TY - JOUR T1 - Electromyography in near-total laryngectomy. AN - 85407218; pmid-9708709 AB - OBJECTIVE: To investigate the dynamics of speech shunt muscle in patients with Pearson near-total laryngectomy by needle electromyography and correlation of ability to activate shunt muscle with speech production. DESIGN AND SETTINGS: Prospective study of patients with near-total laryngectomy at 2 hospital-based academic tertiary care centers. PARTICIPANTS AND INTERVENTION: Fourteen patients with near-total laryngectomy were subjected to percutaneous needle electromyographic study of the shunt muscle. MAIN OUTCOME MEASURES: Speech ability, electromyographic evidence of viable muscle in shunt wall, and ability to activate shunt muscle were recorded. RESULTS: Twelve of 14 patients had good speech; 11 had evidence of viable shunt muscle; and 9 were able to activate muscle by phonation, swallowing, or deep breathing, indicating preserved innervation. Six of the 12 patients with speech ability and 1 of the 2 patients without speech ability were able to recruit motor units during attempted phonation. CONCLUSIONS: Electromyography demonstrated viable muscle with retained innervation in 64% of the patients with near-total laryngectomy, proving its "dynamic" nature. However, the usefulness of shunt muscle activation in speech and prevention of aspiration needs further confirmation. JF - Archives of otolaryngology--head & neck surgery AU - Arunodaya, G R AU - Shenoy, A M AU - Premalata, S AD - Department of Neurology, National Institute of Mental Health and Neurosciences, Bangalore, India. Y1 - 1998/08// PY - 1998 DA - August 1998 SP - 857 EP - 860 VL - 124 IS - 8 SN - 0886-4470, 0886-4470 KW - Abridged Index Medicus; Index Medicus KW - National Library of Medicine KW - Prospective Studies KW - Humans KW - Adult KW - Laryngeal Neoplasms -- surgery KW - Aged KW - Middle Aged KW - Female KW - Male KW - Laryngectomy -- methods KW - Electromyography KW - Speech -- physiology KW - Laryngeal Muscles -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85407218?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+otolaryngology--head+%26+neck+surgery&rft.atitle=Electromyography+in+near-total+laryngectomy.&rft.au=Arunodaya%2C+G+R%3BShenoy%2C+A+M%3BPremalata%2C+S&rft.aulast=Arunodaya&rft.aufirst=G&rft.date=1998-08-01&rft.volume=124&rft.issue=8&rft.spage=857&rft.isbn=&rft.btitle=&rft.title=Archives+of+otolaryngology--head+%26+neck+surgery&rft.issn=08864470&rft_id=info:doi/ LA - English DB - ComDisDome N1 - Date revised - 2008-01-14 N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Functional coupling and regional activation of human cortical motor areas during simple, internally paced and externally paced finger movements. AN - 85228564; pmid-9712013 AB - We studied the activation and interaction of cortical motor regions during simple, internally paced and externally paced right-hand finger extensions in healthy volunteers. We recorded EEGs from 28 scalp electrodes and analysed task-related coherence, task-related power and movement-related cortical potentials. Task-related coherence reflects inter-regional functional coupling of oscillatory neuronal activity, task-related power reflects regional oscillatory activity of neuronal assemblies and movement-related cortical potentials reflect summated potentials of apical dendrites of pyramidal cells. A combination of these three analytical techniques allows comprehensive evaluation of different aspects of information processing in neuronal assemblies. For both externally and internally paced finger extensions, movement-related regional activation was predominant over the contralateral premotor and primary sensorimotor cortex, and functional coupling occurred between the primary sensorimotor cortex of both hemispheres and between the primary sensorimotor cortex and the mesial premotor areas, probably including the supplementary motor area. The main difference between the different types of movement pacing was enhanced functional coupling of central motor areas during internally paced finger extensions, particularly inter-hemispherically between the left and right primary sensorimotor cortexes and between the contralateral primary sensorimotor cortex and the mesial premotor areas. Internally paced finger extensions were also associated with additional regional (premovement) activation over the mesial premotor areas. The maximal task-related coherence differences between internally and externally paced finger extensions occurred in the frequency range of 20-22 Hz rather than in the range of maximal task-related power differences (9-11 Hz). This suggests that important aspects of information processing in the human motor system could be based on network-like oscillatory cortical activity and might be modulated on at least two levels, which to some extent can operate independently from each other: (i) regional activation (task-related power) and (ii) inter-regional functional coupling. We propose that internal pacing of movement poses higher demands on the motor system than external pacing, and that the motor system responds not only by increasing regional activation of the mesial premotor system, including the supplementary motor area, but also by enhancing information flow between lateral and mesial premotor and sensorimotor areas of both hemispheres, even if the movements are simple and unimanual. JF - Brain AU - Gerloff, C AU - Richard, J AU - Hadley, J AU - Schulman, A E AU - Honda, M AU - Hallett, M AD - Human Motor Control Section, Medical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-1428, USA. Y1 - 1998/08// PY - 1998 DA - August 1998 SP - 1513 EP - 1531 VL - 121 ( Pt 8) SN - 0006-8950, 0006-8950 KW - Human KW - Electroencephalography KW - Electromyography KW - Movement KW - Motor Cortex KW - Fingers KW - Brain Mapping KW - Evoked Potentials, Motor KW - Adult KW - Cues KW - Support, Non-U.S. Gov't KW - Middle Age KW - Periodicity KW - Male KW - Female KW - Reaction Time UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85228564?accountid=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&rft.atitle=Functional+coupling+and+regional+activation+of+human+cortical+motor+areas+during+simple%2C+internally+paced+and+externally+paced+finger+movements.&rft.au=Gerloff%2C+C%3BRichard%2C+J%3BHadley%2C+J%3BSchulman%2C+A+E%3BHonda%2C+M%3BHallett%2C+M&rft.aulast=Gerloff&rft.aufirst=C&rft.date=1998-08-01&rft.volume=121+%28+Pt+8%29&rft.issue=&rft.spage=1513&rft.isbn=&rft.btitle=&rft.title=Brain&rft.issn=00068950&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - A dominant negative mutant of the insulin-like growth factor-I receptor inhibits the adhesion, invasion, and metastasis of breast cancer. AN - 80057451; 9699666 AB - The 5-year survival rate for women with metastatic breast cancer is only 25-30%; thus, the need to improve treatment is apparent. Overexpression of insulin-like growth factor-I receptor (IGF-IR) correlates with poor prognosis and local recurrence. In this study, we addressed whether functional impairment of IGF-IR affects adhesion, invasion, and metastasis of breast cancer. Impairment of IGF-IR function was achieved by transfecting a dominant negative form of the receptor, termed 486stop, into MDA-MB-435 metastatic breast cancer cells. The protein product of 486stop is secreted extracellularly, resulting in a bystander effect. Cellular adhesion to laminin and collagen was inhibited 94 and 88%, respectively. Furthermore, 486stop inhibited insulin-like growth factor-I-stimulated invasion through collagen IV by 75%. The dominant negative receptor was secreted, as evidenced by the observation that MDA-MB-435 and MDA-MB-231 cells were prevented from binding to laminin by 90% when treated with conditioned medium (CM) from 486stop-transfected cells. CM also inhibited the invasion of MDA-MB-231 cells across collagen IV by 80%. Finally, CM made MDA-MB-231 cells 30% more sensitive to Taxol-induced cell death. Growth in soft agar was suppressed by 486stop, but growth in monolayer was unaffected. When injected into the mammary fat pad, 486stop did not significantly suppress growth of the primary tumor, but metastasis to the lungs, livers, lymph nodes, and lymph vessels was significantly decreased compared to the vector control. In conclusion, inhibition of IGF-IR resulted in suppression of adhesion, invasion, and metastasis, providing a mechanistic rationale for targeting IGF-IR in the treatment of metastatic breast cancer. JF - Cancer research AU - Dunn, S E AU - Ehrlich, M AU - Sharp, N J AU - Reiss, K AU - Solomon, G AU - Hawkins, R AU - Baserga, R AU - Barrett, J C AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1998/08/01/ PY - 1998 DA - 1998 Aug 01 SP - 3353 EP - 3361 VL - 58 IS - 15 SN - 0008-5472, 0008-5472 KW - Antineoplastic Agents, Phytogenic KW - 0 KW - Codon KW - Culture Media, Conditioned KW - Laminin KW - Insulin-Like Growth Factor I KW - 67763-96-6 KW - Collagen KW - 9007-34-5 KW - Receptor, IGF Type 1 KW - EC 2.7.10.1 KW - Paclitaxel KW - P88XT4IS4D KW - Index Medicus KW - Neoplasm Invasiveness KW - Insulin-Like Growth Factor I -- physiology KW - Laminin -- metabolism KW - Cell Adhesion -- physiology KW - Collagen -- metabolism KW - Humans KW - Antineoplastic Agents, Phytogenic -- pharmacology KW - Cell Division -- physiology KW - Paclitaxel -- pharmacology KW - Precipitin Tests KW - Signal Transduction -- physiology KW - Polymerase Chain Reaction KW - Tumor Cells, Cultured KW - Point Mutation KW - Neoplasm Metastasis KW - Female KW - Breast Neoplasms -- genetics KW - Receptor, IGF Type 1 -- physiology KW - Breast Neoplasms -- pathology KW - Receptor, IGF Type 1 -- genetics KW - Breast Neoplasms -- ultrastructure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80057451?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=A+dominant+negative+mutant+of+the+insulin-like+growth+factor-I+receptor+inhibits+the+adhesion%2C+invasion%2C+and+metastasis+of+breast+cancer.&rft.au=Dunn%2C+S+E%3BEhrlich%2C+M%3BSharp%2C+N+J%3BReiss%2C+K%3BSolomon%2C+G%3BHawkins%2C+R%3BBaserga%2C+R%3BBarrett%2C+J+C&rft.aulast=Dunn&rft.aufirst=S&rft.date=1998-08-01&rft.volume=58&rft.issue=15&rft.spage=3353&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 - 1998-08-27 N1 - Date created - 1998-08-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regulation of cyclin G1 during murine hepatic regeneration following Dipin-induced DNA damage. AN - 80053390; 9696022 AB - Cyclin G1 has been linked to both positive and negative growth regulation. The expression of cyclin G1 is induced by transforming growth factor beta1 and p53, as well as by multiple mitogenic stimuli in mammalian cells in culture. However, the physiological role of cyclin G1 remains unclear. To examine the cell-cycle regulation of cyclin G1 in vivo, two models of coordinated cell proliferation induced by partial hepatectomy (PH) in the presence or absence of DNA damage were used. To introduce DNA damage, mice were treated with the alkylating drug, 1,4-bis[N,N'-di(ethylene)-phosphamide]piperazine (Dipin) 2 hours before PH. Cell-cycle progression was monitored by 5-bromo-2-deoxyuridine (BrdU) incorporation into the DNA, the frequency of mitoses, the expression of cell-cycle control genes, and by flow cytometry. Dipin treatment resulted in cell-cycle arrest at the G2/M boundary without affecting G0/G1 and G1/S transitions. While the hepatocytes progressively entered G2 phase arrest, the cyclin G1 mRNA and protein levels increased more than five- and eightfold, respectively. Cyclin G1 had a nuclear localization in all interphase cells with clear absence from nucleoli. In contrast, during mitosis, cyclin G1 was undetectable by immunohistochemistry. Taken together, our data provide evidence for a putative role of cyclin G1 in G2/M checkpoint control. JF - Hepatology (Baltimore, Md.) AU - Jensen, M R AU - Factor, V M AU - Thorgeirsson, S S AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA. Y1 - 1998/08// PY - 1998 DA - August 1998 SP - 537 EP - 546 VL - 28 IS - 2 SN - 0270-9139, 0270-9139 KW - Aziridines KW - 0 KW - Ccnb1 protein, mouse KW - Ccng1 protein, mouse KW - Cyclin A KW - Cyclin B KW - Cyclin B1 KW - Cyclin G KW - Cyclin G1 KW - Cyclins KW - CDC2 Protein Kinase KW - EC 2.7.11.22 KW - dipin KW - L16KNK08VM KW - Index Medicus KW - Cyclin A -- metabolism KW - Mice, Inbred Strains KW - Animals KW - CDC2 Protein Kinase -- metabolism KW - Kinetics KW - Cyclin B -- metabolism KW - Mice KW - Tissue Distribution KW - Male KW - Liver -- cytology KW - Liver -- drug effects KW - DNA Damage KW - Liver -- metabolism KW - Cyclins -- metabolism KW - Liver Regeneration -- physiology KW - Aziridines -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80053390?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Regulation+of+cyclin+G1+during+murine+hepatic+regeneration+following+Dipin-induced+DNA+damage.&rft.au=Jensen%2C+M+R%3BFactor%2C+V+M%3BThorgeirsson%2C+S+S&rft.aulast=Jensen&rft.aufirst=M&rft.date=1998-08-01&rft.volume=28&rft.issue=2&rft.spage=537&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 - 1998-08-31 N1 - Date created - 1998-08-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Side effects of morphine administration in cancer patients. AN - 80043961; 9691512 AB - According to the World Health Organization (WHO) guidelines, oral morphine is the first choice drug for treating moderate to severe cancer-related pain. The fear of the side effects caused by this drug and the scarce information about prevention and management of these effects are the main reasons for the underuse of morphine. The aim of this paper is to provide a review of the literature on the side effects most frequently present both in the titration phase and during chronic administration of oral morphine and to describe the appropriate treatment. JF - Cancer nursing AU - Vanegas, G AU - Ripamonti, C AU - Sbanotto, A AU - De Conno, F AD - Pain Therapy and Palliative Care Division, National Cancer Institute, Milan, Italy. Y1 - 1998/08// PY - 1998 DA - August 1998 SP - 289 EP - 297 VL - 21 IS - 4 SN - 0162-220X, 0162-220X KW - Analgesics, Opioid KW - 0 KW - Morphine KW - 76I7G6D29C KW - Index Medicus KW - Nursing KW - Administration, Oral KW - Humans KW - Pain -- etiology KW - Pain -- drug therapy KW - Morphine -- therapeutic use KW - Neoplasms -- complications KW - Morphine -- adverse effects KW - Analgesics, Opioid -- therapeutic use KW - Analgesics, Opioid -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80043961?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Side+effects+of+morphine+administration+in+cancer+patients.&rft.au=Vanegas%2C+G%3BRipamonti%2C+C%3BSbanotto%2C+A%3BDe+Conno%2C+F&rft.aulast=Vanegas&rft.aufirst=G&rft.date=1998-08-01&rft.volume=21&rft.issue=4&rft.spage=289&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 - 1998-08-20 N1 - Date created - 1998-08-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Serum cotinine concentration and self-reported smoking during pregnancy. AN - 80043377; 9690362 AB - Although during pregnancy there is a better correlation between maternal serum cotinine concentration and adverse outcome than between self-reported smoking and such an outcome, few studies of pregnancy have measured cotinine concentration to determine how much a woman smokes. This study assessed the accuracy of self-reported smoking during pregnancy by performing serum cotinine assays on 448 women registered in the Collaborative Perinatal Project (1959-1966). Based on the assumption that a serum cotinine concentration of >10 ng/ml represented active smoking, 94.9% of women who denied smoking and 87.0% of women who stated that they smoked (kappa=0.83) reported their status accurately. Among smokers, the correlation coefficient between cotinine concentration and number of cigarettes smoked per day was 0.44. Serum cotinine concentration correlated more strongly than self-reported smoking with infant birth weight (r=0.246 vs. 0.200). In conclusion, this study showed that pregnant women accurately reported whether they smoked, but cotinine concentration was a better measure than self-report of the actual tobacco dose received. JF - American journal of epidemiology AU - Klebanoff, M A AU - Levine, R J AU - Clemens, J D AU - DerSimonian, R AU - Wilkins, D G AD - Division of Epidemiology, Statistics and Prevention Research, National Institute of Child Health and Human Development, National Instiutes of Health, Bethesda, MD 20892-7510, USA. Y1 - 1998/08/01/ PY - 1998 DA - 1998 Aug 01 SP - 259 EP - 262 VL - 148 IS - 3 SN - 0002-9262, 0002-9262 KW - Cotinine KW - K5161X06LL KW - Index Medicus KW - Reproducibility of Results KW - Humans KW - Gestational Age KW - Adult KW - Retrospective Studies KW - Infant, Newborn KW - Incidence KW - United States -- epidemiology KW - Immunoenzyme Techniques KW - Female KW - Pregnancy KW - Self Disclosure KW - Smoking -- blood KW - Cotinine -- blood KW - Smoking -- epidemiology KW - Maternal Exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80043377?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Biological+Chemistry&rft.atitle=Targeted+Disruption+of+the+Acid+alpha+-Glucosidase+Gene+in+Mice+Causes+an+Illness+with+Critical+Features+of+Both+Infantile+and+Adult+Human+Glycogen+Storage+Disease+Type+II&rft.au=Raben%2C+N%3BNagaraju%2C+K%3BLee%2C+E%3BKessler%2C+P%3BByrne%2C+B%3BLee%2C+L%3BLaMarca%2C+M%3BKing%2C+C%3BWard%2C+J%3BSauer%2C+B%3BPlotz%2C+P&rft.aulast=Raben&rft.aufirst=N&rft.date=1998-07-01&rft.volume=273&rft.issue=30&rft.spage=19086&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-08-14 N1 - Date created - 1998-08-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Neurotoxicity of interferon-alpha in melanoma therapy: results from a randomized controlled trial. AN - 80039014; 9690541 AB - The objective of this study was to evaluate the neurologic and quality of life impact of low dose adjuvant interferon (IFN)-alpha immunotherapy in patients with malignant melanoma metastatic to regional lymph nodes after radical surgery. One hundred and thirteen patients were randomized to receive IFN-alpha, 3 x 10(6) IU three times weekly by subcutaneous injection for 36 months or until melanoma recurrence (IFN group), or to act as controls (CTR group). Seventy-five of these patients (66%) entered the toxicity study and underwent formal neurologic, neuropsychologic, psychologic, and quality of life assessments. Patients were assessed at baseline and after 1, 3, 6, and 12 months of follow-up. For each variable, maximum worsening of symptoms from baseline was considered as a response variable. The differences between the two groups regarding this variable were evaluated by means of the Hodges-Lehmann median unbiased point estimates and their 95% confidence interval. A significant degree of action tremor was found in eight patients in the IFN group and in none of the controls. No differences were found during psychiatric evaluation and for cognitive tests. There was a greater increase in anxiety in the IFN group on both trait and state anxiety. With regard to quality of life the analysis showed a significant worsening of at most one level on only three questionnaire items and on the fatigue scale. Neurologic dysfunction associated with IFN therapy was mild. Psychiatric symptoms and neuropsychologic impairment were not found. Levels of fatigue and anxiety were increased in the IFN group but without a sizable impact on quality of life measures. JF - Cancer AU - Caraceni, A AU - Gangeri, L AU - Martini, C AU - Belli, F AU - Brunelli, C AU - Baldini, M AU - Mascheroni, L AU - Lenisa, L AU - Cascinelli, N AD - Pain Therapy and Palliative Care Division, National Cancer Institute of Milan, Italy. Y1 - 1998/08/01/ PY - 1998 DA - 1998 Aug 01 SP - 482 EP - 489 VL - 83 IS - 3 SN - 0008-543X, 0008-543X KW - Interferon-alpha KW - 0 KW - Recombinant Proteins KW - interferon alfa-2a KW - 47RRR83SK7 KW - Abridged Index Medicus KW - Index Medicus KW - Cognition Disorders -- etiology KW - Prospective Studies KW - Humans KW - Adult KW - Middle Aged KW - Male KW - Female KW - Anxiety -- etiology KW - Interferon-alpha -- adverse effects KW - Melanoma -- psychology KW - Brain -- drug effects KW - Melanoma -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80039014?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Neurotoxicity+of+interferon-alpha+in+melanoma+therapy%3A+results+from+a+randomized+controlled+trial.&rft.au=Caraceni%2C+A%3BGangeri%2C+L%3BMartini%2C+C%3BBelli%2C+F%3BBrunelli%2C+C%3BBaldini%2C+M%3BMascheroni%2C+L%3BLenisa%2C+L%3BCascinelli%2C+N&rft.aulast=Caraceni&rft.aufirst=A&rft.date=1998-08-01&rft.volume=83&rft.issue=3&rft.spage=482&rft.isbn=&rft.btitle=&rft.title=Cancer&rft.issn=0008543X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-08-13 N1 - Date created - 1998-08-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - POU transcription factors control expression of CNS stem cell-specific genes. AN - 80026120; 9671582 AB - Multipotential stem cells throughout the developing central nervous system have common properties. Among these is expression of the intermediate filament protein nestin and the brain fatty acid binding protein (B-FABP). To determine if common mechanisms control transcription in CNS stem cells, the regulatory elements of these two genes were mapped in transgenic mice. A 257 basepair enhancer of the rat nestin gene is sufficient for expression throughout the embryonic neuroepithelium. This enhancer contains two sites bound by the class III POU proteins Brn-1, Brn-2, Brn-4, and Tst-1. Only one of the two POU sites is required for CNS expression. An adjacent hormone response element is necessary for expression in the dorsal midbrain and forebrain. The regulatory sites of the B-FABP gene are strikingly similar to those of the nestin gene. A hybrid POU/Pbx binding site is recognized in vitro by Pbx-1, Brn-1 and Brn-2. This site is essential for expression in most of the CNS. In addition, a hormone response element is necessary for forebrain expression. Both the nestin and B-FABP genes therefore depend on POU binding sites for general CNS expression, with hormone response elements additionally required for activity in the anterior CNS. These data indicate that regulation by POU proteins and hormone receptors is a general mechanism for CNS stem cell-specific transcription. JF - Development (Cambridge, England) AU - Josephson, R AU - Müller, T AU - Pickel, J AU - Okabe, S AU - Reynolds, K AU - Turner, P A AU - Zimmer, A AU - McKay, R D AD - Laboratory of Molecular Biology, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892-4157, USA. Y1 - 1998/08// PY - 1998 DA - August 1998 SP - 3087 EP - 3100 VL - 125 IS - 16 SN - 0950-1991, 0950-1991 KW - Carrier Proteins KW - 0 KW - Fabp5 protein, mouse KW - Fabp7 protein, mouse KW - Fabp7 protein, rat KW - Fatty Acid-Binding Protein 7 KW - Fatty Acid-Binding Proteins KW - Intermediate Filament Proteins KW - Myelin P2 Protein KW - Neoplasm Proteins KW - Nerve Tissue Proteins KW - Nes protein, mouse KW - Nes protein, rat KW - Nestin KW - Transcription Factors KW - Index Medicus KW - Animals KW - DNA Mutational Analysis KW - Mice KW - Mutagenesis -- genetics KW - Histocytochemistry KW - Nerve Tissue Proteins -- genetics KW - Mice, Transgenic KW - Base Sequence KW - DNA Footprinting KW - Molecular Sequence Data KW - Enhancer Elements, Genetic -- genetics KW - Genes, Reporter KW - Promoter Regions, Genetic -- genetics KW - Binding Sites -- genetics KW - Transcription Factors -- physiology KW - Intermediate Filament Proteins -- genetics KW - Central Nervous System -- growth & development KW - Gene Expression Regulation, Developmental -- genetics KW - Carrier Proteins -- genetics KW - Stem Cells -- physiology KW - Myelin P2 Protein -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80026120?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Development+%28Cambridge%2C+England%29&rft.atitle=POU+transcription+factors+control+expression+of+CNS+stem+cell-specific+genes.&rft.au=Josephson%2C+R%3BM%C3%BCller%2C+T%3BPickel%2C+J%3BOkabe%2C+S%3BReynolds%2C+K%3BTurner%2C+P+A%3BZimmer%2C+A%3BMcKay%2C+R+D&rft.aulast=Josephson&rft.aufirst=R&rft.date=1998-08-01&rft.volume=125&rft.issue=16&rft.spage=3087&rft.isbn=&rft.btitle=&rft.title=Development+%28Cambridge%2C+England%29&rft.issn=09501991&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-09-28 N1 - Date created - 1998-09-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Novel benztropine [3a-(diphenylmethoxy)tropane] analogs as probes for the dopamine transporter. AN - 80019225; 9668197 AB - The design, synthesis and pharmacological evaluation of novel dopamine transporter ligands, based on Benztropine [3a-(diphenylmethoxy) tropane], has been a focus of our research efforts toward the development of novel cocaine-abuse pharmacotherapeutics. Structure-activity relationships at the dopamine transporter, for this series of compounds, have been derived and compared to those of cocaine and GBR 12909. These studies suggest that structurally diverse dopamine uptake inhibitors may access different binding domains on the dopamine transporter. The distinctive behavioral profile displayed in this series of compounds, as compared to cocaine and other dopamine uptake inhibitors, is of particular interest and is proposed to be relevant to the pharmacodynamic and pharmacokinetic properties of this class of tropane-based molecules. JF - Current medicinal chemistry AU - Newman, A H AU - Agoston, G E AD - Psychobiology Section, National Institute on Drug Abuse - Intramural Research Program, National Institutes of Health, 5500 Nathan Shock Drive, Baltimore, Maryland 21224, USA. Y1 - 1998/08// PY - 1998 DA - August 1998 SP - 305 EP - 319 VL - 5 IS - 4 SN - 0929-8673, 0929-8673 KW - Carrier Proteins KW - 0 KW - Dopamine Plasma Membrane Transport Proteins KW - Dopamine Uptake Inhibitors KW - Membrane Glycoproteins KW - Membrane Transport Proteins KW - Nerve Tissue Proteins KW - Piperazines KW - Benztropine KW - 1NHL2J4X8K KW - vanoxerine KW - 90X28IKH43 KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Stereoisomerism KW - Humans KW - Drug Design KW - Cocaine -- adverse effects KW - Structure-Activity Relationship KW - Carrier Proteins -- drug effects KW - Substance-Related Disorders -- etiology KW - Benztropine -- analogs & derivatives KW - Substance-Related Disorders -- drug therapy KW - Piperazines -- pharmacology KW - Dopamine Uptake Inhibitors -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80019225?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+medicinal+chemistry&rft.atitle=Novel+benztropine+%5B3a-%28diphenylmethoxy%29tropane%5D+analogs+as+probes+for+the+dopamine+transporter.&rft.au=Newman%2C+A+H%3BAgoston%2C+G+E&rft.aulast=Newman&rft.aufirst=A&rft.date=1998-08-01&rft.volume=5&rft.issue=4&rft.spage=305&rft.isbn=&rft.btitle=&rft.title=Current+medicinal+chemistry&rft.issn=09298673&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-10-27 N1 - Date created - 1998-10-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of single benzo[a]pyrene diol epoxide-deoxyguanosine adducts on the action of DNA polymerases in vitro. AN - 80006274; 9664121 AB - Neither Sequenase 2.0 nor Klenow fragment were able to extend 12-mer primers using the eight templates (16-mers) derived by placing each of the four isomeric benzo[a]pyrene diol epoxide-deoxyguanosine adducts at the 13th nucleotide from the 3'-end of two different sequence contexts. Using an 11-mer primer to get a running start did not overcome the adduct induced block of primer extension except for the Klenow fragment and one of the two sequence contexts, indicating primer extension is dependent on both the polymerase and sequence context. In this case, purine nucleoside triphosphates (dATP>dGTP) were incorporated opposite each of the four adducts. JF - International journal of oncology AU - Lipinski, L J AU - Ross, H L AU - Zajc, B AU - Sayer, J M AU - Jerina, D M AU - Dipple, A AD - Laboratory of Molecular Genetics, National Institute on Aging, NIH, Baltimore, MD 21224, USA. Y1 - 1998/08// PY - 1998 DA - August 1998 SP - 269 EP - 273 VL - 13 IS - 2 SN - 1019-6439, 1019-6439 KW - DNA Adducts KW - 0 KW - Oligonucleotides 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 - DNA Polymerase I KW - EC 2.7.7.- KW - Deoxyguanosine KW - G9481N71RO KW - Index Medicus KW - Templates, Genetic KW - Oligonucleotides -- metabolism KW - Mutation KW - DNA Replication KW - 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide -- metabolism KW - Deoxyguanosine -- metabolism KW - DNA Polymerase I -- metabolism KW - DNA Adducts -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80006274?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+journal+of+oncology&rft.atitle=Effect+of+single+benzo%5Ba%5Dpyrene+diol+epoxide-deoxyguanosine+adducts+on+the+action+of+DNA+polymerases+in+vitro.&rft.au=Lipinski%2C+L+J%3BRoss%2C+H+L%3BZajc%2C+B%3BSayer%2C+J+M%3BJerina%2C+D+M%3BDipple%2C+A&rft.aulast=Lipinski&rft.aufirst=L&rft.date=1998-08-01&rft.volume=13&rft.issue=2&rft.spage=269&rft.isbn=&rft.btitle=&rft.title=International+journal+of+oncology&rft.issn=10196439&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-08-14 N1 - Date created - 1998-08-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Localization of endogenous ARF6 to sites of cortical actin rearrangement and involvement of ARF6 in cell spreading. AN - 80002693; 9664047 AB - To study the function of the endogenous ARF6 GTP binding protein in cells, we generated an antibody which specifically recognizes ARF6, and not the other ARF proteins. Using this antibody, ARF6 was detected in all mouse organs tested and in a variety of cultured cell lines including RBL, MDCK, NRK, BHK, COS, and HeLa cells. In NRK cells, by immunofluorescence, ARF6 localized to the plasma membrane, especially at regions exhibiting membrane ruffling, and was also concentrated in a fine punctate distribution in the juxtanuclear region. This pattern of localization of the endogenous protein was similar to the localization of ARF6 when overexpressed in NRK, or HeLa, cells. Treatments which perturb cortical actin in NRK cells, such as replating of cells after trypsinization or treatment with phorbol ester, resulted in the recruitment of endogenous ARF6 to the regions of cortical actin rearrangement. ARF6 activation and subsequent membrane recycling was required for cell spreading activity since expression of the dominant-negative, GTP-binding defective mutant of ARF6, T27N, previously shown to inhibit ARF6-regulated membrane recycling, inhibited cell attachment and spreading in HeLa cells. Furthermore, phorbol ester treatment enhanced the cell spreading activities in NRK cells, and in HeLa cells, but was not observed in cells expressing T27N. Taken together, these observations support a role for endogenous ARF6 in modeling the plasma membrane and cortical actin cytoskeleton. JF - Journal of cell science AU - Song, J AU - Khachikian, Z AU - Radhakrishna, H AU - Donaldson, J G AD - Laboratory of Cell Biology, NHLBI, Bld 3, Room B1-22, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1998/08// PY - 1998 DA - August 1998 SP - 2257 EP - 2267 VL - 111 ( Pt 15) SN - 0021-9533, 0021-9533 KW - Actins KW - 0 KW - Cytochalasin D KW - 22144-77-0 KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - ADP-Ribosylation Factors KW - EC 3.6.5.2 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - Cell Adhesion -- physiology KW - Humans KW - Organ Specificity KW - Amino Acid Sequence KW - Mice KW - Antibody Specificity KW - Transfection KW - Molecular Sequence Data KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Cell Membrane -- chemistry KW - Cytochalasin D -- pharmacology KW - Actin Cytoskeleton KW - Cell Line KW - Cell Size -- physiology KW - Actins -- metabolism KW - GTP-Binding Proteins -- physiology KW - GTP-Binding Proteins -- analysis KW - GTP-Binding Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80002693?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+cell+science&rft.atitle=Localization+of+endogenous+ARF6+to+sites+of+cortical+actin+rearrangement+and+involvement+of+ARF6+in+cell+spreading.&rft.au=Song%2C+J%3BKhachikian%2C+Z%3BRadhakrishna%2C+H%3BDonaldson%2C+J+G&rft.aulast=Song&rft.aufirst=J&rft.date=1998-08-01&rft.volume=111+%28+Pt+15%29&rft.issue=&rft.spage=2257&rft.isbn=&rft.btitle=&rft.title=Journal+of+cell+science&rft.issn=00219533&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-09-17 N1 - Date created - 1998-09-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The effect of exercise training in cold on shivering and nonshivering thermogenesis in adult and aged C57BL/6J mice. AN - 73983327; 9762524 AB - To understand the mechanisms of improvement of cold-induced heat production in aged mice following exercise training, the relative contributions of shivering and nonshivering thermogenesis to cold-induced metabolic responses were assessed in adult and aged C57BL/6J male mice, which inhabited sedentarily at room temperature, or were subjected either to a regimen of moderate intensity exercise training at 6 degrees C, or to sedentary repeated exposures to the same temperature. The main findings were that (1) aged mice had greater cold-induced nonshivering thermogenesis, but lower shivering than adult mice; (2) exercise training in a cold environment enhanced cold-induced nonshivering thermogenesis in adult mice, but suppressed it in aged animals; (3) exercise training in a cold environment increased shivering thermogenesis in both age groups, but this increase was much greater in aged mice; (4) the increase of cold-induced shivering thermogenesis was mainly responsible for increased cold tolerance in aged mice after exercise training in a cold environment. JF - Experimental gerontology AU - Shefer, V I AU - Talan, M I AD - Laboratory of Behavioral Sciences, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA. Y1 - 1998/08// PY - 1998 DA - August 1998 SP - 467 EP - 476 VL - 33 IS - 5 SN - 0531-5565, 0531-5565 KW - Anesthetics KW - 0 KW - Neuromuscular Nondepolarizing Agents KW - Urethane KW - 3IN71E75Z5 KW - Vecuronium Bromide KW - 7E4PHP5N1D KW - Index Medicus KW - Animals KW - Analysis of Variance KW - Oxygen Consumption -- drug effects KW - Anesthetics -- pharmacology KW - Body Temperature -- drug effects KW - Body Weight -- physiology KW - Mice KW - Vecuronium Bromide -- pharmacology KW - Oxygen Consumption -- physiology KW - Mice, Inbred C57BL KW - Body Temperature -- physiology KW - Urethane -- pharmacology KW - Neuromuscular Nondepolarizing Agents -- pharmacology KW - Male KW - Aging -- physiology KW - Physical Conditioning, Animal -- physiology KW - Body Temperature Regulation -- physiology KW - Cold Temperature KW - Shivering -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73983327?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+effect+of+exercise+training+in+cold+on+shivering+and+nonshivering+thermogenesis+in+adult+and+aged+C57BL%2F6J+mice.&rft.au=Shefer%2C+V+I%3BTalan%2C+M+I&rft.aulast=Shefer&rft.aufirst=V&rft.date=1998-08-01&rft.volume=33&rft.issue=5&rft.spage=467&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 - 1998-12-03 N1 - Date created - 1998-12-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The eosinophil ribonucleases. AN - 73970978; 9760988 AB - The eosinophil ribonucleases, eosinophilderived neurotoxin (EDN/RNase 2) and eosinophil cationic protein (ECP/RNase 3) are two closely related proteins with intriguing functional and evolutionary properties. While both EDN and ECP maintain the structural and catalytic residues typical of the RNase A superfamily, the role of ribonuclease activity in the physiologic function of these proteins remains unclear. The biochemistry and physiology of EDN, ECP and the recently discovered ribonuclease k6 (RNase 6) will be reviewed in this chapter. JF - Cellular and molecular life sciences : CMLS AU - Rosenberg, H F AD - Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. hr2k@nih.gov Y1 - 1998/08// PY - 1998 DA - August 1998 SP - 795 EP - 803 VL - 54 IS - 8 SN - 1420-682X, 1420-682X KW - Ribonucleases KW - EC 3.1.- KW - Index Medicus KW - History of medicine KW - Phylogeny KW - Animals KW - History, 20th Century KW - Humans KW - Molecular Sequence Data KW - History, 19th Century KW - Amino Acid Sequence KW - Sequence Homology, Amino Acid KW - Ribonucleases -- history KW - Ribonucleases -- physiology KW - Eosinophils -- enzymology KW - Ribonucleases -- chemistry KW - Eosinophils -- ultrastructure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73970978?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cellular+and+molecular+life+sciences+%3A+CMLS&rft.atitle=The+eosinophil+ribonucleases.&rft.au=Rosenberg%2C+H+F&rft.aulast=Rosenberg&rft.aufirst=H&rft.date=1998-08-01&rft.volume=54&rft.issue=8&rft.spage=795&rft.isbn=&rft.btitle=&rft.title=Cellular+and+molecular+life+sciences+%3A+CMLS&rft.issn=1420682X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-10-22 N1 - Date created - 1998-10-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chemopreventive effects of the aromatase inhibitor vorozole (R 83842) in the methylnitrosourea-induced mammary cancer model. AN - 73949832; 9744527 AB - The chemopreventive activity of the highly specific nonsteroidal aromatase inhibitor, vorozole, was examined in the methylnitrosourea (MNU)-induced rat model of mammary carcinogenesis. Various doses of vorozole (0.08-1.25 mg/kg body wt/day) were administered daily (by gavage) to female Sprague-Dawley rats starting at 43 days of age. Seven days later, the rats were given a single i.v. dose of MNU (50 mg/kg body wt). Rats were continually treated with vorozole until the end of the experiment (120 days post-MNU). Vorozole caused a dose dependent inhibition of mammary cancer multiplicity. The highest dose of vorozole (1.25 mg/kg body wt/day) decreased cancer multiplicity by approximately 90%, and simultaneously decreased cancer incidence from 100 to 44%. The next two highest doses of vorozole (0.63 and 0.31 mg/kg body wt/day) inhibited MNU-induced mammary cancer multiplicity by 70-80%. Even the two lowest doses of vorozole (0.16 and 0.08 mg/kg body wt/ day) decreased cancer multiplicity -50%. Serum level determinations were performed on a variety of endpoints at either 4 or 24 h following the last dose of vorozole. Insulin-like growth factor (IGF)-1 levels were slightly, but significantly, increased by vorozole treatment. Vorozole induced striking increases in serum testosterone levels at 4 h at all the dose levels employed. Testosterone levels were significantly elevated over controls at 24 h in rats given the lower doses of vorozole (0.08-0.31 mg/kg body wt/day), but were significantly lower than in rats administered the higher doses of vorozole (0.63 or 1.25 mg/kg body wt/ day). This result presumably reflects the limited half-life of vorozole in rats. In a second series of experiments, the effects of limited duration of dosing with vorozole (2.5 mg/kg body wt/day) or intermittent dosing with vorozole were determined. Treatment of rats with vorozole for limited time periods, from 3 days post-MNU administration until 30 or 60 days post-MNU treatment, resulted in significant delays in the time to appearance of palpable cancers. However, these limited treatments did not greatly affect the overall incidence or multiplicity of mammary cancers when compared with the MNU controls at the end of the study (150 days post-MNU). Finally, the effects of intermittent dosing with vorozole (2.5 mg/kg body wt/day) were examined. Rats were administered cycles of vorozole daily for a period of 3 weeks followed by treatment with the vorozole vehicle for the next 3 weeks (total of four cycles). Although this intermittent treatment did inhibit the appearance of new tumors during each of the periods that vorozole was administered, it did not cause regression of palpable cancers. JF - Carcinogenesis AU - Lubet, R A AU - Steele, V E AU - DeCoster, R AU - Bowden, C AU - You, M AU - Juliana, M M AU - Eto, I AU - Kelloff, G J AU - Grubbs, C J AD - NCI-DCP, Bethesda, MD 20892, USA. lubetr@dcpcepn.nci.nih.gov Y1 - 1998/08// PY - 1998 DA - August 1998 SP - 1345 EP - 1351 VL - 19 IS - 8 SN - 0143-3334, 0143-3334 KW - Antineoplastic Agents KW - 0 KW - Aromatase Inhibitors KW - Carcinogens KW - Triazoles KW - vorozole KW - 1E2S9YXV2A KW - Testosterone KW - 3XMK78S47O KW - Estradiol KW - 4TI98Z838E KW - Insulin-Like Growth Factor I KW - 67763-96-6 KW - Methylnitrosourea KW - 684-93-5 KW - Index Medicus KW - Animals KW - Drug Screening Assays, Antitumor KW - Drug Administration Schedule KW - Genes, ras -- drug effects KW - Insulin-Like Growth Factor I -- metabolism KW - Estrus -- drug effects KW - Rats KW - Rats, Sprague-Dawley KW - Estradiol -- blood KW - Testosterone -- blood KW - Body Weight -- drug effects KW - Female KW - Mammary Neoplasms, Experimental -- chemically induced KW - Antineoplastic Agents -- administration & dosage KW - Triazoles -- therapeutic use KW - Mammary Neoplasms, Experimental -- prevention & control KW - Antineoplastic Agents -- therapeutic use KW - Mammary Neoplasms, Experimental -- blood KW - Triazoles -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73949832?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Pigment+epithelium-derived+factor+%28PEDF%29+differentially+protects+immature+but+not+mature+cerebellar+granule+cells+against+apoptotic+cell+death.&rft.au=Araki%2C+T%3BTaniwaki%2C+T%3BBecerra%2C+S+P%3BChader%2C+G+J%3BSchwartz%2C+J+P&rft.aulast=Araki&rft.aufirst=T&rft.date=1998-07-01&rft.volume=53&rft.issue=1&rft.spage=7&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 - 1998-09-24 N1 - Date created - 1998-09-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Differences in kinetics of induction and reversibility of TCDD-induced changes in cell proliferation and CYP1A1 expression in female Sprague-Dawley rat liver. AN - 73920008; 9744539 AB - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent tumor promoter in two-stage initiation-promotion models and induces cell proliferation and development of enzyme-altered hepatic foci. It is believed that increased cell proliferation is a necessary step in carcinogenesis. Therefore, the analysis of the effect of TCDD on cell proliferation in rat liver may aid in the understanding of the mechanism of hepatocarcinogenesis induced by TCDD. The aim of this study was to investigate the time course and reversibility of cell proliferation in non-initiated and diethylnitrosamine-initiated female rats exposed biweekly to a daily averaged dose of 125 ng TCDD/kg/day for up to 60 weeks. In addition we evaluated the suitability of different dose metrics for the evaluation of TCDD-induced changes in cell proliferation and CYP1A1 enzyme induction. Cell proliferation was measured as the incorporation of 5-bromo-2'-deoxyuridine (BrdU) into hepatocytes undergoing replicative DNA synthesis. Mean BrdU labeling indices in TCDD-treated animals were not increased over controls after 14 weeks exposure, but were increased 8- and 2-fold after 30 and 60 weeks' treatment respectively, despite similar liver levels of TCDD at all these times (23-30 p.p.b.). In comparison, CYP1A1 activity, as measured by ethoxyresorufin deethylase activity, was significantly induced at all times points analyzed. Sixteen weeks following cessation of TCDD treatment, labeling indices were still significantly elevated over controls, but after 30 weeks of withdrawal, labeling indices were no different from controls, indicating that TCDD-induced changes in cell proliferation were reversible. Dosimetric analysis indicated that rat liver tissue burden was suitable for prediction of CYP1A1 expression but not cell proliferation and that the area under the curve was unsuitable for prediction of both TCDD-induced changes in CYP1A1 expression and cell proliferation. JF - Carcinogenesis AU - Walker, N J AU - Miller, B D AU - Kohn, M C AU - Lucier, G W AU - Tritscher, A M AD - Laboratory of Computational Biology and Risk Analysis, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. walker3@niehs.nih.gov Y1 - 1998/08// PY - 1998 DA - August 1998 SP - 1427 EP - 1435 VL - 19 IS - 8 SN - 0143-3334, 0143-3334 KW - Carcinogens KW - 0 KW - Polychlorinated Dibenzodioxins KW - Diethylnitrosamine KW - 3IQ78TTX1A KW - Cytochrome P-450 CYP1A1 KW - EC 1.14.14.1 KW - Bromodeoxyuridine KW - G34N38R2N1 KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - ROC Curve KW - Cell Division -- drug effects KW - Enzyme Induction KW - Female KW - Organ Size -- drug effects KW - Bromodeoxyuridine -- metabolism KW - Liver -- drug effects KW - Polychlorinated Dibenzodioxins -- toxicity KW - Liver -- metabolism KW - Cytochrome P-450 CYP1A1 -- metabolism KW - Polychlorinated Dibenzodioxins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73920008?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Differences+in+kinetics+of+induction+and+reversibility+of+TCDD-induced+changes+in+cell+proliferation+and+CYP1A1+expression+in+female+Sprague-Dawley+rat+liver.&rft.au=Walker%2C+N+J%3BMiller%2C+B+D%3BKohn%2C+M+C%3BLucier%2C+G+W%3BTritscher%2C+A+M&rft.aulast=Walker&rft.aufirst=N&rft.date=1998-08-01&rft.volume=19&rft.issue=8&rft.spage=1427&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-09-24 N1 - Date created - 1998-09-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Induction of hepatic CYP1A in channel catfish increases binding of 2-aminoanthracene to DNA in vitro and in vivo. AN - 73914562; 9744548 AB - Data are presented from in vitro and in vivo studies that indicate cytochrome P4501A (CYP1A) in channel catfish (Ictalurus punctatus) hepatic tissue activates 2-amino-anthracene (AA) to a reactive metabolite that binds to DNA. Channel catfish were injected i.p. with vehicle or 10 mg/kg beta-naphthoflavone (betaNF) on two consecutive days. Two days after the final injection of vehicle or betaNF, vehicle or [3H]AA was injected i.p. at 10 mg/kg, creating four different treatments: vehicle only, betaNF only, [3H]AA only, and betaNF/[3H]AA. Hepatic tissue was examined for CYP1A-associated ethoxyresorufin-O-de-ethylase (EROD) activity, and for DNA adducts at 1, 2, 4 and 7 days following administration of vehicle or [3H]AA. Hepatic EROD activity in betaNF-treated fish was 17-fold higher at day 0 and remained significantly greater than untreated animals for the 7-day experiment. Hepatic DNA adducts, as measured by tritium-associated DNA, ranged from 4.8 to 8.6 pmol/mg DNA in vehicle-pretreated fish injected with [3H]AA, but ranged from 12.6 to 22.7 pmol/mg DNA in betaNF-pretreated fish injected with [3H]AA. Thus, pretreatment with betaNF significantly increased binding of [3H]AA to hepatic DNA in vivo at all four times. Analysis by 32P-post-labeling and thin layer chromatography of hepatic DNA from channel catfish treated with AA revealed two major and several minor spots, which are indicative of DNA adduct formation. Hepatic microsomes from betaNF-pretreated fish were more effective at catalysing the binding of [3H]AA to DNA in vitro than were microsomes from non-treated fish. In addition, binding was decreased by the CYP1A inhibitor 3,3',4,4'-tetrachlorobiphenyl. Collectively, these data demonstrate that CYP1A is involved in the activation of AA in channel catfish. JF - Carcinogenesis AU - Watson, D E AU - Reichert, W AU - Di Giulio, R T AD - Ecotoxicology Laboratory, Nicholas School of the Environment, Duke University, Durham, NC 27708-0328, USA. watson2@niehs.nih.gov Y1 - 1998/08// PY - 1998 DA - August 1998 SP - 1495 EP - 1501 VL - 19 IS - 8 SN - 0143-3334, 0143-3334 KW - Anthracenes KW - 0 KW - Carcinogens KW - DNA Adducts KW - Enzyme Inhibitors KW - beta-Naphthoflavone KW - 6051-87-2 KW - 2-anthramine KW - 8240818JGU KW - DNA KW - 9007-49-2 KW - Cytochrome P-450 CYP1A1 KW - EC 1.14.14.1 KW - Index Medicus KW - Animals KW - Ictaluridae KW - Biotransformation KW - beta-Naphthoflavone -- pharmacology KW - Enzyme Inhibitors -- pharmacology KW - Enzyme Induction KW - Time Factors KW - DNA Adducts -- metabolism KW - Carcinogens -- metabolism KW - Anthracenes -- metabolism KW - Microsomes, Liver -- metabolism KW - DNA -- metabolism KW - Microsomes, Liver -- drug effects KW - Cytochrome P-450 CYP1A1 -- metabolism KW - DNA -- drug effects KW - Cytochrome P-450 CYP1A1 -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73914562?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Induction+of+hepatic+CYP1A+in+channel+catfish+increases+binding+of+2-aminoanthracene+to+DNA+in+vitro+and+in+vivo.&rft.au=Watson%2C+D+E%3BReichert%2C+W%3BDi+Giulio%2C+R+T&rft.aulast=Watson&rft.aufirst=D&rft.date=1998-08-01&rft.volume=19&rft.issue=8&rft.spage=1495&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-09-24 N1 - Date created - 1998-09-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pediatric psychopharmacology and the interaction between drugs and the developing brain. AN - 73909353; 9729684 AB - With increasing frequency, psychotropic medications are being prescribed to young children, often for long periods of time. The interaction between psychotropics and the developing brain has not been systematically investigated in humans. Data collected from animals suggest that developing neurotransmitter systems can be exquisitely sensitive to early inhibition or stimulation by pharmacological agents, which can lead to permanent changes in adult life. Most of these data are collected from rodents, and their extrapolation to humans is difficult. More relevant models could be developed for instance using primates. In humans, the focus of research has traditionally been on the possible teratogenic effects of prenatal drug exposure. Recently introduced quantitative imaging techniques can offer new approaches to studying the effects of psychotropics on the developing brain. This research has clear implications for the safety and efficacy of psychopharmacologic drug in children. JF - Canadian journal of psychiatry. Revue canadienne de psychiatrie AU - Vitiello, B AD - Child and Adolescent Treatment and Preventive Intervention Research Branch, National Institute of Mental Health, Rockville, MD 20857, USA. bvitiell@nih.gov Y1 - 1998/08// PY - 1998 DA - August 1998 SP - 582 EP - 584 VL - 43 IS - 6 SN - 0706-7437, 0706-7437 KW - Psychotropic Drugs KW - 0 KW - Index Medicus KW - Animals KW - Age Factors KW - Pediatrics KW - Humans KW - Child KW - Neural Pathways -- growth & development KW - Child Psychiatry KW - Neural Pathways -- drug effects KW - Psychotropic Drugs -- pharmacology KW - Brain -- drug effects KW - Child Development -- drug effects KW - Brain -- growth & development UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73909353?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Canadian+journal+of+psychiatry.+Revue+canadienne+de+psychiatrie&rft.atitle=Pediatric+psychopharmacology+and+the+interaction+between+drugs+and+the+developing+brain.&rft.au=Vitiello%2C+B&rft.aulast=Vitiello&rft.aufirst=B&rft.date=1998-08-01&rft.volume=43&rft.issue=6&rft.spage=582&rft.isbn=&rft.btitle=&rft.title=Canadian+journal+of+psychiatry.+Revue+canadienne+de+psychiatrie&rft.issn=07067437&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-01-26 N1 - Date created - 1999-01-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characterization of the human dihydropyrimidine dehydrogenase gene. AN - 73889291; 9721209 AB - Dihydropyrimidine dehydrogenase (DPD) catabolizes endogenous pyrimidines and pyrimidine-based antimetabolite drugs. A deficiency in human DPD is associated with congenital thymine-uraciluria in pediatric patients and severe 5-fluorouracil toxicity in cancer patients. The dihydropyrimidine dehydrogenase gene (DPYD) was isolated, and its physical map and exon-intron organization were determined by analysis of P1, PAC, BAC, and YAC clones. The DPYD gene was found to contain 23 exons ranging in size from 69 bp (exon 15) to 961 bp (exon 23). A physical map derived from a YAC clone indicated that DPYD is at least 950 kb in length with 3 kb of coding sequence and an average intron size of about 43 kb. The previously reported 5' donor splice site mutation present in pediatric thymine-uraciluria and cancer patients can now be assigned to exon 14. All 23 exons were sequenced from a series of human DNA samples, and three point mutations were identified in three racial groups as G1601A (exon 13, Ser534Asn), A1627G (exon 13, Ile543Val), and G2194A (exon 18, Val732Ile). These studies, which have established that the DPYD gene is unusually large, lay a framework for uncovering new mutations that are responsible for thymine-uraciluria and toxicity to fluoropyrimidine drugs. Copyright 1998 Academic Press. JF - Genomics AU - Wei, X AU - Elizondo, G AU - Sapone, A AU - McLeod, H L AU - Raunio, H AU - Fernandez-Salguero, P AU - Gonzalez, F J AD - National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/08/01/ PY - 1998 DA - 1998 Aug 01 SP - 391 EP - 400 VL - 51 IS - 3 SN - 0888-7543, 0888-7543 KW - Neoplasm Proteins KW - 0 KW - RNA, Messenger KW - Uracil KW - 56HH86ZVCT KW - Oxidoreductases KW - EC 1.- KW - Dihydrouracil Dehydrogenase (NADP) KW - EC 1.3.1.2 KW - Thymine KW - QR26YLT7LT KW - Fluorouracil KW - U3P01618RT KW - Index Medicus KW - Point Mutation -- genetics KW - Thymine -- urine KW - Humans KW - RNA, Messenger -- genetics KW - Introns -- genetics KW - Cloning, Molecular KW - Exons -- genetics KW - Leukocytes -- enzymology KW - RNA Splicing -- genetics KW - Polymerase Chain Reaction KW - Alleles KW - Fluorouracil -- toxicity KW - Restriction Mapping KW - Neoplasm Proteins -- genetics KW - Gene Dosage KW - Uracil -- urine KW - Oxidoreductases -- genetics KW - Oxidoreductases -- deficiency UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73889291?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Characterization+of+the+human+dihydropyrimidine+dehydrogenase+gene.&rft.au=Wei%2C+X%3BElizondo%2C+G%3BSapone%2C+A%3BMcLeod%2C+H+L%3BRaunio%2C+H%3BFernandez-Salguero%2C+P%3BGonzalez%2C+F+J&rft.aulast=Wei&rft.aufirst=X&rft.date=1998-08-01&rft.volume=51&rft.issue=3&rft.spage=391&rft.isbn=&rft.btitle=&rft.title=Genomics&rft.issn=08887543&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-10-05 N1 - Date created - 1998-10-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pertussis toxin modification of PC12 cells lowers cytoskeletal F-actin and enhances norepinephrine secretion: involvement of protein kinase C and protein phosphatases. AN - 73885460; 9711351 AB - We have investigated the relationship between norepinephrine secretion and cytoskeletal F-actin in rat phaeochromocytoma PC12 cells. Stimulation of PC12 cells with extracellular ATP or high K+ caused both the release of norepinephrine and a decrease in F-actin. The stimulation of secretion and the decrease in F-actin were dependent on extracellular Ca2+. The addition of Ca2+ to digitonin-permeabilized PC12 cells also stimulated norepinephrine release and decreased F-actin. Modification of PC12 cells with pertussis toxin caused a 35% decrease in F-actin, and it enhanced ATP-stimulated and K+ stimulated norepinephrine secretion from intact cells and Ca(2+)-dependent norepinephrine secretion from permeabilized cells. After down regulation of protein kinase C, pertussis toxin still enhanced secretion, but it had no effect on F-actin indicating that the effect of pertussis toxin on F-actin was dependent on protein kinase C activity. The addition of okadaic acid, an inhibitor of serine/threonine protein phosphatases, to PC12 cells caused a decrease F-actin, but it had no effect on ATP-stimulated or K(+)-stimulated norepinephrine secretion. After down regulation of protein kinase C, much higher concentrations of okadaic acid were need to decrease F-actin. The similarity between the effects of pertussis toxin and low concentrations of okadaic acid suggest that the effect of pertussis toxin on cytoskeletal F-actin in PC12 cells may result from an inhibition of protein phosphatase 2A. JF - Archives of physiology and biochemistry AU - Chen, F AU - Wagner, P D AD - Laboratory of Biochemistry, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. f.chen@ic.ac.uk Y1 - 1998/08// PY - 1998 DA - August 1998 SP - 317 EP - 328 VL - 105 IS - 4 SN - 1381-3455, 1381-3455 KW - Actins KW - 0 KW - Virulence Factors, Bordetella KW - Okadaic Acid KW - 1W21G5Q4N2 KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - Pertussis Toxin KW - EC 2.4.2.31 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Phosphoprotein Phosphatases KW - EC 3.1.3.16 KW - Protein Phosphatase 2 KW - Potassium KW - RWP5GA015D KW - Norepinephrine KW - X4W3ENH1CV KW - Index Medicus KW - Secretory Rate -- drug effects KW - Rats KW - Animals KW - Down-Regulation KW - Cell Membrane Permeability -- drug effects KW - Okadaic Acid -- pharmacology KW - Potassium -- pharmacology KW - Membrane Potentials -- drug effects KW - PC12 Cells KW - Adenosine Triphosphate -- pharmacology KW - Protein Kinase C -- metabolism KW - Virulence Factors, Bordetella -- pharmacology KW - Cytoskeleton -- metabolism KW - Phosphoprotein Phosphatases -- metabolism KW - Actins -- metabolism KW - Norepinephrine -- secretion KW - Cytoskeleton -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73885460?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+physiology+and+biochemistry&rft.atitle=Pertussis+toxin+modification+of+PC12+cells+lowers+cytoskeletal+F-actin+and+enhances+norepinephrine+secretion%3A+involvement+of+protein+kinase+C+and+protein+phosphatases.&rft.au=Chen%2C+F%3BWagner%2C+P+D&rft.aulast=Chen&rft.aufirst=F&rft.date=1998-08-01&rft.volume=105&rft.issue=4&rft.spage=317&rft.isbn=&rft.btitle=&rft.title=Archives+of+physiology+and+biochemistry&rft.issn=13813455&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-11-17 N1 - Date created - 1998-11-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Attenuation of cocaine-induced locomotor activity by butyrylcholinesterase. AN - 73879313; 9725111 AB - A primary enzyme for the metabolism of cocaine is butyrylcholinesterase (BChE). To determine whether the systemic administration of BChE can increase the metabolism of cocaine sufficiently to alter a behavioral effect, rats were tested in a locomotor activity chamber after receiving 17 mg of cocaine per kg intraperitoneally. In rats pretreated intravenously with 5,000 IU of horse serum-derived BChE, the locomotor activity effect was significantly attenuated. BChE pretreatment increased plasma BChE levels approximately 400-fold. When added to rat plasma, this amount of BChE reduced the cocaine half-life from over 5 hr to less than 5 min. BChE altered the cocaine metabolic pattern such that the relatively nontoxic metabolite ecgonine methyl ester was produced, rather than benzoylecgonine. These results suggest that systemic administration of BChE can increase the metabolism of cocaine sufficiently to alter a behavioral effect of cocaine and thus should be investigated as a potential treatment for cocaine abuse. JF - Experimental and clinical psychopharmacology AU - Carmona, G N AU - Schindler, C W AU - Shoaib, M AU - Jufer, R AU - Cone, E J AU - Goldberg, S R AU - Greig, N H AU - Yu, Q S AU - Gorelick, D A AD - Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 21224, USA. gcarmona@intra.nida.nih.gov Y1 - 1998/08// PY - 1998 DA - August 1998 SP - 274 EP - 279 VL - 6 IS - 3 SN - 1064-1297, 1064-1297 KW - Narcotics KW - 0 KW - Butyrylcholinesterase KW - EC 3.1.1.- KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Drug Interactions KW - Male KW - Butyrylcholinesterase -- pharmacology KW - Narcotics -- metabolism KW - Motor Activity -- drug effects KW - Cocaine -- pharmacology KW - Cocaine -- metabolism KW - Narcotics -- pharmacology KW - Butyrylcholinesterase -- metabolism KW - Butyrylcholinesterase -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73879313?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Experimental+and+clinical+psychopharmacology&rft.atitle=Attenuation+of+cocaine-induced+locomotor+activity+by+butyrylcholinesterase.&rft.au=Carmona%2C+G+N%3BSchindler%2C+C+W%3BShoaib%2C+M%3BJufer%2C+R%3BCone%2C+E+J%3BGoldberg%2C+S+R%3BGreig%2C+N+H%3BYu%2C+Q+S%3BGorelick%2C+D+A&rft.aulast=Carmona&rft.aufirst=G&rft.date=1998-08-01&rft.volume=6&rft.issue=3&rft.spage=274&rft.isbn=&rft.btitle=&rft.title=Experimental+and+clinical+psychopharmacology&rft.issn=10641297&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-12-03 N1 - Date created - 1998-12-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of moderate alcohol consumption on the central nervous system. AN - 73879079; 9726269 AB - The concept of moderate consumption of ethanol (beverage alcohol) has evolved over time from considering this level of intake to be nonintoxicating and noninjurious, to encompassing levels defined as "statistically" normal in particular populations, and the public health-driven concepts that define moderate drinking as the level corresponding to the lowest overall rate of morbidity or mortality in a population. The various approaches to defining moderate consumption of ethanol provide for a range of intakes that can result in blood ethanol concentrations ranging from 5 to 6 mg/dl, to levels of over 90 mg/dl (i.e., approximately 20 mM). This review summarizes available information regarding the effects of moderate consumption of ethanol on the adult and the developing nervous systems. The metabolism of ethanol in the human is reviewed to allow for proper appreciation of the important variables that interact to influence the level of exposure of the brain to ethanol once ethanol is orally consumed. At the neurochemical level, the moderate consumption of ethanol selectively affects the function of GABA, glutamatergic, serotonergic, dopaminergic, cholinergic, and opioid neuronal systems. Ethanol can affect these systems directly, and/or the interactions between and among these systems become important in the expression of ethanol's actions. The behavioral consequences of ethanol's actions on brain neurochemistry, and the neurochemical effects themselves, are very much dose- and time-related, and the collage of ethanol's actions can change significantly even on the rising and falling phases of the blood ethanol curve. The behavioral effects of moderate ethanol intake can encompass events that the human or other animal can perceive as reinforcing through either positive (e.g., pleasurable, activating) or negative (e.g., anxiolysis, stress reduction) reinforcement mechanisms. Genetic factors and gender play an important role in the metabolism and behavioral actions of ethanol, and doses of ethanol producing pleasurable feelings, activation, and reduction of anxiety in some humans/animals can have aversive, sedative, or no effect in others. Research on the cognitive effects of acute and chronic moderate intake of ethanol is reviewed, and although a number of studies have noted a measurable diminution in neuropsychologic parameters in habitual consumers of moderate amounts of ethanol, others have not found such changes. Recent studies have also noted some positive effects of moderate ethanol consumption on cognitive performance in the aging human. The moderate consumption of ethanol by pregnant women can have significant consequences on the developing nervous system of the fetus. Consumption of ethanol during pregnancy at levels considered to be in the moderate range can generate fetal alcohol effects (behavioral, cognitive anomalies) in the offspring. A number of factors--including gestational period, the periodicity of the mother's drinking, genetic factors, etc.--play important roles in determining the effect of ethanol on the developing central nervous system. A series of recommendations for future research endeavors, at all levels, is included with this review as part of the assessment of the effects of moderate ethanol consumption on the central nervous system. JF - Alcoholism, clinical and experimental research AU - Eckardt, M J AU - File, S E AU - Gessa, G L AU - Grant, K A AU - Guerri, C AU - Hoffman, P L AU - Kalant, H AU - Koob, G F AU - Li, T K AU - Tabakoff, B AD - Office of Scientific Affairs, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland, USA. Y1 - 1998/08// PY - 1998 DA - August 1998 SP - 998 EP - 1040 VL - 22 IS - 5 SN - 0145-6008, 0145-6008 KW - Ethanol KW - 3K9958V90M KW - Index Medicus KW - Central Nervous System -- metabolism KW - Animals KW - Ethanol -- pharmacokinetics KW - Dose-Response Relationship, Drug KW - Humans KW - Adult KW - Infant, Newborn KW - Central Nervous System -- drug effects KW - Fetal Alcohol Spectrum Disorders -- blood KW - Female KW - Pregnancy KW - Fetal Alcohol Spectrum Disorders -- diagnosis KW - Alcohol-Related Disorders -- diagnosis KW - Alcohol-Related Disorders -- blood KW - Alcohol Drinking -- adverse effects KW - Central Nervous System Diseases -- blood KW - Central Nervous System Diseases -- diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73879079?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Alcoholism%2C+clinical+and+experimental+research&rft.atitle=Effects+of+moderate+alcohol+consumption+on+the+central+nervous+system.&rft.au=Eckardt%2C+M+J%3BFile%2C+S+E%3BGessa%2C+G+L%3BGrant%2C+K+A%3BGuerri%2C+C%3BHoffman%2C+P+L%3BKalant%2C+H%3BKoob%2C+G+F%3BLi%2C+T+K%3BTabakoff%2C+B&rft.aulast=Eckardt&rft.aufirst=M&rft.date=1998-08-01&rft.volume=22&rft.issue=5&rft.spage=998&rft.isbn=&rft.btitle=&rft.title=Alcoholism%2C+clinical+and+experimental+research&rft.issn=01456008&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-12-15 N1 - Date created - 1998-12-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of nitric oxide in cardiovascular disease: focus on the endothelium. AN - 73836613; 9702990 AB - Nitric oxide is a soluble gas continuously synthesized by the endothelium. This substance has a wide range of biological properties that maintain vascular homeostasis, including modulation of vascular dilator tone, regulation of local cell growth, and protection of the vessel from injurious consequences of platelets and cells circulating in blood. A growing list of conditions, including those commonly associated as risk factors for atherosclerosis such as hypertension and hypercholesterolemia, are associated with diminished release of nitric oxide into the arterial wall either because of impaired synthesis or excessive oxidative degradation. Diminished nitric oxide bioactivity may cause constriction of coronary arteries during exercise or during mental stress and contribute to provocation of myocardial ischemia in patients with coronary artery disease. Additionally, diminished nitric oxide bioactivity may facilitate vascular inflammation that could lead to oxidation of lipoproteins and foam cell formation, the precursor of the atherosclerotic plaque. Numerous therapies have been investigated to assess the possibility of reversing endothelial dysfunction by enhancing the release of nitric oxide from the endothelium, either through stimulation of nitric oxide synthesis or protection of nitric oxide from oxidative inactivation and conversion to toxic molecules such as peroxynitrite. Accordingly, causal relationships between improved endothelial function and reduction in myocardial ischemia and acute coronary events can now be investigated. JF - Clinical chemistry AU - Cannon, R O AD - Cardiology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. cannonr@gwgate.nhlbi.nih.gov Y1 - 1998/08// PY - 1998 DA - August 1998 SP - 1809 EP - 1819 VL - 44 IS - 8 Pt 2 SN - 0009-9147, 0009-9147 KW - Nitric Oxide KW - 31C4KY9ESH KW - Index Medicus KW - Animals KW - Hypertension -- physiopathology KW - Humans KW - Hypercholesterolemia -- physiopathology KW - Vasomotor System -- physiopathology KW - Myocardial Ischemia -- physiopathology KW - Stress, Physiological -- physiopathology KW - Arteriosclerosis -- physiopathology KW - Endothelium, Vascular -- metabolism KW - Nitric Oxide -- physiology KW - Cardiovascular Diseases -- physiopathology KW - Endothelium, Vascular -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73836613?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+chemistry&rft.atitle=Role+of+nitric+oxide+in+cardiovascular+disease%3A+focus+on+the+endothelium.&rft.au=Cannon%2C+R+O&rft.aulast=Cannon&rft.aufirst=R&rft.date=1998-08-01&rft.volume=44&rft.issue=8+Pt+2&rft.spage=1809&rft.isbn=&rft.btitle=&rft.title=Clinical+chemistry&rft.issn=00099147&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-08-14 N1 - Date created - 1998-08-14 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Clin Chem 1998 Sep;44(9):2070 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phase I trial of anti-CD3-stimulated CD4+ T cells, infusional interleukin-2, and cyclophosphamide in patients with advanced cancer. AN - 73818230; 9704728 AB - We performed a phase I trial to determine whether in vivo expansion of activated CD4+ T cells was possible in cancer patients. 111Indium labeling was used to observe trafficking patterns of the infused stimulated CD4+ T cells. The influence of cyclophosphamide (CTX) dosing on immunologic outcome was also examined. Patients with advanced solid tumors or non-Hodgkin's lymphoma received CTX at 300 or 1,000 mg/m2 intravenously (i.v.). Leukapheresis was performed to harvest peripheral-blood mononuclear cells (PBMCs) either just before the CTX dose, or when the patient was either entering or recovering from the leukocyte nadir induced by CTX. An enriched population of CD4+ T cells was obtained by negative selection. The CD4+ T cells were activated ex vivo with anti-CD3, cultured with interleukin-2 (IL-2) for 4 days, and adoptively transferred. After adoptive transfer, patients received IL-2 (9.0 x 10(6) IU/m2/d) by continuous infusion for 7 days. The absolute number of CD4+, CD4+/DR+, and CD4+/CD45RO+ T cells increased in a statistically significant fashion in all cohorts after the first course of therapy. The degree of CD4 expansion was much greater than CD8 expansion, which resulted in a CD4:CD8 ratio that increased in 26 of 31 patients. The greatest in vivo CD4 expansion occurred when cells were harvested as patients entered the CTX-induced nadir. One complete response (CR), two partial responses (PRs), and eight minor responses were observed. Trafficking of 111Indium-labeled CD4 cells to subcutaneous melanoma deposits was also documented. CD4+ T cells can be expanded in vivo in cancer patients, which results in increased CD4:CD8 ratios. The timing of pheresis in relation to CTX administration influences the degree of CD4 expansion. Tumor responses with this regimen were observed in a variety of tumors, including melanoma and non-Hodgkin's lymphoma; a high percentage of patients had at least some tumor regression from the regimen that produced the greatest CD4+ T-cell expansion. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Curti, B D AU - Ochoa, A C AU - Powers, G C AU - Kopp, W C AU - Alvord, W G AU - Janik, J E AU - Gause, B L AU - Dunn, B AU - Kopreski, M S AU - Fenton, R AU - Zea, A AU - Dansky-Ullmann, C AU - Strobl, S AU - Harvey, L AU - Nelson, E AU - Sznol, M AU - Longo, D L AD - Investigational Drug Branch, Cancer Therapy Evaluation Program, Division of Cancer Treatment, National Cancer Institute, Bethesda, MD, USA. bcurti@psghs.edu Y1 - 1998/08// PY - 1998 DA - August 1998 SP - 2752 EP - 2760 VL - 16 IS - 8 SN - 0732-183X, 0732-183X KW - Antigens, CD3 KW - 0 KW - Antineoplastic Agents KW - Indium Radioisotopes KW - Interleukin-2 KW - Cyclophosphamide KW - 8N3DW7272P KW - Index Medicus KW - Leukapheresis KW - Infusions, Intravenous KW - Combined Modality Therapy KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Male KW - Female KW - Lymphocyte Activation KW - Cyclophosphamide -- administration & dosage KW - Antigens, CD3 -- immunology KW - Interleukin-2 -- administration & dosage KW - Antineoplastic Agents -- administration & dosage KW - Immunotherapy, Adoptive KW - CD4-Positive T-Lymphocytes -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73818230?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Medicine&rft.atitle=Familial+Mediterranean+fever+at+the+millennium.+Clinical+spectrum%2C+ancient+mutations%2C+and+a+survey+of+100+American+referrals+to+the+National+Institutes+of+Health.&rft.au=Samuels%2C+J%3BAksentijevich%2C+I%3BTorosyan%2C+Y%3BCentola%2C+M%3BDeng%2C+Z%3BSood%2C+R%3BKastner%2C+D+L&rft.aulast=Samuels&rft.aufirst=J&rft.date=1998-07-01&rft.volume=77&rft.issue=4&rft.spage=268&rft.isbn=&rft.btitle=&rft.title=Medicine&rft.issn=00257974&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-08-31 N1 - Date created - 1998-08-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In vivo use of adenoviral vectors: effects on salivary gland structure. AN - 70074103; 9825894 AB - Recently there has been considerable progress in the development of in vivo gene transfer technology. By this means, new genetic information may be introduced directly to cells, while the cells remain in their natural milieu. The ability to express exogenous proteins makes it possible to explore the functions of native or altered proteins and thereby develop new insights into cell function and dysfunction. We have demonstrated that the major salivary glands are efficiently infected by recombinant adenovirus vectors. These vectors are capable of expressing transgenes in both acinar and ductal cell types. Recently, we have developed vectors that contain cell-specific promoters so that proteins may be expressed in selected subpopulations of salivary cells. Early generations of adenoviral vectors elicited potent immune responses in vivo. However, modified vectors and adjunctive measures have improved the safety of gene transfer to salivary glands. Future studies will aim to increase the duration of adenovirus-based gene expression and to produce vector systems that are not toxic to the host. JF - European journal of morphology AU - O'Connell, B C AU - Redman, R S AU - Zheng, C AD - Gene Transfer Unit, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892-1190, USA. Y1 - 1998/08// PY - 1998 DA - August 1998 SP - 55 EP - 60 VL - 36 Suppl SN - 0924-3860, 0924-3860 KW - Index Medicus KW - Rats KW - Animals KW - Gene Expression Regulation, Viral KW - Rats, Wistar KW - Transgenes -- physiology KW - Microscopy, Electron KW - Male KW - Adenoviridae KW - Submandibular Gland -- virology KW - Parotid Gland -- physiology KW - Gene Transfer Techniques KW - Parotid Gland -- ultrastructure KW - Submandibular Gland -- ultrastructure KW - Submandibular Gland -- physiology KW - Parotid Gland -- virology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70074103?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Microbiology&rft.atitle=Evidence+of+past+recombination+events+among+the+genes+encoding+the+Erp+antigens+of+Borrelia+burgdorferi&rft.au=Stevenson%2C+B%3BCasjens%2C+S%3BRosa%2C+P&rft.aulast=Stevenson&rft.aufirst=B&rft.date=1998-07-01&rft.volume=144&rft.issue=7&rft.spage=1869&rft.isbn=&rft.btitle=&rft.title=Microbiology&rft.issn=13500872&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-01-15 N1 - Date created - 1999-01-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Serum concentrations of organochlorine compounds and endometrial cancer risk (United States). AN - 70005476; 9794174 AB - Endogenous and exogenous estrogens are important in the development of endometrial cancer. Several organochlorine compounds, such as o,p'-DDT, have estrogenic properties. The objective of this case-control analysis was to examine serum concentrations of organochlorine compounds and risk of endometrial cancer. Analyses were based on a sample of 90 endometrial cancer cases and 90 individually matched community controls from a multicenter case-control study in five geographic regions of the United States. Information on potential confounders, including menstrual and reproductive factors, cigarette smoking, diet, and weight, was obtained by interview. The adjusted relative risk of endometrial cancer in the highest quartile of exposure compared with women in the lowest quartile was 0.7 (95 percent confidence interval [CI] = 0.2-2.0) for p,p'-DDE, and 0.9 for total polychlorinated biphenyls (PCBs) (CI = 0.4-2.5). These findings do not support the hypothesis that organochlorine compounds are linked to the development of endometrial cancer. JF - Cancer causes & control : CCC AU - Sturgeon, S R AU - Brock, J W AU - Potischman, N AU - Needham, L L AU - Rothman, N AU - Brinton, L A AU - Hoover, R N AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA. Y1 - 1998/08// PY - 1998 DA - August 1998 SP - 417 EP - 424 VL - 9 IS - 4 SN - 0957-5243, 0957-5243 KW - Hydrocarbons, Chlorinated KW - 0 KW - Insecticides KW - Index Medicus KW - Logistic Models KW - Risk Factors KW - Humans KW - Adult KW - Case-Control Studies KW - Incidence KW - Confidence Intervals KW - Aged KW - Middle Aged KW - Adolescent KW - United States -- epidemiology KW - Female KW - Risk Assessment KW - Endometrial Neoplasms -- epidemiology KW - Carcinoma -- epidemiology KW - Endometrial Neoplasms -- blood KW - Carcinoma -- blood KW - Insecticides -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70005476?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Serum+concentrations+of+organochlorine+compounds+and+endometrial+cancer+risk+%28United+States%29.&rft.au=Sturgeon%2C+S+R%3BBrock%2C+J+W%3BPotischman%2C+N%3BNeedham%2C+L+L%3BRothman%2C+N%3BBrinton%2C+L+A%3BHoover%2C+R+N&rft.aulast=Sturgeon&rft.aufirst=S&rft.date=1998-08-01&rft.volume=9&rft.issue=4&rft.spage=417&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 - 1999-01-12 N1 - Date created - 1999-01-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Skin tumor risk among atomic-bomb survivors in Japan. AN - 69997741; 9794171 AB - Elevated risks of skin cancer following high doses of ionizing radiation have long been known. Recent reports on atomic-bomb survivors indicate that nonmelanoma skin cancer can be induced at low to medium doses. We studied atomic-bomb survivors to determine the effects of radiation on specific histologic types of skin cancer and to describe the dose-response relationship. Cases of melanoma, nonmelanoma skin cancers, and Bowen's disease were ascertained between 1958 and 1987 for the 80,000 cohort members through the population-based Hiroshima and Nagasaki (Japan) tumor registries augmented by searches of other records. An excess of basal cell carcinoma (n = 80), with some suggestion of a non-linear dose-response, was observed. The excess risk decreased markedly as age at exposure increased, and there was no evidence for an interaction between ionizing and ultraviolet radiation. No dose-response was found for squamous cell carcinoma (n = 69). The excess relative risk point-estimates were large, but statistically nonsignificant for both melanoma (n = 10) and Bowen's disease (n = 26). The basal layer of the epidermis appears to be quite sensitive to radiation carcinogenesis, particularly at a young age. The suprabasal layer seems to be more resistant, as shown by the lack of an association for squamous cell carcinomas. JF - Cancer causes & control : CCC AU - Ron, E AU - Preston, D L AU - Kishikawa, M AU - Kobuke, T AU - Iseki, M AU - Tokuoka, S AU - Tokunaga, M AU - Mabuchi, K AD - Radiation Epidemiology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1998/08// PY - 1998 DA - August 1998 SP - 393 EP - 401 VL - 9 IS - 4 SN - 0957-5243, 0957-5243 KW - Index Medicus KW - Bowen's Disease -- etiology KW - Melanoma -- etiology KW - Humans KW - Aged KW - Child KW - Poisson Distribution KW - Dose-Response Relationship, Radiation KW - Melanoma -- epidemiology KW - Child, Preschool KW - Registries KW - Japan -- epidemiology KW - Bowen's Disease -- epidemiology KW - Risk Factors KW - Adult KW - Cohort Studies KW - Incidence KW - Confidence Intervals KW - Middle Aged KW - Adolescent KW - Male KW - Female KW - Survivors -- statistics & numerical data KW - Carcinoma, Squamous Cell -- etiology KW - Carcinoma, Squamous Cell -- epidemiology KW - Carcinoma, Basal Cell -- etiology KW - Skin Neoplasms -- etiology KW - Nuclear Warfare KW - Skin Neoplasms -- epidemiology KW - Carcinoma, Basal Cell -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69997741?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Skin+tumor+risk+among+atomic-bomb+survivors+in+Japan.&rft.au=Ron%2C+E%3BPreston%2C+D+L%3BKishikawa%2C+M%3BKobuke%2C+T%3BIseki%2C+M%3BTokuoka%2C+S%3BTokunaga%2C+M%3BMabuchi%2C+K&rft.aulast=Ron&rft.aufirst=JPM&rft.date=1998-07-01&rft.volume=29&rft.issue=1&rft.spage=369&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 - 1999-01-12 N1 - Date created - 1999-01-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Gene disruption to evaluate the role of fungal candidate virulence genes. AN - 69187707; 10066511 AB - Gene disruption is a powerful genetic tool that can define pathogenic or virulence factors. In the past two years gene disruption approaches have been used to identify fungal virulence genes. The capsule genes, an alpha subunit of G protein and certain kinases of Cryptococcus neoformans have clearly been demonstrated to be associated with pathogenicity. In Candida albicans at least four genes involved in hyphal formation have been disrupted and tested for virulence. In other fungi, such as Histoplasma capsulatum, however, more efficient gene disruption methods need to be developed before such approaches can be regularly used for identifying virulence genes. JF - Current opinion in microbiology AU - Kwon-Chung, K AD - Molecular Microbiology Section, Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, Building 10, 11C304, National Institutes of Health, Bethesda MD 20892, USA. June_Kwon-Chung@nih.gov Y1 - 1998/08// PY - 1998 DA - August 1998 SP - 381 EP - 389 VL - 1 IS - 4 SN - 1369-5274, 1369-5274 KW - Index Medicus KW - Virulence -- genetics KW - Gene Deletion KW - Candida -- genetics KW - Genes, Fungal KW - Cryptococcus neoformans -- genetics KW - Candida -- pathogenicity KW - Cryptococcus neoformans -- pathogenicity KW - Mutagenesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69187707?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+microbiology&rft.atitle=Gene+disruption+to+evaluate+the+role+of+fungal+candidate+virulence+genes.&rft.au=Kwon-Chung%2C+K&rft.aulast=Kwon-Chung&rft.aufirst=K&rft.date=1998-08-01&rft.volume=1&rft.issue=4&rft.spage=381&rft.isbn=&rft.btitle=&rft.title=Current+opinion+in+microbiology&rft.issn=13695274&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-05-05 N1 - Date created - 1999-05-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Indications for, and use of, cytotoxic agents in SLE. AN - 69136810; 9890110 AB - Over the past decade, cytotoxic drugs have come to assume an increasingly important role in the management of systemic lupus erythematosus. Intravenous cyclophosphamide has become the standard treatment for lupus affecting major organs, in particular lupus nephritis. Cytotoxics with less potential for adverse side effects such as azathioprine and methotrexate are widely used in the management of non-major organ lupus and as an adjunct to reduce corticosteroid requirements. Recent clinical experience in lupus with newer cytotoxic drugs such as cyclosporin A, adenosine analogues, and mycophenolate mofetil appear promising and may offer improvements in lupus management in the future. JF - Bailliere's clinical rheumatology AU - Klippel, J H AD - Clinical Investigations Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892-1828, USA. Y1 - 1998/08// PY - 1998 DA - August 1998 SP - 511 EP - 527 VL - 12 IS - 3 SN - 0950-3579, 0950-3579 KW - Immunosuppressive Agents KW - 0 KW - Cyclophosphamide KW - 8N3DW7272P KW - Azathioprine KW - MRK240IY2L KW - Methotrexate KW - YL5FZ2Y5U1 KW - Index Medicus KW - Azathioprine -- toxicity KW - Humans KW - Azathioprine -- administration & dosage KW - Methotrexate -- administration & dosage KW - Methotrexate -- toxicity KW - Cyclophosphamide -- administration & dosage KW - Lupus Erythematosus, Systemic -- drug therapy KW - Immunosuppressive Agents -- toxicity KW - Cyclophosphamide -- toxicity KW - Immunosuppressive Agents -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69136810?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Bailliere%27s+clinical+rheumatology&rft.atitle=Indications+for%2C+and+use+of%2C+cytotoxic+agents+in+SLE.&rft.au=Klippel%2C+J+H&rft.aulast=Klippel&rft.aufirst=J&rft.date=1998-08-01&rft.volume=12&rft.issue=3&rft.spage=511&rft.isbn=&rft.btitle=&rft.title=Bailliere%27s+clinical+rheumatology&rft.issn=09503579&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-01-29 N1 - Date created - 1999-01-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Potentiometric study of resting potential, contributing K super(+) channels and the onset of Na super(+) channel excitability in embryonic rat cortical cells AN - 21023931; 8527841 AB - Resting membrane potential (RMP), K super(+) channel contribution to RMP and the development of excitability were investigated in the entire population of acutely dissociated embryonic (E) rat cortical cells over E11-22 using a voltage-sensitive fluorescent indicator dye and flow cytometry. During the period of intense proliferation (E11-13), two cell subpopulations with distinct estimated RMPs were recorded: one polarized at similar to -70 mV and the other relatively less-polarized at similar to -40 mV. Ca super(2+) sub(o) was critical in sustaining the RMP of the majority of less-polarized cells, while the well-polarized cells were characterized by membrane potentials exhibiting a similar to Nernstian relationship between RMP and [K super(+)] sub(o). Analysis of these two subpopulations revealed that > 80% of less-polarized cells were proliferative, while > 90% of well-polarized cells were postmitotic. Throughout embryonic development, the disappearance of Ca super(2+) sub(o)-sensitive, less-polarized cells correlated with the disappearance of the proliferating population, while the appearance of the K super(+) sub(o)-sensitive, well-polarized population correlated with the appearance of terminally postmitotic neurons, immuno-identified as BrdU super(-), tetanus toxin super(+) cells. Differentiating neurons were estimated to contain increased K super(+) sub(i) relative to less-polarized cells, coinciding with the developmental expression of Cs super(+)-Ba super(2+)-sensitive and Ca super(2+)-dependent K super(+) channels. Both K super(+) channels contributed to the RMP of well-polarized cells, which became more negative toward the end of neurogenesis. Depolarizing effects of veratridine, first observed at E11, progressively changed from Ca super(2+) sub(o)-dependent and tetrodotoxin-insensitive to Na super(+) sub(o)-dependent and tetrodotoxin-sensitive response by E18. The results reveal a dynamic development of RMP, contributing K super(+) channels and voltage-dependent Na super(+) channels in the developing cortex as it transforms from proliferative to primarily differentiating tissue. JF - European Journal of Neuroscience AU - Maric, Dragan AU - Maric, Irina AU - Smith, Susan V AU - Serafini, Ruggero AU - Hu, Qian AU - Barker, Jeffery L AD - Laboratory of Neurophysiology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA, dragan@codon.nih.gov Y1 - 1998/08// PY - 1998 DA - Aug 1998 SP - 2532 EP - 2546 PB - Blackwell Publishing Ltd., 9600 Garsington Road VL - 10 IS - 8 SN - 0953-816X, 0953-816X KW - Microbiology Abstracts B: Bacteriology; CSA Neurosciences Abstracts; Calcium & Calcified Tissue Abstracts KW - central nervous system KW - development KW - flow cytometry KW - oxonol KW - Potassium channels (calcium-gated) KW - Developmental stages KW - Tetanus KW - Excitability KW - Calcium (extracellular) KW - Flow cytometry KW - Embryogenesis KW - Neurogenesis KW - Nervous system KW - Cortex KW - veratridine KW - Potassium channels (voltage-gated) KW - Fluorescent indicators KW - Sodium channels KW - Potassium channels KW - Membrane potential KW - Depolarization KW - T 2000:Cellular Calcium KW - N3 11029:Neurophysiology & biophysics KW - J 02320:Cell Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/21023931?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=European+Journal+of+Neuroscience&rft.atitle=Potentiometric+study+of+resting+potential%2C+contributing+K+super%28%2B%29+channels+and+the+onset+of+Na+super%28%2B%29+channel+excitability+in+embryonic+rat+cortical+cells&rft.au=Maric%2C+Dragan%3BMaric%2C+Irina%3BSmith%2C+Susan+V%3BSerafini%2C+Ruggero%3BHu%2C+Qian%3BBarker%2C+Jeffery+L&rft.aulast=Maric&rft.aufirst=Dragan&rft.date=1998-08-01&rft.volume=10&rft.issue=8&rft.spage=2532&rft.isbn=&rft.btitle=&rft.title=European+Journal+of+Neuroscience&rft.issn=0953816X&rft_id=info:doi/10.1046%2Fj.1460-9568.1998.00284.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2008-11-01 N1 - Last updated - 2015-03-27 N1 - SubjectsTermNotLitGenreText - Potassium channels (calcium-gated); Developmental stages; Excitability; Tetanus; Calcium (extracellular); Flow cytometry; Nervous system; Neurogenesis; Embryogenesis; Cortex; veratridine; Potassium channels (voltage-gated); Fluorescent indicators; Sodium channels; Potassium channels; Depolarization; Membrane potential DO - http://dx.doi.org/10.1046/j.1460-9568.1998.00284.x ER - TY - JOUR T1 - Epidermal Growth Factor and Transforming Growth Factor- alpha -associated Overexpression of Cyclin D1, Cdk4, and c-Myc during Hepatocarcinogenesis in Helicobacter hepaticus-infected A/JCr Mice AN - 17208484; 4495653 AB - Helicobacter hepaticus is a new bacterial species that is homologous to Helicobacter pylori, a human gastric carcinogen. H. hepaticus causes chronic active hepatitis, with progression to hepatocellular tumors. We hypothesized that chronic up-regulation of epidermal growth factor (EGF), transforming growth factor- alpha , and nuclear oncogenes (cyclin D1 and c-Myc), all known to transform by overexpression, might contribute to tumorigenesis. Livers from mice that were 6-18 months old were analyzed, including nonneoplastic and preneoplastic tissues and tumors, along with age-matched controls, by immunohistochemistry and immunoblotting. EGF and transforming growth factor- alpha were increased at the earliest stage, with a further increase in EGF in tumors. Cyclin D1, cyclin-dependent kinase 4, and c-Myc were strongly increased in all infected livers, with even greater increases in tumors. An increase in cyclin D1/cyclin-dependent kinase 4 complex was also demonstrated in tumors, and its functionality was confirmed by an increase in the hyperphosphorylated:hypophosphorylated retinoblastoma protein ratio. Our findings suggest a possible cooperation of growth factors, cell cycle proteins, and transcription factors during the development of H. hepaticus-associated liver tumors and may have relevance to human cancers associated with bacterial, viral, or parasitic infections. JF - Cancer Research AU - Ramljak, D AU - Jones, AB AU - Diwan, BA AU - Perantoni, A O AU - Hochadel, J F AU - Anderson, L M AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute-Frederick Cancer Research and Development Center, Building 538, Room 206, Frederick, MD 21702-1201, USA, ramljak@mail.ncifcrf.gov Y1 - 1998/08// PY - 1998 DA - Aug 1998 SP - 3590 EP - 3597 VL - 58 IS - 16 SN - 0008-5472, 0008-5472 KW - Cdk4 kinase KW - Helicobacter hepaticus KW - c-Myc protein KW - cyclin D1 KW - mice KW - Microbiology Abstracts B: Bacteriology; Oncogenes & Growth Factors Abstracts KW - Carcinogenesis KW - Liver KW - Epidermal growth factor KW - B 26020:EGF & EGF receptor family/TGF alpha /Her/ErbB-2 (Neu)/ErbB-3/ErbB-4/amphiregulin KW - J 02855:Human Bacteriology: Others UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17208484?accountid=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=Cancer+Research&rft.atitle=Epidermal+Growth+Factor+and+Transforming+Growth+Factor-+alpha+-associated+Overexpression+of+Cyclin+D1%2C+Cdk4%2C+and+c-Myc+during+Hepatocarcinogenesis+in+Helicobacter+hepaticus-infected+A%2FJCr+Mice&rft.au=Ramljak%2C+D%3BJones%2C+AB%3BDiwan%2C+BA%3BPerantoni%2C+A+O%3BHochadel%2C+J+F%3BAnderson%2C+L+M&rft.aulast=Ramljak&rft.aufirst=D&rft.date=1998-08-01&rft.volume=58&rft.issue=16&rft.spage=3590&rft.isbn=&rft.btitle=&rft.title=Cancer+Research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Helicobacter hepaticus; Carcinogenesis; Liver; Epidermal growth factor ER - TY - JOUR T1 - Development of a Retrovirus-based Complementary DNA Expression System for the Cloning of Tumor Antigens AN - 17203392; 4495642 AB - A new retroviral system has been developed for the generation of a cDNA library and the functional cloning of tumor antigens. These retroviral vectors contain a cytomegalovirus promoter in the 5 theta long terminal repeat, an extended packaging signal for rapid production of high-titer retroviral particles, and many convenient cloning sites for cDNA library construction. The vesicular stomatitis virus G protein has been used to generate pseudotype retroviral particles to enable efficient viral infection. Using this system, viral titers in the range of 10 super(6) colony-forming units/ml could be generated routinely, and a high transduction efficiency in human primary cells, including fibroblasts, was achieved. In addition, a new procedure has been devised for screening a retrovirus-based cDNA library without a functional selection. The utility of this system was demonstrated by constructing a retrovirus-based cDNA library and re-isolating the NY-ESO-1 tumor antigen from a cDNA library using an antigenspecific CTL. This approach can facilitate the identification of novel tumor antigens recognized by T cells without knowledge of MHC class I restriction elements and is generally applicable for the isolation of any gene as long as a biological assay is available. JF - Cancer Research AU - Wang, R-F AU - Wang, X AU - Johnston, S L AU - Zeng, G AU - Robbins, P F AU - Rosenberg, SA AD - Surgery Branch, Building 10, 2B42, National Cancer Institute, NIH, 9000 Rockville Pike, Bethesda, MD 20892-1502, USA, rongfu@pop.nci.nih.gov Y1 - 1998/08// PY - 1998 DA - Aug 1998 SP - 3519 EP - 3525 VL - 58 IS - 16 SN - 0008-5472, 0008-5472 KW - Retrovirus KW - cDNA KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Gene therapy KW - Antigen (tumor-associated) KW - Lymphocytes T KW - Cloning vectors KW - Tumors KW - W3 33181:Gene therapy vectors KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17203392?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Research&rft.atitle=Development+of+a+Retrovirus-based+Complementary+DNA+Expression+System+for+the+Cloning+of+Tumor+Antigens&rft.au=Wang%2C+R-F%3BWang%2C+X%3BJohnston%2C+S+L%3BZeng%2C+G%3BRobbins%2C+P+F%3BRosenberg%2C+SA&rft.aulast=Wang&rft.aufirst=R-F&rft.date=1998-08-01&rft.volume=58&rft.issue=16&rft.spage=3519&rft.isbn=&rft.btitle=&rft.title=Cancer+Research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Gene therapy; Cloning vectors; Antigen (tumor-associated); Tumors; Lymphocytes T ER - TY - JOUR T1 - Topography of the Interaction of HPr(Ser) Kinase with HPr AN - 17152443; 4450666 AB - The phosphocarrier protein, HPr, from Gram-positive organisms and mycoplasmas is a substrate for an ATP-dependent kinase that phosphorylates serine 46. In Gram-negative organisms, the corresponding HPr is not phosphorylated on serine 46 and the ATP-dependent kinase is absent. To determine the specificity requirements for phosphorylation of Mycoplasma capricolum HPr, a chimera in which residues 43-57 were replaced by the Escherichia coli sequence was constructed. The chimeric protein folded properly, but was not phosphorylated on either serine 46 or histidine 15. A dissection of the region required for phosphorylation specificity was carried out by further mutagenesis. The deficiency in phosphorylation at histidine 15 was localized primarily to the region including residues 51-57. Activity studies revealed that residues 48, 49, and 51-53 are important for recognition of M. capricolum HPr by its cognate HPr(Ser) kinase. The characteristics of this region suggest that the kinase-HPr interaction occurs mainly through a hydrophobic region. Molecular modeling comparisons of M. capricolum HPr and the chimeric construct provided a basis for interpreting the results of the activity assays. JF - Biochemistry (Washington) AU - Zhu, Peng-Peng AU - Herzberg, O AU - Peterkofsky, A AD - National Institutes of Health, Building 36, Room 4C-11, Bethesda, MD 20892, USA, alan@codon.nih.gov Y1 - 1998/08// PY - 1998 DA - Aug 1998 SP - 11762 EP - 11770 VL - 37 IS - 34 SN - 0006-2960, 0006-2960 KW - HPr protein KW - kinase KW - Microbiology Abstracts B: Bacteriology KW - Chimeras KW - Phosphorylation KW - Hydrophobicity KW - Mycoplasma capricolum KW - Topography KW - J 02728:Enzymes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17152443?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemistry+%28Washington%29&rft.atitle=Topography+of+the+Interaction+of+HPr%28Ser%29+Kinase+with+HPr&rft.au=Zhu%2C+Peng-Peng%3BHerzberg%2C+O%3BPeterkofsky%2C+A&rft.aulast=Zhu&rft.aufirst=Peng-Peng&rft.date=1998-08-01&rft.volume=37&rft.issue=34&rft.spage=11762&rft.isbn=&rft.btitle=&rft.title=Biochemistry+%28Washington%29&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Mycoplasma capricolum; Chimeras; Phosphorylation; Hydrophobicity; Topography ER - TY - JOUR T1 - Growth Inhibition of Chronic Myelogenous Leukemia Cells by ODN-1, an Aptameric Inhibitor of p210 super(bcr-abl) Tyrosine Kinase Activity AN - 16497269; 4402691 AB - p210 super(bcr-abl)-Related tyrosine kinase activity has been shown to cause chronic myelogenous leukemia (CML), a disease of bone marrow stem cells. Having previously demonstrated that the aptameric oligonucleotide, ODN-1, could inhibit p210 super(bcr-abl) kinase activity, the current study sought to determine if ODN-1 could selectively inhibit the growth of CML cells relative to that of normal bone marrow. ODN-1, when introduced by electroporation into peripheral blood mononuclear cells (PBMC) from patients with CML, decreased the number of committed progenitors (CML CFU-GM) by an average of 67% plus or minus 19% (mean plus or minus SEM, range 28-98%). Treatment of CML PBMC with ODN-1 was also shown to decrease the number of more primitive cobblestone area-forming cells (CAFC) by 35%-87%. In contrast, there was little suppressive effect by the combination of electroporation and ODN-1 on either CFU-GM or CAFC numbers from normal donor bone marrow. These studies suggest that inhibition of p210 super(bcr-abl) protein-tyrosine kinase (PTK) activity by ODN-1 is associated with some degree of selective growth inhibition of p210 super(bcr-abl)-transformed cells. p210 super(bcr-abl) kinase inhibitory agents may be useful for the ex vivo purging of bone marrow or peripheral blood progenitor/stem cells in the setting of autologous transplantation for CML. JF - Antisense and Nucleic Acid Drug Development AU - Schwartz, G N AU - Liu, Yue-Qin AU - Tisdale, J AU - Walshe, K AU - Fowler, D AU - Gress, R AU - Bergan, R C AD - Building 10, Room 12N226, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20897, USA Y1 - 1998/08// PY - 1998 DA - Aug 1998 SP - 329 EP - 339 VL - 8 IS - 4 SN - 1087-2906, 1087-2906 KW - Abl gene KW - BCR gene KW - ODN-1 KW - aptamers KW - man KW - oligonucleotides KW - p210 protein KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - W3 33385:DNA/RNA KW - N 14250:Biological properties KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16497269?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antisense+and+Nucleic+Acid+Drug+Development&rft.atitle=Growth+Inhibition+of+Chronic+Myelogenous+Leukemia+Cells+by+ODN-1%2C+an+Aptameric+Inhibitor+of+p210+super%28bcr-abl%29+Tyrosine+Kinase+Activity&rft.au=Schwartz%2C+G+N%3BLiu%2C+Yue-Qin%3BTisdale%2C+J%3BWalshe%2C+K%3BFowler%2C+D%3BGress%2C+R%3BBergan%2C+R+C&rft.aulast=Schwartz&rft.aufirst=G&rft.date=1998-08-01&rft.volume=8&rft.issue=4&rft.spage=329&rft.isbn=&rft.btitle=&rft.title=Antisense+and+Nucleic+Acid+Drug+Development&rft.issn=10872906&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Early Child Care and Self-Control, Compliance, and Problem Behavior at Twenty-Four and Thirty-Six Months AN - 1634078544 JF - Child Development Y1 - 1998/08/01/ PY - 1998 DA - 1998 Aug 01 SP - 1145 CY - Chicago, etc. PB - University of Chicago Press for the Society for Research in Child Development, etc. VL - 69 IS - 4 SN - 0009-3920 KW - Medical Sciences--Pediatrics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1634078544?accountid=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=Child+Development&rft.atitle=Early+Child+Care+and+Self-Control%2C+Compliance%2C+and+Problem+Behavior+at+Twenty-Four+and+Thirty-Six+Months&rft.au=&rft.aulast=&rft.aufirst=&rft.date=1998-08-01&rft.volume=69&rft.issue=4&rft.spage=1145&rft.isbn=&rft.btitle=&rft.title=Child+Development&rft.issn=00093920&rft_id=info:doi/ DB - Periodicals Index Online N1 - Last updated - 2014-12-08 ER - TY - JOUR T1 - Defective retrovirus insertion activates c-Ha-ras protooncogene in an MNU-induced rat mammary carcinoma. AN - 73853948; 9704014 AB - Endogenous retrovirus sequences are present in the genome of a wide variety of animal species. The activation of the proto-oncogenes of the ras family, particularly c-Ha-ras, by either point mutation or overexpression, has been shown to be associated with a vast number, of different cancers. here we report that the insertion of a defective retrovirus in the -1 intron of rat c-Ha-ras is responsible for the activation of the gene by over 10-fold overexpression in an MNU-induced rat mammary cancer. A portion of the 3' end of the retroviral sequence is expressed as a part of the c-Ha-ras transcript in the carcinoma tissue, indicating the direct involvement of this element in the transcription of the c-Ha-ras gene. The c-Ha-ras structural gene transcribed by the promoter of the defective retroviral element can neoplastically transform the NIH 3T3 cell line upon transfection. JF - Biochemical and biophysical research communications AU - Bera, T K AU - Tsukamoto, T AU - Panda, D K AU - Huang, T AU - Guzman, R C AU - Hwang, S I AU - Nandi, S AD - Cancer Research Laboratory, University of California at Berkeley 94720, USA. tkbera@helix.nih.gov Y1 - 1998/07/30/ PY - 1998 DA - 1998 Jul 30 SP - 835 EP - 840 VL - 248 IS - 3 SN - 0006-291X, 0006-291X KW - Recombinant Proteins KW - 0 KW - Methylnitrosourea KW - 684-93-5 KW - Proto-Oncogene Proteins p21(ras) KW - EC 3.6.5.2 KW - Index Medicus KW - AIDS/HIV KW - 3T3 Cells KW - Animals KW - Recombinant Proteins -- biosynthesis KW - Exons KW - Mice KW - Rats KW - Base Sequence KW - Transfection KW - Genes, env KW - Introns KW - Molecular Sequence Data KW - Repetitive Sequences, Nucleic Acid KW - Female KW - Genes, ras KW - Mammary Neoplasms, Experimental -- chemically induced KW - Promoter Regions, Genetic KW - Defective Viruses -- genetics KW - Proto-Oncogene Proteins p21(ras) -- biosynthesis KW - Retroviridae -- physiology KW - Mammary Neoplasms, Experimental -- genetics KW - Retroviridae -- genetics KW - Mammary Neoplasms, Experimental -- metabolism KW - Defective Viruses -- physiology KW - Cell Transformation, Neoplastic UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73853948?