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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 19353014; 8733159 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. Images 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 PB - Oxford University Press, Oxford Journals, Great Clarendon Street VL - 21 IS - 11 SN - 0305-1048, 0305-1048 KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - Crystallin KW - Data processing KW - Cerebrum KW - Regulatory sequences KW - Transgenes KW - Muscles KW - Cardiac muscle KW - Spleen KW - Transgenic mice KW - alpha -Crystallin KW - Mutagenesis KW - Promoters KW - Gene deletion KW - Chloramphenicol O-acetyltransferase KW - Lung KW - Reporter gene KW - Transfection KW - Hybrids KW - CAT gene KW - Kidney KW - Liver KW - Mutation KW - J 02310:Genetics & Taxonomy KW - N 14845:Miscellaneous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19353014?accountid=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=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 revised - 2008-12-01 N1 - Last updated - 2015-03-27 N1 - SubjectsTermNotLitGenreText - Crystallin; Data processing; Cerebrum; Regulatory sequences; Transgenes; Muscles; Spleen; Cardiac muscle; Transgenic mice; alpha -Crystallin; Mutagenesis; Promoters; Chloramphenicol O-acetyltransferase; Gene deletion; Transfection; Reporter gene; Lung; Hybrids; CAT gene; Liver; Kidney; Mutation 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 - 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 - 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 - Nonpromoting 12-deoxyphorbol 13-esters inhibit phorbol 12-myristate 13-acetate induced tumor promotion in CD-1 mouse skin. AN - 75746033; 8495413 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 mumol 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 micrograms/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. JF - Cancer research AU - Szallasi, Z AU - Krsmanovic, L AU - Blumberg, P M AD - Molecular Mechanisms of Tumor Promotion Section, National Cancer Institute, NIH, Bethesda, Maryland 20892. Y1 - 1993/06/01/ PY - 1993 DA - 1993 Jun 01 SP - 2507 EP - 2512 VL - 53 IS - 11 SN - 0008-5472, 0008-5472 KW - Phorbol Esters KW - 0 KW - 9,10-Dimethyl-1,2-benzanthracene KW - 57-97-6 KW - 12-deoxyphorbolphenylacetate KW - 58821-98-0 KW - prostratin KW - 60857-08-1 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - Drug Administration Schedule KW - Dose-Response Relationship, Drug KW - Mice KW - Female KW - Phorbol Esters -- pharmacology KW - Papilloma -- prevention & control KW - Skin Neoplasms -- chemically induced KW - Phorbol Esters -- administration & dosage KW - Skin Neoplasms -- prevention & control KW - Papilloma -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75746033?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=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 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 - 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 - 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 - 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 - 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 - 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 - 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