National Cancer Institute, NIH Bethesda, MD 20892. Y1 - 1993/04// PY - 1993 DA - April 1993 SP - 545 EP - 550 VL - 14 IS - 4 SN - 0143-3334, 0143-3334 KW - Deoxyguanine Nucleotides KW - 0 KW - Phosphorus Radioisotopes KW - 7-methyl-2'-deoxyguanosine 3'-monophosphate KW - 123497-14-3 KW - 7-ethyl-2'-deoxyguanosine-3'-monophosphate KW - 149206-55-3 KW - Methylnitrosourea KW - 684-93-5 KW - Guanosine Monophosphate KW - 85-32-5 KW - DNA KW - 9007-49-2 KW - Ethylnitrosourea KW - P8M1T4190R KW - Index Medicus KW - Animals KW - Cattle KW - Humans KW - Methylnitrosourea -- pharmacology KW - Ethylnitrosourea -- pharmacology KW - Deoxyguanine Nucleotides -- analysis KW - Guanosine Monophosphate -- analysis KW - Guanosine Monophosphate -- analogs & derivatives KW - DNA -- analysis KW - Chromatography, High Pressure Liquid -- methods KW - DNA -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75686122?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=7-Alkyldeoxyguanosine+adduct+detection+by+two-step+HPLC+and+the+32P-postlabeling+assay.&rft.au=Kato%2C+S%3BPetruzzelli%2C+S%3BBowman%2C+E+D%3BTurteltaub%2C+K+W%3BBlomeke%2C+B%3BWeston%2C+A%3BShields%2C+P+G&rft.aulast=Kato&rft.aufirst=S&rft.date=1993-04-01&rft.volume=14&rft.issue=4&rft.spage=545&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-05-17 N1 - Date created - 1993-05-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - 4-Chloro-3-hydroxyanthranilate, 6-chlorotryptophan and norharmane attenuate quinolinic acid formation by interferon-gamma-stimulated monocytes (THP-1 cells). AN - 75685230; 8471029 AB - Accumulation of quinolinic acid and L-kynurenine occurs in the brain and/or blood following immune activation, and may derive from L-tryptophan following induction of indoleamine 2,3-dioxygenase and other kynurenine-pathway enzymes. In the present study a survey of various cell lines derived from either brain or systemic tissues showed that, while all cells examined responded to interferon-gamma by increased conversion of L-[13C6]tryptophan into L-kynurenine (human: B-lymphocytes, neuroblastoma, glioblastoma, lung, liver, kidney; rat brain: microglia, astrocytes and oligodendrocytes), only macrophage-derived cells (peripheral-blood mononuclear cells; THP-1, U-937) and certain liver cells (SKHep1) synthesized [13C6]quinolinic acid. Tumour necrosis factor-alpha enhanced the effects of interferon-gamma in THP-1 cells. Norharmane, 6-chloro-DL-tryptophan and 4-chloro-3-hydroxyanthranilate attenuated quinolinic acid formation by THP-1 cells with IC50 values of 51 microM, 58 microM and 0.11 microM respectively. Norharmane and 6-chloro-DL-tryptophan attenuated L-kynurenine formation with IC50 values of 43 microM and 51 microM respectively, whereas 4-chloro-3-hydroxyanthranilate had no effect on L-kynurenine accumulation. The reductions in L-kynurenine and quinolinic acid formation are consistent with the reports that norharmane is an inhibitor of indoleamine 2,3-dioxygenase, 6-chloro-DL-tryptophan is metabolized through the kynurenine pathway, and 4-chloro-3-hydroxyanthranilate is an inhibitor of 3-hydroxyanthranilate 3,4-dioxygenase. These results suggest that many tissues may contribute to the production of L-kynurenine following indoleamine 2,3-dioxygenase induction and immune activation. Quinolinic acid may be directly synthesized from L-tryptophan in both macrophages and certain types of liver cells, although uptake of quinolinic acid precursors from blood may contribute to quinolinic acid synthesis in cells that cannot convert L-kynurenine into quinolinic acid. JF - The Biochemical journal AU - Saito, K AU - Chen, C Y AU - Masana, M AU - Crowley, J S AU - Markey, S P AU - Heyes, M P AD - Section on Analytical Biochemistry, National Institute of Mental Health, Bethesda, MD 20892. Y1 - 1993/04/01/ PY - 1993 DA - 1993 Apr 01 SP - 11 EP - 14 VL - 291 ( Pt 1) SN - 0264-6021, 0264-6021 KW - Carbolines KW - 0 KW - Tumor Necrosis Factor-alpha KW - 6-chlorotryptophan KW - 17808-35-4 KW - 3-Hydroxyanthranilic Acid KW - 1UQB1BT4OT KW - 4-chloro-3-hydroxyanthranilic acid KW - 23219-33-2 KW - Kynurenine KW - 343-65-7 KW - Harmine KW - 4FHH5G48T7 KW - Interferon-gamma KW - 82115-62-6 KW - Tryptophan KW - 8DUH1N11BX KW - norharman KW - 94HMA1I78O KW - Quinolinic Acid KW - F6F0HK1URN KW - Index Medicus KW - Rats KW - Animals KW - Tumor Cells, Cultured KW - Brain -- cytology KW - Humans KW - Brain -- drug effects KW - Tumor Necrosis Factor-alpha -- pharmacology KW - Kynurenine -- metabolism KW - Brain -- metabolism KW - Macrophages -- drug effects KW - Cell Line KW - Macrophages -- metabolism KW - Tryptophan -- pharmacology KW - Tryptophan -- analogs & derivatives KW - 3-Hydroxyanthranilic Acid -- pharmacology KW - Quinolinic Acid -- metabolism KW - Leukocytes, Mononuclear -- metabolism KW - Harmine -- analogs & derivatives KW - Interferon-gamma -- pharmacology KW - Tryptophan -- metabolism KW - Leukocytes, Mononuclear -- drug effects KW - 3-Hydroxyanthranilic Acid -- analogs & derivatives KW - Harmine -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75685230?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Biochemical+journal&rft.atitle=4-Chloro-3-hydroxyanthranilate%2C+6-chlorotryptophan+and+norharmane+attenuate+quinolinic+acid+formation+by+interferon-gamma-stimulated+monocytes+%28THP-1+cells%29.&rft.au=Saito%2C+K%3BChen%2C+C+Y%3BMasana%2C+M%3BCrowley%2C+J+S%3BMarkey%2C+S+P%3BHeyes%2C+M+P&rft.aulast=Saito&rft.aufirst=K&rft.date=1993-04-01&rft.volume=291+%28+Pt+1%29&rft.issue=&rft.spage=11&rft.isbn=&rft.btitle=&rft.title=The+Biochemical+journal&rft.issn=02646021&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-05-12 N1 - Date created - 1993-05-12 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Cell Biol. 1980 Jun;85(3):890-902 [6248568] Neuroscience. 1992 Nov;51(1):25-39 [1465184] Mol Aspects Med. 1983;6(2):101-97 [6371429] Arch Biochem Biophys. 1984 Aug 1;232(2):602-9 [6431906] Neuroscience. 1985 Jul;15(3):597-617 [2866466] J Neuroimmunol. 1987 Jul-Aug;15(3):263-78 [3110208] J Neurochem. 1993 Jan;60(1):180-92 [8417138] Proc Natl Acad Sci U S A. 1988 Jun;85(11):4079-81 [2967497] Anal Biochem. 1988 Aug 1;172(2):518-25 [3189792] Biochim Biophys Acta. 1989 Jul 11;1012(2):140-7 [2500976] Biol Chem Hoppe Seyler. 1989 Sep;370(9):1063-9 [2482041] J Neurochem. 1990 Sep;55(3):738-44 [2384749] Ann Neurol. 1991 Feb;29(2):202-9 [1826418] Neurosci Lett. 1991 Jan 28;122(2):265-9 [1827518] Brain Res. 1991 Feb 1;540(1-2):353-6 [1647247] Brain Res. 1991 Apr 12;546(1):151-4 [1830237] J Comp Neurol. 1991 Dec 1;314(1):125-35 [1797868] Biochem J. 1992 May 1;283 ( Pt 3):633-5 [1534219] FASEB J. 1992 Aug;6(11):2977-89 [1322853] J Neuropsychiatry Clin Neurosci. 1992 Summer;4(3):270-9 [1386770] J Neuroimmunol. 1992 Sep;40(1):71-80 [1387655] Brain. 1992 Oct;115 ( Pt 5):1249-73 [1422788] Arch Biochem Biophys. 1980 Aug;203(1):161-6 [6893263] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regulation of thymidylate synthase in human colon cancer cells treated with 5-fluorouracil and interferon-gamma. AN - 75683739; 8474431 AB - The effects of fluorouracil (5-FU) and interferon-gamma (IFN-gamma) on the regulation of thymidylate synthase (TS) gene expression were investigated in the human colon cancer H630 cell line. By Western immunoblot analysis, TS protein levels in H630 cells were increased 3-, 5.5-, 5-, and 2.5-fold after 8-, 16-, 24-, and 36-hr exposure to 1 microM 5-FU, respectively. When H630 cells were exposed to varying concentrations of 5-FU (0.3-10 microM) for 24 hr, increases in TS protein up to 5.5-fold were observed. A 24-hr exposure to 1 microM 5-FU resulted in a 4.5-fold increase in the level of TS protein, whereas in 5-FU/IFN-gamma-treated cells TS protein was increased by only 1.8-fold, compared with control cells. IFN-gamma treatment alone did not affect TS protein levels, relative to control. Northern blot analysis revealed no changes in TS mRNA levels when H630 cells were exposed either to 1 microM 5-FU for 8-36 hr, to varying concentrations of 5-FU (0.3-10 microM) for 24 hr, or to the combination of 5-FU and IFN-gamma. Pulse-labeling studies with [35S]methionine demonstrated a 3.5-fold increase in net synthesis of TS in cells treated with 1 microM 5-FU, whereas the level of newly synthesized TS increased only 1.5-fold in cells treated with 5-FU/IFN-gamma, compared with control cells. Pulse-chase studies revealed that the half-lives of TS protein in control and 5-FU-treated cells were equivalent. These findings demonstrate that the increase in TS protein after 5-FU exposure and the subsequent inhibitory effect of IFN-gamma on TS protein expression are both regulated at the post-transcriptional level. JF - Molecular pharmacology AU - Chu, E AU - Koeller, D M AU - Johnston, P G AU - Zinn, S AU - Allegra, C J AD - NCI-Navy Medical Oncology Branch, Bethesda, Maryland 20889. Y1 - 1993/04// PY - 1993 DA - April 1993 SP - 527 EP - 533 VL - 43 IS - 4 SN - 0026-895X, 0026-895X KW - RNA, Messenger KW - 0 KW - RNA, Neoplasm KW - Interferon-gamma KW - 82115-62-6 KW - Thymidylate Synthase KW - EC 2.1.1.45 KW - Fluorouracil KW - U3P01618RT KW - Index Medicus KW - Protein Biosynthesis -- drug effects KW - Tumor Cells, Cultured KW - Enzyme Induction -- drug effects KW - RNA, Neoplasm -- drug effects KW - Humans KW - RNA, Messenger -- drug effects KW - Enzyme Stability -- drug effects KW - Drug Synergism KW - Gene Expression Regulation, Neoplastic -- drug effects KW - Thymidylate Synthase -- genetics KW - Thymidylate Synthase -- drug effects KW - Interferon-gamma -- pharmacology KW - Fluorouracil -- pharmacology KW - Thymidylate Synthase -- biosynthesis KW - Colonic Neoplasms -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75683739?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Regulation+of+thymidylate+synthase+in+human+colon+cancer+cells+treated+with+5-fluorouracil+and+interferon-gamma.