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Defective+retrovirus+insertion+activates+c-Ha-ras+protooncogene+in+an+MNU-induced+rat+mammary+carcinoma.&rft.au=Bera%2C+T+K%3BTsukamoto%2C+T%3BPanda%2C+D+K%3BHuang%2C+T%3BGuzman%2C+R+C%3BHwang%2C+S+I%3BNandi%2C+S&rft.aulast=Bera&rft.aufirst=T&rft.date=1998-07-30&rft.volume=248&rft.issue=3&rft.spage=835&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 - 1998-09-08 N1 - Date created - 1998-09-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Non-narcotic analgesics: renal and gastrointestinal considerations. Introduction. AN - 73861271; 9715827 JF - The American journal of medicine AU - Hamilton, F A AD - National Institute of Diabetes and Digestive Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-6600, USA. Y1 - 1998/07/27/ PY - 1998 DA - 1998 Jul 27 VL - 105 IS - 1B SN - 0002-9343, 0002-9343 KW - Anti-Inflammatory Agents, Non-Steroidal KW - 0 KW - Abridged Index Medicus KW - Index Medicus KW - Pain -- drug therapy KW - Humans KW - Anti-Inflammatory Agents, Non-Steroidal -- therapeutic use KW - Intestinal Diseases -- chemically induced KW - Anti-Inflammatory Agents, Non-Steroidal -- adverse effects KW - Kidney Diseases -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73861271?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+of+medicine&rft.atitle=Non-narcotic+analgesics%3A+renal+and+gastrointestinal+considerations.+Introduction.&rft.au=Hamilton%2C+F+A&rft.aulast=Hamilton&rft.aufirst=F&rft.date=1998-07-27&rft.volume=105&rft.issue=1B&rft.spage=1S&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+medicine&rft.issn=00029343&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-08-27 N1 - Date created - 1998-08-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - On the origins of BSE. AN - 80044533; 9690401 JF - Lancet (London, England) AU - Brown, P AD - Laboratory of CNS Studies, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1998/07/25/ PY - 1998 DA - 1998 Jul 25 SP - 252 EP - 253 VL - 352 IS - 9124 SN - 0140-6736, 0140-6736 KW - Biological Products KW - 0 KW - Minerals KW - bone meal KW - TRS31EO6ZN KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Cattle KW - Bone and Bones KW - Animal Feed KW - Food Microbiology KW - United Kingdom -- epidemiology KW - Sheep KW - Humans KW - Creutzfeldt-Jakob Syndrome -- transmission KW - Creutzfeldt-Jakob Syndrome -- epidemiology KW - Scrapie -- transmission KW - Meat-Packing Industry -- standards KW - Encephalopathy, Bovine Spongiform -- epidemiology KW - Encephalopathy, Bovine Spongiform -- transmission UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80044533?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Lancet+%28London%2C+England%29&rft.atitle=On+the+origins+of+BSE.&rft.au=Brown%2C+P&rft.aulast=Brown&rft.aufirst=P&rft.date=1998-07-25&rft.volume=352&rft.issue=9124&rft.spage=252&rft.isbn=&rft.btitle=&rft.title=Lancet+%28London%2C+England%29&rft.issn=01406736&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-08-19 N1 - Date created - 1998-08-19 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Lancet. 1998 Sep 26;352(9133):1068-9 [9759783] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Gating modifier toxins reveal a conserved structural motif in voltage-gated Ca2+ and K+ channels. AN - 80029816; 9671721 AB - Protein toxins from venomous animals exhibit remarkably specific and selective interactions with a wide variety of ion channels. Hanatoxin and grammotoxin are two related protein toxins found in the venom of the Chilean Rose Tarantula, Phrixotrichus spatulata. Hanatoxin inhibits voltage-gated K+ channels and grammotoxin inhibits voltage-gated Ca2+ channels. Both toxins inhibit their respective channels by interfering with normal operation of the voltage-dependent gating mechanism. The sequence homology of hanatoxin and grammotoxin, as well as their similar mechanism of action, raises the possibility that they interact with the same region of voltage-gated Ca2+ and K+ channels. Here, we show that each toxin can interact with both voltage-gated Ca2+ and K+ channels and modify channel gating. Moreover, mutagenesis of voltage-gated K+ channels suggests that hanatoxin and grammotoxin recognize the same structural motif. We propose that these toxins recognize a voltage-sensing domain or module present in voltage-gated ion channels and that this domain has a highly conserved three-dimensional structure. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Li-Smerin, Y AU - Swartz, K J AD - Molecular Physiology and Biophysics Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1998/07/21/ PY - 1998 DA - 1998 Jul 21 SP - 8585 EP - 8589 VL - 95 IS - 15 SN - 0027-8424, 0027-8424 KW - Calcium Channels KW - 0 KW - Peptides KW - Peptides, Cyclic KW - Potassium Channels KW - hanatoxin KW - omega-grammotoxin SIA KW - Index Medicus KW - Xenopus laevis KW - Animals KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Sequence Homology, Amino Acid KW - Ion Channel Gating KW - Potassium Channels -- chemistry KW - Calcium Channels -- drug effects KW - Calcium Channels -- chemistry KW - Peptides -- chemistry KW - Peptides, Cyclic -- chemistry KW - Potassium Channels -- drug effects KW - Peptides, Cyclic -- pharmacology KW - Peptides -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80029816?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Gating+modifier+toxins+reveal+a+conserved+structural+motif+in+voltage-gated+Ca2%2B+and+K%2B+channels.&rft.au=Li-Smerin%2C+Y%3BSwartz%2C+K+J&rft.aulast=Li-Smerin&rft.aufirst=Y&rft.date=1998-07-21&rft.volume=95&rft.issue=15&rft.spage=8585&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 - 1998-08-20 N1 - Date created - 1998-08-20 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Physiol. 1975 Jan;244(2):511-34 [1079869] Mol Pharmacol. 1997 Dec;52(6):1095-104 [9415720] J Biol Chem. 1978 Oct 25;253(20):7393-6 [29897] J Gen Physiol. 1979 Sep;74(3):375-91 [479827] J Gen Physiol. 1985 Nov;86(5):739-62 [2415671] J Gen Physiol. 1987 Feb;89(2):253-74 [2435840] J Gen Physiol. 1988 Mar;91(3):335-49 [2454283] Science. 1988 Sep 23;241(4873):1661-4 [2458626] Nature. 1989 Aug 24;340(6235):642-5 [2770868] Science. 1989 Sep 22;245(4924):1382-5 [2476850] J Membr Biol. 1989 Aug;109(3):269-81 [2477548] Neuron. 1988 Dec;1(10):1003-6 [2483092] Neuron. 1988 Aug;1(6):449-61 [2856097] Nature. 1991 Apr 4;350(6317):398-402 [1849233] Mol Pharmacol. 1991 Oct;40(4):572-6 [1921987] FEBS Lett. 1991 Oct 21;291(2):253-8 [1657644] J Biol Chem. 1991 Nov 15;266(32):21943-7 [1718988] Proc Biol Sci. 1991 Aug 22;245(1313):101-7 [1682932] Neuron. 1992 Aug;9(2):307-13 [1379820] Biochemistry. 1993 Jul 13;32(27):6982-7 [7687466] Mol Pharmacol. 1993 Aug;44(2):451-60 [8394998] Neuron. 1995 Jun;14(6):1293-301 [7605638] Neuron. 1995 Jul;15(1):5-10 [7542463] Neuron. 1995 Oct;15(4):941-9 [7576642] J Gen Physiol. 1995 Oct;106(4):601-16 [8576699] Science. 1996 Jan 12;271(5246):213-6 [8539623] Neuron. 1996 Jan;16(1):113-22 [8562074] Neuron. 1996 Jun;16(6):1159-67 [8663992] Neuron. 1996 Jun;16(6):1169-77 [8663993] J Biol Chem. 1996 Jul 5;271(27):15950-62 [8663157] Neuron. 1996 Feb;16(2):387-97 [8789953] Pflugers Arch. 1996 Nov-Dec;433(1-2):91-7 [9019737] Biophys J. 1997 May;72(5):2117-28 [9129813] Neuron. 1997 Apr;18(4):665-73 [9136774] Neuron. 1997 Apr;18(4):675-82 [9136775] Biochemistry. 1997 Jun 10;36(23):6936-40 [9188688] Neuron. 1997 Nov;19(5):1127-40 [9390525] J Biol Chem. 1977 Dec 10;252(23):8660-8 [72754] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characterization of the native and recombinant catalytic subunit of human DNA polymerase gamma: identification of residues critical for exonuclease activity and dideoxynucleotide sensitivity. AN - 80028937; 9671525 AB - The human DNA polymerase gamma catalytic subunit was overexpressed in recombinant baculovirus-infected insect cells, and the 136 000 Da protein was purified to homogeneity. Application of the same purification protocol to HeLa mitochondrial lysates permitted isolation of native DNA polymerase gamma as a single subunit, allowing direct comparison of the native and recombinant enzymes without interference of other polypeptides. Both forms exhibited identical properties, and the DNA polymerase and 3' --> 5' exonuclease activities were shown unambiguously to reside in the catalytic polypeptide. The salt sensitivity and moderate processivity of the isolated catalytic subunit suggest other factors could be required to restore the salt tolerance and highly processive DNA synthesis typical of gamma polymerases. To facilitate our understanding of mitochondrial DNA replication and mutagenesis as well as cytotoxicity mediated by antiviral nucleotide analogues, we also constructed two site-directed mutant proteins of the human DNA polymerase gamma. Substituting alanine for two essential acidic residues in the exonuclease motif selectively eliminated the 3' --> 5' exonucleolytic function of the purified mutant polymerase gamma. Replacement of a tyrosine residue critical for sugar recognition with phenylalanine in polymerase motif B reduced dideoxynucleotide inhibition by a factor of 5000 with only minor effects on overall polymerase function. JF - Biochemistry AU - Longley, M J AU - Ropp, P A AU - Lim, S E AU - Copeland, W C AD - Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1998/07/21/ PY - 1998 DA - 1998 Jul 21 SP - 10529 EP - 10539 VL - 37 IS - 29 SN - 0006-2960, 0006-2960 KW - Amino Acids KW - 0 KW - Deoxyribonucleotides KW - Peptide Fragments KW - Recombinant Proteins KW - DNA polymerase gamma KW - EC 2.7.7.- KW - DNA-Directed DNA Polymerase KW - EC 2.7.7.7 KW - Exonucleases KW - EC 3.1.- KW - Index Medicus KW - Peptide Fragments -- metabolism KW - Mutagenesis, Site-Directed KW - Peptide Fragments -- chemistry KW - Peptide Fragments -- genetics KW - Humans KW - Escherichia coli -- genetics KW - Escherichia coli -- enzymology KW - Amino Acid Sequence KW - Substrate Specificity -- genetics KW - Catalysis KW - Recombinant Proteins -- isolation & purification KW - Recombinant Proteins -- biosynthesis KW - Deoxyribonucleotides -- metabolism KW - Amino Acids -- metabolism KW - Recombinant Proteins -- chemistry KW - DNA-Directed DNA Polymerase -- genetics KW - Exonucleases -- metabolism KW - DNA-Directed DNA Polymerase -- metabolism KW - DNA-Directed DNA Polymerase -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80028937?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Characterization+of+the+native+and+recombinant+catalytic+subunit+of+human+DNA+polymerase+gamma%3A+identification+of+residues+critical+for+exonuclease+activity+and+dideoxynucleotide+sensitivity.&rft.au=Longley%2C+M+J%3BRopp%2C+P+A%3BLim%2C+S+E%3BCopeland%2C+W+C&rft.aulast=Longley&rft.aufirst=M&rft.date=1998-07-21&rft.volume=37&rft.issue=29&rft.spage=10529&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-08-05 N1 - Date created - 1998-08-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Up-regulation of inducible nitric oxide synthase expression in cancer-prone p53 knockout mice. AN - 80019505; 9671763 AB - High concentrations of nitric oxide (NO) cause DNA damage and apoptosis in many cell types. Thus, regulation of NO synthase (NOS) activity is essential for minimizing effects of cytotoxic and genotoxic nitrogen oxide species. We have shown previously that NO-induced p53 protein accumulation down-regulates basal and cytokine-modulated inducible NOS (NOS2) expression in human cells in vitro. To further characterize the feedback loop between NOS2 and p53, we have investigated NO production, i.e., urinary nitrate plus nitrite excretion, and NOS2 expression in homozygous p53 knockout (KO) mice. We report here that untreated p53 KO mice excreted 70% more nitrite plus nitrate than mice with wild-type (wt) p53. NOS2 protein expression was constitutively detected in the spleen of untreated p53 KO mice, whereas it was undetectable in the spleen of wt p53 controls. Upon treatment with heat-inactivated Corynebacterium parvum, urinary nitrite plus nitrate excretion of p53 KO mice exceeded that of wt controls by approximately 200%. C. parvum treatment also induced p53 accumulation in the liver. Splenectomy reduced the NO output of C. parvum-treated p53 KO mice but not of wt p53 controls. Although NO production and NOS2 protein expression were increased similarly in KO and wt p53 mice 10 days after injection of C. parvum, NOS2 expression returned to baseline levels only in wt p53 controls while remaining up-regulated in p53 KO mice. These genetic and functional data indicate that p53 is an important transrepressor of NOS2 expression in vivo and attenuates excessive NO production in a regulatory negative feedback loop. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Ambs, S AU - Ogunfusika, M O AU - Merriam, W G AU - Bennett, W P AU - Billiar, T R AU - Harris, C C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1998/07/21/ PY - 1998 DA - 1998 Jul 21 SP - 8823 EP - 8828 VL - 95 IS - 15 SN - 0027-8424, 0027-8424 KW - Nitric Oxide KW - 31C4KY9ESH KW - Nitric Oxide Synthase KW - EC 1.14.13.39 KW - Nitric Oxide Synthase Type II KW - Nos2 protein, mouse KW - Index Medicus KW - Animals KW - Promoter Regions, Genetic KW - Mice, Inbred C57BL KW - Mice KW - Feedback KW - Nitric Oxide -- biosynthesis KW - Genetic Predisposition to Disease KW - Mice, Knockout KW - Gene Expression Regulation, Enzymologic KW - Nitric Oxide Synthase -- genetics KW - Neoplasms, Experimental -- genetics KW - Up-Regulation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80019505?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Up-regulation+of+inducible+nitric+oxide+synthase+expression+in+cancer-prone+p53+knockout+mice.&rft.au=Ambs%2C+S%3BOgunfusika%2C+M+O%3BMerriam%2C+W+G%3BBennett%2C+W+P%3BBilliar%2C+T+R%3BHarris%2C+C+C&rft.aulast=Ambs&rft.aufirst=S&rft.date=1998-07-21&rft.volume=95&rft.issue=15&rft.spage=8823&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 - 1998-08-20 N1 - Date created - 1998-08-20 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Immunol. 1987 Jul 15;139(2):518-25 [3110273] Cancer Res. 1998 Jan 15;58(2):334-41 [9443414] Biochem Biophys Res Commun. 1990 May 16;168(3):1034-40 [2346476] J Leukoc Biol. 1990 Dec;48(6):565-9 [2230601] Science. 1990 Nov 30;250(4985):1233-8 [1978757] Pharmacol Rev. 1991 Jun;43(2):109-42 [1852778] J Exp Med. 1991 Oct 1;174(4):761-7 [1717630] Cancer Res. 1991 Dec 1;51(23 Pt 1):6304-11 [1933891] Science. 1991 Nov 15;254(5034):1001-3 [1948068] Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10480-4 [1720542] Nature. 1992 Mar 19;356(6366):215-21 [1552940] Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):3030-4 [1557408] J Exp Med. 1992 Jul 1;176(1):261-4 [1377225] J Biol Chem. 1992 Aug 25;267(24):16771-4 [1512218] J Biol Chem. 1992 Oct 25;267(30):21277-80 [1383221] J Physiol. 1992 Aug;454:451-65 [1282159] Science. 1993 Jan 1;259(5091):84-7 [8418500] Proc Natl Acad Sci U S A. 1993 Jan 15;90(2):522-6 [7678458] Nature. 1993 Apr 29;362(6423):847-9 [8479522] J Exp Med. 1993 Jun 1;177(6):1779-84 [7684434] Biochem Biophys Res Commun. 1993 Jun 30;193(3):1076-82 [8323533] J Exp Med. 1993 Aug 1;178(2):605-13 [7688028] Cell. 1993 Sep 24;74(6):957-67 [8402885] Proc Natl Acad Sci U S A. 1993 Oct 15;90(20):9730-4 [7692452] Cell. 1993 Nov 19;75(4):765-78 [8242748] Cell. 1993 Nov 19;75(4):817-25 [8242752] Cancer Res. 1994 Jun 15;54(12):3131-5 [8205530] Cell. 1994 Sep 23;78(6):915-8 [7522969] J Biol Chem. 1994 Oct 21;269(42):26066-75 [7929318] FEBS Lett. 1994 Nov 21;355(1):23-6 [7525358] Br J Pharmacol. 1995 Feb;114(3):689-93 [7537593] Proc Natl Acad Sci U S A. 1995 May 9;92(10):4392-6 [7538668] J Immunol. 1995 Sep 15;155(6):2858-65 [7673702] Chem Res Toxicol. 1995 Apr-May;8(3):473-7 [7578935] J Biol Chem. 1995 Dec 8;270(49):29350-5 [7493969] Adv Pharmacol. 1995;34:17-43 [8562432] Proc Natl Acad Sci U S A. 1996 Feb 6;93(3):1054-9 [8577713] Hypertension. 1996 Mar;27(3 Pt 2):823-6 [8613247] Proc Natl Acad Sci U S A. 1996 Mar 19;93(6):2442-7 [8637893] Curr Top Cell Regul. 1996;34:159-87 [8646847] Cancer Res. 1996 Feb 15;56(4):866-74 [8631026] Mol Carcinog. 1996 May;16(1):20-31 [8634091] Proc Natl Acad Sci U S A. 1996 Mar 5;93(5):1776-80 [8700834] Proc Natl Acad Sci U S A. 1996 Aug 6;93(16):8175-82 [8710843] Biochem J. 1996 Oct 1;319 ( Pt 1):299-305 [8870682] Biochim Biophys Acta. 1996 Oct 9;1288(2):F31-6 [8876631] Proc Natl Acad Sci U S A. 1996 Dec 24;93(26):15102-7 [8986771] J Biol Chem. 1997 Jan 10;272(2):1402-11 [8995451] J Exp Med. 1997 Feb 17;185(4):601-7 [9034139] FASEB J. 1997 May;11(6):443-8 [9194524] Nature. 1997 Jul 31;388(6641):432-3 [9242400] Cancer Res. 1997 Aug 15;57(16):3365-9 [9269997] FASEB J. 1997 Sep;11(11):887-95 [9285487] J Biol Chem. 1997 Sep 26;272(39):24125-8 [9305857] J Biol Chem. 1997 Dec 5;272(49):31138-48 [9388267] Proc Natl Acad Sci U S A. 1990 Jan;87(2):682-5 [1689048] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Replacement of tyrosine 1251 in the carboxyl terminus of the insulin-like growth factor-I receptor disrupts the actin cytoskeleton and inhibits proliferation and anchorage-independent growth. AN - 79999468; 9660809 AB - Insulin-like growth factor (IGF)-I signaling through the IGF-I receptor modulates cellular adhesion and proliferation and the transforming ability of cells overexpressing the IGF-I receptor. Tyrosine phosphorylation of intracellular proteins is essential for this transduction of the IGF-I-induced mitogenic and tumorigenic signals. IGF-I induces specific cytoskeletal structure and the phosphorylation of proteins in the associated focal adhesion complexes. The determination of the exact pathways emanating from the IGF-I receptor that are involved in mediating these signals will contribute greatly to the understanding of IGF-I action. We have previously shown that replacement of tyrosine residues 1250 and 1251 in the carboxyl terminus of the IGF-I receptor abrogates IGF-I-induced cellular proliferation and tumor formation in nude mice. In this study, replacement of either tyrosine 1250 or 1251 similarly reduces the cells ability to grow in an anchorage-independent manner. The actin cytoskeleton and cellular localization of vinculin are disrupted by replacement of tyrosine 1251. Tyrosine residues 1250 and 1251 are not essential for tyrosine phosphorylation of two known substrates; insulin receptor substrate-1 and SHC, nor association of known downstream adaptor proteins to these substrates. In addition, these mutant IGF-I receptors do not affect IGF-I-stimulated p42/p44 mitogen-activated protein kinase activation or phosphatidylinositol (PI) 3'-kinase activity. Thus, it appears that in fibroblasts expressing tyrosine 1250 and 1251 mutant IGF-I receptors, the signal transduction pathways impacting on mitogenesis and tumorigenesis do not occur exclusively through the PI 3'-kinase or mitogen-activated protein kinase pathways. JF - The Journal of biological chemistry AU - Blakesley, V A AU - Koval, A P AU - Stannard, B S AU - Scrimgeour, A AU - LeRoith, D AD - Diabetes Branch, NIDDK, National Institutes of Health, Bethesda, Maryland 20892-1770, USA. Y1 - 1998/07/17/ PY - 1998 DA - 1998 Jul 17 SP - 18411 EP - 18422 VL - 273 IS - 29 SN - 0021-9258, 0021-9258 KW - Actins KW - 0 KW - IRS1 protein, human KW - Insulin Receptor Substrate Proteins KW - Irs1 protein, mouse KW - Phosphoproteins KW - Vinculin KW - 125361-02-6 KW - Tyrosine KW - 42HK56048U KW - Insulin-Like Growth Factor I KW - 67763-96-6 KW - Phosphatidylinositol 3-Kinases KW - EC 2.7.1.- KW - Receptor, IGF Type 1 KW - EC 2.7.10.1 KW - Calcium-Calmodulin-Dependent Protein Kinases KW - EC 2.7.11.17 KW - Index Medicus KW - 3T3 Cells KW - Animals KW - Calcium-Calmodulin-Dependent Protein Kinases -- metabolism KW - Phosphatidylinositol 3-Kinases -- metabolism KW - Enzyme Activation KW - Humans KW - Cell Division -- drug effects KW - Mice KW - Mice, Nude KW - Insulin-Like Growth Factor I -- pharmacology KW - Structure-Activity Relationship KW - Mutagenesis, Site-Directed KW - Vinculin -- metabolism KW - Phosphorylation KW - Cell Adhesion -- drug effects KW - Protein Conformation KW - Phosphoproteins -- metabolism KW - Cytoskeleton -- metabolism KW - Receptor, IGF Type 1 -- metabolism KW - Actins -- metabolism KW - Tyrosine -- genetics KW - Receptor, IGF Type 1 -- genetics KW - Tyrosine -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79999468?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Replacement+of+tyrosine+1251+in+the+carboxyl+terminus+of+the+insulin-like+growth+factor-I+receptor+disrupts+the+actin+cytoskeleton+and+inhibits+proliferation+and+anchorage-independent+growth.&rft.au=Blakesley%2C+V+A%3BKoval%2C+A+P%3BStannard%2C+B+S%3BScrimgeour%2C+A%3BLeRoith%2C+D&rft.aulast=Blakesley&rft.aufirst=V&rft.date=1998-07-17&rft.volume=273&rft.issue=29&rft.spage=18411&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 - 1998-08-13 N1 - Date created - 1998-08-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Complex formation by all five homologues of mammalian translation initiation factor 3 subunits from yeast Saccharomyces cerevisiae. AN - 79995283; 9660829 AB - The PRT1, TIF34, GCD10, and SUI1 proteins of Saccharomyces cerevisiae were found previously to copurify with eukaryotic translation initiation factor 3 (eIF3) activity. Although TIF32, NIP1, and TIF35 are homologous to subunits of human eIF3, they were not known to be components of the yeast factor. We detected interactions between PRT1, TIF34, and TIF35 by the yeast two-hybrid assay and in vitro binding assays. Discrete segments (70-150 amino acids) of PRT1 and TIF35 were found to be responsible for their binding to TIF34. Temperature-sensitive mutations mapping in WD-repeat domains of TIF34 were isolated that decreased binding between TIF34 and TIF35 in vitro. The lethal effect of these mutations was suppressed by increasing TIF35 gene dosage, suggesting that the TIF34-TIF35 interaction is important for TIF34 function in translation. Pairwise in vitro interactions were also detected between PRT1 and TIF32, TIF32 and NIP1, and NIP1 and SUI1. Furthermore, PRT1, NIP1, TIF34, TIF35, and a polypeptide with the size of TIF32 were specifically coimmunoprecipitated from the ribosomal salt wash fraction. We propose that all five yeast proteins homologous to human eIF3 subunits are components of a stable heteromeric complex in vivo and may comprise the conserved core of yeast eIF3. JF - The Journal of biological chemistry AU - Asano, K AU - Phan, L AU - Anderson, J AU - Hinnebusch, A G AD - Laboratory of Eukaryotic Gene Regulation, NICHD, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/07/17/ PY - 1998 DA - 1998 Jul 17 SP - 18573 EP - 18585 VL - 273 IS - 29 SN - 0021-9258, 0021-9258 KW - DNA-Binding Proteins KW - 0 KW - Eukaryotic Initiation Factor-3 KW - Fungal Proteins KW - NIP1 protein, S cerevisiae KW - Nuclear Proteins KW - Peptide Initiation Factors KW - Prt1 protein, S cerevisiae KW - Saccharomyces cerevisiae Proteins KW - TIF34 protein, S cerevisiae KW - Transcription Factors KW - Index Medicus KW - Animals KW - Nuclear Proteins -- genetics KW - Transcription Factors -- metabolism KW - Humans KW - Temperature KW - Amino Acid Sequence KW - Transcription Factors -- genetics KW - Protein Binding KW - Saccharomyces cerevisiae KW - Mutagenesis, Site-Directed KW - Transcription Factors -- chemistry KW - Molecular Sequence Data KW - Point Mutation KW - Nuclear Proteins -- chemistry KW - Nuclear Proteins -- metabolism KW - Protein Conformation KW - Fungal Proteins -- chemistry KW - Peptide Initiation Factors -- metabolism KW - Peptide Initiation Factors -- genetics KW - Fungal Proteins -- metabolism KW - DNA-Binding Proteins -- chemistry KW - DNA-Binding Proteins -- genetics KW - Peptide Initiation Factors -- chemistry KW - Fungal Proteins -- genetics KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79995283?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Complex+formation+by+all+five+homologues+of+mammalian+translation+initiation+factor+3+subunits+from+yeast+Saccharomyces+cerevisiae.&rft.au=Asano%2C+K%3BPhan%2C+L%3BAnderson%2C+J%3BHinnebusch%2C+A+G&rft.aulast=Asano&rft.aufirst=K&rft.date=1998-07-17&rft.volume=273&rft.issue=29&rft.spage=18573&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 - 1998-08-13 N1 - Date created - 1998-08-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of curcumin on the aryl hydrocarbon receptor and cytochrome P450 1A1 in MCF-7 human breast carcinoma cells. AN - 80057339; 9698073 AB - We examined the interaction of curcumin, a dietary constituent and chemopreventive compound, with the carcinogen activation pathway mediated by the aryl hydrocarbon receptor (AhR) in MCF-7 mammary epithelial carcinoma cells. Curcumin caused a rapid accumulation of cytochrome P450 1A1 (CYP1A1) mRNA in a time- and concentration-dependent manner, and CYP1A1 monooxygenase activity increased as measured by ethoxyresorufin-O-deethylation. Curcumin activated the DNA-binding capacity of the AhR for the xenobiotic responsive element of CYP1A1 as measured by the electrophoretic-mobility shift assay (EMSA). Curcumin was able to compete with the prototypical AhR ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin for binding to the AhR in isolated MCF-7 cytosol, indicating that it interacts directly with the receptor. Although curcumin could activate the AhR on its own, it partially inhibited the activation of AhR, as measured by EMSA, and partially decreased the accumulation of CYP1A1 mRNA caused by the mammary carcinogen dimethylbenzanthracene (DMBA). Curcumin competitively inhibited CYP1A1 activity in DMBA-treated cells and in microsomes isolated from DMBA-treated cells. Curcumin also inhibited the metabolic activation of DMBA, as measured by the formation of DMBA-DNA adducts, and decreased DMBA-induced cytotoxicity. These results suggest that the chemopreventive effect of curcumin may be due, in part, to its ability to compete with aryl hydrocarbons for both the AhR and CYP1A1. Curcumin may thus be a natural ligand and substrate of the AhR pathway. JF - Biochemical pharmacology AU - Ciolino, H P AU - Daschner, P J AU - Wang, T T AU - Yeh, G C AD - Cellular Defense and Carcinogenesis Section, National Cancer Institute-Frederick Cancer Research and Development Center, National Institutes of Health, Frederick, MD 21702-1201, USA. hciolino@mail.ncifcrf.gov Y1 - 1998/07/15/ PY - 1998 DA - 1998 Jul 15 SP - 197 EP - 206 VL - 56 IS - 2 SN - 0006-2952, 0006-2952 KW - Anticarcinogenic Agents KW - 0 KW - Carcinogens KW - DNA-Binding Proteins KW - Polychlorinated Dibenzodioxins KW - RNA, Messenger KW - Receptors, Aryl Hydrocarbon KW - 9,10-Dimethyl-1,2-benzanthracene KW - 57-97-6 KW - Cytochrome P-450 CYP1A1 KW - EC 1.14.14.1 KW - Curcumin KW - IT942ZTH98 KW - Index Medicus KW - 9,10-Dimethyl-1,2-benzanthracene -- pharmacokinetics KW - Tumor Cells, Cultured KW - RNA, Messenger -- metabolism KW - Biotransformation KW - Humans KW - Carcinogens -- pharmacokinetics KW - DNA-Binding Proteins -- genetics KW - RNA, Messenger -- genetics KW - Protein Binding KW - Polychlorinated Dibenzodioxins -- metabolism KW - Breast Neoplasms -- genetics KW - Cytochrome P-450 CYP1A1 -- genetics KW - Breast Neoplasms -- pathology KW - Anticarcinogenic Agents -- pharmacology KW - Receptors, Aryl Hydrocarbon -- metabolism KW - Receptors, Aryl Hydrocarbon -- genetics KW - Curcumin -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80057339?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Effect+of+curcumin+on+the+aryl+hydrocarbon+receptor+and+cytochrome+P450+1A1+in+MCF-7+human+breast+carcinoma+cells.&rft.au=Ciolino%2C+H+P%3BDaschner%2C+P+J%3BWang%2C+T+T%3BYeh%2C+G+C&rft.aulast=Ciolino&rft.aufirst=H&rft.date=1998-07-15&rft.volume=56&rft.issue=2&rft.spage=197&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 - 1998-08-21 N1 - Date created - 1998-08-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - 5-fluorouracil-mediated thymidylate synthase induction in malignant and nonmalignant human cells. AN - 80056309; 9698077 AB - Thymidylate synthase (TS, EC 2.1.1.45) is an important target enzyme for the fluoropyrimidines used in cancer chemotherapy. Studies have documented a 2- to 4-fold induction of TS protein following 5-fluorouracil (5-FU) treatment of malignant cells. We measured the effect that 5-FU exposure had on TS protein expression in nonmalignant human breast (MCF-10 and HBL-100), colorectal (ATCC Co18, Co112, and Co33), and bone marrow cells along with malignant breast (MCF-7) and colon (NCI-H630) cells. Twenty-four hours after plating, cells were treated with 0.01 to 10 microM of 5-FU for a period of 24 hr. TS was quantitated by Western immunoblot using monoclonal antibody TS106. Absolute levels of TS in nonmalignant cells were substantially lower than in the malignant lines, ranging from approximately 40% in HBL-100 cells to less than 10% in the colon lines. An approximately two-fold induction in the level of TS was found for all cell lines examined, and there was a strong dependence on 5-FU exposure concentration in free TS levels of MCF-WT, and total TS levels of H630-WT, normal bone marrow, and MCF-10 cells. The induction of TS following 5-FU exposure is a generally observed phenomenon in both malignant and nonmalignant cells, suggesting that a selective means for inhibiting this induction may be critical for the development of alternative therapeutic strategies using 5-FU and the antifolate TS inhibitors. JF - Biochemical pharmacology AU - Parr, A L AU - Drake, J C AU - Gress, R E AU - Schwartz, G AU - Steinberg, S M AU - Allegra, C J AD - National Cancer Institute, Medicine Branch, National Naval Medical Center, Bethesda, MD 20889-5101, USA. parra@navmed.nci.nih.gov Y1 - 1998/07/15/ PY - 1998 DA - 1998 Jul 15 SP - 231 EP - 235 VL - 56 IS - 2 SN - 0006-2952, 0006-2952 KW - Antimetabolites, Antineoplastic KW - 0 KW - Thymidylate Synthase KW - EC 2.1.1.45 KW - Fluorouracil KW - U3P01618RT KW - Index Medicus KW - Tumor Cells, Cultured KW - Humans KW - Enzyme Induction KW - Cell Line KW - Fluorouracil -- pharmacology KW - Thymidylate Synthase -- biosynthesis KW - Antimetabolites, Antineoplastic -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80056309?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=5-fluorouracil-mediated+thymidylate+synthase+induction+in+malignant+and+nonmalignant+human+cells.&rft.au=Parr%2C+A+L%3BDrake%2C+J+C%3BGress%2C+R+E%3BSchwartz%2C+G%3BSteinberg%2C+S+M%3BAllegra%2C+C+J&rft.aulast=Parr&rft.aufirst=A&rft.date=1998-07-15&rft.volume=56&rft.issue=2&rft.spage=231&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 - 1998-08-21 N1 - Date created - 1998-08-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of a naturally occurring Pro15-Ser15 substitution in the serotonin5A receptor gene in alcoholics and healthy volunteers. AN - 80044174; 9685650 AB - We screened the serotonin5A receptor gene coding region in 186 unrelated alcoholic patients and 187 controls. A relatively abundant amino acid substitution and two synonymous DNA substitutions were detected. Two synonymous variants, A12T and C789T, had rarer-allele frequencies of 23% and 1%, respectively. The Pro15Ser substitution is located in the amino terminal, extracellular domain of the receptor adjacent to a putative phosphorylation site. Pro15Ser had rarer-allele frequencies of 8.1% and 5.9% in Finnish alcoholic patients and controls, respectively (p=n.s.). Copyright 1998 Elsevier Science B.V. All rights reserved. JF - Brain research. Molecular brain research AU - Iwata, N AU - Virkkunen, M AU - Linnoila, M AU - Goldman, D AD - Laboratory of Neurogenetics, DICBR, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892-8110, USA. nakao@box-n.nih.gov Y1 - 1998/07/15/ PY - 1998 DA - 1998 Jul 15 SP - 217 EP - 220 VL - 58 IS - 1-2 SN - 0169-328X, 0169-328X KW - DNA Primers KW - 0 KW - Receptors, Serotonin KW - serotonin 5 receptor KW - Serine KW - 452VLY9402 KW - Proline KW - 9DLQ4CIU6V KW - Index Medicus KW - Polymerase Chain Reaction KW - Reference Values KW - Gene Frequency KW - Polymorphism, Restriction Fragment Length KW - Exons KW - Humans KW - Amino Acid Substitution KW - Receptors, Serotonin -- chemistry KW - Point Mutation KW - Alcoholism -- genetics KW - Receptors, Serotonin -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80044174?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain+research.+Molecular+brain+research&rft.atitle=Identification+of+a+naturally+occurring+Pro15-Ser15+substitution+in+the+serotonin5A+receptor+gene+in+alcoholics+and+healthy+volunteers.&rft.au=Iwata%2C+N%3BVirkkunen%2C+M%3BLinnoila%2C+M%3BGoldman%2C+D&rft.aulast=Iwata&rft.aufirst=N&rft.date=1998-07-15&rft.volume=58&rft.issue=1-2&rft.spage=217&rft.isbn=&rft.btitle=&rft.title=Brain+research.+Molecular+brain+research&rft.issn=0169328X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-09-21 N1 - Date created - 1998-09-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Single gene complementation of the hPMS2 defect in HEC-1-A endometrial carcinoma cells. AN - 80029972; 9679958 AB - Results from the analysis of human tumor cell lines with mutations in DNA mismatch repair genes have contributed to the understanding of the functions of these gene products in DNA mismatch repair, microsatellite instability, cell cycle checkpoint control, transcription-coupled nucleotide excision repair, and resistance to cytotoxic agents. However, complementation of human DNA mismatch repair defects by introduction of a single cloned gene or cDNA, which would serve to directly prove or disprove their involvement in these processes, has not been accomplished. Here, we introduce a wild-type copy of the hPMS2 cDNA by stable transfection into the PMS2 mutant HEC-1-A cell line. HEC-1-A cells expressing wild-type hPMS2 exhibit increased microsatellite stability, have a reduced mutation rate at the endogenous hypoxanthine phosphoribosyltransferase locus and extracts from these cells are able to perform strand-specific mismatch repair. These results demonstrate that the hPMS2 gene is integral to the maintenance of genome stability. JF - Cancer research AU - Risinger, J I AU - Umar, A AU - Glaab, W E AU - Tindall, K R AU - Kunkel, T A AU - Barrett, J C AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1998/07/15/ PY - 1998 DA - 1998 Jul 15 SP - 2978 EP - 2981 VL - 58 IS - 14 SN - 0008-5472, 0008-5472 KW - DNA, Neoplasm KW - 0 KW - DNA-Binding Proteins KW - Neoplasm Proteins KW - Proteins KW - Adenosine Triphosphatases KW - EC 3.6.1.- KW - PMS2 protein, human KW - Mismatch Repair Endonuclease PMS2 KW - EC 3.6.1.3 KW - DNA Repair Enzymes KW - EC 6.5.1.- KW - Index Medicus KW - HeLa Cells KW - Humans KW - Genetic Complementation Test KW - Mutation -- genetics KW - DNA, Neoplasm -- metabolism KW - Female KW - DNA Repair -- genetics KW - Neoplasm Proteins -- genetics KW - Endometrial Neoplasms -- genetics KW - Proteins -- metabolism KW - Proteins -- genetics KW - Neoplasm Proteins -- metabolism KW - Carcinoma -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80029972?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+reports&rft.atitle=A+phase+II+study+of+bromocriptine+in+patients+with+androgen-independent+prostate+cancer.&rft.au=Horti%2C+J%3BFigg%2C+W+D%3BWeinberger%2C+B%3BKohler%2C+D%3BSartor%2C+O&rft.aulast=Horti&rft.aufirst=J&rft.date=1998-07-01&rft.volume=5&rft.issue=4&rft.spage=893&rft.isbn=&rft.btitle=&rft.title=Oncology+reports&rft.issn=1021335X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-08-07 N1 - Date created - 1998-08-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Direct binding and functional transfer of NK cell inhibitory receptors reveal novel patterns of HLA-C allotype recognition. AN - 80016190; 9670929 AB - Cytotoxicity of human NK cells is under negative control of killer cell Ig-like receptors (KIR) specific for HLA class I. To determine the specificity of five KIR containing two Ig domains (KIR2D), direct binding of soluble recombinant KIR2D to a panel of HLA class I transfectants was assayed. One soluble KIR2D, derived from an inhibitory receptor with a long cytoplasmic tail (KIR2DL1), bound to HLA-C allotypes containing asparagine 77 and lysine 80 in the heavy chain, as expected, since these allotypes inhibit lysis by NK cells expressing KIR2DL1. Surprisingly, another KIR2D (KIR2DL2), which inhibits NK lysis of cells expressing HLA-C molecules with serine 77 and asparagine 80, bound to HLA-C allotypes carrying either amino acid motif. Expression of the KIR2DL receptors in NK cells using recombinant vaccinia viruses confirmed these patterns of recognition, and identified KIR2DL3 as another KIR reacting with both groups of HLA-C allotypes. Mutagenesis of amino acid 44 in KIR2DL1 and KIR2DL2 suggested this residue controls the affinity of KIR for the 77/80 motif of HLA-C molecules. Two other soluble KIR2D, derived from noninhibitory receptors with short cytoplasmic tails (KIR2DS), did not bind to any of the HLA class I allotypes tested. One of these receptors (KIR2DS2) is closely related in sequence to KIR2DL2. Substitution of tyrosine 45 with the phenylalanine conserved in other KIR was sufficient to permit specific binding of KIR2DS2 to HLA-C. These results show that KIR2DL receptors are specific for HLA-C, but that recognition of HLA-C allotypes appears more permissive than indicated by previous functional experiments. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Winter, C C AU - Gumperz, J E AU - Parham, P AU - Long, E O AU - Wagtmann, N AD - Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, Rockville, MD 20852-1727, USA. Y1 - 1998/07/15/ PY - 1998 DA - 1998 Jul 15 SP - 571 EP - 577 VL - 161 IS - 2 SN - 0022-1767, 0022-1767 KW - HLA-C Antigens KW - 0 KW - KIR2DL2 protein, human KW - KIR2DL3 protein, human KW - Receptors, Immunologic KW - Receptors, KIR KW - Receptors, KIR2DL1 KW - Receptors, KIR2DL2 KW - Receptors, KIR2DL3 KW - Recombinant Fusion Proteins KW - Phenylalanine KW - 47E5O17Y3R KW - Abridged Index Medicus KW - Index Medicus KW - Transfection -- immunology KW - Solubility KW - Phenylalanine -- metabolism KW - Recombinant Fusion Proteins -- immunology KW - Humans KW - Protein Binding -- immunology KW - Recombinant Fusion Proteins -- metabolism KW - Mutagenesis, Site-Directed KW - Amino Acid Substitution -- genetics KW - Phenylalanine -- genetics KW - Protein Binding -- genetics KW - Receptors, Immunologic -- genetics KW - HLA-C Antigens -- metabolism KW - Alleles KW - Receptors, Immunologic -- physiology KW - Receptors, Immunologic -- metabolism KW - HLA-C Antigens -- immunology KW - Killer Cells, Natural -- metabolism KW - Killer Cells, Natural -- immunology KW - HLA-C Antigens -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80016190?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Direct+binding+and+functional+transfer+of+NK+cell+inhibitory+receptors+reveal+novel+patterns+of+HLA-C+allotype+recognition.&rft.au=Winter%2C+C+C%3BGumperz%2C+J+E%3BParham%2C+P%3BLong%2C+E+O%3BWagtmann%2C+N&rft.aulast=Winter&rft.aufirst=C&rft.date=1998-07-15&rft.volume=161&rft.issue=2&rft.spage=571&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 - 1998-07-30 N1 - Date created - 1998-07-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Critical role of arg433 in rat transketolase activity as probed by site-directed mutagenesis. AN - 80004242; 9657977 AB - It has been shown that one arginine per monomer at an unknown position is essential for enzyme activity of the homodimeric transketolase (TK) [Kremer, Egan and Sable (1980) J. Biol. Chem. 255, 2405-2410]. To identify the critical arginine, four highly conserved arginine residues of rat TK (Arg102, Arg350, Arg433 and Arg506) were replaced with alanine by site-directed mutagenesis. Wild-type and mutant TK proteins were produced in Escherichia coli and characterized. The Arg102-->Ala mutant exhibited similar catalytic activity to the wild-type enzyme, whereas Arg350-->Ala, Arg506-->Ala and Arg433-->Ala mutants exhibited 36.7, 37.0 and 6.1% of the wild-type activity respectively. Three recombinant proteins (wild-type, Arg350-->Ala and Arg433-->Ala) were purified to apparent homogeneity using Ni2+-affinity chromatography and further characterized. All these proteins were able to form homodimers (148 kDa), as shown by immunoblot analysis subsequent to non-denaturing gel electrophoresis. The Arg433-->Ala mutant protein was less stable than the wild-type and Arg350-->Ala proteins at 55 degrees C. Kinetic analyses revealed that both Vmax and Km values were markedly affected in the Arg433-->Ala mutant. The Km values for two substrates xylulose 5-phosphate and ribose 5-phosphate were 11.5- and 24.3-fold higher respectively. The kcat/Km values of the Arg433-->Ala mutant for the two substrates were less than 1% of those of the wild-type protein. Molecular modelling of the rat TK revealed that Arg433 of one monomer has three potential hydrogen-bond interactions with the catalytically important highly conserved loop of the other monomer. Thus, our biochemical analyses and modelling data suggest the critical role of the previously uncharacterized Arg433 in TK activity. JF - The Biochemical journal AU - Soh, Y AU - Song, B J AU - Jeng, J AU - Kallarakal, A T AD - Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, 12501 Washington Avenue, Rockville, MD 20852, USA. Y1 - 1998/07/15/ PY - 1998 DA - 1998 Jul 15 SP - 367 EP - 372 VL - 333 ( Pt 2) SN - 0264-6021, 0264-6021 KW - Arginine KW - 94ZLA3W45F KW - Transketolase KW - EC 2.2.1.1 KW - Index Medicus KW - Rats KW - Mutagenesis, Site-Directed KW - Animals KW - Models, Molecular KW - Kinetics KW - Enzyme Stability KW - Image Processing, Computer-Assisted KW - Structure-Activity Relationship KW - Protein Conformation KW - Catalysis KW - Transketolase -- metabolism KW - Arginine -- metabolism KW - Arginine -- genetics KW - Transketolase -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80004242?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Biochemical+journal&rft.atitle=Critical+role+of+arg433+in+rat+transketolase+activity+as+probed+by+site-directed+mutagenesis.&rft.au=Soh%2C+Y%3BSong%2C+B+J%3BJeng%2C+J%3BKallarakal%2C+A+T&rft.aulast=Soh&rft.aufirst=Y&rft.date=1998-07-15&rft.volume=333+%28+Pt+2%29&rft.issue=&rft.spage=367&rft.isbn=&rft.btitle=&rft.title=The+Biochemical+journal&rft.issn=02646021&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-09-10 N1 - Date created - 1998-09-10 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Neurochem. 1986 Jul;47(1):278-81 [3711903] Clin Chem. 1984 May;30(5):658-61 [6713626] Arch Neurol. 1988 Aug;45(8):841-5 [3395257] Gene. 1989 Apr 15;77(1):51-9 [2744487] Biochem Biophys Res Commun. 1990 Oct 30;172(2):396-401 [2241941] Biochemistry. 1992 Feb 18;31(6):1892-6 [1737042] Biochem Biophys Res Commun. 1992 Mar 31;183(3):1159-66 [1567394] EMBO J. 1992 Jul;11(7):2373-9 [1628611] J Mol Biol. 1992 Jul 20;226(2):507-33 [1640463] FEBS Lett. 1992 Nov 30;313(3):229-31 [1446740] J Biol Chem. 1993 Jan 15;268(2):1397-404 [8419340] Alcohol Clin Exp Res. 1993 Feb;17(1):31-7 [8452206] Eur J Biochem. 1993 Oct 1;217(1):487-92 [7916691] J Biol Chem. 1993 Nov 15;268(32):24346-52 [8226984] Alcohol Clin Exp Res. 1993 Oct;17(5):1084-8 [8279670] J Mol Biol. 1994 May 6;238(3):387-404 [8176731] J Biol Chem. 1994 Dec 23;269(51):32144-50 [7798210] Arch Biochem Biophys. 1996 Feb 1;326(1):137-44 [8579361] J Biol Chem. 1997 Jan 17;272(3):1864-9 [8999873] Eur J Biochem. 1997 Mar 1;244(2):646-52 [9119035] J Biol Chem. 1953 Dec;205(2):661-82 [13129245] J Clin Invest. 1968 Oct;47(10):2268-80 [5676522] Arch Biochem Biophys. 1975 Dec;171(2):527-32 [1106327] N Engl J Med. 1977 Dec 22;297(25):1367-70 [927453] J Biol Chem. 1980 Mar 25;255(6):2405-10 [7358678] J Biol Chem. 1981 May 25;256(10):4877-83 [7014563] Arch Biochem Biophys. 1983 Apr 15;222(2):489-96 [6847198] J Biol Chem. 1983 Oct 25;258(20):12405-8 [6355086] J Clin Invest. 1987 Apr;79(4):1039-43 [3558815] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Eosinophil cationic protein/RNase 3 is another RNase A-family ribonuclease with direct antiviral activity AN - 16532718; 4395030 AB - Eosinophil cationic protein (ECP) is one of two RNase A-superfamily ribonucleases found in secretory granules of human eosinophilic leukocytes. Although the physiologic function of eosinophils [and thus of the two eosinophil ribonucleases, ECP and eosinophil-derived neurotoxin (EDN)] remains controversial, we have recently shown that isolated human eosinophils promote ribonuclease-dependent toxicity toward extracellular virions of the single-stranded RNA virus, respiratory syncytial virus, group B (RSV-B). We have also shown that recombinant human EDN (rhEDN) can act alone as a ribonuclease-dependent antiviral agent. In this work, we provide a biochemical characterization of recombinant human ECP (rhECP) prepared in baculovirus, and demonstrate that rhECP also promotes ribonuclease-dependent antiviral activity. The rhECP described here is N-glycosylated, as is native ECP, and has similar to 100-fold more ribonuclease activity than non-glycosylated rhECP prepared in bacteria. The enzymatic activity of rhECP was sensitive to inhibition by placental ribonuclease inhibitor (RI). Although rhECP was not as effective as rhEDN at reducing viral infectivity (500 nM rhECP reduced infectivity of RSV-B similar to 6 fold; 500 nM rhEDN, >50 fold), the antiviral activity appears to be unique to the eosinophil ribonucleases; no reduction in infectivity was promoted by bovine RNase A, by the amphibian ribonuclease, onconase, nor by the closely-related human ribonuclease, RNase k6. Interestingly, combinations of rhEDN and rhECP did not result in either a synergistic or even an additive antiviral effect. Taken together, these results suggest that that the interaction between the eosinophil ribonucleases and the extracellular virions of RSV-B may be specific and saturable. JF - Nucleic Acids Research AU - Domachowske, J B AU - Dyer, K D AU - Adams, A G AU - Leto, T L AU - Rosenberg, H F AD - Department of Pediatrics, State University of New York Health Science Center at Syracuse, Syracuse, NY 13210, USA, hr2k@nih.gov Y1 - 1998/07/15/ PY - 1998 DA - 1998 Jul 15 SP - 3358 EP - 3363 VL - 26 IS - 14 SN - 0305-1048, 0305-1048 KW - Eosinophil cationic protein KW - Eosinophil-derived neurotoxin KW - RNase A KW - Ribonuclease KW - Ribonuclease A KW - Virology & AIDS Abstracts; Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts A: Industrial & Applied Microbiology KW - N 14711:RNases KW - A 01068:Antiviral & viricidal KW - V 22100:Antiviral agents UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16532718?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologya&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nucleic+Acids+Research&rft.atitle=Eosinophil+cationic+protein%2FRNase+3+is+another+RNase+A-family+ribonuclease+with+direct+antiviral+activity&rft.au=Domachowske%2C+J+B%3BDyer%2C+K+D%3BAdams%2C+A+G%3BLeto%2C+T+L%3BRosenberg%2C+H+F&rft.aulast=Domachowske&rft.aufirst=J&rft.date=1998-07-15&rft.volume=26&rft.issue=14&rft.spage=3358&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 - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - In vivo studies with [125I]5-I-A-85380, a nicotinic acetylcholine receptor radioligand. AN - 80048523; 9694220 AB - 5-[125I]iodo-3-(2(S)-azetidinylmethoxy)pyridine ([125I]5-I-A-85380) was evaluated in the mouse as a potential in vivo imaging ligand for central nicotinic acetylcholine receptors (nAChRs). After i.v. administration of [125I]5-I-A-85380, peak brain levels of radioactivity were measured within 1 h and declined slowly over 4 h. [125I]5-I-A-85380 binding was saturable, and both its pharmacology, based upon inhibition studies, and its pattern of accumulation in brain regions having high nAChR densities were consistent with an interaction at alpha4beta2 nAChR agonist binding sites. The thalamus:cerebellum radioactivity ratio, a measure of specific labeling, reached 37. Therefore, radiolabeled 5-I-A-85380 has excellent potential as an imaging radiotracer for nAChRs, particularly with single photon emission computed tomography, when 123I is incorporated into the molecule. JF - Neuroreport AU - Vaupel, D B AU - Mukhin, A G AU - Kimes, A S AU - Horti, A G AU - Koren, A O AU - London, E D AD - Brain Imaging Center, Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD 21224, USA. Y1 - 1998/07/13/ PY - 1998 DA - 1998 Jul 13 SP - 2311 EP - 2317 VL - 9 IS - 10 SN - 0959-4965, 0959-4965 KW - A 85380 KW - 0 KW - Azetidines KW - Cholinergic Antagonists KW - Iodine Radioisotopes KW - Ligands KW - Receptors, Nicotinic KW - Index Medicus KW - Seizures -- chemically induced KW - Behavior, Animal -- drug effects KW - Animals KW - Tomography, Emission-Computed, Single-Photon KW - Mice KW - Cholinergic Antagonists -- pharmacology KW - Brain -- metabolism KW - Tissue Distribution KW - Radioligand Assay KW - Autoradiography KW - Male KW - Azetidines -- pharmacokinetics KW - Receptors, Nicotinic -- drug effects KW - Azetidines -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80048523?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuroreport&rft.atitle=In+vivo+studies+with+%5B125I%5D5-I-A-85380%2C+a+nicotinic+acetylcholine+receptor+radioligand.&rft.au=Vaupel%2C+D+B%3BMukhin%2C+A+G%3BKimes%2C+A+S%3BHorti%2C+A+G%3BKoren%2C+A+O%3BLondon%2C+E+D&rft.aulast=Vaupel&rft.aufirst=D&rft.date=1998-07-13&rft.volume=9&rft.issue=10&rft.spage=2311&rft.isbn=&rft.btitle=&rft.title=Neuroreport&rft.issn=09594965&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-10-14 N1 - Date created - 1998-10-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Functional characterization of a series of mutant G protein alphaq subunits displaying promiscuous receptor coupling properties. AN - 79985017; 9651394 AB - The N termini of two G protein alpha subunits, alphaq and alpha11, differ from those of other alpha subunits in that they display a unique, highly conserved six-amino acid extension (MTLESI(M)). We recently showed that an alphaq deletion mutant lacking these six amino acids (in contrast to wild type alphaq) was able to couple to several different Gs- and Gi/o-coupled receptors, apparently due to promiscuous receptor/G protein coupling (Kostenis, E., Degtyarev, M. Y., Conklin, B. R., and Wess, J. (1997) J. Biol. Chem. 272, 19107-19110). To study which specific amino acids within the N-terminal segment of alphaq/11 are critical for constraining the receptor coupling selectivity of these subunits, this region of alphaq was subjected to systematic deletion and alanine scanning mutagenesis. All mutant alphaq constructs (or wild type alphaq as a control) were coexpressed (in COS-7 cells) with the m2 muscarinic or the D2 dopamine receptors, two prototypical Gi/o-coupled receptors, and ligand-induced increases in inositol phosphate production were determined as a measure of G protein activation. Surprisingly, all 14 mutant G proteins studied (but not wild type alphaq) gained the ability to productively interact with the two Gi/o-linked receptors. Similar results were obtained when we examined the ability of selected mutant alphaq subunits to couple to the Gs-coupled beta2-adrenergic receptor. Additional experiments indicated that the functional promiscuity displayed by all investigated mutant alphaq constructs was not due to overexpression (as compared with wild type alphaq), lack of palmitoylation, or initiation of translation at a downstream ATG codon (codon seven). These data are consistent with the notion that the six-amino acid extension characteristic for alphaq/11 subunits forms a tightly folded protein subdomain that is critical for regulating the receptor coupling selectivity of these subunits. JF - The Journal of biological chemistry AU - Kostenis, E AU - Zeng, F Y AU - Wess, J AD - Laboratory of Bioorganic Chemistry, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/07/10/ PY - 1998 DA - 1998 Jul 10 SP - 17886 EP - 17892 VL - 273 IS - 28 SN - 0021-9258, 0021-9258 KW - Receptors, Adrenergic, beta-2 KW - 0 KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Protein Biosynthesis KW - Animals KW - COS Cells KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Protein Binding KW - Sequence Deletion KW - GTP-Binding Proteins -- metabolism KW - GTP-Binding Proteins -- chemistry KW - GTP-Binding Proteins -- genetics KW - Receptors, Adrenergic, beta-2 -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79985017?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Functional+characterization+of+a+series+of+mutant+G+protein+alphaq+subunits+displaying+promiscuous+receptor+coupling+properties.&rft.au=Kostenis%2C+E%3BZeng%2C+F+Y%3BWess%2C+J&rft.aulast=Kostenis&rft.aufirst=E&rft.date=1998-07-10&rft.volume=273&rft.issue=28&rft.spage=17886&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 - 1998-08-06 N1 - Date created - 1998-08-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Involvement of retinoic acid/retinoid receptors in the regulation of murine alphaB-crystallin/small heat shock protein gene expression in the lens. AN - 79983555; 9651402 AB - Crystallins are a diverse group of abundant soluble proteins that are responsible for the refractive properties of the transparent eye lens. We showed previously that Pax-6 can activate the alphaB-crystallin/small heat shock protein promoter via the lens-specific regulatory regions LSR1 (-147/-118) and LSR2 (-78/-46). Here we demonstrate that retinoic acid can induce the accumulation of alphaB-crystallin in N/N1003A lens cells and that retinoic acid receptor heterodimers (retinoic acid receptor/retinoid X receptor; RAR/RXR) can transactivate LSR1 and LSR2 in cotransfection experiments. DNase I footprinting experiments demonstrated that purified RAR/RXR heterodimers will occupy sequences resembling retinoic acid response elements within LSR1 and LSR2. Electrophoretic mobility shift assays using antibodies indicated that LSR1 and LSR2 can interact with endogenous RAR/RXR complexes in extracts of cultured lens cells. Pax-6 and RAR/RXR together had an additive effect on the activation of alphaB-promoter in the transfected lens cells. Thus, the alphaB-crystallin gene is activated by Pax-6 and retinoic acid receptors, making these transcription factors examples of proteins that have critical roles in early development as well as in the expression of proteins characterizing terminal differentiation. JF - The Journal of biological chemistry AU - Gopal-Srivastava, R AU - Cvekl, A AU - Piatigorsky, J AD - Laboratory of Molecular and Developmental Biology, NEI, National Institutes of Health, Bethesda, Maryland 20892-2730, USA. Y1 - 1998/07/10/ PY - 1998 DA - 1998 Jul 10 SP - 17954 EP - 17961 VL - 273 IS - 28 SN - 0021-9258, 0021-9258 KW - Crystallins KW - 0 KW - DNA, Complementary KW - Heat-Shock Proteins KW - RNA, Messenger KW - Receptors, Retinoic Acid KW - Tretinoin KW - 5688UTC01R KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Animals KW - Blotting, Western KW - Base Sequence KW - Blotting, Northern KW - Transfection KW - Molecular Sequence Data KW - Mice KW - RNA, Messenger -- genetics KW - Cell Line KW - Receptors, Retinoic Acid -- physiology KW - Gene Expression Regulation -- physiology KW - Lens, Crystalline -- metabolism KW - Tretinoin -- physiology KW - Crystallins -- genetics KW - Heat-Shock Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79983555?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Involvement+of+retinoic+acid%2Fretinoid+receptors+in+the+regulation+of+murine+alphaB-crystallin%2Fsmall+heat+shock+protein+gene+expression+in+the+lens.&rft.au=Gopal-Srivastava%2C+R%3BCvekl%2C+A%3BPiatigorsky%2C+J&rft.aulast=Gopal-Srivastava&rft.aufirst=R&rft.date=1998-07-10&rft.volume=273&rft.issue=28&rft.spage=17954&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 - 1998-08-06 N1 - Date created - 1998-08-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Specific interaction of conformational polypeptides derived from HIV gp120 with human T lymphocyte CD4 receptor AN - 16500241; 4385244 AB - Specifically cross-linked peptides (peptomers) have been prepared from the repeating sequences of the C4 domains of glycoproteins 120 present in different isolates of human immunodeficiency virus (HIV). In order to investigate if the HIV C4 peptomers could function as gp120 protein, we have used a novel protein-binding assay to examine if and which components of the peptomers could interact with CD4 receptor in vitro. Here, we demonstrate that all the polymeric components of the HIV-1 C4 peptomer could bind to recombinant soluble CD4 protein. A similar result was also obtained with HIV-2 C4 peptomer except that the binding occurred only in those of constituents having molecular weights higher than that of trimer. Remarkably, the CD4-binding was demonstrated to be specific to the HIV C4 peptomers as it did not occur with control peptomers such as Poly V3 MN and Poly NINA whose peptide sequences bore no homology to those of the HIV C4 peptomers. Furthermore, consistent with previous findings, no interaction of HIV-1 C4 monomeric peptide (419-436) with CD4 was detected under the same conditions. Since it is known that the HIV C4 peptomers have much higher contents of alpha -helical conformation than those of their monomeric peptides, we conclude that the secondary structure is a pivotal determinant for the successful CD4-binding by the peptomers. Our finding reveals a more defined molecular nature of the gp120-CD4 interaction and may be important for designing HIV vaccines and therapeutics which target the first step in the virus infection. JF - Immunology Letters AU - Liu, M AU - Zeng, J AU - Robey, F A AD - Oral and Pharyngeal Cancer Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892 USA Y1 - 1998/07/08/ PY - 1998 DA - 1998 Jul 08 SP - 27 EP - 32 PB - Elsevier Science B.V. VL - 63 IS - 1 SN - 0165-2478, 0165-2478 KW - CD4 antigen KW - Cross-linked peptides KW - HIV-1 KW - binding KW - glycoprotein gp120 KW - human immunodeficiency virus KW - man KW - peptomers KW - Biotechnology and Bioengineering Abstracts; Virology & AIDS Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - W3 33340:Other proteins, peptides, amino acids KW - F 06840:Immunotherapy of immune diseases KW - V 22003:AIDS: Immunological aspects KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16500241?accountid=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=Immunology+Letters&rft.atitle=Specific+interaction+of+conformational+polypeptides+derived+from+HIV+gp120+with+human+T+lymphocyte+CD4+receptor&rft.au=Liu%2C+M%3BZeng%2C+J%3BRobey%2C+F+A&rft.aulast=Liu&rft.aufirst=M&rft.date=1998-07-08&rft.volume=63&rft.issue=1&rft.spage=27&rft.isbn=&rft.btitle=&rft.title=Immunology+Letters&rft.issn=01652478&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Conformationally constrained analogues of diacylglycerol (DAG). 14. Dissection of the roles of the sn-1 and sn-2 carbonyls in DAG mimetics by isopharmacophore replacement. AN - 69115868; 9873429 AB - The replacement of the sn-1 and sn-2 carbonyl esters in DAG-surrogate lactones by sulfonate esters showed that their isosteric properties in protein kinase C binding are controlled by the location of the hydrophobic alkyl chain on the molecule. The CO and SO2 groups appear to be true isosteres only when they are adjacent to the alkyl chain, which is presumed to insert normal to the lipid bilayer. JF - Bioorganic & medicinal chemistry letters AU - Marquez, V E AU - Sharma, R AU - Wang, S AU - Lewin, N E AU - Blumberg, P M AU - Kim, I S AU - Lee, J AD - Laboratory of Medicinal Chemistry, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/07/07/ PY - 1998 DA - 1998 Jul 07 SP - 1757 EP - 1762 VL - 8 IS - 13 SN - 0960-894X, 0960-894X KW - Diglycerides KW - 0 KW - Lipid Bilayers KW - Phorbol 12,13-Dibutyrate KW - 37558-16-0 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Index Medicus KW - Protein Kinase C -- metabolism KW - Phorbol 12,13-Dibutyrate -- metabolism KW - Molecular Conformation KW - Diglycerides -- chemistry KW - Molecular Mimicry KW - Diglycerides -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69115868?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Bioorganic+%26+medicinal+chemistry+letters&rft.atitle=Conformationally+constrained+analogues+of+diacylglycerol+%28DAG%29.+14.+Dissection+of+the+roles+of+the+sn-1+and+sn-2+carbonyls+in+DAG+mimetics+by+isopharmacophore+replacement.&rft.au=Marquez%2C+V+E%3BSharma%2C+R%3BWang%2C+S%3BLewin%2C+N+E%3BBlumberg%2C+P+M%3BKim%2C+I+S%3BLee%2C+J&rft.aulast=Marquez&rft.aufirst=V&rft.date=1998-07-07&rft.volume=8&rft.issue=13&rft.spage=1757&rft.isbn=&rft.btitle=&rft.title=Bioorganic+%26+medicinal+chemistry+letters&rft.issn=0960894X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-01-29 N1 - Date created - 1999-01-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Varicella-zoster virus ORF61 deletion mutants replicate in cell culture, but a mutant with stop codons in ORF61 reverts to wild-type virus. AN - 80002413; 9657949 AB - Varicella-zoster virus (VZV) ORF61 encodes a phosphoprotein that transactivates VZV promoters. Transfection of cells with cosmid DNAs, including a cosmid with a large deletion in ORF61, resulted in a VZV ORF61 deletion mutant that was impaired for growth in vitro and could be partially complemented by growth in neuroblastoma or osteosarcoma cell lines. Cells infected with the VZV ORF61 deletion mutant expressed normal levels of an immediate-early VZV protein, but had reduced levels of a late protein and showed abnormal syncytia. Carboxy terminal truncation mutants of VZV ORF61 protein have a transrepressing phenotype and inhibit the infectivity of cotransfected wild-type viral DNA. Transfection of cells with cosmid DNAs, including a cosmid with stop codons that should result in an ORF61 truncation mutant expressing a transrepressing protein that retains the RING finger domain, resulted in a viral genome which reverted back to the wild-type sequence. BAL-31 exonuclease was used to produce deletions at the site of the stop codons in ORF61 of the cosmid, resulting in loss of the RING finger domain. Transfection of tissue culture cells with the ORF61 BAL-31 deletion mutants and other cosmid DNAs yielded viable viruses. Thus, while deletion mutants lacking the RING finger domain of ORF61 replicate in cell culture, a mutant with stop codons that retains this domain could not be propagated and reverted to wild-type virus. JF - Virology AU - Cohen, J I AU - Nguyen, H AD - Medical Virology Section, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland 20892, USA. Y1 - 1998/07/05/ PY - 1998 DA - 1998 Jul 05 SP - 306 EP - 316 VL - 246 IS - 2 SN - 0042-6822, 0042-6822 KW - Codon, Terminator KW - 0 KW - Repressor Proteins KW - Viral Proteins KW - protein 61, Varicella-zoster virus KW - 106121-63-5 KW - Index Medicus KW - Tumor Cells, Cultured KW - Humans KW - Genes, Viral KW - Giant Cells KW - Sequence Deletion KW - Virus Replication KW - Herpesvirus 3, Human -- growth & development KW - Viral Proteins -- genetics KW - Repressor Proteins -- metabolism KW - Herpesvirus 3, Human -- metabolism KW - Repressor Proteins -- genetics KW - Viral Proteins -- physiology KW - Mutagenesis KW - Herpesvirus 3, Human -- genetics KW - Repressor Proteins -- physiology KW - Viral Proteins -- metabolism KW - Herpesvirus 3, Human -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80002413?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Varicella-zoster+virus+ORF61+deletion+mutants+replicate+in+cell+culture%2C+but+a+mutant+with+stop+codons+in+ORF61+reverts+to+wild-type+virus.&rft.au=Cohen%2C+J+I%3BNguyen%2C+H&rft.aulast=Cohen&rft.aufirst=J&rft.date=1998-07-05&rft.volume=246&rft.issue=2&rft.spage=306&rft.isbn=&rft.btitle=&rft.title=Virology&rft.issn=00426822&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-08-05 N1 - Date created - 1998-08-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Five discrete cis-active domains direct cell type-specific transcription of the vasoactive intestinal peptide (VIP) gene. AN - 79972726; 9642274 AB - Vasoactive intestinal peptide (VIP) is a neuromodulator expressed with great anatomical specificity throughout the nervous system. Cell-specific expression of the VIP gene is mediated by a tissue specifier element (TSE) located within a 2.7-kilobase (kb) region between -5.2 and -2.5 kb upstream from the transcription start site, and requires an intact promoter proximal VIP-CRE (cyclic AMP-responsive element) (Hahm, S. H., and Eiden, L. E. (1997) J. Neurochem. 67, 1872-1881). We now report that the TSE comprises a 425-base pair domain located between -4.7 and -4.2 kb containing two AT-rich octamer-like sequences. The 425-base pair TSE is sufficient to provide full cell-specific regulation of the VIP gene, when fused to the 5' proximal 1.55 kb of the VIP gene. Mutational analysis and gel shift assays of these octamer-like sequences indicate that the binding of proteins related to the ubiquitously expressed POU-homeodomain proteins Oct-1 and/or Oct-2 to these octamer-like sequences plays a central role for the function of the TSE. The TSE interacts with three additional discrete domains besides the cAMP response element, which are located within the proximal 1.55 kb of the VIP gene, to provide cell-specific expression. An upstream domain from -1.55 to -1.37 kb contains E-boxes and MEF2-like motifs, and deletion of this domain results in complete abrogation of cell-specific transcriptional activity. The region from -1.37 to -1. 28 kb contains a STAT motif, and further removal of this domain allows the upstream TSE to act as an enhancer in both SH-EP and HeLa cells. The sequence from -1.28 to -0.9 kb containing a non-canonical AP-1 binding sequence (Symes, A., Gearan, T., Eby, J., and Fink, J. S. (1997) J. Biol. Chem. 272, 9648-9654), is absolutely required for TSE-dependent cellspecific expression of the VIP gene. Thus, five discrete domains of the VIP gene provide a combination of enhancer and repressor activities, each completely contingent on VIP gene context, that together result in cell-specific transcription of the VIP gene. JF - The Journal of biological chemistry AU - Hahm, S H AU - Eiden, L E AD - Section on Molecular Neuroscience, Laboratory of Cellular and Molecular Regulation, National Institute of Mental Health, Bethesda, Maryland 20892-4090, USA. sungho@codon.nih.gov Y1 - 1998/07/03/ PY - 1998 DA - 1998 Jul 03 SP - 17086 EP - 17094 VL - 273 IS - 27 SN - 0021-9258, 0021-9258 KW - Vasoactive Intestinal Peptide KW - 37221-79-7 KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Tumor Cells, Cultured KW - Humans KW - Molecular Sequence Data KW - Genes, Reporter KW - Transcription, Genetic KW - Vasoactive Intestinal Peptide -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79972726?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Five+discrete+cis-active+domains+direct+cell+type-specific+transcription+of+the+vasoactive+intestinal+peptide+%28VIP%29+gene.&rft.au=Hahm%2C+S+H%3BEiden%2C+L+E&rft.aulast=Hahm&rft.aufirst=S&rft.date=1998-07-03&rft.volume=273&rft.issue=27&rft.spage=17086&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 - 1998-08-06 N1 - Date created - 1998-08-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tumor promoter induces high mobility group HMG-Y protein expression in transformation-sensitive but not -resistant cells. AN - 80043835; 9692546 AB - Elevated levels of high mobility group (HMG) nonhistone chromosomal proteins I and Y, alternatively spliced members of the HMG-I(Y) family of architectural transcription factors, have been linked with human cancer and with neo-plastic and metastatic phenotypes in model systems. To investigate whether HMG-I(Y) proteins may influence susceptibility to neoplastic transformation, HMG-I(Y) mRNA and protein levels were compared in the JB6 murine model of neoplastic progression. HMG-I(Y) mRNAs were expressed at very low levels in preneoplastic, transformation-resistant (P-) cell lines and were constitutively expressed at much higher levels in both transformation-sensitive (P +) and transformed (Tx) tumorigenic cell lines. HMG-I(Y) mRNAs were induced to higher levels by the tumor promoter 12-O-tetradecanoylphorbol acetate (TPA) and were sustained longer in P+ than in P- cells. Nevertheless, in both P- and P+ cells, primer extension analysis revealed that the same four major HMG-I(Y) gene transcription start sites were utilized with or without TPA treatment. RT-PCR revealed that there was always slightly more Y than I form mRNA present in all of the variant JB6 cell lines. Immunoblotting indicated that both HMG-I and -Y proteins increased in P + cells in response to TPA treatment. Remarkably, in P- cells treated with TPA, only HMG-I (and not HMG-Y) protein levels increased. This unique differential TPA-induction of the HMG-Y protein in JB6 variants suggests a role for HMG-Y in mediating tumor promoter-induced neoplastic transformation. Furthermore, these results demonstrate that HMG-I and Y protein translation and/or stability is differently regulated in JB6 P- cells and provide the first indication that I and Y proteins may have different functions. JF - Oncogene AU - Cmarik, J L AU - Li, Y AU - Ogram, S A AU - Min, H AU - Reeves, R AU - Colburn, N H AD - Laboratory of Biochemical Physiology, Frederick Cancer Research and Development Center, National Cancer Institute, Maryland 21702, USA. Y1 - 1998/07/02/ PY - 1998 DA - 1998 Jul 02 SP - 3387 EP - 3396 VL - 16 IS - 26 SN - 0950-9232, 0950-9232 KW - Carcinogens KW - 0 KW - High Mobility Group Proteins KW - RNA, Messenger KW - RNA, Neoplasm KW - Transcription Factors KW - HMGA1a Protein KW - 124544-67-8 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Polymerase Chain Reaction KW - Genetic Variation KW - Carcinogens -- pharmacology KW - Animals KW - Alternative Splicing KW - RNA, Messenger -- analysis KW - Transcription, Genetic KW - Mice KW - RNA, Neoplasm -- analysis KW - Gene Expression Regulation, Neoplastic KW - High Mobility Group Proteins -- biosynthesis KW - High Mobility Group Proteins -- genetics KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Transcription Factors -- genetics KW - Transcription Factors -- biosynthesis KW - Skin Neoplasms -- metabolism KW - Cell Transformation, Neoplastic -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80043835?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Tumor+promoter+induces+high+mobility+group+HMG-Y+protein+expression+in+transformation-sensitive+but+not+-resistant+cells.&rft.au=Cmarik%2C+J+L%3BLi%2C+Y%3BOgram%2C+S+A%3BMin%2C+H%3BReeves%2C+R%3BColburn%2C+N+H&rft.aulast=Cmarik&rft.aufirst=J&rft.date=1998-07-02&rft.volume=18&rft.issue=13&rft.spage=5078&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 - 1998-08-20 N1 - Date created - 1998-08-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Goal-directed and stimulus-driven attention in cross-dimensional texture segregation. AN - 85408498; pmid-9682607 AB - Goal-directed and stimulus-driven control of attention was examined in a visual texture segregation task. Recent published reports have debated the existence and efficiency of goal-directed guidance of attention. Some of this research has focused on the apparent stimulus-driven attentional priority given to salient distractors, even when they are known to be irrelevant to the task. In the present study, subjects searched a texture array for targets defined along one dimension. These displays also included distractors created by variation in an irrelevant dimension. Targets were of three different overall shapes. On each trial, distractors could be the same shape as the target or one of the other two shapes. In two experiments subjects were informed of the overall shape of the target prior to stimulus presentation. In these experiments, distractors that did not match the overall shape of the target caused less interference than distractors that matched the target's shape. In the third experiment, subjects were not informed of the overall shape of the target. In this experiment all distractors caused roughly equal interference. The results of these experiments demonstrate that if subjects are given information about the overall shape of the target, they are able to use this information to reduce interference from distractors that do not match the overall target shape. While acknowledging some stimulus-driven interference, this illustrates a previously unexplored source of goal-directed guidance that can reduce interfering effects of even salient distractors and argues against purely stimulus-driven control of attention. JF - Perception & psychophysics AU - Ghirardelli, T G AU - Egeth, H E AD - Johns Hopkins University, Baltimore, Maryland, USA. ghirardelli@nih.gov Y1 - 1998/07// PY - 1998 DA - July 1998 SP - 826 EP - 838 VL - 60 IS - 5 SN - 0031-5117, 0031-5117 KW - Index Medicus; Space life sciences KW - National Library of Medicine KW - Humans KW - Reaction Time KW - Visual Perception -- physiology KW - Goals KW - Attention -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85408498?accountid=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=Perception+%26+psychophysics&rft.atitle=Goal-directed+and+stimulus-driven+attention+in+cross-dimensional+texture+segregation.&rft.au=Ghirardelli%2C+T+G%3BEgeth%2C+H+E&rft.aulast=Ghirardelli&rft.aufirst=T&rft.date=1998-07-01&rft.volume=60&rft.issue=5&rft.spage=826&rft.isbn=&rft.btitle=&rft.title=Perception+%26+psychophysics&rft.issn=00315117&rft_id=info:doi/ LA - English DB - ComDisDome N1 - Date revised - 2008-01-14 N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Case ascertainment uncertainties in prevalence surveys of Parkinson's disease. AN - 85407420; pmid-9686765 AB - Using unpublished data from five completed prevalence surveys of Parkinson's disease (PD), we investigated case ascertainment uncertainties that potentially have a direct effect on prevalence. These uncertainties arise from the choice of diagnostic criteria, the choice of screening method, and the amount of information lost because of nonresponse. The surveys were conducted in Argentina, India, China, Italy, and the Netherlands. Our analyses consisted of simple comparisons of prevalence results, positive predictive values (a screening measure), and nonresponse percentages. We found that (a) prevalence comparisons between surveys have diminished value if the surveys used different diagnostic criteria for PD; (b) screening performance may be affected adversely if symptom questions are answered by one family member for the entire family living together rather than by each family member individually; and (c) nonresponse from refusal or unavailability does not necessarily lead to bias, but special caution may be appropriate with prevalence results pertaining to elderly women. JF - Movement disorders : official journal of the Movement Disorder Society AU - Anderson, D W AU - Rocca, W A AU - de Rijk, M C AU - Grigoletto, F AU - Melcon, M O AU - Breteler, M M AU - Maraganore, D M AD - Biometry and Field Studies Branch, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland 20892-9135, USA. Y1 - 1998/07// PY - 1998 DA - July 1998 SP - 626 EP - 632 VL - 13 IS - 4 SN - 0885-3185, 0885-3185 KW - Index Medicus KW - National Library of Medicine KW - Data Collection -- statistics & numerical data KW - Mass Screening -- statistics & numerical data KW - Humans KW - Cross-Cultural Comparison KW - Aged KW - Parkinson Disease -- diagnosis KW - Cross-Sectional Studies KW - Aged, 80 and over KW - Incidence KW - Bias (Epidemiology) KW - Male KW - Female KW - Parkinson Disease -- epidemiology KW - Health Surveys UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85407420?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Movement+disorders+%3A+official+journal+of+the+Movement+Disorder+Society&rft.atitle=Case+ascertainment+uncertainties+in+prevalence+surveys+of+Parkinson%27s+disease.&rft.au=Anderson%2C+D+W%3BRocca%2C+W+A%3Bde+Rijk%2C+M+C%3BGrigoletto%2C+F%3BMelcon%2C+M+O%3BBreteler%2C+M+M%3BMaraganore%2C+D+M&rft.aulast=Anderson&rft.aufirst=D&rft.date=1998-07-01&rft.volume=13&rft.issue=4&rft.spage=626&rft.isbn=&rft.btitle=&rft.title=Movement+disorders+%3A+official+journal+of+the+Movement+Disorder+Society&rft.issn=08853185&rft_id=info:doi/ LA - English DB - ComDisDome N1 - Date revised - 2008-01-14 N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Regional cerebral blood flow during auditory responsive naming: evidence for cross-modality neural activation. AN - 85280703; pmid-9694237 AB - One issue of continuing debate in language research concerns whether the brain holds separate representations for semantic information through the auditory vs visual modalities. Regardless of whether we hear, see or read meaningful information, our brains automatically activate both auditory and visual semantic associations to the sensory input. The prominent models for how the brain makes these cross-modality associations holds that semantic information conveyed through either sensory input modality is represented in a shared semantic system comprising the traditionally identified language areas in the brain. A few recent case reports as well as activation imaging studies, have challenged this notion by demonstrating category-specific organization within the semantic system in spatially discrete brain regions. Neither view posits a role for primary sensory cortices in semantic processing. We obtained positron emission tomographic (PET) images while subjects performed an auditory responsive naming task, an auditory analog to visual object naming. Subjects heard and responded to descriptions of concrete objects while blindfolded to prevent visual stimulation. Our results showed that, in addition to traditional language centers, auditory language input produced reciprocal activation in primary and secondary visual brain regions, just as if the language stimuli had entered in the visual modality. These findings provide evidence for a distributed semantic system in which sensory-specific semantic modules are mutually interactive, operating directly onto early sensory processing centers. JF - Neuroreport AU - Bookheimer, S Y AU - Zeffiro, T A AU - Blaxton, T A AU - Gaillard, W D AU - Malow, B AU - Theodore, W H AD - Epilepsy Research Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. PY - 1998 SP - 2409 EP - 2413 VL - 9 IS - 10 SN - 0959-4965, 0959-4965 KW - Auditory Cortex KW - Verbal Behavior KW - Human KW - Neurons KW - Adult KW - Tomography, Emission-Computed KW - Cerebrovascular Circulation KW - Female KW - Acoustic Stimulation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85280703?accountid=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=Neuroreport&rft.atitle=Regional+cerebral+blood+flow+during+auditory+responsive+naming%3A+evidence+for+cross-modality+neural+activation.&rft.au=Bookheimer%2C+S+Y%3BZeffiro%2C+T+A%3BBlaxton%2C+T+A%3BGaillard%2C+W+D%3BMalow%2C+B%3BTheodore%2C+W+H&rft.aulast=Bookheimer&rft.aufirst=S&rft.date=1998-07-01&rft.volume=9&rft.issue=10&rft.spage=2409&rft.isbn=&rft.btitle=&rft.title=Neuroreport&rft.issn=09594965&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Rural-urban differences in depression treatment and suicidality. AN - 85264754; pmid-9674626 AB - OBJECTIVES: Because there are fewer per capita providers trained to deliver mental health services in rural areas, the authors hypothesized that depressed rural individuals would receive less outpatient treatment and report higher rates of hospital admittance and suicide attempts than their urban counterparts. METHODS: The authors recruited 74% of eligible participants (n = 470) from a 1992 telephone survey and followed up 95% of subjects for 1 year. The authors collected data from subjects on psychiatric problems and service use and from insurers/providers on treatment and expenditures. RESULTS: Although there were no rural-urban differences in the rate, type, or quality of outpatient depression treatment, rural subjects made significantly fewer specialty care visits for depression. Depressed rural individuals had 3.05 times the odds of being admitted to the hospital for physical problems (P = 0.02) and 3.06 times the odds of being admitted for mental health problems (P = 0.08) during the year. Elevated rates of hospital admittance disappear in models controlling for number of specialty care depression visits in the previous month. Rural subjects reported significantly more suicide attempts during the period of 1 year (P = 0.05). CONCLUSIONS: Additional work is warranted to determine how to alter barriers to outpatient specialty care if the rural health care delivery system is to provide cost-effective depression care. JF - Medical Care AU - Rost, K AU - Zhang, M AU - Fortney, J AU - Smith, J AU - Smith, G R AD - VAHSR&D Field Program for Mental Health and NIMH Center for Rural Mental Healthcare Research, Department of Psychiatry, University of Arkansas for Medical Sciences, Little Rock, USA. PY - 1998 SP - 1098 EP - 1107 VL - 36 IS - 7 SN - 0025-7079, 0025-7079 KW - Odds Ratio KW - Support, U.S. Gov't, P.H.S. KW - Suicide, Attempted KW - Questionnaires KW - Patient Admission KW - Quality of Health Care KW - Human KW - Aged KW - Depressive Disorder KW - Health Services Accessibility KW - Ambulatory Care KW - Comparative Study KW - Health Care Surveys KW - Aged, 80 and over KW - Adult KW - Middle Age KW - Follow-Up Studies KW - Mental Health Services KW - Adolescent KW - Female KW - Arkansas KW - Male KW - Rural Population KW - Urban Population UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85264754?accountid=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=Medical+Care&rft.atitle=Rural-urban+differences+in+depression+treatment+and+suicidality.&rft.au=Rost%2C+K%3BZhang%2C+M%3BFortney%2C+J%3BSmith%2C+J%3BSmith%2C+G+R&rft.aulast=Rost&rft.aufirst=K&rft.date=1998-07-01&rft.volume=36&rft.issue=7&rft.spage=1098&rft.isbn=&rft.btitle=&rft.title=Medical+Care&rft.issn=00257079&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Role of the M2 subunit of ribonucleotide reductase in regulation by hydroxyurea of the activity of the anti-HIV-1 agent 2',3'-dideoxyinosine. AN - 80055972; 9698094 AB - The ribonucleotide reductase inhibitor hydroxyurea exhibits potent synergism, even at low, non-cytotoxic concentrations, with the anti-HIV-1 dideoxynucleoside 2',3'-dideoxyinosine, bringing about failure of HIV DNA synthesis and, thus, of HIV replication. To elucidate the incompletely defined role of hydroxyurea in the hydroxyurea/dideoxyinosine interaction and, in particular, to identify the reasons for the unusual selective inhibitory action of the combination on retroviral rather than on cellular DNA synthesis, we prepared specific cDNA probes to determine the effects of low-level hydroxyurea on mammalian cell ribonucleotide reductase M1 and M2 subunit mRNA, while simultaneously quantitating the effects of the drug on cell cycle and on deoxynucleoside triphosphate pools. While dTTP, dCTP, and dGTP pools changed little or even increased in the presence of low-level hydroxyurea, there took place a rapid and specific inhibition of M2-subunit-catalyzed generation of dATP, with consequent slowing of cellular DNA synthesis and prolongation of S phase. However, the latter effect, in turn, resulted in increased M2 subunit mRNA transcription (a process blocked in Go/G1-phase cells, with full-length functional M2 transcripts being generated only during S phase) and, hence, in a return to normal levels of dATP and to a normal rate of cellular DNA synthesis. Because of this self-regulating mechanism, hydroxyurea-induced host-cell toxicity was obviated under conditions where HIV DNA synthesis, a process sensitive to both dATP depletion and the chain-terminating properties of the other inhibitory component of the combination (ddATP derived from dideoxyinosine), was unable to recover. JF - Biochemical pharmacology AU - Gao, W Y AU - Zhou, B S AU - Johns, D G AU - Mitsuya, H AU - Yen, Y AD - Experimental Retrovirology Section, Medicine Branch, Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. wygao@box-w.nih.gov Y1 - 1998/07/01/ PY - 1998 DA - 1998 Jul 01 SP - 105 EP - 112 VL - 56 IS - 1 SN - 0006-2952, 0006-2952 KW - Anti-HIV Agents KW - 0 KW - DNA Primers KW - Enzyme Inhibitors KW - RNA, Messenger KW - Reverse Transcriptase Inhibitors KW - Ribonucleotide Reductases KW - EC 1.17.4.- KW - Didanosine KW - K3GDH6OH08 KW - Hydroxyurea KW - X6Q56QN5QC KW - Index Medicus KW - AIDS/HIV KW - Base Sequence KW - Humans KW - Cell Division -- drug effects KW - RNA, Messenger -- genetics KW - Drug Synergism KW - DNA Replication -- drug effects KW - Cell Line KW - Cell Cycle -- drug effects KW - Ribonucleotide Reductases -- genetics KW - Ribonucleotide Reductases -- metabolism KW - Reverse Transcriptase Inhibitors -- pharmacology KW - Anti-HIV Agents -- pharmacology KW - Ribonucleotide Reductases -- antagonists & inhibitors KW - Enzyme Inhibitors -- pharmacology KW - Hydroxyurea -- pharmacology KW - Didanosine -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80055972?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Role+of+the+M2+subunit+of+ribonucleotide+reductase+in+regulation+by+hydroxyurea+of+the+activity+of+the+anti-HIV-1+agent+2%27%2C3%27-dideoxyinosine.&rft.au=Gao%2C+W+Y%3BZhou%2C+B+S%3BJohns%2C+D+G%3BMitsuya%2C+H%3BYen%2C+Y&rft.aulast=Gao&rft.aufirst=W&rft.date=1998-07-01&rft.volume=56&rft.issue=1&rft.spage=105&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 - 1998-08-24 N1 - Date created - 1998-08-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A phase I/II study of the protease inhibitor indinavir in children with HIV infection. AN - 80052713; 9651421 AB - Indinavir, an inhibitor of the human immunodeficiency virus type 1 (HIV-1) protease, is approved for the treatment of HIV infection in adults when antiretroviral therapy is indicated. We evaluated the safety and pharmacokinetic profile of the indinavir free-base liquid suspension and the sulfate salt dry-filled capsules in HIV-infected children, and studied its preliminary antiviral and clinical activity in this patient population. In addition, we evaluated the pharmacokinetic profile of a jet-milled suspension after a single dose. Previously untreated children or patients with progressive HIV disease despite antiretroviral therapy or with treatment-associated toxicity were eligible for this phase I/II study. Three dose levels (250 mg/m2, 350 mg/m2, and 500 mg/m2 per dose given orally every 8 h) were evaluated in 2 age groups (/=12 years). Indinavir was initially administered as monotherapy and then in combination with zidovudine and lamivudine after 16 weeks. Fifty-four HIV-infected children (ages 3.1 to 18.9 years) were enrolled. The indinavir free-base suspension was less bioavailable than the dry-filled capsule formulation, and therapy was changed to capsules in all children. Hematuria was the most common side effect, occurring in 7 (13%) children, and associated with nephrolithiasis in 1 patient. The combination of indinavir, lamivudine, and zidovudine was well tolerated. The median CD4 cell count increased after 2 weeks of indinavir monotherapy by 64 cells/mm3, and this was sustained at all dose levels. Plasma ribonucleic acid levels decreased rapidly in a dose-dependent way, but increased toward baseline after a few weeks of indinavir monotherapy. Indinavir dry-filled capsules are relatively well tolerated by children with HIV infection, although hematuria occurs at higher doses. Future studies need to evaluate the efficacy of indinavir when combined de novo with zidovudine and lamivudine. JF - Pediatrics AU - Mueller, B U AU - Sleasman, J AU - Nelson, R P AU - Smith, S AU - Deutsch, P J AU - Ju, W AU - Steinberg, S M AU - Balis, F M AU - Jarosinski, P F AU - Brouwers, P AU - Mistry, G AU - Winchell, G AU - Zwerski, S AU - Sei, S AU - Wood, L V AU - Zeichner, S AU - Pizzo, P A AD - HIV and AIDS Malignancy Branch, National Cancer Institute, Bethesda, Maryland, USA. Y1 - 1998/07// PY - 1998 DA - July 1998 SP - 101 EP - 109 VL - 102 IS - 1 Pt 1 SN - 0031-4005, 0031-4005 KW - Capsules KW - 0 KW - HIV Protease Inhibitors KW - Suspensions KW - Lamivudine KW - 2T8Q726O95 KW - Zidovudine KW - 4B9XT59T7S KW - Indinavir KW - 5W6YA9PKKH KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Zidovudine -- therapeutic use KW - HIV -- drug effects KW - Drug Administration Schedule KW - Dose-Response Relationship, Drug KW - Humans KW - Lamivudine -- adverse effects KW - Lamivudine -- therapeutic use KW - Child KW - CD4 Lymphocyte Count KW - Biological Availability KW - Child, Preschool KW - Viral Load KW - Infant KW - Drug Therapy, Combination KW - Zidovudine -- pharmacokinetics KW - Lamivudine -- pharmacokinetics KW - Zidovudine -- adverse effects KW - Virus Replication -- drug effects KW - Adult KW - Adolescent KW - Male KW - Female KW - HIV Infections -- virology KW - HIV Infections -- blood KW - HIV Infections -- drug therapy KW - Indinavir -- pharmacokinetics KW - Indinavir -- therapeutic use KW - HIV Protease Inhibitors -- pharmacokinetics KW - HIV Protease Inhibitors -- therapeutic use KW - HIV Protease Inhibitors -- adverse effects KW - Indinavir -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80052713?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pediatrics&rft.atitle=A+phase+I%2FII+study+of+the+protease+inhibitor+indinavir+in+children+with+HIV+infection.&rft.au=Mueller%2C+B+U%3BSleasman%2C+J%3BNelson%2C+R+P%3BSmith%2C+S%3BDeutsch%2C+P+J%3BJu%2C+W%3BSteinberg%2C+S+M%3BBalis%2C+F+M%3BJarosinski%2C+P+F%3BBrouwers%2C+P%3BMistry%2C+G%3BWinchell%2C+G%3BZwerski%2C+S%3BSei%2C+S%3BWood%2C+L+V%3BZeichner%2C+S%3BPizzo%2C+P+A&rft.aulast=Mueller&rft.aufirst=B&rft.date=1998-07-01&rft.volume=102&rft.issue=1+Pt+1&rft.spage=101&rft.isbn=&rft.btitle=&rft.title=Pediatrics&rft.issn=00314005&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-08-14 N1 - Date created - 1998-08-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cancer mortality following treatment for adult hyperthyroidism. Cooperative Thyrotoxicosis Therapy Follow-up Study Group. AN - 80039468; 9686552 AB - High-dose iodine 131 is the treatment of choice in the United States for most adults with hyperthyroid disease. Although there is little evidence to link therapeutic (131)I to the development of cancer, its extensive medical use indicates the need for additional evaluation. To evaluate cancer mortality among hyperthyroid patients, particularly after (131)I treatment. A retrospective cohort study. Twenty-five clinics in the United States and 1 clinic in England. A total of 35 593 hyperthyroid patients treated between 1946 and 1964 in the original Cooperative Thyrotoxicosis Therapy Follow-up Study; 91 % had Graves disease, 79% were female, and 65% were treated with (131)I. Standardized cancer mortality ratios (SMRs) after 3 treatment modalities for hyperthyroidism. Of the study cohort, 50.5% had died by the end of follow-up in December 1990. The total number of cancer deaths was close to that expected based on mortality rates in the general population (2950 vs 2857.6), but there was a small excess of mortality from cancers of the lung, breast, kidney, and thyroid, and a deficit of deaths from cancers of the uterus and the prostate gland. Patients with toxic nodular goiter had an SMR of 1.16 (95% confidence interval [CI], 1.03-1.30). More than 1 year after treatment, an increased risk of cancer mortality was seen among patients treated exclusively with antithyroid drugs (SMR, 1.31; 95% CI, 1.06-1.60). Radioactive iodine was not linked to total cancer deaths (SMR, 1.02; 95% CI, 0.98-1.07) or to any specific cancer with the exception of thyroid cancer (SMR, 3.94; 95% CI, 2.52-5.86). Neither hyperthyroidism nor (131)I treatment resulted in a significantly increased risk of total cancer mortality. While there was an elevated risk of thyroid cancer mortality following (131)I treatment, in absolute terms the excess number of deaths was small, and the underlying thyroid disease appeared to play a role. Overall, (131)I appears to be a safe therapy for hyperthyroidism. JF - JAMA AU - Ron, E AU - Doody, M M AU - Becker, D V AU - Brill, A B AU - Curtis, R E AU - Goldman, M B AU - Harris, B S AU - Hoffman, D A AU - McConahey, W M AU - Maxon, H R AU - Preston-Martin, S AU - Warshauer, M E AU - Wong, F L AU - Boice, J D AD - Radiation Epidemiology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. PY - 1998 SP - 347 EP - 355 VL - 280 IS - 4 SN - 0098-7484, 0098-7484 KW - Iodine Radioisotopes KW - 0 KW - Abridged Index Medicus KW - Index Medicus KW - Risk KW - Neoplasms, Radiation-Induced -- epidemiology KW - Humans KW - Adult KW - Retrospective Studies KW - Follow-Up Studies KW - Poisson Distribution KW - Likelihood Functions KW - Male KW - Female KW - Iodine Radioisotopes -- therapeutic use KW - Neoplasms -- complications KW - Neoplasms -- mortality KW - Iodine Radioisotopes -- adverse effects KW - Hyperthyroidism -- therapy KW - Hyperthyroidism -- complications KW - Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80039468?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cancer+mortality+following+treatment+for+adult+hyperthyroidism.+Cooperative+Thyrotoxicosis+Therapy+Follow-up+Study+Group.&rft.au=Ron%2C+E%3BDoody%2C+M+M%3BBecker%2C+D+V%3BBrill%2C+A+B%3BCurtis%2C+R+E%3BGoldman%2C+M+B%3BHarris%2C+B+S%3BHoffman%2C+D+A%3BMcConahey%2C+W+M%3BMaxon%2C+H+R%3BPreston-Martin%2C+S%3BWarshauer%2C+M+E%3BWong%2C+F+L%3BBoice%2C+J+D&rft.aulast=Ron&rft.aufirst=E&rft.date=1998-07-01&rft.volume=151&rft.issue=1&rft.spage=110&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 - 1998-08-06 N1 - Date created - 1998-08-06 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: JAMA. 1998 Jul 22-29;280(4):375-6 [9686558] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Plasma marinobufagenin-like and ouabain-like immunoreactivity in adrenocorticotropin-treated rats. AN - 80035805; 9683040 AB - Recently, an endogenous digitalis-like factor (EDLF) was shown to be stimulated in corticotropin (ACTH) hypertension in the rat. We have shown that mammalian plasma contains a vasoconstrictor Na,K-ATPase inhibitor, which cross-reacts with an antibody to amphibian EDLF, marinobufagenin. In the present experiment, the effect of 8 days of intramuscular ACTH treatment (0.5 mg/kg/day) of male Fisher 344 x NB rats on blood pressure, plasma ouabain-like and marinobufagenin-like immunoreactivity, and on the activity of Na,K-ATPase in aortic sarcolemma were studied. The ACTH treatment for 8 days resulted in increased systolic blood pressure (151 +/- 12.4 v 121 +/- 4.0 mm Hg, P < .01), inhibition of Na,K-ATPase in aortic sarcolemma (2.99 +/- 0.35 v 5.43 +/- 0.17 micromol ADP/mg(prot)/h), and increases in plasma concentration of marinobufagenin-like (0.44 +/- 0.06 v 0.21 +/- 0.05 nmol/L), but not ouabain-like (0.09 +/- 0.01 v 0.10 +/- 0.04 nmol/L) immunoreactivity. In dissociation enhanced lanthanide fluoroimmunoassay (DELFIA), serial dilutions of plasma from ACTH-treated rats extracted with 25% and 80% acetonitrile, respectively, demonstrated parallelism to the calibration curves of ouabain and marinobufagenin. These findings suggest that an endogenous bufodienolide Na,K-ATPase inhibitor, rather than an endogenous ouabain-like compound, is increased after 8 days of treatment of rats with ACTH. JF - American journal of hypertension AU - Fedorova, O V AU - Anderson, D E AU - Bagrov, A Y AD - Laboratory of Cardiovascular Science, National Institute on Aging, Baltimore, Maryland 21224, USA. fedorovo@grc.nia.nih.gov Y1 - 1998/07// PY - 1998 DA - July 1998 SP - 796 EP - 802 VL - 11 IS - 7 SN - 0895-7061, 0895-7061 KW - Bufanolides KW - 0 KW - marinobufagenin KW - 470-42-8 KW - Ouabain KW - 5ACL011P69 KW - Adrenocorticotropic Hormone KW - 9002-60-2 KW - Sodium KW - 9NEZ333N27 KW - Sodium-Potassium-Exchanging ATPase KW - EC 3.6.3.9 KW - Index Medicus KW - Animals KW - Erythrocytes -- drug effects KW - Hypertension -- blood KW - Sodium-Potassium-Exchanging ATPase -- drug effects KW - Rats KW - Erythrocytes -- enzymology KW - Heart Rate -- drug effects KW - Hypertension -- chemically induced KW - Rats, Inbred F344 KW - Sodium-Potassium-Exchanging ATPase -- metabolism KW - Sarcolemma -- enzymology KW - Body Weight -- drug effects KW - Sodium -- blood KW - Blood Pressure -- drug effects KW - Systole KW - Sarcolemma -- drug effects KW - Male KW - Immunoassay KW - Ouabain -- blood KW - Bufanolides -- blood KW - Adrenocorticotropic Hormone -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80035805?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+hypertension&rft.atitle=Plasma+marinobufagenin-like+and+ouabain-like+immunoreactivity+in+adrenocorticotropin-treated+rats.&rft.au=Fedorova%2C+O+V%3BAnderson%2C+D+E%3BBagrov%2C+A+Y&rft.aulast=Fedorova&rft.aufirst=O&rft.date=1998-07-01&rft.volume=11&rft.issue=7&rft.spage=796&rft.isbn=&rft.btitle=&rft.title=American+journal+of+hypertension&rft.issn=08957061&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-11-06 N1 - Date created - 1998-11-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Proliferation, development and DNA adduct levels in the mammary gland of rats given 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and a high fat diet. AN - 80034784; 9683179 AB - 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a heterocyclic amine derived from cooked meat that is a mammary gland carcinogen in rats. A carcinogenic dose-regimen of PhIP (75 mg/kg, p.o., 10 doses, once per day) was administered to 43-day old female Sprague-Dawley rats, and the rats were then placed on a defined high fat (23.5% corn oil) or low fat (5% corn oil) diet for up to 6 weeks. At various times after carcinogen and diet, and prior to carcinogenesis, we examined the percentage of proliferating cells in terminal end bud (TEB) epithelial structures of the rat mammary gland by proliferating cell nuclear antigen staining, mammary gland architecture by whole mounting, and PhIP-DNA adduct levels in mammary epithelial cells by the 32P-post-labeling assay. Immediately after dosing, the percentage of proliferating epithelial cells in TEBs was significantly higher in PhIP-treated rats than in control rats receiving vehicle only [7.5 +/- 0.9% (n = 99) versus 4.2 +/- 0.6% (n = 127), respectively]. The mammary glands of PhIP-treated rats showed a significantly lower density of alveolar buds (ABs) and a higher density of TEBs than control rats, which suggests that PhIP exposure partially inhibited the normal glandular differentiation of TEBs to ABs. After 6 weeks on the diet, proliferation in TEBs was statistically higher in rats given PhIP plus a high fat diet than in rats given vehicle plus a low fat diet. The mammary glands from rats on a high fat diet also showed a statistically higher density of TEBs when compared with rats on a low fat diet [2.08 +/- 0.34% versus 1.04 +/- 0.20%, respectively (n = 6)]. PhIP-DNA adduct levels were relatively high in mammary epithelial cells of treated rats. At 3 h after the last dose of PhIP, DNA adduct levels [relative adduct labeling (RAL) x 10(7), mean +/- SE] were 10.5 +/- 1.7 (n = 8) and 0.9 +/- 0.2 (n = 7) in epithelial cells isolated from mammary gland and in the liver, respectively. DNA adduct removal rates from the mammary gland were not different between rats on the high fat and low fat diets. Adducts were still detected after 6 weeks on either diet. Thus, events that occurred prior to neoplasia in the mammary glands of PhIP-treated rats include formation of PhIP-DNA adducts at relatively high levels, and enhanced proliferation in TEBs (putative sites of origin of mammary gland carcinomas) and partial inhibition of TEB differentiation. The high fat diet, a promoter of PhIP-induced mammary gland carcinogenesis, appeared to sustain the proliferative effect of PhIP in mammary gland TEBs at a time when PhIP-DNA adducts are still detectable. These early events may contribute to the targeting and carcinogenicity of PhIP to the mammary gland of rats. JF - Carcinogenesis AU - Snyderwine, E G AU - Davis, C D AU - Schut, H A AU - Roberts-Thomson, S J AD - Chemical Carcinogenesis Section, Laboratory of Experimental Carcinogenesis, Division of Basic Sciences, National Cancer Institute, NIH, Bethesda, MD 20892-4255, USA. Y1 - 1998/07// PY - 1998 DA - July 1998 SP - 1209 EP - 1215 VL - 19 IS - 7 SN - 0143-3334, 0143-3334 KW - Carcinogens KW - 0 KW - DNA Adducts KW - Dietary Fats KW - Imidazoles KW - 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine KW - 909C6UN66T KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Cell Division -- drug effects KW - Female KW - Mammary Neoplasms, Experimental -- chemically induced KW - Imidazoles -- toxicity KW - Mammary Glands, Animal -- drug effects KW - Cocarcinogenesis KW - Carcinogens -- metabolism KW - Mammary Glands, Animal -- cytology KW - Mammary Glands, Animal -- metabolism KW - Imidazoles -- metabolism KW - Carcinogens -- toxicity KW - Mammary Neoplasms, Experimental -- etiology KW - Dietary Fats -- toxicity KW - DNA Adducts -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80034784?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Proliferation%2C+development+and+DNA+adduct+levels+in+the+mammary+gland+of+rats+given+2-amino-1-methyl-6-phenylimidazo%5B4%2C5-b%5Dpyridine+and+a+high+fat+diet.&rft.au=Snyderwine%2C+E+G%3BDavis%2C+C+D%3BSchut%2C+H+A%3BRoberts-Thomson%2C+S+J&rft.aulast=Snyderwine&rft.aufirst=E&rft.date=1998-07-01&rft.volume=19&rft.issue=7&rft.spage=1209&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-08-06 N1 - Date created - 1998-08-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cell cycle arrest, apoptosis and p53 expression in nickel(II) acetate-treated Chinese hamster ovary cells. AN - 80032452; 9683178 AB - Nickel(II) compounds are known human and animal carcinogens. In this study, the effects of nickel(II) acetate on cell cycle, apoptosis and p53 expression were investigated in order to unveil the elements of early cellular responses to the metal. Chinese hamster ovary (CHO) cells were grown for 72 h in Ham's F-12 medium containing 0, 40, 80, 160, 240, 320, 480 or 640 microM nickel(II) acetate. DNA fragmentation, representative of apoptosis, was examined by agarose gel electrophoresis. The distribution of cells among various phases of cell cycle was determined by DNA flow cytometry. Expression of p53 protein was measured by the Western blotting technique. DNA fragmentation was detectable in cells treated with > or = 160 microM nickel(II) and its intensity increased with increasing nickel(II) concentration. The proportion of cells at S phase declined in a nickel(II) concentration-dependent manner. The decline was accompanied by an increase of cell proportion in G2/M phase and the increase became statistically significant in cells exposed to at least 480 microM nickel(II). Expression of p53 protein was not different from that in the control among samples treated with < or = 480 microM nickel(II). However, an extra fraction that migrated close to the p53 protein fraction was detected in cells treated with 640 microM nickel(II). Our findings suggest that nickel(II) modulates cellular response through effectors involved in both G2/M arrest and apoptosis regulatory pathways. The proportion of cells arrested at G2/M phase or undergoing apoptosis depends directly on nickel(II) concentration. High concentration of nickel(II) appears to up-regulate protein(s) other than the common form of p53 protein. JF - Carcinogenesis AU - Shiao, Y H AU - Lee, S H AU - Kasprzak, K S AD - Laboratory of Comparative Carcinogenesis, NCI-FCRDC, NIH, Frederick, MD 21702, USA. shiao@ncifcrf.gov Y1 - 1998/07// PY - 1998 DA - July 1998 SP - 1203 EP - 1207 VL - 19 IS - 7 SN - 0143-3334, 0143-3334 KW - Acetates KW - 0 KW - Carcinogens KW - Tumor Suppressor Protein p53 KW - Nickel KW - 7OV03QG267 KW - Index Medicus KW - Gene Expression -- drug effects KW - Animals KW - Cell Transformation, Neoplastic -- drug effects KW - Flow Cytometry KW - Cell Cycle -- drug effects KW - Cricetinae KW - Tumor Suppressor Protein p53 -- biosynthesis KW - CHO Cells -- metabolism KW - CHO Cells -- drug effects KW - Apoptosis -- drug effects KW - Carcinogens -- toxicity KW - Nickel -- toxicity KW - CHO Cells -- cytology KW - Acetates -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80032452?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cell+cycle+arrest%2C+apoptosis+and+p53+expression+in+nickel%28II%29+acetate-treated+Chinese+hamster+ovary+cells.&rft.au=Shiao%2C+Y+H%3BLee%2C+S+H%3BKasprzak%2C+K+S&rft.aulast=Shiao&rft.aufirst=Y&rft.date=1998-07-01&rft.volume=19&rft.issue=7&rft.spage=1203&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-08-06 N1 - Date created - 1998-08-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Vascular endothelial growth factor and nitric oxide synthase expression in human lung cancer and the relation to p53. AN - 80032196; 9683299 AB - Vascular endothelial growth factor (VEGF) expression and mutations of cancer-related genes increase with cancer progression. This correlation suggests the hypothesis that oncogenes and tumour suppressors regulate VEGF, and a significant correlation between p53 alteration and increased VEGF expression in human lung cancer was reported recently. To further examine this hypothesis, we analysed VEGF protein expression and mutations in p53 and K-ras in 27 non-small-cell lung cancers (NSCLC): 16 squamous cell, six adenocarcinomas, one large cell, two carcinoids and two undifferentiated tumours. VEGF was expressed in 50% of the squamous cell carcinomas (SCC) and carcinoids but none of the others. p53 mutations occurred in 14 tumours (52%), and K-ras mutations were found in two adenocarcinomas and one SCC; there was no correlation between the mutations and VEGF expression. As nitric oxide also regulates angiogenesis, we examined NOS expression in NSCLC. The Ca2+-dependent NOS activity, which indicates NOS1 and NOS3 expression, was significantly reduced in lung carcinomas compared with adjacent non-tumour tissue (P < 0.004). Although the Ca2+-independent NOS activity, which indicates NOS2 expression, was low or undetectable in non-tumour tissues and most carcinomas, significant activity occurred in three SCC. In summary, our data do not show a direct regulation of VEGF by p53 in NSCLC. Finally, we did not find the up-regulation of NOS isoforms during NSCLC progression that has been suggested for gynaecological and breast cancers. JF - British journal of cancer AU - Ambs, S AU - Bennett, W P AU - Merriam, W G AU - Ogunfusika, M O AU - Oser, S M AU - Khan, M A AU - Jones, R T AU - Harris, C C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, MD 20892-4255, USA. Y1 - 1998/07// PY - 1998 DA - July 1998 SP - 233 EP - 239 VL - 78 IS - 2 SN - 0007-0920, 0007-0920 KW - Endothelial Growth Factors KW - 0 KW - Lymphokines KW - Vascular Endothelial Growth Factor A KW - Vascular Endothelial Growth Factors KW - NOS2 protein, human KW - EC 1.14.13.39 KW - Nitric Oxide Synthase KW - Nitric Oxide Synthase Type II KW - Index Medicus KW - Genes, ras KW - Humans KW - Carcinoma, Squamous Cell -- genetics KW - Mutation KW - Carcinoma, Squamous Cell -- chemistry KW - Carcinoma, Small Cell -- genetics KW - Carcinoma, Small Cell -- chemistry KW - Lung Neoplasms -- chemistry KW - Genes, p53 -- physiology KW - Endothelial Growth Factors -- analysis KW - Lung Neoplasms -- genetics KW - Lymphokines -- analysis KW - Nitric Oxide Synthase -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80032196?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=British+journal+of+cancer&rft.atitle=Vascular+endothelial+growth+factor+and+nitric+oxide+synthase+expression+in+human+lung+cancer+and+the+relation+to+p53.&rft.au=Ambs%2C+S%3BBennett%2C+W+P%3BMerriam%2C+W+G%3BOgunfusika%2C+M+O%3BOser%2C+S+M%3BKhan%2C+M+A%3BJones%2C+R+T%3BHarris%2C+C+C&rft.aulast=Ambs&rft.aufirst=S&rft.date=1998-07-01&rft.volume=78&rft.issue=2&rft.spage=233&rft.isbn=&rft.btitle=&rft.title=British+journal+of+cancer&rft.issn=00070920&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-08-06 N1 - Date created - 1998-08-06 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cancer Res. 1991 Aug 1;51(15):4090-6 [1855224] Clin Cancer Res. 1997 Jun;3(6):861-5 [9815760] FEBS Lett. 1991 Oct 7;291(1):145-9 [1718778] Cancer Res. 1992 May 1;52(9 Suppl):2665s-2669s [1562997] Nature. 1992 Oct 29;359(6398):843-5 [1279431] Nature. 1993 Apr 29;362(6423):841-4 [7683111] Am J Respir Cell Mol Biol. 1993 Oct;9(4):371-7 [7691109] Cancer Res. 1993 Oct 1;53(19):4727-35 [8402650] Nature. 1994 Feb 10;367(6463):576-9 [8107827] Oncogene. 1994 Mar;9(3):963-9 [8108142] Cancer Res. 1994 Mar 1;54(5):1352-4 [7509718] Jpn J Cancer Res. 1994 Apr;85(4):331-4 [7515384] Cancer Res. 1994 Sep 15;54(18):4855-78 [8069852] Science. 1994 Sep 9;265(5178):1582-4 [7521539] Int J Cancer. 1994 Nov 15;59(4):520-9 [7525492] Proc Natl Acad Sci U S A. 1995 May 9;92(10):4392-6 [7538668] Br J Cancer. 1995 Jul;72(1):41-4 [7541238] Proc Natl Acad Sci U S A. 1995 Aug 15;92(17):7809-13 [7544004] Cancer Res. 1995 Sep 15;55(18):3964-8 [7664263] Cancer Res. 1995 Oct 15;55(20):4575-80 [7553632] J Exp Med. 1995 Dec 1;182(6):1683-93 [7500013] Cancer Res. 1995 Dec 15;55(24):6161-5 [8521408] Naunyn Schmiedebergs Arch Pharmacol. 1995 Oct;352(4):351-64 [8532063] Proc Natl Acad Sci U S A. 1996 Mar 19;93(6):2442-7 [8637893] Cell. 1996 Aug 9;86(3):353-64 [8756718] Mol Cell Biol. 1996 Sep;16(9):4604-13 [8756616] Cancer Res. 1996 Aug 1;56(15):3436-40 [8758908] Cancer Res. 1996 Dec 1;56(23):5391-6 [8968091] Cancer Res. 1997 Mar 1;57(5):948-55 [9041200] Br J Cancer. 1997;75(9):1295-301 [9155049] J Clin Invest. 1997 Jun 1;99(11):2625-34 [9169492] Cancer Res. 1997 Aug 1;57(15):3300-4 [9242464] Int J Cancer. 1997 Oct 21;74(5):502-7 [9355971] Cancer Res. 1997 Oct 15;57(20):4474-7 [9377555] Oncogene. 1991 Oct;6(10):1775-8 [1656362] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Deamination and Dimroth rearrangement of deoxyadenosine-styrene oxide adducts in DNA. AN - 80026980; 9671547 AB - In reactions between styrene oxide and the ring nitrogen at the 1-position of deoxyadenosine, the epoxide is opened at both the alpha- (benzylic) and beta-carbons. The 1-substituted nucleosides formed are unstable and subsequently undergo either Dimroth rearrangement to give N6-substituted deoxyadenosines or deamination to give 1-substituted deoxyinosines. alphaN6-Substituted compounds are also formed from direct reaction at the exocyclic nitrogen. Kinetic experiments revealed that relative rates of deamination of 1-substituted deoxyadenosine-styrene oxides and 1-substituted adenosine-styrene oxides were similar. However, the rate of Dimroth rearrangement in beta1-substituted adenosine-styrene oxides was approximately 2.3-fold greater than that of beta1-substituted deoxyadenosine-styrene oxides and approximately 1.5-fold greater in alpha1-substituted adenosine-styrene oxides relative to alpha1-substituted deoxyadenosine-styrene oxides. Analysis of the products formed from reactions of styrene oxide with [3H]deoxyadenosine and [3H]deoxyadenosine incorporated into native and denatured DNA showed that the double-helical DNA structure reduced the levels of adducts formed 5-fold relative to denatured DNA but did not present a complete barrier to formation of either N6-substituted deoxyadenosine- or 1-substituted deoxyinosine-styrene oxide adducts in native DNA. Additionally, in denatured and native DNA the product distributions were altered in favor of formation of beta1-substituted deoxyinosine-styrene oxide adducts with respect to reactions of the nucleoside. The ratio of retained to inverted configuration of alphaN6-substituted products was higher in DNA than in nucleoside reactions. These experiments indicate that in addition to the N6-position, the ring nitrogen at the 1-position of deoxyadenosine is available, to some extent, for reaction in native DNA. In styrene oxide-DNA reactions, formation of 1-substituted adenines can lead to deaminated products where both Watson-Crick hydrogen-bonding sites are disrupted. JF - Chemical research in toxicology AU - Barlow, T AU - Takeshita, J AU - Dipple, A AD - Chemistry of Carcinogenesis Laboratory, ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, P.O. Box B, Frederick, Maryland 21702, USA. Y1 - 1998/07// PY - 1998 DA - July 1998 SP - 838 EP - 845 VL - 11 IS - 7 SN - 0893-228X, 0893-228X KW - DNA Adducts KW - 0 KW - Deoxyadenosines KW - Epoxy Compounds KW - DNA KW - 9007-49-2 KW - styrene oxide KW - 9QH06NGT6O KW - Index Medicus KW - Stereoisomerism KW - Kinetics KW - Deamination KW - Spectrophotometry, Ultraviolet KW - Circular Dichroism KW - Chromatography, High Pressure Liquid KW - DNA Adducts -- chemistry KW - Epoxy Compounds -- chemistry KW - DNA -- chemistry KW - Deoxyadenosines -- chemistry KW - DNA Adducts -- chemical synthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80026980?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Deamination+and+Dimroth+rearrangement+of+deoxyadenosine-styrene+oxide+adducts+in+DNA.&rft.au=Barlow%2C+T%3BTakeshita%2C+J%3BDipple%2C+A&rft.aulast=Barlow&rft.aufirst=T&rft.date=1998-07-01&rft.volume=11&rft.issue=7&rft.spage=838&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 - 1998-09-21 N1 - Date created - 1998-09-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dextromethorphan improves levodopa-induced dyskinesias in Parkinson's disease. AN - 80019795; 9674803 AB - This study assessed the effects of the N-methyl-D-aspartate (NMDA) antagonist dextromethorphan (DM) on levodopa-induced dyskinesias in Parkinson's disease (PD). Recent experimental evidence suggests that increased synaptic efficacy of NMDA receptors expressed on basal ganglia neurons may play a role in the pathophysiology of levodopa-induced motor response complications. DM was given to six PD patients with motor fluctuations in a double-blind, placebo-controlled, cross-over study. At the end of each 3-week study arm, patients received several brief i.v. levodopa infusions while parkinsonian symptoms and dyskinesias were frequently scored. Levodopa dose-response curves for antiparkinsonian and dyskinetic effects were then compared for each study arm. With DM, average and maximum dyskinesia scores improved by >50%, without compromising the antiparkinsonian response magnitude or duration of levodopa, although in some subjects the levodopa threshold dose was slightly higher with DM than with placebo. These findings support the view that drugs acting to inhibit glutamatergic transmission at the NMDA receptors can ameliorate levodopa-associated dyskinesias. JF - Neurology AU - Verhagen Metman, L AU - Del Dotto, P AU - Natté, R AU - van den Munckhof, P AU - Chase, T N AD - Experimental Therapeutics Branch, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, MD 20892-1406, USA. Y1 - 1998/07// PY - 1998 DA - July 1998 SP - 203 EP - 206 VL - 51 IS - 1 SN - 0028-3878, 0028-3878 KW - Antiparkinson Agents KW - 0 KW - Antitussive Agents KW - Excitatory Amino Acid Antagonists KW - Receptors, N-Methyl-D-Aspartate KW - Levodopa KW - 46627O600J KW - Dextromethorphan KW - 7355X3ROTS KW - Abridged Index Medicus KW - Index Medicus KW - Drug Therapy, Combination KW - Humans KW - Receptors, N-Methyl-D-Aspartate -- antagonists & inhibitors KW - Aged KW - Middle Aged KW - Excitatory Amino Acid Antagonists -- administration & dosage KW - Male KW - Antiparkinson Agents -- adverse effects KW - Dextromethorphan -- administration & dosage KW - Dyskinesia, Drug-Induced -- drug therapy KW - Levodopa -- adverse effects KW - Parkinson Disease -- drug therapy KW - Antitussive Agents -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80019795?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurology&rft.atitle=Dextromethorphan+improves+levodopa-induced+dyskinesias+in+Parkinson%27s+disease.&rft.au=Verhagen+Metman%2C+L%3BDel+Dotto%2C+P%3BNatt%C3%A9%2C+R%3Bvan+den+Munckhof%2C+P%3BChase%2C+T+N&rft.aulast=Verhagen+Metman&rft.aufirst=L&rft.date=1998-07-01&rft.volume=51&rft.issue=1&rft.spage=203&rft.isbn=&rft.btitle=&rft.title=Neurology&rft.issn=00283878&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-07-30 N1 - Date created - 1998-07-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pigment epithelium-derived factor (PEDF) differentially protects immature but not mature cerebellar granule cells against apoptotic cell death. AN - 80019455; 9670988 AB - We have shown previously that pigment epithelium-derived factor (PEDF) acts as a survival factor for cerebellar granule cell neurons in culture, as well as protecting them against glutamate toxicity. In this study we have examined effects of PEDF on apoptotic cell death. We find that the granule cells die of apoptosis throughout the culture period, what we have termed "natural" apoptosis. PEDF prevents this natural apoptosis if added to immature cells, within the first 2 days in vitro (DIV), and the effect is maintained for up to DIV12. However, PEDF has no effect if added to mature cells at DIV5. Similar results are obtained when apoptosis is induced by shifting the cells from a serum- and 25 mM KCl-containing medium to serum-free medium with 5 mM KCl. PEDF most effectively blocks induced apoptosis in immature cells (DIV2) when added 24 hr prior to the change of medium, but still provides some protection when added simultaneously. However, 24 hr pretreatment with PEDF has a minimal effect when apoptosis is induced in mature DIV6 cells; addition at the same time is completely ineffective. Two polypeptide fragments of PEDF, only one of which contains the serine-protease inhibitory site, are equally active, supporting previous results which suggest that the neurotrophic effects of PEDF are not mediated by protease inhibition. We conclude that PEDF protects immature but not mature granule cells against both natural and induced apoptosis. JF - Journal of neuroscience research AU - Araki, T AU - Taniwaki, T AU - Becerra, S P AU - Chader, G J AU - Schwartz, J P AD - Molecular Genetics Section, Clinical Neuroscience Branch, NINDS, Bethesda, Maryland 20892-4126, USA. Y1 - 1998/07/01/ PY - 1998 DA - 1998 Jul 01 SP - 7 EP - 15 VL - 53 IS - 1 SN - 0360-4012, 0360-4012 KW - Eye Proteins KW - 0 KW - Nerve Growth Factors KW - Neuroprotective Agents KW - Nucleosomes KW - Proteins KW - Serpins KW - Tetrazolium Salts KW - Thiazoles KW - pigment epithelium-derived factor KW - 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium KW - 138169-43-4 KW - Trypan Blue KW - I2ZWO3LS3M KW - Potassium KW - RWP5GA015D KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Cell Count KW - Cells, Cultured KW - Nucleosomes -- metabolism KW - Potassium -- pharmacology KW - Proteins -- pharmacology KW - Cerebellum -- cytology KW - Serpins -- pharmacology KW - Cerebellum -- growth & development KW - Nerve Growth Factors -- pharmacology KW - Cerebellum -- drug effects KW - Apoptosis -- drug effects KW - Cytoprotection -- drug effects KW - Neuroprotective Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80019455?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Pigment+epithelium-derived+factor+%28PEDF%29+differentially+protects+immature+but+not+mature+cerebellar+granule+cells+against+apoptotic+cell+death.&rft.au=Araki%2C+T%3BTaniwaki%2C+T%3BBecerra%2C+S+P%3BChader%2C+G+J%3BSchwartz%2C+J+P&rft.aulast=Araki&rft.aufirst=T&rft.date=1998-07-01&rft.volume=53&rft.issue=1&rft.spage=7&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 - 1998-09-24 N1 - Date created - 1998-09-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - New prospects in the treatment of indolent lymphomas with purine analogues. AN - 80019036; 9672772 AB - To review the activity of the purine analogues fludarabine, cladribine (2-chlorodeoxyadenosine [2-CdA]), and pentostatin (2'-deoxycoformycin) in the treatment of indolent lymphoid malignancies, including chronic lymphocytic leukemia, hairy cell leukemia, and indolent non-Hodgkin's lymphomas (NHLs). Patients with previously untreated, relapsed, or refractory indolent NHL and other indolent lymphoid malignancies who have been treated with purine analogues. Purine analogues have revolutionized the treatment of indolent lymphomas. Fludarabine induces responses in almost 50% of patients with relapsed or refractory indolent NHL and produces complete remissions (CRs) in 10% to 15% of patients. In patients receiving fludarabine as initial treatment, CRs are achieved in almost 40%, with an overall response rate of 70% and a median time to progression > 1 year. Response rates with 2-CdA in previously treated patients appear similar to those with fludarabine, although less durable. Fludarabine and 2-CdA achieve a higher number of durable responses in Waldenström's macroglobulinemia than are generally achieved with alkylating agents in this disease. Pentostatin appears to be less active in NHL. Newer purine analogues currently in clinical trials in lymphomas include gemcitabine and compound 506U. Promising activity has been reported with the combination of fludarabine, mitoxantrone, dexamethasone, and fludarabine plus cyclophosphamide. Combinations of 2-CdA with other agents are also in development. Toxicities associated with these purine analogues primarily include moderate myelosuppression, profound immunosuppression, neurotoxicity at higher than recommended doses, and a possible increase in secondary malignancies. The purine analogues should provide the basis for new treatment strategies with the goal of curing patients with indolent NHL. For progress to continue, patients must be referred to important and innovative clinical research trials. JF - The cancer journal from Scientific American AU - Cheson, B D AD - Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, Maryland 20892-7436, USA. Y1 - 1998/07// PY - 1998 DA - July 1998 SP - S27 EP - S36 VL - 4 Suppl 2 SN - 1081-4442, 1081-4442 KW - Antineoplastic Agents KW - 0 KW - Deoxycytidine KW - 0W860991D6 KW - Pentostatin KW - 395575MZO7 KW - Cladribine KW - 47M74X9YT5 KW - gemcitabine KW - B76N6SBZ8R KW - Vidarabine KW - FA2DM6879K KW - fludarabine KW - P2K93U8740 KW - Index Medicus KW - Lymphoma, Non-Hodgkin -- drug therapy KW - Humans KW - Deoxycytidine -- analogs & derivatives KW - Deoxycytidine -- therapeutic use KW - Drug Resistance, Neoplasm KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Vidarabine -- analogs & derivatives KW - Cladribine -- adverse effects KW - Pentostatin -- adverse effects KW - Cladribine -- therapeutic use KW - Lymphoma -- drug therapy KW - Vidarabine -- therapeutic use KW - Antineoplastic Agents -- therapeutic use KW - Vidarabine -- adverse effects KW - Pentostatin -- therapeutic use KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80019036?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+cancer+journal+from+Scientific+American&rft.atitle=New+prospects+in+the+treatment+of+indolent+lymphomas+with+purine+analogues.&rft.au=Cheson%2C+B+D&rft.aulast=Cheson&rft.aufirst=B&rft.date=1998-07-01&rft.volume=4+Suppl+2&rft.issue=&rft.spage=S27&rft.isbn=&rft.btitle=&rft.title=The+cancer+journal+from+Scientific+American&rft.issn=10814442&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-09-21 N1 - Date created - 1998-09-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phase 1 trial of transforming growth factor beta 2 in chronic progressive MS. AN - 80016863; 9674825 AB - Transforming growth factor (TGF)-beta2 is a pleiotropic cytokine associated with remissions in multiple sclerosis (MS) and amelioration of allergic encephalomyelitis. We assessed the safety of TGF-beta2 in an open-label trial of 11 patients with secondary progressive (SP) MS. Five patients had a reversible decline in the glomerular filtration rate. There was no change in expanded disability status scale or MRI lesions during treatment. Systemic TGF-beta2 may be associated with reversible nephrotoxicity, and further investigation of its therapeutic potential in MS should be performed with caution. JF - Neurology AU - Calabresi, P A AU - Fields, N S AU - Maloni, H W AU - Hanham, A AU - Carlino, J AU - Moore, J AU - Levin, M C AU - Dhib-Jalbut, S AU - Tranquill, L R AU - Austin, H AU - McFarland, H F AU - Racke, M K AD - Neuroimmunology Branch of the National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-1400, USA. Y1 - 1998/07// PY - 1998 DA - July 1998 SP - 289 EP - 292 VL - 51 IS - 1 SN - 0028-3878, 0028-3878 KW - Transforming Growth Factor beta KW - 0 KW - Abridged Index Medicus KW - Index Medicus KW - Cerebrospinal Fluid -- cytology KW - Renal Circulation -- drug effects KW - Humans KW - Glomerular Filtration Rate -- drug effects KW - Adult KW - Middle Aged KW - Chronic Disease KW - Blood Urea Nitrogen KW - Male KW - Female KW - Transforming Growth Factor beta -- administration & dosage KW - Transforming Growth Factor beta -- toxicity KW - Multiple Sclerosis -- drug therapy KW - Transforming Growth Factor beta -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80016863?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurology&rft.atitle=Phase+1+trial+of+transforming+growth+factor+beta+2+in+chronic+progressive+MS.&rft.au=Calabresi%2C+P+A%3BFields%2C+N+S%3BMaloni%2C+H+W%3BHanham%2C+A%3BCarlino%2C+J%3BMoore%2C+J%3BLevin%2C+M+C%3BDhib-Jalbut%2C+S%3BTranquill%2C+L+R%3BAustin%2C+H%3BMcFarland%2C+H+F%3BRacke%2C+M+K&rft.aulast=Calabresi&rft.aufirst=P&rft.date=1998-07-01&rft.volume=51&rft.issue=1&rft.spage=289&rft.isbn=&rft.btitle=&rft.title=Neurology&rft.issn=00283878&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-07-30 N1 - Date created - 1998-07-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A tryptophan hydroxylase gene marker for suicidality and alcoholism. AN - 80015446; 9672049 AB - Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in the synthesis of serotonin. Low turnover rate of this monoamine neurotransmitter is associated with impaired impulse control. We previously reported that, in Finns, TPH genotype was associated with suicidality, a pathophysiological mechanism that may involve impaired impulse control. Association and sib-pair linkage analyses of a polymorphism in intron 7 of the TPH gene with suicidality, alcoholism, and the Karolinska Scales of Personality were conducted in 804 Finnish alcoholic offenders, controls, and their relatives, in a sample that included 369 sib pairs. The association of the TPH 17 779C (L) allele to suicidality in impulsive offenders reported previously was replicated in a new group of Finnish offenders (P=.001, n=122). The intron 7 variant in the TPH gene showed significant evidence for linkage to suicidality (P=.006 in unaffected sib pairs), severe suicide attempts (P=.006 in unaffected sib pairs; regression: P=.01), alcoholism (P=.003 in unaffected sib-pairs; regression: P=.02), and Karolinska Scales of Personality socialization score (regression: P=.002). The status of the TPH A779C allele as a marker for suicidality was replicated and linkage with alcoholism and Karolinska Scales of Personality socialization score was also observed. A functional variant(s) in or close to the TPH gene may predispose individuals to suicidality and other behaviors thought to be influenced by serotonin. JF - Archives of general psychiatry AU - Nielsen, D A AU - Virkkunen, M AU - Lappalainen, J AU - Eggert, M AU - Brown, G L AU - Long, J C AU - Goldman, D AU - Linnoila, M AD - Section of Molecular Genetics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA. nielsen@helix.nih.gov Y1 - 1998/07// PY - 1998 DA - July 1998 SP - 593 EP - 602 VL - 55 IS - 7 SN - 0003-990X, 0003-990X KW - Genetic Markers KW - 0 KW - Serotonin KW - 333DO1RDJY KW - Tryptophan Hydroxylase KW - EC 1.14.16.4 KW - Abridged Index Medicus KW - Index Medicus KW - Disruptive, Impulse Control, and Conduct Disorders -- genetics KW - Genetic Linkage KW - Regression Analysis KW - Genetic Variation KW - Polymorphism, Genetic KW - Humans KW - Personality -- genetics KW - Prisoners -- statistics & numerical data KW - Personality -- classification KW - Disruptive, Impulse Control, and Conduct Disorders -- epidemiology KW - Genotype KW - Models, Genetic KW - Adult KW - Introns KW - Family KW - Finland -- epidemiology KW - Serotonin -- genetics KW - Male KW - Tryptophan Hydroxylase -- genetics KW - Alcoholism -- epidemiology KW - Suicide, Attempted -- statistics & numerical data KW - Alcoholism -- diagnosis KW - Suicide, Attempted -- classification KW - Alcoholism -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80015446?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuroreport&rft.atitle=In+vivo+studies+with+%5B125I%5D5-I-A-85380%2C+a+nicotinic+acetylcholine+receptor+radioligand.&rft.au=Vaupel%2C+D+B%3BMukhin%2C+A+G%3BKimes%2C+A+S%3BHorti%2C+A+G%3BKoren%2C+A+O%3BLondon%2C+E+D&rft.aulast=Vaupel&rft.aufirst=D&rft.date=1998-07-13&rft.volume=9&rft.issue=10&rft.spage=2311&rft.isbn=&rft.btitle=&rft.title=Neuroreport&rft.issn=09594965&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-07-23 N1 - Date created - 1998-07-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Solving the puzzle of follicular lymphoma. AN - 80014702; 9672768 JF - The cancer journal from Scientific American AU - Longo, D L AD - National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA. Y1 - 1998/07// PY - 1998 DA - July 1998 SP - S1 EP - S4 VL - 4 Suppl 2 SN - 1081-4442, 1081-4442 KW - Antibodies, Monoclonal KW - 0 KW - Antibodies, Monoclonal, Murine-Derived KW - Antineoplastic Agents KW - Immunotoxins KW - Interferon-alpha KW - Rituximab KW - 4F4X42SYQ6 KW - Index Medicus KW - Interferon-alpha -- therapeutic use KW - Disease-Free Survival KW - Lymphoma -- classification KW - Humans KW - Immunotoxins -- therapeutic use KW - Antineoplastic Agents -- therapeutic use KW - Remission Induction KW - Antibodies, Monoclonal -- therapeutic use KW - Lymphoma, Follicular -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80014702?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+cancer+journal+from+Scientific+American&rft.atitle=Solving+the+puzzle+of+follicular+lymphoma.&rft.au=Longo%2C+D+L&rft.aulast=Longo&rft.aufirst=D&rft.date=1998-07-01&rft.volume=4+Suppl+2&rft.issue=&rft.spage=S1&rft.isbn=&rft.btitle=&rft.title=The+cancer+journal+from+Scientific+American&rft.issn=10814442&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-09-21 N1 - Date created - 1998-09-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Lithium protects rat cerebellar granule cells against apoptosis induced by anticonvulsants, phenytoin and carbamazepine. AN - 80006077; 9655900 AB - We have studied the neuroprotective actions of lithium against various insults in cultured cerebellar granule cells of rats. The anticonvulsants, phenytoin and carbamazepine, have been shown to induce apoptosis of cerebellar granule cells at high concentrations. Here we found that co-presence of LiCl (1-10 mM) dose-dependently protected against phenytoin (20 microM)- and carbamazepine (100 microM)-induced neuronal apoptosis as assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide metabolism, morphological inspection, chromatin condensation and DNA fragmentation. These neuroprotective effects were not prevented by inclusion of myoinositol nor mimicked by a potent inositol monophosphatase inhibitor, suggestive of a mechanism independent of inositol monophosphatase blockade. Lithium also significantly protected against apoptosis of cerebellar granule cells induced by aging of the cultures. Additionally, lithium suppressed death of cerebellar granule cells exposed to a low concentration of extracellular potassium. In contrast, it had no protective effect on cell death induced by Ca++ ionophores, a Na+ channel opener, a protein kinase inhibitor, a nitric oxide donor or H2O2. Thus, lithium has robust neuroprotective effects against apoptotic cell death induced by multiple insults with limited selectivity. These actions provide a new avenue to study the molecular and cellular mechanisms of this drug. JF - The Journal of pharmacology and experimental therapeutics AU - Nonaka, S AU - Katsube, N AU - Chuang, D M AD - Section on Molecular Neurobiology, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1998/07// PY - 1998 DA - July 1998 SP - 539 EP - 547 VL - 286 IS - 1 SN - 0022-3565, 0022-3565 KW - Anticonvulsants KW - 0 KW - Neuroprotective Agents KW - Carbamazepine KW - 33CM23913M KW - Inositol KW - 4L6452S749 KW - Phenytoin KW - 6158TKW0C5 KW - Lithium KW - 9FN79X2M3F KW - Phosphatidylinositol 3-Kinases KW - EC 2.7.1.- KW - 5'-Nucleotidase KW - EC 3.1.3.5 KW - Potassium KW - RWP5GA015D KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Cells, Cultured KW - Phosphatidylinositol 3-Kinases -- physiology KW - Inositol -- pharmacology KW - 5'-Nucleotidase -- antagonists & inhibitors KW - Potassium -- pharmacology KW - Phenytoin -- toxicity KW - Cerebellum -- drug effects KW - Carbamazepine -- toxicity KW - Anticonvulsants -- toxicity KW - Neuroprotective Agents -- pharmacology KW - Lithium -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80006077?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Lithium+protects+rat+cerebellar+granule+cells+against+apoptosis+induced+by+anticonvulsants%2C+phenytoin+and+carbamazepine.&rft.au=Nonaka%2C+S%3BKatsube%2C+N%3BChuang%2C+D+M&rft.aulast=Nonaka&rft.aufirst=S&rft.date=1998-07-01&rft.volume=286&rft.issue=1&rft.spage=539&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 - 1998-08-03 N1 - Date created - 1998-08-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tumor lysis syndrome: an uncommon complication of fludarabine therapy of chronic lymphocytic leukemia. AN - 80002876; 9667245 AB - To quantify the incidence and severity of tumor lysis syndrome (TLS) as a consequence of fludarabine therapy in patients with advanced chronic lymphocytic leukemia (CLL). A retrospective review and questionnaire follow-up of clinical and laboratory data were performed on patients with intermediate or high-risk CLL on the National Cancer Institute Group C protocol or special exception mechanisms, or phase II trials of fludarabine, for whom adverse drug reports of TLS were available. Fludarabine was administered at a dose of 20 to 40 mg/m2 per day for 5 days at monthly intervals. Among the 6,137 patients, TLS was suspected in 26 (0.42%), with clinical and laboratory features consistent with TLS present in 20 (0.33%). Prophylaxis against TLS had been administered to 60% of these patients. Clinical or laboratory features were similar to patients who did not develop TLS. Of the patients with TLS, 90% had high-risk CLL, 60 months of prior disease duration, with a median pretreatment WBC of 109 x 10(9)/L, two prior regimens, lymphadenopathy in 89%, splenomegaly and/or hepatomegaly in 90%. TLS developed on approximately day 7 and lasted a median of 9.5 days. Dialysis was required in 30% during the TLS episode; 20% of patients died during cycle one of fludarabine therapy with renal failure, and another 20% died of infection or congestive heart failure. Six patients were retreated with fludarabine without recurrent TLS. TLS after fludarabine therapy is extremely uncommon, but may be associated with significant morbidity and mortality. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Cheson, B D AU - Frame, J N AU - Vena, D AU - Quashu, N AU - Sorensen, J M AD - Cancer Therapy Evaluation Program, Division of Cancer Diagnosis and Treatment, National Cancer Institute, Bethesda, MD 20892, USA. chesonb@ctep.nci.nih.gov Y1 - 1998/07// PY - 1998 DA - July 1998 SP - 2313 EP - 2320 VL - 16 IS - 7 SN - 0732-183X, 0732-183X KW - Antineoplastic Agents KW - 0 KW - Vidarabine KW - FA2DM6879K KW - fludarabine KW - P2K93U8740 KW - Index Medicus KW - Severity of Illness Index KW - Aged, 80 and over KW - Humans KW - Adult KW - Treatment Outcome KW - Retrospective Studies KW - Incidence KW - Aged KW - Middle Aged KW - Male KW - Female KW - Survival Analysis KW - Vidarabine -- analogs & derivatives KW - Tumor Lysis Syndrome -- blood KW - Leukemia, Lymphocytic, Chronic, B-Cell -- drug therapy KW - Leukemia, Lymphocytic, Chronic, B-Cell -- blood KW - Tumor Lysis Syndrome -- etiology KW - Tumor Lysis Syndrome -- therapy KW - Vidarabine -- adverse effects KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80002876?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Tumor+lysis+syndrome%3A+an+uncommon+complication+of+fludarabine+therapy+of+chronic+lymphocytic+leukemia.&rft.au=Cheson%2C+B+D%3BFrame%2C+J+N%3BVena%2C+D%3BQuashu%2C+N%3BSorensen%2C+J+M&rft.aulast=Cheson&rft.aufirst=B&rft.date=1998-07-01&rft.volume=16&rft.issue=7&rft.spage=2313&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 - 1998-08-12 N1 - Date created - 1998-08-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Association of v-Ha-ras transgene expression with development of erythroleukemia in Tg.AC transgenic mice. AN - 80002656; 9665485 AB - A transgenic mouse line (Tg.AC) carrying an activated v-Ha-ras oncogene fused to the embryonic zeta-globin promoter develops an array of spontaneous epithelial and mesenchymal neoplasms. In this report we describe the morphological, immunophenotypic, and molecular features of a unique hematopoietic neoplasm in these mice. The cardinal lesion of this disease is marked hepatomegaly due to leukemic proliferation and infiltration. In the peripheral blood, there is a marked increase in the number of metarubricytes and other less differentiated erythroid progenitor cells. Leukemic cells stain positively with an erythroid-associated nuclear transcription factor (GATA-1). Using a reverse transcription polymerase chain reaction assay, co-expression of GATA-1 and endogenous zeta-globin genes is detected in hematopoietic tissues of nonleukemic transgenic and nontransgenic mice. ras transgene expression is, however, detected only in normal bone marrow and leukemic tissues of transgenic mice, and 5' mapping experiments using S1 protection analysis of total RNA from leukemic tissue indicates that transcription of the transgene mRNA is initiated from the natural zeta-globin promoter start site, supporting the belief that the zeta-globin promoter directs v-Ha-ras expression in erythroid progenitor cells, ultimately leading to leukemic transformation. JF - The American journal of pathology AU - Trempus, C S AU - Ward, S AU - Farris, G AU - Malarkey, D AU - Faircloth, R S AU - Cannon, R E AU - Mahler, J F AD - Laboratory of Environmental Carcinogenesis and Mutagenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1998/07// PY - 1998 DA - July 1998 SP - 247 EP - 254 VL - 153 IS - 1 SN - 0002-9440, 0002-9440 KW - DNA-Binding Proteins KW - 0 KW - Erythroid-Specific DNA-Binding Factors KW - GATA1 Transcription Factor KW - Gata1 protein, mouse KW - Transcription Factors KW - Globins KW - 9004-22-2 KW - ras Proteins KW - EC 3.6.5.2 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Liver -- pathology KW - Transcription Factors -- metabolism KW - Spleen -- metabolism KW - Spleen -- pathology KW - Bone Marrow -- metabolism KW - Liver -- metabolism KW - Transcription, Genetic KW - Mice KW - Mice, Transgenic KW - Organ Size KW - Blood Cell Count KW - Polymerase Chain Reaction KW - Blood Cells -- metabolism KW - ras Proteins -- metabolism KW - Globins -- metabolism KW - DNA-Binding Proteins -- metabolism KW - Genes, ras -- genetics KW - Leukemia, Erythroblastic, Acute -- genetics KW - Leukemia, Erythroblastic, Acute -- pathology KW - Leukemia, Erythroblastic, Acute -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80002656?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Association+of+v-Ha-ras+transgene+expression+with+development+of+erythroleukemia+in+Tg.AC+transgenic+mice.&rft.au=Trempus%2C+C+S%3BWard%2C+S%3BFarris%2C+G%3BMalarkey%2C+D%3BFaircloth%2C+R+S%3BCannon%2C+R+E%3BMahler%2C+J+F&rft.aulast=Trempus&rft.aufirst=C&rft.date=1998-07-01&rft.volume=153&rft.issue=1&rft.spage=247&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 - 1998-07-23 N1 - Date created - 1998-07-23 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Carcinogenesis. 1996 Sep;17(9):1825-33 [8824502] Leukemia. 1996 Jan;10(1):83-90 [8558943] Mol Carcinog. 1997 Sep;20(1):68-77 [9328437] Blood. 1985 Mar;65(3):705-12 [2982442] Mol Cell Biol. 1985 Apr;5(4):667-74 [2985965] Mol Cell Biol. 1985 May;5(5):1025-33 [4000117] Lab Invest. 1988 May;58(5):484-502 [3285096] Am J Pathol. 1989 Jul;135(1):39-61 [2672826] Leukemia. 1990 Mar;4(3):210-5 [2156115] Lab Anim Sci. 1990 Jul;40(4):418-9 [2166875] Cell. 1990 Nov 16;63(4):665-72 [2225071] Proc Natl Acad Sci U S A. 1990 Dec;87(23):9178-82 [2251261] Nature. 1991 Jan 17;349(6306):257-60 [1987478] Blood. 1992 Aug 1;80(3):575-81 [1638017] Am J Pathol. 1993 Apr;142(4):1199-207 [8475993] Nat Genet. 1992 May;1(2):92-8 [1302015] Carcinogenesis. 1993 Jul;14(7):1335-41 [8330346] Eur J Morphol. 1993 Mar-Jun;31(1-2):144-50 [8398549] Toxicol Pathol. 1993;21(2):206-18 [8210943] Mol Carcinog. 1994 Mar;9(3):143-54 [7908201] Br J Haematol. 1994 Feb;86(2):410-2 [8199039] Leukemia. 1994 Jun;8(6):1034-8 [8207977] Genes Dev. 1994 May 15;8(10):1184-97 [7926723] Oncogene. 1994 Dec;9(12):3527-33 [7970713] Development. 1995 Jan;121(1):163-72 [7867497] Proc Natl Acad Sci U S A. 1995 Oct 10;92(21):9623-7 [7568185] Nat Genet. 1995 Sep;11(1):9-11 [7550322] Toxicol Pathol. 1996 Nov-Dec;24(6):710-6 [8994298] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phase II and dose-escalation with or without granulocyte colony-stimulating factor study of 9-aminocamptothecin in relapsed and refractory lymphomas. AN - 80002040; 9667249 AB - To assess the efficacy and maximum dose-intensity of a new topoisomerase I (topo I)-targeting agent, 9-aminocamptothecin (9-AC), in patients with relapsed or refractory lymphomas. Eligible patients had measurable disease and were considered incurable. 9-AC was infused over 72 hours at an initial dose rate of 40 microg/m2/h every 3 weeks with subsequent intrapatient escalations or reductions in 10-microg/m2/h increments based on toxicity. To assess the impact of granulocyte-colony stimulating factor (G-CSF) on dose-intensity, the first 16 patients received no G-CSF and the subsequent 29 patients received G-CSF on all cycles. Forty-five patients received a total of 142 cycles of 9-AC. The patients' median age was 55 years, 73% had stage IV disease, and histologies included indolent and aggressive non-Hodgkin's lymphoma (NHL) in 33% and 58% of patients, respectively, and Hodgkin's lymphoma in 9%. Patients had received a median of two prior chemotherapy regimens, and 67% of patients had chemotherapy-sensitive disease. Of 40 assessable patients, 10 (25%) achieved a partial response (PR). Chemotherapy-sensitive patients had a 32% response rate compared with 8% in chemotherapy-resistant patients. With a median follow-up duration of 35 months, the median event-free survival (EFS) and overall survival times were 1.5 and 12.5 months, respectively, and the median duration of response was 5 months (range, 1 to 10). G-CSF significantly reduced the incidence of neutropenia and diarrhea, but did not permit a significant increase in dose-intensity. 9-AC had a reasonable response rate of 25% in heavily pretreated patients. The low response rate in patients with chemotherapy-resistant disease suggests that there is cross-resistance between 9-AC and standard chemotherapy. However, there was no association between 9-AC response and the number of prior regimens. Due to dose-limiting thrombocytopenia, G-CSF support did not increase dose-intensity, although individual patients benefited from the use of G-CSF. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Wilson, W H AU - Little, R AU - Pearson, D AU - Jaffe, E S AU - Steinberg, S M AU - Cheson, B D AU - Humphrey, R AU - Kohler, D R AU - Elwood, P AD - Medicine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. wilsonw@box-w.nih.gov Y1 - 1998/07// PY - 1998 DA - July 1998 SP - 2345 EP - 2351 VL - 16 IS - 7 SN - 0732-183X, 0732-183X KW - Antineoplastic Agents KW - 0 KW - Granulocyte Colony-Stimulating Factor KW - 143011-72-7 KW - 9-aminocamptothecin KW - 5MB77ICE2Q KW - Camptothecin KW - XT3Z54Z28A KW - Index Medicus KW - Drug Administration Schedule KW - Disease-Free Survival KW - Infusions, Intravenous KW - Maximum Allowable Concentration KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Drug Resistance, Neoplasm KW - Recurrence KW - Male KW - Female KW - Granulocyte Colony-Stimulating Factor -- therapeutic use KW - Antineoplastic Agents -- administration & dosage KW - Camptothecin -- analogs & derivatives KW - Lymphoma -- drug therapy KW - Lymphoma -- pathology KW - Camptothecin -- adverse effects KW - Camptothecin -- administration & dosage KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80002040?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Single+gene+complementation+of+the+hPMS2+defect+in+HEC-1-A+endometrial+carcinoma+cells.&rft.au=Risinger%2C+J+I%3BUmar%2C+A%3BGlaab%2C+W+E%3BTindall%2C+K+R%3BKunkel%2C+T+A%3BBarrett%2C+J+C&rft.aulast=Risinger&rft.aufirst=J&rft.date=1998-07-15&rft.volume=58&rft.issue=14&rft.spage=2978&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 - 1998-08-12 N1 - Date created - 1998-08-12 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: J Clin Oncol 1999 Jun;17(6):1964 J Clin Oncol 1998 Aug;16(8):2895 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Anti-p53 antibodies in patients with Barrett's esophagus or esophageal carcinoma can predate cancer diagnosis. AN - 79999386; 9649454 AB - We previously discovered anti-p53 antibodies predating a cancer diagnosis in subjects at increased risk for liver, lung, breast, and prostate cancer. Recently, we reported a significant correlation (P < 0.017) between p53 antibodies and p53 mutations in patients with late-stage esophageal carcinoma. Because others have reported p53 mutations and overexpression of p53 protein in Barrett's esophagus, we studied p53 antibodies in plasma of 88 serially endoscoped patients: 36 with Barrett's metaplasia, 23 with esophageal squamous cell carcinoma, 10 with esophageal adenocarcinoma, and 19 with esophagitis or normal esophagus. We used enzyme immunoassay, immunoblotting, and immunoprecipitation assays for p53 antibodies; polymerase chain reaction, denaturant gradient gel electrophoresis, and sequencing for p53 mutations; and immunohistochemistry for p53 protein. p53 antibodies were detected in 4 patients with Barrett's esophagus, including 1 with dysplasia that later progressed to adenocarcinoma, and in 10 cancer patients (P = 0.002) (8 squamous and 2 adenocarcinoma), 2 of whom (1 squamous, 1 adenocarcinoma) had antibodies before cancer was diagnosed. Other patient groups were too small for informative statistical analysis. Six antibody-positive cancer patients had p53 mutations, whereas 2 patients with cancer and 1 with Barrett's esophagus with antibodies had p53 protein overexpressed in esophageal tissues. Patients with Barrett's esophagus and esophageal cancer can develop p53 antibodies that may predate the clinical diagnosis of malignancy. JF - Gastroenterology AU - Cawley, H M AU - Meltzer, S J AU - De Benedetti, V M AU - Hollstein, M C AU - Muehlbauer, K R AU - Liang, L AU - Bennett, W P AU - Souza, R F AU - Greenwald, B D AU - Cottrell, J AU - Salabes, A AU - Bartsch, H AU - Trivers, G E AD - Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, Maryland, USA. Y1 - 1998/07// PY - 1998 DA - July 1998 SP - 19 EP - 27 VL - 115 IS - 1 SN - 0016-5085, 0016-5085 KW - Antibodies KW - 0 KW - Tumor Suppressor Protein p53 KW - DNA KW - 9007-49-2 KW - Abridged Index Medicus KW - Index Medicus KW - Carcinoma, Squamous Cell -- immunology KW - Humans KW - Adult KW - DNA -- analysis KW - Aged KW - Middle Aged KW - Adenocarcinoma -- immunology KW - Mutation KW - Immunohistochemistry KW - Male KW - Barrett Esophagus -- immunology KW - Antibodies -- blood KW - Esophageal Neoplasms -- diagnosis KW - Tumor Suppressor Protein p53 -- immunology KW - Esophageal Neoplasms -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79999386?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Eosinophil+cationic+protein%2FRNase+3+is+another+RNase+A-family+ribonuclease+with+direct+antiviral+activity&rft.au=Domachowske%2C+J+B%3BDyer%2C+K+D%3BAdams%2C+A+G%3BLeto%2C+T+L%3BRosenberg%2C+H+F&rft.aulast=Domachowske&rft.aufirst=J&rft.date=1998-07-15&rft.volume=26&rft.issue=14&rft.spage=3358&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 - 1998-07-23 N1 - Date created - 1998-07-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transforming growth factor-beta1 is a new form of tumor suppressor with true haploid insufficiency. AN - 79998682; 9662371 AB - Components of the transforming growth factor-beta (TGF-beta) signal pathway function as classic tumor suppressors, but the role of the TGF-betas themselves is less clear. Here we show that mice heterozygous for deletion of the TGF-beta1 gene express only 10-30% of wild-type TGF-beta1 protein levels. Although grossly normal, these mice have a subtly altered proliferative phenotype, with increased cell turnover in the liver and lung. Treatment of these mice with chemical carcinogens resulted in enhanced tumorigenesis when compared with wild-type littermates. However, tumors in the heterozygous mice did not lose the remaining wild-type TGF-beta1 allele, indicating that the TGF-beta1 ligand is a new form of tumor suppressor that shows true haploid insufficiency in its ability to protect against tumorigenesis. JF - Nature medicine AU - Tang, B AU - Böttinger, E P AU - Jakowlew, S B AU - Bagnall, K M AU - Mariano, J AU - Anver, M R AU - Letterio, J J AU - Wakefield, L M AD - Laboratory of Cell Regulation and Carcinogenesis (formerly Laboratory of Chemoprevention), National Cancer Institute, Bethesda, Maryland 20892-5055, USA. Y1 - 1998/07// PY - 1998 DA - July 1998 SP - 802 EP - 807 VL - 4 IS - 7 SN - 1078-8956, 1078-8956 KW - Cell Cycle Proteins KW - 0 KW - Transforming Growth Factor beta KW - Index Medicus KW - Animals KW - Liver -- cytology KW - Liver Neoplasms -- metabolism KW - Apoptosis KW - Neoplasms, Experimental -- metabolism KW - Mice KW - Neoplasms, Experimental -- pathology KW - Liver Neoplasms -- pathology KW - Cell Cycle Proteins -- genetics KW - Mice, Inbred C57BL KW - Carcinogenicity Tests KW - Gene Targeting KW - Male KW - Cell Division KW - Lung Neoplasms -- metabolism KW - Lung Neoplasms -- pathology KW - Genes, Tumor Suppressor KW - Transforming Growth Factor beta -- genetics KW - Transforming Growth Factor beta -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79998682?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+medicine&rft.atitle=Transforming+growth+factor-beta1+is+a+new+form+of+tumor+suppressor+with+true+haploid+insufficiency.&rft.au=Tang%2C+B%3BB%C3%B6ttinger%2C+E+P%3BJakowlew%2C+S+B%3BBagnall%2C+K+M%3BMariano%2C+J%3BAnver%2C+M+R%3BLetterio%2C+J+J%3BWakefield%2C+L+M&rft.aulast=Tang&rft.aufirst=B&rft.date=1998-07-01&rft.volume=4&rft.issue=7&rft.spage=802&rft.isbn=&rft.btitle=&rft.title=Nature+medicine&rft.issn=10788956&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-04-07 N1 - Date created - 1999-04-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mechanical stretch alters the actin cytoskeletal network and signal transduction in human trabecular meshwork cells. AN - 79993212; 9660484 AB - Human trabecular meshwork (HTM) cells were mechanically stretched in vitro as a potential model for the distension of this tissue that can occur in vivo in response to increased pressure gradients. Cell morphology and certain components of the signal transduction pathways, including the mitogen-activated protein kinase (MAPK) and c-Jun N-terminal protein kinase (JNK) pathways, were evaluated for stretch-induced alterations. Primary HTM cells grown in tissue culture were subjected to a mechanical stretch lasting from 10 seconds to 4 days. The actin cytoskeletal network was visualized by phalloidin staining. Proteins phosphorylated on their tyrosine residues were isolated using an immunoaffinity system and were analyzed by gel electrophoresis and immunostaining. Mitogen-activated protein kinase activity was evaluated using an in-gel assay system, and the mRNA levels of c-fos and c-jun were determined by quantitation of competitive reverse transcription-polymerase chain reaction. In addition, the amount of c-Fos protein was estimated by chemiluminescent immunoblot analysis. On stretching, the HTM cells elongated but regained their normal morphologic characteristics within 24 hours. Unstretched HTM cells displayed a diffuse F-actin microfilament network, whereas stretched cells exhibited complex geodesic patterns. Ten seconds after stretching began, the level of tyrosine phosphorylation on the six major phosphoproteins significantly decreased between 80% and 100%, whereas the level of paxillin tyrosine phosphorylation significantly increased 39%. Stretching caused MAPK activity and the amount of mRNA and protein of the immediate-early gene c-fos to decrease more than 60% within 2 minutes, but within 15 to 30 minutes they increased above or equivalent to normal levels. The level of c-jun mRNA was unchanged by stretching. In response to a mechanical stretch, major cytoskeletal alterations occur in HTM cells, which involve changes in the levels of tyrosine phosphorylation. Mechanotransduction (signal transduction by mechanical stimulation) through the MAPK signaling pathway was significantly depressed immediately after stretching; however, the JNK pathway appeared to be unaffected. The data suggest that HTM cells adapt to mechanical stress by altering the cytoskeletal network and signaling cascades. JF - Investigative ophthalmology & visual science AU - Tumminia, S J AU - Mitton, K P AU - Arora, J AU - Zelenka, P AU - Epstein, D L AU - Russell, P AD - Laboratory for Mechanisms of Ocular Diseases, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892-2735, USA. Y1 - 1998/07// PY - 1998 DA - July 1998 SP - 1361 EP - 1371 VL - 39 IS - 8 SN - 0146-0404, 0146-0404 KW - Actins KW - 0 KW - Proto-Oncogene Proteins c-fos KW - Proto-Oncogene Proteins c-jun KW - RNA, Messenger KW - Phalloidine KW - 17466-45-4 KW - Tyrosine KW - 42HK56048U KW - Calcium-Calmodulin-Dependent Protein Kinases KW - EC 2.7.11.17 KW - Index Medicus KW - Space life sciences KW - Calcium-Calmodulin-Dependent Protein Kinases -- metabolism KW - Proto-Oncogene Proteins c-fos -- metabolism KW - Electrophoresis, Polyacrylamide Gel KW - Humans KW - Aged KW - Proto-Oncogene Proteins c-jun -- metabolism KW - RNA, Messenger -- metabolism KW - Phosphorylation KW - Cells, Cultured KW - Proto-Oncogene Proteins c-fos -- genetics KW - Adult KW - Proto-Oncogene Proteins c-jun -- genetics KW - Middle Aged KW - Tyrosine -- metabolism KW - Adolescent KW - Trabecular Meshwork -- metabolism KW - Stress, Mechanical KW - Actin Cytoskeleton -- metabolism KW - Actins -- metabolism KW - Trabecular Meshwork -- cytology KW - Signal Transduction UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79993212?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mechanical+stretch+alters+the+actin+cytoskeletal+network+and+signal+transduction+in+human+trabecular+meshwork+cells.&rft.au=Tumminia%2C+S+J%3BMitton%2C+K+P%3BArora%2C+J%3BZelenka%2C+P%3BEpstein%2C+D+L%3BRussell%2C+P&rft.aulast=Tumminia&rft.aufirst=S&rft.date=1998-07-01&rft.volume=39&rft.issue=8&rft.spage=1361&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 - 1998-07-14 N1 - Date created - 1998-07-14 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Invest Ophthalmol Vis Sci. 1999 Jul;40(8):1888-9 [10393068] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Diosmin and diosmetin are agonists of the aryl hydrocarbon receptor that differentially affect cytochrome P450 1A1 activity. AN - 79992061; 9661887 AB - We investigated the effect of the chemopreventive compound diosmin and its aglycone form, diosmetin, on the carcinogen activation pathway mediated by the aryl hydrocarbon receptor (AhR) in MCF-7 human breast epithelial cancer cells. Treatment of the cells with diosmin caused a dose-dependent increase in the metabolism of the mammary carcinogen 7,12-dimethylbenz(a)anthracene (DMBA), as assessed by increased formation of DMBA-DNA adducts and by DMBA-induced cytotoxicity. In contrast, treatment of the cells with diosmetin decreased both parameters. Diosmetin, but not diosmin, directly inhibited cytochrome P450 1A1 (CYP1A1) activity in a noncompetitive manner in microsomes isolated from DMBA-treated cells, as assayed by ethyoxyresorufin-O-deethylase activity. Treatment of the cells with diosmin or diosmetin, on the other hand, caused a dose- and time-dependent increase in CYP1A1 activity in intact cells that was comparable to that induced by DMBA or by the aryl hydrocarbon benzo(a)pyrene. Both diosmin and diosmetin caused an increase in the transcription of the CYP1A1 gene, as measured by increased levels of CYP1A1 mRNA. Both compounds caused the activation of the DNA-binding capacity of the AhR for the xenobiotic-responsive element of CYP1A1. These results indicate that diosmin and diosmetin are natural dietary agonists of the AhR, causing a potent increase in CYP1A1 transcription and CYP1A1 activity; however, only diosmetin is capable of inhibiting CYP1A1 enzyme activity, thus inhibiting carcinogen activation. JF - Cancer research AU - Ciolino, H P AU - Wang, T T AU - Yeh, G C AD - Cellular Defense and Carcinogenesis Section, Division of Basic Sciences, National Cancer Institute-Frederick Cancer Research and Development Center, NIH, Maryland 21702-1201, USA. hciolino@mail.ncifcrf.gov Y1 - 1998/07/01/ PY - 1998 DA - 1998 Jul 01 SP - 2754 EP - 2760 VL - 58 IS - 13 SN - 0008-5472, 0008-5472 KW - 7,12-dimethylbenz(a)anthracene-DNA adduct KW - 0 KW - Carcinogens KW - DNA Adducts KW - Flavonoids KW - RNA, Messenger KW - Receptors, Aryl Hydrocarbon KW - 9,10-Dimethyl-1,2-benzanthracene KW - 57-97-6 KW - Diosmin KW - 7QM776WJ5N KW - Cytochrome P-450 CYP1A1 KW - EC 1.14.14.1 KW - diosmetin KW - TWZ37241OT KW - Index Medicus KW - Carcinogens -- pharmacology KW - Carcinogens -- metabolism KW - 9,10-Dimethyl-1,2-benzanthracene -- analogs & derivatives KW - Tumor Cells, Cultured KW - RNA, Messenger -- metabolism KW - 9,10-Dimethyl-1,2-benzanthracene -- pharmacology KW - Dose-Response Relationship, Drug KW - Humans KW - 9,10-Dimethyl-1,2-benzanthracene -- metabolism KW - DNA Adducts -- metabolism KW - Diosmin -- pharmacology KW - Receptors, Aryl Hydrocarbon -- agonists KW - Cytochrome P-450 CYP1A1 -- metabolism KW - Receptors, Aryl Hydrocarbon -- metabolism KW - Flavonoids -- pharmacology KW - Cytochrome P-450 CYP1A1 -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79992061?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Diosmin+and+diosmetin+are+agonists+of+the+aryl+hydrocarbon+receptor+that+differentially+affect+cytochrome+P450+1A1+activity.&rft.au=Ciolino%2C+H+P%3BWang%2C+T+T%3BYeh%2C+G+C&rft.aulast=Ciolino&rft.aufirst=H&rft.date=1998-07-01&rft.volume=58&rft.issue=13&rft.spage=2754&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 - 1998-07-23 N1 - Date created - 1998-07-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Protein-linked DNA strand breaks induced by NSC 314622, a novel noncamptothecin topoisomerase I poison. AN - 79991650; 9658189 AB - NSC 314622 was found to have a cytotoxicity profile comparable to the topoisomerase I (top1) inhibitors camptothecin (CPT) and saintopin in the National Cancer Institute In Vitro Anticancer Drug Discovery Screen using the COMPARE analysis. In vitro data showed that NSC 314622 induced DNA cleavage in the presence of top1 at micromolar concentrations. Cleavage specificity was different from CPT in that NSC 314622 did not cleave all sites induced by CPT whereas some sites were unique to the NSC 314622 treatment. Top1-induced DNA cleavage was also more stable than cleavage induced by CPT. NSC 314622 did not induce DNA cleavage in the presence of human topoisomerase II. High concentrations of NSC 314622 did not produce detectable DNA unwinding, which suggests that NSC 314622 is not a DNA intercalator. DNA damage analyzed in human breast carcinoma MCF7 cells by alkaline elution showed that NSC 314622 induced protein-linked DNA single-strand breaks that reversed more slowly than CPT-induced strand breaks. CEM/C2, a CPT-resistant cell line because of a top1 point mutation [Cancer Res 55:1339-1346 (1995)], was cross-resistant to NSC 314622. These results demonstrate that NSC 314622 is a novel top1-targeted drug with a unique chemical structure. JF - Molecular pharmacology AU - Kohlhagen, G AU - Paull, K D AU - Cushman, M AU - Nagafuji, P AU - Pommier, Y AD - Laboratory of Molecular Pharmacology, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4255, USA. Y1 - 1998/07// PY - 1998 DA - July 1998 SP - 50 EP - 58 VL - 54 IS - 1 SN - 0026-895X, 0026-895X KW - Antineoplastic Agents, Phytogenic KW - 0 KW - DNA, Neoplasm KW - Indenes KW - Isoquinolines KW - NSC 314622 KW - Topoisomerase I Inhibitors KW - Camptothecin KW - XT3Z54Z28A KW - Index Medicus KW - Drug Screening Assays, Antitumor KW - Camptothecin -- pharmacology KW - Tumor Cells, Cultured -- drug effects KW - Humans KW - Antineoplastic Agents, Phytogenic -- pharmacology KW - Carcinoma -- enzymology KW - Breast Neoplasms -- enzymology KW - Indenes -- chemical synthesis KW - DNA, Neoplasm -- drug effects KW - Isoquinolines -- pharmacology KW - Indenes -- pharmacology KW - DNA Damage KW - Isoquinolines -- chemical synthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79991650?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Protein-linked+DNA+strand+breaks+induced+by+NSC+314622%2C+a+novel+noncamptothecin+topoisomerase+I+poison.&rft.au=Kohlhagen%2C+G%3BPaull%2C+K+D%3BCushman%2C+M%3BNagafuji%2C+P%3BPommier%2C+Y&rft.aulast=Kohlhagen&rft.aufirst=G&rft.date=1998-07-01&rft.volume=54&rft.issue=1&rft.spage=50&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 - 1998-08-06 N1 - Date created - 1998-08-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Lipoxygenase inhibitors prevent lung carcinogenesis and inhibit non-small cell lung cancer growth. AN - 79991303; 9659587 AB - The effects of lipoxygenase inhibitors were investigated using human lung cancer cell lines and A/J mice. By RT-PCR, 5-, 12-, and 15-lipoxygenase mRNA was detected in NSCLC cells. NDGA inhibited 5-LO activity in adenocarcinoma cell line NCI-H1264. Using an MTT assay, NDGA, MK591 and AA861 inhibited the growth of NSCLC cell lines tested with IC50 values of 3, 2, and 7 microM, respectively. Using a clonogenic assay, 10 microM NDGA significantly reduced NSCLC colony number. NDGA significantly slowed NSCLC xenograft growth in nude mice. When the tumors were excised and analyzed, nude mice treated with NDGA had significantly more apoptotic figures than did untreated tumors. A/J mice treated with urethane developed adenomas after 4 months and NDGA administration significantly reduced lung adenoma number. These data indicate that lipoxygenase inhibitors inhibit lung cancer growth and prevent lung carcinogenesis. JF - Experimental lung research AU - Moody, T W AU - Leyton, J AU - Martinez, A AU - Hong, S AU - Malkinson, A AU - Mulshine, J L AD - Cell and Cancer Biology Department, National Cancer Institute, Rockville, Maryland, USA. moodyt@bprb.nci.nih.gov PY - 1998 SP - 617 EP - 628 VL - 24 IS - 4 SN - 0190-2148, 0190-2148 KW - Benzoquinones KW - 0 KW - DNA Primers KW - DNA, Neoplasm KW - Indoles KW - Lipoxygenase Inhibitors KW - Quinolines KW - RNA, Messenger KW - MK 0591 KW - 136668-42-3 KW - Masoprocol KW - 7BO8G1BYQU KW - 2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone KW - 80809-81-0 KW - Lipoxygenase KW - EC 1.13.11.12 KW - Index Medicus KW - Animals KW - Lipoxygenase -- genetics KW - Humans KW - Mice, Nude KW - DNA, Neoplasm -- analysis KW - Mice KW - Mice, Inbred BALB C KW - RNA, Messenger -- biosynthesis KW - Neoplasm Transplantation KW - Mice, Inbred A KW - Quinolines -- pharmacology KW - Tumor Cells, Cultured KW - Benzoquinones -- pharmacology KW - Indoles -- pharmacology KW - Immunoenzyme Techniques KW - DNA Primers -- chemistry KW - Masoprocol -- pharmacology KW - Carcinoma, Non-Small-Cell Lung -- prevention & control KW - Adenocarcinoma -- enzymology KW - Lung Neoplasms -- enzymology KW - Lung Neoplasms -- prevention & control KW - Lipoxygenase Inhibitors -- pharmacology KW - Carcinoma, Non-Small-Cell Lung -- enzymology KW - Adenocarcinoma -- prevention & control KW - Lung Neoplasms -- pathology KW - Carcinoma, Non-Small-Cell Lung -- pathology KW - Adenocarcinoma -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79991303?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+lung+research&rft.atitle=Lipoxygenase+inhibitors+prevent+lung+carcinogenesis+and+inhibit+non-small+cell+lung+cancer+growth.&rft.au=Moody%2C+T+W%3BLeyton%2C+J%3BMartinez%2C+A%3BHong%2C+S%3BMalkinson%2C+A%3BMulshine%2C+J+L&rft.aulast=Moody&rft.aufirst=T&rft.date=1998-07-01&rft.volume=24&rft.issue=4&rft.spage=617&rft.isbn=&rft.btitle=&rft.title=Experimental+lung+research&rft.issn=01902148&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-09-17 N1 - Date created - 1998-09-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transforming growth factor-beta expression in mouse lung carcinogenesis. AN - 79990475; 9659584 AB - Transforming growth factor-beta (TGF-beta) is a multifunctional growth modulator that inhibits the proliferation of many epithelial cells while stimulating the proliferation of most fibroblasts. To examine the role of TGF-beta in mouse lung chemically induced tumorigenesis, expression of the TGF-beta 1, -beta 2, and -beta 3 proteins was examined in A/J mice treated with the carcinogen urethane to induce lung adenomas using immunohistochemical staining analysis. Immunostaining for the TGF-beta ligands was detected in the epithelium of the bronchioles of untreated A/J mice with immunostaining being more intense for TGF-beta 1 than for TGF-beta 2 and TGF-beta 3; immunostaining for each TGF-beta ligand was also detected in the bronchiolar epithelium of urethane-treated A/J mice at levels similar to untreated mice. Immunostaining for the TGF-beta ligands was also detected in adenomas by 2 months; staining for TGF-beta 1, -beta 2, and -beta 3 in adenomas was detected at levels comparable with bronchioles. Following treatment with urethane for 8 months, immunostaining for TGF-beta s 1, 2, and 3 in bronchioles persisted at levels comparable to that in normal bronchioles and also persisted in adenomas, with staining for the TGF-beta ligands being very prominent on the edge of the tumor. Expression of TGF-beta 1 mRNA was examined in urethane-treated mouse lung tissue using Northern blot hybridization; here, expression of TGF-beta 1 mRNA increased 2-fold in 3-month urethane-treated lung tissue and an additional 2.5-fold by 8 months following urethane administration. Expression of TGF-beta 1 mRNA was also examined in nontumorigenic and tumorigenic mouse lung cells; in these cells, expression of TGF-beta 1 mRNA was higher in the tumorigenic cells than in the nontumorigenic cell line. These data show that there is an increase in expression of TGF-beta 1 during tumorigenesis and suggest that TGF-beta may play an important role in mouse lung carcinogenesis induced by urethane. JF - Experimental lung research AU - Jakowlew, S B AU - Moody, T W AU - You, L AU - Mariano, J M AD - National Cancer Institute, Medicine Branch, Rockville, Maryland, USA. PY - 1998 SP - 579 EP - 593 VL - 24 IS - 4 SN - 0190-2148, 0190-2148 KW - Carcinogens KW - 0 KW - DNA Primers KW - Ligands KW - RNA, Messenger KW - Transforming Growth Factor beta KW - Urethane KW - 3IN71E75Z5 KW - Index Medicus KW - Animals KW - Blotting, Northern KW - Lung -- cytology KW - Carcinogens -- toxicity KW - Disease Progression KW - Mice KW - Lung -- metabolism KW - RNA, Messenger -- biosynthesis KW - Epithelial Cells -- metabolism KW - Polymerase Chain Reaction KW - Mice, Inbred A KW - Tumor Cells, Cultured KW - Bronchi -- cytology KW - Bronchi -- metabolism KW - Urethane -- toxicity KW - Female KW - Immunoenzyme Techniques KW - DNA Primers -- chemistry KW - Adenoma -- metabolism KW - Adenoma -- chemically induced KW - Lung Neoplasms -- chemically induced KW - Transforming Growth Factor beta -- genetics KW - Adenoma -- pathology KW - Transforming Growth Factor beta -- metabolism KW - Lung Neoplasms -- pathology KW - Lung Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79990475?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+lung+research&rft.atitle=Transforming+growth+factor-beta+expression+in+mouse+lung+carcinogenesis.&rft.au=Jakowlew%2C+S+B%3BMoody%2C+T+W%3BYou%2C+L%3BMariano%2C+J+M&rft.aulast=Jakowlew&rft.aufirst=S&rft.date=1998-07-01&rft.volume=24&rft.issue=4&rft.spage=579&rft.isbn=&rft.btitle=&rft.title=Experimental+lung+research&rft.issn=01902148&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-09-17 N1 - Date created - 1998-09-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characterization of an unstable allele of the Arabidopsis HY4 locus. AN - 79985922; 9649544 AB - The Arabidopsis HY4 gene encodes the nonessential blue light photoreceptor CRY1. Loss-of-function hy4 mutants have an elongated hypocotyl phenotype after germination under blue light. We previously analyzed 20 independent hy4 alleles produced by fast neutron mutagenesis. These alleles were grouped into two classes based on their genetic behavior and corresponding deletion size: (1) null hy4 alleles that were semidominant over wild type and contained small or moderate-sized deletions at HY4 and (2) null hy4 alleles that were recessive lethal and contained large HY4 deletions. Here we describe one additional fast neutron hy4 mutant, B144, that did not fall into either of these two classes. Mutant B144 was isolated as a heterozygote with an intermediate hy4 phenotype. One allele from this mutant, hy4-B144(Delta), contains a large deletion at HY4 and is recessive lethal. The other allele from this mutant, HY4-B144*, appears to be intact and functional but is unstable and spontaneously converts to a nonfunctional hy4 allele. In addition, HY4-B144* is lethal in homozygotes and suppresses local recombination. We discuss genetic and epigenetic mechanisms that may account for the unusual behavior of the HY4-B144* allele. JF - Genetics AU - Bruggemann, E P AU - Doan, B AU - Handwerger, K AU - Storz, G AD - Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-5430, USA. Y1 - 1998/07// PY - 1998 DA - July 1998 SP - 1575 EP - 1585 VL - 149 IS - 3 SN - 0016-6731, 0016-6731 KW - Arabidopsis Proteins KW - 0 KW - CRY1 protein, Arabidopsis KW - CRY1 protein, human KW - Cryptochromes KW - Drosophila Proteins KW - Eye Proteins KW - Flavoproteins KW - Plant Proteins KW - Receptors, G-Protein-Coupled KW - cryptochrome protein, Drosophila KW - Index Medicus KW - Phenotype KW - Neutrons KW - Genotype KW - Alleles KW - Crosses, Genetic KW - Light KW - Mutagenesis KW - Plant Proteins -- biosynthesis KW - Arabidopsis -- genetics KW - Flavoproteins -- biosynthesis KW - Flavoproteins -- genetics KW - Plant Proteins -- genetics KW - Genes, Plant KW - Arabidopsis -- physiology KW - Photoreceptor Cells, Invertebrate KW - Chromosome Mapping UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79985922?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Up-regulation+of+inducible+nitric+oxide+synthase+expression+in+cancer-prone+p53+knockout+mice.&rft.au=Ambs%2C+S%3BOgunfusika%2C+M+O%3BMerriam%2C+W+G%3BBennett%2C+W+P%3BBilliar%2C+T+R%3BHarris%2C+C+C&rft.aulast=Ambs&rft.aufirst=S&rft.date=1998-07-21&rft.volume=95&rft.issue=15&rft.spage=8823&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 - 1998-08-24 N1 - Date created - 1998-08-24 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Plant J. 1993 Aug;4(2):403-10 [8106085] Plant J. 1993 Mar;3(3):493-4 [8220456] Plant Cell. 1994 May;6(5):613-28 [8038602] Biochemistry. 1995 May 23;34(20):6892-9 [7756321] Science. 1995 Aug 18;269(5226):968-70 [7638620] Proc Natl Acad Sci U S A. 1995 Aug 29;92(18):8423-7 [7667306] Planta. 1995;197(2):213-8 [8547813] Planta. 1995;197(2):233-9 [8547814] Plant J. 1996 May;9(5):755-65 [8653121] Plant J. 1996 Oct;10(4):755-60 [8893551] Plant J. 1996 Nov;10(5):893-902 [8953250] Nucleic Acids Res. 1986 May 27;14(10):4051-64 [3012462] Mol Cell Biol. 1988 May;8(5):1985-92 [3386631] Proc Natl Acad Sci U S A. 1988 Sep;85(18):6856-60 [2901107] Nature. 1993 Nov 11;366(6451):162-6 [8232555] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Use of quantitative trait loci to map murine lung tumor susceptibility genes. AN - 79985094; 9659574 AB - During the last decade new methods for mapping quantitative trait loci (QTLs) have helped geneticists uncover disease-associated genes. Genetic dissection of complex multigenic diseases such as cancer is being accomplished in part by mapping QTLs in experimental crosses of mice [1]. With the recent construction of dense genetic linkage maps for the mouse, mapping of quantitative trait loci has become practical [2]. Over 6000 polymorphic simple sequence length repeat markers (microsatellite markers) have been mapped in the mouse genome [3], and new analytical approaches to linkage analysis have made QTL mapping a powerful technique for identifying cancer genes [4-7]. In this overview we discuss the design of QTL mapping studies and some of the findings from studies on the mapping of murine lung tumor susceptibility loci. JF - Experimental lung research AU - Devereux, T R AU - Kaplan, N L AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA. devereux@niehs.nih.gov PY - 1998 SP - 407 EP - 417 VL - 24 IS - 4 SN - 0190-2148, 0190-2148 KW - DNA, Neoplasm KW - 0 KW - Index Medicus KW - Quantitative Trait, Heritable KW - Genetic Linkage KW - Microsatellite Repeats KW - Mice, Inbred A KW - Animals KW - Mice, Inbred C57BL KW - Disease Models, Animal KW - Mice KW - Inbreeding KW - Genetic Predisposition to Disease KW - Gene Expression Regulation, Neoplastic KW - Lung Neoplasms -- genetics KW - DNA, Neoplasm -- analysis KW - Chromosome Mapping KW - Lung Neoplasms -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79985094?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+lung+research&rft.atitle=Use+of+quantitative+trait+loci+to+map+murine+lung+tumor+susceptibility+genes.&rft.au=Devereux%2C+T+R%3BKaplan%2C+N+L&rft.aulast=Devereux&rft.aufirst=T&rft.date=1998-07-01&rft.volume=24&rft.issue=4&rft.spage=407&rft.isbn=&rft.btitle=&rft.title=Experimental+lung+research&rft.issn=01902148&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-09-17 N1 - Date created - 1998-09-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Contribution of proton release to the B2 photocurrent of bacteriorhodopsin. AN - 79978795; 9649395 AB - The contribution of proton release from the so-called proton release group to the microsecond B2 photocurrent from bacteriorhodopsin (bR) oriented in polyacrylamide gels was determined. The fraction of the B2 current due to proton release was resolved by titration of the proton release group in M. At pH values below the pKa of the proton release group in M, the proton release group cannot release its proton during the first half of the bacteriorhodopsin photocycle. At these pH values, the B2 photocurrent is due primarily to translocation of the Schiff base proton to Asp85. The B2 photocurrent was measured in wild-type bR gels at pH 4.5-7.5, in 100 mM KCl/50 mM phosphate. The B2 photocurrent area (proportional to the amount of charge moved) exhibits a pH dependence with a pKa of 6.1. This is suggested to be the pKa of the proton release group in M; the value obtained is in good agreement with previous results obtained by examining photocycle kinetics and pH-sensitive dye signals. In the mutant Glu204Gln, the B2 photocurrent of the mutant membranes was pH independent between pH 4 and 7. Because the proton release group is incapacitated, and early proton release is eliminated in the Glu204Gln mutant, this supports the idea that the pH dependence of the B2 photocurrent in the wild type reflects the titration of the proton release group. In wild-type bacteriorhodopsin, proton release contributes approximately half of the B2 area at pH 7.5. The B2 area in the Glu204Gln mutant is similar to that in the wild type at pH 4.5; in both cases, the B2 current is likely due only to movement of the Schiff base proton to Asp85. JF - Biophysical journal AU - Misra, S AD - Center for Biophysics and Computational Biology, and Department of Cell and Structural Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801 USA. misra@mimsy.niddk.nih.gov Y1 - 1998/07// PY - 1998 DA - July 1998 SP - 382 EP - 388 VL - 75 IS - 1 SN - 0006-3495, 0006-3495 KW - Protons KW - 0 KW - Schiff Bases KW - Glutamine KW - 0RH81L854J KW - Aspartic Acid KW - 30KYC7MIAI KW - Glutamic Acid KW - 3KX376GY7L KW - Bacteriorhodopsins KW - 53026-44-1 KW - Index Medicus KW - Photochemistry KW - Mutagenesis, Site-Directed KW - Kinetics KW - Hydrogen-Ion Concentration KW - Glutamic Acid -- chemistry KW - Glutamine -- chemistry KW - Schiff Bases -- chemistry KW - Biophysical Phenomena KW - Aspartic Acid -- chemistry KW - Biophysics KW - Bacteriorhodopsins -- chemistry KW - Bacteriorhodopsins -- radiation effects KW - Bacteriorhodopsins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79978795?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biophysical+journal&rft.atitle=Contribution+of+proton+release+to+the+B2+photocurrent+of+bacteriorhodopsin.&rft.au=Misra%2C+S&rft.aulast=Misra&rft.aufirst=S&rft.date=1998-07-01&rft.volume=75&rft.issue=1&rft.spage=382&rft.isbn=&rft.btitle=&rft.title=Biophysical+journal&rft.issn=00063495&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-08-12 N1 - Date created - 1998-08-12 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: FEBS Lett. 1992 Nov 30;313(3):248-50 [1446744] Biochemistry. 1992 Sep 15;31(36):8535-43 [1327104] FEBS Lett. 1993 Sep 27;331(1-2):31-4 [8405405] FEBS Lett. 1994 Mar 7;340(3):207-10 [8131847] Biophys J. 1995 Apr;68(4):1518-30 [7787037] J Biol Chem. 1995 Nov 10;270(45):27122-6 [7592966] Biochemistry. 1996 Apr 2;35(13):4054-62 [8672439] Biophys J. 1996 Jan;70(1):473-81 [8770224] Biophys J. 1996 Aug;71(2):1011-23 [8842238] Biophys J. 1997 Feb;72(2 Pt 1):886-98 [9017214] J Biochem. 1997 Mar;121(3):399-406 [9133606] Biochemistry. 1997 Jul 22;36(29):8671-6 [9289012] Science. 1997 Sep 12;277(5332):1676-81 [9287223] Nature. 1997 Sep 11;389(6647):206-11 [9296502] Photochem Photobiol. 1997 Dec;66(6):774-83 [9421964] Biochemistry. 1998 Feb 24;37(8):2496-506 [9485398] Prep Biochem. 1975;5(2):161-78 [1144313] Biophys J. 1979 Mar;25(3):465-72 [45397] Biophys J. 1980 May;30(2):231-42 [7260274] J Biochem Biophys Methods. 1985 Mar;10(5-6):295-300 [3998383] Biophys J. 1988 Aug;54(2):321-9 [3207828] Photochem Photobiol. 1990 Jun;51(6):793-818 [2195566] Biophys J. 1991 Jul;60(1):204-16 [1883939] Proc Natl Acad Sci U S A. 1993 Feb 15;90(4):1166-71 [8433978] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - On the discrepancy between epidemiologic studies in individuals of lung cancer and residential radon and Cohen's ecologic regression. AN - 79976232; 9645660 AB - There is still substantial confusion in the radiation effects community about the inherent limitations of ecologic analysis. As a result, inordinate attention has been given to the discrepant results of Cohen, in which a negative estimate is observed for the regression of county mortality rates for lung cancer on estimated county radon levels. This paper demonstrates that Cohen's ecologic analysis cannot produce valid inference on the exposure-response relationship for individuals unless lung cancer risk factors (smoking, age, occupation, etc.) for individuals are statistically uncorrelated with indoor radon level within counties or unless risk effects for radon and other factors are additive. Both of these assumptions are contradicted in the literature. Thus, contrary to common assumption, when a linear no-threshold model is the true model for radon risk for individuals, higher average radon concentration for a county does not necessarily imply a higher lung cancer rate for the county. In addition, valid inference from county-level ecologic analysis and the elimination of the ecologic bias cannot be achieved with the addition of county-wide summary variables (including "stratification" variables) to the regression equation. Using hypothetical data for smoking and radon and assuming a true positive association for radon and lung cancer for individuals, the analysis demonstrates that a negative county-level ecologic regression can be induced when correlation coefficients for smoking and radon within county are in the range -0.05 to 0.05. Since adverse effects for radon at low exposures are supported by analysis of miner data (all data and data restricted only to low cumulative exposures), a meta-analysis of indoor radon studies, and molecular and cellular studies, and since ecologic regressions are burdened by severe limitations, the negative results from Cohen's analysis are most likely due to bias and should be rejected. JF - Health physics AU - Lubin, J H AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1998/07// PY - 1998 DA - July 1998 SP - 4 EP - 10 VL - 75 IS - 1 SN - 0017-9078, 0017-9078 KW - Air Pollutants, Radioactive KW - 0 KW - Radon KW - Q74S4N8N1G KW - Index Medicus KW - Regression Analysis KW - Humans KW - Models, Statistical KW - Lung Neoplasms -- etiology KW - Lung Neoplasms -- epidemiology KW - Neoplasms, Radiation-Induced -- etiology KW - Neoplasms, Radiation-Induced -- epidemiology KW - Air Pollutants, Radioactive -- adverse effects KW - Radon -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79976232?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+of+medicine&rft.atitle=Non-narcotic+analgesics%3A+renal+and+gastrointestinal+considerations.+Introduction.&rft.au=Hamilton%2C+F+A&rft.aulast=Hamilton&rft.aufirst=F&rft.date=1998-07-27&rft.volume=105&rft.issue=1B&rft.spage=1S&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+medicine&rft.issn=00029343&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-07-08 N1 - Date created - 1998-07-08 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Health Phys. 1999 Mar;76(3):316-9 [10025660] Health Phys. 1998 Jul;75(1):18-22; discussion 29-30 [9645662] Comment On: Health Phys. 1997 Apr;72(4):623-8 [9119688] Health Phys. 1995 Feb;68(2):157-74 [7814250] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Concentrating defect in experimental nephrotic syndrone: altered expression of aquaporins and thick ascending limb Na+ transporters. AN - 79974596; 9648076 AB - Several pathophysiological states associated with deranged water balance are associated with altered expression and/or intracellular distribution of aquaporin water channels. The possible role of dysregulation of thick ascending limb NaCl transporters, which are responsible for countercurrent multiplication in the kidney, has not been evaluated. Semiquantitative immunoblotting and immunocytochemistry were carried out in the kidneys of rat with adriamycin-induced nephrotic syndrome and in vehicle-injected control rats. Preliminary studies confirmed the presence of a severe concentrating defect. Semiquantitative immunoblotting of outer medullary homogenates demonstrated a marked decrease in the abundance of three thick ascending limb Na+ transporters in nephrotic rats, namely the bumetanide-sensitive Na-K-2Cl cotransporter (BSC-1), the type 3 Na/H exchanger (NHE-3), and the alpha 1-subunit of the Na-K-ATPase. These results are predictive of a decrease in the NaCl transport capacity of the medullary thick ascending limb and therefore a decrease in countercurrent multiplication. Immunocytochemistry of outer medullary thin sections demonstrated broad (but highly variable) suppression of BSC-1 expression in the outer medullas of adriamycin-nephrotic rats. There was also a large decrease in outer medullary expression of two collecting duct water channels (aquaporin-2 and -3) and the major water channel of the thin descending limb of Henle's loop (aquaporin-1). The concentrating defect in adriamycin-induced nephrotic syndrome in rats is a consequence of multiple defects in water and solute transporter expression, which would alter both the generation of medullary interstitial hypertonicity and osmotic equilibration in the collecting duct. Whether a similar widespread defect in transporter expression is present in idiopathic nephrotic syndrome is, at this point, untested. JF - Kidney international AU - Fernández-Llama, P AU - Andrews, P AU - Ecelbarger, C A AU - Nielsen, S AU - Knepper, M AD - Laboratory of Kidney and Electrolyte Metabolism, National Heart, Lung and Blood Institute, National Institute of Health, Bethesda, Maryland, USA. Y1 - 1998/07// PY - 1998 DA - July 1998 SP - 170 EP - 179 VL - 54 IS - 1 SN - 0085-2538, 0085-2538 KW - Antibiotics, Antineoplastic KW - 0 KW - Aqp1 protein, rat KW - Aqp2 protein, rat KW - Aqp3 protein, rat KW - Aquaporin 2 KW - Aquaporin 6 KW - Aquaporins KW - Carrier Proteins KW - Ion Channels KW - Membrane Proteins KW - Mucoproteins KW - Sodium-Hydrogen Antiporter KW - Sodium-Potassium-Chloride Symporters KW - Umod protein, rat KW - Uromodulin KW - Aquaporin 1 KW - 146410-94-8 KW - Aquaporin 3 KW - 158801-98-0 KW - Doxorubicin KW - 80168379AG KW - Sodium-Potassium-Exchanging ATPase KW - EC 3.6.3.9 KW - Index Medicus KW - Specific Pathogen-Free Organisms KW - Animals KW - Mucoproteins -- metabolism KW - Membrane Proteins -- metabolism KW - Disease Models, Animal KW - Rabbits KW - Loop of Henle -- chemistry KW - Membrane Proteins -- analysis KW - Osmosis KW - Kidney Concentrating Ability -- physiology KW - Rats KW - Rats, Sprague-Dawley KW - Loop of Henle -- enzymology KW - Immunohistochemistry KW - Male KW - Mucoproteins -- analysis KW - Sodium-Potassium-Exchanging ATPase -- analysis KW - Sodium-Hydrogen Antiporter -- analysis KW - Sodium-Potassium-Exchanging ATPase -- metabolism KW - Nephrotic Syndrome -- physiopathology KW - Carrier Proteins -- metabolism KW - Sodium-Hydrogen Antiporter -- metabolism KW - Nephrotic Syndrome -- metabolism KW - Ion Channels -- analysis KW - Nephrotic Syndrome -- chemically induced KW - Carrier Proteins -- analysis KW - Ion Channels -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79974596?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Concentrating+defect+in+experimental+nephrotic+syndrone%3A+altered+expression+of+aquaporins+and+thick+ascending+limb+Na%2B+transporters.&rft.au=Fern%C3%A1ndez-Llama%2C+P%3BAndrews%2C+P%3BEcelbarger%2C+C+A%3BNielsen%2C+S%3BKnepper%2C+M&rft.aulast=Fern%C3%A1ndez-Llama&rft.aufirst=T&rft.date=1998-07-30&rft.volume=248&rft.issue=3&rft.spage=835&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 - 1998-09-16 N1 - Date created - 1998-09-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A functionally deficient DRD2 variant [Ser311Cys] is not linked to alcoholism and substance abuse. AN - 79973294; 9650635 AB - Association studies with the DRD2 Taq1A marker have been variable in implicating DRD2 as a "Reward Deficiency Syndrome Gene" for alcoholism and substance abuse. Given that the Taq1A marker is not functionally significant, second-generation studies on the DRD2 receptor to identify functional variants and evaluate their effect on the phenotype are the logical step towards confirming and extending the DRD2 hypothesis. This article discusses the implications and process of progress made in these directions. The new findings are the description of structural variants in the D2 receptor, the demonstration that one of these, Ser311Cys, largely prevents signal transduction following receptor activation and the use of Ser311Cys in a large association and sib-pair linkage anlysis in an American Indian isolate. In this particular population, the Cys311 variant is far more abundant (0.16) than in Caucasians (0.03). Genotyping of Ser311Cys, the DRD2 intron 2 STR, and the Taq1A marker in 459 subjects, including 373 sib-pairs and 15 Cys311/Cys311 homozygous individuals, revealed no association to alcoholism, substance use disorders, or schizophrenia. The implication is that a DRD2 variant that dramatically impairs receptor function was not sufficient to significantly alter alcoholism vulnerability in a relatively large and also genetically and environmentally homogeneous sample. JF - Alcohol (Fayetteville, N.Y.) AU - Goldman, D AU - Urbanek, M AU - Guenther, D AU - Robin, R AU - Long, J C AD - Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, Rockville, MD, USA. dgneuro@box-d.nih.gov Y1 - 1998/07// PY - 1998 DA - July 1998 SP - 47 EP - 52 VL - 16 IS - 1 SN - 0741-8329, 0741-8329 KW - Receptors, Dopamine D2 KW - 0 KW - Index Medicus KW - Humans KW - Amino Acid Sequence KW - Indians, North American -- genetics KW - Genetic Linkage KW - Genetic Variation -- genetics KW - Receptors, Dopamine D2 -- genetics KW - Alcoholism -- genetics KW - Substance-Related Disorders -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79973294?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Alcohol+%28Fayetteville%2C+N.Y.%29&rft.atitle=A+functionally+deficient+DRD2+variant+%5BSer311Cys%5D+is+not+linked+to+alcoholism+and+substance+abuse.&rft.au=Goldman%2C+D%3BUrbanek%2C+M%3BGuenther%2C+D%3BRobin%2C+R%3BLong%2C+J+C&rft.aulast=Goldman&rft.aufirst=D&rft.date=1998-07-01&rft.volume=16&rft.issue=1&rft.spage=47&rft.isbn=&rft.btitle=&rft.title=Alcohol+%28Fayetteville%2C+N.Y.%29&rft.issn=07418329&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-09-11 N1 - Date created - 1998-09-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Glucocorticoids increase vasopressin V1b receptor coupling to phospholipase C. AN - 79972523; 9645696 AB - Vasopressin (VP) stimulates pituitary ACTH secretion after binding to V1b VP receptors (V1b-R) coupled to phospholipase C (PLC). This effect of VP on ACTH secretion, unlike that of CRH, is resistant to glucocorticoid feedback. To determine whether changes in V1b-R expression or signaling mediate the refractoriness to glucocorticoids, the effects of glucocorticoids on pituitary VP binding, V1b-R messenger RNA (mRNA) and VP-stimulated inositol phosphate (IP) formation were studied in vivo and in vitro in the rat. Dexamethasone injection for 7 days decreased VP binding but increased V1b-R mRNA, indicating that mRNA levels do not reflect receptor number. In spite of the binding loss, VP-stimulated IP formation was enhanced in dexamethasone-treated rats, suggesting that glucocorticoids increase the coupling efficiency of the V1b receptor to phospholipase C. Pretreatment of pituitary cells in vitro with dexamethasone or corticosterone, also potentiated IP formation by low and high doses of VP, indicating that glucocorticoids act directly in the pituitary and not through changes in hypothalamic factors. The effect is mediated by glucocorticoid receptors because it was blocked by glucocorticoid but not mineralocorticoid antagonists. Dexamethasone potentiated the stimulation of IP by other PLC-dependent ligands (GnRH, TRH) but not that by the calcium ionophore, ionomycin, suggesting a site of action between the receptor and PLC. After treatment with dexamethasone, in vivo or in vitro, Western blot analysis revealed marked increases in the GTP binding protein, Galpha(q), which may account for the potentiating effect of glucocorticoid on ligand-stimulated IP. The data demonstrate that glucocorticoids increase coupling of the V1b-R with PLC thereby providing a mechanism by which VP facilitates corticotroph responsiveness in spite of elevated levels of plasma glucocorticoids during stress. JF - Endocrinology AU - Rabadan-Diehl, C AU - Aguilera, G AD - Section on Endocrine, Physiology, Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA. rabadanc@cc1.nichd.nih.gov Y1 - 1998/07// PY - 1998 DA - July 1998 SP - 3220 EP - 3226 VL - 139 IS - 7 SN - 0013-7227, 0013-7227 KW - Glucocorticoids KW - 0 KW - Inositol Phosphates KW - Receptors, Vasopressin KW - Vasopressins KW - 11000-17-2 KW - Dexamethasone KW - 7S5I7G3JQL KW - Type C Phospholipases KW - EC 3.1.4.- KW - Abridged Index Medicus KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Inositol Phosphates -- biosynthesis KW - Pituitary Gland, Anterior -- metabolism KW - Cells, Cultured KW - Dexamethasone -- pharmacology KW - Vasopressins -- pharmacology KW - Pituitary Gland, Anterior -- cytology KW - Drug Synergism KW - Male KW - Receptors, Vasopressin -- metabolism KW - Glucocorticoids -- pharmacology KW - Type C Phospholipases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79972523?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Glucocorticoids+increase+vasopressin+V1b+receptor+coupling+to+phospholipase+C.&rft.au=Rabadan-Diehl%2C+C%3BAguilera%2C+G&rft.aulast=Rabadan-Diehl&rft.aufirst=C&rft.date=1998-07-01&rft.volume=139&rft.issue=7&rft.spage=3220&rft.isbn=&rft.btitle=&rft.title=Endocrinology&rft.issn=00137227&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-07-17 N1 - Date created - 1998-07-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Statistical modeling of carcinogenic risks in dogs that inhaled 238PuO2. AN - 79972034; 9650604 AB - Combined analyses of data on 260 life-span beagle dogs that inhaled 238PuO2 at the Inhalation Toxicology Research Institute (ITRI) and at Pacific Northwest National Laboratory (PNNL) were conducted. The hazard functions (age-specific risks) for incidence of lung, bone and liver tumors were modeled as a function of cumulative radiation dose, and estimates of lifetime risks based on the combined data were developed. For lung tumors, linear-quadratic functions provided an adequate fit to the data from both laboratories, and linear functions provided an adequate fit when analyses were restricted to doses less than 20 Gy. The estimated risk coefficients for these functions were significantly larger when based on ITRI data compared to PNNL data, and dosimetry biases are a possible explanation for this difference. There was also evidence that the bone tumor response functions differed for the two laboratories, although these differences occurred primarily at high doses. These functions were clearly nonlinear (even when restricted to average skeletal doses less than 1 Gy), and evidence of radiation-induced bone tumors was found for doses less than 0.5 Gy in both laboratories. Liver tumor risks were similar for the two laboratories, and linear functions provided an adequate fit to these data. Lifetime risk estimates for lung and bone tumors derived from these data had wide confidence intervals, but were consistent with estimates currently used in radiation protection. The dog-based lifetime liver tumor risk estimate was an order of magnitude larger than that used in radiation protection, but the latter also carries large uncertainties. The application of common statistical methodology to data from two studies has allowed the identification of differences in these studies and has provided a basis for common risk estimates based on both data sets. JF - Radiation research AU - Gilbert, E S AU - Griffith, W C AU - Boecker, B B AU - Dagle, G E AU - Guilmette, R A AU - Hahn, F F AU - Muggenburg, B A AU - Park, J F AU - Watson, C R AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1998/07// PY - 1998 DA - July 1998 SP - 66 EP - 82 VL - 150 IS - 1 SN - 0033-7587, 0033-7587 KW - plutonium dioxide KW - 12059-95-9 KW - Plutonium KW - 53023GN24M KW - Index Medicus KW - Space life sciences KW - Bone Neoplasms -- etiology KW - Animals KW - Lung Neoplasms -- etiology KW - Liver Neoplasms, Experimental -- etiology KW - Risk Factors KW - Linear Models KW - Dogs KW - Data Interpretation, Statistical KW - Dose-Response Relationship, Radiation KW - Administration, Inhalation KW - Male KW - Female KW - Proportional Hazards Models KW - Neoplasms, Radiation-Induced -- etiology KW - Plutonium -- administration & dosage KW - Plutonium -- toxicity KW - Models, Statistical UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79972034?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Statistical+modeling+of+carcinogenic+risks+in+dogs+that+inhaled+238PuO2.&rft.au=Gilbert%2C+E+S%3BGriffith%2C+W+C%3BBoecker%2C+B+B%3BDagle%2C+G+E%3BGuilmette%2C+R+A%3BHahn%2C+F+F%3BMuggenburg%2C+B+A%3BPark%2C+J+F%3BWatson%2C+C+R&rft.aulast=Gilbert&rft.aufirst=E&rft.date=1998-07-01&rft.volume=150&rft.issue=1&rft.spage=66&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 - 1998-07-16 N1 - Date created - 1998-07-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Sonography of gallbladder abnormalities in acromegaly patients following octreotide and ursodiol therapy: incidence and time course. AN - 79960468; 9641388 AB - We studied the effects of octreotide and ursodiol on the gallbladders of patients with acromegaly. We performed gallbladder sonography in patients with acromegaly at various intervals during treatment. Group I (18 patients) was treated with subcutaneous injections of the somatostatin analogue octreotide. Group II (10 patients) was treated with ursodiol while receiving octreotide therapy. Seventy-eight percent of patients receiving octreotide developed gallbladder abnormalities: sludge in 72% (13/18) and calculi in 39% (7/18). Ursodiol reversed the gallbladder abnormalities in 7 of 10 patients. A majority of patients receiving octreotide develop gallbladder abnormalities. Ursodiol appears to reverse the abnormalities in most cases. JF - Journal of clinical ultrasound : JCU AU - Avila, N A AU - Shawker, T H AU - Roach, P AU - Bradford, M H AU - Skarulis, M C AU - Eastman, R AD - Diagnostic Radiology Department, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland 20892-1182, USA. PY - 1998 SP - 289 EP - 294 VL - 26 IS - 6 SN - 0091-2751, 0091-2751 KW - Cholagogues and Choleretics KW - 0 KW - Hormones KW - Ursodeoxycholic Acid KW - 724L30Y2QR KW - Octreotide KW - RWM8CCW8GP KW - Index Medicus KW - Humans KW - Adult KW - Middle Aged KW - Ultrasonography KW - Time Factors KW - Male KW - Female KW - Gallbladder -- diagnostic imaging KW - Cholagogues and Choleretics -- therapeutic use KW - Octreotide -- therapeutic use KW - Octreotide -- adverse effects KW - Ursodeoxycholic Acid -- therapeutic use KW - Gallbladder Diseases -- diagnostic imaging KW - Hormones -- therapeutic use KW - Acromegaly -- drug therapy KW - Gallbladder Diseases -- chemically induced KW - Hormones -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79960468?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+ultrasound+%3A+JCU&rft.atitle=Sonography+of+gallbladder+abnormalities+in+acromegaly+patients+following+octreotide+and+ursodiol+therapy%3A+incidence+and+time+course.&rft.au=Avila%2C+N+A%3BShawker%2C+T+H%3BRoach%2C+P%3BBradford%2C+M+H%3BSkarulis%2C+M+C%3BEastman%2C+R&rft.aulast=Avila&rft.aufirst=N&rft.date=1998-07-01&rft.volume=26&rft.issue=6&rft.spage=289&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+ultrasound+%3A+JCU&rft.issn=00912751&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-08-21 N1 - Date created - 1998-08-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Coadministration of galanin antagonist M40 with a muscarinic M1 agonist improves delayed nonmatching to position choice accuracy in rats with cholinergic lesions. AN - 79953989; 9634573 AB - The neuropeptide galanin is overexpressed in the basal forebrain in Alzheimer's disease (AD). In rats, galanin inhibits evoked hippocampal acetylcholine release and impairs performance on several memory tasks, including delayed nonmatching to position (DNMTP). Galanin(1-13)-Pro2-(Ala-Leu)2-Ala-NH2 (M40), a peptidergic galanin receptor ligand, has been shown to block galanin-induced impairment on DNMTP in rats. M40 injected alone, however, does not improve DNMTP choice accuracy deficits in rats with selective cholinergic immunotoxic lesions of the basal forebrain. The present experiments used a strategy of combining M40 with an M1 cholinergic agonist in rats lesioned with the cholinergic immunotoxin 192IgG-saporin. Coadministration of intraventricular M40 with intraperitoneal 3-(3-S-n-pentyl-1,2,5-thiadiazol-4-yl)-1,2,5, 6-tetrahydro-1-methylpyridine (TZTP), an M1 agonist, improved choice accuracy significantly more than a threshold dose of TZTP alone. These results suggest that a galanin antagonist may enhance the efficacy of cholinergic treatments for the cognitive deficits of AD. JF - The Journal of neuroscience : the official journal of the Society for Neuroscience AU - McDonald, M P AU - Willard, L B AU - Wenk, G L AU - Crawley, J N AD - Section on Behavioral Neuropharmacology, Experimental Therapeutics Branch, National Institute of Mental Health, Bethesda, Maryland 20982, USA. Y1 - 1998/07/01/ PY - 1998 DA - 1998 Jul 01 SP - 5078 EP - 5085 VL - 18 IS - 13 SN - 0270-6474, 0270-6474 KW - 192 IgG-saporin KW - 0 KW - Antibodies, Monoclonal KW - Cholinergic Agents KW - Immunotoxins KW - M40 KW - Muscarinic Agonists KW - Peptide Fragments KW - Pyridines KW - Receptor, Muscarinic M1 KW - Receptors, Muscarinic KW - Ribosome Inactivating Proteins, Type 1 KW - Thiadiazoles KW - Galanin KW - 88813-36-9 KW - xanomeline KW - 9ORI6L73CJ KW - N-Glycosyl Hydrolases KW - EC 3.2.2.- KW - Acetylcholine KW - N9YNS0M02X KW - Index Medicus KW - Animals KW - Memory -- drug effects KW - Dose-Response Relationship, Drug KW - Cholinergic Fibers -- physiology KW - Memory -- physiology KW - Disease Models, Animal KW - Thiadiazoles -- pharmacology KW - Antibodies, Monoclonal -- pharmacology KW - Rats KW - Cognition -- physiology KW - Acetylcholine -- metabolism KW - Rats, Sprague-Dawley KW - Cognition -- drug effects KW - Muscarinic Agonists -- pharmacology KW - Cholinergic Agents -- pharmacology KW - Cholinergic Fibers -- drug effects KW - Immunotoxins -- pharmacology KW - Pyridines -- pharmacology KW - Male KW - Behavior, Animal -- drug effects KW - Galanin -- pharmacology KW - Choice Behavior -- drug effects KW - Alzheimer Disease -- physiopathology KW - Peptide Fragments -- pharmacology KW - Receptors, Muscarinic -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79953989?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Coadministration+of+galanin+antagonist+M40+with+a+muscarinic+M1+agonist+improves+delayed+nonmatching+to+position+choice+accuracy+in+rats+with+cholinergic+lesions.&rft.au=McDonald%2C+M+P%3BWillard%2C+L+B%3BWenk%2C+G+L%3BCrawley%2C+J+N&rft.aulast=McDonald&rft.aufirst=M&rft.date=1998-07-01&rft.volume=18&rft.issue=13&rft.spage=5078&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 - 1998-07-02 N1 - Date created - 1998-07-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characterization of structural p53 mutants which show selective defects in apoptosis but not cell cycle arrest. AN - 79952028; 9632751 AB - Suppression of tumor cell growth by p53 results from the activation of both apoptosis and cell cycle arrest, functions which have been shown to be separable activities of p53. We have characterized a series of p53 mutants with amino acid substitutions at residue 175 and show that these mutants fall into one of three classes: class I, which is essentially wild type for apoptotic and cell cycle arrest functions; class II, which retains cell cycle arrest activity but is impaired in the induction of apoptosis; and class III, which is defective in both activities. Several residue 175 mutants which retain cell cycle arrest function have been detected in cancers, and we show that these have lost apoptotic function. Furthermore, several class II mutants have been found to be temperature sensitive for apoptotic activity while showing constitutive cell cycle arrest function. Taken together, these mutants comprise an excellent system with which to investigate the biochemical nature of p53-mediated apoptosis, the function of principal importance in tumor suppression. All of the mutants that showed loss of apoptotic function also showed defects in the activation of promoters from the potential apoptotic targets Bax and the insulin-like growth factor-binding protein 3 gene (IGF-BP3), and a correlation between full apoptotic activity and activation of both of these promoters was also seen with the temperature-sensitive mutants. However, a role for additional apoptotic activities of p53 was suggested by the observation that some mutants retained significant apoptotic function despite being impaired in the activation of Bax- and IGF-BP3-derived promoters. In contrast to the case of transcriptional activation, a perfect correlation between transcriptional repression of the c-fos promoter and the ability to induce apoptosis was seen, although the observation that Bax expression induced a similar repression of transcription from this promoter suggests that this may be a consequence, rather than a cause, of apoptotic death. JF - Molecular and cellular biology AU - Ryan, K M AU - Vousden, K H AD - ABL Basic Research Program, NCI-FCRDC, Frederick, Maryland 21702, USA. Y1 - 1998/07// PY - 1998 DA - July 1998 SP - 3692 EP - 3698 VL - 18 IS - 7 SN - 0270-7306, 0270-7306 KW - BAX protein, human KW - 0 KW - CDKN1A protein, human KW - Cyclin-Dependent Kinase Inhibitor p21 KW - Cyclins KW - Insulin-Like Growth Factor Binding Protein 3 KW - Proto-Oncogene Proteins KW - Proto-Oncogene Proteins c-bcl-2 KW - Proto-Oncogene Proteins c-fos KW - Tumor Suppressor Protein p53 KW - bcl-2-Associated X Protein KW - Index Medicus KW - Insulin-Like Growth Factor Binding Protein 3 -- genetics KW - Tumor Cells, Cultured KW - Proto-Oncogene Proteins c-fos -- genetics KW - Humans KW - Temperature KW - Proto-Oncogene Proteins c-bcl-2 -- genetics KW - Proto-Oncogene Proteins -- genetics KW - Transcriptional Activation KW - Cyclins -- genetics KW - Mutagenesis, Site-Directed KW - Tumor Suppressor Protein p53 -- physiology KW - Apoptosis KW - Tumor Suppressor Protein p53 -- genetics KW - Cell Cycle UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79952028?