&rft.au=Chu%2C+E%3BKoeller%2C+D+M%3BJohnston%2C+P+G%3BZinn%2C+S%3BAllegra%2C+C+J&rft.aulast=Chu&rft.aufirst=E&rft.date=1993-04-01&rft.volume=43&rft.issue=4&rft.spage=527&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 - 1993-05-18 N1 - Date created - 1993-05-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Reexamination of the microsomal transformation of N-hydroxynorcocaine to norcocaine nitroxide. AN - 75682950; 8386313 AB - Cocaine is known to be associated with hepatotoxicity in laboratory animals, and there is recent evidence that it also induces liver damage in humans. In both cases an N-oxidative pathway is responsible. Cocaine (NCN) is first N-demethylated to norcocaine, followed by oxidation to N-hydroxynorcocaine (NCNOH) and norcocaine nitroxide (NCNO.). On the basis of ESR studies of NCNOH with rat liver microsomes, it has been proposed that NCNO. induces hepatotoxicity by futile redox cycling between NCNO. and NCNOH at the expense of NADPH. The reaction is reported to be accompanied by formation of superoxide and lipid peroxyl radicals. It has also been reported that the same toxic sequence occurs with rat brain microsomes, leading to the formation of reactive free radicals in the brain. We have reexamined the microsomal metabolism of NCNOH to investigate the mechanism more thoroughly. Spin traps [5,5-dimethyl-1-pyrroline N-oxide and alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone] were used to investigate the formation of reactive free radicals, including superoxide, in liver and brain microsomal incubations. In agreement with the literature, we detected a six-line spectrum of a radical adduct of alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone from liver microsome incubations. In contrast, our results showed that brain microsomes were completely inactive, contrary to the literature. In addition, we did not find any NCNO.- or NCNOH-dependent formation of superoxide with either brain or liver microsomes. JF - Molecular pharmacology AU - Lloyd, R V AU - Shuster, L AU - Mason, R P AD - Laboratory for Molecular Biophysics, National Institutes of Health Research Triangle Park, North Carolina 27709. Y1 - 1993/04// PY - 1993 DA - April 1993 SP - 645 EP - 648 VL - 43 IS - 4 SN - 0026-895X, 0026-895X KW - Lipid Peroxides KW - 0 KW - Superoxides KW - 11062-77-4 KW - 8-hydroxynorcocaine KW - 72182-43-5 KW - norcocaine nitroxide KW - 81652-42-8 KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Rats KW - Animals KW - Superoxides -- metabolism KW - Rats, Sprague-Dawley KW - Biotransformation KW - Microsomes, Liver -- metabolism KW - Electron Spin Resonance Spectroscopy KW - In Vitro Techniques KW - Lipid Peroxides -- metabolism KW - Male KW - Female KW - Cocaine -- analogs & derivatives KW - Microsomes -- metabolism KW - Brain -- metabolism KW - Cocaine -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75682950?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Reexamination+of+the+microsomal+transformation+of+N-hydroxynorcocaine+to+norcocaine+nitroxide.&rft.au=Lloyd%2C+R+V%3BShuster%2C+L%3BMason%2C+R+P&rft.aulast=Lloyd&rft.aufirst=R&rft.date=1993-04-01&rft.volume=43&rft.issue=4&rft.spage=645&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 - 1993-05-18 N1 - Date created - 1993-05-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Granulocyte-macrophage colony-stimulating factor induces human melanoma-cell migration. AN - 75682503; 8473054 AB - Tumor metastasis is the primary cause of death for cancer patients. The metastatic cascade requires successful tumor cell invasion into and through vascular and parenchymal barriers. We have shown that autocrine motility factor (AMF, autotaxin) and the insulin-like growth factors (IGFs) induce tumor-cell migration. Since granulocyte-macrophage colony-stimulating factor (GM-CSF) has been shown to prime neutrophils for chemotaxis, we have therefore studied the influence of GM-CSF upon tumor cells and report that GM-CSF stimulates migration of these cells in a dose-dependent fashion. The ED50 for A2058 human melanoma cell line chemotaxis to GM-CSF is approx. 60 pM. The motile response to GM-CSF was additive to that of IGF-I and AMF, both of which are potent attractants for tumor cells. Pre-treatment of cells for 2 hr with non-toxic concentrations of pertussis toxin (PT) or amiloride resulted in a 50% inhibition of chemotaxis to GM-CSF. Therefore, GM-CSF, through PT- and amiloride-sensitive signal pathways, is a potent attractant for melanoma cells, the response to which is additive to that of other attractants. The presence of the GM-CSF receptor in A2058 melanoma cells was indicated by Northern-blot analysis which identified message transcripts of 2.1 and 3.0 kb. These data emphasize the versatility of the melanoma cell migration response to an array of cytokines, including GM-CSF. JF - International journal of cancer AU - Kohn, E C AU - Hollister, G H AU - DiPersio, J D AU - Wahl, S AU - Liotta, L A AU - Schiffmann, E AD - Medicine Branch, National Cancer Institute, Bethesda, MD 20892. Y1 - 1993/04/01/ PY - 1993 DA - 1993 Apr 01 SP - 968 EP - 972 VL - 53 IS - 6 SN - 0020-7136, 0020-7136 KW - Chemotactic Factors KW - 0 KW - Receptors, Granulocyte-Macrophage Colony-Stimulating Factor KW - Recombinant Proteins KW - Granulocyte-Macrophage Colony-Stimulating Factor KW - 83869-56-1 KW - Index Medicus KW - Sensitivity and Specificity KW - Recombinant Proteins -- pharmacology KW - Tumor Cells, Cultured -- drug effects KW - Humans KW - Signal Transduction -- drug effects KW - Cell Movement -- drug effects KW - Receptors, Granulocyte-Macrophage Colony-Stimulating Factor -- analysis KW - Melanoma -- pathology KW - Melanoma -- secondary KW - Granulocyte-Macrophage Colony-Stimulating Factor -- pharmacology KW - Chemotactic Factors -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75682503?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+journal+of+cancer&rft.atitle=Granulocyte-macrophage+colony-stimulating+factor+induces+human+melanoma-cell+migration.&rft.au=Kohn%2C+E+C%3BHollister%2C+G+H%3BDiPersio%2C+J+D%3BWahl%2C+S%3BLiotta%2C+L+A%3BSchiffmann%2C+E&rft.aulast=Kohn&rft.aufirst=E&rft.date=1993-04-01&rft.volume=53&rft.issue=6&rft.spage=968&rft.isbn=&rft.btitle=&rft.title=International+journal+of+cancer&rft.issn=00207136&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-05-14 N1 - Date created - 1993-05-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evaluation of the stereoisomers of deprenyl for amphetamine-like discriminative stimulus effects in rats. AN - 75679714; 8473997 AB - The antiparkinsonian agent l-deprenyl, a selective monoamine oxidase (MAO)-B inhibitor, is a phenylalkylamine derivative which is metabolized in part to l-methamphetamine and l-amphetamine. As the clinical use of amphetamine-like psychostimulants is limited by their potential for abuse, we evaluated l-deprenyl for amphetamine-like discriminative stimulus effects over a range of experimental conditions. Male Fisher rats were trained under a 5-response, fixed-ratio schedule of stimulus-shock termination or a 10-response, fixed-ratio schedule of food-presentation to discriminate between d-amphetamine (1.0 mg/kg i.p.) and saline in a two-lever, operant conditioning procedure. Full generalization was obtained to l-amphetamine (1.0-2.0 mg/kg), d-deprenyl (10.0-17.0 mg/kg) and l-deprenyl (17.0 and 30.0 mg/kg) under both the food-presentation and stimulus-shock termination schedules, and increases in responding on the lever appropriate to d-amphetamine were dose-dependent. The dose-effect functions for l-amphetamine, l-deprenyl and d-deprenyl were shifted slightly to the left under the stimulus-shock termination schedule compared to the food-presentation schedule. When l-deprenyl (3.0 or 5.6 mg/kg i.p.) was given 30 min before d-amphetamine it produced a small shift to the left in the dose-effect function for d-amphetamine under the food-presentation schedule. l-Deprenyl produced clear generalization to the d-amphetamine stimulus only at very high doses of 17.0 to 30.0 mg/kg, doses about 10-fold higher than those that have a selective action on MAO-B vs. MAO-A and which start to have marked rate decreasing actions on food-reinforced responding.(ABSTRACT TRUNCATED AT 250 WORDS) JF - The Journal of pharmacology and experimental therapeutics AU - Yasar, S AU - Schindler, C W AU - Thorndike, E B AU - Szelenyi, I AU - Goldberg, S R AD - Behavioral Pharmacology and Genetics Section, National Institute on Drug Abuse Addiction Research Center, Baltimore, Maryland. Y1 - 1993/04// PY - 1993 DA - April 1993 SP - 1 EP - 6 VL - 265 IS - 1 SN - 0022-3565, 0022-3565 KW - Amphetamines KW - 0 KW - Selegiline KW - 2K1V7GP655 KW - Index Medicus KW - Rats KW - Eating KW - Animals KW - Stereoisomerism KW - Rats, Inbred F344 KW - Drug Interactions KW - Discrimination Learning KW - Dose-Response Relationship, Drug KW - Electric Stimulation KW - Male KW - Selegiline -- pharmacology KW - Amphetamines -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75679714?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Evaluation+of+the+stereoisomers+of+deprenyl+for+amphetamine-like+discriminative+stimulus+effects+in+rats.&rft.au=Yasar%2C+S%3BSchindler%2C+C+W%3BThorndike%2C+E+B%3BSzelenyi%2C+I%3BGoldberg%2C+S+R&rft.aulast=Yasar&rft.aufirst=S&rft.date=1993-04-01&rft.volume=265&rft.issue=1&rft.spage=1&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 - 1993-05-18 N1 - Date created - 1993-05-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - N-acetylation phenotype and genotype and risk of bladder cancer in benzidine-exposed workers. AN - 75678511; 8472331 AB - Several studies in subjects occupationally exposed to arylamine carcinogens have shown increased risks for bladder cancer associated with the slow acetylator phenotype. To follow up these reports, a case-control study of N-acetylation and bladder cancer risk was carried out among subjects occupationally exposed to benzidine, in benzidine dye production and use facilities in China. Thirty-eight bladder cancer cases and 43 controls from these factories were included for study of acetylation phenotype, by dapsone administration, and for polymorphisms in the NAT2 gene, by a polymerase chain reaction (PCR)-based test. In contrast to previous studies, no increase in bladder cancer risk was found for the slow N-acetylation phenotype (OR = 0.3; 95% CI = 0.1-1.3) or for slow N-acetylation-associated double mutations in NAT2 (OR = 0.5; 95% CI = 0.1-1.8). Examination of specific mutations and adjustment for age, weight, city and tobacco use did not alter the results. When examined by level of benzidine exposure in the cases, the bladder cancer risks associated with low (OR = 0.3, 95% CI = 0.0-2.2), medium (OR = 0.7, 95% CI = 0.1-4.5) and high (OR = 0.6, 95% CI = 0.1-3.5) exposure showed no interaction between genotype and benzidine exposure, within the range of exposures experienced by subjects in this study. This study, which is the first to incorporate phenotypic and genotypic analyses, provides evidence that the NAT2-related slow N-acetylation polymorphism is not associated with an increased risk of bladder cancer in workers exposed to benzidine, and may have a protective effect. JF - Carcinogenesis AU - Hayes, R B AU - Bi, W AU - Rothman, N AU - Broly, F AU - Caporaso, N AU - Feng, P AU - You, X AU - Yin, S AU - Woosley, R L AU - Meyer, U A AD - Environmental Epidemiology Branch, National Cancer Institute, Bethesda, MD. Y1 - 1993/04// PY - 1993 DA - April 1993 SP - 675 EP - 678 VL - 14 IS - 4 SN - 0143-3334, 0143-3334 KW - Benzidines KW - 0 KW - benzidine KW - 2X02101HVF KW - Dapsone KW - 8W5C518302 KW - Index Medicus KW - Phenotype KW - Genotype KW - Acetylation KW - Risk Factors KW - Humans KW - Case-Control Studies KW - Aged KW - Middle Aged KW - Dapsone -- metabolism KW - Male KW - China KW - Occupational Exposure -- adverse effects KW - Urinary Bladder Neoplasms -- metabolism KW - Urinary Bladder Neoplasms -- chemically induced KW - Benzidines -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75678511?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=N-acetylation+phenotype+and+genotype+and+risk+of+bladder+cancer+in+benzidine-exposed+workers.&rft.au=Hayes%2C+R+B%3BBi%2C+W%3BRothman%2C+N%3BBroly%2C+F%3BCaporaso%2C+N%3BFeng%2C+P%3BYou%2C+X%3BYin%2C+S%3BWoosley%2C+R+L%3BMeyer%2C+U+A&rft.aulast=Hayes&rft.aufirst=R&rft.date=1993-04-01&rft.volume=14&rft.issue=4&rft.spage=675&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-05-17 N1 - Date created - 1993-05-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Species differences in the production and clearance of 1,3-butadiene metabolites: a mechanistic model indicates predominantly physiological, not biochemical, control. AN - 75678471; 8472325 AB - Inhaled 1,3-butadiene, a monomer used in the production of synthetic rubber and other resins, is metabolized to mutagenic and carcinogenic epoxide intermediates. A physiologically based pharmacokinetic model of the uptake, tissue distribution, and metabolism of butadiene was constructed to determine if the biochemical kinetic constants obtained from in vitro studies are consistent with the observed in vivo uptake and metabolism. The model includes compartments for lung, blood, fat, liver, other rapidly perfused tissues ('viscera') and slowly perfused tissues. Metabolism of butadiene was assumed to occur in viscera in addition to lung and liver. Enzymatic reaction rate equations for the formation of 1,2-epoxy-3-butene, for hydrolysis of this epoxide, and for its conjugation with glutathione were also included. Physiological and biochemical parameters for the mouse, rat and human were obtained from the literature; they were not adjusted to produce a fit to experimental data. The model was used to test the hypothesis that differences in uptake and clearance of butadiene by the three species are due to differences in the activities of the metabolizing enzymes. The model reproduces whole-body observations for the mouse and rat. It predicts that inhalation uptake of butadiene and formation and retention of epoxybutene are controlled to a much greater extent by physiological parameters than by biochemical parameters and that storage in the fat represents a significant fraction of the retained butadiene. Accumulation of epoxybutene in the blood is predicted to be higher in mice than in rats or humans, but accumulation of the epoxide intermediate in the liver is predicted to be highest in humans. The epoxide tissue concentrations predicted by the model do not, by themselves, correlate with tumor incidence in mice and rats, indicating that other factors are crucial for carcinogenesis induced by butadiene. JF - Carcinogenesis AU - Kohn, M C AU - Melnick, R L AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1993/04// PY - 1993 DA - April 1993 SP - 619 EP - 628 VL - 14 IS - 4 SN - 0143-3334, 0143-3334 KW - Butadienes KW - 0 KW - Epoxy Compounds KW - Mutagens KW - 3,4-epoxy-1-butene KW - 478ERR5NKR KW - 1,3-butadiene KW - JSD5FGP5VD KW - Index Medicus KW - Rats KW - Animals KW - Epoxy Compounds -- blood KW - Humans KW - Body Burden KW - Adsorption KW - Mice KW - Time Factors KW - Species Specificity KW - Mutagens -- metabolism KW - Mutagens -- pharmacokinetics KW - Butadienes -- metabolism KW - Models, Biological KW - Butadienes -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75678471?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Species+differences+in+the+production+and+clearance+of+1%2C3-butadiene+metabolites%3A+a+mechanistic+model+indicates+predominantly+physiological%2C+not+biochemical%2C+control.&rft.au=Kohn%2C+M+C%3BMelnick%2C+R+L&rft.aulast=Kohn&rft.aufirst=M&rft.date=1993-04-01&rft.volume=14&rft.issue=4&rft.spage=619&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-05-17 N1 - Date created - 1993-05-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Oral gossypol in the treatment of metastatic adrenal cancer. AN - 75670844; 8473376 AB - Medical treatment of metastatic adrenal cancer is largely unsuccessful and has considerable toxicity. We previously demonstrated the activity of the plant toxin gossypol against human adrenal cancers in nude mice. We therefore examined the efficacy and toxicity of oral gossypol as a treatment for adrenal cancer in humans. Twenty-one patients with metastatic adrenal cancer received oral gossypol at doses of 30-70 mg/day. Patients were monitored for side effects of gossypol, changes in hormone secretion, and tumor response. Eighteen patients completed at least 6 weeks of gossypol treatment. Three of these patients, whose tumors were refractory to other chemotherapeutic agents, had partial tumor responses (> or = 50% decrease in tumor volume) that lasted from several months to over 1 yr. One patient had a minor response followed by resection of her remaining disease, 1 patient had stable disease, and 13 patients had disease progression. Three patients died of their disease without receiving sufficient gossypol to achieve detectable drug levels, and were eliminated from the final analysis. The side effects of gossypol were generally well tolerated; the only serious side effect was abdominal ileus that resolved when the drug was temporarily withheld and restarted at a lower dose. We conclude that oral gossypol can be used relatively safely on an outpatient basis for the treatment of metastatic adrenal cancer. The response rate is similar to the other agents currently available for adrenal cancer, and responses were seen in patients who had failed other chemotherapeutic regimens. This study provides the first indication that gossypol may have activity against cancer in humans, suggesting the need for further investigation of gossypol as an antitumor agent. JF - The Journal of clinical endocrinology and metabolism AU - Flack, M R AU - Pyle, R G AU - Mullen, N M AU - Lorenzo, B AU - Wu, Y W AU - Knazek, R A AU - Nisula, B C AU - Reidenberg, M M AD - Developmental Endocrinology Branch, National Institute of Child Health and Human Development, Bethesda, Maryland 20892. Y1 - 1993/04// PY - 1993 DA - April 1993 SP - 1019 EP - 1024 VL - 76 IS - 4 SN - 0021-972X, 0021-972X KW - Gossypol KW - KAV15B369O KW - Abridged Index Medicus KW - Index Medicus KW - Aged, 80 and over KW - Humans KW - Adult KW - Treatment Outcome KW - Tomography, X-Ray Computed KW - Aged KW - Middle Aged KW - Adolescent KW - Male KW - Female KW - Radiography, Thoracic KW - Adrenal Gland Neoplasms -- diagnostic imaging KW - Gossypol -- administration & dosage KW - Gossypol -- therapeutic use KW - Adrenal Gland Neoplasms -- secondary KW - Gossypol -- adverse effects KW - Adrenal Gland Neoplasms -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75670844?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Oral+gossypol+in+the+treatment+of+metastatic+adrenal+cancer.&rft.au=Flack%2C+M+R%3BPyle%2C+R+G%3BMullen%2C+N+M%3BLorenzo%2C+B%3BWu%2C+Y+W%3BKnazek%2C+R+A%3BNisula%2C+B+C%3BReidenberg%2C+M+M&rft.aulast=Flack&rft.aufirst=M&rft.date=1993-04-01&rft.volume=76&rft.issue=4&rft.spage=1019&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 - 1993-05-18 N1 - Date created - 1993-05-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The assessment and clinical implications of haloperidol acute-dose, steady-state, and withdrawal pharmacokinetics. AN - 75668790; 8463444 AB - In order to evaluate comprehensively haloperidol pharmacokinetics under fixed-dose treatment conditions, psychiatric patients were studied after treatment with an acute dose, during maintenance therapy, and after withdrawal from haloperidol following steady-state conditions. After single doses, haloperidol appeared rapidly in serum, achieving peak concentration at a mean of 4.5 hours. The range of observed elimination half-life was broad, between 8.5 and 66.6 hours, with a mean of 19.5 hours. Under conditions of chronic dosing, serial measurements of steady-state serum concentration revealed intrapatient coefficients of variation between 2 and 72%. The mean for all patients was 26.4%. Body clearance decreased nonsignificantly, and elimination half-life increased significantly after chronic dosing compared with kinetic parameters determined after a single dose. The concentration of haloperidol in serum obtained at 8 hours after a single dose correlated most strongly (r = 0.73; p < 0.0001) with steady-state concentration resulting from chronic dosing. A value of 4 ng/ml or lower determined 8 hours after a single oral dose of 0.2 mg/kg identified patients who did not accumulate haloperidol during chronic dosing of 0.4 mg/kg per day above a presumed therapeutic range for haloperidol of 5 to 15 ng/ml. The implications of these data for the clinical use of haloperidol are discussed. JF - Journal of clinical psychopharmacology AU - Khot, V AU - DeVane, C L AU - Korpi, E R AU - Venable, D AU - Bigelow, L B AU - Wyatt, R J AU - Kirch, D G AD - Neuropsychiatry Branch, National Institute of Mental Health Neuroscience Center, Saint Elizabeths, Washington, DC. Y1 - 1993/04// PY - 1993 DA - April 1993 SP - 120 EP - 127 VL - 13 IS - 2 SN - 0271-0749, 0271-0749 KW - Haloperidol KW - J6292F8L3D KW - Index Medicus KW - Drug Administration Schedule KW - Psychiatric Status Rating Scales KW - Half-Life KW - Double-Blind Method KW - Dose-Response Relationship, Drug KW - Humans KW - Metabolic Clearance Rate -- physiology KW - Drug Monitoring KW - Adult KW - Male KW - Female KW - Haloperidol -- adverse effects KW - Schizophrenia -- blood KW - Haloperidol -- pharmacokinetics KW - Haloperidol -- administration & dosage KW - Schizophrenic Psychology KW - Schizophrenia -- drug therapy KW - Substance Withdrawal Syndrome -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75668790?