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+and+cellular+biology&rft.atitle=Characterization+of+structural+p53+mutants+which+show+selective+defects+in+apoptosis+but+not+cell+cycle+arrest.&rft.au=Ryan%2C+K+M%3BVousden%2C+K+H&rft.aulast=Ryan&rft.aufirst=K&rft.date=1998-07-01&rft.volume=18&rft.issue=7&rft.spage=3692&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 - 1998-07-16 N1 - Date created - 1998-07-16 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: EMBO J. 1994 Aug 1;13(15):3496-504 [8062826] Nature. 1994 Jul 21;370(6486):220-3 [8028670] Proc Natl Acad Sci U S A. 1994 Sep 13;91(19):8940-4 [8090749] Nucleic Acids Res. 1994 Sep;22(17):3551-5 [7937055] Genes Dev. 1994 Nov 1;8(21):2540-51 [7958916] Genes Dev. 1994 Dec 1;8(23):2817-30 [7995520] Cell. 1994 Dec 2;79(5):817-27 [8001119] Mol Cell Biol. 1995 Feb;15(2):1060-70 [7823921] Cell. 1995 Jan 27;80(2):293-9 [7834749] Genes Dev. 1995 Sep 1;9(17):2170-83 [7657168] Cell. 1995 Aug 25;82(4):675-84 [7664346] Science. 1995 Oct 6;270(5233):96-9 [7569956] Nature. 1995 Oct 12;377(6549):552-7 [7566157] Nature. 1995 Oct 19;377(6550):646-9 [7566179] Cancer Res. 1995 Nov 15;55(22):5187-90 [7585571] EMBO J. 1996 Feb 15;15(4):827-38 [8631304] Genes Dev. 1996 May 1;10(9):1054-72 [8654922] Genes Dev. 1996 Aug 1;10(15):1945-52 [8756351] Mol Cell Biol. 1996 Sep;16(9):4952-60 [8756654] Mol Cell Biol. 1996 Sep;16(9):4961-71 [8756655] Curr Opin Genet Dev. 1996 Feb;6(1):12-8 [8791489] Genes Dev. 1996 Oct 1;10(19):2438-51 [8843196] Genes Dev. 1996 Dec 1;10(23):2971-80 [8956998] Nature. 1997 Feb 13;385(6617):637-40 [9024662] Cell. 1997 Feb 7;88(3):323-31 [9039259] Proc Natl Acad Sci U S A. 1997 Mar 18;94(6):2345-9 [9122197] Nature. 1997 May 15;387(6630):296-9 [9153395] Nature. 1997 May 15;387(6630):299-303 [9153396] Oncogene. 1997 May 8;14(18):2137-47 [9174049] Science. 1997 Jul 18;277(5324):370-2 [9219694] Oncogene. 1997 Aug 14;15(7):857-69 [9266973] Cell. 1986 Aug 15;46(4):567-74 [3524858] Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):9979-83 [1946467] Nature. 1992 Jul 2;358(6381):15-6 [1614522] Cell. 1992 Jun 26;69(7):1237-45 [1535557] J Virol. 1992 Aug;66(8):4757-62 [1352831] Nature. 1993 May 20;363(6426):281-3 [8387645] EMBO J. 1993 Jul;12(7):2705-13 [8334989] Cell. 1993 Sep 24;74(6):957-67 [8402885] Oncogene. 1994 Apr;9(4):1225-30 [8134125] Proc Natl Acad Sci U S A. 1994 Mar 15;91(6):1998-2002 [8134338] Science. 1994 Jul 15;265(5170):346-55 [8023157] Cell. 1994 Aug 26;78(4):703-11 [8069917] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A novel assay of 8-oxo-2'-deoxyguanosine 5'-triphosphate pyrophosphohydrolase (8-oxo-dGTPase) activity in cultured cells and its use for evaluation of cadmium(II) inhibition of this activity. AN - 79945687; 9628918 AB - 8-Oxo-2'-deoxyguanosine 5'-triphosphate (8-oxo-dGTP) is a product of oxidative modification of dGTP, thatcan be misincorporated into DNA, causing AT-->CG mutations. Cells are protected against 8-oxo-dGTP by 8-oxo-dGTP 5'-pyrophosphohydrolases (8-oxo-dGTP-ases) that convert it to 8-oxo-dGMP. Thus, inhibition of 8-oxo-dGTPases may lead to cancer. To elucidate the involvement of 8-oxo-dGTPases in carcinogenesis, an assay of the 8-oxo-dGTPase activity is required. This paper presents such an assay developed for Chinese hamster ovary (CHO) cells that can be applied to any biological material. It includes: (i) a convenient method for preparing 8-oxo-2'-deoxyguanosine 5'-phosphates; (ii) an HPLC/UV quantification of 8-oxo-dGTP hydrolysis products and (iii) separation of 8-oxo-dGTPase activity from interfering 8-oxo-dGTP phosphatase(s). The 8-oxo-dGTPase activity of CHO cells depends on magnesium, has a pH optimum of 8.5, Km for 8-oxo-dGTP of 9.3 microM, and is inhibited by 8-oxo-dGDP, the product of interfering 8-oxo-dGTP phosphatases. The latter must be removed from the assayed samples by ultrafiltration through 30 kDa cut-off membranes. The method was used to test the inhibition by cadmium ions of the activity of 8-oxo-dGTPase in CHO cells. The cells cultured with 0.3-3 microM cadmium(II) acetate for up to 24 h had their 8-oxo-dGTPase activity suppressed in a Cd(II) concentration-dependent manner, down to 70% of the control value. JF - Nucleic acids research AU - Bialkowski, K AU - Kasprzak, K S AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute-FCRDC, Building 538, Room 205E, Frederick, MD 21702, USA. karolb@mail.ncifcrf.gov Y1 - 1998/07/01/ PY - 1998 DA - 1998 Jul 01 SP - 3194 EP - 3201 VL - 26 IS - 13 SN - 0305-1048, 0305-1048 KW - Deoxyguanine Nucleotides KW - 0 KW - Enzyme Inhibitors KW - Cadmium KW - 00BH33GNGH KW - Phosphoric Monoester Hydrolases KW - EC 3.1.3.2 KW - 8-oxodGTPase KW - EC 3.6.1.55 KW - DNA Repair Enzymes KW - EC 6.5.1.- KW - Index Medicus KW - Evaluation Studies as Topic KW - Deoxyguanine Nucleotides -- biosynthesis KW - Animals KW - Reproducibility of Results KW - Chromatography, DEAE-Cellulose KW - Kinetics KW - CHO Cells KW - Hydrolysis KW - Cricetinae KW - Cadmium -- pharmacology KW - Enzyme Inhibitors -- pharmacology KW - Phosphoric Monoester Hydrolases -- metabolism KW - Phosphoric Monoester Hydrolases -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79945687?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Bailliere%27s+clinical+rheumatology&rft.atitle=Indications+for%2C+and+use+of%2C+cytotoxic+agents+in+SLE.&rft.au=Klippel%2C+J+H&rft.aulast=Klippel&rft.aufirst=J&rft.date=1998-08-01&rft.volume=12&rft.issue=3&rft.spage=511&rft.isbn=&rft.btitle=&rft.title=Bailliere%27s+clinical+rheumatology&rft.issn=09503579&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-08-05 N1 - Date created - 1998-08-05 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nucleic Acids Res. 1994 Sep 25;22(19):3930-5 [7937115] Biochemistry. 1994 Apr 19;33(15):4695-701 [8161527] Mutat Res. 1995 May;336(3):257-67 [7739614] J Biol Chem. 1995 Jun 16;270(24):14659-65 [7782328] J Biol Chem. 1995 Oct 27;270(43):25942-8 [7592783] Carcinogenesis. 1995 Oct;16(10):2343-50 [7586133] J Biol Chem. 1996 Oct 11;271(41):25059-62 [8810257] Chem Res Toxicol. 1996 Dec;9(8):1360-7 [8951241] Chem Res Toxicol. 1996 Dec;9(8):1375-81 [8951243] J Biol Chem. 1997 Feb 28;272(9):5892-8 [9038207] Genes Cells. 1996 Feb;1(2):139-45 [9140059] Cancer Lett. 1997 May 19;115(2):141-8 [9149117] Science. 1997 Oct 3;278(5335):128-30 [9311918] Carcinogenesis. 1997 Sep;18(9):1785-91 [9328176] Proc Natl Acad Sci U S A. 1966 Feb;55(2):274-81 [5328724] Nucleic Acids Res. 1984 Feb 24;12(4):2137-45 [6701097] Anal Biochem. 1985 Oct;150(1):76-85 [3843705] J Biol Chem. 1988 Jun 25;263(18):8953-7 [3288626] Proc Natl Acad Sci U S A. 1989 Jun;86(11):3949-52 [2657730] J Biol Chem. 1992 Jan 5;267(1):166-72 [1730583] Nature. 1992 Jan 16;355(6357):273-5 [1309939] Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):11021-5 [1332067] Nucleic Acids Res. 1993 Apr 11;21(7):1563-8 [8479906] Trends Genet. 1993 Jul;9(7):246-9 [8379000] J Biol Chem. 1993 Nov 5;268(31):23524-30 [8226881] Biochemistry. 1995 Jan 10;34(1):89-95 [7819228] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A phase II study of bromocriptine in patients with androgen-independent prostate cancer. AN - 79938585; 9625840 AB - Prolactin is an important physiological regulator of prostate development and growth in preclinical models. In prostate cancer there is strong evidence that prolactin exerts a trophic effect independent of testosterone. In addition, patients with prostate cancer that have an elevated prolactin level correlated with a poorer prognosis. Based on these data, we evaluated the clinical effect of prolactin suppression using bromocriptine in patients with androgen-independent prostate cancer. We conducted an open-label phase II trial of bromocriptine in patients with progressive metastatic prostate cancer. Basal and thyrotropin releasing hormone (TRH)-stimulated prolactin levels were utilized as biological endpoints for determining the dose of bromocriptine. All patients continued to receive complete androgen blockade. Thirteen patients were enrolled (median age 69.5 years). There were no complete or partial responses associated with bromocriptine in 11 of the evaluable patients. The mean duration of bromocriptine treatment was 8.2 weeks (2-14 weeks). One patient had a clinically insignificant decrease in prostate-specific antigen (PSA) and another patient had a 19.9% decrease in PSA with progression of a soft tissue mass. The vast majority of patients (10 of 11) had suppression of prolactin with a bromocriptine dose of 2.5 mg three times a day. One patient required a dose adjustment due to inadequate suppression, with a final maintenance dose of bromocriptine 12.5 mg per day resulting in complete suppression. No serious treatment-related toxicities were observed. The most common complications noted were nausea, headaches, dizziness, and fatigue. Our data showed that 2.5 mg three times per day of bromocriptine suppressed prolactin in 90% of the patients. Furthermore, this dose appears to be well tolerated. JF - Oncology reports AU - Horti, J AU - Figg, W D AU - Weinberger, B AU - Kohler, D AU - Sartor, O AD - Medicine Branch, Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. PY - 1998 SP - 893 EP - 896 VL - 5 IS - 4 SN - 1021-335X, 1021-335X KW - Androgens KW - 0 KW - Antineoplastic Agents KW - Bromocriptine KW - 3A64E3G5ZO KW - Index Medicus KW - Humans KW - Adult KW - Treatment Outcome KW - Aged KW - Follow-Up Studies KW - Male KW - Bromocriptine -- adverse effects KW - Bromocriptine -- therapeutic use KW - Androgens -- physiology KW - Adenocarcinoma -- secondary KW - Prostatic Neoplasms -- physiopathology KW - Prostatic Neoplasms -- drug therapy KW - Antineoplastic Agents -- therapeutic use KW - Adenocarcinoma -- drug therapy KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79938585?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+reports&rft.atitle=A+phase+II+study+of+bromocriptine+in+patients+with+androgen-independent+prostate+cancer.&rft.au=Horti%2C+J%3BFigg%2C+W+D%3BWeinberger%2C+B%3BKohler%2C+D%3BSartor%2C+O&rft.aulast=Horti&rft.aufirst=J&rft.date=1998-07-01&rft.volume=5&rft.issue=4&rft.spage=893&rft.isbn=&rft.btitle=&rft.title=Oncology+reports&rft.issn=1021335X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-07-29 N1 - Date created - 1998-07-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Differential expression and activity of phosphatases and protein kinases in adriamycin sensitive and resistant human breast cancer MCF-7 cells. AN - 79936937; 9625806 AB - Multidrug resistance is one of the major obstacles in cancer chemotherapy. In tumor cells, overexpression of the transmembrane P-glycoprotein 170 (P-gp) is associated with the multidrug resistance phenotype and serves as a drug efflux pump. The activation of P-gp has been suggested to occur at the post-translational level. Protein kinase C mediated phosphorylation may be associated with the drug effux mechanism but the overall phosphorylation pathway has not been completely defined. we report the novel finding of an increase in phosphatase 1B (a tyrosine phosphatase) and a decrease in PP1 and PP2A (serine/threonine phosphatases) expression and activity in our series of early (R65) and late (R500) stage adriamycin resistant MCF-7 cells. In addition, we show a decrease in protein kinase A (PKA) activity and an increase in protein kinase C (PKC) in our drug resistant cells. Analyses of PKC isoforms alpha through epsilon revealed that PKCbeta was not expressed and that all other isoforms increased with increasing resistance, except PKCgamma which was detected only in R65 cells. Our findings suggest that in drug resistant cells, there is a pattern consistant with the maintenance of serine and threonine residues in a phosphorylated state. JF - International journal of oncology AU - Ratnasinghe, D AU - Phang, J M AU - Yeh, G C AD - Cellular Defense and Carcinogenesis Section, Laboratory of Nutritional and Molecular Regulation, National Cancer Institute, Frederick, MD 21702, USA. Y1 - 1998/07// PY - 1998 DA - July 1998 SP - 79 EP - 84 VL - 13 IS - 1 SN - 1019-6439, 1019-6439 KW - Antibiotics, Antineoplastic KW - 0 KW - Isoenzymes KW - P-Glycoprotein KW - Doxorubicin KW - 80168379AG KW - Protein Kinases KW - EC 2.7.- KW - Cyclic AMP-Dependent Protein Kinases KW - EC 2.7.11.11 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Phosphoric Monoester Hydrolases KW - EC 3.1.3.2 KW - Index Medicus KW - Protein Kinase C -- metabolism KW - Cyclic AMP-Dependent Protein Kinases -- metabolism KW - Tumor Cells, Cultured KW - Phosphorylation KW - P-Glycoprotein -- metabolism KW - Humans KW - Drug Resistance, Neoplasm KW - Isoenzymes -- metabolism KW - Female KW - Drug Resistance, Multiple KW - Protein Kinases -- metabolism KW - Doxorubicin -- pharmacology KW - Antibiotics, Antineoplastic -- pharmacology KW - Breast Neoplasms -- enzymology KW - Phosphoric Monoester Hydrolases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79936937?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+journal+of+oncology&rft.atitle=Differential+expression+and+activity+of+phosphatases+and+protein+kinases+in+adriamycin+sensitive+and+resistant+human+breast+cancer+MCF-7+cells.&rft.au=Ratnasinghe%2C+D%3BPhang%2C+J+M%3BYeh%2C+G+C&rft.aulast=Ratnasinghe&rft.aufirst=D&rft.date=1998-07-01&rft.volume=13&rft.issue=1&rft.spage=79&rft.isbn=&rft.btitle=&rft.title=International+journal+of+oncology&rft.issn=10196439&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-08-20 N1 - Date created - 1998-08-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inhibition of the cytotoxicity of protein toxins by a novel plant metabolite, mansonone-D. AN - 79917980; 9618143 AB - We have studied the effect of several structurally related mansonones on the cytotoxicity of plant and bacterial toxins in Vero and BER-40, a brefeldin A-resistant mutant of Vero cells. Mansonone-D (MD), a sesquiterpenoid ortho-naphthoquinone, inhibited the cytotoxicity of ricin, modeccin, Pseudomonas toxin, and diphtheria toxin in Vero cells to different extents. The inhibition of ricin cytotoxicity was dose dependent and reversed upon removal of the drug. Protection of ricin cytotoxicity was also observed in the presence of cycloheximide, indicating that de novo protein synthesis is not required for the protective effect. Although MD inhibited the degradation and excretion of ricin, the binding and internalization of ricin was not affected. In contrast, MD strongly reduced the specific binding of diphtheria toxin in Vero cells. Fluorescence microscopic studies show that MD treatment dramatically alters the morphology of the Golgi apparatus in Vero cells. The kinetic studies reveal that the protection of ricin cytotoxicity is the consequence of decreased toxin translocation to the cytosol in MD-treated cells. The reactive ortho-quinone moiety of MD is important for the protective effect as thespesone, a para-naphthoquinone with a heterocyclic ring structure identical to that of MD, did not inhibit the cytotoxicity of toxins. Thespone, a dehydromansonone-D, lacking two hydrogens from the heterocyclic dihydrofuran ring of MD, inhibited the cytotoxicity of ricin, but was albeit less potent than MD. Neither mansonone-E nor mansonone-H with reactive ortho-quinone moiety, but with a different heterocyclic structure, had any effect on the cytotoxicity of ricin indicating that the protective effect of MD is specifically related to the overall structure of the metabolite. JF - Journal of cellular physiology AU - Nambiar, M P AU - Murugesan, R AU - Wu, H C AD - Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA. gopi@helix.nih.gov Y1 - 1998/07// PY - 1998 DA - July 1998 SP - 40 EP - 49 VL - 176 IS - 1 SN - 0021-9541, 0021-9541 KW - Antitoxins KW - 0 KW - Diphtheria Toxin KW - Naphthoquinones KW - Plant Extracts KW - Plant Lectins KW - Sesquiterpenes KW - Toxins, Biological KW - mansonone D KW - Ricin KW - 9009-86-3 KW - Cycloheximide KW - 98600C0908 KW - Index Medicus KW - Molecular Structure KW - Animals KW - Golgi Apparatus -- drug effects KW - Diphtheria Toxin -- metabolism KW - Diphtheria Toxin -- antagonists & inhibitors KW - Microscopy, Fluorescence KW - Plants -- chemistry KW - Ricin -- antagonists & inhibitors KW - Ricin -- metabolism KW - Protein Binding -- drug effects KW - Cycloheximide -- pharmacology KW - Kinetics KW - Cercopithecus aethiops KW - Endocytosis -- drug effects KW - Vero Cells KW - Immunohistochemistry KW - Antitoxins -- pharmacology KW - Plant Extracts -- pharmacology KW - Toxins, Biological -- toxicity KW - Naphthoquinones -- pharmacology KW - Sesquiterpenes -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79917980?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Inhibition+of+the+cytotoxicity+of+protein+toxins+by+a+novel+plant+metabolite%2C+mansonone-D.&rft.au=Nambiar%2C+M+P%3BMurugesan%2C+R%3BWu%2C+H+C&rft.aulast=Nambiar&rft.aufirst=M&rft.date=1998-07-01&rft.volume=176&rft.issue=1&rft.spage=40&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 - 1998-07-01 N1 - Date created - 1998-07-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Combined nicotinic and muscarinic blockade in elderly normal volunteers: cognitive, behavioral, and physiologic responses. AN - 79911311; 9608577 AB - Establishing a pharmacologic model of the memory deficits of Alzheimer's disease could be an important tool in understanding how memory fails. We examined the combined effects of the muscarinic antagonist scopolamine and the nicotinic antagonist mecamylamine in eight normal elderly volunteers (age 61.9 +/- 8.3 yrs, SD). Each received four separate drug challenges (scopolamine (0.4 mg i.v.), mecamylamine (0.2 mg/kg up to 15 mg PO), mecamylamine + scopolamine, and placebo). There was a trend toward increased impairment in explicit memory for the mecamylamine + scopolamine condition as compared to scopolamine alone. Increased impairment was also seen for the mecamylamine + scopolamine condition as compared to scopolamine alone in selected behavioral ratings. Pupil size increased when mecamylamine was added to scopolamine, while systolic blood pressure and pulse changed in concordance with ganglionic blockade. These data together with previous brain-imaging results suggest that this muscarinic-nicotinic drug combination may better model Alzheimer's disease than either drug alone. JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology AU - Little, J T AU - Johnson, D N AU - Minichiello, M AU - Weingartner, H AU - Sunderland, T AD - Geriatric Psychiatry Branch, National Institute of Mental Health, Bethesda, Maryland 20892, USA. Y1 - 1998/07// PY - 1998 DA - July 1998 SP - 60 EP - 69 VL - 19 IS - 1 SN - 0893-133X, 0893-133X KW - Muscarinic Antagonists KW - 0 KW - Nicotinic Antagonists KW - Scopolamine Hydrobromide KW - 451IFR0GXB KW - Mecamylamine KW - 6EE945D3OK KW - Index Medicus KW - Reaction Time -- drug effects KW - Memory -- drug effects KW - Alzheimer Disease -- physiopathology KW - Humans KW - Aged KW - Learning -- drug effects KW - Brief Psychiatric Rating Scale KW - Heart Rate -- drug effects KW - Pupil -- drug effects KW - Middle Aged KW - Blood Pressure -- drug effects KW - Drug Synergism KW - Female KW - Male KW - Behavior -- drug effects KW - Scopolamine Hydrobromide -- pharmacology KW - Cognition -- drug effects KW - Muscarinic Antagonists -- pharmacology KW - Nicotinic Antagonists -- pharmacology KW - Mecamylamine -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79911311?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Combined+nicotinic+and+muscarinic+blockade+in+elderly+normal+volunteers%3A+cognitive%2C+behavioral%2C+and+physiologic+responses.&rft.au=Little%2C+J+T%3BJohnson%2C+D+N%3BMinichiello%2C+M%3BWeingartner%2C+H%3BSunderland%2C+T&rft.aulast=Little&rft.aufirst=J&rft.date=1998-07-01&rft.volume=19&rft.issue=1&rft.spage=60&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 - 1998-07-20 N1 - Date created - 1998-07-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of cocaine-related environmental stimuli on the spontaneous electroencephalogram in polydrug abusers. AN - 79910064; 9608572 AB - Relationships between the spontaneous electroencephalogram (EEG), self-reports of cocaine craving, and cerebral glucose metabolism, determined using 2-[18F]fluoro-2-deoxy-D-glucose and positron emission tomography, were assessed during the presentation of either neutral or cocaine-related environmental stimuli. In cocaine users but not non-drug-abusing controls, EEG power in the alpha1 and alpha2 frequency bands was significantly lowered during presentation of the drug-related stimuli when compared with the neutral test session. Decreases in alpha1 power were negatively correlated with increases in global glucose metabolism but were not correlated with either the time course or the magnitude of craving throughout the 30-min test session. Although EEG desynchronization is related to global brain metabolism, the difference in the time courses between EEG power and craving suggests that self-reports of cue-elicited cocaine craving do not simply reflect increases in the state of cortical arousal. JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology AU - Liu, X AU - Vaupel, D B AU - Grant, S AU - London, E D AD - Brain Imaging Center, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 21224, USA. Y1 - 1998/07// PY - 1998 DA - July 1998 SP - 10 EP - 17 VL - 19 IS - 1 SN - 0893-133X, 0893-133X KW - Blood Glucose KW - 0 KW - Radiopharmaceuticals KW - Fluorodeoxyglucose F18 KW - 0Z5B2CJX4D KW - Glucose KW - IY9XDZ35W2 KW - Index Medicus KW - Blood Glucose -- metabolism KW - Arousal KW - Humans KW - Glucose -- metabolism KW - Adult KW - Tomography, Emission-Computed KW - Brain -- metabolism KW - Time Factors KW - Male KW - Female KW - Electroencephalography KW - Cocaine-Related Disorders -- psychology KW - Cues KW - Cocaine-Related Disorders -- physiopathology KW - Cocaine-Related Disorders -- metabolism KW - Cocaine-Related Disorders -- diagnostic imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79910064?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Effect+of+cocaine-related+environmental+stimuli+on+the+spontaneous+electroencephalogram+in+polydrug+abusers.&rft.au=Liu%2C+X%3BVaupel%2C+D+B%3BGrant%2C+S%3BLondon%2C+E+D&rft.aulast=Liu&rft.aufirst=X&rft.date=1998-07-01&rft.volume=19&rft.issue=1&rft.spage=10&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 - 1998-07-20 N1 - Date created - 1998-07-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Metabolic conversion of 1,1-dichloro-2,2-bis(p-chlorophenyl)ethane (DDD) to 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE) in the male F344/NCr Rat. AN - 79900162; 9601927 AB - 1,1-Dichloro-2,2-bis(p-chlorophenyl)ethane (DDD) and 1,1-dichloro-2, 2-bis(p-chlorophenyl)ethylene (DDE) levels were measured by capillary gas chromatography with electron capture detection in liver and blood serum of male F344/NCr rats exposed for 2 weeks to DDD at dietary concentrations ranging from 8.51 ppm to 2,000 ppm. DDD burdens in serum ranged from <0.006 microM (limit of detection) in control rats to 1.1 microM in the rats fed DDD at 2,000 ppm. The corresponding liver burdens in these animals ranged from <0.006 micromol/kg liver (controls) to 11 micromol/kg liver in rats fed DDD at 2,000 ppm. Levels of DDE in serum or liver were undetectable (<0. 006 microM in serum; <0.006 micromol/kg liver) in rats fed control diet or diet containing 8.51 or 25.5 ppm DDD. The liver and serum burdens of DDE increased with dietary DDD concentration, reaching a maximum of 0.53 microM in serum and 4.7 micromol/kg liver in rats fed 2,000 ppm DDD. As a percentage of total DDD equivalents detected in liver or serum, the DDE burdens increased to a maximum of 36% and 31% in the serum and liver, respectively, of rats fed 689 ppm DDD. The possibility that the DDE might have been generated artifactually in the diet prior to administration to the rats was ruled out by analysis with capillary gas chromatography of the diet containing 2, 000 ppm DDD. The identification of DDE as a metabolite in liver extracts of rats fed 2,000 ppm DDD was confirmed with GC-MS. The results confirmed the presence of DDE as a metabolite of DDD. JF - Archives of environmental contamination and toxicology AU - Fox, S D AU - Roman, J M AU - Issaq, H J AU - Nims, R W AD - Chemical Synthesis and Analysis Laboratory, SAIC Frederick, NCI-Frederick Cancer Research and Development Center, Frederick, Maryland 21702-1201, USA. Y1 - 1998/07// PY - 1998 DA - July 1998 SP - 104 EP - 108 VL - 35 IS - 1 SN - 0090-4341, 0090-4341 KW - Insecticides KW - 0 KW - Dichlorodiphenyl Dichloroethylene KW - 4M7FS82U08 KW - Dichlorodiphenyldichloroethane KW - V14159DF29 KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Drug Administration Schedule KW - Biotransformation KW - Gas Chromatography-Mass Spectrometry KW - Animal Feed -- analysis KW - Liver -- metabolism KW - Male KW - Dichlorodiphenyldichloroethane -- blood KW - Dichlorodiphenyl Dichloroethylene -- metabolism KW - Dichlorodiphenyl Dichloroethylene -- blood KW - Dichlorodiphenyldichloroethane -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79900162?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+contamination+and+toxicology&rft.atitle=Metabolic+conversion+of+1%2C1-dichloro-2%2C2-bis%28p-chlorophenyl%29ethane+%28DDD%29+to+1%2C1-dichloro-2%2C2-bis%28p-chlorophenyl%29ethylene+%28DDE%29+in+the+male+F344%2FNCr+Rat.&rft.au=Fox%2C+S+D%3BRoman%2C+J+M%3BIssaq%2C+H+J%3BNims%2C+R+W&rft.aulast=Fox&rft.aufirst=S&rft.date=1998-07-01&rft.volume=35&rft.issue=1&rft.spage=104&rft.isbn=&rft.btitle=&rft.title=Archives+of+environmental+contamination+and+toxicology&rft.issn=00904341&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-09-15 N1 - Date created - 1998-09-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chlorambucil-induced pulmonary disease: a case report and review of the literature. AN - 73961382; 9760160 AB - A 77-year-old man developed pneumonitis while on chlorambucil therapy for chronic lymphocytic leukemia, with a cumulative dose of 2700 mg. The condition improved promptly with the discontinuation of the drug and initiation of steroids. A case report and review of the literature are presented in this paper. JF - Annals of hematology AU - Khong, H T AU - McCarthy, J AD - Medicine Branch, National Cancer Institute, Bethesda, MD 20892, USA. PY - 1998 SP - 85 EP - 87 VL - 77 IS - 1-2 SN - 0939-5555, 0939-5555 KW - Antineoplastic Agents, Alkylating KW - 0 KW - Chlorambucil KW - 18D0SL7309 KW - Index Medicus KW - Leukemia, Lymphocytic, Chronic, B-Cell -- drug therapy KW - Humans KW - Aged KW - Male KW - Antineoplastic Agents, Alkylating -- therapeutic use KW - Lung Diseases -- chemically induced KW - Chlorambucil -- adverse effects KW - Antineoplastic Agents, Alkylating -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73961382?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+hematology&rft.atitle=Chlorambucil-induced+pulmonary+disease%3A+a+case+report+and+review+of+the+literature.&rft.au=Khong%2C+H+T%3BMcCarthy%2C+J&rft.aulast=Khong&rft.aufirst=H&rft.date=1998-07-01&rft.volume=77&rft.issue=1-2&rft.spage=85&rft.isbn=&rft.btitle=&rft.title=Annals+of+hematology&rft.issn=09395555&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-10-16 N1 - Date created - 1998-10-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Lipid formulations of amphotericin B: clinical perspectives for the management of invasive fungal infections in children with cancer. AN - 73915317; 9743964 AB - During the past four decades, amphotericin B deoxycholate has been the cornerstone of systemic chemotherapy for life-threatening fungal infections. Despite a broad spectrum of antifungal activity, its utility is greatly hampered by renal toxicity and limited clinical efficacy, in particular in patients with profound and persistent neutropenia. The novel lipid formulations of amphotericin B have distinct physicochemical properties resulting in different distribution patterns. Nevertheless, they all share a considerable reduction of nephrotoxicity, which allows for the delivery of higher daily dosages of amphotericin B. Preliminary efficacy data indicate that these compounds are overall at least as effective as amphotericin B deoxycholate. However, information for children is limited, and comparative studies for their use as first line agents are only in their beginnings. In this article, we review the clinical pharmacokinetics, safety, and efficacy of the lipid formulations of amphotericin B with special emphasis on pediatric data, and we seek to provide a rational framework for the determination of their current role in patients with cancer and proven or suspected invasive fungal infections. JF - Klinische Padiatrie AU - Groll, A H AU - Müller, F M AU - Piscitelli, S C AU - Walsh, T J AD - Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. PY - 1998 SP - 264 EP - 273 VL - 210 IS - 4 SN - 0300-8630, 0300-8630 KW - Antifungal Agents KW - 0 KW - Drug Carriers KW - Liposomes KW - Amphotericin B KW - 7XU7A7DROE KW - Index Medicus KW - Drug Administration Schedule KW - Dose-Response Relationship, Drug KW - Humans KW - Treatment Outcome KW - Child KW - Antifungal Agents -- pharmacokinetics KW - Antifungal Agents -- adverse effects KW - Amphotericin B -- pharmacokinetics KW - Opportunistic Infections -- microbiology KW - Amphotericin B -- adverse effects KW - Amphotericin B -- administration & dosage KW - Mycoses -- microbiology KW - Mycoses -- drug therapy KW - Antifungal Agents -- administration & dosage KW - Neoplasms -- microbiology KW - Opportunistic Infections -- drug therapy KW - Neutropenia -- microbiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73915317?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Klinische+Padiatrie&rft.atitle=Lipid+formulations+of+amphotericin+B%3A+clinical+perspectives+for+the+management+of+invasive+fungal+infections+in+children+with+cancer.&rft.au=Groll%2C+A+H%3BM%C3%BCller%2C+F+M%3BPiscitelli%2C+S+C%3BWalsh%2C+T+J&rft.aulast=Groll&rft.aufirst=A&rft.date=1998-07-01&rft.volume=210&rft.issue=4&rft.spage=264&rft.isbn=&rft.btitle=&rft.title=Klinische+Padiatrie&rft.issn=03008630&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-12-16 N1 - Date created - 1998-12-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The potential of genetically altered mice as animal models for carcinogen identification. AN - 73873031; 9715518 JF - Toxicologic pathology AU - Maronpot, R R AD - Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. PY - 1998 SP - 579 EP - 581 VL - 26 IS - 4 SN - 0192-6233, 0192-6233 KW - Carcinogens KW - 0 KW - Mutagens KW - Index Medicus KW - Animals KW - Mutagens -- toxicity KW - Disease Models, Animal KW - Mice KW - Carcinogenicity Tests -- trends KW - Carcinogens -- toxicity KW - Carcinogenicity Tests -- methods KW - Mice, Transgenic UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73873031?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicologic+pathology&rft.atitle=The+potential+of+genetically+altered+mice+as+animal+models+for+carcinogen+identification.&rft.au=Maronpot%2C+R+R&rft.aulast=Maronpot&rft.aufirst=R&rft.date=1998-07-01&rft.volume=26&rft.issue=4&rft.spage=579&rft.isbn=&rft.btitle=&rft.title=Toxicologic+pathology&rft.issn=01926233&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-11-16 N1 - Date created - 1998-11-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Morphological characterization of spindle cell tumors induced in transgenic Tg.AC mouse skin. AN - 73867162; 9715510 AB - Transgenic Tg.AC mice carry a v-Ha-ras coding region flanked by a zeta-globin promoter and an SV40 polyadenylation signal sequence. These mice respond to carcinogens by developing epidermal papillomas. In some cases, malignancies develop at the sites of these papillomas. Various patterns of squamous cell differentiation were observed in these malignancies. One malignancy that developed at the site of the papillomas was composed of bundles of spindle cells. This lesion is difficult to distinguish from fibrosarcomas by light microscopy. We characterized 16 of these malignancies (tentatively classified as spindle cell tumors) to determine if they were of epithelial or mesenchymal origin. Papillomas were induced in Tg.AC mice by full thickness wounding, 12-O-tetradecanoyl-13-phorbol acetate treatment, or ultraviolet radiation. With time, some papillomas became broad-based, downwardly invading lesions. These lesions were examined by light microscopy with immunohistochemical analysis for cytokeratins and by electron microscopy. Immunohistochemical examination with a polyclonal anti-cytokeratin antibody demonstrated various degrees of keratin staining in all tumors examined. Attenuated desmosomes were also observed in these lesions by electron microscopy. These results indicate an epithelial origin for these malignancies; therefore, they should be classified as spindle cell carcinomas. JF - Toxicologic pathology AU - Asano, S AU - Trempus, C S AU - Spalding, J W AU - Tennant, R W AU - Battalora, M S AD - Laboratory of Environmental Carcinogenesis and Mutagenesis, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. PY - 1998 SP - 512 EP - 519 VL - 26 IS - 4 SN - 0192-6233, 0192-6233 KW - Index Medicus KW - Animals KW - Microscopy, Electron KW - Mice KW - Histiocytoma, Benign Fibrous -- pathology KW - Reverse Transcriptase Polymerase Chain Reaction KW - Mice, Transgenic KW - Histiocytoma, Benign Fibrous -- chemically induced KW - Immunohistochemistry KW - Female KW - Carcinoma -- pathology KW - Skin Neoplasms -- chemically induced KW - Skin Neoplasms -- pathology KW - Carcinoma -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73867162?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicologic+pathology&rft.atitle=Morphological+characterization+of+spindle+cell+tumors+induced+in+transgenic+Tg.AC+mouse+skin.&rft.au=Asano%2C+S%3BTrempus%2C+C+S%3BSpalding%2C+J+W%3BTennant%2C+R+W%3BBattalora%2C+M+S&rft.aulast=Asano&rft.aufirst=S&rft.date=1998-07-01&rft.volume=26&rft.issue=4&rft.spage=512&rft.isbn=&rft.btitle=&rft.title=Toxicologic+pathology&rft.issn=01926233&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-11-16 N1 - Date created - 1998-11-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Familial Mediterranean fever at the millennium. Clinical spectrum, ancient mutations, and a survey of 100 American referrals to the National Institutes of Health. AN - 73862386; 9715731 AB - Regarded as the most common and best understood of the hereditary periodic fever syndromes, familial Mediterranean fever (FMF) is a recessively inherited disease of episodic fever with some combination of severe abdominal pain, pleurisy, arthritis, and a characteristic ankle rash. The flares typically last for up to 3 days at a time, and most patients are completely asymptomatic between attacks; if untreated with prophylactic colchicine, some patients later develop amyloidosis and renal failure. The recent cloning of the FMF gene on the short arm of chromosome 16p, and the subsequent finding that its tissue expression is limited to granulocytes, has helped to explain the dramatic accumulation of neutrophils at the symptomatic serosal sites; the wild-type gene likely acts as an upregulator of an anti-inflammatory molecule or as a downregulator of a pro-inflammatory molecule. For nearly half a century, FMF was thought to cluster primarily in non-Ashkenazi Jews, Arabs, Armenians, and Turks, although the screening of the 8 known mutations in an American cohort has identified substantial numbers of people from the Ashkenazi Jewish and Italian populations in the United States who also have this disease. Nevertheless, the symptoms often go unrecognized and patients remain undiagnosed for years, not receiving the highly efficacious colchicine therapy; their histories often include multiple laparotomies, laparoscopies, and psychiatric evaluations. The combinations of clinical manifestations among FMF patients are quite heterogeneous, but our American cohort did not establish any connections between individual mutations and specific clinical pictures--as is seen in other diseases like cystic fibrosis, in which distinct genotypes target certain organ systems. Specifically, the data from our American series are insufficient to evaluate the hypothesis that the M694V/M694V genotype confers a more severe phenotype, or increases the risk of amyloidosis; but both our data and the recent literature (160) indicate that amyloidosis can occur in FMF patients with only 1 copy, or no copies, of the M694V mutation. It appears that specific MEFV mutations are probably not the sole determinants of phenotype, and that unknown environmental factors or modifying genes act as accomplices in this disease. Although we hope the discovery of the FMF gene will allow the diagnosis of FMF to become genetically accurate, the reality is that both clinical and genetic tools must still be used together unless mutations are identified on both of a patient's chromosomes. Physicians should be careful not to rule out the diagnosis in patients of high-risk ethnic backgrounds just because of atypical clinical features, as our data indicate that MEFV mutations are sometimes demonstrable in such patients. At the same time, physicians cannot yet rely solely on a genetic diagnosis because we have not yet identified a sufficient spectrum of mutations, and it is not currently feasible to examine every patient's full DNA sequence for the entire gene; screening an ethnically consistent and clinically positive patient for the 8 known mutations frequently identifies a mutation on only 1 chromosome, and genetic analysis of other classic cases will often reveal none of the 8 mutations. Still, our data suggest that ethnic background is an important predictor of finding 1 of the presently known mutations, and the knowledge of ancestries atypical for FMF can suggest the diagnosis of other hereditary periodic fever syndromes. As the list of FMF-associated MEFV mutations is expanded, and/or new sequencing technologies permit more rapid screening, the value and interpretation of genetic testing for FMF will become more straightforward. Moreover, as the pathophysiology of this disorder becomes less of a hypothesis and more of an understood entity, it is likely that treatment options will broaden beyond the use of daily prophylactic colchicine. (ABSTRACT TRUNCATED) JF - Medicine AU - Samuels, J AU - Aksentijevich, I AU - Torosyan, Y AU - Centola, M AU - Deng, Z AU - Sood, R AU - Kastner, D L AD - Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892-1820, USA. Y1 - 1998/07// PY - 1998 DA - July 1998 SP - 268 EP - 297 VL - 77 IS - 4 SN - 0025-7974, 0025-7974 KW - Amino Acids KW - 0 KW - DNA, Complementary KW - Gout Suppressants KW - Colchicine KW - SML2Y3J35T KW - Abridged Index Medicus KW - Index Medicus KW - United States KW - Severity of Illness Index KW - Point Mutation -- genetics KW - Gout Suppressants -- adverse effects KW - Amyloidosis -- complications KW - Diagnosis, Differential KW - Humans KW - Amino Acids -- genetics KW - Referral and Consultation KW - Child, Preschool KW - Cloning, Molecular KW - Genotype KW - Haplotypes -- genetics KW - Kidney Diseases -- complications KW - National Institutes of Health (U.S.) KW - Health Surveys KW - Adult KW - Middle Aged KW - Colchicine -- adverse effects KW - Male KW - Female KW - Familial Mediterranean Fever -- drug therapy KW - Familial Mediterranean Fever -- epidemiology KW - Familial Mediterranean Fever -- genetics KW - Familial Mediterranean Fever -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73862386?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Medicine&rft.atitle=Familial+Mediterranean+fever+at+the+millennium.+Clinical+spectrum%2C+ancient+mutations%2C+and+a+survey+of+100+American+referrals+to+the+National+Institutes+of+Health.&rft.au=Samuels%2C+J%3BAksentijevich%2C+I%3BTorosyan%2C+Y%3BCentola%2C+M%3BDeng%2C+Z%3BSood%2C+R%3BKastner%2C+D+L&rft.aulast=Samuels&rft.aufirst=J&rft.date=1998-07-01&rft.volume=77&rft.issue=4&rft.spage=268&rft.isbn=&rft.btitle=&rft.title=Medicine&rft.issn=00257974&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-09-24 N1 - Date created - 1998-09-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The National Toxicology Program evaluation of genetically altered mice as predictive models for identifying carcinogens. AN - 73857119; 9715504 AB - National Institute of Environmental Health Sciences researchers are exploring the utility of genetically altered mice to study mechanisms of carcinogenesis. Two of these mouse models, the Tg.AC (carrier of an activated mouse H-ras oncogene) and the p53+/- (heterozygous for the wild-type tumor suppressor gene Trp53), have genetic alterations that appear to hasten their expression of chemically induced tumors. These 2 models have been proposed as a basis for new strategies for identifying chemical carcinogens and for assessing risk. The National Toxicology Program (NTP) is conducting a series of studies with these 2 genetically altered strains to further examine their strengths and weaknesses for identification of documented rodent and human carcinogens. In this first evaluation, candidates for study were drawn from the NTP historical database of 2-yr rodent carcinogenicity studies and the open literature (primarily for drugs). Results with this first set of 11 chemicals tested in genetically altered mice, compared with previous findings in the traditional 2-yr rodent assays and literature on human tumor findings, appear to support the premise advanced by Tennant et al that these models have the potential to serve as more rapid and less expensive test systems to identify carcinogens. JF - Toxicologic pathology AU - Eastin, W C AU - Haseman, J K AU - Mahler, J F AU - Bucher, J R AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709-2233, USA. Eastin@niehs.nih.gov PY - 1998 SP - 461 EP - 473 VL - 26 IS - 4 SN - 0192-6233, 0192-6233 KW - Carcinogens KW - 0 KW - Index Medicus KW - Animals KW - Neoplasms, Experimental -- genetics KW - Genes, p53 -- genetics KW - Disease Models, Animal KW - Predictive Value of Tests KW - Mice KW - Neoplasms, Experimental -- pathology KW - Male KW - Female KW - Survival Analysis KW - Carcinogens -- administration & dosage KW - Mice, Transgenic -- physiology KW - Carcinogens -- toxicity KW - Carcinogenicity Tests UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73857119?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicologic+pathology&rft.atitle=The+National+Toxicology+Program+evaluation+of+genetically+altered+mice+as+predictive+models+for+identifying+carcinogens.&rft.au=Eastin%2C+W+C%3BHaseman%2C+J+K%3BMahler%2C+J+F%3BBucher%2C+J+R&rft.aulast=Eastin&rft.aufirst=W&rft.date=1998-07-01&rft.volume=26&rft.issue=4&rft.spage=461&rft.isbn=&rft.btitle=&rft.title=Toxicologic+pathology&rft.issn=01926233&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-11-16 N1 - Date created - 1998-11-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Spontaneous and chemically induced proliferative lesions in Tg.AC transgenic and p53-heterozygous mice. AN - 73847883; 9715509 AB - Recently, the use of selected genetically altered mouse models in the detection of carcinogens after short-term chemical exposures has been evaluated. Studies of several chemicals conducted by the National Toxicology Program in Tg.AC transgenic and heterozygous p53-deficient mice have been completed recently and represent a major contribution to this effort, as well as the largest accumulation to date of toxicologic pathology data in these 2 lines of mice. The purpose of this report is to describe the proliferative target organ effects observed in this set of studies, as well as to present the tumor profile in the control groups of this data set. These findings provide a comprehensive toxicologic assessment of these 2 genetically altered mouse strains, which are of emerging importance in toxicologic pathology. JF - Toxicologic pathology AU - Mahler, J F AU - Flagler, N D AU - Malarkey, D E AU - Mann, P C AU - Haseman, J K AU - Eastin, W AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. PY - 1998 SP - 501 EP - 511 VL - 26 IS - 4 SN - 0192-6233, 0192-6233 KW - Carcinogens KW - 0 KW - Index Medicus KW - Animals KW - Neoplasms, Experimental -- chemically induced KW - Neoplasms, Experimental -- genetics KW - Heterozygote KW - Mice KW - Neoplasms, Experimental -- pathology KW - Mice, Transgenic -- physiology KW - Genes, p53 -- genetics KW - Carcinogens -- toxicity KW - Carcinogenicity Tests -- methods KW - Mice, Transgenic -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73847883?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicologic+pathology&rft.atitle=Spontaneous+and+chemically+induced+proliferative+lesions+in+Tg.AC+transgenic+and+p53-heterozygous+mice.&rft.au=Mahler%2C+J+F%3BFlagler%2C+N+D%3BMalarkey%2C+D+E%3BMann%2C+P+C%3BHaseman%2C+J+K%3BEastin%2C+W&rft.aulast=Mahler&rft.aufirst=J&rft.date=1998-07-01&rft.volume=26&rft.issue=4&rft.spage=501&rft.isbn=&rft.btitle=&rft.title=Toxicologic+pathology&rft.issn=01926233&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-11-16 N1 - Date created - 1998-11-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The human capsaicin model of allodynia and hyperalgesia: sources of variability and methods for reduction. AN - 73847515; 9707653 AB - Intradermal and topical application of capsaicin have been used to study mechanisms of mechanical allodynia (MA) and pinprick hyperalgesia (PPH) and the efficacy of drugs in relieving these symptoms. However, it is associated with significant inter- and intra-subject variability. In order to improve the model's sensitivity, we examined several potential sources of variability of capsaicin-evoked MA and PPH in healthy volunteers, including skin temperature fluctuations, method (intradermal vs. topical) and site (volar forearm vs. foot dorsum) of administration. In study I, 12 subjects received, in a 6-session, randomized, crossover trial, 1) 250 micrograms of intradermal (ID) CAP to the volar forearm with skin temperature fixed at 36 degrees C (36 ID). 2) 250 micrograms ID CAP with varying skin temperature (VT ID), or 3) 250 microliters of l% CAP patch placed on the skin at 36 degrees C. The resulting MA and PPH areas observed with each method were measured. In study II, a 4-session, randomized crossover trial, 12 subjects were given 100 micrograms ID CAP in the volar forearm or foot dorsum and subsequent areas of MA and PPH recorded. In study I, 5/12 subjects had small MA areas (< or = 5 cm2) and one subject had small PPH areas in at least 4/6 sessions. The most consistent intra-subject responses were seen with the 36 ID method. Correlation coefficients for the two sessions using the same method of administration were: MA; 36 ID r = 0.83, VT ID = 0.19. Topical r = 0.81; PPH: 36 ID r = 0.93; VT ID r = 0.38, Topical r = 0.78. In study II, 4/12 subjects had little MA for both forearm and foot though all subjects developed PPH. However, greater intra-subject consistency (MA: foot: r = 0.84; arm: r = 0.49; PPH: r = 0.87; r = 0.39) and significantly larger areas of MA (15.8 +/- 4.2 vs 9.1 +/- 2.5, p < 0.05) were seen with the foot. (PPH: foot: 28.9 +/- 6.7; arm: 21.6 +/- 4.2, NS). Large variability exists among subjects receiving CAP, with some developing minimal MA. However, these subjects may be screened out prior to entry, increasing the sensitivity of the model, which may be further improved by clamping the skin temperature. JF - Journal of pain and symptom management AU - Liu, M AU - Max, M B AU - Robinovitz, E AU - Gracely, R H AU - Bennett, G J AD - Neurobiology and Anesthesiology Branch, National Institute of Dental, Research, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1998/07// PY - 1998 DA - July 1998 SP - 10 EP - 20 VL - 16 IS - 1 SN - 0885-3924, 0885-3924 KW - Capsaicin KW - S07O44R1ZM KW - Index Medicus KW - Double-Blind Method KW - Humans KW - Adult KW - Cross-Over Studies KW - Male KW - Female KW - Pain Measurement -- methods KW - Pain Measurement -- drug effects KW - Hyperalgesia -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73847515?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+pain+and+symptom+management&rft.atitle=The+human+capsaicin+model+of+allodynia+and+hyperalgesia%3A+sources+of+variability+and+methods+for+reduction.&rft.au=Liu%2C+M%3BMax%2C+M+B%3BRobinovitz%2C+E%3BGracely%2C+R+H%3BBennett%2C+G+J&rft.aulast=Liu&rft.aufirst=M&rft.date=1998-07-01&rft.volume=16&rft.issue=1&rft.spage=10&rft.isbn=&rft.btitle=&rft.title=Journal+of+pain+and+symptom+management&rft.issn=08853924&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-09-10 N1 - Date created - 1998-09-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of pamidronate disodium in the treatment of metastatic bone disease. AN - 70069682; 9824995 AB - Bone metastases are a common feature of advanced neoplastic disease and are considered to be among the most frequent causes of pain and complications in oncologic patients. The main objective of the treatment of such patients is to control their symptoms and improve their quality of life. Pamidronate disodium is a second-generation bisphosphonate capable of inhibiting bone resorption (particularly osteoclast activity) without affecting bone remineralization. After a brief introduction concerning the pathophysiology of bone metastases and neoplastic bone pain, we herein present data on the clinical pharmacology and toxicity of bisphosphonates in general, and pamidronate in particular. We conclude by reviewing the literature on the use of pamidronate in phase II and III trials involving patients with metastatic bone disease. The paper is based on a review of articles published between 1984 and 1997 selected from the Cancerline and Medline databases. In the considered phase II and III studies involving patients with bone metastases (breast cancer and multiple myeloma in particular), pamidronate proved to be efficacious in reducing the incidence of pain and skeletal complications, decreasing the excretion of metabolic markers of bone resorption and improving the quality of life. Intravenous infusions of 60-90 mg over a period of 2 hr every 3-4 weeks did not cause any significant toxic effects and was easily managed. Pamidronate is a bisphosphonate that is efficacious in the treatment of symptomatic bone metastases and can be considered an important therapeutic option in association with systemic treatments, radiotherapy and normal supportive care, especially in patients with breast cancer and multiple myeloma. Further randomized studies are necessary to confirm the positive preliminary results in other neoplasms, analyze the cost/benefit ratio of the treatment, and verify the possibility that, in addition to being used for palliative purposes, pamidronate may also prevent or delay the appearance of bone metastases. JF - Tumori AU - Ripamonti, C AU - Fulfaro, F AU - Ticozzi, C AU - Casuccio, A AU - De Conno, F AD - Pain Therapy and Palliative Care Division, National Cancer Institute, Milan, Italy. tdpint@tin.it PY - 1998 SP - 442 EP - 455 VL - 84 IS - 4 SN - 0300-8916, 0300-8916 KW - Antineoplastic Agents KW - 0 KW - Diphosphonates KW - pamidronate KW - OYY3447OMC KW - Index Medicus KW - Bone Resorption -- etiology KW - Bone Remodeling -- drug effects KW - Humans KW - Clinical Trials as Topic KW - Diphosphonates -- therapeutic use KW - Bone Neoplasms -- physiopathology KW - Bone Neoplasms -- drug therapy KW - Antineoplastic Agents -- therapeutic use KW - Bone Neoplasms -- secondary UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70069682?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Tumori&rft.atitle=Role+of+pamidronate+disodium+in+the+treatment+of+metastatic+bone+disease.&rft.au=Ripamonti%2C+C%3BFulfaro%2C+F%3BTicozzi%2C+C%3BCasuccio%2C+A%3BDe+Conno%2C+F&rft.aulast=Ripamonti&rft.aufirst=C&rft.date=1998-07-01&rft.volume=84&rft.issue=4&rft.spage=442&rft.isbn=&rft.btitle=&rft.title=Tumori&rft.issn=03008916&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-12-09 N1 - Date created - 1998-12-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Postscript: where do we go from here? AN - 70025073; 9798797 JF - Journal of psychoactive drugs AU - Sloboda, Z AU - Stephens, R C AU - Alemagno, S AD - Division of Epidemiology and Prevention Research, National Institute on Drug Abuse, Rockville, Maryland 20857, USA. PY - 1998 SP - 307 EP - 314 VL - 30 IS - 3 SN - 0279-1072, 0279-1072 KW - Index Medicus KW - AIDS/HIV KW - United States KW - Sexual Behavior KW - Needle Sharing KW - Humans KW - National Institutes of Health (U.S.) KW - Research Support as Topic KW - Acquired Immunodeficiency Syndrome -- prevention & control KW - Risk-Taking KW - Health Promotion -- methods KW - HIV Infections -- prevention & control KW - HIV Infections -- etiology KW - Substance-Related Disorders -- complications KW - Substance-Related Disorders -- psychology KW - Acquired Immunodeficiency Syndrome -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70025073?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Postscript%3A+where+do+we+go+from+here%3F&rft.au=Sloboda%2C+Z%3BStephens%2C+R+C%3BAlemagno%2C+S&rft.aulast=Sloboda&rft.aufirst=Z&rft.date=1998-07-01&rft.volume=58&rft.issue=16&rft.spage=3590&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 - 1999-01-06 N1 - Date created - 1999-01-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - An overview of topoisomerase I-targeting agents. AN - 69976937; 9779876 AB - The camptothecins are a new class of antitumor agents that target topoisomerase I. Irinotecan and topotecan are the most widely used camptothecin analogs in clinical practice, with documented clinical activity in colorectal and ovarian cancer. Ongoing clinical trials with these agents are further characterizing their spectra of clinical activity and determining their optimal schedule of administration in combination with other anticancer agents. Newer camptothecin analogs in clinical development, such as 9-aminocamptothecin, 9-nitrocamptothecin, GI1147211, and DX-8951f, are also being studied to determine if they have improved toxicity and efficacy profiles compared with existing analogs. The successful development of the camptothecins as antitumor agents demonstrates the importance of topoisomerase 1 as a target for cancer chemotherapy. JF - Seminars in hematology AU - Arbuck, S G AU - Takimoto, C H AD - Division of Cancer Treatment, Diagnosis, and Centers, National Cancer Institute, Bethesda Naval Hospital, MD 20892, USA. Y1 - 1998/07// PY - 1998 DA - July 1998 SP - 3 EP - 12 VL - 35 IS - 3 Suppl 4 SN - 0037-1963, 0037-1963 KW - Antineoplastic Agents KW - 0 KW - Enzyme Inhibitors KW - Topoisomerase I Inhibitors KW - irinotecan KW - 0H43101T0J KW - Topotecan KW - 7M7YKX2N15 KW - DNA Topoisomerases, Type I KW - EC 5.99.1.2 KW - Camptothecin KW - XT3Z54Z28A KW - Index Medicus KW - Humans KW - Drug Resistance, Neoplasm KW - Neoplasms -- drug therapy KW - Enzyme Inhibitors -- therapeutic use KW - Neoplasms -- enzymology KW - Camptothecin -- pharmacology KW - Camptothecin -- therapeutic use KW - Topotecan -- therapeutic use KW - Topotecan -- pharmacology KW - DNA Topoisomerases, Type I -- physiology KW - Camptothecin -- analogs & derivatives KW - Enzyme Inhibitors -- pharmacology KW - Antineoplastic Agents -- therapeutic use KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69976937?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+hematology&rft.atitle=An+overview+of+topoisomerase+I-targeting+agents.&rft.au=Arbuck%2C+S+G%3BTakimoto%2C+C+H&rft.aulast=Arbuck&rft.aufirst=S&rft.date=1998-07-01&rft.volume=35&rft.issue=3+Suppl+4&rft.spage=3&rft.isbn=&rft.btitle=&rft.title=Seminars+in+hematology&rft.issn=00371963&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-01-04 N1 - Date created - 1999-01-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Neural Networks for Braille Reading by the Blind AN - 58353712; 9900162 AB - To explore the neural networks used for Braille reading, we measured regional cerebral blood flow with PET during tactile tasks performed both by Braille readers blinded early in life & by sighted subjects. Eight proficient Braille readers were studied during Braille reading with both right & left index fingers. Eight-character, non-contrasted Braille-letter strings were used, & subjects were asked to discriminate between words & non-words. To compare the behavior of the brain of the blind & the sighted directly, non-Braille tactile tasks were performed by 6 different blind subjects & 10 sighted control subjects using the right index finger. The tasks included a nondiscrimination task & three discrimination tasks (angle, width & character). Irrespective of reading finger (right or left), Braille reading by the blind activated the inferior parietal lobule, primary visual cortex, superior occipital gyri, fusiform gyri, ventral premotor area, superior parietal lobule, cerebellum & primary sensorimotor area bilaterally, also the right dorsal premotor cortex, right middle occipital gyrus & right prefrontal area. During non-Braille discrimination tasks, in blind subjects, the ventral occipital regions, including the primary visual cortex & fusiform gyri bilaterally were activated while the secondary somatosensory area was deactivated. The reverse pattern was found in sighted subjects where the secondary somatosensory area was activated while the ventral occipital regions were suppressed. These findings suggest that the tactile processing pathways usually linked in the secondary somatosensory area are rerouted in blind subjects to the ventral & occipital cortical regions originally reserved for visual shape discrimination. 7 Tables, 6 Figures, 63 References. Adapted from the source document JF - Brain AU - Sadato, Norihiro AU - Pascual-Leone, Alvaro AU - Grafman, Jordan AU - Deiber, Marie-Pierre AU - Ibanez, Vicente AU - Hallett, Mark AD - c/o Hallett-National Instits Health, 10 Center Dr MSC 1428 Bethesda MD 20892-1428 hallett@codon.nih.gov Y1 - 1998/07// PY - 1998 DA - July 1998 SP - 1213 EP - 1229 VL - 121 IS - 7 SN - 0006-8950, 0006-8950 KW - Neural Networks (57240) KW - Reading Aids for the Blind (70700) KW - Brain (09350) KW - Vision Disorders (94350) KW - article KW - 4018: psycholinguistics; neurolinguistics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/58353712?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Allba&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain&rft.atitle=Neural+Networks+for+Braille+Reading+by+the+Blind&rft.au=Sadato%2C+Norihiro%3BPascual-Leone%2C+Alvaro%3BGrafman%2C+Jordan%3BDeiber%2C+Marie-Pierre%3BIbanez%2C+Vicente%3BHallett%2C+Mark&rft.aulast=Sadato&rft.aufirst=Norihiro&rft.date=1998-07-01&rft.volume=121&rft.issue=7&rft.spage=1213&rft.isbn=&rft.btitle=&rft.title=Brain&rft.issn=00068950&rft_id=info:doi/ LA - English DB - Linguistics and Language Behavior Abstracts (LLBA) N1 - Date revised - 2003-10-01 N1 - Last updated - 2016-09-27 N1 - CODEN - BRAIAK N1 - SubjectsTermNotLitGenreText - Vision Disorders (94350); Reading Aids for the Blind (70700); Neural Networks (57240); Brain (09350) ER - TY - JOUR T1 - Role of the Endogenous Production of Interleukin 12 in Immunotherapy AN - 17204719; 4492286 AB - Previous studies demonstrated that injecting mice with the cytokine interleukin 12 (IL-12) could significantly suppress the growth of a number of tumors, including murine B16 melanoma. In this report, the persistence of the antitumor effects of IL-12 is investigated. The i.p. injection of IL-12 (0.1 mu g) on days 14, 16, 18, 20, and 22 was found to significantly suppress the growth of s.c. inoculated B16 melanoma for up to 2 weeks after the last injection of IL-12. Interestingly, the IL-12 serum level 4 days after the last injection of IL-12 was significantly elevated in tumor-bearing mice compared with that of IL-12-treated normal mice. The in vivo depletion of either CD4 super(+) or CD8 super(+) T cells abrogated the antitumor activity of IL-12 and diminished the apparent autocrine stimulation of IL-12 release seen after IL-12 treatment. Resection of the tumor-draining lymph nodes (LNs) but not of the spleen abrogated the antitumor effect of IL-12 treatment as well as the elevation of serum IL-12. Expression of mRNA encoding IL-12 as well as CD40 ligand (CD40L) was detected in the tumor-draining LNs but not in the spleen of tumor-bearing mice after IL-12 treatment. Furthermore, the antitumor activity observed after IL-12 treatment was diminished by the in vivo administration of either anti-IL-12 or anti-CD40L monoclonal antibodies. Collectively, these results suggest that the endogenous production of IL-12 resulting from the CD40-CD40L interaction between antigen-presenting cells and CD4 super(+) T cells in the tumor-draining LNs may play a role in the persistence of the antitumor effects seen after IL-12 treatment. JF - Cancer Research AU - Harada, M AU - Tamada, K AU - Abe, K AU - Yasumoto, K AU - Kimura, G AU - Nomoto, K AD - Surgery Branch, National Cancer Institute, NIH, Building 10, Room 2B42, Bethesda, MD 20892, USA, haradam@pop.nci.nih.gov Y1 - 1998/07// PY - 1998 DA - Jul 1998 SP - 3073 EP - 3077 VL - 58 IS - 14 SN - 0008-5472, 0008-5472 KW - CD4 antigen KW - CD40 antigen KW - CD40L protein KW - CD8 antigen KW - mice KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Interleukin 12 KW - Immunotherapy KW - Lymphocytes T KW - Melanoma KW - W3 33150:Cytokine based KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17204719?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Research&rft.atitle=Role+of+the+Endogenous+Production+of+Interleukin+12+in+Immunotherapy&rft.au=Harada%2C+M%3BTamada%2C+K%3BAbe%2C+K%3BYasumoto%2C+K%3BKimura%2C+G%3BNomoto%2C+K&rft.aulast=Harada&rft.aufirst=M&rft.date=1998-07-01&rft.volume=58&rft.issue=14&rft.spage=3073&rft.isbn=&rft.btitle=&rft.title=Cancer+Research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Melanoma; Interleukin 12; Immunotherapy; Lymphocytes T ER - TY - JOUR T1 - Evidence of past recombination events among the genes encoding the Erp antigens of Borrelia burgdorferi AN - 17157149; 4442966 AB - A single Borrelia burgdorferi bacterium may contain six or more different 32 kb circular plasmids (cp32s). Although these plasmids are homologous throughout much of their sequences, two loci have been identified at which they can very significantly. The cp32 plasmids and their relatives each contain two adjacent genes, orfc and orf3, that vary in sequence between plasmids found within clones of individual bacteria. The orfC gene product is homologous to proteins involved in partitioning of bacterial plasmids, and the differences at this locus between plasmids may account for their compatibility. The orfC-orf3 loci are located approximately 5 kb from another variable locus called erp. The orfC-orf3 loci were used as physically linked markers to assess genetic rearrangements in the erp loci; this revealed examples of recombination involving both individual genes and entire erp loci. Recombination of the genes encoding the Erp antigens might contribute to the evasion of the mammalian immune response and could play roles in the establishment and persistence of B. burgdorferi infections in mammalian hosts. JF - Microbiology AU - Stevenson, B AU - Casjens, S AU - Rosa, P AD - Laboratory of Microbial Structure and Function, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, MT 59840, USA, lkpsic00@pop.uky.edu Y1 - 1998/07// PY - 1998 DA - Jul 1998 SP - 1869 EP - 1879 VL - 144 IS - 7 SN - 1350-0872, 1350-0872 KW - Erp antigen KW - antigens KW - erp gene KW - nucleotide sequence KW - orf3 gene KW - orfc gene KW - partitioning KW - plasmid cp32 KW - plasmids KW - Genetics Abstracts; Microbiology Abstracts B: Bacteriology KW - Recombination KW - Borrelia burgdorferi KW - G 07320:Bacterial genetics KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17157149?accountid=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=Microbiology&rft.atitle=Evidence+of+past+recombination+events+among+the+genes+encoding+the+Erp+antigens+of+Borrelia+burgdorferi&rft.au=Stevenson%2C+B%3BCasjens%2C+S%3BRosa%2C+P&rft.aulast=Stevenson&rft.aufirst=B&rft.date=1998-07-01&rft.volume=144&rft.issue=7&rft.spage=1869&rft.isbn=&rft.btitle=&rft.title=Microbiology&rft.issn=13500872&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Borrelia burgdorferi; Recombination ER - TY - JOUR T1 - Using structural information to create physiologically based pharmacokinetic models for all polychlorinated biphenyls II: Rates of metabolism AN - 17108571; 4422632 AB - Physiologically based pharmacokinetic (PBPK) models are useful in describing the distribution, metabolism, and fate of xenobiotics across multiple species. The eventual goal of the present research is to create PBPK models for all 209 polychlorinated biphenyls (PCBs). Key parameters in any PBPK model are the metabolic rates. Data on metabolic rates of PCBs were derived from in vitro experiments and from fitting of PBPK models to in vivo data. The rate of metabolism was assumed to be a linear function of PCB concentration. Structural descriptors suggested by the literature were used in a stepwise regression to find an expression for the metabolic rate of PCBs as a function of five structural descriptors related to the degree and pattern of chlorine substitution. R super(2) for the fit of the model to the data is 0.9606. JF - Toxicology and Applied Pharmacology AU - Parham, F M AU - Portier, C J AD - OAO/National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA Y1 - 1998/07// PY - 1998 DA - Jul 1998 SP - 110 EP - 116 VL - 151 IS - 1 SN - 0041-008X, 0041-008X KW - pharmacokinetics KW - polychlorinated biphenyls KW - structure-activity relationships KW - Toxicology Abstracts KW - PCB KW - Models KW - X 24153:Metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17108571?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+and+Applied+Pharmacology&rft.atitle=Using+structural+information+to+create+physiologically+based+pharmacokinetic+models+for+all+polychlorinated+biphenyls+II%3A+Rates+of+metabolism&rft.au=Parham%2C+F+M%3BPortier%2C+C+J&rft.aulast=Parham&rft.aufirst=F&rft.date=1998-07-01&rft.volume=151&rft.issue=1&rft.spage=110&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 revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Models; PCB ER - TY - JOUR T1 - Phase 1 evaluation of Vibrio cholerae O1, serotype Inaba, polysaccharide-cholera toxin conjugates in adult volunteers AN - 17107012; 4401440 AB - Conjugate vaccines were prepared by binding hydrazine-treated lipopolysaccharide (DeALPS) from Vibrio cholerae O1, serotype Inaba, to cholera toxin (CT) variants CT-1 and CT-2. Volunteers (n = 75) were injected with either 25 mu g of DeALPS, alone or as a conjugate, or the licensed cellular vaccine containing 4 times 10 super(9) organisms each of serotypes Inaba and Ogawa per ml. No serious adverse reactions were observed. DeALPS alone did not elicit serum LPS or vibriocidal antibodies in mice and only low levels of immunoglobulin M (IgM) anti-LPS in the volunteers. Recipients of the cellular vaccine had the highest IgM anti-LPS levels, but the difference was not statistically significant from that elicited by the conjugates. The conjugates elicited the highest levels of IgG anti-LPS (DeALPS-CT-2 > DeALPS-CT-1 > cellular vaccine). Both conjugates and the cellular vaccine elicited vibriocidal antibodies: after 8 months, recipients of cellular vaccine had the highest geometric mean titer (1,249), followed by DeALPS-CT-2 (588) and DeALPS-CT-1 (330). The correlation coefficient between IgG anti-LPS and 2-mercaptoethanol (2-ME)-resistant vibriocidal antibodies was 0.81 (P = 0.0004). Convalescent sera from cholera patients had a mean vibriocidal titer of 2,525 that was removed by treatment with 2-ME. The vibriocidal activities of sera from all vaccine groups and from the patients were absorbed (>75%) by LPS but not by either CT-1 or CT-2. Conjugate-induced IgG vibriocidal antibodies persisted longer than those elicited by the whole-cell vaccine. Both conjugates, but not the cellular vaccine, elicited IgG anti-CT. JF - Infection and Immunity AU - Gupta, R K AU - Taylor, D N AU - Bryla, DA AU - Robbins, J B AU - Szu, ShC AD - Building 6, Room 424, NIH, 8800 Rockville Pike, Bethesda, MD 20892, USA, scszu@Helix.nih.gov Y1 - 1998/07// PY - 1998 DA - Jul 1998 SP - 3095 EP - 3099 VL - 66 IS - 7 SN - 0019-9567, 0019-9567 KW - 2-mercaptoethanol KW - Lipopolysaccharides KW - Vibrio cholerae KW - man KW - polysaccharides KW - Microbiology Abstracts B: Bacteriology; Immunology Abstracts KW - Toxins KW - Cholera toxin KW - Immunogenicity KW - Cholera KW - Vaccines KW - Immunoglobulin M KW - Immunoglobulins KW - J 02834:Vaccination and immunization KW - F 06807:Active immunization UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17107012?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Infection+and+Immunity&rft.atitle=Phase+1+evaluation+of+Vibrio+cholerae+O1%2C+serotype+Inaba%2C+polysaccharide-cholera+toxin+conjugates+in+adult+volunteers&rft.au=Gupta%2C+R+K%3BTaylor%2C+D+N%3BBryla%2C+DA%3BRobbins%2C+J+B%3BSzu%2C+ShC&rft.aulast=Gupta&rft.aufirst=R&rft.date=1998-07-01&rft.volume=66&rft.issue=7&rft.spage=3095&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Vibrio cholerae; Immunoglobulins; Vaccines; Toxins; Immunogenicity; Immunoglobulin M; Cholera toxin; Cholera ER - TY - JOUR T1 - Factors associated with self-reported, pesticide-related visits to health care providers in the agricultural health study AN - 17096284; 4410092 AB - To investigate factors associated with pesticide-related visits to health care providers (i.e., doctor or hospital visits), responses to self-administered questionnaires received from 35,879 licensed restricted-use pesticide applicators participating in the Agricultural Health Study were analyzed. The cohort reported a total of more than 10.9 million pesticide-application days. The odds of a pesticide-related health care visit were increased for commercial applicators compared to private applicators [odds ratio (OR = 1.77; 95% confidence interval (CI), 1.52-2.06) and for applicators who used insecticides 70 times or more in their lifetime compared to those who used insecticides less frequently (OR = 1.43; CI, 1.26-1.63). After adjusting for the number of applications in a logistic regression model, significantly higher odds of health care visits were observed among North Carolina applicators compared to Iowa applicators (OR = 1.35; CI, 1.17-1.52), among applicators who mixed their own pesticides (OR = 1.65; CI, 1.22-2.23), and among applicators who personally repaired their pesticide application equipment at least once per year (OR = 1.12; CI, 1.06-1.25). Significantly lower odds were found among female versus male applicators (OR = 0.68; CI, 0.46-0.99) and among applicators who graduated from high school versus those who did not (OR = 0.82; CI, 0.71-0.94 for high school graduates and OR = 0.79; CI, 0.68-0.91 for those with at least some college). These observations suggest that several steps can be taken to reduce the number of health care visits resulting from occupational exposure to pesticides. The implications of this pattern of pesticide-related health care visits may have etiologic implications for cancer and other chronic diseases. JF - Environmental Health Perspectives AU - Alavanja, MCR AU - Sandler, D P AU - McDonnell, C J AU - Lynch, C F AU - Pennybacker, M AU - Zahm, SH AU - Lubin, J AU - Mage, D AU - Steen, W C AU - Wintersteen, W AU - Blair, A AD - Epidemiology and Biostatistics Program, National Cancer Institute, EPN/418, 6130 Executive Boulevard, Bethesda, MD 20892 USA Y1 - 1998/07// PY - 1998 DA - Jul 1998 SP - 415 EP - 420 VL - 106 IS - 7 SN - 0091-6765, 0091-6765 KW - USA, Iowa KW - USA, North Carolina KW - health care KW - man KW - Toxicology Abstracts; Health & Safety Science Abstracts; Pollution Abstracts KW - Risk assessment KW - Occupational diseases KW - Pesticide applications KW - Insecticides KW - occupational diseases KW - Regression analysis KW - Occupational exposure KW - Sprays KW - Agrochemicals KW - Cancer KW - Pesticides KW - H 5000:Pesticides KW - X 24132:Chronic exposure KW - P 6000:TOXICOLOGY AND HEALTH UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17096284?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+Health+Perspectives&rft.atitle=Factors+associated+with+self-reported%2C+pesticide-related+visits+to+health+care+providers+in+the+agricultural+health+study&rft.au=Alavanja%2C+MCR%3BSandler%2C+D+P%3BMcDonnell%2C+C+J%3BLynch%2C+C+F%3BPennybacker%2C+M%3BZahm%2C+SH%3BLubin%2C+J%3BMage%2C+D%3BSteen%2C+W+C%3BWintersteen%2C+W%3BBlair%2C+A&rft.aulast=Alavanja&rft.aufirst=MCR&rft.date=1998-07-01&rft.volume=106&rft.issue=7&rft.spage=415&rft.isbn=&rft.btitle=&rft.title=Environmental+Health+Perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Pesticides; Risk assessment; Insecticides; occupational diseases; Agrochemicals; Occupational exposure; Sprays; Cancer; Occupational diseases; Regression analysis; Pesticide applications ER - TY - JOUR T1 - The influence of cigarette smoking on the association between body weight and mortality. The Framingham Heart Study revisited AN - 16556263; 4397851 AB - To calculate for two measures of obesity, the Metropolitan Relative Weight (MRW) and body mass index (BMI), the value at which minimum mortality occurs. This was done to retest the hypothesis, in the Framingham Heart Study data, that the association between obesity and mortality can be obscured by an interaction between the measure of obesity and smoking. In the original analysis of the Framingham data it was suggested that there was a U- or J-shaped relationship between MRW and death in smokers but a linear relationship in nonsmokers. The design and setting were those of the NHLBI Framingham Heart Study. The 5209 members of the Framingham Heart Study underwent a baseline examination in 1948-1952 (Exam 1) and they were reexamined at approximately two-year intervals over a 30-year period. The study included both men (n = 2336) and women (n = 2873) in the age range of 28 to 62 years. After excluding persons with missing baseline data, the analytic sample size was 5163. Additional analyses were conducted by deleting persons with cardiovascular disease (CVD) at baseline (n = 135), the sample used by the original paper by Garrison and colleagues, and persons who died within the first four years of follow-up (n = 62). The main outcome measures consisted of thirty-year survival through Exam 16, approximately in 1980, as influenced by MRW or BMI, age, and smoking status at baseline (Exam 1). We were able to show that the sample sizes of male nonsmokers were too small to test the hypothesis within age groups < 40 and 40-49 years. In men ages 50-62 there was a significant age-adjusted quadratic relationship between BMI or MRW, and risk of death. The estimated BMI at the minimum risk of death for smokers (24.5) and nonsmokers (23.8) were not statistically different. Identical results were found for MRW (minimum: smokers = 112.5, nonsmokers = 111.4). In men and women ages 28-62 there appeared to be a u- or j-shaped relationship between the 30-year crude mortality rate and MRW. After excluding persons with missing data, CVD at baseline, and persons who died within the first four years of follow-up, the age adjusted estimated BMI value at the minimum risk of death was nearly identical for men and women and for smokers and nonsmokers (Men: smokers = 22.8, nonsmokers = 22.8; Women: smokers = 22.9, nonsmokers = 23.3). Additionally, the estimates of the minimum were always below the mean. Identical results were found without deleting persons with CVD at baseline and deaths in the first four years of follow-up. Identical results were found for MRW. Reanalysis of the Framingham Heart Study data does not support the hypothesis that there is an interaction between smoking and measures of obesity. Moreover, the estimated BMI or MRW at the minimum risk of death was similar for men and women smokers and nonsmokers alike even after deleting prevalent cases of CVD and deaths within the first four years of follow-up. JF - Annals of Epidemiology AU - Sempos, C T AU - Durazo-Arvizu, R AU - McGee, D L AU - Cooper, R S AU - Prewitt, TE AD - Epidemiology and Biometry Program, Division of Epidemiology and Clinical Applications, National Heart, Lung, and Blood Institute, 6701 Rockledge Drive, Room 8150, Bethesda, Maryland 20892-7934, USA Y1 - 1998/07// PY - 1998 DA - Jul 1998 SP - 289 EP - 300 VL - 8 IS - 5 SN - 1047-2797, 1047-2797 KW - body weight KW - man KW - Risk Abstracts; Health & Safety Science Abstracts; Toxicology Abstracts KW - Risk assessment KW - Mortality KW - Body weight KW - Cigarette smoking KW - R2 23060:Medical and environmental health KW - H 12000:Epidemiology and Public Health KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16556263?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+Epidemiology&rft.atitle=The+influence+of+cigarette+smoking+on+the+association+between+body+weight+and+mortality.+The+Framingham+Heart+Study+revisited&rft.au=Sempos%2C+C+T%3BDurazo-Arvizu%2C+R%3BMcGee%2C+D+L%3BCooper%2C+R+S%3BPrewitt%2C+TE&rft.aulast=Sempos&rft.aufirst=C&rft.date=1998-07-01&rft.volume=8&rft.issue=5&rft.spage=289&rft.isbn=&rft.btitle=&rft.title=Annals+of+Epidemiology&rft.issn=10472797&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Risk assessment; Mortality; Body weight; Cigarette smoking ER - TY - JOUR T1 - Cryocrystallography and microspectrophotometry of a mutant ( alpha D60N) tryptophan synthase alpha sub(2) beta sub(2) complex reveals allosteric roles of alpha Asp60 AN - 16556208; 4397839 AB - We have investigated the role of Asp60 of the alpha -subunit in allosteric communication between the tryptophan synthase alpha - and beta -subunits. Crystallographic and microspectrophotometric studies have been carried out on a mutant ( alpha D60N) tryptophan synthase alpha sub(2) beta sub(2) complex which has no observable alpha -activity, but has substantial beta -activity. Single-crystal polarized absorption spectra indicate that the external aldimine is the predominant L-serine intermediate and that the amount of the intermediate formed is independent of pH, monovalent cations, and allosteric effectors. The three-dimensional structure is reported for this mutant enzyme complexed with indole 3-propanol phosphate bound to the alpha -site and L-serine bound to the beta -site ( alpha D60N-IPP-Ser), and this structure is compared with that of the unliganded mutant enzyme ( alpha D60N). In the complex, L-serine forms a stable external aldimine with the pyridoxal phosphate coenzyme at the active site of the beta -subunit. The conformation of the unliganded mutant is almost identical to that of the wild type enzyme. However, the structure of the mutant complexed with IPP and serine exhibits ligand-induced conformational changes much smaller than those observed previously for another mutant enzyme in the presence of the same ligands ( beta K87T-IPP-Ser) [Rhee, S., Parris, K. D., Hyde, C. C., Ahmed, S. A., Miles, E. W., and Davies, D. R. (1997) Biochemistry 36, 7664-7680]. The alpha D60N-IPP-Ser alpha sub(2) beta sub(2) complex does not undergo the following ligand-induced conformational changes: (1) the closure of the alpha -subunit loop 6 (residues 178-191), (2) the movement of the mobile subdomain (residues 93-189) of the beta -subunit, and (3) the rotation of the alpha -subunit relative to the beta -subunit. These observations show that alpha Asp60 plays important roles in the closure of loop 6 and in allosteric communication between the alpha - and beta -subunits. JF - Biochemistry (Washington) AU - Rhee, S AU - Miles, E W AU - Mozzarelli, A AU - Davies AD - National Institutes of Health, Bldg. 5, Rm. 338, Bethesda, MD 20892-0560, USA Y1 - 1998/07// PY - 1998 DA - Jul 1998 SP - 10653 EP - 10659 VL - 37 IS - 30 SN - 0006-2960, 0006-2960 KW - Microbiology Abstracts B: Bacteriology KW - Bacteria KW - Absorption spectroscopy KW - Aspartic acid KW - Allosteric properties KW - Crystallography KW - Tryptophan synthase KW - Conformational analysis KW - Mutants KW - J 02728:Enzymes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16556208?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemistry+%28Washington%29&rft.atitle=Cryocrystallography+and+microspectrophotometry+of+a+mutant+%28+alpha+D60N%29+tryptophan+synthase+alpha+sub%282%29+beta+sub%282%29+complex+reveals+allosteric+roles+of+alpha+Asp60&rft.au=Rhee%2C+S%3BMiles%2C+E+W%3BMozzarelli%2C+A%3BDavies&rft.aulast=Rhee&rft.aufirst=S&rft.date=1998-07-01&rft.volume=37&rft.issue=30&rft.spage=10653&rft.isbn=&rft.btitle=&rft.title=Biochemistry+%28Washington%29&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Absorption spectroscopy; Aspartic acid; Mutants; Conformational analysis; Tryptophan synthase; Crystallography; Bacteria; Allosteric properties ER - TY - JOUR T1 - Sources of the neurotoxin quinolinic acid in the brain of HIV-1-infected patients and retrovirus-infected macaques AN - 16553756; 4372792 AB - This study investigated the sources of quinolinic acid, a neurotoxic tryptophan-kynurenine pathway metabolite, in the brain and blood of HIV-infected patients and retrovirus-infected macaques. In brain, quinolinic acid concentrations in HIV-infected patients were elevated by >300-fold to concentrations that exceeded cerebrospinal fluid (CSF) by 8.9-fold. There were no significant correlations between elevated serum quinolinic acid levels with those in CSF and brain parenchyma. Because nonretrovirus-induced encephalitis confounds the interpretation of human postmortem data, rhesus macaques infected with retrovirus were used to examine the mechanisms of increased quinolinic acid accumulations and determine the relationships of quinolinic acid to encephalitis and systemic responses. The largest kynurenine pathway responses in brain were associated with encephalitis and were independent of systemic responses. CSF quinolinic acid levels were also elevated in all infected macaques, but particularly those with retrovirus-induced encephalitis. In contrast to the brain changes, there was no difference in any systemic measure between macaques with encephalitis vs. those without. Direct measures of the amount of quinolinic acid in brain derived from blood in a macaque with encephalitis showed that almost all quinolinic acid (>98%) was synthesized locally within the brain. These results demonstrate a role for induction of indoleamine-2,3-dioxygenase in accelerating the local formation of quinolinic acid within the brain tissue, particularly in areas of encephalitis, rather than entry of quinolinic acid into the brain from the meninges or blood. Strategies to reduce QUIN production, targeted at intracerebral sites, are potential approaches to therapy. JF - FASEB Journal AU - Heyes, M P AU - Saito, K AU - Lackner, A AU - Wiley, CA AU - Achim, CL AU - Markey, S P AD - Laboratory of Neurotoxicology, Building 10, Room 3D40, NIMH, 9000 Rockville Pike, Bethesda, MD 20892-1262, USA Y1 - 1998/07// PY - 1998 DA - Jul 1998 SP - 881 EP - 896 VL - 12 IS - 10 SN - 0892-6638, 0892-6638 KW - HIV-1 KW - Macaca KW - Rhesus macaque KW - human immunodeficiency virus 1 KW - man KW - quinolinic acid KW - Toxicology Abstracts; CSA Neurosciences Abstracts; Virology & AIDS Abstracts KW - Cerebrospinal fluid KW - Retrovirus KW - Human immunodeficiency virus 1 KW - Macaca mulatta KW - Parenchyma KW - Brain KW - Encephalitis KW - Neurotoxins KW - N3 11130:Neurovirology KW - X 24240:Miscellaneous KW - V 22004:AIDS: Clinical aspects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16553756?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=FASEB+Journal&rft.atitle=Sources+of+the+neurotoxin+quinolinic+acid+in+the+brain+of+HIV-1-infected+patients+and+retrovirus-infected+macaques&rft.au=Heyes%2C+M+P%3BSaito%2C+K%3BLackner%2C+A%3BWiley%2C+CA%3BAchim%2C+CL%3BMarkey%2C+S+P&rft.aulast=Heyes&rft.aufirst=M&rft.date=1998-07-01&rft.volume=12&rft.issue=10&rft.spage=881&rft.isbn=&rft.btitle=&rft.title=FASEB+Journal&rft.issn=08926638&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Human immunodeficiency virus 1; Macaca mulatta; Retrovirus; Neurotoxins; Brain; Cerebrospinal fluid; Parenchyma; Encephalitis ER - TY - JOUR T1 - High-frequency DNA rearrangements in the chromosomes of clinically isolated Mycoplasma fermentans AN - 16529489; 4383426 AB - Mycoplasma fermentans is currently being examined as an agent potentially associated with human disease. Several strains of M. fermentans were isolated from patients with respiratory tract disease and AIDS. Two of these clinical strains, M64 and SK6, were triple-filter-cloned and designated as the parental clones in this study. Genomic DNA of randomly picked subclones in four and five subsequent generations passed from the parental M64 and SK6 clones were analyzed by using a radiolabeled M. fermentans-specific insertion sequence (IS)-like element as the probe. The hybridization patterns of DNA restriction fragments revealed high frequencies of chromosomal changes accompanied with excision or new insertion of the IS-like element in M. fermentans chromosome. The findings indicate M. fermentans has an effective mechanism(s) to produce a rapid gene rearrangement that may be mediated by one or more copies of the IS-like element. JF - Current Microbiology AU - Hu, Wensi S AU - Hayes, M M AU - Wang, RYuan-Hu AU - Shih, JWai-Kuo AU - Lo, Shyh-Ching AD - Department of Transfusion Medicine, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA Y1 - 1998/07// PY - 1998 DA - Jul 1998 SP - 1 EP - 5 VL - 37 IS - 1 SN - 0343-8651, 0343-8651 KW - gene rearrangements KW - hybridization analysis KW - Genetics Abstracts; Microbiology Abstracts B: Bacteriology KW - G 07320:Bacterial genetics KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16529489?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+Microbiology&rft.atitle=High-frequency+DNA+rearrangements+in+the+chromosomes+of+clinically+isolated+Mycoplasma+fermentans&rft.au=Hu%2C+Wensi+S%3BHayes%2C+M+M%3BWang%2C+RYuan-Hu%3BShih%2C+JWai-Kuo%3BLo%2C+Shyh-Ching&rft.aulast=Hu&rft.aufirst=Wensi&rft.date=1998-07-01&rft.volume=37&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Current+Microbiology&rft.issn=03438651&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Pertussis toxin modification of PC12 cells inhibits a protein phosphatase 2A-like phosphatase AN - 16520973; 4365153 AB - We have found that modification of rat PC12 cells with pertussis toxin resulted in an similar to 50% inhibition of a protein phosphatase 2A-like phosphatase. Protein phosphatase 2A (PP2A) is a major cellular serine/threonine-specific protein phosphatase. Treatment of extracts from pertussis toxin-modified PC12 cells with either immobilized alkaline phosphatase or Ca super(2+) reversed this inhibition. Reactivation of the PP2A-like phosphatase in Ca super(2+) appears to result from the dephosphorylation of a protein by the Ca super(2+)/calmodulin-dependent protein phosphatase calcineurin. The PP2A-like phosphatase in extracts from pertussis toxin-modified PC12 cells eluted from a Mono Q column at a higher ionic strength than did the PP2A-like phosphatase in extracts from control cells. After incubation in Ca super(2+), the PP2A-like phosphatase in extracts from pertussis toxin-modified cells eluted from a Mono Q column at the same ionic strength as did the PP2A-like phosphatase in extracts from control cells. These results indicate that the effect of pertussis toxin on this PP2A-like activity results from the phosphorylation of either one of the subunits of the PP2A-like phosphatase or a protein that when phosphorylated binds to and inhibits this phosphatase. Pertussis toxin modification did not result in the phosphorylation of the catalytic subunit of PP2A. Because phosphorylation regulates the activities of many enzymes and cell surface receptors, a pertussis toxin-induced decrease in PP2A activity could alter signaling pathways and other cellular processes in which G proteins are not directly involved. JF - Journal of Neurochemistry AU - Chen, Fusheng AU - Vu, Ngoc-Diep AU - Wagner, P D AD - Bldg. 37, Rm. 4C24, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA Y1 - 1998/07// PY - 1998 DA - Jul 1998 SP - 248 EP - 257 VL - 71 IS - 1 SN - 0022-3042, 0022-3042 KW - Bordetella pertussis KW - pertussis toxin KW - pheochromocytoma cells KW - protein phosphatase 2A-like phosphatase KW - rats KW - CSA Neurosciences Abstracts; Toxicology Abstracts; Microbiology Abstracts B: Bacteriology; Calcium & Calcified Tissue Abstracts KW - N3 11104:Mammals (except primates) KW - X 24171:Microbial KW - J 02823:In vitro and in vivo effects KW - T 20019:Cellular calcium, channels and currents UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16520973?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cellular+and+molecular+life+sciences+%3A+CMLS&rft.atitle=The+eosinophil+ribonucleases.&rft.au=Rosenberg%2C+H+F&rft.aulast=Rosenberg&rft.aufirst=H&rft.date=1998-08-01&rft.volume=54&rft.issue=8&rft.spage=795&rft.isbn=&rft.btitle=&rft.title=Cellular+and+molecular+life+sciences+%3A+CMLS&rft.issn=1420682X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Targeted Disruption of the Acid alpha -Glucosidase Gene in Mice Causes an Illness with Critical Features of Both Infantile and Adult Human Glycogen Storage Disease Type II AN - 16497823; 4396481 AB - We have used gene targeting to create a mouse model of glycogen storage disease type II, a disease in which distinct clinical phenotypes present at different ages. As in the severe human infantile disease (Pompe Syndrome), mice homozygous for disruption of the acid alpha -glucosidase gene (6 super(neo)/6 super(neo)) lack enzyme activity and begin to accumulate glycogen in cardiac and skeletal muscle lysosomes by 3 weeks of age, with a progressive increase thereafter. By 3.5 weeks of age, these mice have markedly reduced mobility and strength. They grow normally, however, reach adulthood, remain fertile, and, as in the human adult disease, older mice accumulate glycogen in the diaphragm. By 8-9 months of age animals develop obvious muscle wasting and a weak, waddling gait. This model, therefore, recapitulates critical features of both the infantile and the adult forms of the disease at a pace suitable for the evaluation of enzyme or gene replacement. In contrast, in a second model, mutant mice with deletion of exon 6 ( Delta 6/ Delta 6), like the recently published acid alpha -glucosidase knockout with disruption of exon 13, have unimpaired strength and mobility (up to 6.5 months of age) despite indistinguishable biochemical and pathological changes. The genetic background of the mouse strains appears to contribute to the differences among the three models. JF - Journal of Biological Chemistry AU - Raben, N AU - Nagaraju, K AU - Lee, E AU - Kessler, P AU - Byrne, B AU - Lee, L AU - LaMarca, M AU - King, C AU - Ward, J AU - Sauer, B AU - Plotz, P AD - National Institutes of Health, Bldg. 10, Rm. 9N244, 9000 Rockville Pike, Bethesda, MD 20892, USA, rabenn@arb.niams.nih.gov Y1 - 1998/07// PY - 1998 DA - Jul 1998 SP - 19086 EP - 19092 VL - 273 IS - 30 SN - 0021-9258, 0021-9258 KW - glycogen storage disease II KW - mice KW - Biotechnology and Bioengineering Abstracts; Genetics Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - G 07397:Rodentia (mice) KW - W3 33056:Animal models of human disease KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16497823?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Biological+Chemistry&rft.atitle=Targeted+Disruption+of+the+Acid+alpha+-Glucosidase+Gene+in+Mice+Causes+an+Illness+with+Critical+Features+of+Both+Infantile+and+Adult+Human+Glycogen+Storage+Disease+Type+II&rft.au=Raben%2C+N%3BNagaraju%2C+K%3BLee%2C+E%3BKessler%2C+P%3BByrne%2C+B%3BLee%2C+L%3BLaMarca%2C+M%3BKing%2C+C%3BWard%2C+J%3BSauer%2C+B%3BPlotz%2C+P&rft.aulast=Raben&rft.aufirst=N&rft.date=1998-07-01&rft.volume=273&rft.issue=30&rft.spage=19086&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Entry of OpaA super(+) gonococci into HEp-2 cells requires concerted action of glycosaminoglycans, fibronectin and integrin receptors AN - 16480102; 4356615 AB - Heparan sulphate proteoglycans are increasingly implicated as eukaryotic cell surface receptors for bacterial pathogens. Here, we report that Neisseria gonorrhoeae adheres to proteoglycan receptors on HEp-2 epithelial cells but that internalization of the bacterium by this cell type requires the serum glycoprotein fibronectin. Fibronectin was shown to bind specifically to gonococci producing the OpaA adhesin. Binding assays with fibronectin fragments located the bacterial binding site near the N-terminal end of the molecule. However, none of the tested fibronectin fragments supported gonococcal entry into the eukaryotic cells; a 120 kDa fragment carrying the cell adhesion domain with the amino acid sequence RGD even inhibited the fibronectin-mediated uptake of MS11-OpaA. This inhibition could be mimicked by an RGD-containing hexapeptide and by alpha 5 beta 1 integrin-specific antibodies, suggesting that interaction of the central region of fibronectin with integrin receptors facilitated bacterial uptake. Fibronectin was unable to promote gonococcal entry into HEp-2 cells that had been treated with the enzyme heparinase III, which degrades the glycosaminoglycan side-chains of proteoglycan receptors. On the basis of these results, we propose a novel cellular uptake pathway for bacteria, which involves the binding of the pathogen to glycosaminoglycans that, in turn, act as co-receptors facilitating fibronectin-mediated bacterial uptake through integrin receptors. In this scenario, fibronectin would act as a molecular bridge linking the Opa-proteoglycan complex with host cell integrin receptors. JF - Molecular Microbiology AU - Van Putten, JPM AU - Duensing, T D AU - Cole, R L AD - Laboratory of Microbial Structure and Function, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 South 4th Street, Hamilton, MT 59840, USA, jos_van_putten@nih.gov Y1 - 1998/07// PY - 1998 DA - Jul 1998 SP - 369 EP - 379 VL - 29 IS - 1 SN - 0950-382X, 0950-382X KW - HEp-2 cells KW - fibronectin KW - glycosaminoglycans KW - Microbiology Abstracts B: Bacteriology KW - J 02849:Sexually-transmitted diseases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16480102?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+Microbiology&rft.atitle=Entry+of+OpaA+super%28%2B%29+gonococci+into+HEp-2+cells+requires+concerted+action+of+glycosaminoglycans%2C+fibronectin+and+integrin+receptors&rft.au=Van+Putten%2C+JPM%3BDuensing%2C+T+D%3BCole%2C+R+L&rft.aulast=Van+Putten&rft.aufirst=JPM&rft.date=1998-07-01&rft.volume=29&rft.issue=1&rft.spage=369&rft.isbn=&rft.btitle=&rft.title=Molecular+Microbiology&rft.issn=0950382X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Anti-prostate immunotoxins: Cytotoxicity of E4 antibody-pseudomonas exotoxin constructs AN - 16456595; 4352455 AB - E4 is a monoclonal antibody (MAb) that reacts with a surface antigen present on normal prostate- and prostate cancers. Using this antibody, 2 immunotoxins were generated, one being a chemical conjugate with a mutant truncated form of Pseudomonas exotoxin A (PE), E4-PE35KDEL. The other is a recombinant single chain immunotoxin, E4(Fv)-PE38KDEL. The affinity of the conjugated immunotoxin was similar to the hybridoma-produced MAb E4, revealing that conjugation did not impair the binding ability. The affinity of the recombinant immunotoxin (10 nM) was 10-fold lower than that of the MAb, probably reflecting differences of bivalent (MAb) vs. monovalent (Fv) binding. Antigen positive prostate, breast and colon carcinoma cell lines showed cytotoxic response to the E4 immunotoxins while antigen negative cells were not affected. The IC sub(50) value, representing a 50% inhibition of cellular protein synthesis, ranged from 0.3 to 20 ng/ml for E4-PE35KDEL and from 2 to 100 ng/ml for E4(Fv)-PE38KDEL. Therefore, the E4-derived immunotoxins may be useful for the treatment of prostate as well as breast and colon cancers. JF - International Journal of Cancer AU - Essand, M AU - Pastan, I AD - Laboratory of Molecular Biology, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Building 37, Room 4E16, Bethesda, MD 02892, USA, pasta@helix.nih.gov Y1 - 1998/07// PY - 1998 DA - Jul 1998 SP - 123 EP - 127 VL - 77 IS - 1 SN - 0020-7136, 0020-7136 KW - immunotoxins KW - prostate cancer KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - W3 33374:Antitumor agents KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16456595?accountid=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=International+Journal+of+Cancer&rft.atitle=Anti-prostate+immunotoxins%3A+Cytotoxicity+of+E4+antibody-pseudomonas+exotoxin+constructs&rft.au=Essand%2C+M%3BPastan%2C+I&rft.aulast=Essand&rft.aufirst=M&rft.date=1998-07-01&rft.volume=77&rft.issue=1&rft.spage=123&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Cancer&rft.issn=00207136&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Tissue microarrays for high-throughput molecular profiling of tumor specimens AN - 16448184; 4347922 AB - Many genes and signalling pathways controlling cell proliferation, death and differentiation, as well as genomic integrity, are involved in cancer development. New techniques, such as serial analysis of gene expression and cDNA microarrays, have enabled measurement of the expression of thousands of genes in a single experiment, revealing many new, potentially important cancer genes. These genome screening tools can comprehensively survey one tumor at a time; however, analysis of hundreds of specimens from patients in different stages of disease is needed to establish the diagnostic, prognostic and therapeutic importance of each of the emerging cancer gene candidates. Here we have developed an array-based high-throughput technique that facilitates gene expression and copy number surveys of very large numbers of tumors. As many as 1000 cylindrical tissue biopsies from individual tumors can be distributed in a single tumor tissue microarray. Sections of the microarray provide targets for parallel in situ detection of DNA, RNA and protein targets in each specimen on the array, and consecutive sections allow the rapid analysis of hundreds of molecular markers in the same set of specimens. Our detection of six gene amplifications as well as p53 and estrogen receptor expression in breast cancer demonstrates the power of this technique for defining new subgroups of tumors. JF - Nature Medicine AU - Kononen, J AU - Bubendorf, L AU - Kallioniemi, A AU - Baerlund, M AU - Schraml, P AU - Leighton, S AU - Torhorst, J AU - Mihatsch, MJ AU - Sauter, G AU - Kallioniemi, O-P AD - Laboratory of Cancer Genetics, National Human Genome Research Institute, National Institutes of Health, 49 Convent Drive MSC 4470, Room 4A24, Bethesda, MD 20892-4470, USA, okalli@nhgri.nih.gov Y1 - 1998/07// PY - 1998 DA - Jul 1998 SP - 844 EP - 847 VL - 4 IS - 7 SN - 1078-8956, 1078-8956 KW - high-throughput screening KW - tissue microarrays KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - W3 33135:Diagnosis: Other KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16448184?