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+psychopharmacology&rft.atitle=The+assessment+and+clinical+implications+of+haloperidol+acute-dose%2C+steady-state%2C+and+withdrawal+pharmacokinetics.&rft.au=Khot%2C+V%3BDeVane%2C+C+L%3BKorpi%2C+E+R%3BVenable%2C+D%3BBigelow%2C+L+B%3BWyatt%2C+R+J%3BKirch%2C+D+G&rft.aulast=Khot&rft.aufirst=V&rft.date=1993-04-01&rft.volume=13&rft.issue=2&rft.spage=120&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+psychopharmacology&rft.issn=02710749&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-05-06 N1 - Date created - 1993-05-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Surgical management of pulmonary infections in chronic granulomatous disease of childhood. AN - 75663963; 8466336 AB - Chronic granulomatous disease of childhood is an inheritable disorder of phagocytic cell respiratory burst resulting in recurrent, life-threatening, catalase-positive infections. The lung is the most common site of infection, and pulmonary disease is the primary cause of death in greater than 50% of children with chronic granulomatous disease. Still, the role of surgery in management of this disease remains undefined. Between 1974 and 1990, 19 patients with chronic granulomatous disease required 31 thoracic interventions at our institution. Patients ranged in age from 2.5 to 27 years (mean age, 15 years). Seventeen of 19 patients (89%) had had previous pulmonary infections. Patients presented as toxic (temperature > 38.5 degrees C, chest pain, and cough) in 22 instances before the 31 procedures. Aggressive surgical intervention for diagnosis and extirpation of localized infections was undertaken with lobectomy/pneumonectomy with or without other procedures (5), bisegmentectomy (2), segmentectomy with or without other procedures (5), or wedge with or without other procedures (13). In five instances, an empyema was drained; a chest tube for a sterile collection was placed in one instance. There was one intraoperative death, and 3 patients died 22 to 600 days postoperatively with overwhelming sepsis. The mean hospitalization was 101 days (range, 24 to 600 days). Wound complications occurred in 5 patients, requiring 17 separate anesthetic debridements. A change in therapy was dictated by the results of the procedure in 23 of 31 instances (74%). Thoracic surgeons must be aware of this rare cause of immunosuppression in these children and, due to the unusual nature of the pulmonary infections, should follow an aggressive approach in their diagnosis and management. JF - The Annals of thoracic surgery AU - Pogrebniak, H W AU - Gallin, J I AU - Malech, H L AU - Baker, A R AU - Moskaluk, C A AU - Travis, W D AU - Pass, H I AD - Thoracic Oncology Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/04// PY - 1993 DA - April 1993 SP - 844 EP - 849 VL - 55 IS - 4 SN - 0003-4975, 0003-4975 KW - Abridged Index Medicus KW - Index Medicus KW - Humans KW - Adult KW - Child KW - Adolescent KW - Male KW - Female KW - Child, Preschool KW - Aspergillosis -- microbiology KW - Lung Diseases, Fungal -- microbiology KW - Aspergillosis -- surgery KW - Bacterial Infections -- microbiology KW - Bacterial Infections -- surgery KW - Lung Diseases, Fungal -- surgery KW - Granulomatous Disease, Chronic -- complications KW - Lung Diseases -- microbiology KW - Lung Diseases -- surgery UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75663963?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Surgical+management+of+pulmonary+infections+in+chronic+granulomatous+disease+of+childhood.&rft.au=Pogrebniak%2C+H+W%3BGallin%2C+J+I%3BMalech%2C+H+L%3BBaker%2C+A+R%3BMoskaluk%2C+C+A%3BTravis%2C+W+D%3BPass%2C+H+I&rft.aulast=Pogrebniak&rft.aufirst=H&rft.date=1993-04-01&rft.volume=55&rft.issue=4&rft.spage=844&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 - 1993-05-04 N1 - Date created - 1993-05-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cloning of the cDNA encoding a myosin heavy chain B isoform of Xenopus nonmuscle myosin with an insert in the head region. AN - 75662845; 8464900 AB - The complete amino acid sequence of Xenopus laevis nonmuscle myosin heavy chain B (MHC-B) has been deduced from overlapping cDNA clones isolated from an XTC cell library. RNA blots of various developmental stages, adult tissues, and XTC cells detect a single transcript of 7.5 kb which is expressed at similar levels throughout development. MHC-B mRNA was detected in XTC cells, heart, lung, spleen, and brain, at lower levels in ovary, testis, pancreas, stomach, liver, and eye, but not in kidney and skeletal muscle. Protein expression in adult tissues, as detected by immunoblot analysis, correlates well with mRNA expression. In chickens and humans, a fraction of the mRNA encoding the MHC-B isoform was found previously to contain a 10-amino acid insert at amino acid 211 near the ATP-binding site. As reported elsewhere, in the chicken this insert-bearing isoform is nervous system-specific. The Xenopus sequence shows a 16-amino acid insertion at the same position; 7 of 16 residues are identical to those in the chicken and human insertion, and these identical residues include a consensus target sequence for cyclin-p34cdc2 kinase. In contrast to chicken, all frog tissues and embryonic stages tested contained the insert-bearing form, and no evidence for a non-insert-bearing MHC-B isoform was found in Xenopus. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Bhatia-Dey, N AU - Adelstein, R S AU - Dawid, I B AD - Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/04/01/ PY - 1993 DA - 1993 Apr 01 SP - 2856 EP - 2859 VL - 90 IS - 7 SN - 0027-8424, 0027-8424 KW - Oligodeoxyribonucleotides KW - 0 KW - RNA, Messenger KW - DNA KW - 9007-49-2 KW - Myosins KW - EC 3.6.4.1 KW - Index Medicus KW - Animals KW - Genetic Variation KW - Protein Structure, Secondary KW - Humans KW - Organ Specificity KW - Amino Acid Sequence KW - RNA, Messenger -- genetics KW - Cloning, Molecular KW - Aging -- physiology KW - Base Sequence KW - Chickens KW - Polymerase Chain Reaction -- methods KW - Molecular Sequence Data KW - Sequence Homology, Amino Acid KW - Muscles -- physiology KW - Gene Library KW - Xenopus laevis -- genetics KW - DNA -- genetics KW - Myosins -- chemistry KW - Myosins -- genetics KW - Mutagenesis, Insertional UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75662845?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cloning+of+the+cDNA+encoding+a+myosin+heavy+chain+B+isoform+of+Xenopus+nonmuscle+myosin+with+an+insert+in+the+head+region.&rft.au=Bhatia-Dey%2C+N%3BAdelstein%2C+R+S%3BDawid%2C+I+B&rft.aulast=Bhatia-Dey&rft.aufirst=N&rft.date=1993-04-01&rft.volume=90&rft.issue=7&rft.spage=2856&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 - 1993-05-04 N1 - Date created - 1993-05-04 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - L11231; GENBANK; L09740 N1 - SuppNotes - Cited By: J Cell Biol. 1977 Jul;74(1):251-63 [141455] J Biol Chem. 1992 Sep 5;267(25):17864-71 [1355479] Cell. 1985 Oct;42(3):769-77 [2414011] Science. 1985 Nov 15;230(4727):767-70 [2932797] Science. 1987 May 29;236(4805):1081-6 [3576221] Science. 1987 May 29;236(4805):1086-91 [3576222] EMBO J. 1987 Nov;6(11):3499-505 [3322809] Annu Rev Biophys Biophys Chem. 1988;17:23-45 [3293586] Proc Natl Acad Sci U S A. 1988 Nov;85(21):8086-90 [3186710] Dev Biol. 1989 Jun;133(2):562-8 [2731640] Proc Natl Acad Sci U S A. 1989 Oct;86(20):7726-30 [2813355] J Cell Biol. 1990 Feb;110(2):367-78 [2404992] Differentiation. 1990 Mar;43(1):1-9 [1694800] Proc Natl Acad Sci U S A. 1990 Nov;87(22):9028-32 [2247479] Proc Natl Acad Sci U S A. 1990 Dec;87(23):9088-92 [2174552] J Cell Biol. 1991 Mar;112(5):915-24 [1999462] Development. 1991 Jan;111(1):1-14 [1901784] Mol Cell Biol. 1991 May;11(5):2481-8 [1850097] Annu Rev Physiol. 1991;53:653-81 [2042976] Science. 1991 Jul 12;253(5016):194-6 [1677215] Curr Opin Cell Biol. 1991 Feb;3(1):98-104 [1854490] Circ Res. 1991 Aug;69(2):530-9 [1860190] Methods Enzymol. 1991;200:62-81 [1956339] Genes Dev. 1992 Mar;6(3):356-66 [1347750] Curr Opin Cell Biol. 1992 Feb;4(1):27-35 [1558751] Methods Cell Biol. 1991;36:19-34 [1811134] Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387-95 [6546423] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evaluation of ketamine-xylazine in Syrian hamsters. AN - 75661126; 8467701 AB - Few parenteral anesthetics are safe and effective in the Syrian hamster. This study evaluated the anesthetic efficacy and potential for tissue damage of ketamine-xylazine (KX). Two dosage levels were administered intraperitoneally. Ketamine at 50 mg/kg combined with 10 mg/kg xylazine did not produce a consistent, reliable level of immobilization or anesthesia. Ketamine at 150 mg/kg combined with 10 mg/kg xylazine administered IP produced an adequate level of anesthesia without tissue damage for most procedures, but supplementation with lidocaine was necessary for peritoneal incision. Careful positioning of male hamsters for IP injection is imperative to prevent inadvertent injection into the testes with subsequent tissue damage. JF - The Cornell veterinarian AU - Payton, A J AU - Forsythe, D B AU - Dixon, D AU - Myers, P H AU - Clark, J A AU - Snipe, J R AD - Comparative Medicine Branch, National Institute of Environmental Health Science, National Institutes of Health, Research Triangle Park, NC 27709. Y1 - 1993/04// PY - 1993 DA - April 1993 SP - 153 EP - 161 VL - 83 IS - 2 SN - 0010-8901, 0010-8901 KW - Drug Combinations KW - 0 KW - Xylazine KW - 2KFG9TP5V8 KW - Ketamine KW - 690G0D6V8H KW - Index Medicus KW - Specific Pathogen-Free Organisms KW - Injections, Intraperitoneal KW - Evaluation Studies as Topic KW - Animals KW - Muscle Relaxation -- drug effects KW - Male KW - Female KW - Cricetinae KW - Xylazine -- adverse effects KW - Ketamine -- adverse effects KW - Xylazine -- administration & dosage KW - Anesthesia -- veterinary KW - Anesthesia -- methods KW - Mesocricetus KW - Ketamine -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75661126?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Cornell+veterinarian&rft.atitle=Evaluation+of+ketamine-xylazine+in+Syrian+hamsters.