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+Medicine&rft.atitle=Tissue+microarrays+for+high-throughput+molecular+profiling+of+tumor+specimens&rft.au=Kononen%2C+J%3BBubendorf%2C+L%3BKallioniemi%2C+A%3BBaerlund%2C+M%3BSchraml%2C+P%3BLeighton%2C+S%3BTorhorst%2C+J%3BMihatsch%2C+MJ%3BSauter%2C+G%3BKallioniemi%2C+O-P&rft.aulast=Kononen&rft.aufirst=J&rft.date=1998-07-01&rft.volume=4&rft.issue=7&rft.spage=844&rft.isbn=&rft.btitle=&rft.title=Nature+Medicine&rft.issn=10788956&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Weight change and obesity after liver transplantation: Incidence and risk factors AN - 1011212697; 11807145 AB - Obesity is a concern in the long-term management of patients following liver transplantation, yet the risk of obesity and the factors that influence its development have not been well defined. We evaluated posttransplantation weight change among a cohort of 774 adults who had their height and weight recorded before liver transplantation at three major centers. Obesity was defined as a body mass index (BMI) of at least 30 kg/m2. Weight at transplantation was adjusted by the amount of ascites removed. Mean BMI increased from 24.8 kg/m2 pretransplantation to 27.0 kg/m2 in the first posttransplantation year, to 28.1 kg/m2 in the second year, and very little with subsequent observation. Among 320 patients who were not obese before transplantation, 21.6% became obese within 2 years after transplantation. On evaluation of numerous potential donor and pretransplantation risk factors, greater recipient BMI, greater donor BMI, and being married were found to be predictors of subsequent obesity (P < .05). Posttransplantation predictors of obesity included absence of acute cellular rejection, higher cumulative prednisone dose in the second year, and cyclosporine-based immunosuppression, although only rejection and prednisone dose remained predictors on multivariate analysis. Despite the marked weight gain after transplantation, prevalence of obesity at 2 years was only slightly greater than in the general US population. Obesity occurred commonly after liver transplantation, sometimes with a striking gain in weight. In addition to BMI at transplantation, donor BMI, marital status, occurrence of acute rejection, and prednisone dose affected the incidence of obesity. JF - Liver Transplantation AU - James E Everhart, AU - Vmph AU - Lombardero, Manuel AU - Lake, John R AU - Wiesner, Russell H AU - Zetterman, Rowen K AU - Hoofnagle, Jay H AD - Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD Y1 - 1998/07// PY - 1998 DA - Jul 1998 SP - 285 EP - 296 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 USA VL - 4 IS - 4 SN - 1527-6465, 1527-6465 KW - Physical Education Index KW - Obesity KW - Weight KW - Body mass KW - Risk factors KW - Analysis KW - Organ transplants KW - Liver KW - Height KW - Patients KW - PE 030:Exercise, Health & Physical Fitness UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1011212697?accountid=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=Liver+Transplantation&rft.atitle=Weight+change+and+obesity+after+liver+transplantation%3A+Incidence+and+risk+factors&rft.au=James+E+Everhart%2C%3BVmph%3BLombardero%2C+Manuel%3BLake%2C+John+R%3BWiesner%2C+Russell+H%3BZetterman%2C+Rowen+K%3BHoofnagle%2C+Jay+H&rft.aulast=James+E+Everhart&rft.aufirst=&rft.date=1998-07-01&rft.volume=4&rft.issue=4&rft.spage=285&rft.isbn=&rft.btitle=&rft.title=Liver+Transplantation&rft.issn=15276465&rft_id=info:doi/10.1002%2Flt.500040402 LA - English DB - Physical Education Index N1 - Date revised - 2012-05-01 N1 - Last updated - 2012-05-07 N1 - SubjectsTermNotLitGenreText - Obesity; Weight; Analysis; Risk factors; Body mass; Liver; Organ transplants; Height; Patients DO - http://dx.doi.org/10.1002/lt.500040402 ER - TY - JOUR T1 - Stimulatory effect of endogenous tissue inhibitor of metalloproteinases-1 (TIMP-1) overexpression on type IV collagen and laminin gene expression in rat mammary carcinoma cells. AN - 79993781; 9647740 AB - We recently reported enhanced tumor growth and stimulation of vascular endothelial growth factor (VEGF) expression in rat mammary carcinoma cells transfected with a human tissue inhibitor of metalloproteinases-1 (hTIMP-1) cDNA (1). In the present study, we examined if the composition of the stroma was altered in the tumors with the highest hTIMP-1 production. Immunohistological examination revealed increased amounts of the basement membrane (BM) components, type IV collagen and laminin, in the hTIMP-1 overexpressing tumors compared to that of the control. In vitro studies also revealed upregulation of type IV collagen and laminin gene expression associated with the hTIMP-1 overexpression. Endogenous RNA levels of rat TIMP-1 and the rat matrix metalloproteinases (MMPs), MMP-2, MMP-3, and MMP-9, were not affected by the hTIMP-1 transfection, suggesting that the increase in BM deposition was not a result of decreased collagenolytic activity. This is the first report to show an association between overexpression of TIMP-1 and increased tumor BM matrix production through stimulation of type IV collagen and laminin gene expression. JF - Biochemical and biophysical research communications AU - Yoshiji, H AU - Buck, T B AU - Harris, S R AU - Ritter, L M AU - Lindsay, C K AU - Thorgeirsson, U P AD - Tumor Biology and Carcinogenesis Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/06/29/ PY - 1998 DA - 1998 Jun 29 SP - 605 EP - 609 VL - 247 IS - 3 SN - 0006-291X, 0006-291X KW - Laminin KW - 0 KW - RNA, Messenger KW - Tissue Inhibitor of Metalloproteinase-1 KW - Collagen KW - 9007-34-5 KW - Index Medicus KW - Up-Regulation -- physiology KW - Rats KW - Animals KW - Tumor Cells, Cultured KW - RNA, Messenger -- metabolism KW - Basement Membrane -- metabolism KW - Humans KW - Transfection -- genetics KW - Neoplasms, Experimental -- metabolism KW - Neoplasms, Experimental -- pathology KW - Immunohistochemistry KW - Collagen -- genetics KW - Laminin -- genetics KW - Tissue Inhibitor of Metalloproteinase-1 -- genetics KW - Gene Expression Regulation, Neoplastic -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79993781?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Stimulatory+effect+of+endogenous+tissue+inhibitor+of+metalloproteinases-1+%28TIMP-1%29+overexpression+on+type+IV+collagen+and+laminin+gene+expression+in+rat+mammary+carcinoma+cells.&rft.au=Yoshiji%2C+H%3BBuck%2C+T+B%3BHarris%2C+S+R%3BRitter%2C+L+M%3BLindsay%2C+C+K%3BThorgeirsson%2C+U+P&rft.aulast=Yoshiji&rft.aufirst=H&rft.date=1998-06-29&rft.volume=247&rft.issue=3&rft.spage=605&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 - 1998-07-31 N1 - Date created - 1998-07-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Four amino acid residues are critical for high affinity binding of neuromedin B to the neuromedin B receptor. AN - 79951236; 9632639 AB - Three mammalian bombesin receptor subtypes have been characterized: the gastrin-releasing peptide receptor (GRP-R), the neuromedin B receptor (NMB-R), and bombesin receptor subtype 3 (BRS-3). In a previous report we identified four amino acids that are critical for high affinity binding of bombesin and gastrin-releasing peptide (GRP) to the GRP-R. These four amino acids are conserved in all species variants of the GRP-R and NMB-R which bind bombesin with high affinity, but they are diverged in BRS-3, the bombesin receptor subtype that binds bombesin with much lower affinity. Substituting these four divergent amino acids in BRS-3 for the conserved amino acids in either GRP-R or NMB-R increased the affinity of the mutated BRS-3 (4DeltaBRS-3) for bombesin compared with wild-type BRS-3. We hypothesized that the same four amino acids might be critical for high affinity NMB binding to the NMB-R. In this study we confirm this hypothesis by showing that the affinity of NMB is increased in a mutant BRS-3 receptor (4DeltaBRS-3) that contains these four substitutions resulting in an affinity that is close to the affinity of wild-type NMB-R for NMB. In contrast, these four amino acid substitutions in BRS-3 did not result in the formation of a high affinity binding site for the recently described non-peptide NMB-R antagonist PD168368. JF - The Journal of biological chemistry AU - Sainz, E AU - Akeson, M AU - Mantey, S A AU - Jensen, R T AU - Battey, J F AD - Laboratory of Molecular Biology, NIDCD, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/06/26/ PY - 1998 DA - 1998 Jun 26 SP - 15927 EP - 15932 VL - 273 IS - 26 SN - 0021-9258, 0021-9258 KW - Amino Acids KW - 0 KW - Receptors, Bombesin KW - bombesin receptor subtype 3 KW - Neurokinin B KW - 86933-75-7 KW - neuromedin B KW - 87096-84-2 KW - Index Medicus KW - Rats KW - Mutagenesis, Site-Directed KW - Animals KW - 3T3 Cells KW - Protein Structure, Secondary KW - Sequence Alignment KW - Molecular Sequence Data KW - Mice KW - Amino Acid Sequence KW - Structure-Activity Relationship KW - Binding Sites KW - Amino Acids -- metabolism KW - Receptors, Bombesin -- metabolism KW - Receptors, Bombesin -- antagonists & inhibitors KW - Neurokinin B -- metabolism KW - Neurokinin B -- analogs & derivatives KW - Neurokinin B -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79951236?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Four+amino+acid+residues+are+critical+for+high+affinity+binding+of+neuromedin+B+to+the+neuromedin+B+receptor.&rft.au=Sainz%2C+E%3BAkeson%2C+M%3BMantey%2C+S+A%3BJensen%2C+R+T%3BBattey%2C+J+F&rft.aulast=Sainz&rft.aufirst=E&rft.date=1998-06-26&rft.volume=273&rft.issue=26&rft.spage=15927&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 - 1998-08-03 N1 - Date created - 1998-08-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Structural basis of an embryonically lethal single Ala --> Thr mutation in the vnd/NK-2 homeodomain. AN - 79955099; 9636163 AB - The structural and DNA binding behavior is described for an analog of the vnd/NK-2 homeodomain, which contains a single amino acid residue alanine to threonine replacement in position 35 of the homeodomain. Multidimensional nuclear magnetic resonance, circular dichroism, and electrophoretic gel retardation assays were carried out on recombinant 80-aa residue proteins that encompass the wild-type and mutant homeodomains. The mutant A35T vnd/NK-2 homeodomain is unable to adopt a folded conformation free in solution at temperatures down to -5 degreesC in contrast to the behavior of the corresponding wild-type vnd/NK-2 homeodomain, which is folded into a functional three-dimensional structure below 25 degreesC. The A35T vnd/NK-2 binds specifically to the vnd/NK-2 target DNA sequence, but with an affinity that is 50-fold lower than that of the wild-type homeodomain. Although the three-dimensional structure of the mutant A35T vnd/NK-2 in the DNA bound state shows characteristic helix-turn-helix behavior similar to that of the wild-type homeodomain, a notable structural deviation in the mutant A35T analog is observed for the amide proton of leucine-40. The wild-type homeodomain forms an unusual i,i-5 hydrogen bond with the backbone amide oxygen of residue 35. In the A35T mutant this amide proton resonance is shifted upfield by 1.27 ppm relative to the resonance frequency for the wild-type analog, thereby indicating a significant alteration of this i,i-5 hydrogen bond. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Xiang, B AU - Weiler, S AU - Nirenberg, M AU - Ferretti, J A AD - Laboratory of Biophysical Chemistry, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1998/06/23/ PY - 1998 DA - 1998 Jun 23 SP - 7412 EP - 7416 VL - 95 IS - 13 SN - 0027-8424, 0027-8424 KW - Drosophila Proteins KW - 0 KW - Homeodomain Proteins KW - Transcription Factors KW - vnd protein, Drosophila KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Drosophila melanogaster -- embryology KW - Animals KW - Drosophila melanogaster -- genetics KW - DNA -- metabolism KW - Temperature KW - Circular Dichroism KW - Amino Acid Sequence KW - Magnetic Resonance Spectroscopy KW - Mutagenesis, Site-Directed KW - Protein Folding KW - Molecular Sequence Data KW - Genes, Lethal KW - Amino Acid Substitution KW - Protein Conformation KW - Homeodomain Proteins -- genetics KW - Homeodomain Proteins -- metabolism KW - Mutation KW - Homeodomain Proteins -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79955099?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Structural+basis+of+an+embryonically+lethal+single+Ala+--%26gt%3B+Thr+mutation+in+the+vnd%2FNK-2+homeodomain.&rft.au=Xiang%2C+B%3BWeiler%2C+S%3BNirenberg%2C+M%3BFerretti%2C+J+A&rft.aulast=Xiang&rft.aufirst=B&rft.date=1998-06-23&rft.volume=95&rft.issue=13&rft.spage=7412&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 - 1998-08-06 N1 - Date created - 1998-08-06 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Mech Dev. 1997 May;63(2):187-98 [9203141] Biochemistry. 1997 May 6;36(18):5372-80 [9154919] Neuron. 1997 Jul;19(1):27-37 [9247261] Hum Mutat. 1997;10(3):207-11 [9298820] J Biol Chem. 1998 May 1;273(18):10994-1000 [9556579] Genetics. 1983 Jul;104(3):433-48 [6411520] Cell. 1989 Nov 3;59(3):573-80 [2572329] Proc Natl Acad Sci U S A. 1989 Oct;86(20):7716-20 [2573058] Neuron. 1990 Jul;5(1):81-9 [2114885] EMBO J. 1990 Oct;9(10):3085-92 [1976507] Cell. 1990 Nov 2;63(3):579-90 [1977522] Cell. 1991 Nov 1;67(3):517-28 [1682054] Methods Enzymol. 1991;208:103-17 [1779832] J Biomol NMR. 1993 Mar;3(2):185-204 [8477186] Development. 1994 Jun;120(6):1517-24 [8050360] Biochemistry. 1994 Dec 20;33(50):15053-60 [7999763] Ann N Y Acad Sci. 1995 Jun 30;758:224-42 [7625694] EMBO J. 1995 Jul 17;14(14):3487-95 [7628450] J Mol Biol. 1995 Aug 11;251(2):297-307 [7643404] Dev Biol. 1995 Oct;171(2):306-16 [7556915] Science. 1995 Oct 13;270(5234):262-9 [7569974] J Biomol NMR. 1995 Nov;6(3):277-93 [8520220] Nat Genet. 1996 Aug;13(4):417-21 [8696335] Nature. 1996 Nov 28;384(6607):327-33 [8934515] Hum Mol Genet. 1996 Dec;5(12):1915-20 [8968743] Nat Genet. 1997 Jan;15(1):106-10 [8988180] Hum Hered. 1997 Jan-Feb;47(1):38-41 [9017978] Nat Genet. 1997 Feb;15(2):179-80 [9020844] Genes Dev. 1997 Mar 15;11(6):726-37 [9087427] Genetics. 1997 Jul;146(3):939-49 [9215898] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mortality in neonatal rats is increased by moderate prenatal exposure to some monoamine reuptake inhibitors. A brief review. AN - 80008978; 9668441 JF - Annals of the New York Academy of Sciences AU - Sparenborg, S AD - Pharmacology & Toxicology Branch, National Institutes of Health, Rockville, Maryland 20857, USA. ss292q@nih.gov Y1 - 1998/06/21/ PY - 1998 DA - 1998 Jun 21 SP - 423 EP - 426 VL - 846 SN - 0077-8923, 0077-8923 KW - Adrenergic Uptake Inhibitors KW - 0 KW - Dopamine Uptake Inhibitors KW - Serotonin Uptake Inhibitors KW - Norepinephrine KW - X4W3ENH1CV KW - Index Medicus KW - Rats KW - Animals, Newborn KW - Animals KW - Death KW - Norepinephrine -- metabolism KW - Female KW - Pregnancy KW - Dopamine Uptake Inhibitors -- toxicity KW - Adrenergic Uptake Inhibitors -- toxicity KW - Serotonin Uptake Inhibitors -- toxicity KW - Prenatal Exposure Delayed Effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80008978?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mortality+in+neonatal+rats+is+increased+by+moderate+prenatal+exposure+to+some+monoamine+reuptake+inhibitors.+A+brief+review.&rft.au=Sparenborg%2C+S&rft.aulast=Sparenborg&rft.aufirst=S&rft.date=1998-06-21&rft.volume=846&rft.issue=&rft.spage=423&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 - 1998-07-31 N1 - Date created - 1998-07-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Binding of c-Raf1 kinase to a conserved acidic sequence within the carboxyl-terminal region of the HIV-1 Nef protein. AN - 79939175; 9624170 AB - Nef is a membrane-associated cytoplasmic phosphoprotein that is well conserved among the different human (HIV-1 and HIV-2) and simian immunodeficiency viruses and has important roles in down-regulating the CD4 receptor and modulating T-cell signaling pathways. The ability to modulate T-cell signaling pathways suggests that Nef may physically interact with T-cell signaling proteins. In order to identify Nef binding proteins and map their site(s) of interaction, we targeted a highly conserved acidic sequence at the carboxyl-terminal region of Nef sharing striking similarity with an acidic sequence at the c-Raf1-binding site within the Ras effector region. Here, we used deletion and site-specific mutagenesis to generate mutant Nef proteins fused to bacterial glutathione S-transferase in in vitro precipitation assays and immunoblot analysis to map the specific interaction between the HIV-1LAI Nef and c-Raf1 to a conserved acidic sequence motif containing the core sequence Asp-Asp-X-X-X-Glu (position 174-179). Significantly, we demonstrate that substitution of the nonpolar glycine residue for either or both of the conserved negatively charged aspartic acid residues at positions 174 and 175 in the full-length recombinant Nef protein background completely abrogated binding of c-Raf1 in vitro. In addition, lysates from a permanent CEM T-cell line constitutively expressing the native HIV-1 Nef protein was used to coimmunoprecipitate a stable Nef-c-Raf1 complex, suggesting that molecular interactions between Nef and c-Raf1, an important downstream transducer of cell signaling through the c-Raf1-MAP kinase pathway, occur in vivo. This interaction may account for the Nef-induced perturbations of T-cell signaling and activation pathways in vitro and in vivo. JF - The Journal of biological chemistry AU - Hodge, D R AU - Dunn, K J AU - Pei, G K AU - Chakrabarty, M K AU - Heidecker, G AU - Lautenberger, J A AU - Samuel, K P AD - Laboratory of Leukocyte Biology, NCI-Frederick Cancer Research and Development Center, Frederick, Maryland 21702, USA. Y1 - 1998/06/19/ PY - 1998 DA - 1998 Jun 19 SP - 15727 EP - 15733 VL - 273 IS - 25 SN - 0021-9258, 0021-9258 KW - Gene Products, nef KW - 0 KW - nef Gene Products, Human Immunodeficiency Virus KW - Proto-Oncogene Proteins c-raf KW - EC 2.7.11.1 KW - Index Medicus KW - AIDS/HIV KW - Mutagenesis, Site-Directed KW - Tumor Cells, Cultured KW - Peptide Mapping KW - Conserved Sequence KW - Humans KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Binding Sites -- genetics KW - Amino Acid Substitution KW - Gene Products, nef -- metabolism KW - Gene Products, nef -- genetics KW - Proto-Oncogene Proteins c-raf -- metabolism KW - HIV-1 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79939175?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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+c-Raf1+kinase+to+a+conserved+acidic+sequence+within+the+carboxyl-terminal+region+of+the+HIV-1+Nef+protein.&rft.au=Hodge%2C+D+R%3BDunn%2C+K+J%3BPei%2C+G+K%3BChakrabarty%2C+M+K%3BHeidecker%2C+G%3BLautenberger%2C+J+A%3BSamuel%2C+K+P&rft.aulast=Hodge&rft.aufirst=D&rft.date=1998-06-19&rft.volume=273&rft.issue=25&rft.spage=15727&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 - 1998-07-09 N1 - Date created - 1998-07-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phospholipid- and GTP-dependent activation of cholera toxin and phospholipase D by human ADP-ribosylation factor-like protein 1 (HARL1). AN - 79937821; 9624189 AB - ADP-ribosylation factors (ARFs), 20-kDa guanine nucleotide-binding proteins named for their ability to activate cholera toxin (CT) ADP-ribosyltransferase activity, have a critical role in vesicular transport and activate a phospholipase D (PLD) isoform. Although ARF-like (ARL) proteins are very similar in sequence to ARFs, they were initially believed not to activate CT or PLD. mRNA for human ARL1 (hARL1), which is 57% identical in amino acid sequence to hARF1, is present in all tissues, with the highest amounts in kidney and pancreas and barely detectable amounts in brain. Relative amounts of hARL1 protein were similar to mRNA levels. Purified hARL1 (rARL1) synthesized in Escherichia coli had less activity toward PLD than did rARF1, although PLD activation by both proteins was guanosine guanosine 5'-(gamma-thio)triphosphate (GTPgammaS)-dependent. ARL1 stimulation of CT-catalyzed ADP-ribosylation was considerably less than that by rARF1 and was phospholipid dependent. GTPgammaS-binding by rARL1 was also phospholipid- and detergent-dependent, and in assays containing phosphatidylserine, was greater than that by rARF1. In vitro, the activities of rARL1 and rARF1 are similar. Rather than being a member of a separate subfamily, hARL1, which activates PLD and CT in a phospholipiddependent manner, appears to be part of a continuum of ARF family proteins. JF - The Journal of biological chemistry AU - Hong, J X AU - Lee, F J AU - Patton, W A AU - Lin, C Y AU - Moss, J AU - Vaughan, M AD - Pulmonary-Critical Care Medicine Branch, NHLBI, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/06/19/ PY - 1998 DA - 1998 Jun 19 SP - 15872 EP - 15876 VL - 273 IS - 25 SN - 0021-9258, 0021-9258 KW - Membrane Proteins KW - 0 KW - Phospholipids KW - Adenosine Diphosphate Ribose KW - 20762-30-5 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 - Poly(ADP-ribose) Polymerases KW - EC 2.4.2.30 KW - Phospholipase D KW - EC 3.1.4.4 KW - ADP-ribosylation factor related proteins KW - EC 3.6.1.- KW - GTP Phosphohydrolases KW - ADP-Ribosylation Factors KW - EC 3.6.5.2 KW - Index Medicus KW - Enzyme Activation KW - Humans KW - Brain Chemistry KW - In Vitro Techniques KW - Guanosine 5'-O-(3-Thiotriphosphate) -- metabolism KW - Tissue Distribution KW - Poly(ADP-ribose) Polymerases -- metabolism KW - Catalysis KW - Phospholipase D -- metabolism KW - Membrane Proteins -- metabolism KW - GTP Phosphohydrolases -- metabolism KW - Phospholipids -- metabolism KW - Adenosine Diphosphate Ribose -- metabolism KW - Guanosine Triphosphate -- metabolism KW - Cholera Toxin -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79937821?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Phospholipid-+and+GTP-dependent+activation+of+cholera+toxin+and+phospholipase+D+by+human+ADP-ribosylation+factor-like+protein+1+%28HARL1%29.&rft.au=Hong%2C+J+X%3BLee%2C+F+J%3BPatton%2C+W+A%3BLin%2C+C+Y%3BMoss%2C+J%3BVaughan%2C+M&rft.aulast=Hong&rft.aufirst=J&rft.date=1998-06-19&rft.volume=273&rft.issue=25&rft.spage=15872&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 - 1998-07-09 N1 - Date created - 1998-07-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The NIMH multisite HIV prevention trial: Reducing HIV sexual risk behavior AN - 213554659; 9632382; 03783771 AB - The efficacy of a behavioral intervention to reduce human immunodeficiency virus (HIV) risk behaviors was tested in a randomized, controlled trial with three high-risk populations at 37 clinics from seven sites across the United States. Compared with the 1855 individuals in the control condition, the 1851 participants assigned to a small-group, seven-session HIV risk reduction program reported fewer unprotected sexual acts, had higher levels of condom use, and were more likely to use condoms consistently over a 12-month follow-up period. On the basis of clinical record review, no difference in overall sexually transmitted disease (STD) reinfection rate was found between intervention and control condition participants. However, among men recruited from STD clinics, those assigned to the intervention condition had a gonorrhea incidence rate one-half that of those in the control condition. Intervention condition participants also reported fewer STD symptoms over the 12-month follow-up period. Study outcomes suggest that behavioral interventions can reduce HIV-related sexual risk behavior among low-income women and men served in public health settings. Studies that test strategies for reducing sexual risk behavior over longer periods of time are needed, especially with populations that remain most vulnerable to HIV infection. JF - Science AU - The National Institute of Mental Health (NIMH) Multisite HIV Prevention Trial Group AD - The National Institute of Mental Health (NIMH) Multisite HIV Prevention Trial Group Y1 - 1998/06/19/ PY - 1998 DA - 1998 Jun 19 SP - 1889 EP - 94 CY - Washington PB - The American Association for the Advancement of Science VL - 280 IS - 5371 SN - 00368075 KW - Technology: Comprehensive Works KW - Human immunodeficiency virus KW - HIV KW - Clinical trials KW - Medical research KW - Sexual behavior KW - Sex Behavior KW - HIV Infections -- prevention control KW - Health Behavior KW - Health Education UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/213554659?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthcompleteshell&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Science&rft.atitle=The+NIMH+multisite+HIV+prevention+trial%3A+Reducing+HIV+sexual+risk+behavior&rft.au=The+National+Institute+of+Mental+Health+%28NIMH%29+Multisite+HIV+Prevention+Trial+Group&rft.aulast=The+National+Institute+of+Mental+Health+%28NIMH%29+Multisite+HIV+Prevention+Trial+Group&rft.aufirst=&rft.date=1998-06-19&rft.volume=280&rft.issue=5371&rft.spage=1889&rft.isbn=&rft.btitle=&rft.title=Science&rft.issn=00368075&rft_id=info:doi/ LA - English DB - ProQuest Central; ProQuest Environmental Science Collection N1 - Copyright - Copyright American Association for the Advancement of Science Jun 19, 1998 N1 - Last updated - 2010-06-08 N1 - CODEN - SCIEAS ER - TY - JOUR T1 - Disruption of redox homeostasis in the transforming growth factor- alpha /c-myc transgenic mouse model of accelerated hepatocarcinogenesis AN - 16450418; 4348464 AB - In previous studies we have demonstrated that transforming growth factor (TGF)- alpha /c-myc double transgenic mice exhibit an enhanced rate of cell proliferation, accumulate extensive DNA damage, and develop multiple liver tumors between 4 and 8 months of age. To clarify the biochemical events that may be responsible for the genotoxic and carcinogenic effects observed in this transgenic model, several parameters of redox homeostasis in the liver were examined prior to development of hepatic tumors. By 2 months of age, production of reactive oxygen species, determined by the peroxidation-sensitive fluorescent dye, 2',7'-dichlorofluorescin diacetate, was significantly elevated in TGF- alpha /c-myc transgenic hepatocytes versus either wild type or c-myc single transgenic cells, and occurred in parallel with an increase in lipid peroxidation. Concomitantly with a rise in oxidant levels, antioxidant defenses were decreased, including total glutathione content and the activity of glutathione peroxidase, whereas thioredoxin reductase activity was not changed. However, hepatic tumors which developed in TGF- alpha /c-myc mice exhibited an increase in thioredoxin reductase activity and a very low activity of glutathione peroxidase. Furthermore, specific deletions were detected in mtDNA as early as 5 weeks of age in the transgenic mice. These data provide experimental evidence that co-expression of TGF- alpha and c-myc transgenes in mouse liver promotes overproduction of reactive oxygen species and thus creates an oxidative stress environment. This phenomenon may account for the massive DNA damage and acceleration of hepatocarcinogenesis observed in the TGF- alpha /c-myc mouse model. JF - Journal of Biological Chemistry AU - Factor, V M AU - Kiss, A AU - Woitach, J T AU - Wirth, P J AU - Thorgeirsson, S S AD - 37 Convent Drive MSC4255, Bldg. 37, Rm. 3C28, National Cancer Institute, NIH, Bethesda, MD 20892-4255, USA, snorri_thorgeirsson@nih.gov Y1 - 1998/06/19/ PY - 1998 DA - 1998 Jun 19 SP - 15846 EP - 15853 VL - 273 IS - 25 SN - 0021-9258, 0021-9258 KW - c-Myc gene KW - c-myc gene KW - hepatocarcinogenesis KW - redox homeostasis KW - transforming growth factor- alpha KW - Biotechnology and Bioengineering Abstracts; Genetics Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - G 07397:Rodentia (mice) KW - W3 33056:Animal models of human disease KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16450418?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Biological+Chemistry&rft.atitle=Disruption+of+redox+homeostasis+in+the+transforming+growth+factor-+alpha+%2Fc-myc+transgenic+mouse+model+of+accelerated+hepatocarcinogenesis&rft.au=Factor%2C+V+M%3BKiss%2C+A%3BWoitach%2C+J+T%3BWirth%2C+P+J%3BThorgeirsson%2C+S+S&rft.aulast=Factor&rft.aufirst=V&rft.date=1998-06-19&rft.volume=273&rft.issue=25&rft.spage=15846&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Bloodstream- versus tick-associated variants of a relapsing fever bacterium AN - 16438974; 4333706 AB - The relapsing fever spirochete, Borrelia hermsii, alternates infections between a mammal and a tick vector. Whether the spirochete changes phenotypically in the different hosts was examined by allowing the tick vector Ornithodoros hermsi to feed on mice infected with serotype 7 or serotype 8 of B. hermisii. Upon infection of ticks, the spirochetal serotype-specific variable major proteins (Vmps) 7 and 8 became undetectable and were replaced by Vmp33. This swtich from a bloodstream- to tick-associated phenotype could be induced in culture by a decrease in temperature. After tick-bite transmission back to mice, the process was reversed and the spirochetes resumed expression of the same Vmp present in the previous infectious blood meal. JF - Science (Washington) AU - Schwan, T G AU - Hinnebusch, B J AD - Lab. Microb. Struct. and Function, Rocky Mt. Lab., Natl. Inst. Allergy and Infect. Dis., NIH, Hamilton, MT 59840, USA, tom_schwan@nih.gov Y1 - 1998/06/19/ PY - 1998 DA - 1998 Jun 19 SP - 1938 EP - 1940 PB - American Association for the Advancement of Science VL - 280 IS - 5371 SN - 0036-8075, 0036-8075 KW - Acari KW - Vmp33 protein KW - Vmp7 protein KW - Vmp8 protein KW - mice KW - Entomology Abstracts; Microbiology Abstracts B: Bacteriology KW - J 02855:Human Bacteriology: Others KW - J 02870:Invertebrate bacteriology KW - Z 05206:Medical & veterinary entomology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16438974?accountid=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=Experimental+and+clinical+psychopharmacology&rft.atitle=Attenuation+of+cocaine-induced+locomotor+activity+by+butyrylcholinesterase.&rft.au=Carmona%2C+G+N%3BSchindler%2C+C+W%3BShoaib%2C+M%3BJufer%2C+R%3BCone%2C+E+J%3BGoldberg%2C+S+R%3BGreig%2C+N+H%3BYu%2C+Q+S%3BGorelick%2C+D+A&rft.aulast=Carmona&rft.aufirst=G&rft.date=1998-08-01&rft.volume=6&rft.issue=3&rft.spage=274&rft.isbn=&rft.btitle=&rft.title=Experimental+and+clinical+psychopharmacology&rft.issn=10641297&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Complementation of mismatch repair gene defects by chromosome transfer. AN - 80032705; 9675233 AB - The study of the multiple functions of mismatch repair genes in humans is being facilitated by the use of human tumor cell lines carrying defined MMR gene mutations. Such cell lines have elevated spontaneous mutation rates and may accumulate mutations in other genes, some of which could be causally related to the phenotypes of these cells. One approach to establish a cause-effect relationship between a MMR gene defect and a phenotype is to determine if that phenotype is reversed when a normal chromosome carrying a wild-type MMR gene is introduced by microcell fusion. This approach has the advantage of presenting the gene in its natural chromosomal environment with normal regulatory controls and at a reasonable dosage. The approach also limits candidate genes to only those encoded by the introduced chromosome and not elsewhere in the genome. Here we review studies demonstrating that hMSH2, hMSH3, hMSH6 and hMLH1 gene defects can each be complemented by transferring human chromosome 2, 5, 2 or 3, respectively. These transfers restore MMR activity, sensitivity to killing by MNNG, stability to microsatellite sequences and low spontaneous HPRT gene mutation rates. Copyright 1998 Elsevier Science B.V. All rights reserved. JF - Mutation research AU - Tindall, K R AU - Glaab, W E AU - Umar, A AU - Risinger, J I AU - Koi, M AU - Barrett, J C AU - Kunkel, T A AD - Laboratory of Environmental Carcinogenesis and Mutagenesis, National Institute of Environmental Health Sciences, P.O. Box 12233, Research Triangle Park, NC 27709, USA. Y1 - 1998/06/18/ PY - 1998 DA - 1998 Jun 18 SP - 15 EP - 22 VL - 402 IS - 1-2 SN - 0027-5107, 0027-5107 KW - Nucleic Acid Heteroduplexes KW - 0 KW - Index Medicus KW - Cell Fusion KW - Humans KW - Hybrid Cells KW - Mutation KW - DNA Repair -- genetics KW - Chromosomes, Human KW - Genetic Complementation Test UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80032705?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=unknown&rft.jtitle=Federal+News+Service+-+Congressional+Hearing+Prepared+Testimonies&rft.atitle=PREPARED+STATEMENT+OF+THE+HONORABLE+CAROL+M.+BROWNER+ADMINISTRATOR+OF+THE+ENVIRONMENTAL+PROTECTION+AGENCY+BEFORE+THE+SENATE+COMMITTEE+ON+FINANCE+THURSDAY%2C+JANUARY+28%2C+1999&rft.au=&rft.aulast=&rft.aufirst=&rft.date=1999-01-28&rft.volume=&rft.issue=&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Federal+News+Service+-+Congressional+Hearing+Prepared+Testimonies&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-09-01 N1 - Date created - 1998-09-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of Escherichia coli dnaE antimutator mutants on mutagenesis by the base analog N4-aminocytidine. AN - 80028759; 9675236 AB - Previous studies in our laboratory have identified a set of mutations in the Escherichia coli dnaE gene that confer increased accuracy of DNA replication (antimutators). The dnaE gene encodes the polymerase subunit of DNA polymerase III holoenzyme that replicates the E. coli chromosome. Here, we have investigated their effect on mutagenesis by the base analog N4-aminocytidine (4AC). For three different mutational markers, rifampicin resistance, nalidixic acid resistance and lacI forward mutagenesis, the dnaE911 allele reduced 4AC-induced mutagenesis by approximately 2.5-fold, while the dnaE915 allele reduced it by 2.5-, 3.5- and 6.5-fold, respectively. We also investigated the dependence of 4AC mutagenesis on mutations in the MutHLS mismatch repair system and the UvrABC nucleotide excision repair system. The results show that mutagenesis by 4AC is unaffected by defects in either system. The combined results point to the critical role of the DNA polymerase in preventing mutations by base analogs. Copyright 1998 Elsevier Science B.V. All rights reserved. JF - Mutation research AU - Schaaper, R M AU - Dunn, R L AD - Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, P.O. Box 12233, Research Triangle Park, NC 27709, USA. schaaper@niehs.nih.gov Y1 - 1998/06/18/ PY - 1998 DA - 1998 Jun 18 SP - 23 EP - 28 VL - 402 IS - 1-2 SN - 0027-5107, 0027-5107 KW - Antimutagenic Agents KW - 0 KW - Mutagens KW - N(4)-aminocytidine KW - 57294-74-3 KW - Cytidine KW - 5CSZ8459RP KW - DNA Polymerase III KW - EC 2.7.7.- KW - DNA polymerase III, alpha subunit KW - Index Medicus KW - Alleles KW - Dose-Response Relationship, Drug KW - Chromosomes, Bacterial KW - DNA Polymerase III -- genetics KW - Mutagens -- toxicity KW - Escherichia coli -- genetics KW - Cytidine -- toxicity KW - Mutation KW - Cytidine -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80028759?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Effect+of+Escherichia+coli+dnaE+antimutator+mutants+on+mutagenesis+by+the+base+analog+N4-aminocytidine.&rft.au=Schaaper%2C+R+M%3BDunn%2C+R+L&rft.aulast=Schaaper&rft.aufirst=R&rft.date=1998-06-18&rft.volume=402&rft.issue=1-2&rft.spage=23&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 - 1998-09-01 N1 - Date created - 1998-09-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Antimutagenic and anticarcinogenic potentials of some Thai vegetables. AN - 80027814; 9675301 AB - Fifteen kinds of commonly consumed Thai vegetables were sequentially extracted with hexane, chloroform and methanol, and then tested for antimutagenic activities against direct-acting (AF-2 and NaN3) and indirect-acting (AFB1 and B(a)P) mutagens using Ames' Salmonella mutagenicity test with Salmonella typhimurium TA100 as tester strain. It was found that only the methanol extract of neem leaves contain weak antimutagen inhibiting the mutagenicities of both direct-acting mutagens. Interestingly, all vegetables studied were found to contain chemical compounds, mainly nonpolar ones, capable of inhibiting the mutagenicity of AFB1, while only some vegetables contain chemical compounds capable of inhibiting the mutagenicity of B(a)P, which is also an indirect-acting mutagen. Studies on anticarcinogenic potentials demonstrated that Thai bitter gourd fruits, but not sweet basil leaves, at the concentration of 6.25% and 12.5% in the diet, partially inhibited DMBA-induced mammary gland carcinogenesis in female Sprague-Dawley rats when fed to the animals 2 weeks prior to DMBA. Results in the present study therefore demonstrated that most Thai vegetables contain antimutagens inhibiting the mutagenicity of some indirect-acting mutagen, particularly AFB1. The mechanism of their antimutagenicity may probably be the inhibition of the activity of metabolic-activating enzymes in rat liver homogenates. Very interestingly, our results clearly reveal that Thai bitter gourd fruits, which possess Phase II enzymes inducing property, as well as the ability to reduce Phase I enzyme activities in rat liver, contain some anticarcinogens or chemopreventive agents. However, sweet basil leaves that possess both Phase I and Phase II enzyme-inducing properties may not contain any anticarcinogen, at least against DMBA-induced mammary gland carcinogenesis. Copyright 1998 Elsevier Science B.V. All rights reserved. JF - Mutation research AU - Kusamran, W R AU - Tepsuwan, A AU - Kupradinun, P AD - Biochemistry and Chemical Carcinogenesis Section, Research Division, National Cancer Institute, Rama VI Road, Bangkok 10400, Thailand. waroran@health.moph.go.th Y1 - 1998/06/18/ PY - 1998 DA - 1998 Jun 18 SP - 247 EP - 258 VL - 402 IS - 1-2 SN - 0027-5107, 0027-5107 KW - Anticarcinogenic Agents KW - 0 KW - Antimutagenic Agents KW - Aniline Hydroxylase KW - EC 1.14.14.- KW - Aminopyrine N-Demethylase KW - EC 1.5.3.- KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Mutagenicity Tests KW - Liver -- enzymology KW - Liver -- drug effects KW - Thailand KW - Aminopyrine N-Demethylase -- antagonists & inhibitors KW - Mammary Neoplasms, Experimental -- prevention & control KW - Salmonella typhimurium -- genetics KW - Female KW - Aniline Hydroxylase -- antagonists & inhibitors KW - Anticarcinogenic Agents -- analysis KW - Vegetables -- chemistry KW - Antimutagenic Agents -- pharmacology KW - Anticarcinogenic Agents -- pharmacology KW - Antimutagenic Agents -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80027814?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Antimutagenic+and+anticarcinogenic+potentials+of+some+Thai+vegetables.&rft.au=Kusamran%2C+W+R%3BTepsuwan%2C+A%3BKupradinun%2C+P&rft.aulast=Kusamran&rft.aufirst=W&rft.date=1998-06-18&rft.volume=402&rft.issue=1-2&rft.spage=247&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 - 1998-09-01 N1 - Date created - 1998-09-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Frequent downregulation of the KAI1(CD82) metastasis suppressor protein in human cancer cell lines. AN - 80009854; 9671393 AB - KAI1 is a metastasis suppressor gene on human chromosome 11p11.2 that encodes a glycoprotein of the transmembrane four superfamily. Reduced KAI1 expression associates with malignant progression of human prostatic, lung and pancreatic cancers, but the role of KAI1 protein in the malignant progression of other human cancers remains to be elucidated. We analysed KAI1 protein in normal and cancer cells of the prostate, ovary, bladder, endometrium, lung and melanocytes by Western blot to determine if KAI1 may be involved in multiple cancers. We also investigated the relationship of KAI1 expression and two other transmembrane four superfamily proteins, CD81 and CD9, in the cells. We found that KAI1 protein was downregulated in 31/42 of the cancer cell lines analysed. Alternatively, some ovarian, bladder and endometrial cells had distinct, heterogeneous KAI1 protein band patterns in Western blots that were due primarily to N-linked glycosylation. Most of the cancer cells expressed two other transmembrane four superfamily proteins, CD81 and CD9. Downregulation of KAI1 protein may be an indicator of metastatic potential in cancers of urogenital, gynecological, and pulmonary origin and in melanomas. KAI1 may also have post-translational modifications specific to tissue type or malignant progression. JF - Oncogene AU - White, A AU - Lamb, P W AU - Barrett, J C AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 1998/06/18/ PY - 1998 DA - 1998 Jun 18 SP - 3143 EP - 3149 VL - 16 IS - 24 SN - 0950-9232, 0950-9232 KW - Antigens, CD KW - 0 KW - Antigens, CD81 KW - Antigens, CD82 KW - Antigens, CD9 KW - CD81 protein, human KW - CD82 protein, human KW - CD9 protein, human KW - Membrane Glycoproteins KW - Membrane Proteins KW - Proto-Oncogene Proteins KW - Index Medicus KW - Humans KW - Prostate -- metabolism KW - Prognosis KW - Neoplasms -- genetics KW - Neoplasm Metastasis -- genetics KW - Neoplasms -- pathology KW - Tumor Cells, Cultured KW - Cells, Cultured KW - Prostate -- cytology KW - Male KW - Neoplasms -- immunology KW - Down-Regulation KW - Antigens, CD -- metabolism KW - Antigens, CD -- genetics KW - Antigens, CD -- immunology KW - Membrane Glycoproteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80009854?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Frequent+downregulation+of+the+KAI1%28CD82%29+metastasis+suppressor+protein+in+human+cancer+cell+lines.&rft.au=White%2C+A%3BLamb%2C+P+W%3BBarrett%2C+J+C&rft.aulast=White&rft.aufirst=A&rft.date=1998-06-18&rft.volume=16&rft.issue=24&rft.spage=3143&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-07-29 N1 - Date created - 1998-07-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Three-dimensional quantitative structure-activity relationship study of nonsteroidal estrogen receptor ligands using the comparative molecular field analysis/cross-validated r2-guided region selection approach. AN - 79948180; 9632359 AB - A newly developed comparative molecular field analysis (CoMFA) technique, the cross-validated r2-guided region selection (CoMFA/q2-GRS) method, has been used to build a quantitative structure-activity relationship (3D-QSAR) for nonsteroidal estrogen receptor (ER) ligands. Ligands included in this study belong to a series of diethylstilbestrol (DES) and indenestrol analogues whose affinities for the mouse ER (mER) have been determined in our laboratory. The final model utilized 30 compounds and yielded a q2GRS (cross-validated r2, guided region selection) of 0.796, as compared to a q2 of 0.720 for conventional CoMFA, with a standard error of prediction of 0.594 at 3 principal components. This model was used to visualize steric and electrostatic features of the ligands that correspond with ER binding affinity. Results obtained from the CoMFA steric and electrostatic plots of this model have also been compared to information from the ER binding affinities of substituted estradiol analogues. This is in an effort to determine structural features of compounds in the CoMFA analysis that may correspond to those of the estradiol analogues and to further clarify the mode of binding of nonsteroidal ER ligands. JF - Journal of medicinal chemistry AU - Sadler, B R AU - Cho, S J AU - Ishaq, K S AU - Chae, K AU - Korach, K S AD - Laboratory of Reproductive and Developmental Biology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 1998/06/18/ PY - 1998 DA - 1998 Jun 18 SP - 2261 EP - 2267 VL - 41 IS - 13 SN - 0022-2623, 0022-2623 KW - Estrogens, Non-Steroidal KW - 0 KW - Indenes KW - Ligands KW - Receptors, Estrogen KW - indenestrol KW - 4A464K3BSI KW - Diethylstilbestrol KW - 731DCA35BT KW - Index Medicus KW - Animals KW - Diethylstilbestrol -- metabolism KW - Diethylstilbestrol -- chemistry KW - Mice KW - Diethylstilbestrol -- analogs & derivatives KW - Molecular Conformation KW - Indenes -- chemistry KW - Indenes -- metabolism KW - Structure-Activity Relationship KW - Models, Molecular KW - Estrogens, Non-Steroidal -- chemistry KW - Receptors, Estrogen -- metabolism KW - Estrogens, Non-Steroidal -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79948180?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+medicinal+chemistry&rft.atitle=Three-dimensional+quantitative+structure-activity+relationship+study+of+nonsteroidal+estrogen+receptor+ligands+using+the+comparative+molecular+field+analysis%2Fcross-validated+r2-guided+region+selection+approach.&rft.au=Sadler%2C+B+R%3BCho%2C+S+J%3BIshaq%2C+K+S%3BChae%2C+K%3BKorach%2C+K+S&rft.aulast=Sadler&rft.aufirst=B&rft.date=1998-06-18&rft.volume=41&rft.issue=13&rft.spage=2261&rft.isbn=&rft.btitle=&rft.title=Journal+of+medicinal+chemistry&rft.issn=00222623&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-07-09 N1 - Date created - 1998-07-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Trends in HIV incidence among young adults in the United States. AN - 79949115; 9634261 AB - Behaviors that result in potential exposure to human immunodeficiency virus (HIV) usually begin in adolescence or young adulthood, but trends in HIV incidence in young people remain unclear. To estimate trends in HIV incidence in teenagers and young adults. Back-calculation of past HIV incidence in persons born between 1960 and 1974 using US national acquired immunodeficiency syndrome (AIDS) incidence data and estimates of the distribution of times between HIV infection and AIDS. Incidence and prevalence of HIV in 1988 and 1993 in persons aged 20 and 25 years, respectively, in each of those years. As of January 1993, about 22000 men and 11000 women aged 18 to 22 years were living with HIV infection in the United States. Homosexual contact was the leading route of infection among young men. Heterosexual contact was the leading route of infection among young women. The HIV incidence attributed to homosexual contact or injection drug use decreased among persons aged 20 and 25 years between 1988 and 1993, but HIV incidence attributed to heterosexual contact was stable or increasing. Notably, in men aged 20 and 25 years, HIV prevalence declined by about 50% in white men but was relatively stable in black and Hispanic men. In contrast, HIV prevalence in women aged 20 and 25 years rose by 36% and 45%, respectively, because of increasing heterosexual transmission. Overall, HIV prevalence in persons aged 20 and 25 years declined by only 14% between 1988 and 1993. In young persons, HIV incidence in homosexual men and injection drug users was slowing by 1993; this favorable trend was offset by increasing heterosexual transmission, especially in minorities. JF - JAMA AU - Rosenberg, P S AU - Biggar, R J AD - Biostatistics Branch, National Cancer Institute, Bethesda, MD 20892, USA. philip_rosenberg@nih.gov Y1 - 1998/06/17/ PY - 1998 DA - 1998 Jun 17 SP - 1894 EP - 1899 VL - 279 IS - 23 SN - 0098-7484, 0098-7484 KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Homosexuality, Male KW - Humans KW - African Americans -- statistics & numerical data KW - European Continental Ancestry Group -- statistics & numerical data KW - Hispanic Americans -- statistics & numerical data KW - Adult KW - Incidence KW - Adolescent KW - United States -- epidemiology KW - Female KW - Male KW - Prevalence KW - Substance Abuse, Intravenous KW - HIV Infections -- transmission KW - HIV Infections -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79949115?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Trends+in+HIV+incidence+among+young+adults+in+the+United+States.&rft.au=Rosenberg%2C+P+S%3BBiggar%2C+R+J&rft.aulast=Rosenberg&rft.aufirst=P&rft.date=1998-06-17&rft.volume=279&rft.issue=23&rft.spage=1894&rft.isbn=&rft.btitle=&rft.title=JAMA&rft.issn=00987484&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-06-26 N1 - Date created - 1998-06-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Failure to down regulate NMDA receptors in the striatum and nucleus accumbens associated with neuroleptic-induced dyskinesia. AN - 80041912; 9689480 AB - The syndrome of vacuous chewing movements (VCMs) in rats is similar in many respects to tardive dyskinesia (TD) in humans. Both syndromes are characterized by delayed onset of persistent orofacial dyskinesias in a sub-group of subjects chronically treated with neuroleptics. Using the rat model, we examined the role of NMDA receptor-mediated corticostriatal neurotransmission in the expression of VCMs. Rats were treated for 36 weeks with haloperidol decanoate or vehicle and then withdrawn for an additional 28 weeks. Chronic persistent VCMs were induced in one subgroup of treated animals (+VCM), but not in another group (-VCM). Rats from +VCM, -VCM groups and vehicle-treated controls were selected for post mortem studies (n = 12 to 14 per group). NMDA receptor levels were assessed using [3H]-MK-801 binding in sections from the mid-striatum and nucleus accumbens. Chronic haloperidol treatment produced a marked reduction of NMDA receptor binding levels throughout the striatum and nucleus accumbens. Post hoc comparisons demonstrated that -VCM rats had lower NMDA receptor binding levels than +VCM and vehicle-treated controls. Ventromedial striatum and nucleus accumbens core were the most affected areas. These findings suggest that down-regulation of striatal NMDA receptor binding levels may protect against the expression of neuroleptic-induced dyskinesia. JF - Brain research AU - Hamid, E H AU - Hyde, T M AU - Baca, S M AU - Egan, M F AD - Clinical Research Services, National Institute of Mental Health, St. Elizabeth's Hospital, Washington, DC, USA. Y1 - 1998/06/15/ PY - 1998 DA - 1998 Jun 15 SP - 291 EP - 295 VL - 796 IS - 1-2 SN - 0006-8993, 0006-8993 KW - Antipsychotic Agents KW - 0 KW - Excitatory Amino Acid Antagonists KW - Receptors, N-Methyl-D-Aspartate KW - Dizocilpine Maleate KW - 6LR8C1B66Q KW - haloperidol decanoate KW - AC20PJ4101 KW - Haloperidol KW - J6292F8L3D KW - Index Medicus KW - Rats KW - Excitatory Amino Acid Antagonists -- metabolism KW - Animals KW - Rats, Sprague-Dawley KW - Dizocilpine Maleate -- metabolism KW - Mastication -- physiology KW - Synaptic Transmission -- physiology KW - Male KW - Dyskinesia, Drug-Induced -- metabolism KW - Down-Regulation -- physiology KW - Nucleus Accumbens -- drug effects KW - Corpus Striatum -- metabolism KW - Nucleus Accumbens -- metabolism KW - Corpus Striatum -- drug effects KW - Receptors, N-Methyl-D-Aspartate -- metabolism KW - Dyskinesia, Drug-Induced -- physiopathology KW - Haloperidol -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80041912?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Failure+to+down+regulate+NMDA+receptors+in+the+striatum+and+nucleus+accumbens+associated+with+neuroleptic-induced+dyskinesia.&rft.au=Hamid%2C+E+H%3BHyde%2C+T+M%3BBaca%2C+S+M%3BEgan%2C+M+F&rft.aulast=Hamid&rft.aufirst=E&rft.date=1998-06-15&rft.volume=796&rft.issue=1-2&rft.spage=291&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 - 1998-10-29 N1 - Date created - 1998-10-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A comparison of one-sided methods to identify significant individual outcomes in a multiple outcome setting: stepwise tests or global tests with closed testing. AN - 80013018; 9670413 AB - We compare two approaches to the identification of individual significant outcomes when a comparison of two groups involves multiple outcome variables. The approaches are all designed to control the familywise error rate (FWE) with any subset of the null hypothesis being true (in the strong sense). The first approach is initially to use a global test of the overall hypothesis that the groups are equivalent for all variables, followed by an application of the closed testing algorithm of Marcus, Peritz and Gabriel. The global tests considered here are ordinary least squares (OLS), generalized least squares (GLS), an approximation to a likelihood ratio test (ALR), and a new test based on an approximation to the most powerful similar test for simple alternatives. The second approach is that of stepwise testing, which tests the univariate hypotheses in a specific order with appropriate adjustment to the univariate p-values for multiplicity. The stepwise tests considered include both step-down and step-up tests of a general type, and likewise permutation tests that incorporate the dependence structure of the data. We illustrate the tests with two examples of birth outcomes: a comparison of cocaine-exposed new-borns to control new-borns on neurobehavioural and physical growth variables, and, in a separate study, a comparison of babies born to diabetic mothers and babies born to non-diabetic mothers on minor malformations. After describing the methods and analysing the birth outcome data, we use simulations on Gaussian data to provide guidelines for the use of these procedures in terms of power and computation. JF - Statistics in medicine AU - Troendle, J F AU - Legler, J M AD - Biometry and Mathematical Statistics Branch, National Institute of Child Health and Human Development, Bethesda, MD 20892, USA. Y1 - 1998/06/15/ PY - 1998 DA - 1998 Jun 15 SP - 1245 EP - 1260 VL - 17 IS - 11 SN - 0277-6715, 0277-6715 KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Probability KW - Analysis of Variance KW - Fetus -- drug effects KW - Infant, Newborn -- growth & development KW - Humans KW - Algorithms KW - Congenital Abnormalities -- etiology KW - Infant, Newborn -- physiology KW - Cocaine -- adverse effects KW - Likelihood Functions KW - Pregnancy KW - Computing Methodologies KW - Maternal Age KW - Adult KW - Pregnancy in Diabetics KW - Male KW - Female KW - Outcome Assessment (Health Care) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80013018?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+cell+science&rft.atitle=Localization+of+endogenous+ARF6+to+sites+of+cortical+actin+rearrangement+and+involvement+of+ARF6+in+cell+spreading.&rft.au=Song%2C+J%3BKhachikian%2C+Z%3BRadhakrishna%2C+H%3BDonaldson%2C+J+G&rft.aulast=Song&rft.aufirst=J&rft.date=1998-08-01&rft.volume=111+%28+Pt+15%29&rft.issue=&rft.spage=2257&rft.isbn=&rft.btitle=&rft.title=Journal+of+cell+science&rft.issn=00219533&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-09-28 N1 - Date created - 1998-09-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CONF T1 - Workgroup 3: transgenic and reconstitution models of prostate cancer. AN - 79976103; 9650918 JF - The Prostate AU - Green, J E AU - Greenberg, N M AU - Ashendel, C L AU - Barrett, J C AU - Boone, C AU - Getzenberg, R H AU - Henkin, J AU - Matusik, R AU - Janus, T J AU - Scher, H I Y1 - 1998/06/15/ PY - 1998 DA - 1998 Jun 15 SP - 59 EP - 63 VL - 36 IS - 1 KW - Androgen-Binding Protein KW - 0 KW - probasin KW - Globins KW - 9004-22-2 KW - Index Medicus KW - Genes, bcl-2 KW - Animals KW - Simian virus 40 -- genetics KW - Globins -- genetics KW - Artificial Gene Fusion KW - Androgen-Binding Protein -- genetics KW - Male KW - Models, Genetic KW - Prostatic Neoplasms -- genetics KW - Animals, Genetically Modified UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79976103?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&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=The+Prostate&rft.atitle=Workgroup+3%3A+transgenic+and+reconstitution+models+of+prostate+cancer.&rft.au=Green%2C+J+E%3BGreenberg%2C+N+M%3BAshendel%2C+C+L%3BBarrett%2C+J+C%3BBoone%2C+C%3BGetzenberg%2C+R+H%3BHenkin%2C+J%3BMatusik%2C+R%3BJanus%2C+T+J%3BScher%2C+H+I&rft.aulast=Green&rft.aufirst=J&rft.date=1998-06-15&rft.volume=36&rft.issue=1&rft.spage=59&rft.isbn=&rft.btitle=&rft.title=The+Prostate&rft.issn=02704137&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-07-16 N1 - Date created - 1998-07-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Allelic deletion analysis of the FHIT gene predicts poor survival in non-small cell lung cancer. AN - 79953258; 9635574 AB - The fragile histidine triad (FHIT) gene at chromosome 3p14.2 is a candidate tumor suppressor gene linked to cancers of the lung, breast, colon, pancreas, and head and neck. Reports of frequent allelic deletion and abnormal transcripts in primary lung tumors plus recent evidence that it is targeted by tobacco smoke carcinogens suggest that it plays an important role in lung carcinogenesis. Non-small cell lung carcinoma still maintains a poor 5-year survival rate with the stage of disease at presentation as a major determinant of prognosis. We examined for allelic deletion at the FHIT locus in a series of 106 non-small cell lung carcinomas for which a full clinical, epidemiological, and 5-year survival profile was available. We found an allelic deletion frequency of 38% at one or two intragenic microsatellites. Allelic deletion of FHIT was related to tumor histology with 4 of 20 adenocarcinomas (20%) displaying loss of heterozygosity (LOH) compared with 12 of 22 (55%) nonadenocarcinomas (P = 0.03). We found that 63% of tumors with LOH of FHIT also had p53 missense mutations whereas only 26% with LOH had wild type p53 negative sequence (P = 0.02). We also found a significant trend toward poorer survival in patients with LOH of at least one locus of the FHIT gene (log rank, P = 0.01). This survival correlation is independent of tumor stage, size, histological subtype, degree of differentiation, and p53 mutation status. Our data support the hypothesis that the loss of the FHIT contributes to the molecular pathogenesis of human lung cancer and is an indicator of poor prognosis. JF - Cancer research AU - Burke, L AU - Khan, M A AU - Freedman, A N AU - Gemma, A AU - Rusin, M AU - Guinee, D G AU - Bennett, W P AU - Caporaso, N E AU - Fleming, M V AU - Travis, W D AU - Colby, T V AU - Trastek, V AU - Pairolero, P C AU - Tazelaar, H D AU - Midthun, D E AU - Liotta, L A AU - Harris, C C AD - National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1998/06/15/ PY - 1998 DA - 1998 Jun 15 SP - 2533 EP - 2536 VL - 58 IS - 12 SN - 0008-5472, 0008-5472 KW - Genetic Markers KW - 0 KW - Neoplasm Proteins KW - Proteins KW - fragile histidine triad protein KW - Acid Anhydride Hydrolases KW - EC 3.6.- KW - Index Medicus KW - Microsatellite Repeats -- genetics KW - Genetic Markers -- genetics KW - Alleles KW - Survival Rate KW - Humans KW - Adult KW - Prognosis KW - Chromosomes, Human, Pair 3 -- genetics KW - Aged KW - Middle Aged KW - Male KW - Female KW - Gene Deletion KW - Carcinoma, Non-Small-Cell Lung -- mortality KW - Genes, Tumor Suppressor -- genetics KW - Carcinoma, Non-Small-Cell Lung -- genetics KW - Neoplasm Proteins -- genetics KW - Lung Neoplasms -- genetics KW - Lung Neoplasms -- mortality KW - Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79953258?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Allelic+deletion+analysis+of+the+FHIT+gene+predicts+poor+survival+in+non-small+cell+lung+cancer.&rft.au=Burke%2C+L%3BKhan%2C+M+A%3BFreedman%2C+A+N%3BGemma%2C+A%3BRusin%2C+M%3BGuinee%2C+D+G%3BBennett%2C+W+P%3BCaporaso%2C+N+E%3BFleming%2C+M+V%3BTravis%2C+W+D%3BColby%2C+T+V%3BTrastek%2C+V%3BPairolero%2C+P+C%3BTazelaar%2C+H+D%3BMidthun%2C+D+E%3BLiotta%2C+L+A%3BHarris%2C+C+C&rft.aulast=Burke&rft.aufirst=L&rft.date=1998-06-15&rft.volume=58&rft.issue=12&rft.spage=2533&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 - 1998-07-01 N1 - Date created - 1998-07-01 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Cancer Res 1998 Aug 1;58(15):3488 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Use of cytotoxic agents and cyclosporine in the treatment of autoimmune disease. Part 1: rheumatologic and renal diseases. AN - 79911895; 9625665 AB - When cytotoxic agents were initially introduced, their ability to disrupt nucleic acid and protein synthesis led to their effective use for the treatment of neoplastic disease. During the course of this use, however, it became apparent that these agents also suppress the immune system. This usually unwelcome effect was subsequently studied and beneficially directed toward the treatment of non-neoplastic diseases in which autoimmune mechanisms were considered important to pathogenesis. As a result of these investigations, cytotoxic agents and, more recently, cyclosporine have emerged to become an important part of the therapeutic regimen for many autoimmune diseases. Nonetheless, these medications may still cause treatment-induced illness or even death. It is therefore particularly important to weigh the benefits and risks of cytotoxic therapy when treating a non-neoplastic disease. This two-part Clinical Staff Conference reviews data on the efficacy and toxicity of cytotoxic drugs and cyclosporine in selected autoimmune diseases. Part 1 examines the manner in which these agents have been used to treat rheumatologic and renal diseases. JF - Annals of internal medicine AU - Langford, C A AU - Klippel, J H AU - Balow, J E AU - James, S P AU - Sneller, M C AD - National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1998/06/15/ PY - 1998 DA - 1998 Jun 15 SP - 1021 EP - 1028 VL - 128 IS - 12 Pt 1 SN - 0003-4819, 0003-4819 KW - Immunosuppressive Agents KW - 0 KW - Cyclosporine KW - 83HN0GTJ6D KW - Abridged Index Medicus KW - Index Medicus KW - United States KW - Drug Therapy, Combination KW - Cell Survival -- drug effects KW - Humans KW - Cyclosporine -- adverse effects KW - Cyclosporine -- therapeutic use KW - Autoimmune Diseases -- drug therapy KW - Immunosuppressive Agents -- therapeutic use KW - Rheumatic Diseases -- drug therapy KW - Kidney Diseases -- drug therapy KW - Immunosuppressive Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79911895?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&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=Annals+of+internal+medicine&rft.atitle=Use+of+cytotoxic+agents+and+cyclosporine+in+the+treatment+of+autoimmune+disease.+Part+1%3A+rheumatologic+and+renal+diseases.&rft.au=Langford%2C+C+A%3BKlippel%2C+J+H%3BBalow%2C+J+E%3BJames%2C+S+P%3BSneller%2C+M+C&rft.aulast=Langford&rft.aufirst=C&rft.date=1998-06-15&rft.volume=128&rft.issue=12+Pt+1&rft.spage=1021&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 - 1998-06-10 N1 - Date created - 1998-06-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Promotion of Met-tRNA sub(i) super(M) super(e) super(t) binding to ribosomes by yIF2, a bacterial IF2 homolog in yeast AN - 16521849; 4327217 AB - Delivery of the initiator methionine transfer RNA (Met-tRNA sub(i) super(M) super(e) super(t)) to the ribosome is a key step in the initiation of protein synthesis. Previous results have indicated that this step is catalyzed by the structurally dissimilar translation factors in prokaryotes and eukaryotes--initiation factor 2 (IF2) and eukaryotic initiation factor 2 (eIF2), respectively. A bacterial IF2 homolog has been identified in both eukaryotes and archaea. By using a combination of molecular genetic and biochemical studies, the Saccharomyces cerevisiae IF2 homolog is shown to function in general translation initiation by promoting Met-tRNA sub(i) super(M) super(e) super(t) binding to ribosomes. Thus, the mechanism of protein synthesis in eukaryotes and prokaryotes is more similar than was previously realized. JF - Science (Washington) AU - Choi, Sang Ki AU - Lee, Joon H AU - Zoll, W L AU - Merrick, W C AU - Dever, TE AD - Lab. Eukaryotic Gene Regul., Natl. Inst. Child Health and Hum. Dev., NIH, Bethesda, MD 20892-2716, USA, tdever@box-t.nih.gov Y1 - 1998/06/12/ PY - 1998 DA - 1998 Jun 12 SP - 1757 EP - 1760 PB - American Association for the Advancement of Science VL - 280 IS - 5370 SN - 0036-8075, 0036-8075 KW - budding yeast KW - initiation factor IF-2 KW - initiation factor eIF-2 KW - tRNA fMet KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Biochemistry Abstracts 2: Nucleic Acids KW - A 01002:Acids, amino acids, peptides & proteins KW - N 14420:Binding of tRNA UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16521849?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologya&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Science+%28Washington%29&rft.atitle=Promotion+of+Met-tRNA+sub%28i%29+super%28M%29+super%28e%29+super%28t%29+binding+to+ribosomes+by+yIF2%2C+a+bacterial+IF2+homolog+in+yeast&rft.au=Choi%2C+Sang+Ki%3BLee%2C+Joon+H%3BZoll%2C+W+L%3BMerrick%2C+W+C%3BDever%2C+TE&rft.aulast=Choi&rft.aufirst=Sang&rft.date=1998-06-12&rft.volume=280&rft.issue=5370&rft.spage=1757&rft.isbn=&rft.btitle=&rft.title=Science+%28Washington%29&rft.issn=00368075&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Lessons from the cat: Feline immunodeficiency virus as a tool to develop intervention strategies against human immunodeficiency virus type 1 AN - 16516483; 4341750 AB - In July 1997 the Division of AIDS of the National Institute of Allergy and Infectious Diseases sponsored a workshop entitled "Use of the FIV/Cat Model for Development of Anti-HIV Vaccines and Therapeutics." The purpose of this workshop was to provide a forum for presenting new data arising from FIV research, assess the utility of the FIV/cat model, identify areas applicable to HIV/AIDS research, and solicit input from investigators on scientific gaps that can benefit from additional support. The meeting brought to the fore numerous areas where the FIV/cat model can serve as a valuable tool for developing new therapeutic strategies and vaccine designs applicable to the treatment and prevention of HIV-1 infection. JF - AIDS Research and Human Retroviruses AU - Elder, J H AU - Dean, G A AU - Hoover, E A AU - Hoxie, JA AU - Malim, M H AU - Mathes, L AU - Neil, J C AU - North, T W AU - Sparger, E AU - Tompkins, M B AU - Tompkins, WAF AU - Yamamoto, J AU - Yuhki, N AU - Miller, R H AD - Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA Y1 - 1998/06/10/ PY - 1998 DA - 1998 Jun 10 SP - 797 EP - 801 VL - 14 IS - 9 SN - 0889-2229, 0889-2229 KW - Cats KW - HIV-1 KW - Virology & AIDS Abstracts; Microbiology Abstracts A: Industrial & Applied Microbiology KW - V 22006:AIDS: Other aspects KW - A 01114:Viruses UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16516483?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologya&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=AIDS+Research+and+Human+Retroviruses&rft.atitle=Lessons+from+the+cat%3A+Feline+immunodeficiency+virus+as+a+tool+to+develop+intervention+strategies+against+human+immunodeficiency+virus+type+1&rft.au=Elder%2C+J+H%3BDean%2C+G+A%3BHoover%2C+E+A%3BHoxie%2C+JA%3BMalim%2C+M+H%3BMathes%2C+L%3BNeil%2C+J+C%3BNorth%2C+T+W%3BSparger%2C+E%3BTompkins%2C+M+B%3BTompkins%2C+WAF%3BYamamoto%2C+J%3BYuhki%2C+N%3BMiller%2C+R+H&rft.aulast=Elder&rft.aufirst=J&rft.date=1998-06-10&rft.volume=14&rft.issue=9&rft.spage=797&rft.isbn=&rft.btitle=&rft.title=AIDS+Research+and+Human+Retroviruses&rft.issn=08892229&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Human Immunodeficiency Virus Type 2 Lentivirus Vectors for Gene Transfer: Expression and Potential for Helper Virus-Free Packaging AN - 16431035; 4332861 AB - In addition to the long-term expression of the transgene provided by all retroviral vectors, lentiviruses present the opportunity to transduce nondividing cells and potentially achieve regulated expression. The development of lentiviral vectors requires the design of transfer vectors to ferry the transgene with efficient encapsidation of the transgene RNA and with full expression capability, and of a packaging vector to provide packaging machinery in trans but without helper virus production. For both vectors, a knowledge of packaging signal is required - the signal to be included in the transfer vector but excluded from the packaging vector. Among the human lentiviruses, human immunodeficiency virus type 1 and type 2 (HIV-1 and HIV-2), we think HIV-2 is better suited for gene transfer than HIV-1. It is less pathogenic and thus safer during design and production; its desirable nuclear import and undesirable cell-cycle arrest functions are segregated on two separate genes. In HIV-1 infection, it is less likely to recombine with the resident HIV-1, and it may itself downregulate HIV-1 expression. Evidently, elements located both upstream and downstream of the splice donor site in the leader sequence participated in RNA encapsidation and these sequences appeared necessary and sufficient. Deletion of both sequence elements resulted in a dramatic curtailment of RNA encapsidation and helper virus production. This was accompanied by some but acceptable loss of gene expression capability. The helper virus-free phenotype and expression capability of the double mutant was maintained upon replacement of its 3' long terminal repeat with a minigene cassette containing a transcriptional termination signal and a drug resistance marker gene. Deletion of the splice donor site itself had a dramatic negative effect on gene expression, supporting the important role of this element in the life of RNA. JF - Human Gene Therapy AU - Arya, S K AU - Zamani, M AU - Kundra, P AD - Basic Research Laboratory, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, 37 Convent Drive MSC 4255, Building 37, Room 6A11, Bethesda, MD 20892-4255, USA Y1 - 1998/06/10/ PY - 1998 DA - 1998 Jun 10 SP - 1371 EP - 1380 VL - 9 IS - 9 SN - 1043-0342, 1043-0342 KW - helper virus KW - human immunodeficiency virus 2 KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - W3 33181:Gene therapy vectors KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16431035?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+Gene+Therapy&rft.atitle=Human+Immunodeficiency+Virus+Type+2+Lentivirus+Vectors+for+Gene+Transfer%3A+Expression+and+Potential+for+Helper+Virus-Free+Packaging&rft.au=Arya%2C+S+K%3BZamani%2C+M%3BKundra%2C+P&rft.aulast=Arya&rft.aufirst=S&rft.date=1998-06-10&rft.volume=9&rft.issue=9&rft.spage=1371&rft.isbn=&rft.btitle=&rft.title=Human+Gene+Therapy&rft.issn=10430342&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Involvement of carboxy-terminal amino acids in secretion of human lysosomal protease cathepsin L. AN - 79930303; 9622510 AB - Cathepsin L, a lysosomal cysteine protease, is overexpressed and secreted by malignantly transformed cells. However, the reason for secretion of this man 6-phosphate-containing lysosomal protease into the extracellular medium is not clear. We wished to determine whether there is a region within the primary sequence of the proenzyme form of cathepsin L which affects its subcellular and extracellular localization. High-level transient expression of human procathepsin L in mouse NIH 3T3 cells results in the secretion of most of this protein into the extracellular medium. At the same time, the endogenous mouse procathepsin L in these nontransformed cells is found in its usual location in lysosomes. Mutants of human procathepsin L with carboxy-terminus deletions involving the last 11 amino acids are not secreted into the medium. Deletion of as little as two amino acids, Thr and Val, from the carboxy terminus, blocked the secretion of the protein but did not affect its enzyme activity, posttranslational processing, or subcellular distribution. Replacement of Thr-Val by two bulky amino acids Tyr-Asn allowed secretion of the procathepsin L, but the replacement of these two amino acids by nonbulky alanines prevented its secretion. Single alanine substitutions of the last six amino acids (ASYPTV) indicated that substitution by alanine of Y or T does not affect the secretion of hproCAT L, but alanine substitutions of S, P, or V completely blocked its secretion into the culture medium. We therefore conclude that the carboxy terminus of procathepsin L contains a sequence essential for its secretion. JF - Biochemistry AU - Chauhan, S S AU - Ray, D AU - Kane, S E AU - Willingham, M C AU - Gottesman, M M AD - Laboratory of Cell Biology, National Cancer Institute, Bethesda, Maryland 20892-4255, USA. Y1 - 1998/06/09/ PY - 1998 DA - 1998 Jun 09 SP - 8584 EP - 8594 VL - 37 IS - 23 SN - 0006-2960, 0006-2960 KW - Bacterial Proteins KW - 0 KW - Culture Media KW - Enzyme Precursors KW - Escherichia coli Proteins KW - Lac Repressors KW - Recombinant Proteins KW - Repressor Proteins KW - Cathepsins KW - EC 3.4.- KW - Endopeptidases KW - Cysteine Endopeptidases KW - EC 3.4.22.- KW - CTSL1 protein, human KW - EC 3.4.22.15 KW - Cathepsin L KW - Ctsl protein, mouse KW - Index Medicus KW - Centrifugation, Density Gradient KW - 3T3 Cells KW - Animals KW - Bacterial Proteins -- genetics KW - Recombinant Proteins -- biosynthesis KW - Humans KW - Mice KW - Glycosylation KW - Repressor Proteins -- genetics KW - Genetic Vectors -- metabolism KW - Culture Media -- metabolism KW - Enzyme Activation -- genetics KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Phosphorylation KW - Transfection KW - Molecular Sequence Data KW - Subcellular Fractions -- enzymology KW - Amino Acid Substitution KW - Sequence Deletion KW - Cathepsins -- secretion KW - Cathepsins -- genetics KW - Enzyme Precursors -- secretion KW - Amino Acid Sequence -- genetics KW - Lysosomes -- enzymology KW - Enzyme Precursors -- genetics KW - Cysteine Endopeptidases -- genetics KW - Cysteine Endopeptidases -- secretion KW - Amino Acid Sequence -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79930303?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Involvement+of+carboxy-terminal+amino+acids+in+secretion+of+human+lysosomal+protease+cathepsin+L.&rft.au=Chauhan%2C+S+S%3BRay%2C+D%3BKane%2C+S+E%3BWillingham%2C+M+C%3BGottesman%2C+M+M&rft.aulast=Chauhan&rft.aufirst=S&rft.date=1998-06-09&rft.volume=37&rft.issue=23&rft.spage=8584&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-06-30 N1 - Date created - 1998-06-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inhibition of a Mycobacterium tuberculosis beta -ketoacyl ACP synthase by isoniazid AN - 16521288; 4327185 AB - Although isoniazid (isonicotinic acid hydrazide, INH) is widely used for the treatment of tuberculosis, its molecular target has remained elusive. In response to INH treatment, saturated hexacosanoic acid (C26:0) accumulated on a 12-kilodalton acyl carrier protein (AcpM) that normally carried mycolic acid precursors as long as C50. A protein species purified from INH-treated Mycobacterium tuberculosis was shown to consist of a covalent complex of INH, AcpM, and a beta -ketoacyl acyl carrier protein synthase, KasA. Amino acid-altering mutations in the KasA protein were identified in INH-resistant patient isolates that lacked other mutations associated with resistance to this drug. JF - Science (Washington) AU - Mdluli, K AU - Slayden, R A AU - Zhu, YaQi AU - Ramaswamy, S AU - Pan, Xi AU - Mead, D AU - Crane, D D AU - Musser, J M AU - Barry, CE III AD - Tuberculosis Res. Unit, Lab. Intracell. Parasites, Rocky Mt. Lab., Natl. Inst. Allergy and Infect. Dis. (NIAID), NIH, Hamilton, MT 59840, USA, clifton_barry@nih.gov Y1 - 1998/06/05/ PY - 1998 DA - 1998 Jun 05 SP - 1607 EP - 1610 PB - American Association for the Advancement of Science VL - 280 IS - 5369 SN - 0036-8075, 0036-8075 KW - Inhibition KW - Isoniazid KW - KasA protein KW - Therapy KW - beta -Ketoacyl ACP synthase KW - beta -ketoacyl ACP synthase KW - Microbiology Abstracts B: Bacteriology; Microbiology Abstracts A: Industrial & Applied Microbiology KW - A 01065:Antimycobacterial KW - J 02812:Antibacterial Agents: Others UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16521288?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Science+%28Washington%29&rft.atitle=Inhibition+of+a+Mycobacterium+tuberculosis+beta+-ketoacyl+ACP+synthase+by+isoniazid&rft.au=Mdluli%2C+K%3BSlayden%2C+R+A%3BZhu%2C+YaQi%3BRamaswamy%2C+S%3BPan%2C+Xi%3BMead%2C+D%3BCrane%2C+D+D%3BMusser%2C+J+M%3BBarry%2C+CE+III&rft.aulast=Mdluli&rft.aufirst=K&rft.date=1998-06-05&rft.volume=280&rft.issue=5369&rft.spage=1607&rft.isbn=&rft.btitle=&rft.title=Science+%28Washington%29&rft.issn=00368075&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Acute intravenous administration of ondansetron and m-CPP, alone and in combination, in patients with obsessive-compulsive disorder (OCD): behavioral and biological results. AN - 80026245; 9676822 AB - Obsessive-compulsive disorder (OCD) has been linked to abnormal function of brain serotonin (5-HT) pathways. Since ondansetron is a highly selective 5-HT3 receptor antagonist, the present study was undertaken to investigate 5-HT3 function in OCD. We administered m-CPP (0.08 mg/kg i.v.) and the potent 5-HT3 antagonist, ondansetron (0.15 mg/kg i.v.), to 11 OCD patients. All of the subjects received four separate challenges (m-CPP + placebo, m-CPP + ondansetron, ondansetron + placebo and placebo + placebo). In comparison to placebo, administration of m-CPP was associated with significant behavioral effects, particularly self-rated measures of anxiety, altered self-reality, functional deficit and OCD symptoms. Pretreatment with ondansetron did not affect any of the self-rated behavioral symptoms. After administration of m-CPP relative to placebo, significant increases in plasma cortisol and prolactin were found. These changes were not affected by ondansetron. In conclusion, our results do not support the hypotheses that 5-HT3 receptor-mediated mechanisms modulate m-CPP's behavioral and neuroendocrine effects in patients with OCD. JF - Psychiatry research AU - Broocks, A AU - Pigott, T A AU - Hill, J L AU - Canter, S AU - Grady, T A AU - L'Heureux, F AU - Murphy, D L AD - Section on Clinical Neuropharmacology, Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, MD, USA. Y1 - 1998/06/02/ PY - 1998 DA - 1998 Jun 02 SP - 11 EP - 20 VL - 79 IS - 1 SN - 0165-1781, 0165-1781 KW - Piperazines KW - 0 KW - Receptors, Serotonin KW - Serotonin Antagonists KW - Serotonin Receptor Agonists KW - Ondansetron KW - 4AF302ESOS KW - 1-(3-chlorophenyl)piperazine KW - REY0CNO998 KW - Index Medicus KW - Drug Interactions KW - Analysis of Variance KW - Psychiatric Status Rating Scales KW - Behavioral Symptoms -- chemically induced KW - Injections, Intravenous KW - Double-Blind Method KW - Humans KW - Adult KW - Neurosecretory Systems -- drug effects KW - Middle Aged KW - Time Factors KW - Male KW - Female KW - Receptors, Serotonin -- physiology KW - Serotonin Receptor Agonists -- administration & dosage KW - Obsessive-Compulsive Disorder -- physiopathology KW - Ondansetron -- administration & dosage KW - Serotonin Antagonists -- administration & dosage KW - Obsessive-Compulsive Disorder -- metabolism KW - Receptors, Serotonin -- classification KW - Piperazines -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80026245?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Acute+intravenous+administration+of+ondansetron+and+m-CPP%2C+alone+and+in+combination%2C+in+patients+with+obsessive-compulsive+disorder+%28OCD%29%3A+behavioral+and+biological+results.&rft.au=Broocks%2C+A%3BPigott%2C+T+A%3BHill%2C+J+L%3BCanter%2C+S%3BGrady%2C+T+A%3BL%27Heureux%2C+F%3BMurphy%2C+D+L&rft.aulast=Broocks&rft.aufirst=A&rft.date=1998-06-02&rft.volume=79&rft.issue=1&rft.spage=11&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 - 1998-10-06 N1 - Date created - 1998-10-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Binding of SH1-SH2-modified myosin subfragment-1 to actin. AN - 79910830; 9609698 AB - Myosin subfragment-1 (S1) was labeled with NPM in the presence of ATP or with pPDM in the presence of ADP at 0 degreesC, conditions which favor linking of maleimide groups to both Cys-707 (SH1) and Cys-697 (SH2). Unmodified S1 was removed by sedimentation with a small amount of F-actin, and the modified protein in the supernatant thoroughly dialyzed. The myosin high-salt EDTA and calcium ATPase activities of the isolated modified S1 were close to zero, suggesting nearly complete modification of SH1 and SH2. The binding of control and these modified myosins to actin was measured at 100 mM ionic strength using a co-sedimentation assay. In the presence of high MgATP concentration, control and NPM- and pPDM-reacted S1 all bind weakly to actin, with binding constants K3 of 4.9, 2.2, and 1.9 x 10(4) M-1, respectively. In the absence of MgATP, the binding constant K2 of pPDM-reacted S1 remains weak, 4.6 x 10(4) M-1,while that of NPM-reacted and control S1 becomes strong, 4.7 and 31 x 10(6) M-1, respectively. The binding constant for ATP to acto-NPM-reacted-S1 is approximately 2 x 10(4) M-1. Our data suggest that the binding of NPM-S1 to F-actin, in contrast to that of pPDM-S1, is ATP sensitive and can be quite strong at very low ATP concentration. They also suggest that while simple alkylation of SH1 and SH2 may be sufficient to inhibit myosin's ability to hydrolyze ATP, actual covalent linkage of SH1 and SH2 may be necessary to inhibit the weakly to strongly binding conformational change. JF - Biochemistry AU - Xie, L AU - Schoenberg, M AD - Laboratory of Physical Biology, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, Maryland 20892, USA. Y1 - 1998/06/02/ PY - 1998 DA - 1998 Jun 02 SP - 8048 EP - 8053 VL - 37 IS - 22 SN - 0006-2960, 0006-2960 KW - Actins KW - 0 KW - Alkylating Agents KW - Maleimides KW - Myosin Subfragments KW - Sulfhydryl Compounds KW - Sulfhydryl Reagents KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - N-phenylmaleimide KW - 9U9KT462VW KW - N,N'-4-phenylenedimaleimide KW - BEC7P1E6J1 KW - Index Medicus KW - Animals KW - Kinetics KW - Rabbits KW - Protein Binding KW - Sulfhydryl Compounds -- metabolism KW - Sulfhydryl Compounds -- chemistry KW - Myosin Subfragments -- chemistry KW - Actins -- metabolism KW - Myosin Subfragments -- metabolism KW - Actins -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79910830?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Binding+of+SH1-SH2-modified+myosin+subfragment-1+to+actin.&rft.au=Xie%2C+L%3BSchoenberg%2C+M&rft.aulast=Xie&rft.aufirst=L&rft.date=1998-06-02&rft.volume=37&rft.issue=22&rft.spage=8048&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-06-22 N1 - Date created - 1998-06-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Vocabulary Competence in Early Childhood: Measurement, Latent Construct, and Predictive Validity AN - 85685810; 9908543 AB - A systematic examination of relations among six measures of child language derived from three sources, including observations of the child's speech with mother, experimenter assessments, & maternal reports. A total of 184 20-month-olds & their mothers contributed complete information about child language comprehension & expression. Correlations of child language measures with socioeconomic status & maternal education were accounted for, as were correlations of child language measures with mothers' verbal intelligence, maternal report measures with mothers' tendency to respond in a socially desirable fashion, & experimenter assessments with child social competence. Structural equation modeling supported (1) strong relations among child language measures derived from observations of the child's speech with mother, experimenter assessments, & maternal reports; (2) the loading of multiple measures of child language from different sources on a single latent construct of vocabulary competence; & (3) the predictive validity of the vocabulary competence latent variable at 20 months, as well as receptive vocabulary specifically, for both verbal & performance IQ (verbal better than performance) at 48 months. Neither an index of child monologing (a nonvocabulary language measure) nor symbolic play (a nonlinguistic representational measure) covaried with vocabulary competence. Girls consistently outperformed boys on individual language measures, but no differences emerged in any model in the fit for boys & girls. 5 Tables, 3 Figures, 82 References. Adapted from the source document JF - Child Development AU - Bornstein, Marc H AU - Haynes, O Maurice AD - Child & Family Research, Laboratory of Comparative Ethology, National Instit of Child Health & Human Development, National Institutes of Health, Bldg 31-Rm B2B15, 9000 Rockville Pike, Bethesda MD 20892-2030 Marc_H_Bornstein@nih.gov Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 654 EP - 671 VL - 69 IS - 3 SN - 0009-3920, 0009-3920 KW - Child Language (11800) KW - Language Acquisition (41600) KW - Verbal Learning (93750) KW - Lexicon (47150) KW - article KW - 4015: psycholinguistics; child language acquisition UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85685810?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Allba&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Child+Development&rft.atitle=Vocabulary+Competence+in+Early+Childhood%3A+Measurement%2C+Latent+Construct%2C+and+Predictive+Validity&rft.au=Bornstein%2C+Marc+H%3BHaynes%2C+O+Maurice&rft.aulast=Bornstein&rft.aufirst=Marc&rft.date=1998-06-01&rft.volume=69&rft.issue=3&rft.spage=654&rft.isbn=&rft.btitle=&rft.title=Child+Development&rft.issn=00093920&rft_id=info:doi/ LA - English DB - Linguistics and Language Behavior Abstracts (LLBA) N1 - Date revised - 2003-10-01 N1 - Last updated - 2016-09-27 N1 - CODEN - CHDEAW N1 - SubjectsTermNotLitGenreText - Language Acquisition (41600); Lexicon (47150); Verbal Learning (93750); Child Language (11800) ER - TY - JOUR T1 - A simplified method to measure the diffusion tensor from seven MR images. AN - 85267352; pmid-9621916 AB - Analytical expressions of the diffusion tensor of water, D, and of scalar invariants derived from it, are given in terms of the intensities of seven diffusion-weighted images (DWIs). These formulas simplify the post-processing steps required in diffusion tensor imaging, including estimating D in each voxel (from the set of b-matrices and their corresponding DWIs), and then computing its eigenvalues, eigenvectors, and scalar invariants. In a study conducted using artifact-free DWIs with high diffusion weighting (bmax approximately 900 s/mm2, maps of Trace(D) and the Relative and Lattice Anisotropy indices calculated analytically and by multivariate linear regression showed excellent agreement in brain parenchyma of a healthy living cat. However, the quality of the analytically computed maps degraded markedly as diffusion weighting was reduced. Although diffusion tensor MRI with seven DWIs may be useful for clinical applications where rapid scanning and data processing are required, it does not provide estimates of the uncertainty of the measured imaging parameters, rendering it susceptible to noise and systematic artifacts. Therefore, care should be taken when using this technique in radiological applications. JF - Magnetic Resonance in Medicine AU - Basser, P J AU - Pierpaoli, C AD - Tissue Biophysics and Biomimetics Section, NICHD, National Institutes of Health, Bethesda, Maryland 20892-5766, USA. PY - 1998 SP - 928 EP - 934 VL - 39 IS - 6 SN - 0740-3194, 0740-3194 KW - Magnetic Resonance Imaging KW - Brain Mapping KW - Reference Values KW - Anisotropy KW - Human KW - Cats KW - Animal KW - Brain KW - Image Enhancement KW - Diffusion KW - Image Processing, Computer-Assisted UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85267352?accountid=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=Magnetic+Resonance+in+Medicine&rft.atitle=A+simplified+method+to+measure+the+diffusion+tensor+from+seven+MR+images.&rft.au=Basser%2C+P+J%3BPierpaoli%2C+C&rft.aulast=Basser&rft.aufirst=P&rft.date=1998-06-01&rft.volume=39&rft.issue=6&rft.spage=928&rft.isbn=&rft.btitle=&rft.title=Magnetic+Resonance+in+Medicine&rft.issn=07403194&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Effects of ketamine on thought disorder, working memory, and semantic memory in healthy volunteers. AN - 85256708; pmid-9611670 AB - BACKGROUND: The N-methyl-D-aspartate receptor antagonist, ketamine, produces a clinical syndrome of thought disorder, perceptual distortion, and cognitive impairment. METHODS: We have administered ketamine to healthy volunteers to characterize the formal thought disorder and specific memory dysfunction associated with ketamine. Ten healthy volunteers underwent a double-blind, placebo-controlled, ketamine infusion (0.12 mg/kg bolus and 0.65 mg/kg/hour). Thought disorder was evaluated with the Scale for the Assessment of Thought, Language and Communication. Cognitive testing involved working and semantic memory tasks. RESULTS: Ketamine produced a formal thought disorder, as well as impairments in working and semantic memory. The degree of ketamine-induced thought disorder significantly correlated with ketamine-induced decreases in working memory and did not correlate with ketamine-induced impairments in semantic memory. CONCLUSIONS: This study characterizes the formal thought disorder associated with ketamine and may suggest that ketamine-induced deficits in working memory are associated with ketamine-induced thought disorder. JF - Biological Psychiatry AU - Adler, C M AU - Goldberg, T E AU - Malhotra, A K AU - Pickar, D AU - Breier, A AD - Experimental Therapeutics Branch, National Institute of Mental Health, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, USA. PY - 1998 SP - 811 EP - 816 VL - 43 IS - 11 SN - 0006-3223, 0006-3223 KW - Verbal Behavior KW - Double-Blind Method KW - Thinking KW - Human KW - Brain KW - Mental Recall KW - Verbal Learning KW - Adult KW - Ketamine KW - Middle Age KW - Neuropsychological Tests KW - Retention (Psychology) KW - Receptors, N-Methyl-D-Aspartate KW - Male KW - Female UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85256708?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biological+Psychiatry&rft.atitle=Effects+of+ketamine+on+thought+disorder%2C+working+memory%2C+and+semantic+memory+in+healthy+volunteers.&rft.au=Adler%2C+C+M%3BGoldberg%2C+T+E%3BMalhotra%2C+A+K%3BPickar%2C+D%3BBreier%2C+A&rft.aulast=Adler&rft.aufirst=C&rft.date=1998-06-01&rft.volume=43&rft.issue=11&rft.spage=811&rft.isbn=&rft.btitle=&rft.title=Biological+Psychiatry&rft.issn=00063223&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Suppressive effect of antiflammin-2 on compound 48/80-induced conjunctivitis. Role of phospholipase A2s and inducible nitric oxide synthase. AN - 80046680; 9689636 AB - Phospholipase A2s (PLA2s) are a family of esterases that initiate the arachidonic acid cascade, which results in the production of numerous inflammatory mediators. We investigated the expression of Group I and II PLA2 proteins and Group II mRNA in normal conjunctivae and in the conjunctivae of mice with compound 48/80-induced conjunctivitis. Conjunctivitis was induced in C57BL/6 mice by topical instillation of compound 48/80 (C48/80). Mice were then treated with corticosteroid (Pred Forte), antiflammin-2 (AF2, a synthetic peptide that inhibits PLA2), or a placebo (Dacriose, an isotonic, buffered, sterile eye irrigating solution). Low levels of PLA2s were detected on the epithelium of normal conjunctivae. One hr after C48/80 instillation, the expression of PLA2s appeared and increased in the substantia propria, peaked at 6 hr, and returned to baseline 72 hr later. Compared to the placebo, the conjunctivitis was moderate in the AF2-treated group and mild in Pred Forte-treated group. The expression of PLA2s was suppressed in mice treated with Pred Forte and AF2. iNOS mRNA was also diminished in the AF2- and Pred Forte-treated groups. The mechanisms by which anti-allergic medications suppress conjunctivitis may involve the inhibition of PLA2s and iNOS. JF - Ocular immunology and inflammation AU - Li, Q AU - Luyo, D AU - Matteson, D M AU - Chan, C C AD - Section on Immunopathology, National Eye Institute, National Institute of Health, Bethesda, MD, USA. Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 65 EP - 73 VL - 6 IS - 2 SN - 0927-3948, 0927-3948 KW - Anti-Inflammatory Agents KW - 0 KW - Anti-Inflammatory Agents, Non-Steroidal KW - DNA Probes KW - Glucocorticoids KW - Oligopeptides KW - Ophthalmic Solutions KW - Peptide Fragments KW - RNA, Messenger KW - antiflammin P2 KW - 118850-72-9 KW - p-Methoxy-N-methylphenethylamine KW - 4091-50-3 KW - prednisolone acetate KW - 8B2807733D KW - Prednisolone KW - 9PHQ9Y1OLM KW - Nitric Oxide Synthase KW - EC 1.14.13.39 KW - Nitric Oxide Synthase Type II KW - Nos2 protein, mouse KW - Phospholipases A KW - EC 3.1.1.32 KW - Phospholipases A2 KW - EC 3.1.1.4 KW - Index Medicus KW - Animals KW - DNA Probes -- chemistry KW - Mice KW - Conjunctiva -- pathology KW - Conjunctiva -- enzymology KW - In Situ Hybridization KW - RNA, Messenger -- metabolism KW - Prednisolone -- analogs & derivatives KW - Prednisolone -- pharmacology KW - Mice, Inbred C57BL KW - Administration, Topical KW - Conjunctiva -- drug effects KW - Female KW - Immunoenzyme Techniques KW - Anti-Inflammatory Agents -- pharmacology KW - Phospholipases A -- genetics KW - Conjunctivitis, Allergic -- pathology KW - Conjunctivitis, Allergic -- chemically induced KW - Nitric Oxide Synthase -- genetics KW - Peptide Fragments -- pharmacology KW - Conjunctivitis, Allergic -- prevention & control KW - Oligopeptides -- pharmacology KW - Nitric Oxide Synthase -- metabolism KW - Phospholipases A -- metabolism KW - Conjunctivitis, Allergic -- enzymology KW - Anti-Inflammatory Agents, Non-Steroidal -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80046680?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Ocular+immunology+and+inflammation&rft.atitle=Suppressive+effect+of+antiflammin-2+on+compound+48%2F80-induced+conjunctivitis.+Role+of+phospholipase+A2s+and+inducible+nitric+oxide+synthase.&rft.au=Li%2C+Q%3BLuyo%2C+D%3BMatteson%2C+D+M%3BChan%2C+C+C&rft.aulast=Li&rft.aufirst=Q&rft.date=1998-06-01&rft.volume=6&rft.issue=2&rft.spage=65&rft.isbn=&rft.btitle=&rft.title=Ocular+immunology+and+inflammation&rft.issn=09273948&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-10-05 N1 - Date created - 1998-10-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Selection and analysis of rare second-site suppressors of Drosophila RNA polymerase II mutations. AN - 80016382; 9669327 AB - We used a mutagenesis and selection procedure in Drosophila melanogaster to recover rare allele-specific suppressor mutations. More than 11 million flies mutant for one of five recessive-lethal mutations in the two largest subunits of RNA polymerase II were selected for additional mutations that restored viability. Forty-one suppressor mutations were recovered. At least 16 are extragenic, identifying a minimum of three loci, two of which do not map near genes known to encode subunits of RNA polymerase II. At most, 25 are intragenic, 4 reverting the initial altered nucleotide back to wild type. Sequence analysis of interacting mutations in the two largest subunits identified a discrete domain in each subunit. These domains might be contact points for the subunits. Finally, our selections were large enough to allow recovery of multiple independent changes in the same nucleotides yet mutations in other equally likely targets were not recovered. The mutations recovered are not random and might provide insights into possible mechanisms for mutagenesis in eukaryotes. JF - Molecular & general genetics : MGG AU - Krasnoselskaya, I AU - Huang, J AU - Jones, T AU - Dezan, C AU - Mortin, M A AD - Laboratory of Biochemistry, NIH/NCI, Bethesda, MD 20892-4255, USA. Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 457 EP - 465 VL - 258 IS - 5 SN - 0026-8925, 0026-8925 KW - RNA Polymerase II KW - EC 2.7.7.- KW - Index Medicus KW - Point Mutation -- genetics KW - Animals KW - Base Sequence KW - Alleles KW - DNA Mutational Analysis KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Mutagenesis KW - RNA Polymerase II -- genetics KW - Drosophila melanogaster -- genetics KW - Suppression, Genetic KW - Drosophila melanogaster -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80016382?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+%26+general+genetics+%3A+MGG&rft.atitle=Selection+and+analysis+of+rare+second-site+suppressors+of+Drosophila+RNA+polymerase+II+mutations.&rft.au=Krasnoselskaya%2C+I%3BHuang%2C+J%3BJones%2C+T%3BDezan%2C+C%3BMortin%2C+M+A&rft.aulast=Krasnoselskaya&rft.aufirst=I&rft.date=1998-06-01&rft.volume=258&rft.issue=5&rft.spage=457&rft.isbn=&rft.btitle=&rft.title=Molecular+%26+general+genetics+%3A+MGG&rft.issn=00268925&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-07-30 N1 - Date created - 1998-07-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular modeling studies on binding of bFGF to heparin and its receptor FGFR1. AN - 80011711; 9669548 AB - Sugar induced protein-protein interactions play an important role in several biological processes. The carbohydrate moieties of proteoglycans, the glycosaminoglycans, bind to growth factors with a high degree of specificity and induce interactions with growth factor receptors, thereby regulate the growth factor activity. We have used molecular modeling method to study the modes of binding of heparin or heparan sulfate proteoglycans (HSPGs) to bFGF that leads to the dimerization of FGF receptor 1 (FGFR1) and activation of receptor tyrosine kinase. Homology model of FGFR1 Ig D(II)-D(III) domains was built to investigate the interactions between heparin, bFGF and FGFR1. The structural requirements to bridge the two monomeric bFGF molecules by heparin or HSPGs and to simulate the dimerization and activation of FGFR1 have been examined. A structural model of the biologically functional dimeric bFGF-heparin complex is proposed based on: (a) the stability of dimeric complex, (b) the favorable binding energies between heparin and bFGF molecules, and (c) its accessibility to FGFR1. The modeled complex between heparin, bFGF and FGFR1 has a stoichiometry of 1 heparin: 2 bFGF: 2 FGFR1. The structural properties of the proposed model of bFGF/heparin/FGFR1 complex are consistent with the binding mechanism of FGF to its receptor, the receptor dimerization, and the reported site-specific mutagenesis and biochemical cross-linking data. In the proposed model heparin bridges the two bFGF monomers in a specific orientation and the resulting complex induces FGF receptor dimerization, suggesting that in the oligosaccharide induced recognition process sugars orient the molecules in a way that brings about specific protein-protein or protein-carbohydrate interactions. JF - Journal of biomolecular structure & dynamics AU - Lam, K AU - Rao, V S AU - Qasba, P K AD - Structural Glycobiology Section, Laboratory of Experimental and Computational Biology, National Cancer Institute, NCI-FCRDC, Frederick, Maryland 21702, USA. Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 1009 EP - 1027 VL - 15 IS - 6 SN - 0739-1102, 0739-1102 KW - Receptors, Fibroblast Growth Factor KW - 0 KW - Trisaccharides KW - Fibroblast Growth Factor 2 KW - 103107-01-3 KW - Heparin KW - 9005-49-6 KW - FGFR1 protein, human KW - EC 2.7.10.1 KW - Receptor Protein-Tyrosine Kinases KW - Receptor, Fibroblast Growth Factor, Type 1 KW - Index Medicus KW - Trisaccharides -- metabolism KW - Humans KW - Dimerization KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Protein Conformation KW - Carbohydrate Conformation KW - Fibroblast Growth Factor 2 -- metabolism KW - Fibroblast Growth Factor 2 -- chemistry KW - Computer Simulation KW - Models, Molecular KW - Heparin -- metabolism KW - Heparin -- chemistry KW - Receptors, Fibroblast Growth Factor -- metabolism KW - Receptor Protein-Tyrosine Kinases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80011711?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+biomolecular+structure+%26+dynamics&rft.atitle=Molecular+modeling+studies+on+binding+of+bFGF+to+heparin+and+its+receptor+FGFR1.&rft.au=Lam%2C+K%3BRao%2C+V+S%3BQasba%2C+P+K&rft.aulast=Lam&rft.aufirst=K&rft.date=1998-06-01&rft.volume=15&rft.issue=6&rft.spage=1009&rft.isbn=&rft.btitle=&rft.title=Journal+of+biomolecular+structure+%26+dynamics&rft.issn=07391102&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-09-28 N1 - Date created - 1998-09-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Multigenic control of skin tumor susceptibility in SENCARA/Pt mice. AN - 80004377; 9667751 AB - Skin tumors induced in mice by initiation-promotion (2 microg DMBA-2 microg TPA) protocols were found to be under multigenic control. Eighty-one N2 mice from the cross (BALB/cAnPt x SENCARA/Pt)F1 x SENCARA/Pt that were either solidly resistant (no papillomas) or highly susceptible (> or = 7 papillomas/mouse) were subjected to a 'genome scan' using 89 microsatellite markers to check for associations with susceptible and resistant phenotypes. A locus on Chr 5 (Skts4) was found to control the susceptibility of SENCARA/Pt mice and the resistance of BALB/cAnPt mice to papilloma formation. In addition, higher than expected linkage scores were seen for the markers D9Mit271, D11Mit268 and D12Mit56. Further work is required to establish whether genes determining papilloma formation are located in these regions of the genome. In general, no evidence was seen for loss of heterozygosity in microsatellite markers on Chrs 5, 9 and 11 in 17 microdissected papillomas from (BALB/c x SENCARA)F1 hybrid mice. JF - Carcinogenesis AU - Mock, B A AU - Lowry, D T AU - Rehman, I AU - Padlan, C AU - Yuspa, S H AU - Hennings, H AD - Laboratory of Genetics, DBS, NCI, National Institutes of Health, Bethesda, MD 20892-4255, USA. Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 1109 EP - 1115 VL - 19 IS - 6 SN - 0143-3334, 0143-3334 KW - Genetic Markers KW - 0 KW - Index Medicus KW - Phenotype KW - Genetic Linkage KW - Microsatellite Repeats KW - Animals KW - Alleles KW - Loss of Heterozygosity KW - Crosses, Genetic KW - Mice KW - Genetic Predisposition to Disease KW - Chromosome Mapping KW - Female KW - Skin Neoplasms -- genetics KW - Papilloma -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80004377?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Multigenic+control+of+skin+tumor+susceptibility+in+SENCARA%2FPt+mice.&rft.au=Mock%2C+B+A%3BLowry%2C+D+T%3BRehman%2C+I%3BPadlan%2C+C%3BYuspa%2C+S+H%3BHennings%2C+H&rft.aulast=Mock&rft.aufirst=B&rft.date=1998-06-01&rft.volume=19&rft.issue=6&rft.spage=1109&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-07-30 N1 - Date created - 1998-07-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Overexpression of CC10 modifies neoplastic potential in lung cancer cells. AN - 80002307; 9663466 AB - CC10 is infrequently expressed in non-small cell lung cancer cell lines, despite being abundantly produced by progenitor cells for normal and neoplastic airway epithelium. We overexpressed CC10 cDNA in the non-small cell lung cancer cell line A549 to determine its effect on the neoplastic phenotype. A549 cells transfected with CC10 demonstrated a marked reduction in invasiveness that was paralleled by diminished 92-kDa and absent 72-kDa metalloproteinase activity by zymography. Western analysis revealed the near absence of the corresponding matrix metalloproteinases (MMPs) MMP-2 and MMP-9 in the CC10-transfected cell lines, but not in the vector-transfected cell lines. The CC10-transfected cell lines also demonstrated decreased adhesiveness to fibronectin compared with the controls. CC10 expression was associated with decreased anchorage-independent growth but not with decreased anchorage-dependent growth. These data suggest that loss of CC10 may contribute to carcinogenesis, because CC10 antagonizes the neoplastic phenotype. JF - Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research AU - Szabo, E AU - Goheer, A AU - Witschi, H AU - Linnoila, R I AD - Department of Cell and Cancer Biology, Medicine Branch, Division of Clinical Sciences, National Cancer Institute, Rockville, Maryland 20850, USA. szaboe@bprb.nci.nih.gov Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 475 EP - 485 VL - 9 IS - 6 SN - 1044-9523, 1044-9523 KW - Enzyme Inhibitors KW - 0 KW - Extracellular Matrix Proteins KW - Proteins KW - RNA, Messenger KW - SCGB1A1 protein, human KW - Uteroglobin KW - 9060-09-7 KW - Metalloendopeptidases KW - EC 3.4.24.- KW - Index Medicus KW - Adenocarcinoma -- metabolism KW - Animals KW - Humans KW - RNA, Messenger -- analysis KW - Cell Division -- physiology KW - Adenocarcinoma -- enzymology KW - Neoplastic Processes KW - Extracellular Matrix Proteins -- metabolism KW - Tumor Cells, Cultured KW - Transfection KW - Neoplasm Invasiveness -- pathology KW - Cell Communication -- physiology KW - Mesocricetus KW - Metalloendopeptidases -- metabolism KW - Cricetinae KW - Lung Neoplasms -- enzymology KW - Carcinoma, Non-Small-Cell Lung -- metabolism KW - Enzyme Inhibitors -- metabolism KW - Carcinoma, Non-Small-Cell Lung -- enzymology KW - Proteins -- metabolism KW - Lung Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80002307?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Overexpression+of+CC10+modifies+neoplastic+potential+in+lung+cancer+cells.&rft.au=Szabo%2C+E%3BGoheer%2C+A%3BWitschi%2C+H%3BLinnoila%2C+R+I&rft.aulast=Szabo&rft.aufirst=E&rft.date=1998-06-01&rft.volume=9&rft.issue=6&rft.spage=475&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 - 1998-09-17 N1 - Date created - 1998-09-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Enhanced analgesia and suppression of plasma beta-endorphin by the S(+)-isomer of ibuprofen. AN - 80001948; 9663185 AB - Peripheral nociceptive barrage after tissue injury results in acute pain and a variety of physiologic responses, including pituitary secretion of beta-endorphin. This study evaluated whether administration of the pharmacologically active S(+)-isomer of ibuprofen suppresses acute pain and plasma beta-endorphin levels in the oral surgery model of acute pain. Subjects in a single-dose, double-blind, parallel-group study received either 200 mg S(+)-ibuprofen, 400 mg S(+)-ibuprofen, 400 mg racemic ibuprofen, or placebo. Both doses of S(+)-ibuprofen resulted in significantly greater analgesia over the first 60 minutes in comparison to racemic ibuprofen and placebo; the 400 mg dose of S(+)-ibuprofen also produced greater analgesia at 2 and 3 hours. Plasma levels of immunoreactive beta-endorphin decreased over time coincident with the onset of analgesia in all groups but were significantly less than placebo after both doses of S(+)-ibuprofen from 30 to 120 minutes. These findings show that, compared with racemic ibuprofen, administration of the S(+)-isomer of ibuprofen results in faster analgesic onset, greater peak analgesia, similar duration of action, and a low incidence of adverse effects, while suppressing nociceptive activation of the pituitary-adrenal axis. JF - Clinical pharmacology and therapeutics AU - Dionne, R A AU - McCullagh, L AD - National Institute of Dental Research, Nursing Department, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 694 EP - 701 VL - 63 IS - 6 SN - 0009-9236, 0009-9236 KW - Analgesics, Non-Narcotic KW - 0 KW - beta-Endorphin KW - 60617-12-1 KW - Ibuprofen KW - WK2XYI10QM KW - Abridged Index Medicus KW - Index Medicus KW - Double-Blind Method KW - Humans KW - Adult KW - Treatment Outcome KW - Isomerism KW - Pain Measurement KW - Oral Surgical Procedures -- adverse effects KW - Time Factors KW - Male KW - Female KW - Analgesics, Non-Narcotic -- adverse effects KW - Pain, Postoperative -- etiology KW - Analgesics, Non-Narcotic -- therapeutic use KW - Pain, Postoperative -- blood KW - Ibuprofen -- therapeutic use KW - Ibuprofen -- adverse effects KW - Pain, Postoperative -- drug therapy KW - Ibuprofen -- administration & dosage KW - beta-Endorphin -- drug effects KW - beta-Endorphin -- blood KW - Analgesics, Non-Narcotic -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80001948?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+pharmacology+and+therapeutics&rft.atitle=Enhanced+analgesia+and+suppression+of+plasma+beta-endorphin+by+the+S%28%2B%29-isomer+of+ibuprofen.&rft.au=Dionne%2C+R+A%3BMcCullagh%2C+L&rft.aulast=Dionne&rft.aufirst=R&rft.date=1998-06-01&rft.volume=63&rft.issue=6&rft.spage=694&rft.isbn=&rft.btitle=&rft.title=Clinical+pharmacology+and+therapeutics&rft.issn=00099236&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-07-30 N1 - Date created - 1998-07-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Estrogen upregulation of BRCA1 expression with no effect on localization. AN - 79980607; 9655254 AB - Alterations in the expression of the breast and ovarian cancer susceptibility gene BRCA1 may contribute to the development of mammary and ovarian neoplasia. The sex-steroid estrogen modulates cell proliferation of normal and neoplastic breast and ovarian epithelial cells, but the role of estrogen regulation on the expression of BRCA1 remains to be defined. In this study, estrogen-regulated BRCA1 expression was examined in breast and ovarian cancer cells. Estrogen stimulated the proliferation of estrogen receptor (ER)-positive breast MCF-7, C7-MCF-7, and ovarian BG-1 cells as well as the expression of the estrogen-inducible pS2 gene. This was concomitant with upregulation of BRCA1 mRNA (2.5- to 5.0-fold) and a 3- to 10-fold induction of BRCA1 protein (230 kDa). Cell fractionation studies localized the BRCA1 protein to the nucleus in both unstimulated and estrogen-stimulated cells. The antiestrogen ICI-182780 inhibited estrogen-induced cell proliferation, BRCA1 mRNA induction, and BRCA1 protein expression in ER-positive cells. Conversely, estrogen did not influence expression of BRCA1 in HBL-100 cells that lacked the estrogen receptor, although the constitutive levels of BRCA1 mRNA (but not protein) in these cells were 5- to 30-fold higher than in other breast and ovarian cancer cells. Secretion of the BRCA1 protein into the cell medium did not account for the discrepancy between the mRNA and protein levels in HBL-100 cells. Proliferation of HBL-100 cells was not affected by either estrogen or ICI-182780. Taken together, these data support a role for the steroid estrogen and the involvement of the estrogen receptor pathway in the modulation of expression of BRCA1. We therefore propose that stimulation of cell proliferation may be a prerequisite for upregulation of BRCA1 in breast and ovarian cancer cells. JF - Molecular carcinogenesis AU - Romagnolo, D AU - Annab, L A AU - Thompson, T E AU - Risinger, J I AU - Terry, L A AU - Barrett, J C AU - Afshari, C A AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 102 EP - 109 VL - 22 IS - 2 SN - 0899-1987, 0899-1987 KW - Antineoplastic Agents KW - 0 KW - BRCA1 Protein KW - Estrogen Antagonists KW - Estrogens KW - RNA, Messenger KW - Receptors, Estrogen KW - fulvestrant KW - 22X328QOC4 KW - Estradiol KW - 4TI98Z838E KW - Index Medicus KW - Breast Neoplasms -- genetics KW - Ovarian Neoplasms -- metabolism KW - Ovarian Neoplasms -- genetics KW - Humans KW - Estradiol -- pharmacology KW - Cell Division -- drug effects KW - Breast Neoplasms -- metabolism KW - Receptors, Estrogen -- metabolism KW - Receptors, Estrogen -- physiology KW - Up-Regulation -- physiology KW - Stimulation, Chemical KW - Estradiol -- analogs & derivatives KW - Estrogen Antagonists -- pharmacology KW - Tumor Cells, Cultured KW - RNA, Messenger -- metabolism KW - Neoplasms, Hormone-Dependent -- metabolism KW - Antineoplastic Agents -- pharmacology KW - Neoplasms, Hormone-Dependent -- genetics KW - Female KW - BRCA1 Protein -- biosynthesis KW - Gene Expression Regulation, Neoplastic -- physiology KW - BRCA1 Protein -- metabolism KW - Estrogens -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79980607?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+carcinogenesis&rft.atitle=Estrogen+upregulation+of+BRCA1+expression+with+no+effect+on+localization.&rft.au=Romagnolo%2C+D%3BAnnab%2C+L+A%3BThompson%2C+T+E%3BRisinger%2C+J+I%3BTerry%2C+L+A%3BBarrett%2C+J+C%3BAfshari%2C+C+A&rft.aulast=Romagnolo&rft.aufirst=D&rft.date=1998-06-01&rft.volume=22&rft.issue=2&rft.spage=102&rft.isbn=&rft.btitle=&rft.title=Molecular+carcinogenesis&rft.issn=08991987&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-07-16 N1 - Date created - 1998-07-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Rescue of targeted regions of mammalian chromosomes by in vivo recombination in yeast. AN - 79979665; 9647640 AB - In contrast to other animal cell lines, the chicken pre-B cell lymphoma line, DT40, exhibits a high level of homologous recombination, which can be exploited to generate site-specific alterations in defined target genes or regions. In addition, the ability to generate human/chicken monochromosomal hybrids in the DT40 cell line opens a way for specific targeting of human genes. Here we describe a new strategy for direct isolation of a human chromosomal region that is based on targeting of the chromosome with a vector containing a yeast selectable marker, centromere, and an ARS element. This procedure allows rescue of the targeted region by transfection of total genomic DNA into yeast spheroplasts. Selection for the yeast marker results in isolation of chromosome sequences in the form of large circular yeast artificial chromosomes (YACs) up to 170 kb in size containing the targeted region. These YACs are generated by homologous recombination in yeast between common repeated sequences in the targeted chromosomal fragment. Alternatively, the targeted region can be rescued as a linear YACs when a YAC fragmentation vector is included in the yeast transformation mixture. Because the entire isolation procedure of the chromosomal region, once a target insertion is obtained, can be accomplished in approximately 1 week, the new method greatly expands the utility of the homologous recombinationproficient DT40 chicken cell system. JF - Genome research AU - Kouprina, N AU - Kawamoto, K AU - Barrett, J C AU - Larionov, V AU - Koi, M AD - Laboratory of Molecular Genetics, Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 666 EP - 672 VL - 8 IS - 6 SN - 1088-9051, 1088-9051 KW - DNA, Circular KW - 0 KW - DNA, Fungal KW - Genetic Markers KW - Index Medicus KW - DNA, Circular -- genetics KW - Animals KW - Chickens KW - Humans KW - Hybrid Cells KW - Mice KW - DNA, Fungal -- genetics KW - Cell Line KW - Gene Targeting -- methods KW - Chromosomes, Artificial, Yeast -- genetics KW - Recombination, Genetic -- genetics KW - Chromosomes, Human, Pair 11 -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79979665?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genome+research&rft.atitle=Rescue+of+targeted+regions+of+mammalian+chromosomes+by+in+vivo+recombination+in+yeast.&rft.au=Kouprina%2C+N%3BKawamoto%2C+K%3BBarrett%2C+J+C%3BLarionov%2C+V%3BKoi%2C+M&rft.aulast=Kouprina&rft.aufirst=N&rft.date=1998-06-01&rft.volume=8&rft.issue=6&rft.spage=666&rft.isbn=&rft.btitle=&rft.title=Genome+research&rft.issn=10889051&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-01-05 N1 - Date created - 1999-01-05 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Anal Biochem. 1984 Feb;137(1):266-7 [6329026] Gene. 1982 Jun;18(3):277-88 [6290331] Nature. 1985 Sep 19-25;317(6034):230-4 [2995814] Mutat Res. 1986 Oct;163(1):3-13 [3018556] Science. 1987 May 15;236(4803):806-12 [3033825] Genetics. 1989 May;122(1):19-27 [2659436] Proc Natl Acad Sci U S A. 1990 Jun;87(12):4645-9 [2162051] Gene. 1991 Sep 30;106(1):125-7 [1937033] Proc Natl Acad Sci U S A. 1992 Sep 15;89(18):8794-7 [1528894] Science. 1993 Apr 16;260(5106):361-4 [8469989] Nat Genet. 1994 Jan;6(1):84-9 [8136839] Proc Natl Acad Sci U S A. 1994 Jun 7;91(12):5513-7 [8202519] Genes Dev. 1994 May 1;8(9):1087-105 [7926789] Hum Mol Genet. 1994 Aug;3(8):1227-37 [7987296] Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):491-6 [8552668] Nat Genet. 1996 Feb;12(2):174-82 [8563756] Gene. 1996 Feb 12;168(2):199-203 [8654944] Proc Natl Acad Sci U S A. 1996 Nov 26;93(24):13925-30 [8943037] Cell. 1996 Nov 29;87(5):917-27 [8945518] Proc Natl Acad Sci U S A. 1997 Jan 7;94(1):190-5 [8990184] Cell. 1997 Apr 18;89(2):185-93 [9108474] Nat Genet. 1997 May;16(1):37-43 [9140393] Cytogenet Cell Genet. 1997;76(1-2):72-6 [9154132] Proc Natl Acad Sci U S A. 1997 Jul 8;94(14):7384-7 [9207100] Proc Natl Acad Sci U S A. 1998 Apr 14;95(8):4469-74 [9539761] Am J Hum Genet. 1985 Jul;37(4):635-49 [9556655] Am J Hum Genet. 1984 Nov;36(6):1159-71 [6097109] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Repression of the telomerase catalytic subunit by a gene on human chromosome 3 that induces cellular senescence. AN - 79978515; 9655250 AB - The cellular senescence program is controlled by multiple genetic pathways, one of which involves the regulation of telomerase and telomere shortening. The introduction of a normal human chromosome 3 into the human renal cell carcinoma cell line RCC23 caused repression of telomerase activity, progressive shortening of telomeres, and restoration of the cellular senescence program. We attributed the repression of telomerase activity to the marked downregulation of the gene encoding the catalytic subunit of telomerase (hEST2/hTRT) but not another protein component (TP1/TLP1) or the RNA component of telomerase. These results suggest that a senescence-inducing gene on chromosome 3 controls hEST2/hTRT gene expression either directly or indirectly and support the notion that hEST2/hTRT is the major determinant of telomerase enzymatic activity in human cells. JF - Molecular carcinogenesis AU - Horikawa, I AU - Oshimura, M AU - Barrett, J C AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 65 EP - 72 VL - 22 IS - 2 SN - 0899-1987, 0899-1987 KW - DNA-Binding Proteins KW - 0 KW - Proteins KW - telomerase RNA KW - RNA KW - 63231-63-0 KW - TERT protein, human KW - EC 2.7.7.49 KW - Telomerase KW - Index Medicus KW - Carcinoma, Renal Cell -- pathology KW - Kidney Neoplasms -- genetics KW - Kidney Neoplasms -- pathology KW - Kidney Neoplasms -- enzymology KW - Humans KW - Cell Aging -- physiology KW - Transcription, Genetic KW - Gene Expression Regulation, Neoplastic KW - Polymerase Chain Reaction KW - Carcinoma, Renal Cell -- enzymology KW - Gene Expression Regulation, Enzymologic KW - Tumor Cells, Cultured KW - Down-Regulation KW - Carcinoma, Renal Cell -- genetics KW - Telomerase -- antagonists & inhibitors KW - Chromosomes, Human, Pair 3 KW - Proteins -- antagonists & inhibitors KW - Telomerase -- genetics KW - Telomerase -- metabolism KW - Proteins -- metabolism KW - Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79978515?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+carcinogenesis&rft.atitle=Repression+of+the+telomerase+catalytic+subunit+by+a+gene+on+human+chromosome+3+that+induces+cellular+senescence.&rft.au=Horikawa%2C+I%3BOshimura%2C+M%3BBarrett%2C+J+C&rft.aulast=Horikawa&rft.aufirst=I&rft.date=1998-06-01&rft.volume=22&rft.issue=2&rft.spage=65&rft.isbn=&rft.btitle=&rft.title=Molecular+carcinogenesis&rft.issn=08991987&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-07-16 N1 - Date created - 1998-07-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ribonuclease k6: chromosomal mapping and divergent rates of evolution within the RNase A gene superfamily. AN - 79976106; 9647635 AB - We have localized the gene encoding human RNase k6 to within approximately 120 kb on the long (q) arm of chromosome 14 by HAPPY mapping. With this information, the relative positions of the six human RNase A ribonucleases that have been mapped to this locus can be inferred. To further our understanding of the individual lineages comprising the RNase A superfamily, we have isolated and characterized 10 novel genes orthologous to that encoding human RNase k6 from Great Ape, Old World, and New World monkey genomes. Each gene encodes a complete ORF with no less than 86% amino acid sequence identity to human RNase k6 with the eight cysteines and catalytic histidines (H15 and H123) and lysine (K38) typically observed among members of the RNase A superfamily. Interesting trends include an unusually low number of synonymous substitutions (Ks) observed among the New World monkey RNase k6 genes. When considering nonsilent mutations, RNase k6 is a relatively stable lineage, with a nonsynonymous substitution rate of 0.40 x 10(-9) nonsynonymous substitutions/nonsynonymous site/year (ns/ns/yr). These results stand in contrast to those determined for the primate orthologs of the two closely related ribonucleases, the eosinophil-derived neurotoxin (EDN) and eosinophil cationic protein (ECP), which have incorporated nonsilent mutations at very rapid rates (1.9 x 10(-9) and 2.0 x 10(-9) ns/ns/yr, respectively). The uneventful trends observed for RNase k6 serve to spotlight the unique nature of EDN and ECP and the unusual evolutionary constraints to which these two ribonuclease genes must be responding. [The sequence data described in this paper have been submitted to the GenBank data library under accession nos. AF037081-AF037090.] JF - Genome research AU - Deming, M S AU - Dyer, K D AU - Bankier, A T AU - Piper, M B AU - Dear, P H AU - Rosenberg, H F AD - Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 599 EP - 607 VL - 8 IS - 6 SN - 1088-9051, 1088-9051 KW - Endoribonucleases KW - EC 3.1.- KW - ribonuclease k6 KW - EC 3.1.27.- KW - Ribonuclease, Pancreatic KW - EC 3.1.27.5 KW - Index Medicus KW - Animals KW - Sequence Alignment KW - Humans KW - Cebidae KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Cercopithecidae KW - Hominidae KW - Multigene Family -- genetics KW - Chromosome Mapping -- methods KW - Endoribonucleases -- genetics KW - Evolution, Molecular KW - Ribonuclease, Pancreatic -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79976106?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genome+research&rft.atitle=Ribonuclease+k6%3A+chromosomal+mapping+and+divergent+rates+of+evolution+within+the+RNase+A+gene+superfamily.&rft.au=Deming%2C+M+S%3BDyer%2C+K+D%3BBankier%2C+A+T%3BPiper%2C+M+B%3BDear%2C+P+H%3BRosenberg%2C+H+F&rft.aulast=Deming&rft.aufirst=M&rft.date=1998-06-01&rft.volume=8&rft.issue=6&rft.spage=599&rft.isbn=&rft.btitle=&rft.title=Genome+research&rft.issn=10889051&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-01-05 N1 - Date created - 1999-01-05 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF037090; GENBANK; AF037082; AF037081; AF037088; AF037086; AF037087; AF037085; AF037084; AF037089; AF037083 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genes and the environment: their impact on children's health. AN - 79974896; 9646043 AB - Because the human population is biologically diverse and genetically heterogeneous, it is not surprising that differences in susceptibility to disease among individuals with or without exposure to environmental agents exist. Individuals vary greatly in their susceptibility to disease. This is true of adults and children. The etiologies of many diseases of childhood are due to a combination of factors, including genetic susceptibility and environmental exposures during vulnerable periods of development. Genes regulate cellular growth and development, DNA replication and repair, the metabolism of endogenous agents in the body, and the metabolism and excretion of exogenous agents that the body comes in contact with in the environment. This regulation varies over the life span, contributing to the cellular consequences of the environmental exposures. This paper summarizes the contributions of genetics in understanding the etiology of environmentally induced diseases in children. The use of biomarkers of genetic susceptibility in the study of these diseases will be discussed. Future research needs for expanding our knowledge of the interactions between genetic and environmental components of childhood diseases will be presented. JF - Environmental health perspectives AU - Suk, W A AU - Collman, G W AD - Office of Program Development, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. suk@niehs.nih.gov Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 817 EP - 820 VL - 106 Suppl 3 SN - 0091-6765, 0091-6765 KW - Environmental Pollutants KW - 0 KW - Index Medicus KW - Age Factors KW - Polymorphism, Genetic KW - Molecular Epidemiology KW - Humans KW - Child KW - Environmental Exposure -- adverse effects KW - Environmental Pollutants -- adverse effects KW - Risk Assessment KW - Environment KW - Causality KW - Genetic Predisposition to Disease KW - Child Welfare UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79974896?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Genes+and+the+environment%3A+their+impact+on+children%27s+health.&rft.au=Suk%2C+W+A%3BCollman%2C+G+W&rft.aulast=Suk&rft.aufirst=W&rft.date=1998-06-01&rft.volume=106+Suppl+3&rft.issue=&rft.spage=817&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 - 1998-09-17 N1 - Date created - 1998-09-17 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Hum Hered. 1983;33(1):62-4 [6840783] Hum Genet. 1982;60(3):289-90 [7106762] Ann N Y Acad Sci. 1987;514:23-9 [3442386] N Engl J Med. 1990 Jan 11;322(2):83-8 [2294437] Am J Epidemiol. 1991 Jul 1;134(1):1-13 [1853854] Am J Hum Genet. 1991 Oct;49(4):757-63 [1716854] Environ Res. 1991 Dec;56(2):109-19 [1769358] Nature. 1992 Nov 19;360(6401):256-8 [1436106] Semin Cancer Biol. 1993 Apr;4(2):93-104 [8513152] Environ Health Perspect. 1993 Oct;101(5):378-84 [8080506] Arch Environ Health. 1994 Mar-Apr;49(2):98-105 [8161248] Arch Dermatol. 1994 Aug;130(8):1018-21 [8053698] Environ Health Perspect. 1995 Mar;103(3):248-53 [7768225] Am J Epidemiol. 1995 Oct 1;142(7):738-45 [7572945] Environ Health Perspect. 1995 Sep;103 Suppl 6:7-12 [8549494] Environ Health Perspect. 1995 Sep;103 Suppl 6:55-8 [8549490] Toxicology. 1996 Jul 17;111(1-3):15-20 [8711731] N Engl J Med. 1996 Sep 12;335(11):783-9 [8703183] Int Arch Occup Environ Health. 1986;58(3):245-7 [3770964] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evidence for a common etiology for endometrial carcinomas and malignant mixed mullerian tumors. AN - 79973616; 9648597 AB - To elucidate factors linked to the development of malignant mixed mullerian tumors (MMMT) and determine whether the risk factor profile for these tumors corresponds with that for the more common endometrial carcinomas. A multicenter case-control study of 424 women diagnosed with endometrial carcinoma, 29 women diagnosed with MMMT, and 320 community controls was conducted. Review of pathological reports and slides was performed to classify cases by histological type. All participants were asked to respond to a questionnaire which ascertained information on exposure to factors postulated to be linked to the development of uterine tumors. Women with endometrial carcinomas and MMMTs were similar with respect to age and educational attainment. Women diagnosed with MMMTs were more likely than those diagnosed with carcinomas to be of African-American descent (28% vs 4%; P = 0.001). Weight, exogenous estrogen use, and nulliparity were related to risk of both tumor types. Marked obesity was associated with a 4.8-fold (95% CI = 3.0,7.6) increase in risk of carcinoma and a 3.2-fold (95% CI = 1.1,9.1) increase in risk of MMMT development. Use of exogenous estrogens increased the odds of developing carcinomas by 2-fold (95% CI = 1.3,3.2) and that of developing MMMTs by 1.8-fold (95% CI = 0.57,5.5). Nulliparity was associated with a 2.9-fold (95% CI = 1.9,4.8) increase in risk of carcinomas and a 1.7-fold (95% CI = 0.53,5.6) increase in risk of MMMTs. Oral contraceptive use protected against the development of both carcinomas (OR = 0.39; 95% CI = 0.26,0.58) and MMMTs (OR = 0.76; 95% CI = 0.25,2.3). Current smokers were at a reduced risk of developing endometrial carcinomas (OR = 0.34; 95% CI = 0.21,0.55) and MMMTs (OR = 0.57; 95% CI = 0.15,2.3), while former smokers were at an increased risk of MMMT (OR = 2.7; 95% CI = 1.1,6.8) but not carcinoma development (OR = 0.81; 95% CI = 0.56,1.2). Results from this study suggest that MMMTs and carcinomas have a similar risk factor profile. This observation is compatible with the hypothesis that the pathogenesis of these two histological types of uterine tumors is similar. JF - Gynecologic oncology AU - Zelmanowicz, A AU - Hildesheim, A AU - Sherman, M E AU - Sturgeon, S R AU - Kurman, R J AU - Barrett, R J AU - Berman, M L AU - Mortel, R AU - Twiggs, L B AU - Wilbanks, G D AU - Brinton, L A AD - Environmental Epidemiology Branch, National Cancer Institute, Bethesda, Maryland 20892-7374, USA. Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 253 EP - 257 VL - 69 IS - 3 SN - 0090-8258, 0090-8258 KW - Contraceptives, Oral KW - 0 KW - Estrogens KW - Index Medicus KW - Demography KW - Contraceptives, Oral -- adverse effects KW - Risk Factors KW - Humans KW - Adult KW - Case-Control Studies KW - Smoking -- adverse effects KW - Aged KW - Middle Aged KW - Estrogens -- adverse effects KW - Female KW - Obesity -- complications KW - Carcinoma -- etiology KW - Uterine Neoplasms -- etiology KW - Endometrial Neoplasms -- etiology KW - Mixed Tumor, Mullerian -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79973616?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Gynecologic+oncology&rft.atitle=Evidence+for+a+common+etiology+for+endometrial+carcinomas+and+malignant+mixed+mullerian+tumors.&rft.au=Zelmanowicz%2C+A%3BHildesheim%2C+A%3BSherman%2C+M+E%3BSturgeon%2C+S+R%3BKurman%2C+R+J%3BBarrett%2C+R+J%3BBerman%2C+M+L%3BMortel%2C+R%3BTwiggs%2C+L+B%3BWilbanks%2C+G+D%3BBrinton%2C+L+A&rft.aulast=Zelmanowicz&rft.aufirst=A&rft.date=1998-06-01&rft.volume=69&rft.issue=3&rft.spage=253&rft.isbn=&rft.btitle=&rft.title=Gynecologic+oncology&rft.issn=00908258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-07-15 N1 - Date created - 1998-07-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Parental occupational exposures and risk of childhood cancer. AN - 79970673; 9646055 AB - Occupational exposures of parents might be related to cancer in their offspring. Forty-eight published studies on this topic have reported relative risks for over 1000 specific occupation/cancer combinations. Virtually all of the studies employed the case-control design. Occupations and exposures of fathers were investigated much more frequently than those of the mother. Information about parental occupations was derived through interviews or from birth certificates and other administrative records. Specific exposures were typically estimated by industrial hygienists or were self-reported. The studies have several limitations related to the quality of the exposure assessment, small numbers of exposed cases, multiple comparisons, and possible bias toward the reporting of positive results. Despite these limitations, they provide evidence that certain parental exposures may be harmful to children and deserve further study. The strongest evidence is for childhood leukemia and paternal exposure to solvents, paints, and employment in motor vehicle-related occupations; and childhood nervous system cancers and paternal exposure to paints. To more clearly evaluate the importance of these and other exposures in future investigations, we need improvements in four areas: a) more careful attention must be paid to maternal exposures; b) studies should employ more sophisticated exposure assessment techniques; c) careful attention must be paid to the postulated mechanism, timing, and route of exposure; and d) if postnatal exposures are evaluated, studies should provide evidence that the exposure is actually transferred from the workplace to the child's environment. JF - Environmental health perspectives AU - Colt, J S AU - Blair, A AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland 20892, USA. coltj@epndce.nci.nih.gov Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 909 EP - 925 VL - 106 Suppl 3 SN - 0091-6765, 0091-6765 KW - Carcinogens KW - 0 KW - Index Medicus KW - Leukemia -- chemically induced KW - Brain Neoplasms -- epidemiology KW - Humans KW - Neoplasms, Radiation-Induced -- epidemiology KW - Child KW - Wilms Tumor -- chemically induced KW - Brain Neoplasms -- chemically induced KW - Wilms Tumor -- epidemiology KW - Risk Factors KW - Leukemia -- epidemiology KW - Neuroblastoma -- epidemiology KW - Case-Control Studies KW - Occupations -- statistics & numerical data KW - Neuroblastoma -- chemically induced KW - Time Factors KW - Female KW - Male KW - Maternal Exposure -- adverse effects KW - Occupational Exposure -- statistics & numerical data KW - Paternal Exposure -- adverse effects KW - Maternal Exposure -- statistics & numerical data KW - Neoplasms -- chemically induced KW - Neoplasms -- epidemiology KW - Occupational Exposure -- adverse effects KW - Paternal Exposure -- statistics & numerical data UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79970673?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Parental+occupational+exposures+and+risk+of+childhood+cancer.&rft.au=Colt%2C+J+S%3BBlair%2C+A&rft.aulast=Colt&rft.aufirst=J&rft.date=1998-06-01&rft.volume=106+Suppl+3&rft.issue=&rft.spage=909&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 - 1998-09-17 N1 - Date created - 1998-09-17 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Am J Epidemiol. 1990 May;131(5):776-80 [2321622] BMJ. 1990 Feb 17;300(6722):423-9 [2107892] Am J Epidemiol. 1990 Aug;132(2):275-92 [2372007] Cancer Res. 1990 Nov 15;50(22):7129-33 [2224847] Tumori. 1990 Oct 31;76(5):413-9 [2256184] Environ Health Perspect. 1990 Aug;88:325-37 [2272330] BMJ. 1991 Mar 23;302(6778):681-7 [2021741] BMJ. 1991 Mar 23;302(6778):687-92 [2021742] J Epidemiol Community Health. 1991 Mar;45(1):11-5 [2045737] Am J Ind Med. 1991;19(5):643-53 [2053579] Eur J Cancer. 1991;27(8):958-65 [1832903] Cancer Res. 1992 Feb 15;52(4):782-6 [1737337] Cancer Causes Control. 1992 Mar;3(2):161-9 [1562706] Am J Ind Med. 1993 Feb;23(2):343-54 [8427262] BMJ. 1993 Mar 6;306(6878):615-21 [8461811] BMJ. 1993 May 1;306(6886):1153-8 [8499814] BMJ. 1993 Oct 16;307(6910):959-66 [8241906] Nature. 1994 Feb 24;367(6465):678-80 [8107860] Am J Ind Med. 1994 Aug;26(2):155-69 [7977393] J Occup Med. 1994 Oct;36(10):1079-92 [7830166] Health Phys. 1995 Mar;68(3):299-310 [7860300] Lancet. 1995 Jul 15;346(8968):177 [7603238] Am J Ind Med. 1995 Jul;28(1):71-8 [7573076] Scand J Work Environ Health. 1996 Oct;22(5):339-45 [8923606] Int J Epidemiol. 1997 Apr;26(2):272-8 [9169161] Environ Health Perspect. 1998 Jun;106 Suppl 3:893-908 [9646054] Br J Prev Soc Med. 1974 May;28(2):98-100 [4853418] Br J Prev Soc Med. 1976 Jun;30(2):138-40 [953378] Am J Epidemiol. 1979 Mar;109(3):309-19 [453168] J Epidemiol Community Health. 1979 Dec;33(4):253-6 [231629] Am J Epidemiol. 1980 Mar;111(3):329-36 [7361757] J Occup Med. 1980 Dec;22(12):792-4 [7218055] Science. 1981 Jul 10;213(4504):235-7 [7244631] J Epidemiol Community Health. 1981 Mar;35(1):11-5 [7264527] J Epidemiol Community Health. 1981 Dec;35(4):245-50 [7338698] J Occup Med. 1982 Aug;24(8):578-84 [6750059] Cancer Res. 1982 Dec;42(12):5240-5 [7139628] Cancer. 1984 Apr 15;53(8):1637-43 [6321012] J Epidemiol Community Health. 1984 Mar;38(1):7-11 [6323612] Am J Epidemiol. 1984 May;119(5):788-95 [6720675] J Occup Med. 1984 Jun;26(6):427-35 [6330324] J Occup Med. 1984 Sep;26(9):679-82 [6207280] Am J Epidemiol. 1985 Feb;121(2):216-24 [3860001] Am J Epidemiol. 1985 Jun;121(6):924-9 [4014183] J Natl Cancer Inst. 1986 Jul;77(1):17-9 [3459911] J Natl Cancer Inst. 1987 Jul;79(1):39-46 [3474448] Am J Epidemiol. 1987 Oct;126(4):605-13 [3631052] Cancer. 1988 Aug 1;62(3):635-44 [3164642] Am J Ind Med. 1988;14(3):299-318 [3189347] Am J Epidemiol. 1988 Dec;128(6):1256-65 [3195566] Cancer Res. 1989 Feb 1;49(3):725-9 [2535965] Cancer Res. 1989 Jul 15;49(14):4030-7 [2736544] Cancer Res. 1989 Aug 1;49(15):4349-52 [2743324] Int J Epidemiol. 1989 Dec;18(4):756-62 [2621010] Am J Epidemiol. 1990 Jun;131(6):995-1008 [2343871] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Biomonitoring of United States Army soldiers serving in Kuwait in 1991. AN - 79966493; 9641500 AB - Biomarkers of polycyclic aromatic hydrocarbon (PAH) exposure and genetic biomarkers of potential cancer susceptibility were determined in a group of United States Army soldiers who were deployed to Kuwait and Saudi Arabia in 1991 in the aftermath of the Persian Gulf War. Because hundreds of oil well fires were still burning, there was concern that ground troops stationed in Kuwait might be exposed to high levels of PAHs and other toxicants. The United States Army Environmental Hygiene Agency monitored air and soil for ambient PAHs. In addition, a group of 61 soldiers was involved in the biomonitoring study reported here. These soldiers kept diaries of daily activities and provided blood and urine samples in Germany (June) before deployment to Kuwait, after 8 weeks in Kuwait (August), and 1 month after the return to Germany (October). Here we present data for PAH-DNA adducts measured by immunoassay in blood cell DNA samples obtained at all three sampling times from 22 soldiers and bulky aromatic adducts measured by 32P-postlabeling in blood cell DNA samples from 20 of the same soldiers. Urinary 1-hydroxypyrene-glucuronide levels were determined by synchronous fluorescence spectrometry in a matched set of samples from 33 soldiers. Contrary to expectations, environmental monitoring showed low ambient PAH levels in the areas where these soldiers were working in Kuwait. For both DNA adduct assays, levels were the lowest in Kuwait in August and increased significantly after the soldiers returned to Germany (October). Urinary 1-hydroxypyrene-glucuronide levels were also lowest in Kuwait and highest in Germany, but the differences were not statistically significant. The PAH-exposure biomarker levels were not significantly influenced by polymorphic variations of CYP1A1 (MspI) and glutathione S-transferases M1 and T1. Overall, the data suggest that this group of soldiers was not exposed to elevated levels of PAHs while deployed in Kuwait. JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology AU - Poirier, M C AU - Weston, A AU - Schoket, B AU - Shamkhani, H AU - Pan, C F AU - McDiarmid, M A AU - Scott, B G AU - Deeter, D P AU - Heller, J M AU - Jacobson-Kram, D AU - Rothman, N AD - Carcinogen-DNA Interactions Section, Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, NIH, Bethesda, Maryland 20892-4255, USA. poirierm@dc37a.nci.nih.gov Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 545 EP - 551 VL - 7 IS - 6 SN - 1055-9965, 1055-9965 KW - DNA Primers KW - 0 KW - Polycyclic Aromatic Hydrocarbons KW - Index Medicus KW - United States KW - Genotype KW - Polymerase Chain Reaction KW - Humans KW - Kuwait KW - Male KW - Population Surveillance KW - Polycyclic Aromatic Hydrocarbons -- blood KW - Military Personnel KW - Occupational Exposure -- adverse effects KW - Environmental Exposure -- adverse effects KW - Polycyclic Aromatic Hydrocarbons -- urine UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79966493?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Biomonitoring+of+United+States+Army+soldiers+serving+in+Kuwait+in+1991.&rft.au=Poirier%2C+M+C%3BWeston%2C+A%3BSchoket%2C+B%3BShamkhani%2C+H%3BPan%2C+C+F%3BMcDiarmid%2C+M+A%3BScott%2C+B+G%3BDeeter%2C+D+P%3BHeller%2C+J+M%3BJacobson-Kram%2C+D%3BRothman%2C+N&rft.aulast=Poirier&rft.aufirst=M&rft.date=1998-06-01&rft.volume=7&rft.issue=6&rft.spage=545&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 - 1998-08-31 N1 - Date created - 1998-08-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dopamine D4 receptors and the risk of cigarette smoking in African-Americans and Caucasians. AN - 79962466; 9641486 AB - An understanding of why people smoke cigarettes can have an important impact on smoking prevention and cessation. People smoke cigarettes to maintain nicotine levels in the body, and nicotine has been implicated in the stimulation of brain reward mechanisms via central neuronal dopaminergic pathways. In this study, we evaluated the association of smoking and smoking cessation with a dopamine D4 receptor 48-bp variable nucleotide tandem repeat polymorphism in which the seven-repeat allele (D4.7) reduces dopamine affinity. Smokers (n = 283) and nonsmokers (n = 192) were recruited through local media for a case-control study of smoking. After giving informed consent and answering a behavioral questionnaire, smokers underwent a single minimal-contact session of smoking cessation counseling and then were followed for up to 1 year. The frequency of the dopamine D4 receptor genetic polymorphism using PCR was determined, and individuals were classified by the number of repeat alleles (two to five repeats as S and six to eight repeats as L). Persons with those genotypes including only S alleles (homozygote S/S) were compared with those with at least one L allele (heterozygote S/L and homozygote L/L). Chi2 tests of association, Fisher's exact test, and Student's t test were used. Ps were two-tailed. The data show that African-Americans (n = 72) who had at least one L allele had a higher risk of smoking (odds ratio, 7.7; 95% confidence interval, 1.5-39.9; P = 0.006), shorter time to the first cigarette in the morning (P = 0.03), and earlier age at smoking initiation (P = 0.09) compared with homozygote S/S genotypes. After smoking cessation counseling, none of the African-American smokers with an L allele were abstinent at 2 months, compared with 35% of the smokers who were homozygote S/S (P = 0.02). The analysis of Caucasians (n = 403) did not suggest a similar smoking risk for the D4 genotypes (odds ratio, 1.0; 95% confidence interval, 0.6-1.6; P = 0.90), or smoking cessation (P = 0.75). Although the number of African-Americans is small, this study is consistent with the hypothesis that the L alleles increase the risk of smoking because these individuals are prone to use nicotine to stimulate synaptic dopamine transmission. If replicated, the data indicate that a single minimal-contact session of cessation counseling, similar to what is typically provided in primary care physician offices, is ineffective in African-American smokers who have at least one L allele. The finding of an effect for these polymorphic loci in African-Americans, but not Caucasians, suggests that the variable nucleotide tandem repeat studied here is a marker for another polymorphic site in African-Americans, but not in Caucasians. 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 - Lerman, C AU - Audrain, J AU - Bowman, E D AU - Main, D AU - Boyd, N R AU - Caporaso, N E AD - Molecular Epidemiology Section, Laboratory of Human Carcinogenesis, Division of Basic Sciences, National Cancer Institute, Bethesda, Maryland 20892, USA. Peter_G_Shields@nih.gov Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 453 EP - 458 VL - 7 IS - 6 SN - 1055-9965, 1055-9965 KW - DRD4 protein, human KW - 0 KW - Receptors, Dopamine D2 KW - Receptors, Dopamine D4 KW - 137750-34-6 KW - Index Medicus KW - Genotype KW - Polymerase Chain Reaction KW - Odds Ratio KW - Alleles KW - Humans KW - Adult KW - Case-Control Studies KW - Male KW - Female KW - African Continental Ancestry Group -- genetics KW - Smoking Cessation KW - Smoking -- prevention & control KW - Receptors, Dopamine D2 -- genetics KW - Smoking -- genetics KW - European Continental Ancestry Group -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79962466?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Dopamine+D4+receptors+and+the+risk+of+cigarette+smoking+in+African-Americans+and+Caucasians.&rft.au=Shields%2C+P+G%3BLerman%2C+C%3BAudrain%2C+J%3BBowman%2C+E+D%3BMain%2C+D%3BBoyd%2C+N+R%3BCaporaso%2C+N+E&rft.aulast=Shields&rft.aufirst=P&rft.date=1998-06-01&rft.volume=7&rft.issue=6&rft.spage=453&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 - 1998-08-31 N1 - Date created - 1998-08-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Arrest among psychotic inpatients: assessing the relationship to diagnosis, gender, number of admissions, and social class. AN - 79960739; 9640096 AB - The present study of psychotic patients investigates the relationship of specific psychotic diagnoses (i.e., psychoactive-substance-induced psychosis, schizophrenia, bipolar disorder, other DSM-III Axis I psychotic disorders), social class, gender, and number of admissions to the rate of arrest in the community. All admissions with psychotic symptoms to hospitals providing inpatient psychiatric services in the Baltimore area were surveyed during a 6-year period. Study participants were assessed using a modified version of the Diagnostic Interview Schedule. During the course of the interview, patients were asked whether they had ever been arrested as a juvenile or as an adult. After adjusting for age, gender, number of admissions, and social class, we found that patients admitted for psychoactive-substance-induced psychosis were more likely to report having been arrested than patients with other psychotic diagnoses. Patients with schizophrenia were not more likely to have an history of arrest than patients with other psychotic disorders. Number of admissions and social class were independent predictors of history of arrest. The relationship between psychotic diagnosis and history of arrest was modified by gender. Psychotic patients with substance-induced diagnosis who were male were more likely to report a prior arrest in the community than their female counterparts. Our results suggest that type of psychotic diagnosis and social class, in addition to gender and number of admissions, are important predictors of differences in arrest-rate histories among psychotic patients. Gender appears to be an effect modifier of the relationship between psychotic diagnosis and history of arrest. JF - Social psychiatry and psychiatric epidemiology AU - Muntaner, C AU - Wolyniec, P AU - McGrath, J AU - Pulver, A E AD - Section Socio-environmental Studies, National Institute of Mental Health, Bethesda, MD 20892, USA. Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 274 EP - 282 VL - 33 IS - 6 SN - 0933-7954, 0933-7954 KW - Index Medicus KW - Socioeconomic Factors KW - Odds Ratio KW - Logistic Models KW - Humans KW - Adult KW - Retrospective Studies KW - Patient Admission -- statistics & numerical data KW - Middle Aged KW - Baltimore -- epidemiology KW - Adolescent KW - Psychoses, Substance-Induced -- epidemiology KW - Male KW - Female KW - Inpatients -- statistics & numerical data KW - Crime -- statistics & numerical data KW - Psychotic Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79960739?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Social+psychiatry+and+psychiatric+epidemiology&rft.atitle=Arrest+among+psychotic+inpatients%3A+assessing+the+relationship+to+diagnosis%2C+gender%2C+number+of+admissions%2C+and+social+class.&rft.au=Muntaner%2C+C%3BWolyniec%2C+P%3BMcGrath%2C+J%3BPulver%2C+A+E&rft.aulast=Muntaner&rft.aufirst=C&rft.date=1998-06-01&rft.volume=33&rft.issue=6&rft.spage=274&rft.isbn=&rft.btitle=&rft.title=Social+psychiatry+and+psychiatric+epidemiology&rft.issn=09337954&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-07-15 N1 - Date created - 1998-07-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Amphotericin B lipid complex for invasive fungal infections: analysis of safety and efficacy in 556 cases. AN - 79958739; 9636868 AB - The safety and antifungal efficacy of amphotericin B lipid complex (ABLC) were evaluated in 556 cases of invasive fungal infection treated through an open-label, single-patient, emergency-use study of patients who were refractory to or intolerant of conventional antifungal therapy. All 556 treatment episodes were evaluable for safety. During the course of ABLC therapy, serum creatinine levels significantly decreased from baseline (P or = 2.5 mg/dL at the start of ABLC therapy (baseline), the mean serum creatinine value decreased significantly from the first week through the sixth week (P < or = .0003). Among the 291 mycologically confirmed cases evaluable for therapeutic response, there was a complete or partial response to ABLC in 167 (57%), including 42% (55) of 130 cases of aspergillosis, 67% (28) of 42 cases of disseminated candidiasis, 71% (17) of 24 cases of zygomycosis, and 82% (9) of 11 cases of fusariosis. Response rates varied according to the pattern of invasive fungal infection, underlying condition, and reason for enrollment (intolerance versus progressive infection). These findings support the use of ABLC in the treatment of invasive fungal infections in patients who are intolerant of or refractory to conventional antifungal therapy. JF - Clinical infectious diseases : an official publication of the Infectious Diseases Society of America AU - Walsh, T J AU - Hiemenz, J W AU - Seibel, N L AU - Perfect, J R AU - Horwith, G AU - Lee, L AU - Silber, J L AU - DiNubile, M J AU - Reboli, A AU - Bow, E AU - Lister, J AU - Anaissie, E J AD - Infectious Diseases Section, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 1383 EP - 1396 VL - 26 IS - 6 SN - 1058-4838, 1058-4838 KW - Antifungal Agents KW - 0 KW - Drug Combinations KW - Phosphatidylcholines KW - Phosphatidylglycerols KW - liposomal amphotericin B KW - Amphotericin B KW - 7XU7A7DROE KW - Creatinine KW - AYI8EX34EU KW - Index Medicus KW - Candidiasis -- drug therapy KW - Humans KW - Cryptococcosis -- drug therapy KW - Aspergillosis -- drug therapy KW - Adult KW - Creatinine -- blood KW - Male KW - Female KW - Phosphatidylcholines -- adverse effects KW - Antifungal Agents -- adverse effects KW - Phosphatidylcholines -- therapeutic use KW - Amphotericin B -- adverse effects KW - Phosphatidylglycerols -- therapeutic use KW - Mycoses -- drug therapy KW - Phosphatidylglycerols -- adverse effects KW - Amphotericin B -- therapeutic use KW - Antifungal Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79958739?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+infectious+diseases+%3A+an+official+publication+of+the+Infectious+Diseases+Society+of+America&rft.atitle=Amphotericin+B+lipid+complex+for+invasive+fungal+infections%3A+analysis+of+safety+and+efficacy+in+556+cases.&rft.au=Walsh%2C+T+J%3BHiemenz%2C+J+W%3BSeibel%2C+N+L%3BPerfect%2C+J+R%3BHorwith%2C+G%3BLee%2C+L%3BSilber%2C+J+L%3BDiNubile%2C+M+J%3BReboli%2C+A%3BBow%2C+E%3BLister%2C+J%3BAnaissie%2C+E+J&rft.aulast=Walsh&rft.aufirst=T&rft.date=1998-06-01&rft.volume=26&rft.issue=6&rft.spage=1383&rft.isbn=&rft.btitle=&rft.title=Clinical+infectious+diseases+%3A+an+official+publication+of+the+Infectious+Diseases+Society+of+America&rft.issn=10584838&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-08-25 N1 - Date created - 1998-08-25 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Clin Infect Dis. 2000 Jan;30(1):236-7 [10619780] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Specific depletion of alloreactive T cells in HLA-identical siblings: a method for separating graft-versus-host and graft-versus-leukaemia reactions. AN - 79951709; 9633903 AB - Accumulating evidence indicates that alloreactive donor T cells confer both graft-versus-host (GVH) and graft-versus-leukaemia (GVL) reactivity following allogeneic bone marrow transplantation. We have developed a method to deplete alloreactive donor T cells with an immunotoxin targeting the alpha chain of the IL-2 receptor. In patients with chronic myeloid leukaemia and their HLA-identical sibling donors, we measured donor helper T-lymphocyte precursor frequencies (HTLPf) against recipient peripheral blood mononuclear cells (PBMNC; donor versus host), recipient leukaemia cells (donor versus leukaemia) and third-party PBMNC, before and after the depletion. In seven pairs there was a 4.3-fold reduction of donor-versus-host HTLPf (P=0.017), without a significant change in the donor frequencies against third party (P=0.96). In eight further donor-recipient pairs, immunotoxin-depleted donor versus patient PBMNC HTLPf 4.5-fold (mean 1/155,000 before and 1/839,000 after depletion, P=0.007). There was a smaller non-significant 1.8-fold reduction in donor-versus-leukaemia HTLPf from 1/192,000 to 1/334,000 (P=0.19). These results suggest that selective T-cell depletion can significantly deplete donor anti-host reactivity while conserving anti-leukaemia reactivity in HLA-matched donor-recipient pairs. JF - British journal of haematology AU - Mavroudis, D A AU - Dermime, S AU - Molldrem, J AU - Jiang, Y Z AU - Raptis, A AU - van Rhee, F AU - Hensel, N AU - Fellowes, V AU - Eliopoulos, G AU - Barrett, A J AD - Bone Marrow Transplantation Unit, Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20894, USA. Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 565 EP - 570 VL - 101 IS - 3 SN - 0007-1048, 0007-1048 KW - Index Medicus KW - Immunoassay -- methods KW - Humans KW - Transplantation, Homologous KW - Immune Tolerance KW - Flow Cytometry -- methods KW - Bone Marrow Transplantation -- methods KW - Graft vs Host Reaction -- immunology KW - Leukemia, Myelogenous, Chronic, BCR-ABL Positive -- immunology KW - Graft vs Host Disease -- immunology KW - Lymphocyte Depletion -- methods KW - Leukemia, Myelogenous, Chronic, BCR-ABL Positive -- therapy KW - T-Lymphocytes, Helper-Inducer -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79951709?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=British+journal+of+haematology&rft.atitle=Specific+depletion+of+alloreactive+T+cells+in+HLA-identical+siblings%3A+a+method+for+separating+graft-versus-host+and+graft-versus-leukaemia+reactions.&rft.au=Mavroudis%2C+D+A%3BDermime%2C+S%3BMolldrem%2C+J%3BJiang%2C+Y+Z%3BRaptis%2C+A%3Bvan+Rhee%2C+F%3BHensel%2C+N%3BFellowes%2C+V%3BEliopoulos%2C+G%3BBarrett%2C+A+J&rft.aulast=Mavroudis&rft.aufirst=D&rft.date=1998-06-01&rft.volume=101&rft.issue=3&rft.spage=565&rft.isbn=&rft.btitle=&rft.title=British+journal+of+haematology&rft.issn=00071048&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-07-31 N1 - Date created - 1998-07-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dose-dependent number of implants and implications in developmental toxicity. AN - 79946230; 9629644 AB - This paper proposes a method for assessing risk in developmental toxicity studies with exposure prior to implantation. The method proposed in this paper was developed to account for a dose-dependent trend in the number of implantation sites per dam, which is a common problem in studies with exposure prior to implantation. Toxins may have the effect of interfering with the early reproductive process, which can prevent implantation in the uterine wall. An imputation procedure is presented for estimating the number of potential fetuses by sampling from the empirical distribution of the number of implants per litter in the control group. The marginal death outcomes and the joint malformation and survival outcomes for each potential fetus can be estimated using multiple imputation or the chained data augmentation algorithm. Logit models can then be fit and used to estimate the effect of dose on reducing the probability of a normal birth. These models accommodate multiple covariate effects and can be applied to low-dose extrapolation. A simulation study is done to evaluate the properties of model-based estimators of the mean response and the virtually safe dose level (VSD). It was found that both estimates were good approximations of the underlying dose effect. A dominant lethal assay data set (Luning et al., 1966, Mutation Research 3, 444-451) is analyzed, and the results are compared with those of Rai and Van Ryzin. JF - Biometrics AU - Dunson, D B AD - Biostatistics Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. dunson@calvin.niehs.nih.gov Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 558 EP - 569 VL - 54 IS - 2 SN - 0006-341X, 0006-341X KW - Index Medicus KW - Rats KW - Probability KW - Animals KW - Litter Size KW - Biometry -- methods KW - Rodentia KW - Monte Carlo Method KW - Congenital Abnormalities KW - Female KW - Risk Assessment KW - Pregnancy KW - Fetal Death KW - Embryo Implantation KW - Teratology -- methods KW - Models, Statistical UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79946230?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Dose-dependent+number+of+implants+and+implications+in+developmental+toxicity.&rft.au=Dunson%2C+D+B&rft.aulast=Dunson&rft.aufirst=D&rft.date=1998-06-01&rft.volume=54&rft.issue=2&rft.spage=558&rft.isbn=&rft.btitle=&rft.title=Biometrics&rft.issn=0006341X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-07-07 N1 - Date created - 1998-07-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Syntaxin and 25-kDa synaptosomal-associated protein: differential effects of botulinum neurotoxins C1 and A on neuronal survival. AN - 79941350; 9632313 AB - The Clostridium botulinum neurotoxins (BoNTs) A and C1 cleave specific proteins required for neuroexocytosis. We demonstrated that, in intact neurons, BoNT A cleaves 25-kDa synaptosomal-associated protein (SNAP-25), and BoNT C1 cleaves both syntaxin and SNAP-25 (Williamson et al.: Mol Biol Cell 6:61a, 1995; J Biol Chem 271:7694-7699, 1996). Here, we compare the actions of BoNT A and BoNT C1 on mature and developing mouse spinal cord neurons in cell culture and demonstrate that BoNT C1 is severely neurotoxic. In mature cultures, synaptic terminals become enlarged shortly after BoNT C1 exposure, and, subsequently, axons, dendrites, and cell bodies degenerate. Electron microscopy confirms that early degenerative changes occur in synaptic terminals when the somatic cytoplasm appears normal. In newly plated cultures, few neurons survive exposure to BoNT C1. Whereas both BoNT A and BoNT C1 cleave SNAP-25, BoNT A has no adverse effect on neurite outgrowth, synaptogenesis, or neuron survival. This cytotoxicity is unique to BoNT C1, is specific to neurons, and is initiated at the synaptic terminal, suggesting either a novel role for syntaxin or additional actions of BoNT C1. The neurodegeneration induced by BoNT C1 may be significant in terms of its efficacy for the clinical treatment of dystonia and spasticity. JF - Journal of neuroscience research AU - Williamson, L C AU - Neale, E A AD - Laboratory of Developmental Neurobiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-4480, USA. Y1 - 1998/06/01/ PY - 1998 DA - 1998 Jun 01 SP - 569 EP - 583 VL - 52 IS - 5 SN - 0360-4012, 0360-4012 KW - Membrane Proteins KW - 0 KW - Nerve Tissue Proteins KW - Qa-SNARE Proteins KW - Snap25 protein, mouse KW - Synaptosomal-Associated Protein 25 KW - Botulinum Toxins KW - EC 3.4.24.69 KW - Botulinum Toxins, Type A KW - botulinum toxin type C KW - FPM7829VMX KW - Index Medicus KW - Presynaptic Terminals -- ultrastructure KW - Animals KW - Cell Survival -- drug effects KW - Cells, Cultured KW - Mice, Inbred C57BL KW - Microscopy, Electron KW - Mice KW - Spinal Cord -- cytology KW - Neurons -- drug effects KW - Membrane Proteins -- metabolism KW - Neurons -- physiology KW - Botulinum Toxins -- pharmacology KW - Nerve Tissue Proteins -- metabolism KW - Botulinum Toxins, Type A -- pharmacology KW - Neurons -- ultrastructure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79941350?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Syntaxin+and+25-kDa+synaptosomal-associated+protein%3A+differential+effects+of+botulinum+neurotoxins+C1+and+A+on+neuronal+survival.&rft.au=Williamson%2C+L+C%3BNeale%2C+E+A&rft.aulast=Williamson&rft.aufirst=L&rft.date=1998-06-01&rft.volume=52&rft.issue=5&rft.spage=569&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 - 1998-08-21 N1 - Date created - 1998-08-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Vascular endothelial growth factor and basic fibroblast growth factor present in Kaposi's sarcoma (KS) are induced by inflammatory cytokines and synergize to promote vascular permeability and KS lesion development. AN - 79941119; 9626048 AB - All forms of Kaposi's sarcoma (KS) are characterized by spindle cell proliferation, angiogenesis, inflammatory cell infiltration, and edema. We have previously reported that spindle cells of primary KS lesions and KS-derived spindle cell cultures express high levels of basic fibroblast growth factor (bFGF), which is promoted by the inflammatory cytokines identified in these lesions. These cytokines, namely, tumor necrosis factor, interleukin-1, and interferon-gamma, induce production and release of bFGF, which stimulates angiogenesis and spindle cell growth in an autocrine fashion. Here we show that both AIDS-KS and classical KS lesions co-express vascular endothelial growth factor (VEGF) and bFGF. VEGF production by KS cells is promoted synergistically by inflammatory cytokines present in conditioned media from activated T cells and in KS lesions. KS cells show synthesis of VEGF isoforms that are mitogenic to endothelial cells but not to KS spindle cells, suggesting a prevailing paracrine effect of this cytokine. This may be due to the level of expression of the flt-1-VEGF receptor that is down-regulated in KS cells as compared with endothelial cells. KS-derived bFGF and VEGF synergize in inducing endothelial cell growth as shown by studies using both neutralizing antibodies and antisense oligodeoxynucleotides directed against these cytokines. In addition, VEGF and bFGF synergize to induce angiogenic KS-like lesions in nude mice and vascular permeability and edema in guinea pigs. These results indicate that inflammatory cytokines present in KS lesions stimulate the production of bFGF and VEGF, which, in turn, cooperate to induce angiogenesis, edema, and KS lesion formation. JF - The American journal of pathology AU - Samaniego, F AU - Markham, P D AU - Gendelman, R AU - Watanabe, Y AU - Kao, V AU - Kowalski, K AU - Sonnabend, J A AU - Pintus, A AU - Gallo, R C AU - Ensoli, B AD - Laboratory of Tumor Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 1433 EP - 1443 VL - 152 IS - 6 SN - 0002-9440, 0002-9440 KW - Cell Extracts KW - 0 KW - Culture Media, Conditioned KW - Cytokines KW - Endothelial Growth Factors KW - Lymphokines KW - Oligonucleotides, Antisense KW - Proto-Oncogene Proteins KW - Receptors, Growth Factor KW - Vascular Endothelial Growth Factor A KW - Vascular Endothelial Growth Factors KW - Fibroblast Growth Factor 2 KW - 103107-01-3 KW - Receptor Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - Receptors, Vascular Endothelial Growth Factor KW - Vascular Endothelial Growth Factor Receptor-1 KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Animals KW - Extracellular Matrix -- metabolism KW - Guinea Pigs KW - Humans KW - Proto-Oncogene Proteins -- metabolism KW - Mice, Nude KW - Receptor Protein-Tyrosine Kinases -- metabolism KW - Endothelium, Vascular -- physiology KW - Endothelium, Vascular -- drug effects KW - Tumor Cells, Cultured KW - Drug Synergism KW - Neovascularization, Pathologic -- physiopathology KW - Endothelium, Vascular -- metabolism KW - Cytokines -- pharmacology KW - Mice KW - Oligonucleotides, Antisense -- pharmacology KW - Culture Media, Conditioned -- metabolism KW - Receptors, Growth Factor -- metabolism KW - Edema -- physiopathology KW - Immunohistochemistry KW - Fibroblast Growth Factor 2 -- metabolism KW - Lymphokines -- metabolism KW - Sarcoma, Kaposi -- physiopathology KW - Sarcoma, Kaposi -- metabolism KW - Endothelial Growth Factors -- metabolism KW - Capillary Permeability -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79941119?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Vascular+endothelial+growth+factor+and+basic+fibroblast+growth+factor+present+in+Kaposi%27s+sarcoma+%28KS%29+are+induced+by+inflammatory+cytokines+and+synergize+to+promote+vascular+permeability+and+KS+lesion+development.&rft.au=Samaniego%2C+F%3BMarkham%2C+P+D%3BGendelman%2C+R%3BWatanabe%2C+Y%3BKao%2C+V%3BKowalski%2C+K%3BSonnabend%2C+J+A%3BPintus%2C+A%3BGallo%2C+R+C%3BEnsoli%2C+B&rft.aulast=Samaniego&rft.aufirst=F&rft.date=1998-06-01&rft.volume=152&rft.issue=6&rft.spage=1433&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 - 1998-07-07 N1 - Date created - 1998-07-07 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: N Engl J Med. 1995 May 4;332(18):1181-5 [7700310] J Immunol. 1995 Apr 1;154(7):3582-92 [7897237] J Neurosurg. 1995 May;82(5):864-73 [7714613] J Biol Chem. 1995 May 26;270(21):12607-13 [7759509] Oncogene. 1995 May 18;10(10):2007-16 [7761101] Proc Assoc Am Physicians. 1995 Apr;107(1):8-18 [8630748] Am J Pathol. 1996 Apr;148(4):1065-74 [8644848] Am J Pathol. 1996 Dec;149(6):1851-69 [8952523] Proc Natl Acad Sci U S A. 1997 Feb 4;94(3):979-84 [9023368] J Immunol. 1997 Feb 15;158(4):1887-94 [9029130] J Immunol. 1997 May 15;158(10):4992-5001 [9144519] Blood. 1998 Feb 1;91(3):956-67 [9446657] Blood. 1998 Feb 1;91(3):968-76 [9446658] J Cereb Blood Flow Metab. 1998 Sep;18(9):968-77 [9740100] Am J Pathol. 1983 Apr;111(1):62-77 [6301283] Ann Intern Med. 1983 Aug;99(2):145-51 [6603806] N Engl J Med. 1985 Jun 6;312(23):1518 [3990755] J Biol Response Mod. 1985 Aug;4(4):358-64 [3928825] Ann Intern Med. 1985 Nov;103(5):744-50 [3901851] J Clin Microbiol. 1987 Sep;25(9):1695-700 [3498739] Am J Dermatopathol. 1987 Oct;9(5):388-98 [2446517] Dermatologica. 1987;175(6):270-9 [3691903] Science. 1989 Jan 13;243(4888):223-6 [2643161] J Acquir Immune Defic Syndr. 1989;2(1):54-8 [2918461] J Biol Response Mod. 1989 Aug;8(4):359-65 [2666585] Clin Exp Immunol. 1989 Dec;78(3):329-33 [2612049] Nature. 1990 May 3;345(6270):84-6 [2184372] Am J Pathol. 1991 Jan;138(1):9-15 [1987771] Clin Exp Immunol. 1991 Apr;84(1):109-15 [1901776] Mol Endocrinol. 1991 Dec;5(12):1806-14 [1791831] Science. 1992 Mar 13;255(5050):1432-4 [1542793] Biochem Biophys Res Commun. 1992 Mar 31;183(3):1167-74 [1567395] Growth Factors. 1992;7(1):53-64 [1380254] J Exp Med. 1992 Nov 1;176(5):1375-9 [1402682] J Immunol. 1992 Dec 1;149(11):3727-34 [1431144] J Biol Chem. 1992 Dec 25;267(36):26031-7 [1464614] Biochem Biophys Res Commun. 1992 Dec 15;189(2):824-31 [1281999] Am J Pathol. 1993 Jul;143(1):240-9 [8100400] Clin Exp Immunol. 1993 Oct;94(1):43-50 [8403516] J Immunol. 1993 Nov 1;151(9):5031-40 [8409454] Curr Opin Oncol. 1993 Sep;5(5):835-44 [8218496] Lab Invest. 1993 Nov;69(5):508-17 [8246443] Am J Pathol. 1994 Jan;144(1):51-9 [7507301] Nature. 1994 Feb 10;367(6463):576-9 [8107827] J Acquir Immune Defic Syndr. 1994 Jul;7(7):695-9 [7911526] Am J Pathol. 1994 Jul;145(1):74-9 [8030759] J Exp Med. 1994 Sep 1;180(3):1141-6 [8064230] Clin Immunol Immunopathol. 1994 Nov;73(2):252-60 [7923932] Nature. 1994 Oct 20;371(6499):674-80 [7935812] J Clin Invest. 1994 Nov;94(5):1736-46 [7525646] J Clin Invest. 1995 Apr;95(4):1723-34 [7535796] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Late effects in long-term survivors of high-grade non-Hodgkin's lymphomas. AN - 79940710; 9626206 AB - To evaluate long-term survivors of high-grade non-Hodgkin's lymphomas (NHLs) for late effects and to attempt to assess the relative contributions of the primary treatment modalities to these late effects. Of 103 young survivors followed up for 1 to 20 years, 74 patients were interviewed and underwent various investigations, and an additional 12 patients were interviewed only. Of the 86 patients, 65 had previously suffered from small non-cleaved-cell lymphoma, 16 from lymphoblastic lymphoma, and five from large-cell lymphoma. Left ventricular dysfunction was identified in eight of 57 (14.0%) patients who had received doxorubicin (DOX) in doses greater than 200 mg/m2, of whom four were symptomatic and four were asymptomatic. A ninth patient required a pacemaker. Of the 86 patients, 23 (26.7%) reported pregnancies, 18 of whom had 30 children. Two of the 86 (2.3%) patients developed second cancers. Other major late effects included posttransfusion viral hepatitis, eight patients; CNS toxicity, two patients; endocrine impairment, 14 patients; vitamin B12 deficiency, two patients; esophageal stricture, one patient; urinary tract problems, two patients; and musculoskeletal defects, three patients. Major late effects occurred in 11 of 21 (52.4%) patients who had received radiation as well as chemotherapy, eight of 22 (36.4%) patients who had surgical resections as well as chemotherapy, and 17 of 74 (23.0%) patients who had received chemotherapy alone. The predominant major late effects observed were late cardiac toxicity related to DOX therapy and hepatitis C virus infection that presumably resulted from blood product transfusions administered before the introduction of screening for the hepatitis C virus. Fertility was not greatly impaired, and second malignancies were uncommon. No patient had clinically significant impairment of growth. Radiation appeared to increase the likelihood of late effects. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Haddy, T B AU - Adde, M A AU - McCalla, J AU - Domanski, M J AU - Datiles, M AU - Meehan, S C AU - Pikus, A AU - Shad, A T AU - Valdez, I AU - Lopez Vivino, L AU - Magrath, I T AD - Pediatric Oncology Branch, National Cancer Institute, Division of Epidemiology and Clinical Applications, National Institutes of Health, Bethesda, MD, USA. Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 2070 EP - 2079 VL - 16 IS - 6 SN - 0732-183X, 0732-183X KW - Index Medicus KW - Hepatitis, Viral, Human -- complications KW - Humans KW - Neoplasms, Second Primary -- diagnosis KW - Child KW - Central Nervous System Diseases -- complications KW - Endocrine System Diseases -- epidemiology KW - Hepatitis, Viral, Human -- epidemiology KW - Musculoskeletal Diseases -- complications KW - Vitamin B 12 Deficiency -- epidemiology KW - Neoplasms, Second Primary -- epidemiology KW - Adult KW - Ventricular Dysfunction, Left -- epidemiology KW - Adolescent KW - Musculoskeletal Diseases -- epidemiology KW - Survivors KW - Esophageal Stenosis -- epidemiology KW - Male KW - Endocrine System Diseases -- complications KW - Infertility -- complications KW - Vitamin B 12 Deficiency -- complications KW - Infertility -- epidemiology KW - Ventricular Dysfunction, Left -- complications KW - Child, Preschool KW - Central Nervous System Diseases -- epidemiology KW - Urologic Diseases -- complications KW - Esophageal Stenosis -- complications KW - Urologic Diseases -- epidemiology KW - Female KW - Lymphoma, Non-Hodgkin -- epidemiology KW - Lymphoma, Non-Hodgkin -- therapy KW - Lymphoma, Non-Hodgkin -- complications KW - Lymphoma, Non-Hodgkin -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79940710?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Late+effects+in+long-term+survivors+of+high-grade+non-Hodgkin%27s+lymphomas.&rft.au=Haddy%2C+T+B%3BAdde%2C+M+A%3BMcCalla%2C+J%3BDomanski%2C+M+J%3BDatiles%2C+M%3BMeehan%2C+S+C%3BPikus%2C+A%3BShad%2C+A+T%3BValdez%2C+I%3BLopez+Vivino%2C+L%3BMagrath%2C+I+T&rft.aulast=Haddy&rft.aufirst=T&rft.date=1998-06-01&rft.volume=16&rft.issue=6&rft.spage=2070&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 - 1998-07-01 N1 - Date created - 1998-07-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of ionic state of 2'-deoxyguanosine and solvent on its aralkylation by benzyl bromide. AN - 79936706; 9625738 AB - To extend studies of the aralkylation of nucleic acid components under a variety of solvent conditions, we determined product distributions from the reactions of benzyl bromide with 2'-deoxyguanosine and the anion of 2'-deoxyguanosine in 2,2, 2-trifluoroethanol (TFE) and compared these distributions with those from the reaction of the anion with benzyl bromide in N, N-dimethylacetamide (DMA). 7-Benzylguanine was the only benzylated product detected in the reaction with the neutral nucleoside in TFE. In striking contrast, the reaction of the anion of 2'-deoxyguanosine with benzyl bromide in TFE produced N2-benzyl-2'-deoxyguanosine in significant yield and with high selectivity. The reaction of the anion of 2'-deoxyguanosine with benzyl bromide in DMA produced products derived only from reaction at the 1- and/or 7-position of the nucleoside. The weakly nucleophilic but protic polar solvent TFE and the iminolate tautomeric form of the 2'-deoxyguanosine anion appear to be essential for benzylation at the exocyclic N2-position. JF - Chemical research in toxicology AU - Moon, K Y AU - Moschel, R C AD - Chemistry of Carcinogenesis Laboratory, ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, P.O. Box B, Frederick, Maryland 21702, USA. Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 696 EP - 702 VL - 11 IS - 6 SN - 0893-228X, 0893-228X KW - Benzyl Compounds KW - 0 KW - Solvents KW - Deoxyguanosine KW - G9481N71RO KW - benzyl bromide KW - XR75BS721D KW - Index Medicus KW - Deoxyguanosine -- metabolism KW - Benzyl Compounds -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79936706?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Effect+of+ionic+state+of+2%27-deoxyguanosine+and+solvent+on+its+aralkylation+by+benzyl+bromide.&rft.au=Moon%2C+K+Y%3BMoschel%2C+R+C&rft.aulast=Moon&rft.aufirst=K&rft.date=1998-06-01&rft.volume=11&rft.issue=6&rft.spage=696&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 - 1998-07-16 N1 - Date created - 1998-07-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Smad2 transduces common signals from receptor serine-threonine and tyrosine kinases. AN - 79926519; 9620846 AB - SMAD proteins mediate signals from receptor serine-threonine kinases (RSKs) of the TGF-beta superfamily. We demonstrate here that HGF and EGF, which signal through RTKs, can also mediate SMAD-dependent reporter gene activation and induce rapid phosphorylation of endogenous SMAD proteins by kinase(s) downstream of MEK1. HGF induces phosphorylation and nuclear translocation of epitope-tagged Smad2 and a mutation that blocks TGF-beta signaling also blocks HGF signal transduction. Smad2 may thus act as a common positive effector of TGF-beta- and HGF-induced signals and serve to modulate cross talk between RTK and RSK signaling pathways. JF - Genes & development AU - de Caestecker, M P AU - Parks, W T AU - Frank, C J AU - Castagnino, P AU - Bottaro, D P AU - Roberts, A B AU - Lechleider, R J AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892-5055 USA. Y1 - 1998/06/01/ PY - 1998 DA - 1998 Jun 01 SP - 1587 EP - 1592 VL - 12 IS - 11 SN - 0890-9369, 0890-9369 KW - DNA-Binding Proteins KW - 0 KW - Receptors, Transforming Growth Factor beta KW - Smad2 Protein KW - Trans-Activators KW - Epidermal Growth Factor KW - 62229-50-9 KW - Hepatocyte Growth Factor KW - 67256-21-7 KW - Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - Index Medicus KW - Animals KW - Transfection KW - Genes, Tumor Suppressor KW - Hepatocyte Growth Factor -- pharmacology KW - Epidermal Growth Factor -- pharmacology KW - Transcriptional Activation KW - Protein-Tyrosine Kinases -- physiology KW - Protein-Serine-Threonine Kinases -- physiology KW - Cell Line KW - Gene Expression Regulation -- physiology KW - Receptors, Transforming Growth Factor beta -- physiology KW - Gene Expression Regulation -- drug effects KW - DNA-Binding Proteins -- physiology KW - Signal Transduction KW - Receptors, Transforming Growth Factor beta -- agonists UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79926519?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genes+%26+development&rft.atitle=Smad2+transduces+common+signals+from+receptor+serine-threonine+and+tyrosine+kinases.&rft.au=de+Caestecker%2C+M+P%3BParks%2C+W+T%3BFrank%2C+C+J%3BCastagnino%2C+P%3BBottaro%2C+D+P%3BRoberts%2C+A+B%3BLechleider%2C+R+J&rft.aulast=de+Caestecker&rft.aufirst=M&rft.date=1998-06-01&rft.volume=12&rft.issue=11&rft.spage=1587&rft.isbn=&rft.btitle=&rft.title=Genes+%26+development&rft.issn=08909369&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-07-01 N1 - Date created - 1998-07-01 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Fed Proc. 1983 Jun;42(9):2621-6 [6303865] Nature. 1997 Dec 4;390(6659):465-71 [9393997] J Biol Chem. 1990 Oct 25;265(30):18518-24 [2170414] Biochem J. 1992 Dec 1;288 ( Pt 2):351-5 [1334404] Nature. 1993 Jan 7;361(6407):68-71 [8421496] Development. 1994 Feb;120(2):415-24 [8149917] J Biol Chem. 1994 May 6;269(18):13231-7 [8175753] Anal Biochem. 1994 Feb 1;216(2):276-84 [8179182] Blood. 1994 Jul 1;84(1):151-7 [7517205] Nature. 1995 Feb 16;373(6515):573-80 [7531822] Science. 1995 Dec 22;270(5244):2008-11 [8533096] Nature. 1996 Jun 13;381(6583):620-3 [8637600] Cell. 1996 Jun 28;85(7):947-50 [8674122] J Biol Chem. 1996 May 31;271(22):13110-5 [8662798] J Biol Chem. 1996 Jul 26;271(30):17617-20 [8663601] J Biol Chem. 1996 Sep 13;271(37):22368-75 [8798398] J Biol Chem. 1996 Oct 4;271(40):24850-5 [8798760] Nature. 1996 Oct 31;383(6603):832-6 [8893010] Cell. 1996 Dec 27;87(7):1215-24 [8980228] J Biol Chem. 1997 Jan 31;272(5):2896-900 [9006934] J Cell Physiol. 1997 Jan;170(1):57-68 [9012785] J Biol Chem. 1997 Mar 7;272(10):6653-62 [9045696] Dev Biol. 1996 Aug 25;178(1):198-202 [8812122] Curr Biol. 1997 Apr 1;7(4):270-6 [9094310] Genes Dev. 1997 Apr 15;11(8):984-95 [9136927] Oncogene. 1997 Apr 24;14(16):1891-9 [9150356] J Biol Chem. 1997 May 23;272(21):13690-6 [9153220] Cell. 1997 Jun 27;89(7):1165-73 [9215638] Nature. 1997 Jul 17;388(6639):304-8 [9230443] Nature. 1997 Sep 4;389(6646):85-9 [9288972] Nature. 1997 Oct 9;389(6651):618-22 [9335504] Development. 1997 Sep;124(18):3511-23 [9342044] Adv Second Messenger Phosphoprotein Res. 1997;31:41-8 [9344240] J Biol Chem. 1997 Oct 31;272(44):27678-85 [9346908] J Biol Chem. 1997 Oct 31;272(44):28107-15 [9346966] Mol Cell Biol. 1997 Dec;17(12):7019-28 [9372933] Genes Dev. 1997 Dec 1;11(23):3157-67 [9389648] J Biol Chem. 1988 Mar 5;263(7):3111-5 [3125175] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Determination of serum creatinine prior to iodinated contrast media: is it necessary in all patients? AN - 79924663; 9623618 AB - The risk of contrast-associated nephrotoxicity (CAN) is increased in the presence of preexisting renal disease. Although routine determination of serum creatinine (Cr) prior to imaging studies is the traditional method of assessing renal function, it is a costly and time-consuming practice. The purpose of this study was to investigate whether a patient survey could identify patients with a high likelihood of having normal Cr values and who, therefore, did not require serum testing. A survey was administered to 673 consecutive adult patients who were scheduled for contrast-enhanced computed tomography. Survey questions were designed to elicit a history of renal disorders as well as additional risk factors for CAN. Each patient had a Cr level determined within 48 hours prior to the injection of iodinated contrast media. Cr levels were assessed in the patients who gave negative responses to all survey questions. The degree to which positive responses to each survey question predicted elevated Cr levels was determined using the odds ratio (OR). Among the 673 respondents, 577 (85%) had normal Cr values (1.7 mg/dL usually do not receive iodinated contrast media. Using this Cr cutoff value, 189 (99%) of 191 patients with negative responses had Cr values less than or equal to the cutoff value. The survey questions most strongly associated with elevated Cr values pertained to preexisting renal disease (OR 13.6), proteinuria (OR 8.7), prior kidney surgery (OR 8.1), hypertension (OR 5.4), gout (OR 4.6), and diabetes (OR 3.2). If the survey had been limited to these six questions, completely negative responses would have occurred in 450 (67%) of 673, 424 (94%) of these 450 would have normal Cr values, and 446 (99%) of 450 would have had Cr values at or below the 1.7 mg/dL cutoff for iodinated contrast. A completely negative response to a simple (six question) patient survey prior to iodinated contrast administration can identify a significant fraction of patients with normal Cr levels. Use of this survey could reduce by 67% the number of patients undergoing routine Cr determinations prior to imaging studies. This could reduce costs, decrease delays, and increase patient satisfaction associated with imaging studies. JF - Techniques in urology AU - Choyke, P L AU - Cady, J AU - DePollar, S L AU - Austin, H AD - Department of Diagnostic Radiology, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland 20892-1182, USA. Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 65 EP - 69 VL - 4 IS - 2 SN - 1079-3259, 1079-3259 KW - Contrast Media KW - 0 KW - Iodine KW - 9679TC07X4 KW - Creatinine KW - AYI8EX34EU KW - Index Medicus KW - Risk Factors KW - Humans KW - Cost-Benefit Analysis KW - Mass Screening -- economics KW - Adult KW - Aged KW - Middle Aged KW - Unnecessary Procedures -- economics KW - Male KW - Female KW - Contrast Media -- adverse effects KW - Tomography, X-Ray Computed -- economics KW - Renal Insufficiency -- chemically induced KW - Kidney Diseases -- complications KW - Iodine -- adverse effects KW - Renal Insufficiency -- prevention & control KW - Creatinine -- blood KW - Renal Insufficiency -- diagnosis KW - Kidney Diseases -- diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79924663?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Techniques+in+urology&rft.atitle=Determination+of+serum+creatinine+prior+to+iodinated+contrast+media%3A+is+it+necessary+in+all+patients%3F&rft.au=Choyke%2C+P+L%3BCady%2C+J%3BDePollar%2C+S+L%3BAustin%2C+H&rft.aulast=Choyke&rft.aufirst=P&rft.date=1998-06-01&rft.volume=4&rft.issue=2&rft.spage=65&rft.isbn=&rft.btitle=&rft.title=Techniques+in+urology&rft.issn=10793259&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-08-27 N1 - Date created - 1998-08-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Analgesic and cognitive effects of intravenous ketamine-alfentanil combinations versus either drug alone after intradermal capsaicin in normal subjects. AN - 79924450; 9620514 AB - Combinations of opioids and N-methyl-D-aspartate (NMDA) antagonists enhance acute antinociception and reduce opioid tolerance in some animal experiments but have received little rigorous study in humans. To quantitatively assess the nature of the interaction of these two classes of drugs in producing analgesia and cognitive impairment, we compared i.v. infusions of ketamine, alfentanil, and ketamine-alfentanil combinations in 12 normal volunteers after an intradermal injection of capsaicin. Drug doses for a 70-kg subject in this six-session, randomized, double-blind, cross-over study were: ketamine 20 mg, ketamine 5 mg, alfentanil 2 mg, alfentanil 0.5 mg, ketamine 10 mg + alfentanil 1 mg, and ketamine 2.5 mg + alfentanil 0.25 mg, given over 35 min. Outcome measures were background pain, area and magnitude of hyperalgesia to pinprick, and cognitive performance on the Digit Symbol Substitution Test and the Perception Speed Test. The results demonstrated simple additivity for the effects of ketamine and alfentanil on pain, pinprick hyperalgesia, and cognitive impairment. We conclude that, at least in this experimental pain model, there is no clear advantage or disadvantage of a ketamine-alfentanil combination over equianalgesic doses of either component. In a double-blind, controlled trial, we administered doses of an opioid analgesic (alfentanil), an N-methyl-D-aspartate receptor antagonist (ketamine), or their combination to normal volunteers and found no advantage of the combination over a larger dose of either drug alone in relieving pain caused by painful chemical stimulation. JF - Anesthesia and analgesia AU - Sethna, N F AU - Liu, M AU - Gracely, R AU - Bennett, G J AU - Max, M B AD - Pain and Neurosensory Mechanisms Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892-1258, USA. Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 1250 EP - 1256 VL - 86 IS - 6 SN - 0003-2999, 0003-2999 KW - Analgesics KW - 0 KW - Analgesics, Opioid KW - Anesthetics, Dissociative KW - Drug Combinations KW - Excitatory Amino Acid Antagonists KW - Irritants KW - Alfentanil KW - 1N74HM2BS7 KW - Ketamine KW - 690G0D6V8H KW - Capsaicin KW - S07O44R1ZM KW - Abridged Index Medicus KW - Index Medicus KW - Hyperalgesia -- prevention & control KW - Double-Blind Method KW - Infusions, Intravenous KW - Humans KW - Injections, Intradermal KW - Psychomotor Performance -- drug effects KW - Adult KW - Treatment Outcome KW - Cross-Over Studies KW - Female KW - Hyperalgesia -- chemically induced KW - Male KW - Capsaicin -- adverse effects KW - Anesthetics, Dissociative -- administration & dosage KW - Excitatory Amino Acid Antagonists -- administration & dosage KW - Irritants -- adverse effects KW - Ketamine -- administration & dosage KW - Alfentanil -- administration & dosage KW - Pain -- prevention & control KW - Irritants -- administration & dosage KW - Anesthetics, Dissociative -- therapeutic use KW - Cognition -- drug effects KW - Pain -- chemically induced KW - Excitatory Amino Acid Antagonists -- therapeutic use KW - Alfentanil -- therapeutic use KW - Analgesics, Opioid -- therapeutic use KW - Ketamine -- therapeutic use KW - Analgesics, Opioid -- administration & dosage KW - Capsaicin -- administration & dosage KW - Analgesics -- administration & dosage KW - Analgesics -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79924450?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Anesthesia+and+analgesia&rft.atitle=Analgesic+and+cognitive+effects+of+intravenous+ketamine-alfentanil+combinations+versus+either+drug+alone+after+intradermal+capsaicin+in+normal+subjects.&rft.au=Sethna%2C+N+F%3BLiu%2C+M%3BGracely%2C+R%3BBennett%2C+G+J%3BMax%2C+M+B&rft.aulast=Sethna&rft.aufirst=N&rft.date=1998-06-01&rft.volume=86&rft.issue=6&rft.spage=1250&rft.isbn=&rft.btitle=&rft.title=Anesthesia+and+analgesia&rft.issn=00032999&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-06-19 N1 - Date created - 1998-06-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Physiologically based pharmacokinetics model of primidone and its metabolites phenobarbital and phenylethylmalonamide in humans, rats, and mice. AN - 79924362; 9616196 AB - Physiologically based pharmacokinetic modeling of the parent chemical primidone and its two metabolites phenobarbital and phenylethylmalonamide (PEMA) was applied to investigate the differences of primidone metabolism among humans, rats, and mice. The model simulated previously published pharmacokinetic data of the parent chemical and its metabolites in plasma and brain tissues from separate studies of the three species. Metabolism of primidone and its metabolites varied widely among a sample of three human subjects from two separate studies. Estimated primidone metabolism, as expressed by the maximal velocity Vmax, ranged from 0 to 0.24 mg. min-1.kg-1 for the production of phenobarbital and from 0.003 to 0. 02 mg.min-1.kg-1 for the production of PEMA among three human subjects. Further model simulations indicated that rats were more efficient at producing and clearing phenobarbital and PEMA than mice. However, the overall metabolism profile of primidone and its metabolites in mice indicated that mice were at higher risk of toxicity owing to higher residence of phenobarbital in their tissues and owing to the carcinogenic potential of phenobarbital as illustrated in long-term bioassays. This result was in agreement with a recently finished National Toxicology Program (NTP) carcinogenicity study of primidone in rats and mice. JF - Drug metabolism and disposition: the biological fate of chemicals AU - El-Masri, H A AU - Portier, C J AD - Laboratory of Computational Biology and Risk Analysis, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 585 EP - 594 VL - 26 IS - 6 SN - 0090-9556, 0090-9556 KW - Anticonvulsants KW - 0 KW - Primidone KW - 13AFD7670Q KW - Phenylethylmalonamide KW - 7206-76-0 KW - Phenobarbital KW - YQE403BP4D KW - Index Medicus KW - Rats KW - Animals KW - Humans KW - Mice KW - Species Specificity KW - Models, Biological KW - Phenylethylmalonamide -- pharmacokinetics KW - Anticonvulsants -- pharmacokinetics KW - Primidone -- pharmacokinetics KW - Phenobarbital -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79924362?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Physiologically+based+pharmacokinetics+model+of+primidone+and+its+metabolites+phenobarbital+and+phenylethylmalonamide+in+humans%2C+rats%2C+and+mice.&rft.au=El-Masri%2C+H+A%3BPortier%2C+C+J&rft.aulast=El-Masri&rft.aufirst=H&rft.date=1998-06-01&rft.volume=26&rft.issue=6&rft.spage=585&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 - 1998-07-01 N1 - Date created - 1998-07-01 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Drug Metab Dispos 1998 Dec;26(12):1222 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription. AN - 79923658; 9620779 AB - CpG methylation in vertebrates correlates with alterations in chromatin structure and gene silencing. Differences in DNA-methylation status are associated with imprinting phenomena and carcinogenesis. In Xenopus laevis oocytes, DNA methylation dominantly silences transcription through the assembly of a repressive nucleosomal array. Methylated DNA assembled into chromatin binds the transcriptional repressor MeCP2 which cofractionates with Sin3 and histone deacetylase. Silencing conferred by MeCP2 and methylated DNA can be relieved by inhibition of histone deacetylase, facilitating the remodelling of chromatin and transcriptional activation. These results establish a direct causal relationship between DNA methylation-dependent transcriptional silencing and the modification of chromatin. JF - Nature genetics AU - Jones, P L AU - Veenstra, G J AU - Wade, P A AU - Vermaak, D AU - Kass, S U AU - Landsberger, N AU - Strouboulis, J AU - Wolffe, A P AD - Laboratory of Molecular Embryology, National Institute of Child Health and Human Development, National Institute of Health, Bethesda, Maryland 20892-5431, USA. Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 187 EP - 191 VL - 19 IS - 2 SN - 1061-4036, 1061-4036 KW - Chromosomal Proteins, Non-Histone KW - 0 KW - DNA-Binding Proteins KW - MECP2 protein, Xenopus KW - Methyl-CpG-Binding Protein 2 KW - Repressor Proteins KW - SIN3 protein, S cerevisiae KW - Saccharomyces cerevisiae Proteins KW - Transcription Factors KW - Xenopus Proteins KW - Histone Deacetylases KW - EC 3.5.1.98 KW - Index Medicus KW - Xenopus laevis KW - Animals KW - Transcription Factors -- metabolism KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Binding Sites KW - DNA Methylation KW - Repressor Proteins -- metabolism KW - Histone Deacetylases -- metabolism KW - Transcription, Genetic KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79923658?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+genetics&rft.atitle=Methylated+DNA+and+MeCP2+recruit+histone+deacetylase+to+repress+transcription.&rft.au=Jones%2C+P+L%3BVeenstra%2C+G+J%3BWade%2C+P+A%3BVermaak%2C+D%3BKass%2C+S+U%3BLandsberger%2C+N%3BStrouboulis%2C+J%3BWolffe%2C+A+P&rft.aulast=Jones&rft.aufirst=P&rft.date=1998-06-01&rft.volume=19&rft.issue=2&rft.spage=187&rft.isbn=&rft.btitle=&rft.title=Nature+genetics&rft.issn=10614036&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-07-01 N1 - Date created - 1998-07-01 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF106951; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The chromo and SET domains of the Clr4 protein are essential for silencing in fission yeast. AN - 79921468; 9620780 AB - Heritable inactivation of specific regions of the genome is a widespread, possibly universal phenomenon for gene regulation in eukaryotes. Self-perpetuating, clonally inherited chromatin structure has been proposed as the explanation for such phenomena as position-effect variegation (PEV) and control of segment determination and differentiation in flies, X-chromosome inactivation and parental imprinting in mammals, gene silencing by paramutation in maize and silencing of the mating-type loci in yeasts. We have now found that the clr4 gene, which is essential for silencing of centromeres and the mating-type loci in Schizosaccharomyces pombe, encodes a protein with high homology to the product of Su(var)3-9, a gene affecting PEV in Drosophila. Like Su(var)3-9p, Clr4p contains SET and chromo domains, motifs found in proteins that modulate chromatin structure. Site-directed mutations in the conserved residues of the chromo domain confirm that it is required for proper silencing and directional switching of the mating type, like SET domain. Surprisingly, RNA differential display experiments demonstrated that clr4+ can mediate transcriptional activation of certain other loci. These results show that clr4 plays a critical role in silencing at mating-type loci and centromeres through the organization of repressive chromatin structure and demonstrate a new, activator function for Clr4p. JF - Nature genetics AU - Ivanova, A V AU - Bonaduce, M J AU - Ivanov, S V AU - Klar, A J AD - NCI-Frederick Cancer Research and Development Center, ABL-Basic Research Program, Gene Regulation and Chromosome Biology Laboratory, Frederick, Maryland 21702-1201, USA. Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 192 EP - 195 VL - 19 IS - 2 SN - 1061-4036, 1061-4036 KW - Cell Cycle Proteins KW - 0 KW - Codon, Terminator KW - Repressor Proteins KW - Schizosaccharomyces pombe Proteins KW - clr4 protein, S pombe KW - Methyltransferases KW - EC 2.1.1.- KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Centromere -- genetics KW - Animals KW - Sequence Alignment KW - Humans KW - Drosophila melanogaster KW - Molecular Sequence Data KW - Mice KW - Amino Acid Sequence KW - Spores KW - Structure-Activity Relationship KW - Cell Cycle Proteins -- physiology KW - Schizosaccharomyces -- genetics KW - Cell Cycle Proteins -- genetics KW - Repressor Proteins -- physiology KW - Schizosaccharomyces -- physiology KW - Repressor Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79921468?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+genetics&rft.atitle=The+chromo+and+SET+domains+of+the+Clr4+protein+are+essential+for+silencing+in+fission+yeast.&rft.au=Ivanova%2C+A+V%3BBonaduce%2C+M+J%3BIvanov%2C+S+V%3BKlar%2C+A+J&rft.aulast=Ivanova&rft.aufirst=A&rft.date=1998-06-01&rft.volume=19&rft.issue=2&rft.spage=192&rft.isbn=&rft.btitle=&rft.title=Nature+genetics&rft.issn=10614036&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-07-01 N1 - Date created - 1998-07-01 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - P23198; GENBANK; AF061854; P23197; P40381; L07515; P26017; P05205; X80070; L34658; A25081 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Rapid extraction of genomic DNA from medically important yeasts and filamentous fungi by high-speed cell disruption. AN - 79920417; 9620390 AB - Current methods of DNA extraction from different fungal pathogens are often time-consuming and require the use of toxic chemicals. DNA isolation from some fungal organisms is difficult due to cell walls or capsules that are not readily susceptible to lysis. We therefore investigated a new and rapid DNA isolation method using high-speed cell disruption (HSCD) incorporating chaotropic reagents and lysing matrices in comparison to standard phenol-chloroform (PC) extraction protocols for isolation of DNA from three medically important yeasts (Candida albicans, Cryptococcus neoformans, and Trichosporon beigelii) and two filamentous fungi (Aspergillus fumigatus and Fusarium solani). Additional extractions by HSCD were performed on Saccharomyces cerevisiae, Pseudallescheria boydii, and Rhizopus arrhizus. Two different inocula (10(8) and 10(7) CFU) were compared for optimization of obtained yields. The entire extraction procedure was performed on as many as 12 samples within 1 h compared to 6 h for PC extraction. In comparison to the PC procedure, HSCD DNA extraction demonstrated significantly greater yields for 10(8) CFU of C. albicans, T. beigelii, A. fumigatus, and F. solani (P < or = 0.005), 10(7) CFU of C. neoformans (P < or = 0.05), and 10(7) CFU of A. fumigatus (P < or = 0.01). Yields were within the same range for 10(8) CFU of C. neoformans and l0(7) CFU of C. albicans for both HSCD extraction and PC extraction. For 10(7) CFU of T. beigelii, PC extraction resulted in a greater yield than did HSCD (P < or = 0.05). Yields obtained from 10(8) and 10(7) CFU were significantly greater for filamentous fungi than for yeasts by the HSCD extraction procedure (P < 0.0001). By the PC extraction procedure, differences were not significant. For all eight organisms, the rapid extraction procedure resulted in good yield, integrity, and quality of DNA as demonstrated by restriction fragment length polymorphism, PCR, and random amplified polymorphic DNA. We conclude that mechanical disruption of fungal cells by HSCD is a safe, rapid, and efficient procedure for extracting genomic DNA from medically important yeasts and especially from filamentous fungi. JF - Journal of clinical microbiology AU - Müller, F M AU - Werner, K E AU - Kasai, M AU - Francesconi, A AU - Chanock, S J AU - Walsh, T J AD - Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. frank.mueller@mail.uni-wuerzburg.de Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 1625 EP - 1629 VL - 36 IS - 6 SN - 0095-1137, 0095-1137 KW - DNA, Fungal KW - 0 KW - Phenol KW - 339NCG44TV KW - Chloroform KW - 7V31YC746X KW - Index Medicus KW - Polymerase Chain Reaction KW - Polymorphism, Restriction Fragment Length KW - Vibration KW - Random Amplified Polymorphic DNA Technique KW - DNA, Fungal -- isolation & purification KW - Mycology -- methods KW - Yeasts -- genetics KW - Fungi -- genetics KW - Mitosporic Fungi -- genetics KW - Fungi -- growth & development UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79920417?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+microbiology&rft.atitle=Rapid+extraction+of+genomic+DNA+from+medically+important+yeasts+and+filamentous+fungi+by+high-speed+cell+disruption.&rft.au=M%C3%BCller%2C+F+M%3BWerner%2C+K+E%3BKasai%2C+M%3BFrancesconi%2C+A%3BChanock%2C+S+J%3BWalsh%2C+T+J&rft.aulast=M%C3%BCller&rft.aufirst=F&rft.date=1998-06-01&rft.volume=36&rft.issue=6&rft.spage=1625&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+microbiology&rft.issn=00951137&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-07-28 N1 - Date created - 1998-07-28 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Anal Biochem. 1982 Jan 1;119(1):158-63 [7041693] J Clin Microbiol. 1997 Jun;35(6):1353-60 [9163443] Anal Biochem. 1987 Jul;164(1):207-13 [2823631] J Infect Dis. 1990 Nov;162(5):1151-8 [1977804] Appl Environ Microbiol. 1991 Apr;57(4):1070-4 [1647749] J Clin Microbiol. 1991 Apr;29(4):810-2 [1909713] Curr Genet. 1991 Nov;20(5):391-6 [1807830] Nucleic Acids Res. 1992 May 11;20(9):2380 [1594460] Biotechnol Prog. 1993 Sep-Oct;9(5):462-7 [7764162] Genet Anal Tech Appl. 1994;11(1):7-11 [8060679] Anal Biochem. 1994 Nov 1;222(2):511-4 [7532381] Biotechniques. 1995 Jan;18(1):62-3 [7702855] J Bacteriol. 1995 Jun;177(11):3220-6 [7539418] Biotechniques. 1995 Apr;18(4):636 [7598897] Biotechniques. 1995 Jun;18(6):975, 978 [7546720] J Clin Microbiol. 1995 Dec;33(12):3216-20 [8586705] Appl Environ Microbiol. 1996 Jun;62(6):1935-43 [8787391] Mol Biotechnol. 1996 Feb;5(1):1-10 [8853011] Microbios. 1985;43(176S):233-43 [3879524] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Spontaneous development of plasmacytoid tumors in mice with defective Fas-Fas ligand interactions. AN - 79906403; 9607923 AB - B cell malignancies arise with increased frequency in aging individuals and in patients with genetic or acquired immunodeficiency (e.g., AIDS) or autoimmune diseases. The mechanisms of lymphomagenesis in these individuals are poorly understood. In this report we investigated the possibility that mutations at the Fas (lpr) and Fasl (gld) loci, which prevent Fas-mediated apoptosis and cause an early onset benign lymphoid hyperplasia and autoimmunity, also predispose mice to malignant lymphomas later in life. Up to 6 mo of age, hyperplasia in lpr and gld mice results from the predominant accumulation of polyclonal T cell subsets and smaller numbers of polyclonal B cells and plasma cells. Here, we examined C3H-lpr, C3H-gld, and BALB-gld mice 6-15 mo of age for the emergence of clonal T and B cell populations and found that a significant proportion of aging mice exclusively developed B cell malignancies with many of the hallmarks of immunodeficiency-associated B lymphomas. By 1 yr of age, approximately 60% of BALB-gld and 30% of C3H-gld mice had monoclonal B cell populations that grew and metastasized in scid recipients but in most cases were rejected by immunocompetent mice. The tumors developed in a milieu greatly enriched for plasma cells, CD23- B cells and immunodeficient memory T cells and variably depleted of B220+ DN T cells. Growth factor-independent cell lines were established from five of the tumors. The majority of the tumors were CD23- and IgH isotype switched and a high proportion was CD5+ and dull Mac-1+. Considering their Ig secretion and morphology in vivo, most tumors were classified as malignant plasmacytoid lymphomas. The delayed development of the gld tumors indicated that genetic defects in addition to the Fas/Fasl mutations were necessary for malignant transformation. Interestingly, none of the tumors showed changes in the genomic organization of c-Myc but many had one or more somatically-acquired MuLV proviral integrations that were transmitted in scid passages and cell lines. Therefore, insertional mutagenesis may be a mechanism for transformation in gld B cells. Our panel of in vivo passaged and in vitro adapted gld lymphomas will be a valuable tool for the future identification of genetic abnormalities associated with B cell transformation in aging and autoimmune mice. JF - The Journal of experimental medicine AU - Davidson, W F AU - Giese, T AU - Fredrickson, T N AD - Laboratory of Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. davidson@hlsun.recross.org Y1 - 1998/06/01/ PY - 1998 DA - 1998 Jun 01 SP - 1825 EP - 1838 VL - 187 IS - 11 SN - 0022-1007, 0022-1007 KW - Antigens, CD95 KW - 0 KW - Fas Ligand Protein KW - Fasl protein, mouse KW - Membrane Glycoproteins KW - Index Medicus KW - T-Lymphocyte Subsets -- cytology KW - Animals KW - Leukemia Virus, Murine -- genetics KW - B-Lymphocyte Subsets -- cytology KW - Mice KW - Virus Integration KW - Mice, Inbred BALB C KW - Phenotype KW - Tumor Cells, Cultured KW - Mice, Inbred C3H KW - Proviruses -- genetics KW - Mice, Inbred MRL lpr KW - Mice, SCID KW - Aging -- immunology KW - Leukemia, Lymphocytic, Chronic, B-Cell -- immunology KW - Leukemia, Lymphocytic, Chronic, B-Cell -- pathology KW - Membrane Glycoproteins -- immunology KW - Antigens, CD95 -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79906403?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Spontaneous+development+of+plasmacytoid+tumors+in+mice+with+defective+Fas-Fas+ligand+interactions.&rft.au=Davidson%2C+W+F%3BGiese%2C+T%3BFredrickson%2C+T+N&rft.aulast=Davidson&rft.aufirst=W&rft.date=1998-06-01&rft.volume=187&rft.issue=11&rft.spage=1825&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 - 1998-07-01 N1 - Date created - 1998-07-01 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Int J Cancer. 1972 Sep 15;10(2):273-82 [4513130] Cancer Res. 1992 Oct 1;52(19 Suppl):5529s-5540s [1394168] Cell. 1980 Nov;22(1 Pt 1):187-96 [6775817] Proc Natl Acad Sci U S A. 1980 Oct;77(10):5774-8 [6255464] Nature. 1981 Apr 2;290(5805):372-8 [6783959] Nature. 1984 Mar 8-14;308(5955):153-8 [6546606] J Immunol. 1985 Jan;134(1):196-203 [3880569] J Exp Med. 1985 Mar 1;161(3):602-16 [2982991] Prog Allergy. 1986;37:259-300 [3515352] J Immunol. 1986 Jun 1;136(11):4075-84 [3009614] J Immunol. 1987 Nov 1;139(9):2970-6 [3117883] J Immunol. 1988 Feb 15;140(4):1022-7 [3125247] Immunol Rev. 1988 Feb;102:5-28 [2966762] J Immunol. 1992 Nov 1;149(9):3097-106 [1383337] Carcinogenesis. 1992 Oct;13(10):1681-97 [1423827] Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):1756-60 [7680478] Proc Natl Acad Sci U S A. 1993 May 15;90(10):4409-13 [8506280] J Immunol. 1993 Jul 15;151(2):597-609 [7687618] Eur J Immunol. 1993 Sep;23(9):2379-82 [8370416] Proc Natl Acad Sci U S A. 1993 Nov 15;90(22):10734-8 [7504280] Cell. 1993 Dec 17;75(6):1169-78 [7505205] J Exp Med. 1994 Mar 1;179(3):873-9 [7509364] Cell. 1994 Mar 25;76(6):969-76 [7511063] N Engl J Med. 1994 May 5;330(18):1267-71 [8145781] J Immunol. 1994 Sep 15;153(6):2831-42 [8077685] AIDS. 1994 Aug;8(8):1025-49 [7986399] J Exp Med. 1995 Feb 1;181(2):641-8 [7530760] J Immunol. 1995 Mar 1;154(5):2063-74 [7868883] J Exp Med. 1995 Mar 1;181(3):1157-67 [7532679] J Immunol. 1995 May 15;154(10):4986-95 [7537297] Science. 1995 Jun 2;268(5215):1347-9 [7539157] In Vivo. 1994 Nov-Dec;8(6):953-9 [7772747] Cell. 1995 Jun 16;81(6):935-46 [7540117] Oncogene. 1995 Jun 15;10(12):2397-401 [7784089] J Exp Med. 1995 Jul 1;182(1):129-37 [7540646] Immunity. 1995 Oct;3(4):509-19 [7584141] Clin Immunol Immunopathol. 1996 Jan;78(1):21-9 [8599880] Biochim Biophys Acta. 1996 May 16;1287(1):29-57 [8639705] J Immunol. 1996 Jun 15;156(12):4932-9 [8648144] N Engl J Med. 1996 Nov 28;335(22):1643-9 [8929361] Blood. 1997 Feb 1;89(3):902-9 [9028321] J Exp Med. 1989 May 1;169(5):1747-56 [2469768] Science. 1989 Jul 21;245(4915):301-5 [2787530] Adv Immunol. 1989;46:221-61 [2528897] Br J Cancer. 1990 Feb;61(2):276-8 [2310679] Immunol Today. 1990 Jul;11(7):234-6 [2201308] Proc Natl Acad Sci U S A. 1990 Sep;87(18):6964-8 [2402486] J Exp Med. 1990 Dec 1;172(6):1625-31 [2124252] Nature. 1991 Jan 24;349(6307):331-4 [1898987] Int Rev Cytol. 1991;124:187-215 [2001916] Eur J Immunol. 1991 Apr;21(4):1081-4 [1902176] J Immunol. 1991 Jun 15;146(12):4138-48 [1674953] Cell. 1991 Jul 26;66(2):233-43 [1713127] Annu Rev Immunol. 1991;9:243-69 [1910678] J Exp Med. 1996 Sep 1;184(3):1149-54 [9064331] Blood. 1997 Dec 1;90(11):4266-70 [9373236] Lancet. 1991 Nov 9;338(8776):1175-6 [1682595] Cancer Res. 1992 Jan 15;52(2):437-43 [1370214] Nature. 1992 Mar 26;356(6367):314-7 [1372394] J Clin Invest. 1992 Aug;90(2):334-41 [1386609] AIDS. 1992 Jul;6(7):607-21 [1503680] J Natl Cancer Inst. 1974 Feb;52(2):377-85 [4361176] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Luteinizing hormone releasing hormone (LHRH) neurons maintained in nasal explants decrease LHRH messenger ribonucleic acid levels after activation of GABA(A) receptors. AN - 79905197; 9607779 AB - Inhibition of the LHRH system appears to play an important role in preventing precocious activation of the hypothalamic-pituitary-gonadal axis. Evidence points to gamma-aminobutyric acid (GABA) as the major negative regulator of postnatal LHRH neuronal activity. Changes in LHRH messenger RNA (mRNA) levels after alterations of GABAergic activity have been reported in vivo. However, the extent to which GABA acts directly on LHRH neurons to effect LHRH mRNA levels has been difficult to ascertain. The present work evaluates the effect of GABAergic activity, via GABA(A) receptors, on LHRH neuropeptide gene expression in LHRH neurons maintained in olfactory explants generated from E11.5 mouse embryos. These explants maintain large numbers of primary LHRH neurons that migrate from bilateral olfactory pits in a directed manner. Using in situ hybridization histochemistry and single cell analysis, we report dramatic alterations in LHRH mRNA levels. Inhibition of spontaneous synaptic activity by GABA(A) antagonists, bicuculline (10(-5) M) or picrotoxin (10(-4) M), or of electrical activity by tetrodotoxin (TTX, 10(-6) M) significantly increased LHRH mRNA levels. In contrast, LHRH mRNA levels decreased in explants cultured with the GABA(A) receptor agonist, muscimol (10(-4) M), or KCl (50 mM). The observed responses suggest that LHRH neurons possess functional pathways linking GABA(A) receptors to repression of neuropeptide gene expression and indicate that gene expression in embryonic LHRH neurons, outside the CNS, is highly responsive to alterations in neuronal activity. JF - Endocrinology AU - Fueshko, S M AU - Key, S AU - Wray, S AD - Laboratory of Neurochemistry, National Institute of Neurological Disease and Stroke, National Institutes of Health, Bethesda, Maryland 20892-4130, USA. Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 2734 EP - 2740 VL - 139 IS - 6 SN - 0013-7227, 0013-7227 KW - GABA Antagonists KW - 0 KW - RNA, Messenger KW - Receptors, GABA-A KW - Gonadotropin-Releasing Hormone KW - 33515-09-2 KW - Tetrodotoxin KW - 4368-28-9 KW - Potassium Chloride KW - 660YQ98I10 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Mice -- embryology KW - Potassium Chloride -- pharmacology KW - Gene Expression Regulation -- drug effects KW - Tetrodotoxin -- pharmacology KW - GABA Antagonists -- pharmacology KW - Gonadotropin-Releasing Hormone -- metabolism KW - Cytological Techniques KW - Receptors, GABA-A -- physiology KW - Neurons -- metabolism KW - RNA, Messenger -- metabolism KW - Neurons -- drug effects KW - Neurons -- physiology KW - Olfactory Mucosa -- physiology KW - Gonadotropin-Releasing Hormone -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79905197?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Luteinizing+hormone+releasing+hormone+%28LHRH%29+neurons+maintained+in+nasal+explants+decrease+LHRH+messenger+ribonucleic+acid+levels+after+activation+of+GABA%28A%29+receptors.&rft.au=Fueshko%2C+S+M%3BKey%2C+S%3BWray%2C+S&rft.aulast=Fueshko&rft.aufirst=S&rft.date=1998-06-01&rft.volume=139&rft.issue=6&rft.spage=2734&rft.isbn=&rft.btitle=&rft.title=Endocrinology&rft.issn=00137227&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-06-24 N1 - Date created - 1998-06-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Recombinant human eosinophil-derived neurotoxin/RNase 2 functions as an effective antiviral agent against respiratory syncytial virus. AN - 79902147; 9607820 AB - A dose-dependent decrease in infectivity was observed on introduction of eosinophils into suspensions of respiratory syncytial virus group B (RSV-B). This antiviral effect was reversed by ribonuclease inhibitor, suggesting a role for the eosinophil secretory ribonucleases. Recombinant eosinophil-derived neurotoxin (rhEDN), the major eosinophil ribonuclease, promoted a dose-dependent decrease in RSV-B infectivity, with a 40-fold reduction observed in response to 50 nM rhEDN. Ribonucleolytically inactivated rhEDN (rhEDNdK38) had no antiviral activity. Semiquantitative reverse transcriptase-polymerase chain reaction demonstrated loss of viral genomic RNA in response to rhEDN, suggesting that this protein promotes the direct ribonucleolytic destruction of extracellular virions. Ribonuclease A had no antiviral activity even at approximately 1000-fold higher concentrations, suggesting that rhEDN has unique features other than ribonuclease activity that are crucial to its effectiveness. These results suggest that rhEDN may have potential as a therapeutic agent for prevention or treatment of disease caused by RSV. JF - The Journal of infectious diseases AU - Domachowske, J B AU - Dyer, K D AU - Bonville, C A AU - Rosenberg, H F AD - Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 1458 EP - 1464 VL - 177 IS - 6 SN - 0022-1899, 0022-1899 KW - Antiviral Agents KW - 0 KW - Placental Hormones KW - Proteins KW - Recombinant Fusion Proteins KW - placental ribonuclease inhibitor KW - 120178-77-0 KW - Eosinophil-Derived Neurotoxin KW - EC 3.1.- KW - Ribonucleases KW - Ribonuclease, Pancreatic KW - EC 3.1.27.5 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Cattle KW - Tumor Cells, Cultured KW - Placental Hormones -- pharmacology KW - Dose-Response Relationship, Drug KW - Cells, Cultured KW - Humans KW - Molecular Sequence Data KW - Recombinant Fusion Proteins -- pharmacology KW - Amino Acid Sequence KW - Sequence Homology, Amino Acid KW - Proteins -- pharmacology KW - Ribonuclease, Pancreatic -- physiology KW - Respiratory Syncytial Virus, Human -- genetics KW - Ribonuclease, Pancreatic -- pharmacology KW - Ribonuclease, Pancreatic -- antagonists & inhibitors KW - Eosinophils -- physiology KW - Eosinophils -- enzymology KW - Antiviral Agents -- pharmacology KW - Respiratory Syncytial Virus, Human -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79902147?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Recombinant+human+eosinophil-derived+neurotoxin%2FRNase+2+functions+as+an+effective+antiviral+agent+against+respiratory+syncytial+virus.&rft.au=Domachowske%2C+J+B%3BDyer%2C+K+D%3BBonville%2C+C+A%3BRosenberg%2C+H+F&rft.aulast=Domachowske&rft.aufirst=J&rft.date=1998-06-01&rft.volume=177&rft.issue=6&rft.spage=1458&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 - 1998-06-18 N1 - Date created - 1998-06-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Borrelia burgdorferi erp proteins are immunogenic in mammals infected by tick bite, and their synthesis is inducible in cultured bacteria. AN - 79889037; 9596729 AB - Borrelia burgdorferi, the causative agent of Lyme disease, can contain multiple genes encoding different members of the Erp lipoprotein family. Some arthropod-borne bacteria increase the synthesis of proteins required for transmission or mammalian infection when cultures are shifted from cool, ambient air temperature to a warmer, blood temperature. We found that all of the erp genes known to be encoded by infectious isolate B31 were differentially expressed in culture after a change in temperature, with greater amounts of message being produced by bacteria shifted from 23 to 35 degrees C than in those maintained at 23 degrees C. Mice infected with B31 by tick bite produced antibodies that recognized each of the Erp proteins within 4 weeks of infection, suggesting that the Erp proteins are produced by the bacteria during the early stages of mammalian infection and may play roles in transmission from ticks to mammals. Several of the B31 Erp proteins were also recognized by antibodies from patients with Lyme disease and may prove to be useful antigens for diagnostic testing or as components of a protective vaccine. JF - Infection and immunity AU - Stevenson, B AU - Bono, J L AU - Schwan, T G AU - Rosa, P AD - Laboratory of Microbial Structure and Function, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840, USA. lkspic00@pop.uky.edu Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 2648 EP - 2654 VL - 66 IS - 6 SN - 0019-9567, 0019-9567 KW - Antibodies, Bacterial KW - 0 KW - Antigens, Bacterial KW - Lipoproteins KW - RNA, Bacterial KW - RNA, Messenger KW - Index Medicus KW - Gene Expression Regulation, Bacterial KW - Animals KW - Genes, Bacterial KW - Peromyscus -- parasitology KW - Humans KW - Temperature KW - Antigens, Bacterial -- immunology KW - RNA, Bacterial -- genetics KW - Sequence Analysis, DNA KW - RNA, Messenger -- genetics KW - Cloning, Molecular KW - Lyme Disease -- blood KW - Antibodies, Bacterial -- blood KW - Molecular Sequence Data KW - Peromyscus -- microbiology KW - Ixodes KW - Borrelia burgdorferi Group -- immunology KW - Lipoproteins -- genetics KW - Lipoproteins -- immunology KW - Bites and Stings KW - Lipoproteins -- biosynthesis KW - Borrelia burgdorferi Group -- pathogenicity KW - Borrelia burgdorferi Group -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79889037?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Infection+and+immunity&rft.atitle=Borrelia+burgdorferi+erp+proteins+are+immunogenic+in+mammals+infected+by+tick+bite%2C+and+their+synthesis+is+inducible+in+cultured+bacteria.&rft.au=Stevenson%2C+B%3BBono%2C+J+L%3BSchwan%2C+T+G%3BRosa%2C+P&rft.aulast=Stevenson&rft.aufirst=B&rft.date=1998-06-01&rft.volume=66&rft.issue=6&rft.spage=2648&rft.isbn=&rft.btitle=&rft.title=Infection+and+immunity&rft.issn=00199567&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-06-25 N1 - Date created - 1998-06-25 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - U78764; GENBANK; AF020657 N1 - SuppNotes - Cited By: Cell. 1997 Jun 27;89(7):1111-9 [9215633] J Bacteriol. 1997 Jul;179(13):4285-91 [9209045] Nature. 1997 Dec 11;390(6660):580-6 [9403685] Microbiology. 1998 Apr;144 ( Pt 4):1033-44 [9579077] Microbiology. 1998 Jul;144 ( Pt 7):1869-79 [9695920] Res Microbiol. 1997 Feb;148(2):109-18 [9765792] Infect Immun. 1978 Aug;21(2):575-84 [211086] Science. 1982 Jun 18;216(4552):1317-9 [7043737] J Exp Med. 1982 Nov 1;156(5):1312-24 [7130901] Infect Immun. 1985 Apr;48(1):234-40 [3980086] J Infect Dis. 1987 Jun;155(6):1300-6 [3572040] J Med Entomol. 1987 Mar;24(2):201-5 [3585913] J Clin Microbiol. 1987 Nov;25(11):2054-8 [3693538] J Clin Microbiol. 1988 Mar;26(3):475-8 [3356787] Infect Immun. 1988 Aug;56(8):1831-6 [3397175] Science. 1989 Feb 17;243(4893):916-22 [2537530] Am J Trop Med Hyg. 1990 Apr;42(4):352-7 [2331043] Microb Pathog. 1990 Feb;8(2):109-18 [2348778] J Clin Microbiol. 1990 Jun;28(6):1329-37 [2380361] J Clin Microbiol. 1991 Feb;29(2):236-43 [2007630] Mol Microbiol. 1992 Feb;6(4):503-9 [1560779] Res Microbiol. 1993 Mar-Apr;144(3):211-9 [8210678] Infect Immun. 1994 Jan;62(1):290-8 [8262642] Infect Immun. 1994 May;62(5):2079-84 [8168973] Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):2909-13 [7708747] Proc Natl Acad Sci U S A. 1995 May 9;92(10):4269-73 [7753795] Infect Immun. 1995 Sep;63(9):3327-35 [7642261] J Clin Microbiol. 1995 Jul;33(7):1867-9 [7665661] Infect Immun. 1995 Nov;63(11):4535-9 [7591099] Am J Trop Med Hyg. 1995 Oct;53(4):397-404 [7485694] J Exp Med. 1996 Jan 1;183(1):271-5 [8551231] Infect Immun. 1996 Feb;64(2):392-8 [8550182] J Bacteriol. 1996 Apr;178(8):2287-98 [8636030] J Bacteriol. 1996 Jun;178(11):3293-307 [8655511] J Bacteriol. 1996 Jun;178(12):3508-16 [8655548] Science. 1996 Jul 19;273(5273):367-70 [8662526] Mol Microbiol. 1995 Nov;18(3):507-20 [8748034] Infect Immun. 1996 Sep;64(9):3870-6 [8751941] J Bacteriol. 1996 Oct;178(19):5615-26 [8824605] J Bacteriol. 1996 Oct;178(20):5946-53 [8830691] J Bacteriol. 1997 Jan;179(1):217-27 [8982001] J Clin Invest. 1997 Mar 1;99(5):987-95 [9062357] Mol Microbiol. 1997 Jul;25(2):361-73 [9282748] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Relationship of the xeroderma pigmentosum group E DNA repair defect to the chromatin and DNA binding proteins UV-DDB and replication protein A. AN - 79886849; 9584159 AB - Cells from complementation groups A through G of the heritable sun-sensitive disorder xeroderma pigmentosum (XP) show defects in nucleotide excision repair of damaged DNA. Proteins representing groups A, B, C, D, F, and G are subunits of the core recognition and incision machinery of repair. XP group E (XP-E) is the mildest form of the disorder, and cells generally show about 50% of the normal repair level. We investigated two protein factors previously implicated in the XP-E defect, UV-damaged DNA binding protein (UV-DDB) and replication protein A (RPA). Three newly identified XP-E cell lines (XP23PV, XP25PV, and a line formerly classified as an XP variant) were defective in UV-DDB binding activity but had levels of RPA in the normal range. The XP-E cell extracts did not display a significant nucleotide excision repair defect in vitro, with either UV-irradiated DNA or a uniquely placed cisplatin lesion used as a substrate. Purified UV-DDB protein did not stimulate repair of naked DNA by DDB- XP-E cell extracts, but microinjection of the protein into DDB- XP-E cells could partially correct the repair defect. RPA stimulated repair in normal, XP-E, or complemented extracts from other XP groups, and so the effect of RPA was not specific for XP-E cell extracts. These data strengthen the connection between XP-E and UV-DDB. Coupled with previous results, the findings suggest that UV-DDB has a role in the repair of DNA in chromatin. JF - Molecular and cellular biology AU - Rapić Otrin, V AU - Kuraoka, I AU - Nardo, T AU - McLenigan, M AU - Eker, A P AU - Stefanini, M AU - Levine, A S AU - Wood, R D AD - Section on DNA Replication, Repair, and Mutagenesis, National Institute of Child Health and Human Development, Bethesda, Maryland 20892-2725, USA. Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 3182 EP - 3190 VL - 18 IS - 6 SN - 0270-7306, 0270-7306 KW - Chromatin KW - 0 KW - DDB1 protein, human KW - DNA-Binding Proteins KW - RPA1 protein, human KW - Replication Protein A KW - Index Medicus KW - Ultraviolet Rays KW - Skin -- radiation effects KW - Cells, Cultured KW - Skin -- metabolism KW - Humans KW - Microinjections KW - DNA Repair KW - Chromatin -- metabolism KW - DNA Damage KW - DNA-Binding Proteins -- pharmacology KW - DNA-Binding Proteins -- genetics KW - Xeroderma Pigmentosum -- genetics KW - DNA-Binding Proteins -- administration & dosage KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79886849?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Relationship+of+the+xeroderma+pigmentosum+group+E+DNA+repair+defect+to+the+chromatin+and+DNA+binding+proteins+UV-DDB+and+replication+protein+A.&rft.au=Rapi%C4%87+Otrin%2C+V%3BKuraoka%2C+I%3BNardo%2C+T%3BMcLenigan%2C+M%3BEker%2C+A+P%3BStefanini%2C+M%3BLevine%2C+A+S%3BWood%2C+R+D&rft.aulast=Rapi%C4%87+Otrin&rft.aufirst=V&rft.date=1998-06-01&rft.volume=18&rft.issue=6&rft.spage=3182&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 - 1998-06-17 N1 - Date created - 1998-06-17 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Mutat Res. 1974 Jan;22(1):87-91 [4842087] J Biol Chem. 1994 Apr 15;269(15):11121-32 [8157639] Science. 1988 Oct 28;242(4878):564-7 [3175673] EMBO J. 1989 Dec 1;8(12):3883-9 [2573521] Biochemistry. 1989 Oct 17;28(21):8287-92 [2605185] Mol Cell Biol. 1990 May;10(5):2041-8 [2325644] Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):4053-6 [8171034] Mutat Res. 1994 Oct 1;310(1):89-102 [7523888] J Biol Chem. 1995 Feb 10;270(6):2415-8 [7852297] Cell. 1995 Mar 24;80(6):859-68 [7697716] Nature. 1995 Apr 6;374(6522):566-9 [7700386] Biochemistry. 1995 Apr 18;34(15):5011-7 [7711023] J Biol Chem. 1995 Jun 2;270(22):12973-6 [7768886] Genomics. 1995 Sep 1;29(1):62-9 [8530102] Mutat Res. 1996 Jan 2;362(1):105-17 [8538642] Proc Natl Acad Sci U S A. 1996 May 14;93(10):5014-8 [8643521] J Biol Chem. 1996 Mar 22;271(12):7177-86 [8636155] J Biol Chem. 1996 Apr 5;271(14):8285-94 [8626523] J Biol Chem. 1996 Jul 19;271(29):17190-8 [8663296] J Biol Chem. 1996 Oct 4;271(40):24317-20 [8798680] EMBO J. 1997 Feb 3;16(3):625-38 [9034344] J Cell Sci. 1997 May;110 ( Pt 10):1159-68 [9191040] Annu Rev Biochem. 1997;66:61-92 [9242902] EMBO J. 1997 Nov 3;16(21):6559-73 [9351836] J Biol Chem. 1998 Jan 16;273(3):1453-61 [9430682] Nature. 1991 Feb 7;349(6309):538-41 [1992355] Biochem Biophys Res Commun. 1991 Mar 29;175(3):1139-43 [2025245] Cancer Res. 1991 Jul 1;51(13):3456-70 [2054785] J Biol Chem. 1991 Nov 25;266(33):22493-500 [1657999] Mutat Res. 1992 Mar;273(2):119-25 [1372095] Cell. 1992 Apr 17;69(2):367-74 [1348971] Mutat Res. 1992 Jan;273(1):49-56 [1376435] Nucleic Acids Res. 1992 Aug 11;20(15):3873-80 [1508673] Nucleic Acids Res. 1992 Nov 11;20(21):5805-10 [1454541] Biochemistry. 1993 Feb 16;32(6):1657-66 [8431446] Nature. 1993 May 13;363(6425):185-8 [8483505] Nucleic Acids Res. 1993 Jul 25;21(15):3399-404 [8346019] Nucleic Acids Res. 1993 Aug 25;21(17):4111-8 [8371985] Electrophoresis. 1993 Aug;14(8):682-92 [8404810] J Biol Chem. 1993 Oct 5;268(28):21293-300 [8407967] J Biol Chem. 1993 Oct 5;268(28):21301-8 [8407968] Am J Hum Genet. 1993 Oct;53(4):817-21 [8213812] Biochemistry. 1993 Nov 16;32(45):12096-104 [8218288] Biochemistry. 1976 Jun 1;15(11):2402-8 [1276148] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of NMDA antagonism on striatal dopamine release in healthy subjects: application of a novel PET approach. AN - 79883017; 9593104 AB - Agents that antagonize the glutamatergic N-methyl-d-aspartate (NMDA) receptor, such as phenylcyclidine (PCP) and ketamine, produce a behavioral state in healthy volunteers that resembles some aspects of schizophrenia. A dysfunction in NMDA-dopaminergic interactions has been proposed as a mechanism for these behavioral effects. In this study, we examined the effects of ketamine on striatal dopamine release in healthy human subjects with a novel 11C-raclopride/PET displacement paradigm and compared these effects to administration of saline and the direct-acting dopamine agonist amphetamine. We found that the percent decreases (mean +/- SD) in specific 11C-raclopride binding from baseline for ketamine (11.2 +/- 8.9) was greater than for saline (1.9 +/- 3.7) (t = 2.4, df = 13, P = 0.003) indicating that ketamine caused increases in striatal synaptic dopamine concentrations. Ketamine-related binding changes were not significantly different than the decreases in percent change (mean +/- SD) in specific 11C-raclopride binding caused by amphetamine (15.5 +/- 6.2) (t = 1.3, df = 19, P = 0.21). Ketamine-induced changes in 11C-raclopride-specific binding were significantly correlated with induction of schizophrenia-like symptoms. The implications of this brain imaging method for studies of schizophrenia and the mechanism of action of antipsychotic drugs are discussed. JF - Synapse (New York, N.Y.) AU - Breier, A AU - Adler, C M AU - Weisenfeld, N AU - Su, T P AU - Elman, I AU - Picken, L AU - Malhotra, A K AU - Pickar, D AD - Experimental Therapeutics Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, USA. Breier_Alan@Lilly.com Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 142 EP - 147 VL - 29 IS - 2 SN - 0887-4476, 0887-4476 KW - Dopamine Antagonists KW - 0 KW - Dopamine Uptake Inhibitors KW - Salicylamides KW - Raclopride KW - 430K3SOZ7G KW - N-Methylaspartate KW - 6384-92-5 KW - Amphetamine KW - CK833KGX7E KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Psychoses, Substance-Induced -- diagnostic imaging KW - Humans KW - Behavior -- drug effects KW - Psychiatric Status Rating Scales KW - Adult KW - Tomography, Emission-Computed KW - Psychoses, Substance-Induced -- psychology KW - Amphetamine -- pharmacology KW - Image Processing, Computer-Assisted KW - Male KW - Dopamine Uptake Inhibitors -- pharmacology KW - Neostriatum -- metabolism KW - N-Methylaspartate -- antagonists & inhibitors KW - Dopamine -- metabolism KW - Neostriatum -- diagnostic imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79883017?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Effects+of+NMDA+antagonism+on+striatal+dopamine+release+in+healthy+subjects%3A+application+of+a+novel+PET+approach.&rft.au=Breier%2C+A%3BAdler%2C+C+M%3BWeisenfeld%2C+N%3BSu%2C+T+P%3BElman%2C+I%3BPicken%2C+L%3BMalhotra%2C+A+K%3BPickar%2C+D&rft.aulast=Breier&rft.aufirst=A&rft.date=1998-06-01&rft.volume=29&rft.issue=2&rft.spage=142&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 - 1998-07-01 N1 - Date created - 1998-07-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetic causes of female infertility: targeted mutagenesis in mice. AN - 79871852; 9585621 JF - American journal of human genetics AU - Greenhouse, S AU - Rankin, T AU - Dean, J AD - Laboratory of Cellular and Developmental Biology, NIDDK, National Institutes of Health, Bethesda, MD 20892-2715, USA. sg162d@nih.gov Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 1282 EP - 1287 VL - 62 IS - 6 SN - 0002-9297, 0002-9297 KW - Index Medicus KW - Zona Pellucida -- physiology KW - Animals KW - Fertilization KW - Ovulation KW - Ovarian Follicle -- physiology KW - Oogenesis -- physiology KW - Mice KW - Female KW - Mutagenesis KW - Infertility, Female -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79871852?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=NBER+Working+Paper+Series&rft.atitle=Trade%2C+Growth+and+the+Environment&rft.au=Copeland%2C+Brian+R%3BTaylor%2C+M+Scott&rft.aulast=Copeland&rft.aufirst=Brian&rft.date=2003-07-01&rft.volume=&rft.issue=&rft.spage=9823&rft.isbn=&rft.btitle=&rft.title=NBER+Working+Paper+Series&rft.issn=&rft_id=info:doi/10.3386%2Fw9823 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-06-24 N1 - Date created - 1998-06-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The serotonin reuptake inhibitor sertraline reduces excessive alcohol consumption in nonhuman primates: effect of stress. AN - 79831539; 9571652 AB - Many monkeys that are reared without adult influence, with only peers, voluntarily consume alcohol in amounts producing intoxication on a relatively regular basis. Using a cross-over design, eight adolescent, peer-reared rhesus monkeys were allowed unfettered access to an 8.4% ethanol solution and treated with 20 mg/kg/24 h of sertraline during three phases: home-cage, social separation, and reunion with cage-mates. Although there was no immediate effect, sertraline reduced alcohol consumption beginning the second week of home-cage treatment, but only in subjects that consumed large amounts of alcohol. Initially, the social separation stress caused the sertaline-treated subjects' alcohol consumption rates to return to baseline levels, but when the stress was repeated, alcohol consumption fell below baseline and placebo levels. Sertraline treatment was ineffective in reducing consumption during the stressful period of home-cage reunion, a period characterized by high levels of aggressive behavior. Behaviorally, sertraline reduced aggression and anxiety-like self-directed behaviors. Our findings provide evidence that sertraline may be an effective pharmacological treatment for excessive alcohol consumption and aggression. On the other hand, stress during treatment may reduce sertraline's effectiveness as a treatment for excessive alcohol consumption. JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology AU - Higley, J AU - Hasert, M AU - Suomi, S AU - Linnoila, M AD - Section on Neurochemistry and Neuro-endocrinology, NIAAA, Poolesville, Maryland 20837, USA. Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 431 EP - 443 VL - 18 IS - 6 SN - 0893-133X, 0893-133X KW - Hormones KW - 0 KW - Serotonin Uptake Inhibitors KW - 1-Naphthylamine KW - 9753I242R5 KW - Sertraline KW - QUC7NX6WMB KW - Index Medicus KW - Eating -- drug effects KW - Weight Gain -- drug effects KW - Animals KW - Hormones -- blood KW - Cross-Over Studies KW - Macaca mulatta KW - Time Factors KW - Male KW - Female KW - Alcohol Drinking -- drug therapy KW - 1-Naphthylamine -- analogs & derivatives KW - Serotonin Uptake Inhibitors -- cerebrospinal fluid KW - Serotonin Uptake Inhibitors -- blood KW - Serotonin Uptake Inhibitors -- therapeutic use KW - Alcohol Drinking -- psychology KW - 1-Naphthylamine -- therapeutic use KW - Stress, Psychological -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79831539?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+serotonin+reuptake+inhibitor+sertraline+reduces+excessive+alcohol+consumption+in+nonhuman+primates%3A+effect+of+stress.&rft.au=Higley%2C+J%3BHasert%2C+M%3BSuomi%2C+S%3BLinnoila%2C+M&rft.aulast=Higley&rft.aufirst=J&rft.date=1998-06-01&rft.volume=18&rft.issue=6&rft.spage=431&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 - 1998-06-23 N1 - Date created - 1998-06-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Specific killing of HIV-infected lymphocytes by a recombinant immunotoxin directed against the HIV-1 envelope glycoprotein. AN - 79622923; 10780881 AB - 3B3 is a high-affinity anti-gp120 antibody that neutralizes a wide range of primary and laboratory isolates of HIV-1. The parental antibody was isolated from a combinatorial phage display library constructed from bone marrow RNA of an HIV-infected individual. We have generated a highly active immunotoxin using the 3B3 single-chain Fv (scFv) which can specifically kill lymphocytes infected by HIV-1. We used recombinant DNA technology to clone the Fv fragment of 3B3 and produce a single-chain Fv (scFv). 3B3 scFv was then fused to a truncated version of Pseudomonas exotoxin A (PE38), giving rise to a recombinant immunotoxin 3B3(Fv)-PE38 that was expressed in E. coli and purified to near homogeneity. 3B3(Fv)-PE38 binds with the same affinity as the parental Fab antibody to the MN strain of gp120. The immunotoxin specifically kills a gp120-expressing transfected cell line and a chronically HIV-infected lymphocytic cell line. The immunotoxin is very stable at 37 degrees C, retaining 80% of its original activity after 24 hr. Potent immunotoxins such as 3B3(Fv)-PE38 could be utilized in combination with multidrug cocktails that limit viral replication to help reduce viral reservoirs in patients with AIDS. JF - Molecular medicine (Cambridge, Mass.) AU - Bera, T K AU - Kennedy, P E AU - Berger, E A AU - Barbas, C F AU - Pastan, I AD - Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4255, USA. Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 384 EP - 391 VL - 4 IS - 6 SN - 1076-1551, 1076-1551 KW - Anti-HIV Agents KW - 0 KW - Antibodies, Viral KW - Antigens, CD4 KW - HIV Envelope Protein gp120 KW - Immunoglobulin Fragments KW - Immunotoxins KW - Recombinant Proteins KW - immunoglobulin Fv KW - Index Medicus KW - AIDS/HIV KW - Recombinant Proteins -- pharmacology KW - Humans KW - Immunoglobulin Fragments -- genetics KW - Recombinant Proteins -- genetics KW - Antibodies, Viral -- immunology KW - Cross Reactions KW - Antigens, CD4 -- metabolism KW - Binding Sites KW - Cytotoxicity, Immunologic KW - Base Sequence KW - Antibodies, Viral -- genetics KW - Molecular Sequence Data KW - Immunoglobulin Fragments -- metabolism KW - Immunoglobulin Fragments -- immunology KW - Antibodies, Viral -- metabolism KW - HIV Envelope Protein gp120 -- immunology KW - Anti-HIV Agents -- pharmacology KW - HIV Infections -- drug therapy KW - Immunotoxins -- isolation & purification KW - Immunotoxins -- genetics KW - HIV Envelope Protein gp120 -- metabolism KW - Immunotoxins -- pharmacology KW - Lymphocytes -- drug effects KW - Lymphocytes -- virology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79622923?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+medicine+%28Cambridge%2C+Mass.%29&rft.atitle=Specific+killing+of+HIV-infected+lymphocytes+by+a+recombinant+immunotoxin+directed+against+the+HIV-1+envelope+glycoprotein.&rft.au=Bera%2C+T+K%3BKennedy%2C+P+E%3BBerger%2C+E+A%3BBarbas%2C+C+F%3BPastan%2C+I&rft.aulast=Bera&rft.aufirst=T&rft.date=1998-06-01&rft.volume=4&rft.issue=6&rft.spage=384&rft.isbn=&rft.btitle=&rft.title=Molecular+medicine+%28Cambridge%2C+Mass.%29&rft.issn=10761551&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-05-25 N1 - Date created - 2000-05-25 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Annu Rev Immunol. 1996;14:49-71 [8717507] Nat Med. 1996 Mar;2(3):350-3 [8612238] Science. 1997 May 9;276(5314):960-4 [9139661] Nature. 1997 May 8;387(6629):188-91 [9144290] Nat Biotechnol. 1996 Oct;14(10):1239-45 [9631086] Science. 1983 May 20;220(4599):868-71 [6189183] Science. 1984 May 4;224(4648):497-500 [6200935] J Mol Biol. 1986 May 5;189(1):113-30 [3537305] Cell. 1987 Jan 16;48(1):129-36 [3098436] Nature. 1988 Sep 22;335(6188):369-72 [2843774] Science. 1988 Nov 25;242(4882):1166-8 [2847316] Proc Natl Acad Sci U S A. 1989 Mar;86(6):1987-91 [2538826] Proc Natl Acad Sci U S A. 1990 Nov;87(22):8889-93 [1701055] J Immunol. 1991 Jun 15;146(12):4315-24 [1710247] Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8616-20 [1924323] Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):10134-7 [1719545] Anal Biochem. 1992 Sep;205(2):263-70 [1332541] Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3809-13 [8170992] J Infect Dis. 1994 Oct;170(4):1009-13 [7930696] J Infect Dis. 1994 Nov;170(5):1180-8 [7963711] Science. 1994 Nov 11;266(5187):1024-7 [7973652] Ann N Y Acad Sci. 1995 Jun 30;758:345-54 [7625703] J Virol. 1995 Nov;69(11):6609-17 [7474069] AIDS Res Hum Retroviruses. 1997 May 1;13(7):575-82 [9135875] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - HIV prevention with drug-using populations--current status and future prospects: introduction and overview. AN - 73919081; 9722806 JF - Public health reports (Washington, D.C. : 1974) AU - Needle, R H AU - Coyle, S L AU - Normand, J AU - Lambert, E AU - Cesari, H AD - National Institute on Drug Abuse, Division of Epidemiology and Prevention Research, Rockville, MD 20857, USA. rn28E@nih.gov Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 4 EP - 18 VL - 113 Suppl 1 SN - 0033-3549, 0033-3549 KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - United States KW - Humans KW - Preventive Health Services KW - Primary Prevention -- methods KW - Disease Transmission, Infectious -- prevention & control KW - HIV Infections -- transmission KW - HIV Infections -- prevention & control KW - Substance-Related Disorders -- complications KW - Public Health -- trends KW - Community-Institutional Relations UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73919081?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Public+health+reports+%28Washington%2C+D.C.+%3A+1974%29&rft.atitle=HIV+prevention+with+drug-using+populations--current+status+and+future+prospects%3A+introduction+and+overview.&rft.au=Needle%2C+R+H%3BCoyle%2C+S+L%3BNormand%2C+J%3BLambert%2C+E%3BCesari%2C+H&rft.aulast=Needle&rft.aufirst=R&rft.date=1998-06-01&rft.volume=113+Suppl+1&rft.issue=&rft.spage=4&rft.isbn=&rft.btitle=&rft.title=Public+health+reports+%28Washington%2C+D.C.+%3A+1974%29&rft.issn=00333549&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-09-21 N1 - Date created - 1998-09-21 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Arch Gen Psychiatry. 1972 Aug;27(2):149-55 [5042822] Rev Infect Dis. 1988 Mar-Apr;10(2):377-84 [3259712] Am J Med. 1984 Mar;76(3):487-92 [6608269] J Subst Abuse Treat. 1984;1(4):237-47 [6100315] Arch Intern Med. 1985 Aug;145(8):1413-7 [3875327] Soc Sci Med. 1985;21(11):1203-16 [3006260] Health Educ Q. 1986 Winter;13(4):383-93 [3781862] Public Health Rep. 1988 May-Jun;103(3):261-6 [3131815] J Health Soc Behav. 1988 Sep;29(3):214-26 [3241064] JAMA. 1989 May 12;261(18):2677-84 [2651732] Am J Community Psychol. 1990 Aug;18(4):587-96 [2075893] NIDA Res Monogr. 1991;106:1-19 [1922282] J Acquir Immune Defic Syndr. 1993 Sep;6(9):1049-56 [8340896] JAMA. 1994 Jun 15;271(23):1825-6; author reply 1826-7 [8196134] Int J Addict. 1994 Nov;29(13):1739-52 [7852000] J Am Med Womens Assoc. 1995 May-Aug;50(3-4):109-14 [7657943] Am J Epidemiol. 1995 Oct 15;142(8):864-74 [7572963] Am J Public Health. 1995 Nov;85(11):1531-7 [7485666] J Infect Dis. 1996 Apr;173(4):997-1000 [8603983] Sex Transm Dis. 1996 Jan-Feb;23(1):24-9 [8801639] J Acquir Immune Defic Syndr Hum Retrovirol. 1996 Jul;12(3):282-9 [8673532] MMWR Morb Mortal Wkly Rep. 1997 Jun 20;46(24):565-8 [9221326] Arch Gen Psychiatry. 1981 Aug;38(8):875-80 [7259424] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Outreach-based HIV prevention for injecting drug users: a review of published outcome data. AN - 73896526; 9722807 AB - Over the past decade, a body of observational research has accrued about the effects of outreach-based human immunodeficiency virus (HIV) interventions for drug users. The authors reviewed the findings related to postintervention behavior changes and integrated findings across studies to provide the best estimate of program impact. The authors conducted a computerized literature search to locate published accounts of HIV intervention effects on drug users. Thirty-six publications covered outreach-based HIV risk reduction interventions for out-of-treatment injecting drug users (IDUs) and reported intervention effects on HIV-related behaviors or HIV seroincidence. Two-thirds of the publications reported that participation in street-based outreach interventions was followed with office-based HIV testing and counseling. The authors described the theoretical underpinnings of outreach intervention components, the content of the interventions, and the outcome measures that investigators used most frequently. The authors also described and critiqued the evaluation study designs that were in place. Because most of the evaluations were based on pretest and posttest measures of behavior rather than on controlled studies, results were examined with respect to accepted criteria for attributing intervention causality, that is, the plausibility of cause and effect, correct temporal sequence, consistency of findings across reports, strength of associations observed, specifically of associations, and dose-response relationships between interventions and observed outcomes. The majority of the published evaluations showed that IDUs in a variety of places and time periods changed their baseline drug-related and sex-related risk behaviors following their participation in a outreach-based HIV risk reduction intervention. More specifically, the publications indicated that IDUs regularly reported significant follow-up reductions in drug injection, multiperson reuse of syringes and needles, multiperson reuse of other injection equipment (cookers, cotton, rinse water), and crack use. The studies also showed significant intervention effects in promoting entry into drug treatment and increasing needle disinfection. Although drug users also significantly reduced sex-related risks and increased condom use, the majority still practiced unsafe sex. One quasi-experimental study found that reductions in injection risk led to significantly reduced HIV seroincidence among outreach participants. Few investigators looked at dosage effects, but two reports suggested that the longer the exposure to outreach-based interventions, the greater the reductions in drug injection frequency. Accumulated evidence from observational and quasi-experimental studies strongly indicate that outreach-based interventions have been effective in reaching out-of-treatment IDUs, providing the means for behavior changes and inducing behavior change in the desired direction. The findings provide sound evidence that participation in outreach-based prevention programs can lead to lower HIV incidence rates among program participants. JF - Public health reports (Washington, D.C. : 1974) AU - Coyle, S L AU - Needle, R H AU - Normand, J AD - National Institute on Drug Abuse, Rockville, MD 20857, USA. sc91m@nih.gov Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 19 EP - 30 VL - 113 Suppl 1 SN - 0033-3549, 0033-3549 KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - United States KW - Needles KW - Randomized Controlled Trials as Topic KW - Risk-Taking KW - Humans KW - Preventive Health Services KW - HIV Infections -- transmission KW - HIV Infections -- prevention & control KW - Substance-Related Disorders -- complications KW - Community-Institutional Relations UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73896526?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Public+health+reports+%28Washington%2C+D.C.+%3A+1974%29&rft.atitle=Outreach-based+HIV+prevention+for+injecting+drug+users%3A+a+review+of+published+outcome+data.&rft.au=Coyle%2C+S+L%3BNeedle%2C+R+H%3BNormand%2C+J&rft.aulast=Coyle&rft.aufirst=S&rft.date=1998-06-01&rft.volume=113+Suppl+1&rft.issue=&rft.spage=19&rft.isbn=&rft.btitle=&rft.title=Public+health+reports+%28Washington%2C+D.C.+%3A+1974%29&rft.issn=00333549&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-09-21 N1 - Date created - 1998-09-21 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Acquir Immune Defic Syndr Hum Retrovirol. 1996 Jul;12(3):282-9 [8673532] AIDS Educ Prev. 1995 Oct;7(5):379-90 [8672391] Drug Alcohol Depend. 1996 Sep;42(1):11-20 [8889399] AIDS Educ Prev. 1998 Feb;10(1):19-33 [9505096] Women Health. 1998;27(1-2):25-48 [9640633] Women Health. 1998;27(1-2):49-66 [9640634] Hosp Community Psychiatry. 1993 Nov;44(11):1066-72 [8288175] Drugs Soc (New York). 1996;9(1-2):173-84 [12348010] Health Educ Q. 1984 Spring;11(1):1-47 [6392204] Rev Infect Dis. 1988 Jan-Feb;10(1):151-8 [3281219] AIDS Educ Prev. 1990 Winter;2(4):253-71 [2099157] Am J Public Health. 1991 May;81(5):568-71 [2014855] Am J Drug Alcohol Abuse. 1991 Sep;17(3):337-53 [1928027] J Addict Dis. 1991;10(4):89-98 [1777502] Br J Addict. 1992 Mar;87(3):393-404 [1559038] Br J Addict. 1992 Apr;87(4):585-90 [1591512] P R Health Sci J. 1993 Apr;12(1):27-34 [8511243] Health Educ Q. 1993 Winter;20(4):523-38 [8307770] AIDS Educ Prev. 1995 Jun;7(3):195-209 [7646944] JAMA. 1995 Oct 18;274(15):1226-31 [7563513] AIDS Educ Prev. 1995 Aug;7(4):308-19 [7577307] AIDS. 1996 Mar;10(3):291-8 [8882669] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - What we have learned from research about the prevention of HIV transmission among drug abusers. AN - 73876589; 9722825 AB - After more than 10 years of experience conducting behavioral changes interventions and with accumulated research results, several emergent principle have been identified for the effective prevention of HIV-transmission among drug abusers. In August 1997, a symposium was held in Flagstaff, Arizona, to achieve tow major purposes: (1) to synthesize the finding from HIV prevention research conducted to date for interventions targeting drug abusers and (2) to extract a preliminary set of prevention principles that could be linked to effectiveness across at least two or more studies. This chapter summarizes the key findings of that symposium. Major finding were abstracted from the conclusion sections of the presentations and from the chapters included in this special volume. Many consistencies regarding intervention approaches across studies were noted. These findings are discussed under the following headings: General Observations, Engagement, Multiple Interventions, Intervention Issues, Methodological Issues, and Translation from Research to Practice. Suggested areas for further research are also presented and discussed. Ten principles that have implications for HIV prevention interventions emerged from this preliminary review of the research. These principles engage drug users into the intervention; specify target behaviors and attitudes for intervention; suggest setting to optimize outreach: and recommend booster approaches to reinforce knowledge, skills, and attitudes learned through the intervention. The drug abuse community is threatened by the incursion of HIV and by the hepatitis viruses A, B, and C. The same behaviors are involved in transmitting all of these viruses. The first generation of research to assess the impact of a variety of interventions delivered among drug abusers to prevent HIV has shown consistently favorable findings, proving that drug abusers can be helped to change their risky drug-using behaviors and, to a lesser extent, their risky sexual behaviors. The need to translate these findings for community practitioners is heightened by the devastating impact of HIV and AIDS. JF - Public health reports (Washington, D.C. : 1974) AU - Sloboda, Z AD - National Institute on Drug Abuse, Division of Epidemiology and Prevention Research, Rockville Md 20857, USA. zs6n@nih.gov Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 194 EP - 204 VL - 113 Suppl 1 SN - 0033-3549, 0033-3549 KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - United States KW - Humans KW - Substance-Related Disorders -- therapy KW - Primary Prevention KW - HIV Infections -- transmission KW - HIV Infections -- prevention & control KW - Substance-Related Disorders -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73876589?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Public+health+reports+%28Washington%2C+D.C.+%3A+1974%29&rft.atitle=What+we+have+learned+from+research+about+the+prevention+of+HIV+transmission+among+drug+abusers.&rft.au=Sloboda%2C+Z&rft.aulast=Sloboda&rft.aufirst=Z&rft.date=1998-06-01&rft.volume=113+Suppl+1&rft.issue=&rft.spage=194&rft.isbn=&rft.btitle=&rft.title=Public+health+reports+%28Washington%2C+D.C.+%3A+1974%29&rft.issn=00333549&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-09-21 N1 - Date created - 1998-09-21 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Med Care. 1977 May;15(5 SUPPL):27-46 [853780] Int J Addict. 1994 Apr;29(6):681-705 [8034380] JAMA. 1995 Apr 12;273(14):1106-12 [7707598] Drug Alcohol Depend. 1997 Sep 25;47(3):227-35 [9306048] Public Health Rep. 1998 Jun;113 Suppl 1:151-9 [9722820] Public Health Rep. 1998 Jun;113 Suppl 1:42-57 [9722809] Public Health Rep. 1998 Jun;113 Suppl 1:97-106 [9722815] Public Health Rep. 1998 Jun;113 Suppl 1:116-28 [9722817] Public Health Rep. 1998 Jun;113 Suppl 1:19-30 [9722807] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Caffeine--an atypical drug of dependence. AN - 73868929; 9716941 AB - Caffeine has both positive effects that contribute to widespread consumption of caffeine-containing beverages and adverse unpleasant effects if doses are increased. Caffeine has weak reinforcing properties, but with little or no evidence for upward dose adjustment, possibly because of the adverse effects of higher doses. Withdrawal symptoms, although relatively limited with respect to severity, do occur, and may contribute to maintenance of caffeine consumption. Health hazards are small if any and caffeine use is not associated with incapacitation. Thus, although caffeine can be argued to fulfill regulatory criteria as a dependence-producing drug, the extensive use of caffeine-containing beverages poses little apparent risk to the consumer or to society. The positive stimulatory effects of caffeine appear in large measure to be due to blockade of A2A receptors that stimulate GABAergic neurons of inhibitory pathways to the dopaminergic reward system of the striatum. However, blockade of striatal A1 receptors may also play a role. The mechanisms underlying negative effects of higher doses of caffeine are as yet not well defined. JF - Drug and alcohol dependence AU - Daly, J W AU - Fredholm, B B AD - Laboratory of Bioorganic Chemistry, National Institutes of Health, Bethesda, MD 20892, USA. PY - 1998 SP - 199 EP - 206 VL - 51 IS - 1-2 SN - 0376-8716, 0376-8716 KW - Central Nervous System Stimulants KW - 0 KW - Phosphodiesterase Inhibitors KW - Receptors, Neurotransmitter KW - Receptors, Purinergic P1 KW - Caffeine KW - 3G6A5W338E KW - Index Medicus KW - Phosphodiesterase Inhibitors -- pharmacology KW - Animals KW - Drug Interactions KW - Substance Withdrawal Syndrome -- physiopathology KW - Receptors, Purinergic P1 -- drug effects KW - Down-Regulation KW - Corpus Striatum -- chemistry KW - Receptors, Neurotransmitter -- metabolism KW - Dose-Response Relationship, Drug KW - Humans KW - Receptors, Neurotransmitter -- drug effects KW - Corpus Striatum -- drug effects KW - Up-Regulation KW - Neural Pathways -- drug effects KW - Substance-Related Disorders -- physiopathology KW - Central Nervous System Stimulants -- pharmacology KW - Caffeine -- pharmacology KW - Caffeine -- adverse effects KW - Central Nervous System Stimulants -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73868929?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Caffeine--an+atypical+drug+of+dependence.&rft.au=Daly%2C+J+W%3BFredholm%2C+B+B&rft.aulast=Daly&rft.aufirst=J&rft.date=1998-06-01&rft.volume=51&rft.issue=1-2&rft.spage=199&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 - 1998-11-12 N1 - Date created - 1998-11-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Drug-activation of brain reward pathways. AN - 73861688; 9716927 JF - Drug and alcohol dependence AU - Wise, R A AD - Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD 21224, USA. PY - 1998 SP - 13 EP - 22 VL - 51 IS - 1-2 SN - 0376-8716, 0376-8716 KW - Central Nervous System Stimulants KW - 0 KW - Hallucinogens KW - Narcotics KW - Nicotinic Agonists KW - Receptors, Neurotransmitter KW - Street Drugs KW - gamma-Aminobutyric Acid KW - 56-12-2 KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Animals KW - Central Nervous System Stimulants -- pharmacology KW - Nucleus Accumbens -- drug effects KW - Humans KW - Dopamine -- physiology KW - gamma-Aminobutyric Acid -- physiology KW - Narcotics -- pharmacology KW - Prefrontal Cortex -- drug effects KW - Neural Pathways -- drug effects KW - Rats KW - Hypothalamus, Middle -- drug effects KW - Hallucinogens -- pharmacology KW - Tegmentum Mesencephali -- drug effects KW - Nicotinic Agonists -- pharmacology KW - gamma-Aminobutyric Acid -- drug effects KW - Self Stimulation -- physiology KW - Substance-Related Disorders -- physiopathology KW - Street Drugs -- pharmacology KW - Reward KW - Brain -- drug effects KW - Receptors, Neurotransmitter -- drug effects KW - Models, Neurological KW - Behavior, Addictive -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73861688?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Drug-activation+of+brain+reward+pathways.&rft.au=Wise%2C+R+A&rft.aulast=Wise&rft.aufirst=R&rft.date=1998-06-01&rft.volume=51&rft.issue=1-2&rft.spage=13&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 - 1998-11-12 N1 - Date created - 1998-11-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Drug addiction research: moving toward the 21st century. AN - 73861630; 9716925 JF - Drug and alcohol dependence AU - Leshner, A I AD - National Institute on Drug Abuse, Rockville, MD 20857, USA. PY - 1998 SP - 5 EP - 7 VL - 51 IS - 1-2 SN - 0376-8716, 0376-8716 KW - Index Medicus KW - United States KW - Brain -- physiopathology KW - Humans KW - National Institutes of Health (U.S.) KW - Behavior, Addictive -- physiopathology KW - Neurobiology -- trends KW - Substance-Related Disorders -- physiopathology KW - Research -- trends KW - Substance-Related Disorders -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73861630?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Drug+addiction+research%3A+moving+toward+the+21st+century.&rft.au=Leshner%2C+A+I&rft.aulast=Leshner&rft.aufirst=A&rft.date=1998-06-01&rft.volume=51&rft.issue=1-2&rft.spage=5&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 - 1998-11-12 N1 - Date created - 1998-11-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of individual versus group caging on the incidence of pituitary and Leydig cell tumors in F344 rats: proposed mechanism. AN - 73854451; 9710329 AB - Recently, an increase in pituitary tumor (pars distalis adenoma) incidence, and decrease in testicular interstitial cell tumor incidence, has been noted in F344 rats, in 2 year National Toxicology Program dermal and inhalation studies. One of the factors that may have contributed to this correlation is the difference in housing protocols. Rats in inhalation and dermal toxicity studies are singly caged, in contrast to other types of studies in which rats are group-caged, such as dosed-feed, dosed-water, or gavage studies. We propose that stress, related to individual caging, particularly among males, directly impairs testosterone synthesis and produces Leydig cell atrophy which leads to a feedback increase in the synthesis of luteinizing hormone by the anterior pituitary. This is followed by anterior pituitary cell functional hypertrophy, hyperplasia, and eventually neoplasia. It is known that individual caging of male rats produces a stress response associated with increased serum corticosteroids. The testicular interstitial cells (Leydig cells) have specific receptors for the glucocorticoid hormones. The Leydig cell enzyme 11-beta-hydroxysteroid dehydrogenase (11-beta-HSD) inactivates gluococorticoids; however, prolonged stress depletes this enzyme, enabling the gluococorticoids to impair steroidogenesis and eventually to lead to compensatory pituitary proliferations, including neoplasms. JF - Medical hypotheses AU - Nyska, A AU - Leininger, J R AU - Maronpot, R R AU - Haseman, J K AU - Hailey, J R AD - National Toxicology Program, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina 27709, USA. Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 525 EP - 529 VL - 50 IS - 6 SN - 0306-9877, 0306-9877 KW - Adrenal Cortex Hormones KW - 0 KW - Testosterone KW - 3XMK78S47O KW - Index Medicus KW - Rats KW - Hypothalamo-Hypophyseal System -- physiology KW - Animals KW - Rats, Inbred F344 KW - Risk Factors KW - Incidence KW - Testosterone -- physiology KW - Reproduction KW - Male KW - Adrenal Cortex Hormones -- physiology KW - Pituitary Neoplasms -- epidemiology KW - Stress, Physiological -- complications KW - Housing, Animal KW - Models, Biological KW - Testicular Neoplasms -- epidemiology KW - Leydig Cell Tumor -- epidemiology KW - Social Environment UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73854451?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Medical+hypotheses&rft.atitle=Effect+of+individual+versus+group+caging+on+the+incidence+of+pituitary+and+Leydig+cell+tumors+in+F344+rats%3A+proposed+mechanism.&rft.au=Nyska%2C+A%3BLeininger%2C+J+R%3BMaronpot%2C+R+R%3BHaseman%2C+J+K%3BHailey%2C+J+R&rft.aulast=Nyska&rft.aufirst=A&rft.date=1998-06-01&rft.volume=50&rft.issue=6&rft.spage=525&rft.isbn=&rft.btitle=&rft.title=Medical+hypotheses&rft.issn=03069877&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-10-22 N1 - Date created - 1998-10-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inhibition of angiogenesis by thalidomide requires metabolic activation, which is species-dependent. AN - 73852929; 9714301 AB - Thalidomide has been shown to be an inhibitor of angiogenesis in a rabbit cornea micropocket model; however, it has failed to demonstrate this activity in other models. These results suggest that the anti-angiogenic effects of thalidomide may only be observed following metabolic activation of the compound. This activation process may be species specific, similar to the teratogenic properties associated with thalidomide. Using a rat aorta model and human aortic endothelial cells, we co-incubated thalidomide in the presence of either human, rabbit, or rat liver microsomes. These experiments demonstrated that thalidomide inhibited microvessel formation from rat aortas and slowed human aortic endothelial cell proliferation in the presence of human or rabbit microsomes, but not in the presence of rat microsomes. In the absence of microsomes, thalidomide had no effect on either microvessel formation or cell proliferation, thus demonstrating that a metabolite of thalidomide is responsible for its anti-angiogenic effects and that this metabolite can be formed in both humans and rabbits, but not in rodents. JF - Biochemical pharmacology AU - Bauer, K S AU - Dixon, S C AU - Figg, W D AD - Medicine Branch, Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1998/06/01/ PY - 1998 DA - 1998 Jun 01 SP - 1827 EP - 1834 VL - 55 IS - 11 SN - 0006-2952, 0006-2952 KW - Antineoplastic Agents KW - 0 KW - Thalidomide KW - 4Z8R6ORS6L KW - Index Medicus KW - AIDS/HIV KW - Rats KW - Coculture Techniques KW - Animals KW - Aorta, Thoracic -- drug effects KW - Tumor Cells, Cultured KW - Cells, Cultured KW - Aorta, Thoracic -- cytology KW - Humans KW - Aorta, Thoracic -- metabolism KW - Cell Division -- drug effects KW - Rabbits KW - Species Specificity KW - Endothelium, Vascular -- metabolism KW - Endothelium, Vascular -- drug effects KW - Endothelium, Vascular -- cytology KW - Microsomes, Liver -- metabolism KW - Antineoplastic Agents -- metabolism KW - Thalidomide -- metabolism KW - Neovascularization, Physiologic -- drug effects KW - Thalidomide -- pharmacology KW - Antineoplastic Agents -- pharmacology KW - Neovascularization, Pathologic -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73852929?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Inhibition+of+angiogenesis+by+thalidomide+requires+metabolic+activation%2C+which+is+species-dependent.&rft.au=Bauer%2C+K+S%3BDixon%2C+S+C%3BFigg%2C+W+D&rft.aulast=Bauer&rft.aufirst=K&rft.date=1998-06-01&rft.volume=55&rft.issue=11&rft.spage=1827&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 - 1998-08-31 N1 - Date created - 1998-08-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The neurobiology of alcohol abuse and alcoholism: building knowledge, creating hope. AN - 73852384; 9716926 JF - Drug and alcohol dependence AU - Gordis, E AD - National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland 20892, USA. PY - 1998 SP - 9 EP - 11 VL - 51 IS - 1-2 SN - 0376-8716, 0376-8716 KW - Index Medicus KW - United States KW - Brain -- physiopathology KW - Animals KW - Humans KW - National Institutes of Health (U.S.) KW - Behavior, Addictive -- physiopathology KW - Alcohol-Related Disorders -- physiopathology KW - Alcohol-Related Disorders -- prevention & control KW - Research -- trends KW - Neurobiology -- trends UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73852384?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+neurobiology+of+alcohol+abuse+and+alcoholism%3A+building+knowledge%2C+creating+hope.&rft.au=Gordis%2C+E&rft.aulast=Gordis&rft.aufirst=E&rft.date=1998-06-01&rft.volume=51&rft.issue=1-2&rft.spage=9&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 - 1998-11-12 N1 - Date created - 1998-11-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - [Dealing with alcoholism--networking of social resources in Kochi prefecture]. AN - 73847813; 9701999 JF - Nihon Arukoru Yakubutsu Igakkai zasshi = Japanese journal of alcohol studies & drug dependence AU - Takeshima, T AU - Tani, N AD - National Institute of Mental Health, NCNP, Ichikawa, Japan. Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 219 EP - 224 VL - 33 IS - 3 SN - 1341-8963, 1341-8963 KW - Index Medicus KW - Humans KW - Health Education KW - Japan KW - Alcoholism -- therapy KW - Community Networks KW - Alcoholism -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73847813?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nihon+Arukoru+Yakubutsu+Igakkai+zasshi+%3D+Japanese+journal+of+alcohol+studies+%26+drug+dependence&rft.atitle=%5BDealing+with+alcoholism--networking+of+social+resources+in+Kochi+prefecture%5D.&rft.au=Takeshima%2C+T%3BTani%2C+N&rft.aulast=Takeshima&rft.aufirst=T&rft.date=1998-06-01&rft.volume=33&rft.issue=3&rft.spage=219&rft.isbn=&rft.btitle=&rft.title=Nihon+Arukoru+Yakubutsu+Igakkai+zasshi+%3D+Japanese+journal+of+alcohol+studies+%26+drug+dependence&rft.issn=13418963&rft_id=info:doi/ LA - Japanese DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-10-15 N1 - Date created - 1998-10-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - [Coordination or competence: an emerging problem in the development of network treatment for alcoholics]. AN - 73841853; 9702000 AB - The author recognizes the significance and relevance of the network treatment for alcoholics is such a way as an effort to respond not only to the medical needs but also to social service needs, in order to support the recovery of alcoholics. Consequently we are faced to an indispensable task to look back historically the developmental process of the treatment service for alcoholics in Japan. A recent policy development in the alcohol treatment is stimulating the shift from the overweight medical approach to a more comprehensive approach including social services. This innovation is bringing about not only a wider treatment options but also a newly emerging problem of "coordination or competence" as well. It was implied in this paper that a concept of "shared function" is promising to consider this new problem. JF - Nihon Arukoru Yakubutsu Igakkai zasshi = Japanese journal of alcohol studies & drug dependence AU - Shimizu, S AD - National Institute of Mental Health, NCNP, Chiba, Japan. Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 225 EP - 233 VL - 33 IS - 3 SN - 1341-8963, 1341-8963 KW - Index Medicus KW - Humans KW - Social Work KW - Health Education KW - Self-Help Groups KW - Japan KW - Alcoholism -- therapy KW - Community Networks KW - Alcoholism -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73841853?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nihon+Arukoru+Yakubutsu+Igakkai+zasshi+%3D+Japanese+journal+of+alcohol+studies+%26+drug+dependence&rft.atitle=%5BCoordination+or+competence%3A+an+emerging+problem+in+the+development+of+network+treatment+for+alcoholics%5D.&rft.au=Shimizu%2C+S&rft.aulast=Shimizu&rft.aufirst=S&rft.date=1998-06-01&rft.volume=33&rft.issue=3&rft.spage=225&rft.isbn=&rft.btitle=&rft.title=Nihon+Arukoru+Yakubutsu+Igakkai+zasshi+%3D+Japanese+journal+of+alcohol+studies+%26+drug+dependence&rft.issn=13418963&rft_id=info:doi/ LA - Japanese DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-10-15 N1 - Date created - 1998-10-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Neuroprotection by nitric oxide against hydroxyl radical-induced nigral neurotoxicity. AN - 73835122; 9704898 AB - We investigated the effects of nitric oxide on an in vitro and in vivo generation of hydroxyl radicals, and in vivo neurotoxicity caused by intranigral infusion of ferrous citrate in rats. The formation of hydroxyl radicals in vitro, without exogenous hydrogen peroxide, was dose-dependent. Some nitric oxide donors (e.g. sodium nitroprusside) stimulated, while others (nitroglycerin, diethylamine/nitric oxide, nitric oxide in Ringer's solution) suppressed hydroxyl radical generation in vitro. A significant increase in extra-cellular hydroxyl radicals was detected in a brain microdialysis study. Intranigral infusion of ferrous citrate caused long-lasting lipid peroxidation and dopamine depletion in the ipsilateral nigral region and striatum, respectively. Sub-acute dopamine depletion in the striatum was positively correlated with acute lipid peroxidation in substantia nigra. Intranigral administration of nitric oxide did not affect striatal dopamine. Interestingly, nitric oxide in Ringer's protected nigral neurones against the oxidative injury. The results demonstrate that a regional increase in the levels of iron can result in hydroxyl radical generation and lipid peroxidation leading to neurotoxicity. It also demonstrates that exogenous nitric oxide can act as hydroxyl radical scavenger and protect neurones from oxidative injury. JF - Journal of chemical neuroanatomy AU - Mohanakumar, K P AU - Hanbauer, I AU - Chiueh, C C AD - Unit on Neurotoxicity and Neuroprotection, Laboratory of Clinical Sciences, NIMH, NIH, Bethesda, MD 20892, USA. iichbio@giasc101.vsn1.net.in Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 195 EP - 205 VL - 14 IS - 3-4 SN - 0891-0618, 0891-0618 KW - Ferrous Compounds KW - 0 KW - Lipid Peroxides KW - Nitric Oxide KW - 31C4KY9ESH KW - Hydroxyl Radical KW - 3352-57-6 KW - monoferrous acid citrate KW - 33KM3X4QQW KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Ferrous Compounds -- metabolism KW - Drug Interactions KW - Corpus Striatum -- metabolism KW - In Vitro Techniques KW - Dopamine -- metabolism KW - Corpus Striatum -- drug effects KW - Lipid Peroxides -- metabolism KW - Male KW - Substantia Nigra -- drug effects KW - Nitric Oxide -- pharmacology KW - Hydroxyl Radical -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73835122?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+chemical+neuroanatomy&rft.atitle=Neuroprotection+by+nitric+oxide+against+hydroxyl+radical-induced+nigral+neurotoxicity.&rft.au=Mohanakumar%2C+K+P%3BHanbauer%2C+I%3BChiueh%2C+C+C&rft.aulast=Mohanakumar&rft.aufirst=K&rft.date=1998-06-01&rft.volume=14&rft.issue=3-4&rft.spage=195&rft.isbn=&rft.btitle=&rft.title=Journal+of+chemical+neuroanatomy&rft.issn=08910618&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-10-20 N1 - Date created - 1998-10-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Histopathology and molecular biology of ovarian epithelial tumors. AN - 70130600; 9845739 AB - Carcinogenesis in the ovary presents special features related to that organ. First, the preinvasive or even invasive lesions are difficult to detect, which explains why most cases are diagnosed at an advanced stage. Second, the group of tumors of low malignant potential (borderline tumors) are still a controversial category of ovarian lesions. Finally, familial ovarian tumors represent an interesting hereditary model of carcinogenesis at the molecular level. Flow cytometry and immunohistochemistry for proliferative markers or oncogenes provide important prognostic information in patients with ovarian tumors. Molecular data, such as loss of heterozygosity at specific genetic loci, also have been correlated with prognosis. Clonality studies in patients with multiple ovarian/pelvian lesions analyzing chromosome X inactivation patterns and genetic deletions or mutations have contributed to the understanding of the origin of these lesions. New technologies to study gene expression patterns, such as cDNA library construction and DNA microarray technologies, are being applied to study histologic phases of tumor progression, such as normal, preinvasive, and tumor tissues. It is hoped that these studies will contribute important information not only for a better understanding of the process of carcinogenesis, but also for assessing the biology and behavior of individual tumors, determining patient prognosis, and eventually influencing therapy. JF - Annals of diagnostic pathology AU - Chuaqui, R F AU - Cole, K A AU - Emmert-Buck, M R AU - Merino, M J AD - Laboratory of Pathology, National Cancer Institute, Bethesda, MD, USA. Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 195 EP - 207 VL - 2 IS - 3 SN - 1092-9134, 1092-9134 KW - Index Medicus KW - Genes, Tumor Suppressor KW - Humans KW - Molecular Biology -- trends KW - Female KW - Ovarian Neoplasms -- genetics KW - Ovarian Neoplasms -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70130600?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+diagnostic+pathology&rft.atitle=Histopathology+and+molecular+biology+of+ovarian+epithelial+tumors.&rft.au=Chuaqui%2C+R+F%3BCole%2C+K+A%3BEmmert-Buck%2C+M+R%3BMerino%2C+M+J&rft.aulast=Chuaqui&rft.aufirst=R&rft.date=1998-06-01&rft.volume=2&rft.issue=3&rft.spage=195&rft.isbn=&rft.btitle=&rft.title=Annals+of+diagnostic+pathology&rft.issn=10929134&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-01-06 N1 - Date created - 1999-01-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Concentrations of airborne Aspergillus compared to the incidence of invasive aspergillosis: lack of correlation. AN - 70121051; 9776829 AB - Air sampling of the rooms and corridors of the oncology wards of the hospital was carried out over a 54-week period to assess the concentration of viable Aspergillus conidia. A. fumigatus and A. flavus were recovered at a mean of 1.83 cfu m-3 air sampled. Individual samplings yielded concentrations of up to 11.6 cfu m-3. Other Aspergillus spp. were recovered at a mean of 2.38 cfu m-3 (maximum 32.6 cfu m-3). Concentration was not correlated with season or hospital ward. Review of autopsy results showed an average of 6.6 cases of aspergillosis annually over a 22-year period. No seasonal variation in case incidence was found. Six cases of invasive aspergillosis were diagnosed on the three cancer wards during the air-sampling period, but no association was seen linking these cases with changes in recovery of airborne Aspergillus. A seasonal pattern was not observed in the overall incidence of aspergillosis cases nor concentrations of airborne conidia. JF - Medical mycology AU - Hospenthal, D R AU - Kwon-Chung, K J AU - Bennett, J E AD - Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. dhospenthal@atlas.niaid.nih.gov Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 165 EP - 168 VL - 36 IS - 3 SN - 1369-3786, 1369-3786 KW - Index Medicus KW - United States KW - Autopsy KW - Air Pollution, Indoor KW - Patients' Rooms KW - Humans KW - National Institutes of Health (U.S.) KW - Retrospective Studies KW - Incidence KW - Aspergillus fumigatus -- isolation & purification KW - Aspergillus flavus -- isolation & purification KW - Air Microbiology KW - Aspergillosis -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70121051?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Medical+mycology&rft.atitle=Concentrations+of+airborne+Aspergillus+compared+to+the+incidence+of+invasive+aspergillosis%3A+lack+of+correlation.&rft.au=Hospenthal%2C+D+R%3BKwon-Chung%2C+K+J%3BBennett%2C+J+E&rft.aulast=Hospenthal&rft.aufirst=D&rft.date=1998-06-01&rft.volume=36&rft.issue=3&rft.spage=165&rft.isbn=&rft.btitle=&rft.title=Medical+mycology&rft.issn=13693786&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-01-28 N1 - Date created - 1999-01-28 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Med Mycol. 1999 Oct;37(5):373-4 [10520163] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of inhibition of ornithine decarboxylase activity in a model of acute hepatocellular necrosis. AN - 70118315; 9855067 AB - The effect of blockade of the enzyme ornithine decarboxylase by difluoromethylornithine (DFMO) on hepatocellular necrosis and survival in rats treated with thioacetamide (TAA) was investigated. In one experiment, the effect of DFMO on survival of rats with TAA-induced acute hepatocellular necrosis was determined. In another experiment, blood and liver specimens were obtained from DFMO or saline-treated rats 24 h after the administration of TAA for determinations of serum alanine aminotransferase (ALT) and liver content of polyamines and microsomal cytochrome P-450 and for assessment of hepatic histology. Liver polyamines were determined by reversed-phase HPLC and microsomal cytochrome P-450 content by dithionite-difference spectroscopy of CO-treated homogenates. The severity of hepatocellular necrosis was scored blindly. TAA-treated rats that received DFMO survived longer than saline-treated controls (P < 0.01). Serum ALT and liver putrescine concentrations were lower and the histological severity of acute hepatocellular necrosis was less in DFMO-treated rats with TAA-induced hepatocellular necrosis than in saline-treated controls (P < 0.05, P < 0.01 and P < 0.05, respectively). Total cytochrome P-450 levels were similar in DFMO and saline-treated rats with TAA-induced hepatocellular necrosis. DFMO increases survival in TAA-induced fulminant hepatic failure by decreasing the severity of acute hepatocellular necrosis. The beneficial effects of DFMO do not appear to be mediated by its effects on polyamine metabolism, but may be attributable to an effect of DFMO on thioacetamide metabolism or on an alternative pathway of ornithine metabolism. JF - European journal of gastroenterology & hepatology AU - Yurdaydin, C AU - Swain, M G AU - Mininberg, E D AU - Vergalla, J AU - Kleiner, D AU - Paul, S M AU - Jones, E A AD - Liver Diseases Section, NIDDK, National Institutes of Health, Bethesda, MD, USA. yurdaydi@dialp.ankara.edu.tr Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 503 EP - 507 VL - 10 IS - 6 SN - 0954-691X, 0954-691X KW - Enzyme Inhibitors KW - 0 KW - Ornithine Decarboxylase Inhibitors KW - Thioacetamide KW - 075T165X8M KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Ornithine Decarboxylase KW - EC 4.1.1.17 KW - Eflornithine KW - ZQN1G5V6SR KW - Index Medicus KW - Rats KW - Ornithine Decarboxylase -- metabolism KW - Animals KW - Rats, Sprague-Dawley KW - Enzyme Inhibitors -- pharmacology KW - Disease Models, Animal KW - Eflornithine -- pharmacology KW - Male KW - Hepatic Encephalopathy -- physiopathology KW - Hepatic Encephalopathy -- enzymology KW - Hepatic Encephalopathy -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70118315?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+gastroenterology+%26+hepatology&rft.atitle=Effect+of+inhibition+of+ornithine+decarboxylase+activity+in+a+model+of+acute+hepatocellular+necrosis.&rft.au=Yurdaydin%2C+C%3BSwain%2C+M+G%3BMininberg%2C+E+D%3BVergalla%2C+J%3BKleiner%2C+D%3BPaul%2C+S+M%3BJones%2C+E+A&rft.aulast=Yurdaydin&rft.aufirst=C&rft.date=1998-06-01&rft.volume=10&rft.issue=6&rft.spage=503&rft.isbn=&rft.btitle=&rft.title=European+journal+of+gastroenterology+%26+hepatology&rft.issn=0954691X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-02-11 N1 - Date created - 1999-02-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Structure-function analysis of muscarinic acetylcholine receptors. AN - 69993070; 9789820 AB - The structural basis underlying the G protein coupling selectivity of different muscarinic receptor subtypes was analyzed by using a combined molecular genetic/biochemical approach. These studies led to the identification of key residues on the receptors as well as the associated G proteins that are critically involved in determining proper receptor/G protein recognition. Mutational analysis of the m3 muscarinic receptor showed that most native cysteine residues are not required for productive receptor/G protein coupling. The putative extracellular disulfide bond was found to be essential for efficient trafficking of the receptor protein to the cell surface but not for receptor-mediated G protein activation. JF - Journal of physiology, Paris AU - Kostenis, E AU - Zeng, F Y AU - Wess, J AD - Laboratory of Bioorganic Chemistry, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA. PY - 1998 SP - 265 EP - 268 VL - 92 IS - 3-4 SN - 0928-4257, 0928-4257 KW - Receptors, Muscarinic KW - 0 KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - Cysteine KW - K848JZ4886 KW - Index Medicus KW - Animals KW - Cysteine -- chemistry KW - GTP-Binding Proteins -- metabolism KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Structure-Activity Relationship KW - Mutagenesis KW - Receptors, Muscarinic -- chemistry KW - Receptors, Muscarinic -- physiology KW - Receptors, Muscarinic -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69993070?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+physiology%2C+Paris&rft.atitle=Structure-function+analysis+of+muscarinic+acetylcholine+receptors.&rft.au=Kostenis%2C+E%3BZeng%2C+F+Y%3BWess%2C+J&rft.aulast=Kostenis&rft.aufirst=E&rft.date=1998-06-01&rft.volume=92&rft.issue=3-4&rft.spage=265&rft.isbn=&rft.btitle=&rft.title=Journal+of+physiology%2C+Paris&rft.issn=09284257&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-01-13 N1 - Date created - 1999-01-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Apoptosis: a novel therapeutic tool? AN - 69260543; 15992005 AB - Apoptosis is a genetically programmed cell death mechanism that appears to occur in all multicellular organisms. It is a normal process that serves to maintain cellular homeostasis. However, in many diseases there is a disruption in the equilibrium between cell proliferation and cell death that contributes directly to the disease. In these cases, a possible therapeutic intervention would be to restore the skewed equilibrium by pushing it in the desired direction through the use of pharmacological agents or genetic approaches. These observations have instigated substantial research in the field of apoptosis, resulting in an increasingly detailed analysis of the molecular mechanisms and the sequence of events that occur in this cell death pathway. In addition, by trying to understand this pathway, several potential therapeutic agents have arisen from those used in chemo-, radio-, and cytokine therapy. While these agents have been relatively successful, it is rare that their effect is complete. Thus, the search continues for a strategy to conquer those cells that are resistant to these regimens. Genetic approaches are novel and have been shown to be quite successful in several in vitro and animal models. They also tend to have low toxicity. It is believed that using a more traditional front-line approach of therapy, supplemented by appropriate genetic intervention, will allow substantial increases in the efficacy of treatment, while at the same time introducing little or no additional toxicity. JF - Expert opinion on investigational drugs AU - Dixon, S C AU - Arah, I N AD - Medicine Branch, Clinical Pharmacokinetics Unit, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. nemra@box-n.nih.gov Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 889 EP - 904 VL - 7 IS - 6 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69260543?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Expert+opinion+on+investigational+drugs&rft.atitle=Apoptosis%3A+a+novel+therapeutic+tool%3F&rft.au=Dixon%2C+S+C%3BArah%2C+I+N&rft.aulast=Dixon&rft.aufirst=S&rft.date=1998-06-01&rft.volume=7&rft.issue=6&rft.spage=889&rft.isbn=&rft.btitle=&rft.title=Expert+opinion+on+investigational+drugs&rft.issn=1744-7658&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-07-14 N1 - Date created - 2005-07-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The first-order giant neurons of the giant fiber system in the squid: electrophysiological and ultrastructural observations. AN - 69189361; 10192523 AB - The giant fiber system controlling mantle contraction used for jet propulsion in squid consists of two sets of three giant neurons organized in tandem. The somata of the 1st- and 2nd-order giant cells are located in the brain, while the perikarya of the 3rd-order giant cells are encountered in the stellate ganglia of the mantle. The somata and dendrites of one fused pair of 1st-order giant cells are thought to receive synaptic input from the eye, statocyst, skin proprioceptors, and supraesophageal lobes. To define the cellular properties for integration of such an extensive synaptic load, especially given its diversity, intracellular recordings and electron microscopic observations were performed on 1st-order giant cells in an isolated head preparation. Spontaneous bursts of action potentials and spikes evoked by extracellular stimulation of the brachial lobe were sensitive to the Na+ channel blocker TTX. Action potentials were also abolished by recording with microelectrodes containing the membrane impermeant, use dependent Na+ channel blocker QX-314. The small action potential amplitude and the abundant synaptic input imply that the spike initiation zone is remotely located from the recording site. The high spontaneous activity in the isolated head preparation, as well as the presence of synaptic junctions resembling inhibitory synapses, suggest; that afferent synapses on 1st-order giant neurons might represent the inhibitory control of the giant fiber system. The characterization of the electroresponsive properties of the 1st-order giant neurons will provide a description of the single cell integrative properties that trigger the rapid jet propulsion necessary for escape behavior in squid. JF - Journal of neurocytology AU - Pozzo-Miller, L D AU - Moreira, J E AU - Llinás, R R AD - Laboratory of Neurobiology, NINDS, NIH, Bethesda, MD 20892, USA. Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 419 EP - 429 VL - 27 IS - 6 SN - 0300-4864, 0300-4864 KW - Anesthetics, Local KW - 0 KW - QX-314 KW - 21306-56-9 KW - Tetrodotoxin KW - 4368-28-9 KW - Lidocaine KW - 98PI200987 KW - Index Medicus KW - Action Potentials -- physiology KW - Animals KW - Anesthetics, Local -- pharmacology KW - Evoked Potentials -- physiology KW - Axons -- ultrastructure KW - Action Potentials -- drug effects KW - Decapodiformes KW - Electric Stimulation KW - Axons -- physiology KW - Synapses -- physiology KW - Synapses -- ultrastructure KW - Cells, Cultured KW - In Vitro Techniques KW - Escape Reaction -- physiology KW - Lidocaine -- pharmacology KW - Tetrodotoxin -- pharmacology KW - Lidocaine -- analogs & derivatives KW - Nerve Fibers -- physiology KW - Neurons -- drug effects KW - Nerve Fibers -- ultrastructure KW - Neurons -- physiology KW - Neurons -- ultrastructure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69189361?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+neurocytology&rft.atitle=The+first-order+giant+neurons+of+the+giant+fiber+system+in+the+squid%3A+electrophysiological+and+ultrastructural+observations.&rft.au=Pozzo-Miller%2C+L+D%3BMoreira%2C+J+E%3BLlin%C3%A1s%2C+R+R&rft.aulast=Pozzo-Miller&rft.aufirst=L&rft.date=1998-06-01&rft.volume=27&rft.issue=6&rft.spage=419&rft.isbn=&rft.btitle=&rft.title=Journal+of+neurocytology&rft.issn=03004864&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-06-22 N1 - Date created - 1999-06-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Coupling of mantle-upwelling and shearing; Mesozoic dyke-swarms in Da-Hinggan Mountains, Northeast China AN - 52483630; 1999-038532 AB - The morphological and petrologico-geochemical features, and the time-space evolution history of Mesozoic dyke-swarms in Da Hinggan Mts. are studied to explore the polytopism and polytrope of the driving forces for deformation of the continental lithosphere. It is found that two dynamic mechanisms were coupled in the deformation of the upper lithosphere when upwelling and intrusion of the mantle-derived magma occurred. JF - Episodes AU - Shao, Ji'an AU - Gai, Fengying AU - Zhang, Luqiao Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 99 EP - 103 PB - International Union of Geological Sciences (IUGS), Ottawa, ON VL - 21 IS - 2 SN - 0705-3797, 0705-3797 KW - upwelling KW - Far East KW - igneous rocks KW - mantle KW - dike swarms KW - plutonic rocks KW - mineral composition KW - Linxi China KW - tectonics KW - rare earths KW - crystal fractionation KW - chemical composition KW - Asia KW - geochemistry KW - China KW - Inner Mongolia China KW - concentration KW - petrology KW - lithosphere KW - deformation KW - Mesozoic KW - orogeny KW - intrusions KW - dikes KW - Da Hinggan Ling KW - metals KW - magmas KW - shear KW - diabase KW - magma chambers KW - 02C:Geochemistry of rocks, soils, and sediments KW - 05A:Igneous and metamorphic petrology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/52483630?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ageorefmodule&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Episodes&rft.atitle=Coupling+of+mantle-upwelling+and+shearing%3B+Mesozoic+dyke-swarms+in+Da-Hinggan+Mountains%2C+Northeast+China&rft.au=Shao%2C+Ji%27an%3BGai%2C+Fengying%3BZhang%2C+Luqiao&rft.aulast=Shao&rft.aufirst=Ji%27an&rft.date=1998-06-01&rft.volume=21&rft.issue=2&rft.spage=99&rft.isbn=&rft.btitle=&rft.title=Episodes&rft.issn=07053797&rft_id=info:doi/ L2 - http://www.episodes.org/ LA - English DB - GeoRef N1 - Copyright - GeoRef, Copyright 2012, American Geosciences Institute. N1 - Date revised - 1999-01-01 N1 - Number of references - 10 N1 - PubXState - ON N1 - Document feature - illus. incl. 4 tables, geol. sketch map N1 - Last updated - 2012-06-07 N1 - SubjectsTermNotLitGenreText - Asia; chemical composition; China; concentration; crystal fractionation; Da Hinggan Ling; deformation; diabase; dike swarms; dikes; Far East; geochemistry; igneous rocks; Inner Mongolia China; intrusions; Linxi China; lithosphere; magma chambers; magmas; mantle; Mesozoic; metals; mineral composition; orogeny; petrology; plutonic rocks; rare earths; shear; tectonics; upwelling ER - TY - JOUR T1 - Epitope Mapping of a Series of Human Thymidylate Synthase Monoclonal Antibodies AN - 17209380; 4495061 AB - We have reported previously the development and application of several monoclonal antibodies to thymidylate synthase (TS). In this study, we used a series of overlapping 17-mer peptides that spanned the entire TS protein to map the epitope recognized by three TS monoclonal antibodies (TS 106, TS 109, and TS 110). Using an ELISA, we identified two peptides (R super(126)-F super(142) and L super(131)-R super(147)) that bound all three antibodies, which suggests that each antibody recognized a similar epitope on TS. A second set of peptides, representing sequential single-residue truncations from either the amino terminus or the carboxyl terminus starting with a G super(129)-E super(145) 17-mer, was synthesized. A 10-amino acid sequence P super(133)-F super(142) (PVYG-FQWRHF) was identified as the binding epitope for all three antibodies. Further investigation via substitution mutational analysis of each residue within this epitope revealed that residues F super(137), W super(139), R super(140), H super(141), and F super(142) were critical for maximal binding of TS 106 and TS 110. TS 109 showed a similar pattern except in regard to R super(140), with which there was no apparent loss of binding. In addition to the utility of the three antibodies in detecting and measuring TS levels, identification of the binding locus permits the potential application of these antibodies in the investigation of TS enzymatic and regulatory function. JF - Cancer Research AU - Behan, KA AU - Johnston, P G AU - Allegra, C J AD - National Cancer Institute, Medicine Branch at the National Naval Medical Center, 8901 Wisconsin Avenue, Building 8, Room 5101, Bethesda, MD 20889-5105, USA Y1 - 1998/06// PY - 1998 DA - Jun 1998 SP - 2606 EP - 2611 VL - 58 IS - 12 SN - 0008-5472, 0008-5472 KW - man KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Monoclonal antibodies KW - Thymidylate synthase KW - W3 33375:Antibodies KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17209380?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Research&rft.atitle=Epitope+Mapping+of+a+Series+of+Human+Thymidylate+Synthase+Monoclonal+Antibodies&rft.au=Behan%2C+KA%3BJohnston%2C+P+G%3BAllegra%2C+C+J&rft.aulast=Behan&rft.aufirst=KA&rft.date=1998-06-01&rft.volume=58&rft.issue=12&rft.spage=2606&rft.isbn=&rft.btitle=&rft.title=Cancer+Research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Thymidylate synthase; Monoclonal antibodies ER - TY - JOUR T1 - Peptides Derived from Self-Proteins as Partial Agonists and Antagonists of Human CD8 super(+) T-Cell Clones Reactive to Melanoma/Melanocyte Epitope MART1 sub(27-35) AN - 17205370; 4494462 AB - The self-peptide MART1 sub(27-35) derives from the melanocyte/melanoma protein Melan A/MART1 and is a target epitope of CD8 super(+) T cells, commonly recovered from tumor-infiltrating lymphocytes of HLA-A2.1 super(+) melanoma patients. Despite their prevalence in such patients, these CTLs generally appear to be ineffective in mediating tumor regression in vivo. We have noted previously that numerous peptides from both endogenous and foreign proteins are similar to MART1 sub(27-35) and, potentially, are capable of productively engaging the T-cell receptors of patient-derived CTLs. This observation raised the question of whether CTLs in vivo might encounter self-peptide analogues of MART1 sub(27-35) that lack full agonist activity, perhaps to the detriment of the antitumor CTL response. This possibility was evaluated using cloned, patient-derived CTLs with a panel of self-derived natural analogues of MART1 sub(27-35) in assays for cytolysis, cytokine release, and phosphorylation of T-cell receptor signaling constituents. Several peptides were identified as partial agonists, capable of eliciting cytolysis and/or release of cytokines tumor necrosis factor- alpha and IFN- gamma but not interleukin 2. Several other peptides showed antagonist behavior, effectively inhibiting cytolysis of MART1 sub(27-35)-pulsed targets, but did not inhibit killing of cells prepulsed with a synthetic, heteroclitic variant of MART1 sub(27-35). Some of these antagonists also had lasting effects on interleukin 2 secretion by CTLs under experimental conditions involving sequential exposure to ligands. Together, these observations suggest that encounters with self-peptide analogues of MART1 sub(27-35) may contribute to the peripheral maintenance of these CTLs, while ultimately impairing the efficacy of this antitumor T-cell response. JF - Cancer Research AU - Loftus, D J AU - Squarcina, P AU - Nielsen, M-B AU - Geisler, C AU - Castelli, C AU - Oedum, N AU - Appella, E AU - Parmiani, G AU - Rivoltini, L AD - Laboratory of Cell Biology, National Cancer Institute, NIH, Building 37, Room 1B03, 37 Convent Drive, MSC 4255, Bethesda, MD 20892, USA Y1 - 1998/06// PY - 1998 DA - Jun 1998 SP - 2433 EP - 2439 VL - 58 IS - 11 SN - 0008-5472, 0008-5472 KW - CD8 antigen KW - MART-1 antigen KW - histocompatibility antigen HLA KW - man KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Lymphocytes T KW - Vaccines KW - Melanocytes KW - Melanoma KW - W3 33350:Cancer vaccines KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17205370?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Research&rft.atitle=Peptides+Derived+from+Self-Proteins+as+Partial+Agonists+and+Antagonists+of+Human+CD8+super%28%2B%29+T-Cell+Clones+Reactive+to+Melanoma%2FMelanocyte+Epitope+MART1+sub%2827-35%29&rft.au=Loftus%2C+D+J%3BSquarcina%2C+P%3BNielsen%2C+M-B%3BGeisler%2C+C%3BCastelli%2C+C%3BOedum%2C+N%3BAppella%2C+E%3BParmiani%2C+G%3BRivoltini%2C+L&rft.aulast=Loftus&rft.aufirst=D&rft.date=1998-06-01&rft.volume=58&rft.issue=11&rft.spage=2433&rft.isbn=&rft.btitle=&rft.title=Cancer+Research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Melanoma; Melanocytes; Vaccines; Lymphocytes T ER - TY - JOUR T1 - Plasmid DNA Encoding Transforming Growth Factor- beta 1 Suppresses Chronic Disease in a Streptococcal Cell Wall-induced Arthritis Model AN - 17191068; 4484320 AB - Transforming growth factor beta is a potent immunomodulator with both pro- and antiinflammatory activities. Based on its immunosuppressive actions, exogenous TGF- beta has been shown to inhibit autoimmune and chronic inflammatory diseases. To further explore the potential therapeutic role of TGF- beta , we administered a plasmid DNA encoding human TGF- beta 1 intramuscularly to rats with streptococcal cell wall-induced arthritis. A single dose of 300 mu g plasmid DNA encoding TGF- beta 1, but not vector DNA, administered at the peak of the acute phase profoundly suppressed the subsequent evolution of chronic erosive disease typified by disabling joint swelling and deformity (articular index = 8.17 plus or minus 0.17 vs. 1.25 plus or minus 0.76, n = 6, day 26, P < 0.01). Moreover, delivery of the TGF- beta 1 DNA even as the chronic phase commenced virtually eliminated subsequent inflammation and arthritis. Both radiologic and histopathologic as well as molecular evidence supported the marked inhibitory effect of TGF- beta 1 DNA on synovial pathology, with decreases in the inflammatory cell infiltration, pannus formation, cartilage and bone destruction, and the expression of proinflammatory cytokines that characterize this model. Increases in TGF- beta 1 protein were detected in the circulation of TGF- beta 1 DNA-treated animals, consistent with the observed therapeutic effects being TGF- beta 1 dependent. These observations provide the first evidence that gene transfer of plasmid DNA encoding TGF- beta 1 provides a mechanism to deliver this potent cytokine that effectively suppresses ongoing inflammatory pathology in arthritis. JF - Journal of Clinical Investigation AU - Song, Xiao-yu AU - Gu, MiLi AU - Jin, Wen-wen AU - Klinman, D M AU - Wahl, S M AD - Bldg. 30, Room 332, 30 Convent Drive, MSC 4352, Bethesda, MD 20892-4352, USA, smwahl@yoda.nidr.nih.gov Y1 - 1998/06// PY - 1998 DA - Jun 1998 SP - 2615 EP - 2621 VL - 101 IS - 12 SN - 0021-9738, 0021-9738 KW - rats KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Gene transfer KW - Arthritis KW - Animal models KW - Plasmids KW - Inflammation KW - W 30965:Miscellaneous, Reviews KW - W3 33180:Gene based (protocols, clinical trials, and animal models) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17191068?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Clinical+Investigation&rft.atitle=Plasmid+DNA+Encoding+Transforming+Growth+Factor-+beta+1+Suppresses+Chronic+Disease+in+a+Streptococcal+Cell+Wall-induced+Arthritis+Model&rft.au=Song%2C+Xiao-yu%3BGu%2C+MiLi%3BJin%2C+Wen-wen%3BKlinman%2C+D+M%3BWahl%2C+S+M&rft.aulast=Song&rft.aufirst=Xiao-yu&rft.date=1998-06-01&rft.volume=101&rft.issue=12&rft.spage=2615&rft.isbn=&rft.btitle=&rft.title=Journal+of+Clinical+Investigation&rft.issn=00219738&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Plasmids; Gene transfer; Animal models; Inflammation; Arthritis ER - TY - JOUR T1 - Clarification of the relationship between free radical spin trapping and carbon tetrachloride metabolism in microsomal systems AN - 17182161; 4480770 AB - It has been proposed that the C-phenyl-N-tert-butylnitrone/trichloromethyl radical adduct PBN/ super( times )CCl sub(3) is metabolized to either the C-phenyl-N-tert-butylnitrone/carbon dioxide anion radical adduct (PBN/ super( times )CO sub(2) super(-)) or the glutathione (GSH) and CCl sub(4)-dependent PBN radical adduct (PBN/[GSH- super( times )CCl sub(3)]). Inclusion of PBN/ super( times )CCl sub(3) in microsomal incubations containing GSH, nicotinamide adenine dinucleotide phosphate (NADPH), or GSH plus NADPH produced no electron spin resonance (ESR) spectral data indicative of the formation of either the PBN/[GSH- super( times )CCl sub(3)] or PBN/ super( times )CO sub(2) super(-) radical adducts. Microsomes alone or with GSH had no effect on the PBN/ super( times )CCl sub(3) radical adduct. Addition of NADPH to a microsomal system containing PBN/ super( times )CCl sub(3) presumably reduced the radical adduct to its ESR-silent hydroxylamine because no ESR signal was observed. The Folch extract of this system produced an ESR spectrum that was a composite of two radicals, one of which had hyperfine coupling constants identical to those of PBN/ super( times )CCl sub(3). We conclude that PBN/ super( times )CCl sub(3) is not metabolized into either PBN/[GSH- super( times )CCl sub(3)] or PBN/ super( times )CO sub(2) super(-) in microsomal systems. JF - Free Radical Biology & Medicine AU - Connor, H D AU - Thurman, R G AU - Chen, G AU - Poyer, J L AU - Janzen, E G AU - Mason, R P AD - National Institute of Environmental Health Sciences, National Institutes of Health, P.O. Box 12233, Research Triangle Park, NC 27709, USA Y1 - 1998/06// PY - 1998 DA - Jun 1998 SP - 1364 EP - 1368 VL - 24 IS - 9 SN - 0891-5849, 0891-5849 KW - metabolism KW - spin trapping KW - Toxicology Abstracts KW - Microsomes KW - Carbon tetrachloride KW - Free radicals KW - X 24153:Metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17182161?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Free+Radical+Biology+%26+Medicine&rft.atitle=Clarification+of+the+relationship+between+free+radical+spin+trapping+and+carbon+tetrachloride+metabolism+in+microsomal+systems&rft.au=Connor%2C+H+D%3BThurman%2C+R+G%3BChen%2C+G%3BPoyer%2C+J+L%3BJanzen%2C+E+G%3BMason%2C+R+P&rft.aulast=Connor&rft.aufirst=H&rft.date=1998-06-01&rft.volume=24&rft.issue=9&rft.spage=1364&rft.isbn=&rft.btitle=&rft.title=Free+Radical+Biology+%26+Medicine&rft.issn=08915849&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Carbon tetrachloride; Microsomes; Free radicals ER - TY - JOUR T1 - Effects of neem flowers, Thai and Chinese bitter gourd fruits and sweet basil leaves on hepatic monooxygenases and glutathione S-transferase activities, and in vitro metabolic activation of chemical carcinogens in rats AN - 17099261; 4403868 AB - The objectives of this study were to determine the effects of feeding of four vegetables commonly consumed in Thailand, namely, flowers of the neem tree (Azadirachta indica var. siamensis), fruits of Thai and the Chinese bitter gourd (Momordica charantia Linn.) and leaves of sweet basil (Ocimum basilicum Linn) on the levels of phase I enzymes, which include cytochrome P450 (P450), aniline hydroxylase (ANH) and aminopyrine-N-demethylase (AMD) as well as the capacity to activate the mutagenicities of aflatoxin B sub(1) (AFB sub(1)) and benzo[a]pyrene (BaP), and to induce the phase II enzymes [i.e. glutathione S-transferase (GST)] in rat liver. It was found that feeding of the diets containing 12.5% neem flowers and Thai bitter gourd fruits for 2 weeks strongly enhanced GST activity, 2.7- and 1.6- fold of the pair-fed control values, respectively, while resulting in a marked reduction of the levels of most phase I reactions. Fruits of the Chinese bitter gourd, which is in the same species as Thai bitter gourd, had no effect on GST activity but decreased AMD activity and the in vitro metabolic activation of AFB sub(1) and BaP. On the other hand, however, dietary sweet basil leaves caused a significant increase in the levels of both GST and all phase I enzymes. Results in the present study clearly demonstrate that neem flowers and Thai bitter gourd fruits contain monofunctional phase II enzyme inducers and compounds capable of repressing some monooxygenases, especially those involved in the metabolic activation of chemical carcinogens, while sweet basil leaves contain compounds, probably bifunctional inducers, capable of inducing both phase I and phase II enzymes and Chinese bitter gourd fruits contain only compounds capable of repressing some monooxygenases. These results therefore suggest that neem flowers and Thai bitter gourd fruits may possess chemopreventive potential, while those of Chinese bitter gourd fruits and sweet basil leaves are uncertain. JF - Food and Chemical Toxicology AU - Kusamran, W R AU - Ratanavila, A AU - Tepsuwan, A AD - Biochemistry and Chemical Carcinogenesis Section, Research Division, National Cancer Institute, Bangkok, Thailand Y1 - 1998/06// PY - 1998 DA - Jun 1998 SP - 475 EP - 484 VL - 36 IS - 6 SN - 0278-6915, 0278-6915 KW - Thailand KW - metabolic activation KW - Toxicology Abstracts KW - Vegetables KW - Liver KW - Carcinogens KW - Glutathione transferase KW - Unspecific monooxygenase KW - X 24240:Miscellaneous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17099261?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Food+and+Chemical+Toxicology&rft.atitle=Effects+of+neem+flowers%2C+Thai+and+Chinese+bitter+gourd+fruits+and+sweet+basil+leaves+on+hepatic+monooxygenases+and+glutathione+S-transferase+activities%2C+and+in+vitro+metabolic+activation+of+chemical+carcinogens+in+rats&rft.au=Kusamran%2C+W+R%3BRatanavila%2C+A%3BTepsuwan%2C+A&rft.aulast=Kusamran&rft.aufirst=W&rft.date=1998-06-01&rft.volume=36&rft.issue=6&rft.spage=475&rft.isbn=&rft.btitle=&rft.title=Food+and+Chemical+Toxicology&rft.issn=02786915&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Carcinogens; Liver; Glutathione transferase; Vegetables; Unspecific monooxygenase ER - TY - JOUR T1 - Design of delta -opioid peptide antagonists for emerging drug applications AN - 16559769; 4400181 AB - The need for delta -receptor-selective opioid antagonists has led to their development based on structure-activity relationships of delta - and mu -opioid agonists. The unusual amino acid 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic), found in a series of H-Tyr-Tic-Phe-(Phe)-OH peptides, is an essential feature of derivatives discussed in this article. Elimination of Phe yields the H-Tyr-Tic-OH dipeptide antagonists, while substitution of Tyr by 2',6'-dimethyl-L-tyrosine (Dmt) gives H-Dmt-Tic-OH and numerous potent, high-affinity and ultraselective delta -opioid antagonists. This article reviews the emergence of derivatives based on the Tyr-Tic and Dmt-Tic pharmacophores as lead structures, and discusses potential clinical and therapeutic applications. JF - Drug Discovery Today AU - Lazarus, L H AU - Bryant, S D AU - Cooper, P S AU - Guerrini, R AU - Balboni, G AU - Salvadori, S AD - Peptide Neurochemistry, LCBRA, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA, lazarus@niehs.nih.gov Y1 - 1998/06// PY - 1998 DA - Jun 1998 SP - 284 EP - 294 VL - 3 IS - 6 SN - 1359-6446, 1359-6446 KW - opioid antagonists KW - opioids (type delta ) KW - Biotechnology and Bioengineering Abstracts; CSA Neurosciences Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Therapeutic applications KW - Drug development KW - Antagonists KW - Reviews KW - W 30965:Miscellaneous, Reviews KW - W3 33390:Products: Others KW - N3 11091:Vertebrate Nervous Systems: General UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16559769?accountid=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=Drug+Discovery+Today&rft.atitle=Design+of+delta+-opioid+peptide+antagonists+for+emerging+drug+applications&rft.au=Lazarus%2C+L+H%3BBryant%2C+S+D%3BCooper%2C+P+S%3BGuerrini%2C+R%3BBalboni%2C+G%3BSalvadori%2C+S&rft.aulast=Lazarus&rft.aufirst=L&rft.date=1998-06-01&rft.volume=3&rft.issue=6&rft.spage=284&rft.isbn=&rft.btitle=&rft.title=Drug+Discovery+Today&rft.issn=13596446&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Antagonists; Reviews; Drug development; Therapeutic applications ER - TY - JOUR T1 - Pesticides and childhood cancer AN - 16554549; 4392662 AB - Children are exposed to potentially carcinogenic pesticides from use in homes, schools, other buildings, lawns and gardens, through food and contaminated drinking water, from agricultural application drift, overspray, or off-gassing, and from carry-home exposures of parents occupationally exposed to pesticides. Parental exposure during the child's gestation or even preconception may also be important. Malignancies linked to pesticides in case reports or case-control studies include leukemia, neuroblastoma, Wilms' tumor, soft-tissue sarcoma, Ewing's sarcoma, non-Hodgkin's lymphoma, and cancers of the brain, colorectum, and testes. Although these studies have been limited by nonspecific pesticide exposure information, small numbers of exposed subjects, and the potential for case-response bias, it is noteworthy that many of the reported increased risks are of greater magnitude than those observed in studies of pesticide-exposed adults, suggesting that children may be particularly sensitive to the carcinogenic effects of pesticides. Future research should include improved exposure assessment, evaluation of risk by age at exposure, and investigation of possible genetic-environment interactions. There is potential to prevent at least some childhood cancer by reducing or eliminating pesticide exposure. JF - Environmental Health Perspectives AU - Zahm, SH AU - Ward, M H AD - National Cancer Institute, 6130 Executive Boulevard, Room 418, Rockville, MD 20892, USA, zahms@epndce.nci.nih.gov Y1 - 1998/06// PY - 1998 DA - Jun 1998 SP - 893 EP - 908 VL - 106 SN - 0091-6765, 0091-6765 KW - man KW - neuroblastoma KW - Pollution Abstracts; Toxicology Abstracts; Health & Safety Science Abstracts KW - Risk assessment KW - Leukemia KW - Ewing's sarcoma KW - Children KW - Cancer KW - Pesticides KW - H 5000:Pesticides KW - P 6000:TOXICOLOGY AND HEALTH KW - X 24136:Environmental impact UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16554549?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+Health+Perspectives&rft.atitle=Pesticides+and+childhood+cancer&rft.au=Zahm%2C+SH%3BWard%2C+M+H&rft.aulast=Zahm&rft.aufirst=SH&rft.date=1998-06-01&rft.volume=106&rft.issue=&rft.spage=893&rft.isbn=&rft.btitle=&rft.title=Environmental+Health+Perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Pesticides; Risk assessment; Children; Leukemia; Cancer; Ewing's sarcoma ER - TY - JOUR T1 - Sequence context profoundly influences the mutagenic potency of trans-opened benzo[a]pyrene 7,8-diol 9,10-epoxide-purine nucleoside adducts in site-specific mutation studies AN - 16554432; 4372346 AB - The postoligomerization method was used to prepare oligonucleotide 16-mers that contained dado or dGuo adducts, derived from trans opening of each enantiomer of the two diastereomeric benzo[a]pyrene 7,8-diol 9,10-epoxides, in two sequence contexts. These 16 oligonucleotides, along with the four corresponding oligonucleotides containing unsubstituted purines, were ligated into single-stranded DNA from bacteriophage M13mp7L2 and transfected into Escherichia coli SMH77. The mutagenic effects of replication past these adducts were then evaluated. The various adduct isomers induced point mutations at different frequencies and with different distributions of mutation types, as was anticipated. However, sequence context had the most substantial effects on mutation frequency. A high frequency of deletions of a single guanine was found in a context where the dGuo adduct was at the 3'-end of a run of five guanines, whereas no single base deletion was found in the other context studied, 5'-CGA-3'. Mutation frequencies in constructs containing dado adducts were much higher in a 5'-TAG-3' context (37-58%, depending on the individual isomer) than in a 5'-GAT-3' context (5-20%), and for a given adduct, mutation frequency was up to 10-fold higher in the former sequence than in the latter. These findings indicate that sequence context effects need more thorough evaluation if the goal of understanding the mechanism through which DNA adducts lead to mutation is to be achieved. JF - Biochemistry (Washington) AU - Page, JE AU - Zajc, B AU - Oh-Hara, T AU - Lakshman, M K AU - Sayer, J M AU - Jerina, D M AU - Dipple, A AD - Chemistry of Carcinogenesis Laboratory, Advanced BioScience Laboratories-Basic Research Program, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, MD 21702, USA Y1 - 1998/06// PY - 1998 DA - Jun 1998 SP - 9127 EP - 9137 VL - 37 IS - 25 SN - 0006-2960, 0006-2960 KW - benzo(a)pyrene-7,8-diol-9,10-epoxide KW - nucleotide sequence KW - transfection KW - Toxicology Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - Phages KW - DNA adducts KW - Point mutation KW - Phage M13 KW - Escherichia coli KW - Benzo(a)pyrene KW - N 14630:Chemical reactions & interactions, including effects of radiation KW - X 24190:Polycyclic hydrocarbons UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16554432?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemistry+%28Washington%29&rft.atitle=Sequence+context+profoundly+influences+the+mutagenic+potency+of+trans-opened+benzo%5Ba%5Dpyrene+7%2C8-diol+9%2C10-epoxide-purine+nucleoside+adducts+in+site-specific+mutation+studies&rft.au=Page%2C+JE%3BZajc%2C+B%3BOh-Hara%2C+T%3BLakshman%2C+M+K%3BSayer%2C+J+M%3BJerina%2C+D+M%3BDipple%2C+A&rft.aulast=Page&rft.aufirst=JE&rft.date=1998-06-01&rft.volume=37&rft.issue=25&rft.spage=9127&rft.isbn=&rft.btitle=&rft.title=Biochemistry+%28Washington%29&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Phage M13; Point mutation; Phages; Benzo(a)pyrene; DNA adducts ER - TY - JOUR T1 - Thermodynamics of a transition state analogue inhibitor binding to Escherichia coli chorismate mutase: Probing the charge state of an active site residue and its role in inhibitor binding and catalysis AN - 16552534; 4372341 AB - Electrostatic interactions play important roles in the catalysis of chorismate to prephenate by chorismate mutase. Mutation of Gln88 to glutamate in the monofunctional chorismate mutase from Escherichia coli results in an enzyme with a pH profile of activity significantly different from that of the wild type protein. To investigate whether the mutation alters the substrate binding process or the catalysis, we have directly determined the thermodynamic parameters of a transition state analogue inhibitor binding to the wild-type chorismate mutase and its Q88E mutant using isothermal titration calorimetry. The results demonstrate that solvent reorganization and hydrophobic interactions contribute the predominant free energy to inhibitor binding. The charge state of Glu88 in the Q88E mutant was experimentally determined and was shown to be protonated at pH 4.5 and ionized at pH 7.8, consistent with earlier hypotheses. Most surprisingly, inhibitor binding energetics do not exhibit significant pH dependency for both enzymes. Our findings indicate that the charge state of Glu88 has a small impact on inhibitor binding but plays an important role in the catalytic process. JF - Biochemistry (Washington) AU - Lee, A Y AU - Zhang, Sheng AU - Kongsaeree, P AU - Clardy, J AU - Ganem, B AU - Erickson, J W AU - Xie, Dong AD - Structural Biochemistry Program, SAIC Frederick, National Cancer Institute-Frederick Cancer Research and Development Center, Bldg. 322, Rm. 27C, Frederick, MD 21702, USA, xie@ncifcrf.gov Y1 - 1998/06// PY - 1998 DA - Jun 1998 SP - 9052 EP - 9057 VL - 37 IS - 25 SN - 0006-2960, 0006-2960 KW - glutamic acid KW - glutamine KW - Microbiology Abstracts B: Bacteriology KW - Escherichia coli KW - Chorismate mutase KW - Mutants KW - J 02728:Enzymes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16552534?