&rft.au=Payton%2C+A+J%3BForsythe%2C+D+B%3BDixon%2C+D%3BMyers%2C+P+H%3BClark%2C+J+A%3BSnipe%2C+J+R&rft.aulast=Payton&rft.aufirst=A&rft.date=1993-04-01&rft.volume=83&rft.issue=2&rft.spage=153&rft.isbn=&rft.btitle=&rft.title=The+Cornell+veterinarian&rft.issn=00108901&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-05-11 N1 - Date created - 1993-05-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Long-term biphasic effects of lithium treatment on phospholipase C-coupled M3-muscarinic acetylcholine receptors in cultured cerebellar granule cells. AN - 75654122; 8384505 AB - We have studied the long-term effects of lithium on neuronal morphology and the functional expression of phospholipase C-coupled m3-muscarinic acetylcholine receptors (mAChRs) in cerebellar granule cells. There was a biphasic dose-dependent effect on cell morphology following treatment with lithium for 7 days. At low concentrations ( or = 3 days. The biphasic effect was also demonstrated by the binding of [3H]ouabain to Na+, K(+)-ATPase, which was shown to be a convenient method for quantifying viable neurons.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Neurochemistry international AU - Gao, X M AU - Fukamauchi, F AU - Chuang, D M AD - Section on Molecular Neurobiology, Biological Psychiatry Branch, National Institute of Mental Health, Bethesda, MD 20892. Y1 - 1993/04// PY - 1993 DA - April 1993 SP - 395 EP - 403 VL - 22 IS - 4 SN - 0197-0186, 0197-0186 KW - Receptors, Muscarinic KW - 0 KW - Ouabain KW - 5ACL011P69 KW - Lithium KW - 9FN79X2M3F KW - Type C Phospholipases KW - EC 3.1.4.- KW - Sodium-Potassium-Exchanging ATPase KW - EC 3.6.3.9 KW - Index Medicus KW - Ouabain -- metabolism KW - Animals KW - Sodium-Potassium-Exchanging ATPase -- metabolism KW - Cells, Cultured KW - Binding Sites -- drug effects KW - Time Factors KW - Cerebellum -- cytology KW - Granulocytes -- metabolism KW - Cerebellum -- drug effects KW - Granulocytes -- drug effects KW - Type C Phospholipases -- metabolism KW - Receptors, Muscarinic -- metabolism KW - Lithium -- pharmacology KW - Cerebellum -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75654122?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurochemistry+international&rft.atitle=Long-term+biphasic+effects+of+lithium+treatment+on+phospholipase+C-coupled+M3-muscarinic+acetylcholine+receptors+in+cultured+cerebellar+granule+cells.&rft.au=Gao%2C+X+M%3BFukamauchi%2C+F%3BChuang%2C+D+M&rft.aulast=Gao&rft.aufirst=X&rft.date=1993-04-01&rft.volume=22&rft.issue=4&rft.spage=395&rft.isbn=&rft.btitle=&rft.title=Neurochemistry+international&rft.issn=01970186&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-04-23 N1 - Date created - 1993-04-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cytotoxic activities of recombinant immunotoxins composed of Pseudomonas toxin or diphtheria toxin toward lymphocytes from patients with adult T-cell leukemia. AN - 75652828; 8464234 AB - We have previously shown that the recombinant single-chain immunotoxin anti-Tac(Fv)-PE40, composed of the variable domains of the anti-Tac monoclonal antibody in a single-chain form joined to a derivative of Pseudomonas exotoxin (PE), is cytotoxic toward malignant cells from adult T-cell leukemia (ATL) patients. Using this assay, we have now compared the activity of anti-Tac(Fv)-PE40 with that of an improved version, anti-Tac(Fv)-PE40KDEL which contains an altered carboxyl terminus, and also with two chimeric toxins made with diphtheria toxin (DT). One of these is a fusion of amino acids 1-388 of DT with anti-Tac(Fv) and is termed DT388-anti-Tac(Fv). The other, DT388-IL2, contains interleukin 2 (IL2) at the carboxyl terminus of the same DT derivative. We incubated these toxins with malignant ATL peripheral blood mononuclear cells (PBMCs) for 1-3 days and then measured [3H]leucine incorporation. We found that anti-Tac(Fv)-PE40KDEL was the most cytotoxic agent and was followed in decreasing order of activity by anti-Tac(Fv)-PE40, DT388-anti-Tac(Fv), and finally DT388-IL2. Trypan blue staining showed that inhibition of protein synthesis correlated with cell death. Time course studies showed that the recombinant toxins containing anti-Tac(Fv) were cytotoxic even if exposed to the cells for only one hour. After intravenous injection into mice, the half-life of anti-Tac(Fv)-PE40 or anti-Tac(Fv)-PE40KDEL was 30 minutes. Normal PBMCs were resistant to all four toxins. Recombinant immunotoxins made with anti-Tac merit further study as potential reagents in the treatment of ATL. JF - Leukemia AU - Kreitman, R J AU - Chaudhary, V K AU - Waldmann, T A AU - Hanchard, B AU - Cranston, B AU - FitzGerald, D J AU - Pastan, I AD - Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/04// PY - 1993 DA - April 1993 SP - 553 EP - 562 VL - 7 IS - 4 SN - 0887-6924, 0887-6924 KW - Antibodies, Monoclonal KW - 0 KW - Diphtheria Toxin KW - Endotoxins KW - Immunotoxins KW - Interleukin-2 KW - Recombinant Fusion Proteins KW - Index Medicus KW - AIDS/HIV KW - Animals KW - Drug Screening Assays, Antitumor KW - Humans KW - Mice KW - Mice, Inbred BALB C KW - Antibodies, Monoclonal -- therapeutic use KW - Cytotoxicity, Immunologic KW - Lymphocytes -- immunology KW - Tumor Cells, Cultured KW - Interleukin-2 -- therapeutic use KW - Adult KW - Time Factors KW - Recombinant Fusion Proteins -- therapeutic use KW - Female KW - Leukemia-Lymphoma, Adult T-Cell -- therapy KW - Immunotoxins -- therapeutic use KW - Diphtheria Toxin -- therapeutic use KW - Pseudomonas -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75652828?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Leukemia&rft.atitle=Cytotoxic+activities+of+recombinant+immunotoxins+composed+of+Pseudomonas+toxin+or+diphtheria+toxin+toward+lymphocytes+from+patients+with+adult+T-cell+leukemia.&rft.au=Kreitman%2C+R+J%3BChaudhary%2C+V+K%3BWaldmann%2C+T+A%3BHanchard%2C+B%3BCranston%2C+B%3BFitzGerald%2C+D+J%3BPastan%2C+I&rft.aulast=Kreitman&rft.aufirst=R&rft.date=1993-04-01&rft.volume=7&rft.issue=4&rft.spage=553&rft.isbn=&rft.btitle=&rft.title=Leukemia&rft.issn=08876924&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-05-06 N1 - Date created - 1993-05-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pancreatitis in human immunodeficiency virus-infected children receiving dideoxyinosine. AN - 75651249; 7681940 AB - To define predictive or contributory risk factors for pancreatitis in human immunodeficiency virus-infected children receiving dideoxyinosine (ddI), the authors evaluated 95 children, 3 months to 18 years of age, who had received ddI at 60 to 540 mg/m2 per day for a mean of 56 weeks. Pancreatitis developed in 7 patients (7%) but resolved in all upon withdrawal of ddI. Neither age, sex, nor CD4 count at study entry was predictive of pancreatitis, but pancreatitis appeared more likely to develop in hemophiliacs than in other patients (4 of 23 vs 3 of 72). Pancreatitis developed only in patients who received ddI at the highest dose levels (7 of 60 patients who received ddI at a dose > or = 360 mg/m2 per day vs 0 of 35 patients who received < or = 270 mg/m2 per day). Patients in whom pancreatitis developed had received a higher mean daily dose of ddI than patients with normal amylase and lipase levels throughout the study (348 mg/m2 vs 282 mg/m2), but no relationship with the cumulative dose or the duration of ddI therapy was observed. Although a statistically significant relationship between ddI plasma concentration (area under the curve) and pancreatitis was not conclusively demonstrated, as the number of patients in whom pancreatitis actually developed was small, such a relationship may have been obscured.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Pediatrics AU - Butler, K M AU - Venzon, D AU - Henry, N AU - Husson, R N AU - Mueller, B U AU - Balis, F M AU - Jacobsen, F AU - Lewis, L L AU - Pizzo, P A AD - Pediatric Branch, National Cancer Institute, Bethesda, MD 20892. Y1 - 1993/04// PY - 1993 DA - April 1993 SP - 747 EP - 751 VL - 91 IS - 4 SN - 0031-4005, 0031-4005 KW - Aspartate Aminotransferases KW - EC 2.6.1.1 KW - Alanine Transaminase KW - EC 2.6.1.2 KW - Lipase KW - EC 3.1.1.3 KW - Amylases KW - EC 3.2.1.- KW - Didanosine KW - K3GDH6OH08 KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Dose-Response Relationship, Drug KW - Humans KW - Child KW - Lipase -- blood KW - Child, Preschool KW - Infant KW - Aspartate Aminotransferases -- blood KW - Alanine Transaminase -- blood KW - Incidence KW - Amylases -- blood KW - Adolescent KW - Male KW - Female KW - Pancreatitis -- enzymology KW - Pancreatitis -- epidemiology KW - HIV Infections -- drug therapy KW - Didanosine -- administration & dosage KW - HIV Infections -- enzymology KW - Didanosine -- pharmacokinetics KW - Pancreatitis -- chemically induced KW - Didanosine -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75651249?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pediatrics&rft.atitle=Pancreatitis+in+human+immunodeficiency+virus-infected+children+receiving+dideoxyinosine.&rft.au=Butler%2C+K+M%3BVenzon%2C+D%3BHenry%2C+N%3BHusson%2C+R+N%3BMueller%2C+B+U%3BBalis%2C+F+M%3BJacobsen%2C+F%3BLewis%2C+L+L%3BPizzo%2C+P+A&rft.aulast=Butler&rft.aufirst=K&rft.date=1993-04-01&rft.volume=91&rft.issue=4&rft.spage=747&rft.isbn=&rft.btitle=&rft.title=Pediatrics&rft.issn=00314005&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-05-03 N1 - Date created - 1993-05-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Overexpression of the HIV-1 gag-pol polyprotein results in intracellular activation of HIV-1 protease and inhibition of assembly and budding of virus-like particles. AN - 75651148; 7681610 AB - Some retroviruses, including HIV-1, regulate the relative amounts of gag and pol gene products by a translational frameshift mechanism. The consequences of altering the ratios of the Gag and Pol proteins were tested using vaccinia virus expression vectors, in which the gag and pol genes were fused by placing them in the same open reading frame. Immunoblotting of cell lysates indicated that a protein of approximately 160 kDa, the expected translation product of the fused gag-pol gene, was the dominant species detected with HIV-specific antiserum during the first several hours of infection with this recombinant virus. Subsequently, the full-length polyprotein diminished in amount and a series of Gag-related intermediate size proteins appeared. Later in infection, p24 and myristoylated p17 Gag proteins predominated and larger amounts of intracellularly processed reverse transcriptase, integrase, and protease were detected compared to the amounts formed with the wild-type gag-pol gene. Large numbers of budding, immature, and mature retrovirus-like particles were visualized by electron microscopy when the wild-type gag-pol gene was expressed, whereas no particles were detected in cells that expressed the fused gag-pol gene. The block to virus assembly was partially overcome by (i) inhibition of the HIV-1 protease with a peptidomimetic inhibitor, (ii) mutagenesis of the active site of the protease, or (iii) shortening of the Gag-Pol polyprotein by deletion of most of the reverse transcriptase gene. Nevertheless, budding was inefficient and the structures appeared immature and frequently aberrant. These results indicated that overproduction of the full-length Gag-Pol polyprotein and increased intracellular protease activity were both detrimental to viral assembly. Further experiments indicated that intracellular processing of Gag and Gag-Pol polyproteins occurred in the absence of particle formation when myristoylation was prevented. JF - Virology AU - Karacostas, V AU - Wolffe, E J AU - Nagashima, K AU - Gonda, M A AU - Moss, B AD - Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland 20892. Y1 - 1993/04// PY - 1993 DA - April 1993 SP - 661 EP - 671 VL - 193 IS - 2 SN - 0042-6822, 0042-6822 KW - gag KW - pol KW - Fusion Proteins, gag-pol KW - 0 KW - Myristic Acids KW - Myristic Acid KW - 0I3V7S25AW KW - HIV Reverse Transcriptase KW - EC 2.7.7.49 KW - RNA-Directed DNA Polymerase KW - HIV Protease KW - EC 3.4.23.- KW - Index Medicus KW - AIDS/HIV KW - Vaccinia virus -- genetics KW - Animals KW - Enzyme Activation KW - HeLa Cells KW - Humans KW - RNA-Directed DNA Polymerase -- metabolism KW - Plasmids KW - Myristic Acids -- metabolism KW - Frameshift Mutation KW - Base Sequence KW - Restriction Mapping KW - Microscopy, Electron KW - Cell Line KW - Sequence Deletion KW - Fusion Proteins, gag-pol -- biosynthesis KW - HIV-1 -- genetics KW - Fusion Proteins, gag-pol -- genetics KW - HIV-1 -- physiology KW - HIV Protease -- metabolism KW - Genes, gag KW - Genes, pol KW - HIV-1 -- ultrastructure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75651148?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Virology&rft.atitle=Overexpression+of+the+HIV-1+gag-pol+polyprotein+results+in+intracellular+activation+of+HIV-1+protease+and+inhibition+of+assembly+and+budding+of+virus-like+particles.&rft.au=Karacostas%2C+V%3BWolffe%2C+E+J%3BNagashima%2C+K%3BGonda%2C+M+A%3BMoss%2C+B&rft.aulast=Karacostas&rft.aufirst=V&rft.date=1993-04-01&rft.volume=193&rft.issue=2&rft.spage=661&rft.isbn=&rft.btitle=&rft.title=Virology&rft.issn=00426822&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-04-23 N1 - Date created - 1993-04-23 N1 - Date revised - 2017-01-13 N1 - Gene symbol - gag; pol N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Intraoperative radiotherapy in retroperitoneal sarcomas. Final results of a prospective, randomized, clinical trial. AN - 75648667; 8457152 AB - Thirty-five patients with surgically resected sarcomas of the retroperitoneum were enrolled in a prospective, randomized, clinical trial comparing 20-Gy intraoperative radiotherapy in combination with postoperative low-dose (35- to 40-Gy) external-beam radiotherapy with postoperative high-dose (50- to 55-Gy) external-beam radiotherapy alone. Chemotherapy with doxorubicin hydrochloride, cyclophosphamide (anhydrous), and methotrexate sodium was used for a portion of the trial. Fifteen patients who received intraoperative radiotherapy and 20 control patients were followed up for a minimum of 5 years (median follow-up, 8 years). Median survival times were similar for the group that received intraoperative radiotherapy (45 months) and the control group (52 months). There were no indications of benefit from adjunctive chemotherapy. The number of locoregional recurrences was significantly lower among those who received intraoperative radiotherapy (six of 15) than control patients (16 of 20). Patients who received intraoperative radiotherapy had fewer complications of disabling radiation-related enteritis (two of 15) than control patients (10 of 20), but radiation-related peripheral neuropathy was more frequent among those who received intraoperative radiotherapy (nine of 15) than among control patients (one of 20). JF - Archives of surgery (Chicago, Ill. : 1960) AU - Sindelar, W F AU - Kinsella, T J AU - Chen, P W AU - DeLaney, T F AU - Tepper, J E AU - Rosenberg, S A AU - Glatstein, E AD - Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1993/04// PY - 1993 DA - April 1993 SP - 402 EP - 410 VL - 128 IS - 4 SN - 0004-0010, 0004-0010 KW - Abridged Index Medicus KW - Index Medicus KW - Neoplasm Recurrence, Local -- epidemiology KW - Neoplasm Staging KW - Combined Modality Therapy KW - Humans KW - Surgical Wound Infection -- etiology KW - Postoperative Complications -- etiology KW - Prospective Studies KW - Survival Rate KW - Radiotherapy Dosage KW - Adult KW - Incidence KW - Follow-Up Studies KW - Intraoperative Period KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Chemotherapy, Adjuvant KW - Radiation Injuries -- etiology KW - Retroperitoneal Neoplasms -- radiotherapy KW - Sarcoma -- radiotherapy KW - Retroperitoneal Neoplasms -- mortality KW - Sarcoma -- mortality KW - Sarcoma -- surgery KW - Retroperitoneal Neoplasms -- pathology KW - Sarcoma -- pathology KW - Retroperitoneal Neoplasms -- surgery UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75648667?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+surgery+%28Chicago%2C+Ill.+%3A+1960%29&rft.atitle=Intraoperative+radiotherapy+in+retroperitoneal+sarcomas.+Final+results+of+a+prospective%2C+randomized%2C+clinical+trial.&rft.au=Sindelar%2C+W+F%3BKinsella%2C+T+J%3BChen%2C+P+W%3BDeLaney%2C+T+F%3BTepper%2C+J+E%3BRosenberg%2C+S+A%3BGlatstein%2C+E&rft.aulast=Sindelar&rft.aufirst=W&rft.date=1993-04-01&rft.volume=128&rft.issue=4&rft.spage=402&rft.isbn=&rft.btitle=&rft.title=Archives+of+surgery+%28Chicago%2C+Ill.+%3A+1960%29&rft.issn=00040010&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-04-22 N1 - Date created - 1993-04-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Calcium potentiates cyclic AMP stimulation of pineal arylalkylamine N-acetyltransferase. AN - 75640865; 7681102 AB - Pineal arylalkylamine N-acetyltransferase (N-acetyltransferase) controls large daily changes in melatonin production. It is generally thought that the activity of this enzyme is controlled by norepinephrine acting exclusively via elevation of cyclic AMP. However, norepinephrine also elevates pineal intracellular Ca2+ concentration ([Ca2+]i), and it is not known whether Ca2+ is involved in regulating N-acetyltransferase activity other than through its established role in cyclic AMP production. In this study, the issue of whether Ca2+ enhances the effects of cyclic AMP on N-acetyltransferase activity was investigated. The effects of cyclic AMP protagonists (isobutylmethylxanthine, N6,2'-O-dibutyryladenosine 3',5'-cyclic monophosphate, 8-bromoadenosine 3',5'-cyclic monophosphate, and adenosine 3',5'-cyclic monophosphothioate, Sp-diastereomer) were examined in combination with [Ca2+]i protagonists (A23187, ionomycin, and phenylephrine). All [Ca2+]i protagonists potentiated the effects of cyclic AMP protagonists. For example, ionomycin potentiated the effects of low concentrations of 8-bromoadenosine 3',5'-cyclic monophosphate, and A23187 potentiated the effects of isobutylmethylxanthine without altering cyclic AMP accumulation. These findings indicate that Ca2+ and cyclic AMP probably act physiologically in a coordinated manner to stimulate N-acetyltransferase activity; these second messengers could act directly at one or more sites or through indirect actions mediated by kinases. JF - Journal of neurochemistry AU - Yu, L AU - Schaad, N C AU - Klein, D C AD - Section on Neuroendocrinology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/04// PY - 1993 DA - April 1993 SP - 1436 EP - 1443 VL - 60 IS - 4 SN - 0022-3042, 0022-3042 KW - Phenylephrine KW - 1WS297W6MV KW - Calcimycin KW - 37H9VM9WZL KW - Cobalt KW - 3G0H8C9362 KW - Bucladesine KW - 63X7MBT2LQ KW - Cyclic AMP KW - E0399OZS9N KW - Arylamine N-Acetyltransferase KW - EC 2.3.1.5 KW - cobaltous chloride KW - EVS87XF13W KW - Calcium KW - SY7Q814VUP KW - 1-Methyl-3-isobutylxanthine KW - TBT296U68M KW - Norepinephrine KW - X4W3ENH1CV KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Norepinephrine -- pharmacology KW - Cells, Cultured KW - Cobalt -- pharmacology KW - Calcimycin -- pharmacology KW - Drug Synergism KW - Bucladesine -- pharmacology KW - 1-Methyl-3-isobutylxanthine -- pharmacology KW - Organ Culture Techniques KW - Female KW - Phenylephrine -- pharmacology KW - Cyclic AMP -- pharmacology KW - Cyclic AMP -- metabolism KW - Cyclic AMP -- analogs & derivatives KW - Pineal Gland -- enzymology KW - Calcium -- pharmacology KW - Arylamine N-Acetyltransferase -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75640865?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Calcium+potentiates+cyclic+AMP+stimulation+of+pineal+arylalkylamine+N-acetyltransferase.&rft.au=Yu%2C+L%3BSchaad%2C+N+C%3BKlein%2C+D+C&rft.aulast=Yu&rft.aufirst=L&rft.date=1993-04-01&rft.volume=60&rft.issue=4&rft.spage=1436&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 - 1993-04-19 N1 - Date created - 1993-04-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interleukin-1 alpha and interleukin-6 act additively to inhibit growth of MCF-7 breast cancer cells in vitro. AN - 75636252; 8453620 AB - We studied the effects of interleukin-1 alpha (IL-1) and interleukin-6 (IL-6) on MCF-7 breast cancer cells to determine whether these cytokines act additively/synergistically to alter cell growth and metabolism. We found that IL-1 alone (1000 units/ml) inhibited cell growth to a greater degree (83.8%) than IL-6 alone (29.2%, P < 0.001). The combination of IL-1 + IL-6 caused greater inhibition of growth (92.9%, P < 0.02) than either cytokine alone. The additive effect was dose dependent for both IL-1 and IL-6. IL-1 and IL-6 also antagonized estradiol (10(-9) M) stimulated growth. Antagonism by the combination was greater than for either cytokine alone (P < 0.001). IL-1 or IL-6 alone each down-regulated the estrogen receptor (36.7%, P < 0.01, and 23.2%, P < 0.05, respectively), but the combination IL-1 + IL-6 did not cause a significantly greater effect than IL-1 alone. Neither IL-1 or IL-6 blocked estradiol stimulation of progesterone receptor (PR) synthesis; however, the combination IL-1 + IL-6 increased PR content by 28.4% (P < 0.01). IL-1, but not IL-6, increased secretion of transforming growth factor-beta (TGF-beta) by 2.45-fold over 72 h (P < 0.01). The increase was time dependent (detectable at 24 h) and dose dependent (maximum increase of 5.3-fold, 10,000 units/ml, P < 0.02). IL-1-induced TGF-beta secretion was blocked by estradiol (10(-9) M). Neither cytokine altered secretion of insulin-like growth factor-1. These findings indicate that IL-1 and IL-6 act additively to inhibit growth in the absence or presence of estradiol and modulate the estrogen receptor and progesterone receptor content of these cells. TGF-beta may mediate the effects of IL-1; however, other pathways appear to be required for the additive effects of these cytokines. JF - Cancer research AU - Danforth, D N AU - Sgagias, M K AD - Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1993/04/01/ PY - 1993 DA - 1993 Apr 01 SP - 1538 EP - 1545 VL - 53 IS - 7 SN - 0008-5472, 0008-5472 KW - Interleukin-1 KW - 0 KW - Interleukin-6 KW - Receptors, Estrogen KW - Receptors, Progesterone KW - Transforming Growth Factor beta KW - Estradiol KW - 4TI98Z838E KW - Insulin-Like Growth Factor I KW - 67763-96-6 KW - Index Medicus KW - Drug Interactions KW - Tumor Cells, Cultured KW - Dose-Response Relationship, Drug KW - Humans KW - Cell Division -- drug effects KW - Insulin-Like Growth Factor I -- metabolism KW - Interleukin-1 -- pharmacology KW - Receptors, Progesterone -- metabolism KW - Interleukin-6 -- secretion KW - Breast Neoplasms -- pathology KW - Estradiol -- pharmacology KW - Breast Neoplasms -- metabolism KW - Interleukin-6 -- pharmacology KW - Receptors, Estrogen -- metabolism KW - Transforming Growth Factor beta -- metabolism KW - Interleukin-1 -- secretion UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75636252?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Interleukin-1+alpha+and+interleukin-6+act+additively+to+inhibit+growth+of+MCF-7+breast+cancer+cells+in+vitro.&rft.au=Danforth%2C+D+N%3BSgagias%2C+M+K&rft.aulast=Danforth&rft.aufirst=D&rft.date=1993-04-01&rft.volume=53&rft.issue=7&rft.spage=1538&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 - 1993-04-21 N1 - Date created - 1993-04-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Recombinant immunotoxins containing the VH or VL domain of monoclonal antibody B3 fused to Pseudomonas exotoxin. AN - 75634224; 8454854 AB - We prepared recombinant immunotoxins in Escherichia coli in which the VH or VL domains of mAb B3 were fused to a truncated form of Pseudomonas exotoxin (PE) (PE38KDEL). mAb B3 binds to a carbohydrate Ag found on the surfaces of many types of cancers and only a few normal tissues. PE38KDEL is a 38-kDa form of PE (66 kDa) that is missing the cell-binding domain of PE and has the carboxyl end changed from REDLK to KDEL. We show that immunotoxins in which the H chain or the L chain V region is fused to PE38KDEL bind to and kill carcinoma cells containing the B3 Ag. B3 Ag-negative cells were not affected. The cytotoxicity of these molecules is between 20- and 100-fold less than B3(Fv)-immunotoxins, containing both the H and L chain V regions. The VL-containing toxin was more active than the VH-containing toxin, indicating that the L chain of mAb B3 probably contributes more to Ag-binding than the H chain. Refolding experiments show that B3(VL)-PE38KDEL aggregates less than the VH-derivative or than a single chain immunotoxin B3(Fv)-PE38KDEL, which contains both domains in a single chain form. Furthermore, in addition to monomers, active homodimers of B3(VH)- and B3(VL)-PE38KDEL were obtained from renaturation experiments. The VL-toxin dimers, which might have their binding regions arranged in a manner similar to Bence Jones proteins (L chain homodimers), were found to have almost the same cytotoxicity as the monomers, whereas the VH-toxin dimers had decreased cytotoxic activity. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Brinkmann, U AU - Lee, B K AU - Pastan, I AD - Laboratory of Molecular Biology, National Cancer Institute, Bethesda, MD 20892. Y1 - 1993/04/01/ PY - 1993 DA - 1993 Apr 01 SP - 2774 EP - 2782 VL - 150 IS - 7 SN - 0022-1767, 0022-1767 KW - Amino Acids KW - 0 KW - Antibodies, Monoclonal KW - Bacterial Toxins KW - Exotoxins KW - Immunoglobulin Heavy Chains KW - Immunoglobulin Light Chains KW - Immunoglobulin Variable Region KW - Immunotoxins KW - Recombinant Fusion Proteins KW - Virulence Factors KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - toxA protein, Pseudomonas aeruginosa KW - EC 2.4.2.31 KW - Abridged Index Medicus KW - Index Medicus KW - Antibody Specificity KW - Base Sequence KW - Antibodies, Monoclonal -- genetics KW - Amino Acids -- chemistry KW - Humans KW - Amino Acids -- genetics KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Antibodies, Monoclonal -- chemistry KW - Plasmids KW - Mutation KW - Immunoglobulin Variable Region -- genetics KW - Recombinant Fusion Proteins -- biosynthesis KW - Exotoxins -- genetics KW - Pseudomonas aeruginosa -- genetics KW - Immunotoxins -- biosynthesis KW - Recombinant Fusion Proteins -- isolation & purification KW - Immunoglobulin Variable Region -- biosynthesis KW - Exotoxins -- immunology KW - Immunoglobulin Variable Region -- isolation & purification KW - Immunoglobulin Heavy Chains -- biosynthesis KW - Immunoglobulin Heavy Chains -- genetics KW - Immunoglobulin Light Chains -- isolation & purification KW - Immunoglobulin Light Chains -- biosynthesis KW - Pseudomonas aeruginosa -- immunology KW - Pseudomonas aeruginosa -- chemistry KW - Recombinant Fusion Proteins -- pharmacology KW - Immunoglobulin Light Chains -- genetics KW - Immunotoxins -- isolation & purification KW - Immunotoxins -- pharmacology KW - Immunoglobulin Heavy Chains -- isolation & purification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75634224?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Recombinant+immunotoxins+containing+the+VH+or+VL+domain+of+monoclonal+antibody+B3+fused+to+Pseudomonas+exotoxin.&rft.au=Brinkmann%2C+U%3BLee%2C+B+K%3BPastan%2C+I&rft.aulast=Brinkmann&rft.aufirst=U&rft.date=1993-04-01&rft.volume=150&rft.issue=7&rft.spage=2774&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 - 1993-04-20 N1 - Date created - 1993-04-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Suppression of oncogene-induced transformation by a deletion mutant of c-jun. AN - 75632918; 8455942 AB - Jun and Fos proteins are DNA-binding proteins that are involved in the control of gene expression through transcriptional regulation. We have made a deletion mutant of the c-jun gene that lacks amino acids 3-122 of c-jun, and thus is missing the major transactivation domain of c-jun, but retains the DNA-binding and leucine zipper domains. Unlike c-Jun, the mutant protein is unable to stimulate the transcription of an AP-1 responsive gene, and unlike c-jun this mutant gene is unable to transform rat embryo cells in cooperation with an activated ras gene. However, this mutant protein blocks in vitro DNA binding of Jun-Jun homodimers and Jun-Fos heterodimers, transcriptional activation induced by c-jun or c-fos and transformation of rat embryo cells induced by an activated ras gene and a deregulated c-jun or c-fos gene. In addition, transformation of rat embryo cells induced by an activated ras gene in the presence of the tumor promoter 12-O-tetradecanoyl phorbol 13-acetate (TPA) or by ras plus SV40 large T antigen is also inhibited by this dominant-negative mutant, suggesting that a member of the jun or fos family is involved in the pathways leading to transformation in these systems as well. The possible molecular mechanisms by which this dominant-negative mutant of c-jun blocks the functions of wild-type jun and fos family members are discussed. JF - Oncogene AU - Brown, P H AU - Alani, R AU - Preis, L H AU - Szabo, E AU - Birrer, M J AD - Biomarkers and Prevention Research Branch, National Cancer Institute, Kensington, Maryland 20895. Y1 - 1993/04// PY - 1993 DA - April 1993 SP - 877 EP - 886 VL - 8 IS - 4 SN - 0950-9232, 0950-9232 KW - c-fos KW - c-jun KW - ras KW - DNA-Binding Proteins KW - 0 KW - Proto-Oncogene Proteins c-fos KW - Proto-Oncogene Proteins c-jun KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - Proto-Oncogene Proteins c-fos -- metabolism KW - DNA Mutational Analysis KW - Humans KW - Rats KW - Genes, ras KW - Base Sequence KW - Genes, Dominant KW - Cells, Cultured KW - Binding, Competitive KW - In Vitro Techniques KW - Molecular Sequence Data KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Genes, Suppressor KW - Sequence Deletion KW - DNA-Binding Proteins -- metabolism KW - Proto-Oncogene Proteins c-jun -- genetics KW - Cell Transformation, Neoplastic -- drug effects KW - Transcriptional Activation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75632918?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Suppression+of+oncogene-induced+transformation+by+a+deletion+mutant+of+c-jun.&rft.au=Brown%2C+P+H%3BAlani%2C+R%3BPreis%2C+L+H%3BSzabo%2C+E%3BBirrer%2C+M+J&rft.aulast=Brown&rft.aufirst=P&rft.date=1993-04-01&rft.volume=8&rft.issue=4&rft.spage=877&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1993-04-20 N1 - Date created - 1993-04-20 N1 - Date revised - 2017-01-13 N1 - Gene symbol - c-fos; c-jun; ras N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Analysis of nonnucleoside drug-resistant variants of human immunodeficiency virus type 1 reverse transcriptase. AN - 75616237; 7680393 AB - A number of chemically distinct nonnucleoside inhibitors of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) have been reported. Several lines of evidence, including the isolation of RT mutants that show cross resistance, suggest that, despite their structural diversity, many of these inhibitors bind to a common site on HIV-1 RT. We have recently reported that, on the basis of analyses of HIV-1/HIV-2 chimeras, the natural product calanolide A may interact with a different site or sites in HIV-1 RT. We have used BspMI cassette mutagenesis to prepare a collection of HIV-1 RT mutants that show resistance to the known members of the general class of nonnucleoside inhibitors. This collection of mutants can be used to determine whether a new drug will show cross resistance with known inhibitors and to define amino acid positions critical for the action of the drugs. The mutants were used to analyze calanolide A, 1H,3H-thiazolo[3,4-a]benzimidazole(4i), and the acyclic nucleoside analog 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine. These analyses suggest that all three drugs interact with HIV-1 RT within the previously defined common binding site for nonnucleoside inhibitors. However, the drugs respond differently to the panel of drug-resistant HIV-1 RTs, indicating that while the binding sites of the drugs overlap they are not identical. JF - Journal of virology AU - Boyer, P L AU - Currens, M J AU - McMahon, J B AU - Boyd, M R AU - Hughes, S H AD - ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Maryland 21702-1201. Y1 - 1993/04// PY - 1993 DA - April 1993 SP - 2412 EP - 2420 VL - 67 IS - 4 SN - 0022-538X, 0022-538X KW - Antiviral Agents KW - 0 KW - Benzimidazoles KW - Coumarins KW - Pyranocoumarins KW - Reverse Transcriptase Inhibitors KW - Thiazoles KW - 1-((2-hydroxyethoxy)methyl)-6-(phenylthio)thymine KW - 123027-56-5 KW - 1H,3H-thiazolo(3,4-a)benzimidazole KW - 35766-04-2 KW - HIV Reverse Transcriptase KW - EC 2.7.7.49 KW - Thymine KW - QR26YLT7LT KW - calanolide A KW - S5A9TQN46W KW - Index Medicus KW - AIDS/HIV KW - Drug Resistance, Microbial KW - Amino Acid Sequence KW - Structure-Activity Relationship KW - Thymine -- pharmacology KW - Thiazoles -- pharmacology KW - HIV -- drug effects KW - Thymine -- analogs & derivatives KW - Coumarins -- pharmacology KW - Benzimidazoles -- pharmacology KW - Antiviral Agents -- chemistry KW - HIV -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75616237?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Analysis+of+nonnucleoside+drug-resistant+variants+of+human+immunodeficiency+virus+type+1+reverse+transcriptase.&rft.au=Boyer%2C+P+L%3BCurrens%2C+M+J%3BMcMahon%2C+J+B%3BBoyd%2C+M+R%3BHughes%2C+S+H&rft.aulast=Boyer&rft.aufirst=P&rft.date=1993-04-01&rft.volume=67&rft.issue=4&rft.spage=2412&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 - 1993-04-08 N1 - Date created - 1993-04-08 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nature. 1990 Feb 1;343(6257):470-4 [1689015] Science. 1990 Dec 7;250(4986):1411-3 [1701568] Proc Natl Acad Sci U S A. 1991 Feb 15;88(4):1451-5 [1705038] Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2356-60 [1706522] J Infect Dis. 1991 May;163(5):966-70 [1708400] Proc Natl Acad Sci U S A. 1991 Aug 1;88(15):6863-7 [1713693] J Virol. 1991 Sep;65(9):4887-92 [1714522] J Virol. 1991 Oct;65(10):5232-6 [1716689] Science. 1991 Sep 27;253(5027):1557-9 [1716788] Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8806-10 [1717988] Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9878-82 [1719542] J Biol Chem. 1991 Dec 15;266(35):23529-36 [1721050] Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11241-5 [1722324] J Virol. 1992 Feb;66(2):1031-9 [1370546] Farmaco. 1991 Jun;46(6):817-23 [1685321] Farmaco. 1991 Jul-Aug;46(7-8):925-33 [1686551] AIDS Res Hum Retroviruses. 1992 Feb;8(2):119-34 [1371690] AIDS Res Hum Retroviruses. 1992 Feb;8(2):145-52 [1371691] Mol Pharmacol. 1992 Mar;41(3):446-51 [1372083] Virology. 1992 Jun;188(2):900-4 [1374986] Science. 1992 Jun 26;256(5065):1783-90 [1377403] J Med Chem. 1992 Jul 24;35(15):2735-43 [1379639] Antimicrob Agents Chemother. 1992 Jul;36(7):1441-6 [1380789] J Biol Chem. 1992 Sep 5;267(25):17526-30 [1381350] Virology. 1992 Sep;190(1):269-77 [1382341] J Virol. 1992 Dec;66(12):7533-7 [1279205] Proc Natl Acad Sci U S A. 1988 Feb;85(4):1218-22 [2448794] J Med Chem. 1989 Dec;32(12):2507-9 [2479745] Science. 1989 Dec 1;246(4934):1155-8 [2479983] Biochem Biophys Res Commun. 1989 Dec 29;165(3):1375-81 [2575380] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Expression of sulfated glycoprotein 2 is associated with carcinogenesis induced by N-nitroso-N-methylurea in rat prostate and seminal vesicle. AN - 75614184; 8453611 AB - To understand the molecular mechanism of carcinogenesis in androgen-dependent tumors, we have searched for new markers which are associated with this process. In normal rat prostate and seminal vesicle, sulfated glycoprotein 2 (SGP-2) messenger RNA is barely detectable. However, we have found high levels of SGP-2 expression in the epithelial component of carcinomas of the prostate and seminal vesicle after initiation with N-nitroso-N-methylurea and promotion with testosterone propionate. We have also observed induction of SGP-2 expression in epithelial cells at early stages in carcinogenesis when cytologically malignant cells first begin to appear. SGP-2 has been reported previously to be associated with a variety of models of programmed cell death (apoptosis), including the prostate following castration. Our present findings provide a novel marker for carcinogenesis in the rat prostate and seminal vesicle. JF - Cancer research AU - Kadomatsu, K AU - Anzano, M A AU - Slayter, M V AU - Winokur, T S AU - Smith, J M AU - Sporn, M B AD - Laboratory of Chemoprevention, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1993/04/01/ PY - 1993 DA - 1993 Apr 01 SP - 1480 EP - 1483 VL - 53 IS - 7 SN - 0008-5472, 0008-5472 KW - Biomarkers, Tumor KW - 0 KW - Clusterin KW - Glycoproteins KW - Molecular Chaperones KW - Methylnitrosourea KW - 684-93-5 KW - Index Medicus KW - Rats KW - Animals KW - Blotting, Northern KW - Epithelium -- metabolism KW - Male KW - Prostatic Neoplasms -- metabolism KW - Biomarkers, Tumor -- metabolism KW - Prostatic Neoplasms -- pathology KW - Seminal Vesicles -- metabolism KW - Glycoproteins -- metabolism KW - Prostatic Neoplasms -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75614184?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Expression+of+sulfated+glycoprotein+2+is+associated+with+carcinogenesis+induced+by+N-nitroso-N-methylurea+in+rat+prostate+and+seminal+vesicle.&rft.au=Kadomatsu%2C+K%3BAnzano%2C+M+A%3BSlayter%2C+M+V%3BWinokur%2C+T+S%3BSmith%2C+J+M%3BSporn%2C+M+B&rft.aulast=Kadomatsu&rft.aufirst=K&rft.date=1993-04-01&rft.volume=53&rft.issue=7&rft.spage=1480&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 - 1993-04-21 N1 - Date created - 1993-04-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Physical and functional characterization of transcriptional control elements in the equine infectious anemia virus promoter. AN - 75610142; 8383228 AB - Equine infectious anemia virus (EIAV) is a lentivirus that causes a chronic disease of horses characterized by cyclic episodes of fever, anemia, and viremia. Although the genome and promoter of EIAV are much less complex than those of its relatives the primate immunodeficiency viruses, the cellular proteins that activate and regulate transcription of EIAV have not yet been identified. In this report, we show by electrophoretic mobility shift assays and DNase I footprinting that the EIAV promoter contains multiple binding sites for ubiquitous, cell type-specific, and inducible cellular proteins. Functional analysis by transient transfection of canine osteosarcoma (D17) and human epithelial carcinoma (HeLa) cells with EIAV promoters containing deletions or individually mutated DNA-binding sites demonstrated that these DNA-binding elements cooperatively regulate transcriptional activity. A methylated DNA-binding site (MDBP; also designated EF-C or EP) acts as either a positive or negative regulator of promoter activity, depending on the cell type or condition. Two PEA2 elements, an AP-1 site, and an ets/PEA3 motif confer a positive effect on promoter activity. The EIAV promoter is shown to be activated by treatment of HeLa cells with phorbol myristate acetate (PMA). DNA-binding activities were induced in PMA-treated HeLa cells and formed complexes on oligonucleotides that contain the EIAV AP-1 and ets/PEA3 elements. Functional analysis of mutated promoters indicated that the ets/PEA3 motif was the principal mediator of PMA activation. JF - Journal of virology AU - Carvalho, M AU - Derse, D AD - Laboratory of Viral Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland 21702-1201. Y1 - 1993/04// PY - 1993 DA - April 1993 SP - 2064 EP - 2074 VL - 67 IS - 4 SN - 0022-538X, 0022-538X KW - DNA-Binding Proteins KW - 0 KW - Oligodeoxyribonucleotides KW - Transcription Factors KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - AIDS/HIV KW - Animals KW - Transcription Factors -- metabolism KW - HeLa Cells KW - Humans KW - Horses KW - Transcription, Genetic KW - Binding Sites KW - Base Sequence KW - Cells, Cultured KW - Oligodeoxyribonucleotides -- chemistry KW - In Vitro Techniques KW - Dogs KW - Molecular Sequence Data KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Methylation KW - Sequence Deletion KW - DNA-Binding Proteins -- metabolism KW - Promoter Regions, Genetic KW - Gene Expression Regulation, Viral KW - Enhancer Elements, Genetic KW - Infectious Anemia Virus, Equine -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75610142?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Physical+and+functional+characterization+of+transcriptional+control+elements+in+the+equine+infectious+anemia+virus+promoter.&rft.au=Carvalho%2C+M%3BDerse%2C+D&rft.aulast=Carvalho&rft.aufirst=M&rft.date=1993-04-01&rft.volume=67&rft.issue=4&rft.spage=2064&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 - 1993-04-08 N1 - Date created - 1993-04-08 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Virol. 1982 May;42(2):502-9 [7086969] J Virol. 1989 Jul;63(7):3001-15 [2542608] Science. 1984 Dec 14;226(4680):1337-9 [6095453] Rev Infect Dis. 1985 Jan-Feb;7(1):83-8 [2984759] Mol Cell Biol. 1985 Apr;5(4):649-58 [2985964] Gene. 1985;33(2):181-9 [3922855] Proc Natl Acad Sci U S A. 1986 Nov;83(22):8550-4 [3022296] J Virol. 1987 Mar;61(3):743-7 [3027401] Nature. 1987 Jul 16-22;328(6127):254-6 [3037385] EMBO J. 1987 May;6(5):1331-7 [3038517] EMBO J. 1987 Dec 1;6(12):3761-70 [3428273] J Virol. 1988 Sep;62(9):3522-6 [2841502] Nucleic Acids Res. 1988 Aug 25;16(16):8029-44 [2901711] Cell. 1988 Dec 2;55(5):917-24 [3142692] EMBO J. 1988 Aug;7(8):2475-83 [3142763] Mol Cell Biol. 1989 Mar;9(3):1327-31 [2498646] Mol Cell Biol. 1989 Apr;9(4):1804-9 [2725524] Oncogene. 1989 May;4(5):629-36 [2498806] Proc Natl Acad Sci U S A. 1989 Aug;86(15):5974-8 [2762307] Mol Cell Biol. 1989 Jul;9(7):2787-97 [2550788] Nucleic Acids Res. 1990 Jan 11;18(1):23-34 [2106664] J Virol. 1990 Apr;64(4):1616-24 [2157047] Genes Dev. 1990 Mar;4(3):401-9 [2186967] Proc Natl Acad Sci U S A. 1990 May;87(10):3723-7 [2187191] Mol Cell Biol. 1990 Jul;10(7):3683-9 [2355919] EMBO J. 1990 Jul;9(7):2241-6 [2162765] Mol Cell Biol. 1990 Nov;10(11):5857-64 [2172787] Nucleic Acids Res. 1990 Nov 11;18(21):6253-60 [2173824] J Virol. 1991 Mar;65(3):1605-10 [1847479] Oncogene. 1991 Apr;6(4):533-42 [1827665] J Virol. 1991 Jul;65(7):3468-74 [1645778] J Virol. 1991 Oct;65(10):5391-400 [1654447] Genes Dev. 1992 Mar;6(3):481-96 [1547944] Cell. 1992 May 29;69(5):751-7 [1591775] Cell Growth Differ. 1992 May;3(5):327-34 [1633115] Nucleic Acids Res. 1989 Jan 25;17(2):499-516 [2536920] Nucleic Acids Res. 1989 Feb 25;17(4):1459-74 [2537959] Nucleic Acids Res. 1983 Mar 11;11(5):1475-89 [6828386] N1 - Last updated - 2017-01-18 ER -