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemistry+%28Washington%29&rft.atitle=Thermodynamics+of+a+transition+state+analogue+inhibitor+binding+to+Escherichia+coli+chorismate+mutase%3A+Probing+the+charge+state+of+an+active+site+residue+and+its+role+in+inhibitor+binding+and+catalysis&rft.au=Lee%2C+A+Y%3BZhang%2C+Sheng%3BKongsaeree%2C+P%3BClardy%2C+J%3BGanem%2C+B%3BErickson%2C+J+W%3BXie%2C+Dong&rft.aulast=Lee&rft.aufirst=A&rft.date=1998-06-01&rft.volume=37&rft.issue=25&rft.spage=9052&rft.isbn=&rft.btitle=&rft.title=Biochemistry+%28Washington%29&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Mutants; Chorismate mutase ER - TY - JOUR T1 - Transient transfection of primary T helper cells by particle-mediated gene transfer AN - 16535265; 4388437 AB - The study of the molecular basis of normal CD4+ T cell function, such as the control of commitment to the TH sub(1) or TH sub(2) phenotypes has been difficult due to the resistance of these cells to transfection by conventional methods. We used antibodies specific to T cell surface molecules to immobilize these cells and optimized conditions for transiently transfecting them by means of particle-mediated gene transfer. Using this technique, a construct encompassing -577 to +1 of the IL-4 promoter allowed transcription of a luciferase reporter gene in recently-differentiated TH2 cells stimulated by anti-CD3, consistent with regulation of endogenous IL-4 gene expression. JF - Journal of Immunological Methods AU - Huang, H AU - Pannetier, C AU - Hu-Li, J AU - Paul, W E AD - Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 10, Room 11N311, 10 Center Drive-MSC 1892, Bethesda, MD 20892-1892, USA Y1 - 1998/06/01/ PY - 1998 DA - 1998 Jun 01 SP - 173 EP - 177 PB - Elsevier Science B.V. VL - 215 IS - 1-2 SN - 0022-1759, 0022-1759 KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - F 06713:Physicochemical methods KW - W3 33243:Molecular methods KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16535265?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Immunological+Methods&rft.atitle=Transient+transfection+of+primary+T+helper+cells+by+particle-mediated+gene+transfer&rft.au=Huang%2C+H%3BPannetier%2C+C%3BHu-Li%2C+J%3BPaul%2C+W+E&rft.aulast=Huang&rft.aufirst=H&rft.date=1998-06-01&rft.volume=215&rft.issue=1-2&rft.spage=173&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immunological+Methods&rft.issn=00221759&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Variables affecting results of sodium chloride tolerance test for identification of rapidly growing mycobacteria AN - 16525737; 4401585 AB - The sodium chloride tolerance test is often used in the identification of rapidly growing mycobacteria, particularly for distinguishing between Mycobacterium abscessus and Mycobacterium chelonae. This test, however, is frequently unreliable for the identification of some species. In this study we examined the following variables: medium manufacturer, inoculum concentration, and atmosphere and temperature of incubation. Results show that reliability is improved if the test and control slants are inoculated with an organism suspension spectrophotometrically equal to a 1 McFarland standard. Slants should be incubated at 35 degree C in ambient air and checked weekly for 4 weeks. Growth on control slants should be critically evaluated to determine the adequacy of the inoculum; colonies should number greater than 50. Salt-containing media should be examined carefully to detect pinpoint or tiny colonies, and colonies should number greater than 50 for a positive reaction. Concurrent use of a citrate slant may be helpful for distinguishing between M. abscessus and M. chelonae. Molecular methodologies are probably the most reliable means for the identification of rapidly growing mycobacteria and should be used, if possible, when unequivocal species identification is of particular importance. JF - Journal of Clinical Microbiology AU - Conville, P S AU - Witebsky, F G AD - Microbiology Service, Clinical Pathology Department, National Institutes of Health, 10 Center Dr. MSC 1508, Bethesda, MD 20892- 1508, USA, pconville@nih.gov Y1 - 1998/06// PY - 1998 DA - Jun 1998 SP - 1555 EP - 1559 VL - 36 IS - 6 SN - 0095-1137, 0095-1137 KW - Salt tolerance test KW - Sodium chloride KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Microbiology Abstracts B: Bacteriology KW - A 01116:Bacteria KW - J 02710:Identification, taxonomy and typing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16525737?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Clinical+Microbiology&rft.atitle=Variables+affecting+results+of+sodium+chloride+tolerance+test+for+identification+of+rapidly+growing+mycobacteria&rft.au=Conville%2C+P+S%3BWitebsky%2C+F+G&rft.aulast=Conville&rft.aufirst=P&rft.date=1998-06-01&rft.volume=36&rft.issue=6&rft.spage=1555&rft.isbn=&rft.btitle=&rft.title=Journal+of+Clinical+Microbiology&rft.issn=00951137&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Enhanced levels of Staphylococcus aureus stress protein GroEL and DnaK homologs early in infection of human epithelial cells AN - 16480747; 4322935 AB - Antibodies to Staphylococcus aureus heat shock proteins (Hsps) are present in the sera of patients with S. aureus endocarditis. Although these proteins are immunogenic, their role in infection has not been established. We developed a cell culture system as a model to examine the potential involvement of staphylococcal Hsps in the initial events of infection. This study supports a model in which a clinical endocarditis isolate responds to host cell signals by selectively regulating the synthesis of numerous proteins, including the stress proteins Hsp60 (GroEL homolog) and Hsp70 (DnaK homolog) and a unique 58-kDa protein. JF - Infection and Immunity AU - Qoronfleh, M W AU - Bortner, CA AU - Schwartzberg, P AU - Wilkinson, B J AD - SAIC Frederick, National Cancer Institute-Frederick Cancer Research and Development Center (NCI-FCRDC), Structural Biochemistry Program (SBP), Bldg. 320, P.O. Box B, Frederick, MD 21702-1201, USA, ooronfle@ncifcrf.gov Y1 - 1998/06// PY - 1998 DA - Jun 1998 SP - 3024 EP - 3027 VL - 66 IS - 6 SN - 0019-9567, 0019-9567 KW - DnaK protein KW - GroEL protein KW - Microbiology Abstracts B: Bacteriology KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16480747?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Infection+and+Immunity&rft.atitle=Enhanced+levels+of+Staphylococcus+aureus+stress+protein+GroEL+and+DnaK+homologs+early+in+infection+of+human+epithelial+cells&rft.au=Qoronfleh%2C+M+W%3BBortner%2C+CA%3BSchwartzberg%2C+P%3BWilkinson%2C+B+J&rft.aulast=Qoronfleh&rft.aufirst=M&rft.date=1998-06-01&rft.volume=66&rft.issue=6&rft.spage=3024&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Acid stress, anaerobiosis and gadCB: lessons from Lactococcus lactis and Escherichia coli AN - 16474193; 4342450 AB - Bacteria employ multiple strategies for maintaining neutral cytoplasmic pH (pH sub(i)) despite an acidic external environment. Although the mechanisms for maintaining pH homeostasis are not fully understood, the genetic basis of these systems has been the subject of intense investigation in the past few years. JF - Trends in Microbiology AU - Small, PLC AU - Waterman AD - NIH, National Institutes of Allergy and Infectious Disease, Rocky Mountain Laboratories, 903 S. 4th Street, Hamilton, MT 59840, USA, pam_small@nih.gov Y1 - 1998/06// PY - 1998 DA - Jun 1998 SP - 214 EP - 216 VL - 6 IS - 6 SN - 0966-842X, 0966-842X KW - gadCB gene KW - Microbiology Abstracts B: Bacteriology KW - J 02732:Other cell constituents and metabolites UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16474193?accountid=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=Trends+in+Microbiology&rft.atitle=Acid+stress%2C+anaerobiosis+and+gadCB%3A+lessons+from+Lactococcus+lactis+and+Escherichia+coli&rft.au=Small%2C+PLC%3BWaterman&rft.aulast=Small&rft.aufirst=PLC&rft.date=1998-06-01&rft.volume=6&rft.issue=6&rft.spage=214&rft.isbn=&rft.btitle=&rft.title=Trends+in+Microbiology&rft.issn=0966842X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - IL-12 Promotes Drug-Induced Clearance of Mycobacterium avium Infection in Mice AN - 16427894; 4321873 AB - The intracellular pathogen Mycobacterium avium is a major cause of opportunistic infection in AIDS patients and is difficult to manage using conventional chemotherapeutic approaches. In the current study, we describe a strategy for the treatment of M. avium in T cell-deficient hosts based on the simultaneous administration of antibiotics and the immunomodulatory cytokine IL-12. In contrast to SCID mice, which were partially resistant, animals lacking a functional IL-12 p40 gene were found to be highly susceptible to M. avium infection, suggesting that the cytokine can control bacterial growth even in immunodeficient mice. Indeed, rIL-12 that was injected into infected SCID mice in high doses caused small but significant reductions in splenic pathogen loads. Moreover, a lower dose of IL-12, when combined with the antimycobacterial drugs clarithromycin or rifabutin, induced a decrease in bacterial numbers that was significantly greater than that resulting from the administration of the cytokine or drug alone. A similar synergistic effect of IL-12 and antibiotics was seen when immunocompetent mice were treated with the same regimen. The activity of IL-12 in these experiments was shown to be dependent upon the induction of endogenous IFN- gamma . Nevertheless, IFN- gamma itself, even when given at a higher dose than IL-12, failed to significantly enhance antibiotic clearance of bacteria. Together these findings suggest that IL-12 may be a particularly potent adjunct for chemotherapy of M. avium infection in immunocompromised individuals and may result in more effective control of the pathogen without the need for increased drug dosage. JF - Journal of Immunology AU - Doherty, T M AU - Sher, A AD - Laboratory of Parasitic Diseases, Building 4, Room B1-06, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA Y1 - 1998/06/01/ PY - 1998 DA - 1998 Jun 01 SP - 5428 EP - 5435 VL - 160 IS - 11 SN - 0022-1767, 0022-1767 KW - Mycobacterium avium KW - mice KW - Microbiology Abstracts B: Bacteriology; Immunology Abstracts KW - F 06801:Bacteria KW - J 02833:Immune response and immune mechanisms KW - F 06840:Immunotherapy of immune diseases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16427894?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Immunology&rft.atitle=IL-12+Promotes+Drug-Induced+Clearance+of+Mycobacterium+avium+Infection+in+Mice&rft.au=Doherty%2C+T+M%3BSher%2C+A&rft.aulast=Doherty&rft.aufirst=T&rft.date=1998-06-01&rft.volume=160&rft.issue=11&rft.spage=5428&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immunology&rft.issn=00221767&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - In vivo correlates of central serotonin function after high-dose fenfluramine administration. AN - 80015192; 9668672 AB - High doses of fenfluramine (FEN) are known to deplete central serotonin (5-HT) in animals, but functional impairments associated with such 5-HT depletion have been difficult to identify. In the present work, we examined neuroendocrine responsiveness in rats exposed to repeated high-dose FEN treatment. Male rats fitted with indwelling catheters received FEN (20 mg/kg, subcutaneously, twice a day) or saline for 4 days. At 1 and 2 weeks after treatment, rats were challenged with intravenous FEN (1.5 & 3 mg/kg) or saline. Repeated blood samples were drawn, and plasma was assayed for prolactin and corticosterone by radioimmunoassay. Acute FEN challenge caused dose-dependent elevations of plasma prolactin and corticosterone in all rats. However, the FEN-induced hormone responses were significantly blunted (p 50%) postmortem 5-HT levels in the mediobasal hypothalamus, basolateral amygdala, and hippocampus, while the lateral hypothalamus was unaffected. These data suggest that high-dose FEN causes alterations in central 5-HT systems involved with pituitary hormone secretion. The relevance of the present data to the clinical use of FEN is unclear. Because the neuroendocrine challenge paradigm is able to identify functional 5-HT deficits in rats, we propose that similar experiments should be performed in humans. Neuroendocrine challenge tests represent a reliable method to test the existence of FEN-induced neurotoxicity in human patients undergoing long-term FEN treatment. JF - Annals of the New York Academy of Sciences AU - Baumann, M H AU - Ayestas, M A AU - Rothman, R B AD - Clinical Psychopharmacology Section, National Institute on Drug Abuse (NIDA), National Institutes of Health (NIH), Baltimore, Maryland 21224, USA. mbaumann@irp.nida.nih.gov Y1 - 1998/05/30/ PY - 1998 DA - 1998 May 30 SP - 138 EP - 152 VL - 844 SN - 0077-8923, 0077-8923 KW - Serotonin Agents KW - 0 KW - Fenfluramine KW - 2DS058H2CF KW - Serotonin KW - 333DO1RDJY KW - Hydroxyindoleacetic Acid KW - 54-16-0 KW - Prolactin KW - 9002-62-4 KW - Corticosterone KW - W980KJ009P KW - Index Medicus KW - Rats KW - Behavior, Animal -- drug effects KW - Animals KW - Rats, Sprague-Dawley KW - Prolactin -- blood KW - Dose-Response Relationship, Drug KW - Corticosterone -- blood KW - Hydroxyindoleacetic Acid -- metabolism KW - Time Factors KW - Male KW - Fenfluramine -- administration & dosage KW - Serotonin Agents -- pharmacology KW - Brain -- drug effects KW - Brain -- metabolism KW - Fenfluramine -- pharmacology KW - Serotonin -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80015192?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=In+vivo+correlates+of+central+serotonin+function+after+high-dose+fenfluramine+administration.&rft.au=Baumann%2C+M+H%3BAyestas%2C+M+A%3BRothman%2C+R+B&rft.aulast=Baumann&rft.aufirst=M&rft.date=1998-05-30&rft.volume=844&rft.issue=&rft.spage=138&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 - 1998-08-13 N1 - Date created - 1998-08-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phentermine and fenfluramine. Preclinical studies in animal models of cocaine addiction. AN - 80011880; 9668665 AB - Combined dopamine (DA) and 5-hydroxytryptamine (5-HT) releases such as phentermine (PHEN) and fenfluramine (FEN) are reported, in open label studies, to reduce craving for alcohol and cocaine and to prevent relapse. The objective of the studies reported here was to assess the actions of these agents alone and in combination in various animal models of drug addiction. Study 1. In vivo microdialysis experiments demonstrate that these agents preferentially release mesolimbic DA (PHEN) and 5-HT (FEN). Patients who relapse and use cocaine while taking these medications report diminished cocaine-like subjective effects. Microdialysis experiments were performed in awake rats, and dialysate samples were analyzed for DA and 5-HT. PHEN (1 mg/kg, intravenously (i.v.)) elevated DA (2-3-fold) for over 1.5 hr. Administration of cocaine (3 mg/kg, i.v.) increased DA 6-fold in saline-treated rats, but only 3-fold in PHEN-treated rats. PHEN did not reduce cocaine-induced increases in 5-HT. Study 2. These agents were assessed in a mouse model of cocaine-conditioned motoric activity (CCMA). Pretreatment with non-activating doses of PHEN (4.6 mg/kg, intraperitoneally (i.p.)) enhanced CCMA, whereas non-depressing doses of FEN (0.1 mg/kg, i.p.) did not alter CCMA or the PHEN-induced increase in CCMA. In contrast, sub-effective doses of FEN reduced CCMA stereotypy-like locomotion, whereas sub-effective doses of PHEN were without effect. PHEN reversed the FEN-induced increase in CCMA stereotypy-like locomotion. Study 3. PHEN and FEN were assessed in the conditional place preference model. FEN produced marked aversions for an environment previously associated with its administration and the minimum dose producing this effect was 3.0 mg/kg. In contrast, administration of PHEN, amphetamine (1.0-3.0 mg/kg) or morphine (3.0-5.0 mg/kg) produced dose-related preferences for the drug-paired place. However, the magnitude of the response to PHEN was less than that produced by the other prototypic drugs of abuse. In rats that received FEN (0.3 or 3.0 mg/kg) in combination with PHEN (3.0 mg/kg), the conditioned rewarding effects of PHEN were abolished. These data demonstrate that the rewarding effects of PHEN can be conditioned to stimuli previously associated with its administration. However, the conditioned response to this agent is less than that produced by prototypic drugs of abuse. The finding that PHEN-induced place preferences were attenuated by doses of FEN demonstrates that the combination of FEN/PHEN is devoid of motivational effects. The preclinical data obtained with PHEN/FEN in various models of drug provide a strong rationale for pursuing controlled clinical trials in humans with agents that act via a similar mechanism of action. JF - Annals of the New York Academy of Sciences AU - Rothman, R B AU - Elmer, G I AU - Shippenberg, T S AU - Rea, W AU - Baumann, M H AD - Clinical Psychopharmacology Section, National Institute on Drug Abuse (NIDA), National Institutes of Health (NIH), Baltimore, Maryland 21224, USA. RRothman@iep.nida.nih.gov Y1 - 1998/05/30/ PY - 1998 DA - 1998 May 30 SP - 59 EP - 74 VL - 844 SN - 0077-8923, 0077-8923 KW - Dopamine Agents KW - 0 KW - Drug Combinations KW - Serotonin Agents KW - Fenfluramine KW - 2DS058H2CF KW - Serotonin KW - 333DO1RDJY KW - Phentermine KW - C045TQL4WP KW - Cocaine KW - I5Y540LHVR KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Animals KW - Limbic System -- metabolism KW - Dopamine -- metabolism KW - Mice KW - Motor Activity -- physiology KW - Cocaine -- administration & dosage KW - Rats KW - Microdialysis KW - Rats, Sprague-Dawley KW - Self Administration KW - Conditioning (Psychology) -- physiology KW - Serotonin -- metabolism KW - Cocaine -- pharmacology KW - Drug Evaluation, Preclinical KW - Male KW - Dopamine Agents -- therapeutic use KW - Fenfluramine -- therapeutic use KW - Cocaine-Related Disorders -- drug therapy KW - Serotonin Agents -- therapeutic use KW - Phentermine -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80011880?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Phentermine+and+fenfluramine.+Preclinical+studies+in+animal+models+of+cocaine+addiction.&rft.au=Rothman%2C+R+B%3BElmer%2C+G+I%3BShippenberg%2C+T+S%3BRea%2C+W%3BBaumann%2C+M+H&rft.aulast=Rothman&rft.aufirst=R&rft.date=1998-05-30&rft.volume=844&rft.issue=&rft.spage=59&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 - 1998-08-13 N1 - Date created - 1998-08-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Methamphetamine-induced changes in antioxidant enzymes and lipid peroxidation in copper/zinc-superoxide dismutase transgenic mice. AN - 80011459; 9668667 AB - The present study was conducted to investigate the effects of methamphetamine (METH)-induced toxicity on brain cortical and striatal antioxidant defense systems. Because METH-induced toxicity is attenuated in copper/zinc-superoxide dismutase transgenic (Cu/Zn-SOD-Tg) mice, we sought to determine if METH had differential effect on antioxidant enzymes on these mice in comparison to non-Tg mice. METH (4 x 1) mg/kg) induced a significant decrease in Cu/Zn-SOD activity in the cortical region without altering striatal enzymatic activity in non-Tg mice; whereas homozygous SOD-Tg mice showed a significant increase in the striatum. In addition, METH caused decrease in catalase (CAT) activity in the striatum of non-Tg mice and significant increase in the cortex of homozygous SOD-Tg mice. METH also induced decreases in glutathione peroxidase (GSH-Px) in both cortical and striatal regions of non-Tg mice and in the striatum of heterozygous SOD-Tg mice. Lipid peroxidation was increased in both cortices and striata of non-Tg and heterozygous SOD-Tg, mice, whereas the homozygous SOD-Tg mice were not affected. These results are discussed in terms of their substantiation of a role for oxygen-based radicals in METH-induced toxicity in rodents. JF - Annals of the New York Academy of Sciences AU - Jayanthi, S AU - Ladenheim, B AU - Cadet, J L AD - Molecular Neuropsychiatry Section, National Institute of Drug Abuse (NIDA), National Institutes of Health (NIH), Baltimore, Maryland 21224, USA. Y1 - 1998/05/30/ PY - 1998 DA - 1998 May 30 SP - 92 EP - 102 VL - 844 SN - 0077-8923, 0077-8923 KW - Dopamine Agents KW - 0 KW - Lipid Peroxides KW - Methamphetamine KW - 44RAL3456C KW - Malondialdehyde KW - 4Y8F71G49Q KW - Oxidoreductases KW - EC 1.- KW - Catalase KW - EC 1.11.1.6 KW - Glutathione Peroxidase KW - EC 1.11.1.9 KW - Superoxide Dismutase KW - EC 1.15.1.1 KW - Glutathione KW - GAN16C9B8O KW - Index Medicus KW - Malondialdehyde -- metabolism KW - Catalase -- metabolism KW - Animals KW - Homozygote KW - Glutathione Peroxidase -- metabolism KW - Frontal Lobe -- drug effects KW - Heterozygote KW - Glutathione -- metabolism KW - Corpus Striatum -- metabolism KW - Frontal Lobe -- metabolism KW - Corpus Striatum -- drug effects KW - Mice KW - Male KW - Dopamine Agents -- poisoning KW - Oxidoreductases -- metabolism KW - Superoxide Dismutase -- metabolism KW - Superoxide Dismutase -- genetics KW - Lipid Peroxides -- metabolism KW - Methamphetamine -- poisoning KW - Mice, Transgenic -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80011459?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Methamphetamine-induced+changes+in+antioxidant+enzymes+and+lipid+peroxidation+in+copper%2Fzinc-superoxide+dismutase+transgenic+mice.&rft.au=Jayanthi%2C+S%3BLadenheim%2C+B%3BCadet%2C+J+L&rft.aulast=Jayanthi&rft.aufirst=S&rft.date=1998-05-30&rft.volume=844&rft.issue=&rft.spage=92&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 - 1998-08-13 N1 - Date created - 1998-08-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Expression of dominant negative Jun inhibits elevated AP-1 and NF-kappaB transactivation and suppresses anchorage independent growth of HPV immortalized human keratinocytes. AN - 79981176; 9652737 AB - AP-1 transactivation appears to be required for mouse JB6 cell neoplastic transformation induced by the tumor promoter TPA or epidermal growth factor (EGF). Exposure to AP-1 transrepressing retinoids and glucocorticoids and expression of a dominant negative c-jun (TAM67) blocked tumor promoter-induced AP-1 transactivation and neoplastic transformation. The aim of the present study was to extend the inquiry of the role of AP-1 and other transcription factors to human neoplastic progression. Expression of human papillomavirus (HPV) 16 or 18 E6 and E7 immortalizes human keratinocytes and inhibits serum/calcium-stimulated differentiation. Further transformation by v-fos co-expression renders these keratinocytes tumorigenic in nude mice. We have analysed two series of E6/E7 immortalized human keratinocyte cell lines that show progressing phenotypes ranging from differentiation sensitive to anchorage-independent to tumorigenic in nude mice. We analysed the activities of AP-1 and NF-kappaB which may 'cross-talk'. Both DNA binding and transactivation of AP-1 and NF-kappaB transcription factors showed elevation in the anchorage-independent (16RH) and tumorigenic (18 v-fos) keratinocyte lines compared to the less progressed but immortalized cell lines. HPV E7 was expressed at a constant level shown by quantitative RT-PCR in both the more and the less progressed lines, indicating that E7 is not the factor limiting this progression. Blocked shift/supershift analysis indicates that Fos family member proteins especially Fra-1 and Fra-2 are related to progression and no changes found in the Jun family member proteins although they are present in the AP-1/DNA binding complex. When a dominant negative mutant c-jun driven by a human keratin 14 promoter was co-transfected with AP-1 or NF-kappaB reporters, both AP-1 and NF-kappaB activities were suppressed in the more progressed cell lines 16RH and 18 v-fos but not in the less progressed 16RL or 18 cell lines. Overexpression of the same dominant negative c-jun did not inhibit p53 dependent reporter transactivation, indicating the specificity of inhibition of AP-1 and NF-kappaB transactivation in the HPV-immortalized cells. Stable transfectants of this mutant c-jun in the two more progressed cell lines 16RH and 18 v-fos showed reduced AP-1 and NF-kappaB activation and reduced anchorage-independent growth. Together, these results indicate that activation of AP-1, NF-kappaB or both may contribute to neoplastic progression in HPV immortalized human keratinocytes and that specific targeting of the elevated levels seen in benign or malignant tumors might be effective for prevention or treatment of human cancer. JF - Oncogene AU - Li, J J AU - Rhim, J S AU - Schlegel, R AU - Vousden, K H AU - Colburn, N H AD - Laboratory of Biochemical Physiology, National Cancer Institute, FCRDC, Frederick, Maryland 21702-1201, USA. Y1 - 1998/05/28/ PY - 1998 DA - 1998 May 28 SP - 2711 EP - 2721 VL - 16 IS - 21 SN - 0950-9232, 0950-9232 KW - DNA-Binding Proteins KW - 0 KW - E6 protein, Human papillomavirus type 16 KW - E6 protein, Human papillomavirus type 18 KW - E7 protein, Human papillomavirus type 18 KW - FOSL2 protein, human KW - Fos-Related Antigen-2 KW - KRT14 protein, human KW - Keratin-14 KW - Krt1-14 protein, mouse KW - NF-kappa B KW - Oncogene Proteins v-fos KW - Oncogene Proteins, Viral KW - Papillomavirus E7 Proteins KW - Proto-Oncogene Proteins c-fos KW - Proto-Oncogene Proteins c-jun KW - Repressor Proteins KW - Transcription Factor AP-1 KW - Transcription Factors KW - fos-related antigen 1 KW - oncogene protein E7, Human papillomavirus type 16 KW - Keratins KW - 68238-35-7 KW - Index Medicus KW - Keratins -- genetics KW - Oncogene Proteins v-fos -- metabolism KW - Proto-Oncogene Proteins c-fos -- metabolism KW - Transcription Factors -- metabolism KW - Humans KW - Mutagenesis KW - Phenotype KW - Promoter Regions, Genetic KW - Transfection KW - Oncogene Proteins, Viral -- genetics KW - Cell Line KW - Cell Transformation, Viral KW - Cell Division KW - DNA-Binding Proteins -- metabolism KW - Proto-Oncogene Proteins c-jun -- genetics KW - Keratinocytes -- cytology KW - Proto-Oncogene Proteins c-jun -- metabolism KW - Papillomaviridae -- genetics KW - Keratinocytes -- metabolism KW - Transcription Factor AP-1 -- genetics KW - Transcriptional Activation KW - NF-kappa B -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79981176?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Expression+of+dominant+negative+Jun+inhibits+elevated+AP-1+and+NF-kappaB+transactivation+and+suppresses+anchorage+independent+growth+of+HPV+immortalized+human+keratinocytes.&rft.au=Li%2C+J+J%3BRhim%2C+J+S%3BSchlegel%2C+R%3BVousden%2C+K+H%3BColburn%2C+N+H&rft.aulast=Li&rft.aufirst=J&rft.date=1998-05-28&rft.volume=16&rft.issue=21&rft.spage=2711&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-07-28 N1 - Date created - 1998-07-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pilot study of the immunologic effects of recombinant human growth hormone and recombinant insulin-like growth factor in HIV-infected patients. AN - 79946227; 9631143 AB - To study the immunologic effects of recombinant human growth hormone (rhGH), recombinant human insulin-like growth factor type 1 (rhIGF-1), or the combination, in patients with moderately advanced HIV infection. Randomized but not blinded trial. Government medical research center. Twenty-four HIV-infected patients with CD4 cell counts of 100-400 x 10(6)/l who were receiving nucleoside antiretroviral therapy. Either rhGH, rhIGF-1, or the combination was administered subcutaneously for 12 weeks. Immunologic parameters, including T-cell subsets and assays of in vitro interleukin (IL)-2 production in response to antigens and mitogens, and safety profile. Plasma IGF-1 levels were low or low-normal prior to treatment and increased with all three therapies. There were no significant changes in CD4 cell counts, RA/RO CD4 cell subsets, natural killer cell function, immunoglobulin levels, or in vitro IL-2 production in response to mitogen or alloantigens. However, there was an upward trend (and for p18IIIB a statistically significant increase) in the in vitro IL-2 production in response to each of five HIV envelope peptides. Potential toxic effects included fatigue, arthralgia, edema, myalgia, and headache. Patients also were noted to have weight gain averaging 4 kg early in the course of treatment. These results suggest that treatment with rhGH/rhIGF-1 was reasonably well tolerated and that modest improvement in HIV-specific immune function was attained. Further studies will help clarify the therapeutic potential of rhGH/rhIGF-1 as an immunostimulator in the setting of HIV infection. JF - AIDS (London, England) AU - Nguyen, B Y AU - Clerici, M AU - Venzon, D J AU - Bauza, S AU - Murphy, W J AU - Longo, D L AU - Baseler, M AU - Gesundheit, N AU - Broder, S AU - Shearer, G AU - Yarchoan, R AD - HIV and AIDS Malignancy Branch, National Cancer Institute (NCI), National Institutes of Health, Bethesda 20892-1906, USA. Y1 - 1998/05/28/ PY - 1998 DA - 1998 May 28 SP - 895 EP - 904 VL - 12 IS - 8 SN - 0269-9370, 0269-9370 KW - HIV Core Protein p24 KW - 0 KW - Immunoglobulins KW - Interleukin-2 KW - Recombinant Proteins KW - Human Growth Hormone KW - 12629-01-5 KW - Insulin-Like Growth Factor I KW - 67763-96-6 KW - Index Medicus KW - AIDS/HIV KW - HIV Core Protein p24 -- blood KW - Humans KW - Interleukin-2 -- biosynthesis KW - Pilot Projects KW - Leukocytes, Mononuclear -- immunology KW - CD4 Lymphocyte Count KW - Body Weight KW - T-Lymphocyte Subsets -- immunology KW - Adult KW - Immunoglobulins -- blood KW - Middle Aged KW - T-Lymphocytes, Helper-Inducer -- physiology KW - Recombinant Proteins -- therapeutic use KW - Female KW - Killer Cells, Natural -- immunology KW - Male KW - Human Growth Hormone -- therapeutic use KW - Insulin-Like Growth Factor I -- therapeutic use KW - Insulin-Like Growth Factor I -- adverse effects KW - HIV Infections -- immunology KW - HIV Infections -- drug therapy KW - Insulin-Like Growth Factor I -- analysis KW - Human Growth Hormone -- adverse effects KW - Human Growth Hormone -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79946227?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Pilot+study+of+the+immunologic+effects+of+recombinant+human+growth+hormone+and+recombinant+insulin-like+growth+factor+in+HIV-infected+patients.&rft.au=Nguyen%2C+B+Y%3BClerici%2C+M%3BVenzon%2C+D+J%3BBauza%2C+S%3BMurphy%2C+W+J%3BLongo%2C+D+L%3BBaseler%2C+M%3BGesundheit%2C+N%3BBroder%2C+S%3BShearer%2C+G%3BYarchoan%2C+R&rft.aulast=Nguyen&rft.aufirst=B&rft.date=1998-05-28&rft.volume=12&rft.issue=8&rft.spage=895&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 - 1998-09-16 N1 - Date created - 1998-09-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Yeast ARMs (DNA at-risk motifs) can reveal sources of genome instability. AN - 80042861; 9685581 AB - The genomes of all organisms contain an abundance of DNA repeats which are at-risk for causing genetic change. We have used the yeast Saccharomyces cerevisiae to investigate various repeat categories in order to understand their potential for causing genomic instability and the role of DNA metabolism factors. Several types of repeats can increase enormously the likelihood of genetic changes such as mutation or recombination when present either in wild type or mutants defective in replication or repair. Specifically, we have investigated inverted repeats, homonucleotide runs, and short distant repeats and the consequences of various DNA metabolism mutants. Because the at-risk motifs (ARMs) that we characterized are sensitive indicators, we have found that they are useful tools to reveal new genetic factors affecting genome stability as well as to distinguish subtle differences between alleles. Copyright 1998 Elsevier Science B.V. All rights reserved. JF - Mutation research AU - Gordenin, D A AU - Resnick, M A AD - Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, 101 Alexander Dr., P.O. Box 12233, Research Triangle Park, NC 27709, USA. gordenin@niehs.nih.gov Y1 - 1998/05/25/ PY - 1998 DA - 1998 May 25 SP - 45 EP - 58 VL - 400 IS - 1-2 SN - 0027-5107, 0027-5107 KW - Hazardous Substances KW - 0 KW - Index Medicus KW - Mutagenesis -- drug effects KW - Animals KW - Humans KW - Genetic Diseases, Inborn -- genetics KW - Mutagenesis -- physiology KW - Mutagenesis -- genetics KW - Hazardous Substances -- toxicity KW - Saccharomyces cerevisiae -- genetics KW - Trinucleotide Repeat Expansion -- genetics KW - Trinucleotide Repeat Expansion -- drug effects KW - Genome, Fungal UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80042861?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Yeast+ARMs+%28DNA+at-risk+motifs%29+can+reveal+sources+of+genome+instability.&rft.au=Gordenin%2C+D+A%3BResnick%2C+M+A&rft.aulast=Gordenin&rft.aufirst=D&rft.date=1998-05-25&rft.volume=400&rft.issue=1-2&rft.spage=45&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 - 1998-09-23 N1 - Date created - 1998-09-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cadmium suppresses apoptosis induced by chromium. AN - 79981104; 9652551 AB - Cadmium and chromium are both well-known human carcinogens, and common exposures to these metals are not infrequent. Recent studies have shown that hexavalent chromium induces apoptosis in Chinese hamster ovary (CHO) cells, suggesting an association of apoptosis with carcinogenesis. In contrast, induction of apoptosis by cadmium has been inconsistently observed. The present study was designed to determine if cadmium could induce apoptosis in CHO cells and if common exposure to cadmium and chromium would modify any apoptotic response. Apoptosis was evaluated by both agarose gel and in situ end-labeling methods. Apoptosis was observed at 48 h after treatment with 300 microM chromium (Na2CrO4) for 2 h. Cadmium alone at concentrations of 1, 5, or 10 microM (as CdCl2) did not induce apoptosis in these cells even at times up to 72 h after treatment. However, when CHO cells were concurrently exposed to cadmium and chromium, chromium-induced apoptosis was markedly suppressed in a cadmium concentration-related fashion. Cadmium did not consistently modify the cytotoxic effects of chromium, and significant increases in metallothionein were not induced by these metal treatments. These findings indicate that cadmium can block chromium-induced apoptosis. The suppression of apoptosis by cadmium may be a significant aspect of its carcinogenic mechanism. JF - Journal of toxicology and environmental health. Part A AU - Shimada, H AU - Shiao, Y H AU - Shibata, M AU - Waalkes, M P AD - Laboratory of Comparative Carcinogenesis and Office of Laboratory Animal Science, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland, USA. Y1 - 1998/05/22/ PY - 1998 DA - 1998 May 22 SP - 159 EP - 168 VL - 54 IS - 2 SN - 1528-7394, 1528-7394 KW - Carcinogens KW - 0 KW - Cadmium KW - 00BH33GNGH KW - Chromium KW - 0R0008Q3JB KW - Metallothionein KW - 9038-94-2 KW - Index Medicus KW - Carcinogens -- pharmacology KW - Animals KW - Drug Interactions KW - Cricetulus KW - In Vitro Techniques KW - Carcinogens -- toxicity KW - CHO Cells KW - Metallothionein -- metabolism KW - Cell Transformation, Neoplastic KW - Cricetinae KW - Cadmium -- pharmacology KW - Apoptosis -- drug effects KW - Chromium -- pharmacology KW - Cadmium -- toxicity KW - Chromium -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79981104?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+toxicology+and+environmental+health.+Part+A&rft.atitle=Cadmium+suppresses+apoptosis+induced+by+chromium.&rft.au=Shimada%2C+H%3BShiao%2C+Y+H%3BShibata%2C+M%3BWaalkes%2C+M+P&rft.aulast=Shimada&rft.aufirst=H&rft.date=1998-05-22&rft.volume=54&rft.issue=2&rft.spage=159&rft.isbn=&rft.btitle=&rft.title=Journal+of+toxicology+and+environmental+health.+Part+A&rft.issn=15287394&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-07-15 N1 - Date created - 1998-07-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Disposition of 2-methylimidazole in rats. AN - 79979736; 9652548 AB - 2-Methylimidazole (2-MI), widely used as a chemical intermediate, is also present in cigarette smoke and may form in food and forage as a result of ammoniation of simple sugars. 2-MI has been shown to be neurotoxic in several animal species and to alter serum levels of T3, T4, and thyroid-stimulating hormone (TSH) in the rat, apparently leading to hyperplasia of thyroid follicular cells. In order to better characterize 2-MI-induced toxicity, the disposition of [2-(14)C]-2-MI has been investigated following p.o. administration of either 5, 50, or 150 mg/kg to male F344 rats. Excretion data indicated that absorption of 2-MI was both rapid and proportional to dose in the range studied. Approximately 90% of the total dose was eliminated in urine within 24 h. Most of the remaining 14C was excreted in feces and as expired 14CO2. Excretion data were similar following i.v. administration of 5 mg/kg. Little or no enterohepatic circulation of compound occurred, since biliary excretion of 2-MI-derived 14C was negligible. Approximately 70% of the 14C excreted in urine, following all dosing, consisted of parent compound. High-performance liquid chromatography (HPLC) chromatograms for all treatment groups were similar, indicating that metabolism of 2-MI in rats was not affected by dose or route of administration. JF - Journal of toxicology and environmental health. Part A AU - Sanders, J M AU - Griffin, R J AU - Burka, L T AU - Matthews, H B AD - Laboratory of Pharmacology and Chemistry, National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1998/05/22/ PY - 1998 DA - 1998 May 22 SP - 121 EP - 132 VL - 54 IS - 2 SN - 1528-7394, 1528-7394 KW - Imidazoles KW - 0 KW - 2-methylimidazole KW - T0049Z45LZ KW - Index Medicus KW - Rats KW - Administration, Oral KW - Animals KW - Rats, Inbred F344 KW - Dose-Response Relationship, Drug KW - Metabolic Clearance Rate KW - Tissue Distribution KW - Male KW - Chromatography, High Pressure Liquid KW - Imidazoles -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79979736?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+toxicology+and+environmental+health.+Part+A&rft.atitle=Disposition+of+2-methylimidazole+in+rats.&rft.au=Sanders%2C+J+M%3BGriffin%2C+R+J%3BBurka%2C+L+T%3BMatthews%2C+H+B&rft.aulast=Sanders&rft.aufirst=J&rft.date=1998-05-22&rft.volume=54&rft.issue=2&rft.spage=121&rft.isbn=&rft.btitle=&rft.title=Journal+of+toxicology+and+environmental+health.+Part+A&rft.issn=15287394&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-07-15 N1 - Date created - 1998-07-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The human poly(A)-binding protein 1 shuttles between the nucleus and the cytoplasm. AN - 79885992; 9582337 AB - We have studied the intracellular localization of poly(A)-binding protein 1 (PABP1) by indirect immunofluorescence as well as by tagging with the green fluorescent protein (GFP) in living cells. We show that PABP1 is able to enter the nucleus. Accumulation of PABP1 in the nuclei was observed upon transcription inhibition, suggesting that active transcription is required for PABP1 export. The nuclear import of PABP1 is an energy-dependent process since PABP1 fails to enter the nucleus upon ATP depletion and at low temperature. Transfection of PABP1 or PABP1-GFP resulted in heterogeneity of intracellular distribution of the protein. In the low expressing cells, PABP1 was localized in the cytoplasm, whereas in the high expressors, we observed accumulation of the protein in the nucleus. Nuclear PABP1 observed either after overexpression or after transcription inhibition was found in speckles and colocalized with splicing factor SC35. The ability of PABP1 to shuttle between nucleus and cytoplasm was also shown by heterokaryon formation upon cell fusion. Deletion mutagenesis showed that the minimal part of PABP1 retaining the ability to shuttle consists of the first two RNA-binding domains. This mutant interacted with poly(A) RNA with high affinity and accumulated in the nucleus. Deletion mutants exhibiting reduced RNA binding affinity did not accumulate in the nucleus. PABP1 has been proposed to participate at various steps of mRNA utilization. Our results suggest involvement of PABP1 in nuclear events associated with the formation and transport of mRNP to the cytoplasm and identify a new trafficking pattern for RNA-binding proteins. JF - The Journal of biological chemistry AU - Afonina, E AU - Stauber, R AU - Pavlakis, G N AD - Human Retrovirus Section, ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Frederick, Maryland 21702-1201, USA. Y1 - 1998/05/22/ PY - 1998 DA - 1998 May 22 SP - 13015 EP - 13021 VL - 273 IS - 21 SN - 0021-9258, 0021-9258 KW - Poly(A)-Binding Proteins KW - 0 KW - RNA-Binding Proteins KW - Index Medicus KW - Transfection KW - HeLa Cells KW - Humans KW - Biological Transport KW - Transcription, Genetic KW - RNA-Binding Proteins -- metabolism KW - Cytoplasm -- metabolism KW - Cell Nucleus -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79885992?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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+human+poly%28A%29-binding+protein+1+shuttles+between+the+nucleus+and+the+cytoplasm.&rft.au=Afonina%2C+E%3BStauber%2C+R%3BPavlakis%2C+G+N&rft.aulast=Afonina&rft.aufirst=E&rft.date=1998-05-22&rft.volume=273&rft.issue=21&rft.spage=13015&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 - 1998-06-25 N1 - Date created - 1998-06-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Highly mutagenic bypass synthesis by T7 RNA polymerase of site-specific benzo[a]pyrene diol epoxide-adducted template DNA. AN - 79883997; 9582358 AB - We have previously developed an in vitro system that allows quantitative evaluation of the fidelity of transcription during synthesis on a natural template in the presence of all four nucleotides. Here, we have employed this system using a TAA ochre codon reversion assay to examine the fidelity of transcription by T7 RNA polymerase past an adenine residue adducted at the N6-position with (-)-anti-trans- or (+)-anti-trans-benzo[a]pyrene diol epoxide (BPDE). T7 RNAP was capable of transcribing past either BPDE isomer to generate full-length run-off transcripts. The extent of bypass was found to be 32% for the (-)-anti-trans-isomer and 18% for the (+)-anti-trans-isomer. Transcription past both adducts was highly mutagenic. The reversion frequency of bypass synthesis of the (-)-anti-trans-isomer was elevated 11,000-fold and that of the (+)-anti-trans-isomer 6000-fold, relative to the reversion frequency of transcription on unadducted template. Adenine was misinserted preferentially, followed by guanine, opposite the adenine adducted with either BPDE isomer. Although base substitution errors were by far the most frequent mutation on the adducted template, three- and six-base deletions were also observed. These results suggest that transcriptional errors, particularly with regard to damage bypass, may contribute to the mutational burden of the cell. JF - The Journal of biological chemistry AU - Remington, K M AU - Bennett, S E AU - Harris, C M AU - Harris, T M AU - Bebenek, K AD - Laboratory of Molecular Genetics, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 1998/05/22/ PY - 1998 DA - 1998 May 22 SP - 13170 EP - 13176 VL - 273 IS - 21 SN - 0021-9258, 0021-9258 KW - DNA Adducts KW - 0 KW - Mutagens KW - Viral Proteins 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 - bacteriophage T7 RNA polymerase KW - EC 2.7.7.- KW - DNA-Directed RNA Polymerases KW - EC 2.7.7.6 KW - Index Medicus KW - Base Sequence KW - Isomerism KW - Transcription, Genetic KW - Templates, Genetic KW - DNA Adducts -- chemistry KW - Mutagens -- metabolism KW - DNA-Directed RNA Polymerases -- metabolism KW - 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide -- chemical synthesis KW - DNA Adducts -- chemical synthesis KW - 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide -- chemistry KW - Bacteriophage T7 -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79883997?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Highly+mutagenic+bypass+synthesis+by+T7+RNA+polymerase+of+site-specific+benzo%5Ba%5Dpyrene+diol+epoxide-adducted+template+DNA.&rft.au=Remington%2C+K+M%3BBennett%2C+S+E%3BHarris%2C+C+M%3BHarris%2C+T+M%3BBebenek%2C+K&rft.aulast=Remington&rft.aufirst=K&rft.date=1998-05-22&rft.volume=273&rft.issue=21&rft.spage=13170&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 - 1998-06-25 N1 - Date created - 1998-06-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Functional magnetic resonance imaging of alprazolam-induced changes in humans with familial alcoholism. AN - 73928317; 9754450 AB - This study sought to identify whether subjects with a family history (FH + ) of alcoholism had changes in regional cerebral blood volume (rCBV) after an alprazolam challenge which distinguished them from subjects without a family history (FH -) of alcoholism using functional MRI (fMRI). Twelve FH + and eight FH - subjects were challenged with 1 mg of alprazolam or placebo in a double-blind crossover design. FMRI scans were obtained at baseline, 1 and 2 h after the challenge using the dynamic susceptibility contrast method with gadolinium. Mood scales, the Tufts Addiction Research Center Inventory-Morphine Benzedrine Group Scale and the drug liking scale, were administered every 30 min to assess drug effects. Global analysis of CBV showed a treatment by time decrease on alprazolam relative to placebo, but no effect by family history. The FH + group showed rCBV decreases at 1 h in the left caudate and left inferior prefrontal region, while the FH - group showed rCBV decreases at 2 h in the right inferior prefrontal region and anterior cingulate in response to alprazolam relative to placebo. FH + subjects reported more mood enhancement with alprazolam. This fMRI technique detected global and regional CBV changes induced by alprazolam. The location and rate of alprazolam-induced rCBV changes differed between FH + and FH - subjects. These changes may be related to the increased mood enhancement found in subjects genetically predisposed to alcoholism. JF - Psychiatry research AU - Streeter, C C AU - Ciraulo, D A AU - Harris, G J AU - Kaufman, M J AU - Lewis, R F AU - Knapp, C M AU - Ciraulo, A M AU - Maas, L C AU - Ungeheuer, M AU - Szulewski, S AU - Renshaw, P F AD - Department of Psychiatry/116A, Outpatient Clinic, Boston National Institute on Drug Abuse/Veterans Administration Medication Development Research Unit, MA 02114, USA. streeter.chris@boston.va.gov Y1 - 1998/05/20/ PY - 1998 DA - 1998 May 20 SP - 69 EP - 82 VL - 82 IS - 2 SN - 0165-1781, 0165-1781 KW - Anti-Anxiety Agents KW - 0 KW - Alprazolam KW - YU55MQ3IZY KW - Index Medicus KW - Affect -- drug effects KW - Double-Blind Method KW - Humans KW - Adult KW - Cross-Over Studies KW - Male KW - Functional Laterality KW - Female KW - Echo-Planar Imaging KW - Anti-Anxiety Agents -- pharmacology KW - Brain -- blood supply KW - Alprazolam -- pharmacology KW - Alcoholism -- metabolism KW - Brain -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73928317?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Functional+magnetic+resonance+imaging+of+alprazolam-induced+changes+in+humans+with+familial+alcoholism.&rft.au=Streeter%2C+C+C%3BCiraulo%2C+D+A%3BHarris%2C+G+J%3BKaufman%2C+M+J%3BLewis%2C+R+F%3BKnapp%2C+C+M%3BCiraulo%2C+A+M%3BMaas%2C+L+C%3BUngeheuer%2C+M%3BSzulewski%2C+S%3BRenshaw%2C+P+F&rft.aulast=Streeter&rft.aufirst=C&rft.date=1998-05-20&rft.volume=82&rft.issue=2&rft.spage=69&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 - 1998-11-25 N1 - Date created - 1998-11-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Murine bone marrow expressing the neomycin resistance gene has no competitive disadvantage assessed in vivo AN - 16412848; 4323879 AB - The neomycin phosphotransferase (neo) gene is one of the most common marker genes used in gene transfer experimentation, but potential effects of neo gene expression in vivo have not been systematically investigated. Several early clinical retroviral gene transfer studies have suggested that neo gene expression could have deleterious effects on hematopoiesis, owing to a discrepancy between the level of neo-marked transduced marrow progenitor cells compared with mature circulating progeny cells posttransplantation. We examined the long-term in vivo repopulating ability of bone marrow from transgenic mice expressing neo from a strong constitutive promoter using a competitive repopulation assay. Different ratios of neo transgenic and wild-type congenic marrow cells were cotransplanted into W/W super(v) recipient mice. The percentages of blood cells containing the neo transgene in each group of recipient mice monitored for 4 months posttransplantation closely matched the input ratios of neo transgenic to congenic control marrow cells. Similar concordances of engraftment with input ratios of neo transgenic cells were also found in spleen, thymus, and whole marrow of recipient mice at 4 months posttransplantation. Analysis of the beta -hemoglobin phenotype ( beta super(single) for the neo transgenic and C57 control cells and beta super(diffuse) for the congenic competitor HW80 cells) in recipients confirmed erythroid repopulation from neo transgenic marrow cells at levels matching the input ratios. We conclude that hematopoietic cells expressing neo had no engraftment or maturation defects detectable in vivo. These results suggest that the low-level contribution of vector-marked cells to circulating populations in clinical trials is not due to direct deleterious effects of neo gene expression on hematopoiesis. JF - Human Gene Therapy AU - Wu, Tong AU - Bloom, M L AU - Yu, Jian-Mei AU - Tisdale, J F AU - Dunbar, CE AD - Hematology Branch, NHLBI, NIH, Building 10, Room 7C103, 9000 Rockville Pike, Bethesda, MD 20892, USA Y1 - 1998/05/20/ PY - 1998 DA - 1998 May 20 SP - 1157 EP - 1164 VL - 9 IS - 8 SN - 1043-0342, 1043-0342 KW - animal models KW - mice KW - neomycin KW - Biotechnology and Bioengineering Abstracts; Genetics Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - G 07443:Gene therapy KW - W 30965:Miscellaneous, Reviews KW - W3 33180:Gene based (protocols, clinical trials, and animal models) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16412848?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+Gene+Therapy&rft.atitle=Murine+bone+marrow+expressing+the+neomycin+resistance+gene+has+no+competitive+disadvantage+assessed+in+vivo&rft.au=Wu%2C+Tong%3BBloom%2C+M+L%3BYu%2C+Jian-Mei%3BTisdale%2C+J+F%3BDunbar%2C+CE&rft.aulast=Wu&rft.aufirst=Tong&rft.date=1998-05-20&rft.volume=9&rft.issue=8&rft.spage=1157&rft.isbn=&rft.btitle=&rft.title=Human+Gene+Therapy&rft.issn=10430342&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Characterization of D10S and K71E mutants of human cytosolic hsp70. AN - 79889186; 9585537 AB - To determine the effect of mutations at the nucleotide-binding site of recombinant Hsp70 on its interaction with protein and peptide substrates, point mutations were made at D10 and K71, two residues at the active site. The D10S mutation weakened both ATP and ADP binding, while the K71E mutation weakened only ATP binding. In binding experiments using Hsp70 with no bound nucleotide, the mutated Hsp70s interacted with clathrin and peptide just like the wild-type Hsp70. However, the D10 mutation completely abolished the effects of both ATP and ADP on peptide and clathrin binding. The K71 mutation also abolished the effect of ATP on substrate binding, but ADP, which still bound tightly, had its normal effect on substrate binding. In addition, the D10S and K71E mutants had greatly reduced ability to uncoat clathrin-coated vesicles at pH 7.0, bind to clathrin baskets at pH 6.0, and undergo polymerization induced by YDJ1 in the presence of ATP. We conclude, first, that nucleotides must bind strongly to Hsp70 to affect substrate binding and, second, that interaction of Hsp70 with DnaJ homologues may also require a strongly bound ATP. JF - Biochemistry AU - Rajapandi, T AU - Wu, C AU - Eisenberg, E AU - Greene, L AD - Laboratory of Cell Biology, National Heart, Lung, and Blood Institute, Bethesda, Maryland 20892, USA. Y1 - 1998/05/19/ PY - 1998 DA - 1998 May 19 SP - 7244 EP - 7250 VL - 37 IS - 20 SN - 0006-2960, 0006-2960 KW - Clathrin KW - 0 KW - Cytochrome c Group KW - HSP40 Heat-Shock Proteins KW - HSP70 Heat-Shock Proteins KW - Heat-Shock Proteins KW - Nucleotides KW - Peptides KW - Recombinant Proteins KW - Aspartic Acid KW - 30KYC7MIAI KW - Glutamic Acid KW - 3KX376GY7L KW - Serine KW - 452VLY9402 KW - Adenosine Diphosphate KW - 61D2G4IYVH KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - Lysine KW - K3Z4F929H6 KW - Index Medicus KW - Heat-Shock Proteins -- metabolism KW - Nucleotides -- metabolism KW - Clathrin -- metabolism KW - Aspartic Acid -- genetics KW - Humans KW - Peptides -- metabolism KW - Lysine -- genetics KW - Serine -- genetics KW - Glutamic Acid -- genetics KW - Recombinant Proteins -- isolation & purification KW - Recombinant Proteins -- metabolism KW - Adenosine Triphosphate -- metabolism KW - Recombinant Proteins -- chemistry KW - Cytochrome c Group -- metabolism KW - Adenosine Diphosphate -- metabolism KW - HSP70 Heat-Shock Proteins -- metabolism KW - HSP70 Heat-Shock Proteins -- genetics KW - Cytosol -- metabolism KW - HSP70 Heat-Shock Proteins -- chemistry KW - Mutagenesis, Insertional UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79889186?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Characterization+of+D10S+and+K71E+mutants+of+human+cytosolic+hsp70.&rft.au=Rajapandi%2C+T%3BWu%2C+C%3BEisenberg%2C+E%3BGreene%2C+L&rft.aulast=Rajapandi&rft.aufirst=T&rft.date=1998-05-19&rft.volume=37&rft.issue=20&rft.spage=7244&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-06-22 N1 - Date created - 1998-06-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chemical lesion of the inferior olive reduces [125I]sarcosine1-angiotensin II binding to AT2 receptors in the cerebellar cortex of young rats. AN - 79950540; 9630617 AB - In young rats, AT2 receptors and AT2 receptor mRNA are discretely localized in neurons of the inferior olive, with highest expression in the medial nucleus. We previously detected AT2 receptor binding, but not AT2 receptor mRNA, in the molecular layer of the cerebellar cortex. To determine whether AT2 receptors are expressed in climbing fiber terminals which arise to the molecular layer from the inferior olive and innervate Purkinje cells, we chemically destroyed olivary neurons of 2-week-old rats by intraperitoneal (i.p.) injection of the neurotoxin 3-acetylpyridine. Lesions of the inferior olive reduced [125I]Sar1-Ang II binding to AT2 receptors and AT2 receptor mRNA levels in this area by 50%, and produced a similar decrease in AT2 receptor binding in the molecular layer of the cerebellar cortex. The extent of binding reduction was similar 3 days and 7 days after the lesion. 3-Acetylpyridine lesions did not change [125I]Sar1-Ang II binding to AT1 receptors in the molecular layer of the cerebellar cortex or AT1 receptor mRNA levels in Purkinje cells. AT2 receptor binding and AT2 receptor mRNA levels in the deep cerebellar nuclei were also not affected by 3-acetylpyridine. Our results support the hypothesis that AT2 receptors are produced by inferior olivary neurons and transported through climbing fibers to the molecular layer of the cerebellar cortex. The high expression of AT2 receptors in the inferior olivary-cerebellar pathway during a crucial time in postnatal development of climbing fiber-Purkinje cell connectivity suggest a role of AT2 receptors in the development of this pathway. Copyright 1998 Elsevier Science B.V. JF - Brain research AU - Jöhren, O AU - Häuser, W AU - Saavedra, J M AD - Section on Pharmacology, National Institute of Mental Health, 10 Center Drive MSC 1514, Building 10, Room 2D-57, Bethesda, MD 20892, USA. johreno@irp.nimh.nih.gov Y1 - 1998/05/18/ PY - 1998 DA - 1998 May 18 SP - 176 EP - 186 VL - 793 IS - 1-2 SN - 0006-8993, 0006-8993 KW - Iodine Radioisotopes KW - 0 KW - Pyridines KW - RNA, Messenger KW - Receptor, Angiotensin, Type 2 KW - Receptors, Angiotensin KW - 3-acetylpyridine KW - 00QT8FX306 KW - 1-Sarcosine-8-Isoleucine Angiotensin II KW - 9088-01-1 KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - In Situ Hybridization KW - RNA, Messenger -- analysis KW - Iodine Radioisotopes -- metabolism KW - Pyridines -- pharmacology KW - Immunohistochemistry KW - Male KW - Olivary Nucleus -- drug effects KW - Receptors, Angiotensin -- metabolism KW - Cerebellar Cortex -- chemistry KW - Olivary Nucleus -- physiology KW - Olivary Nucleus -- metabolism KW - Cerebellar Cortex -- drug effects KW - 1-Sarcosine-8-Isoleucine Angiotensin II -- metabolism KW - Cerebellar Cortex -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79950540?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Chemical+lesion+of+the+inferior+olive+reduces+%5B125I%5Dsarcosine1-angiotensin+II+binding+to+AT2+receptors+in+the+cerebellar+cortex+of+young+rats.&rft.au=J%C3%B6hren%2C+O%3BH%C3%A4user%2C+W%3BSaavedra%2C+J+M&rft.aulast=J%C3%B6hren&rft.aufirst=O&rft.date=1998-05-18&rft.volume=793&rft.issue=1-2&rft.spage=176&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 - 1999-03-29 N1 - Date created - 1999-03-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Filipin-dependent inhibition of cholera toxin: evidence for toxin internalization and activation through caveolae-like domains. AN - 79890138; 9585410 AB - The mechanism by which cholera toxin (CT) is internalized from the plasma membrane before its intracellular reduction and subsequent activation of adenylyl cyclase is not well understood. Ganglioside GM1, the receptor for CT, is predominantly clustered in detergent-insoluble glycolipid rafts and in caveolae, noncoated, cholesterol-rich invaginations on the plasma membrane. In this study, we used filipin, a sterol-binding agent that disrupts caveolae and caveolae-like structures, to explore their role in the internalization and activation of CT in CaCo-2 human intestinal epithelial cells. When toxin internalization was quantified, only 33% of surface-bound toxin was internalized by filipin-treated cells within 1 h compared with 79% in untreated cells. However, CT activation as determined by its reduction to form the A1 peptide and CT activity as measured by cyclic AMP accumulation were inhibited in filipin-treated cells. Another sterol-binding agent, 2-hydroxy-beta-cyclodextrin, gave comparable results. The cationic amphiphilic drug chlorpromazine, an inhibitor of clathrin-dependent, receptor-mediated endocytosis, however, affected neither CT internalization, activation, nor activity in contrast to its inhibitory effects on diphtheria toxin cytotoxicity. As filipin did not inhibit the latter, the two drugs appeared to distinguish between caveolae- and coated pit-mediated processes. In addition to its effects in CaCo-2 cells that express low levels of caveolin, filipin also inhibited CT activity in human epidermoid carcinoma A431 and Jurkat T lymphoma cells that are, respectively, rich in or lack caveolin. Thus, filipin inhibition correlated more closely with alterations in the biochemical characteristics of CT-bound membranes due to the interactions of filipin with cholesterol rather than with the expressed levels of caveolin and caveolar structure. Our results indicated that the internalization and activation of CT was dependent on and mediated through cholesterol- and glycolipid-rich microdomains at the plasma membrane rather than through a specific morphological structure and that these glycolipid microdomains have the necessary components required to mediate endocytosis. JF - The Journal of cell biology AU - Orlandi, P A AU - Fishman, P H AD - Membrane Biochemistry Section, Laboratory of Molecular and Cellular Neurobiology, National Institute of Neurological Disorders and Stroke, The National Institutes of Health, Bethesda, Maryland 20892-4440, USA. Y1 - 1998/05/18/ PY - 1998 DA - 1998 May 18 SP - 905 EP - 915 VL - 141 IS - 4 SN - 0021-9525, 0021-9525 KW - Cyclodextrins KW - 0 KW - Diphtheria Toxin KW - Glycolipids KW - Membrane Lipids KW - Filipin KW - 87Z59R7D14 KW - Cholera Toxin KW - 9012-63-9 KW - Cholesterol KW - 97C5T2UQ7J KW - Cyclic AMP KW - E0399OZS9N KW - Adenylyl Cyclases KW - EC 4.6.1.1 KW - Imipramine KW - OGG85SX4E4 KW - Chlorpromazine KW - U42B7VYA4P KW - Index Medicus KW - Enzyme Activation KW - Humans KW - Diphtheria Toxin -- toxicity KW - Membrane Lipids -- metabolism KW - Jurkat Cells KW - Adenylyl Cyclases -- metabolism KW - Cell Membrane -- ultrastructure KW - Cell Membrane -- physiology KW - Chlorpromazine -- pharmacology KW - Biological Transport -- drug effects KW - Cyclodextrins -- pharmacology KW - Tumor Cells, Cultured KW - Cholesterol -- metabolism KW - Kinetics KW - Imipramine -- pharmacology KW - Endocytosis -- drug effects KW - Cyclic AMP -- metabolism KW - Carcinoma, Squamous Cell KW - Glycolipids -- metabolism KW - Endocytosis -- physiology KW - Coated Pits, Cell-Membrane -- physiology KW - Colonic Neoplasms KW - Intestinal Mucosa -- physiology KW - Cholera Toxin -- pharmacology KW - Intestinal Mucosa -- drug effects KW - Cholera Toxin -- antagonists & inhibitors KW - Cholera Toxin -- pharmacokinetics KW - Filipin -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79890138?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+cell+biology&rft.atitle=Filipin-dependent+inhibition+of+cholera+toxin%3A+evidence+for+toxin+internalization+and+activation+through+caveolae-like+domains.&rft.au=Orlandi%2C+P+A%3BFishman%2C+P+H&rft.aulast=Orlandi&rft.aufirst=P&rft.date=1998-05-18&rft.volume=141&rft.issue=4&rft.spage=905&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+cell+biology&rft.issn=00219525&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-06-17 N1 - Date created - 1998-06-17 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nature. 1982 Apr 15;296(5858):651-3 [7070509] Nature. 1997 Jun 5;387(6633):569-72 [9177342] J Biol Chem. 1982 Oct 25;257(20):12148-52 [6288709] J Cell Biol. 1982 Jun;93(3):860-5 [6288736] J Cell Biol. 1983 Nov;97(5 Pt 1):1592-600 [6415070] Mol Pharmacol. 1984 Sep;26(2):206-13 [6207420] J Cell Biol. 1985 Aug;101(2):548-59 [2862151] Proc Natl Acad Sci U S A. 1987 Nov;84(22):7957-61 [2446314] Biochemistry. 1988 Aug 23;27(17):6197-202 [3064805] J Cell Biol. 1990 Dec;111(6 Pt 2):2931-8 [2148564] Biochemistry. 1991 Mar 12;30(10):2563-70 [1848091] Science. 1992 Jan 24;255(5043):410-1 [1310359] Cell. 1992 Feb 7;68(3):533-44 [1531449] Cell. 1992 Feb 21;68(4):673-82 [1739974] Biochemistry. 1992 May 26;31(20):4773-8 [1317209] J Biol Chem. 1992 Jun 5;267(16):11525-31 [1597480] J Cell Biol. 1992 Jul;118(1):63-9 [1618907] FEBS Lett. 1992 Dec 7;314(1):45-8 [1360410] EMBO J. 1993 Apr;12(4):1597-605 [8385608] J Biol Chem. 1993 Jun 5;268(16):12010-6 [8389369] Biochemistry. 1993 Jun 29;32(25):6365-73 [8518282] J Biol Chem. 1993 Aug 15;268(23):17038-44 [8349592] J Cell Biol. 1993 Aug;122(4):789-807 [8349730] Adv Lipid Res. 1993;25:165-87 [8396312] J Cell Biol. 1993 Dec;123(5):1107-17 [8245121] J Histochem Cytochem. 1994 Feb;42(2):155-66 [8288861] Science. 1994 Jun 24;264(5167):1948-51 [7516582] J Cell Biol. 1994 Dec;127(5):1185-97 [7962084] J Cell Biol. 1994 Dec;127(5):1217-32 [7525606] J Biol Chem. 1994 Dec 9;269(49):30745-8 [7982998] J Cell Biol. 1995 May;129(3):619-27 [7537273] J Biol Chem. 1995 May 19;270(20):12117-22 [7744860] J Biol Chem. 1995 Jun 16;270(24):14399-404 [7782301] Science. 1995 Sep 8;269(5229):1398-9 [7660120] Science. 1995 Sep 8;269(5229):1435-9 [7660128] J Cell Biol. 1995 Nov;131(4):951-62 [7490296] J Membr Biol. 1980;54(1):51-60 [6259358] FEBS Lett. 1995 Nov 13;375(1-2):11-4 [7498456] J Cell Biol. 1996 May;133(4):777-89 [8666663] J Cell Biol. 1996 May;133(4):791-9 [8666664] FEBS Lett. 1996 Jun 24;389(1):52-4 [8682205] J Biol Chem. 1996 Aug 30;271(35):21604-13 [8702948] Curr Opin Cell Biol. 1996 Aug;8(4):542-8 [8791446] Am J Physiol. 1996 Sep;271(3 Pt 1):C887-94 [8843719] Proc Natl Acad Sci U S A. 1996 Oct 29;93(22):12339-43 [8901582] J Biol Chem. 1997 Feb 14;272(7):4591-9 [9020187] Biochim Biophys Acta. 1982 Apr 29;720(2):181-7 [7082684] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inhibitory monoclonal antibody to human cytochrome P450 2B6. AN - 79952007; 9633999 AB - The human cytochrome P450 2B6 metabolizes, among numerous other substrates, diazepam, 7-ethoxycoumarin, testosterone, and phenanthrene. A recombinant baculovirus containing the human 2B6 cDNA was constructed and used to express 2B6 in Sf9 insect cells. The 2B6 was present at 1.8 +/- 0.4% of the total cellular protein and was purified to a specific content of 13.3 nmol/mg protein. Mice were immunized with the purified 2B6, and a total of 811 hybridomas were obtained from the fusion of NS-1 myeloma cells and spleen cells of the immunized mice. Monoclonal antibodies (MAbs) from 24 of the hybrids exhibited immunobinding to 2B6 as determined by ELISA. One of the MAbs, 49-10-20, showed a strong immunoblotting activity and was highly inhibitory to 2B6 enzyme activity. MAb 49-10-20 inhibited cDNA-expressed 2B6-catalyzed metabolism of diazepam, phenanthrene, 7-ethoxycoumarin, and testosterone by 90-91%. MAb 49-10-20 showed extremely high specificity for 2B6 and did not bind to 17 other human and rodent P450s or inhibit the metabolism of phenanthrene catalyzed by human 1A2, 2A6, 2C8, 2C9, 2D6, 2E1, 3A4, and 3A5. MAb 49-10-20 was used to determine the contribution of 2B6 to the metabolism of phenanthrene and diazepam in human liver. In ten liver samples, MAb 49-10-20 inhibited phenanthrene metabolism variably by a wide range of 8-42% and diazepam demethylation by 1-23%. The degree of inhibition by the 2B6 specific MAb 49-10-20 defines the contribution of 2B6 to phenanthrene and diazepam metabolism in each human liver. This technique using inhibitory MAb 49-10-20 determines the contribution of 2B6 to the metabolism of its substrates in a human tissue containing multiple P450s. This study is a prototype for the use of specific and highly inhibitory MAbs to determine individual P450 function. JF - Biochemical pharmacology AU - Yang, T J AU - Krausz, K W AU - Shou, M AU - Yang, S K AU - Buters, J T AU - Gonzalez, F J AU - Gelboin, H V AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1998/05/15/ PY - 1998 DA - 1998 May 15 SP - 1633 EP - 1640 VL - 55 IS - 10 SN - 0006-2952, 0006-2952 KW - Antibodies, Monoclonal KW - 0 KW - Cytochrome P-450 Enzyme Inhibitors KW - Phenanthrenes KW - Recombinant Proteins KW - phenanthrene KW - 448J8E5BST KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Aryl Hydrocarbon Hydroxylases KW - EC 1.14.14.1 KW - CYP2B6 protein, human KW - Cytochrome P-450 CYP2B6 KW - Oxidoreductases, N-Demethylating KW - EC 1.5.- KW - Diazepam KW - Q3JTX2Q7TU KW - Index Medicus KW - Phenanthrenes -- metabolism KW - Animals KW - Liver -- enzymology KW - Spodoptera KW - Diazepam -- metabolism KW - Humans KW - Cytochrome P-450 Enzyme System -- metabolism KW - Mice KW - Substrate Specificity KW - Mice, Inbred BALB C KW - Recombinant Proteins -- antagonists & inhibitors KW - Cell Line KW - Oxidoreductases, N-Demethylating -- antagonists & inhibitors KW - Antibodies, Monoclonal -- pharmacology KW - Oxidoreductases, N-Demethylating -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79952007?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Inhibitory+monoclonal+antibody+to+human+cytochrome+P450+2B6.&rft.au=Yang%2C+T+J%3BKrausz%2C+K+W%3BShou%2C+M%3BYang%2C+S+K%3BButers%2C+J+T%3BGonzalez%2C+F+J%3BGelboin%2C+H+V&rft.aulast=Yang&rft.aufirst=T&rft.date=1998-05-15&rft.volume=55&rft.issue=10&rft.spage=1633&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 - 1998-07-02 N1 - Date created - 1998-07-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Selective depletion of DNA precursors: an evolving strategy for potentiation of dideoxynucleoside activity against human immunodeficiency virus. AN - 79946978; 9633990 AB - Human immunodeficiency virus type 1 (HIV-1) is wholly dependent on its host cell for a variety of essential metabolites. Among the latter are the deoxynucleoside-5'-triphosphates (dNTPs) required for reverse transcription of the single-stranded RNA viral genome into double-stranded viral DNA. Since viral DNA synthesis has an absolute requirement for all four dNTPs, restriction of a single one of these is sufficient to inhibit HIV-1 replication. To date, this therapeutic strategy has been most successful when depletion of the individual dNTP is coupled with exposure to its corresponding chain-terminating dideoxynucleoside (ddN). While several examples of such combined therapy have been defined and studied in vitro, that which has been investigated most extensively at both the laboratory and the clinical level is ddATP exposure combined with dATP depletion [with dATP restriction being induced by the ribonucleotide reductase inhibitor hydroxyurea (HU) and ddATP generated from its prodrug 2',3'-dideoxyinosine (ddI)]. Several long-term clinical trials of the hydroxyurea/2',3'-dideoxyinosine combination have been completed, with plasma viral RNA being reduced to undetectable levels in a substantial fraction (one-third to one-half) of the patients treated. The major advantages of this and analogous combinations discussed in this review are their low cost relative to other current multiple drug protocols and their potential for retention of activity against drug-resistant HIV mutants. JF - Biochemical pharmacology AU - Johns, D G AU - Gao, W Y AD - Laboratory of Medicinal Chemistry, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. johnsd@dc37a.nci.nih.gov Y1 - 1998/05/15/ PY - 1998 DA - 1998 May 15 SP - 1551 EP - 1556 VL - 55 IS - 10 SN - 0006-2952, 0006-2952 KW - Anti-HIV Agents KW - 0 KW - Dideoxynucleosides KW - Enzyme Inhibitors KW - Zidovudine KW - 4B9XT59T7S KW - Ribonucleotide Reductases KW - EC 1.17.4.- KW - Hydroxyurea KW - X6Q56QN5QC KW - Index Medicus KW - AIDS/HIV KW - Drug Therapy, Combination KW - Humans KW - Zidovudine -- pharmacology KW - Ribonucleotide Reductases -- antagonists & inhibitors KW - Clinical Trials as Topic KW - Enzyme Inhibitors -- pharmacology KW - Zidovudine -- administration & dosage KW - Drug Synergism KW - Dideoxynucleosides -- pharmacology KW - Anti-HIV Agents -- pharmacology KW - Anti-HIV Agents -- administration & dosage KW - Hydroxyurea -- pharmacology KW - HIV-1 -- drug effects KW - Hydroxyurea -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79946978?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Selective+depletion+of+DNA+precursors%3A+an+evolving+strategy+for+potentiation+of+dideoxynucleoside+activity+against+human+immunodeficiency+virus.&rft.au=Johns%2C+D+G%3BGao%2C+W+Y&rft.aulast=Johns&rft.aufirst=D&rft.date=1998-05-15&rft.volume=55&rft.issue=10&rft.spage=1551&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 - 1998-07-02 N1 - Date created - 1998-07-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cloning, characterization, and chromosomal localization of a gene frequently deleted in human liver cancer (DLC-1) homologous to rat RhoGAP. AN - 79896772; 9605766 AB - The isolation of genes involved in cancer development is critical for uncovering the molecular basis of cancer. We report here the isolation of the full-length cDNA and chromosomal localization of a new gene frequently deleted in liver cancer (DLC-1) that was identified by representational difference analysis. Loss of heterozygosity was detected for DLC-1 in 7 of 16 primary hepatocellular carcinomas (HCCs) and in 10 of 11 HCC cell lines. Although mRNA for DLC-1 was expressed in all normal human tissues, it was not expressed in 4 of 14 HCC cell lines. Full-length cDNA for DLC-1 of 3800 bp encodes a protein of 1091 amino acids, has 86% homology with rat p122 RhoGAP gene, and was localized by fluorescence in situ hybridization on chromosome 8 at bands p21.3-22. Deletions on the short arm of chromosome 8 are recurrent in liver, breast, lung, and prostate cancers, suggesting the presence of tumor suppressor genes. DLC-1 may be a tumor suppressor gene in liver cancer as well as in other cancers. JF - Cancer research AU - Yuan, B Z AU - Miller, M J AU - Keck, C L AU - Zimonjic, D B AU - Thorgeirsson, S S AU - Popescu, N C AD - Laboratory of Experimental Carcinogenesis, Division of Basic Sciences, National Cancer Institute, NIH, Bethesda, Maryland 20892-4255, USA. Y1 - 1998/05/15/ PY - 1998 DA - 1998 May 15 SP - 2196 EP - 2199 VL - 58 IS - 10 SN - 0008-5472, 0008-5472 KW - DLC1 protein, human KW - 0 KW - GTPase-Activating Proteins KW - Proteins KW - Tumor Suppressor Proteins KW - Index Medicus KW - Rats KW - Animals KW - Loss of Heterozygosity KW - Tumor Cells, Cultured KW - Humans KW - Molecular Sequence Data KW - Chromosome Mapping KW - Gene Deletion KW - Genes, Tumor Suppressor -- genetics KW - Carcinoma, Hepatocellular -- genetics KW - Chromosomes, Human, Pair 8 -- genetics KW - Proteins -- genetics KW - Liver Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79896772?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cloning%2C+characterization%2C+and+chromosomal+localization+of+a+gene+frequently+deleted+in+human+liver+cancer+%28DLC-1%29+homologous+to+rat+RhoGAP.&rft.au=Yuan%2C+B+Z%3BMiller%2C+M+J%3BKeck%2C+C+L%3BZimonjic%2C+D+B%3BThorgeirsson%2C+S+S%3BPopescu%2C+N+C&rft.aulast=Yuan&rft.aufirst=B&rft.date=1998-05-15&rft.volume=58&rft.issue=10&rft.spage=2196&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 - 1998-06-10 N1 - Date created - 1998-06-10 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF035119; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A randomized, controlled clinical trial to evaluate the effects of zinc sulfate on cancer patients with taste alterations caused by head and neck irradiation. AN - 79866613; 9587128 AB - In uncontrolled clinical trials, the administration of oral zinc sulfate has been reported both to prevent and correct taste abnormalities in cancer patients receiving external radiotherapy (ERT) to the head and neck region. Eighteen patients were randomized to receive either zinc sulfate tablets (a dose of 45 mg) or placebo tablets three times a day at the onset of subjective perception of taste alterations during the course of ERT and up to 1 month after ERT termination. Taste acuity was determined by measuring detection and recognition thresholds for four taste qualities. Intolerance of zinc sulfate or placebo administration was investigated, and the oral cavity was examined. All the evaluations were studied prior to, at weekly intervals during, and 1 month after ERT administration. Taste acuity for one or more taste qualities was already impaired before ERT. During ERT treatment, taste alterations were experienced at least once for a minimum of 3 of the 8 measured thresholds by 100% of the patients, and 33.3% of the patients became aware of some alteration within the first week of treatment. The patients treated with placebo experienced a greater worsening of taste acuity during ERT treatment compared with those treated with zinc sulfate. One month after ERT was terminated, the patients receiving zinc sulfate had a quicker recovery of taste acuity than those receiving placebo. Statistically significant differences between the two groups emerged for urea detection and sodium chloride recognition thresholds during ERT treatment and for sodium chloride, saccharose, and hydrogen chloride recognition thresholds after the termination of ERT treatment. This pharmacologic therapy is effective and well tolerated; it could become a routine in clinical practice to improve the supportive care of patients with taste alterations resulting from head and neck cancer. JF - Cancer AU - Ripamonti, C AU - Zecca, E AU - Brunelli, C AU - Fulfaro, F AU - Villa, S AU - Balzarini, A AU - Bombardieri, E AU - De Conno, F AD - Pain Therapy and Palliative Care Division, National Cancer Institute, Milan, Italy. Y1 - 1998/05/15/ PY - 1998 DA - 1998 May 15 SP - 1938 EP - 1945 VL - 82 IS - 10 SN - 0008-543X, 0008-543X KW - Zinc Sulfate KW - 7733-02-0 KW - Abridged Index Medicus KW - Index Medicus KW - Evaluation Studies as Topic KW - Administration, Oral KW - Double-Blind Method KW - Combined Modality Therapy KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Statistics, Nonparametric KW - Male KW - Female KW - Radiotherapy -- adverse effects KW - Zinc Sulfate -- therapeutic use KW - Head and Neck Neoplasms -- complications KW - Taste Disorders -- etiology KW - Head and Neck Neoplasms -- radiotherapy KW - Taste Disorders -- prevention & control KW - Head and Neck Neoplasms -- surgery KW - Taste Disorders -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79866613?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+randomized%2C+controlled+clinical+trial+to+evaluate+the+effects+of+zinc+sulfate+on+cancer+patients+with+taste+alterations+caused+by+head+and+neck+irradiation.&rft.au=Ripamonti%2C+C%3BZecca%2C+E%3BBrunelli%2C+C%3BFulfaro%2C+F%3BVilla%2C+S%3BBalzarini%2C+A%3BBombardieri%2C+E%3BDe+Conno%2C+F&rft.aulast=Ripamonti&rft.aufirst=C&rft.date=1998-05-15&rft.volume=82&rft.issue=10&rft.spage=1938&rft.isbn=&rft.btitle=&rft.title=Cancer&rft.issn=0008543X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-05-27 N1 - Date created - 1998-05-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characterization of Brx, a novel Dbl family member that modulates estrogen receptor action. AN - 79936147; 9627117 AB - Regulation of gene activation by the estrogen receptor (ER) is complex and involves co-regulatory proteins, oncoproteins (such as Fos and Jun), and phosphorylation signaling pathways. Here we report the cloning and initial characterization of a novel protein, Brx, that contains a region of identity to the oncogenic Rho-guanine nucleotide exchange (Rho-GEF) protein Lbc, and a unique region capable of binding to nuclear hormone receptors, including the ER. Western and immunohistochemistry studies showed Brx to be expressed in estrogen-responsive reproductive tissues, including breast ductal epithelium. Brx bound specifically to the ER via an interaction that required distinct regions of ER and Brx. Furthermore, overexpression of Brx in transfection experiments using an estrogen-responsive reporter revealed that Brx augmented gene activation by the ER in an element-specific and ligand-dependent manner. Moreover, activation of ER by Brx could be specifically inhibited by a dominant-negative mutant of Cdc42Hs, but not by dominant negative mutants of RhoA or Rac1. Taken together, these data suggest that Brx represents a novel modular protein that may integrate cytoplasmic signaling pathways involving Rho family GTPases and nuclear hormone receptors. JF - Oncogene AU - Rubino, D AU - Driggers, P AU - Arbit, D AU - Kemp, L AU - Miller, B AU - Coso, O AU - Pagliai, K AU - Gray, K AU - Gutkind, S AU - Segars, J AD - Office of the Scientific Director, National Institute of Child Health and Human Development, and DEB, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/05/14/ PY - 1998 DA - 1998 May 14 SP - 2513 EP - 2526 VL - 16 IS - 19 SN - 0950-9232, 0950-9232 KW - A Kinase Anchor Proteins KW - 0 KW - AKAP13 protein, human KW - Adaptor Proteins, Signal Transducing KW - Cell Cycle Proteins KW - DNA, Complementary KW - Guanine Nucleotide Exchange Factors KW - MCF2 protein, human KW - Minor Histocompatibility Antigens KW - Oncogene Proteins KW - Proto-Oncogene Proteins KW - Receptors, Estrogen KW - Retroviridae Proteins, Oncogenic KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - cdc42 GTP-Binding Protein KW - EC 3.6.5.2 KW - Index Medicus KW - Animals KW - Humans KW - Tissue Distribution KW - Mutagenesis KW - Tumor Cells, Cultured KW - Cell Cycle Proteins -- genetics KW - Molecular Sequence Data KW - Sequence Homology, Amino Acid KW - Breast -- metabolism KW - Male KW - Testis -- immunology KW - Testis -- pathology KW - Amino Acid Sequence KW - Rabbits KW - GTP-Binding Proteins -- genetics KW - Cloning, Molecular KW - Cell Cycle Proteins -- metabolism KW - GTP-Binding Proteins -- metabolism KW - Breast -- pathology KW - Female KW - Oncogene Proteins -- classification KW - Oncogene Proteins -- genetics KW - Receptors, Estrogen -- metabolism KW - Receptors, Estrogen -- physiology KW - Oncogene Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79936147?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Characterization+of+Brx%2C+a+novel+Dbl+family+member+that+modulates+estrogen+receptor+action.&rft.au=Rubino%2C+D%3BDriggers%2C+P%3BArbit%2C+D%3BKemp%2C+L%3BMiller%2C+B%3BCoso%2C+O%3BPagliai%2C+K%3BGray%2C+K%3BGutkind%2C+S%3BSegars%2C+J&rft.aulast=Rubino&rft.aufirst=D&rft.date=1998-05-14&rft.volume=16&rft.issue=19&rft.spage=2513&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-07-01 N1 - Date created - 1998-07-01 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF126008; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Alzheimer's-specific effects of soluble beta-amyloid on protein kinase C-alpha and -gamma degradation in human fibroblasts. AN - 79861686; 9576922 AB - Alzheimer's disease (AD) is a multifactorial disease in which beta-amyloid peptide (betaAP) plays a critical role. We report here that the soluble fraction 1-40 of betaAP differentially degrades protein kinase C-alpha and -gamma (PKCalpha and PKCgamma) isoenzymes in normal (age-matched controls, AC) and AD fibroblasts most likely through proteolytic cascades. Treatment with nanomolar concentrations of betaAP(1-40) induced a 75% decrease in PKCalpha, but not PKCgamma, immunoreactivity in AC fibroblasts. In the AD fibroblasts, a 70% reduction of the PKCgamma, but not PKCalpha, immunoreactivity was observed after betaAP treatment. Preincubation of AC or AD fibroblasts with 50 microM lactacystine, a selective proteasome inhibitor, prevented beta-AP(1-40)-mediated degradation of PKCalpha in the AC cells, and PKCgamma in the AD fibroblasts. The effects of betaAP(1-40) on PKCalpha in AC fibroblasts were prevented by inhibition of protein synthesis and reversed by PKC activation. A 3-hr treatment with 100 nM phorbol 12-myristate 13-acetate restored the PKCalpha signal in treated AC cells but it did not reverse the effects of betaAP(1-40) on PKCgamma in the AD fibroblasts. Pretreatment with the protein synthesis inhibitor, cycloheximide (CHX, 100 microM), inhibited the effects of betaAP(1-40) on PKCalpha and blocked the rescue effect of phorbol 12-myristate 13-acetate in AC fibroblasts but did not modify PKCgamma immunoreactivity in AD cells. These results suggest that betaAP(1-40) differentially affects PKC regulation in AC and AD cells via proteolytic degradation and that PKC activation exerts a protective role via de novo protein synthesis in normal but not AD cells. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Favit, A AU - Grimaldi, M AU - Nelson, T J AU - Alkon, D L AD - Laboratory of Adaptive Systems, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1998/05/12/ PY - 1998 DA - 1998 May 12 SP - 5562 EP - 5567 VL - 95 IS - 10 SN - 0027-8424, 0027-8424 KW - Amyloid beta-Peptides KW - 0 KW - Isoenzymes KW - Peptide Fragments KW - Protein Synthesis Inhibitors KW - amyloid beta-protein (1-40) KW - lactacystin KW - 133343-34-7 KW - Cycloheximide KW - 98600C0908 KW - protein kinase C gamma KW - EC 2.7.1.- KW - PRKCA protein, human KW - EC 2.7.11.13 KW - Protein Kinase C KW - Protein Kinase C-alpha KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Acetylcysteine KW - WYQ7N0BPYC KW - Index Medicus KW - Animals KW - Fibroblasts -- enzymology KW - Acetylcysteine -- analogs & derivatives KW - Brain -- drug effects KW - Humans KW - Acetylcysteine -- pharmacology KW - Rats KW - Brain -- enzymology KW - Blotting, Western KW - Protein Synthesis Inhibitors -- pharmacology KW - Cells, Cultured KW - Cycloheximide -- pharmacology KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Protein Kinase C -- metabolism KW - Peptide Fragments -- metabolism KW - Amyloid beta-Peptides -- metabolism KW - Alzheimer Disease -- metabolism KW - Isoenzymes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79861686?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Alzheimer%27s-specific+effects+of+soluble+beta-amyloid+on+protein+kinase+C-alpha+and+-gamma+degradation+in+human+fibroblasts.&rft.au=Favit%2C+A%3BGrimaldi%2C+M%3BNelson%2C+T+J%3BAlkon%2C+D+L&rft.aulast=Favit&rft.aufirst=A&rft.date=1998-05-12&rft.volume=95&rft.issue=10&rft.spage=5562&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 - 1998-06-19 N1 - Date created - 1998-06-19 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1993 Sep 1;90(17):8209-13 [8367484] N Engl J Med. 1991 Dec 26;325(26):1849-57 [1961223] Proc Natl Acad Sci U S A. 1993 Oct 1;90(19):9195-8 [8415676] J Biol Chem. 1993 Nov 5;268(31):22959-62 [8226807] J Neurochem. 1993 Dec;61(6):2326-9 [8245986] Trends Neurosci. 1993 Oct;16(10):409-14 [7504356] Neurology. 1993 Dec;43(12):2581-6 [8255461] Proc Natl Acad Sci U S A. 1994 Jan 18;91(2):534-8 [8290560] Neurochem Res. 1994 Jan;19(1):89-95 [8139769] Science. 1994 Apr 8;264(5156):276-9 [8146663] FEBS Lett. 1994 Nov 14;354(3):274-8 [7957938] Biochim Biophys Acta. 1994 Nov 29;1227(3):183-7 [7986826] Proc Natl Acad Sci U S A. 1994 Dec 6;91(25):11993-7 [7991571] Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):3060-4 [7708775] Brain Res. 1995 Sep 11;691(1-2):169-79 [8590049] Dev Biol. 1995 Dec;172(2):675-82 [8612981] J Neurochem. 1996 Apr;66(4):1752-61 [8627334] Neurosci Lett. 1995 Dec 1;201(1):1-5 [8830300] Acta Neurol Scand Suppl. 1996;165:25-32 [8740986] Life Sci. 1996;59(5-6):477-89 [8761336] Science. 1996 Oct 4;274(5284):99-102 [8810256] Mol Pharmacol. 1997 Mar;51(3):439-47 [9058599] Mol Med. 1997 Mar;3(3):204-11 [9100226] N Engl J Med. 1986 Apr 10;314(15):964-73 [2870433] Science. 1992 Feb 7;255(5045):726-8 [1738846] Science. 1992 Feb 7;255(5045):728-30 [1738847] J Neurosci. 1992 Feb;12(2):376-89 [1346802] Neurosci Lett. 1991 Nov 25;133(1):89-92 [1792001] Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):3055-9 [1557413] J Cereb Blood Flow Metab. 1992 Jul;12(4):638-45 [1352303] Biochem Biophys Res Commun. 1992 Sep 30;187(3):1285-90 [1417805] Science. 1992 Oct 2;258(5079):126-9 [1439760] Proc Natl Acad Sci U S A. 1993 Jan 15;90(2):567-71 [8380642] Science. 1993 Jan 22;259(5094):514-6 [8424174] Exp Gerontol. 1993 Jan-Feb;28(1):51-8 [8436204] Pharmacol Ther. 1992;56(1):97-117 [1297146] Proc Natl Acad Sci U S A. 1993 Apr 1;90(7):2628-32 [8464868] Nat Genet. 1992 Dec;2(4):340-2 [1303291] J Biol Chem. 1993 Jul 15;268(20):14616-21 [8100816] Neurology. 1993 Jul;43(7):1407-13 [8327146] Biochem Biophys Res Commun. 1993 Aug 31;195(1):97-103 [8395841] J Immunol Methods. 1986 Sep 27;92(2):261-70 [3760586] Arch Neurol. 1989 Nov;46(11):1195-9 [2684108] Science. 1990 Apr 27;248(4954):492-5 [1691865] J Neurosci. 1990 Jul;10(7):2113-24 [2376771] Proc Natl Acad Sci U S A. 1990 Aug;87(15):6003-6 [2116015] Neurobiol Aging. 1990 Jul-Aug;11(4):425-31 [2381502] Science. 1990 Oct 12;250(4978):279-82 [2218531] Brain Res. 1990 Nov 19;533(2):315-20 [2289145] J Biol Chem. 1991 Jun 25;266(18):11915-22 [1646818] Brain Res. 1991 Mar 8;543(1):139-47 [1647256] J Neurosci. 1991 Sep;11(9):2759-67 [1880547] J Biol Chem. 1993 Oct 5;268(28):21097-101 [8407946] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The chromatin unfolding domain of chromosomal protein HMG-14 targets the N-terminal tail of histone H3 in nucleosomes. AN - 79861574; 9576905 AB - Nonhistone chromosomal protein HMG-14 is a nucleosomal binding protein that unfolds the higher-order chromatin structure and enhances the transcriptional potential of chromatin, but not that of DNA. Both the transcriptional enhancement and the chromatin unfolding activities of HMG-14 are mediated through the C-terminal region of the protein. Here we study the molecular interactions of both this region and the N-terminal region of HMG-14 with nucleosome cores. By protein photocrosslinking we demonstrate that the N-terminal domain of HMG-14 targets a restricted region in histone H2B, whereas the C-terminal chromatin unfolding domain of HMG-14 targets a restricted region in the N terminus of histone H3. The N-terminal regions of the core histones are involved in the folding of oligonucleosomes and are the target of various activities associated with chromatin unfolding and transcriptional activation. We suggest that specific interactions between the C-terminal domain of HMG-14 and the N-terminal tail of histone H3 reduce the compaction of chromatin. These findings provide insights into the molecular mechanism whereby HMG-14/-17 proteins reduce the repressive effect of chromatin, and they also broaden the scope of the molecular interactions involving the N termini of the core histones in nucleosomes. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Trieschmann, L AU - Martin, B AU - Bustin, M AD - Protein Section, Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1998/05/12/ PY - 1998 DA - 1998 May 12 SP - 5468 EP - 5473 VL - 95 IS - 10 SN - 0027-8424, 0027-8424 KW - Chromatin KW - 0 KW - Cross-Linking Reagents KW - High Mobility Group Proteins KW - Histones KW - Nucleosomes KW - Index Medicus KW - Photochemistry KW - Mutagenesis, Site-Directed KW - Polymerase Chain Reaction KW - Models, Molecular KW - HeLa Cells KW - Humans KW - Cross-Linking Reagents -- metabolism KW - Binding Sites -- genetics KW - High Mobility Group Proteins -- chemistry KW - Chromatin -- metabolism KW - High Mobility Group Proteins -- genetics KW - Histones -- metabolism KW - Nucleosomes -- metabolism KW - Histones -- chemistry KW - Protein Folding KW - High Mobility Group Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79861574?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+chromatin+unfolding+domain+of+chromosomal+protein+HMG-14+targets+the+N-terminal+tail+of+histone+H3+in+nucleosomes.&rft.au=Trieschmann%2C+L%3BMartin%2C+B%3BBustin%2C+M&rft.aulast=Trieschmann&rft.aufirst=L&rft.date=1998-05-12&rft.volume=95&rft.issue=10&rft.spage=5468&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 - 1998-06-19 N1 - Date created - 1998-06-19 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Anal Biochem. 1987 Nov 1;166(2):368-79 [2449095] Biochemistry. 1986 Mar 25;25(6):1421-8 [3964683] Methods Enzymol. 1989;170:532-49 [2770549] Nucleic Acids Res. 1991 Jun 11;19(11):3115-21 [2057367] Biochemistry. 1992 Jan 21;31(2):364-70 [1731893] Trends Biochem Sci. 1992 May;17(5):187-91 [1595128] J Biol Chem. 1992 Sep 25;267(27):19587-95 [1527076] Cell. 1993 Feb 12;72(3):305-8 [8431942] EMBO J. 1993 Oct;12(10):3855-64 [8404854] Proc Natl Acad Sci U S A. 1993 Nov 15;90(22):10489-93 [8248135] J Biol Chem. 1989 Jan 25;264(3):1799-803 [2912984] J Biol Chem. 1986 Dec 5;261(34):16185-90 [3782113] J Mol Biol. 1994 Feb 11;236(1):189-98 [8107104] Science. 1994 Jul 1;265(5168):90-2 [8016656] Science. 1994 Aug 5;265(5173):796-9 [8047885] Annu Rev Biochem. 1994;63:265-97 [7979240] EMBO J. 1994 Dec 15;13(24):6031-40 [7813441] EMBO J. 1995 Apr 3;14(7):1478-89 [7729423] Genes Dev. 1995 Aug 15;9(16):1978-91 [7649479] Curr Opin Cell Biol. 1995 Jun;7(3):371-5 [7662367] J Mol Biol. 1995 Sep 29;252(4):423-32 [7563062] Mol Cell Biol. 1995 Dec;15(12):6663-9 [8524231] Semin Cell Biol. 1995 Aug;6(4):229-36 [8562915] Semin Cell Biol. 1995 Aug;6(4):247-55 [8562917] Biochem J. 1996 Jun 1;316 ( Pt 2):395-400 [8687379] Curr Opin Genet Dev. 1996 Apr;6(2):176-84 [8722174] Prog Nucleic Acid Res Mol Biol. 1996;54:35-100 [8768072] Proc Natl Acad Sci U S A. 1996 Oct 1;93(20):10548-55 [8855215] Biochemistry. 1997 Sep 23;36(38):11381-8 [9298957] EMBO J. 1997 Aug 1;16(15):4717-26 [9303316] Nature. 1997 Sep 18;389(6648):251-60 [9305837] Nature. 1997 Sep 25;389(6649):349-52 [9311776] Mol Cell Biol. 1997 Oct;17(10):5843-55 [9315642] J Mol Biol. 1997 Oct 31;273(3):503-8 [9356240] J Mol Biol. 1997 Dec 12;274(4):454-65 [9417927] Nature. 1970 Aug 15;227(5259):680-5 [5432063] Cell. 1977 Sep;12(1):101-7 [561660] Science. 1980 Sep 26;209(4464):1534-6 [7433974] Nucleic Acids Res. 1980 Sep 11;8(17):3757-78 [6449690] Biosci Rep. 1984 May;4(5):365-86 [6375755] J Mol Biol. 1985 Sep 20;185(2):329-39 [4057250] Biochem Biophys Res Commun. 1985 Nov 15;132(3):1031-7 [4074344] Erratum In: Proc Natl Acad Sci U S A 1998 Jul 21;95(15):9059 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetic induction of immune tolerance to human clotting factor VIII in a mouse model for hemophilia A AN - 16381328; 4290298 AB - Patients with severe coagulation factor VIII deficiency require frequent infusions of human factor VIII (hFVIII) concentrates to treat life-threatening hemorrhages. Because these patients are immunologically hFVIII-naive, a significant treatment complication is the development of inhibitors or circulating alloantibodies against hFVIII, which bind the replaced glycoprotein, increase its plasma clearance, and inhibit its activity, preventing subsequent treatments from having a therapeutic effect. A genetic approach toward the induction of immunologic unresponsiveness to hFVIII has the conceptual advantage of a long-term, stable elimination of undesired immune responses against hFVIII. Here, we report that in a factor VIII (FVIII)-deficient mouse model for severe hemophilia A, genetic modification of donor bone marrow cells with a retroviral vector encoding hFVIII, and transplant to hemophiliac mouse recipients, results in the induction of immune tolerance to FVIII in 50% of treated animals after immunization with hFVIII, despite the fact that hFVIII protein or activity is undetectable. In tolerized animals, the titers of anti-hFVIII binding antibodies and of hFVIII inhibitor antibodies were significantly reduced, and there was evidence for hFVIII unresponsiveness in CD4 super(+) T cells. Importantly, the plasma clearance of hFVIII was significantly decreased in tolerized animals and was not significantly different from that seen in a FVIII-naive hemophiliac mouse. This model system will prove useful for the evaluation of genetic therapies for hFVIII immunomodulation and bring genetic therapies for hFVIII tolerance closer to clinical application for patients with hemophilia A. JF - Proceedings of the National Academy of Sciences, USA AU - Evans, G L AU - Morgan, R A AD - Clinical Gene Therapy Branch, National Human Genome Research Institute, National Institutes of Health, 10 Center Drive, MSC 1851, Building 10, Room 10C103, Bethesda, MD 20892-1851, rmorgan@nhgri.nih.gov Y1 - 1998/05/12/ PY - 1998 DA - 1998 May 12 SP - 5734 EP - 5739 VL - 95 IS - 10 SN - 0027-8424, 0027-8424 KW - clotting factor VIII KW - coagulation factor VIII KW - man KW - mice KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Genetics Abstracts; Immunology Abstracts KW - G 07480:Hematological disorders KW - F 06878:Blood (non-immunological parts: RBC, platelets) KW - W 30965:Miscellaneous, Reviews KW - W3 33180:Gene based (protocols, clinical trials, and animal models) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16381328?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.atitle=Genetic+induction+of+immune+tolerance+to+human+clotting+factor+VIII+in+a+mouse+model+for+hemophilia+A&rft.au=Evans%2C+G+L%3BMorgan%2C+R+A&rft.aulast=Evans&rft.aufirst=G&rft.date=1998-05-12&rft.volume=95&rft.issue=10&rft.spage=5734&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Evidence for genetic linkage to alcohol dependence on chromosomes 4 and 11 from an autosome-wide scan in an American Indian population. AN - 79888082; 9603607 AB - To identify specific genes affecting vulnerability or resistance, we performed a whole-autosomal genome scan for genetic linkage to alcohol dependence in a Southwestern American Indian tribe. Genotypes at 517 autosomal microsatellite loci and clinical evaluations were available for 152 subjects belonging to extended pedigrees and forming 172 sib-pairs. Highly suggestive evidence for linkage emerged for two genomic regions using two- and multipoint sib-pair regression methods; both regions harbored neurogenetic candidate genes. The best evidence is seen with D11S1984 (nominal P = 0.00007, lod approximately equal to 3.1) on chromosome 11p, in close proximity to the DRD4 dopamine receptor and tyrosine hydroxylase (TH) genes. Good evidence is seen with D4S3242 (nominal P = 0.0002, lod approximately equal to 2.8) on chromosome 4p, near the beta1 GABA receptor gene. Interestingly, three loci in the alcohol dehydrogenase gene cluster on chromosome 4q showed evidence for linkage with two-point analyses, but not multipoint analysis. JF - American journal of medical genetics AU - Long, J C AU - Knowler, W C AU - Hanson, R L AU - Robin, R W AU - Urbanek, M AU - Moore, E AU - Bennett, P H AU - Goldman, D AD - Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland 20892-8110, USA. jeff long@nih.gov Y1 - 1998/05/08/ PY - 1998 DA - 1998 May 08 SP - 216 EP - 221 VL - 81 IS - 3 SN - 0148-7299, 0148-7299 KW - Index Medicus KW - Genotype KW - Humans KW - Adult KW - Genetic Predisposition to Disease KW - Male KW - Female KW - Matched-Pair Analysis KW - Genetic Linkage KW - Chromosomes, Human, Pair 4 -- genetics KW - Chromosomes, Human, Pair 11 -- genetics KW - Alcoholism -- ethnology KW - Alcoholism -- genetics KW - Indians, North American -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79888082?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+medical+genetics&rft.atitle=Evidence+for+genetic+linkage+to+alcohol+dependence+on+chromosomes+4+and+11+from+an+autosome-wide+scan+in+an+American+Indian+population.&rft.au=Long%2C+J+C%3BKnowler%2C+W+C%3BHanson%2C+R+L%3BRobin%2C+R+W%3BUrbanek%2C+M%3BMoore%2C+E%3BBennett%2C+P+H%3BGoldman%2C+D&rft.aulast=Long&rft.aufirst=J&rft.date=1998-05-08&rft.volume=81&rft.issue=3&rft.spage=216&rft.isbn=&rft.btitle=&rft.title=American+journal+of+medical+genetics&rft.issn=01487299&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-06-24 N1 - Date created - 1998-06-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Abnormal properties of prion protein with insertional mutations in different cell types. AN - 79836085; 9565627 AB - Inherited forms of the human transmissible spongiform encephalopathy Creutzfeldt-Jakob disease (CJD) have been associated with mutations in the normal soluble, protease-sensitive form of the host prion protein (PrP-sen). Normal PrP protein contains five copies of a repeating eight-amino acid region, and PrP molecules with six or more copies of this region are associated with disease in familial CJD. It has been hypothesized that these mutations might facilitate spontaneous formation of the abnormal, aggregated protease-resistant PrP isoform, PrP-res, associated with clinical CJD and other transmissible spongiform encephalopathies (TSE). In the present experiments, hamster PrP molecules with 5 (wild-type), 7, 9, or 11 copies of this repeat region were generated and expressed in mouse fibroblast cells or mouse neuroblastoma cells. In mouse fibroblast cells, mutant hamster PrP molecules expressing 7, 9, and 11 copies of the octapeptide repeat sequence showed altered cell surface expression, but both mutant and wild-type hamster PrP-sen molecules demonstrated abnormal properties of aggregation and increased protease resistance. By contrast in mouse neuroblastoma cells, hamster PrP-sen with 5, 9, and 11 octapeptide repeats were expressed normally on the cell surface, but only PrP-sen molecules with 9 or 11 copies of the repeat motif had abnormal properties of aggregation and increased protease resistance. Overall, regardless of cell type, hamster PrP molecules with greater than 7 octapeptide repeats were more aggregated and more protease-resistant than molecules with 7 repeats or less. However, these abnormal molecules were at least 1000-fold less protease-resistant than bona fide PrP-res derived from TSE-infected brain tissue, and they showed no increased ability to form PrP-res in a cell-free system. JF - The Journal of biological chemistry AU - Priola, S A AU - Chesebro, B AD - Laboratory of Persistent Viral Diseases, NIAID, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, Montana 59840, USA. spriola@nih.gov Y1 - 1998/05/08/ PY - 1998 DA - 1998 May 08 SP - 11980 EP - 11985 VL - 273 IS - 19 SN - 0021-9258, 0021-9258 KW - Prions KW - 0 KW - Type C Phospholipases KW - EC 3.1.4.- KW - Endopeptidases KW - EC 3.4.- KW - Endopeptidase K KW - EC 3.4.21.64 KW - Phosphatidylinositol Diacylglycerol-Lyase KW - EC 4.6.1.13 KW - Index Medicus KW - Animals KW - Mice KW - Protein Binding KW - Endopeptidase K -- metabolism KW - Neuroblastoma KW - Type C Phospholipases -- metabolism KW - Structure-Activity Relationship KW - Fibroblasts KW - Mutagenesis KW - Cells, Cultured KW - Cell Compartmentation KW - Endopeptidases -- metabolism KW - Creutzfeldt-Jakob Syndrome -- metabolism KW - Cell Membrane -- metabolism KW - Repetitive Sequences, Nucleic Acid KW - Cricetinae KW - Prions -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79836085?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Abnormal+properties+of+prion+protein+with+insertional+mutations+in+different+cell+types.&rft.au=Priola%2C+S+A%3BChesebro%2C+B&rft.aulast=Priola&rft.aufirst=S&rft.date=1998-05-08&rft.volume=273&rft.issue=19&rft.spage=11980&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 - 1998-06-05 N1 - Date created - 1998-06-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Insulin-like growth factor-1 (IGF-1) receptor-insulin receptor substrate complexes in the uterus. Altered signaling response to estradiol in the IGF-1(m/m) mouse. AN - 79836035; 9565625 AB - Some of the actions of estradiol occur through stimulation of growth factor pathways in target organs. Tyrosine-phosphorylated (Tyr(P)) insulin-like growth factor-1 receptor (IGF-1R) and the insulin receptor substrate (IRS)-1 are found in the uterus of mice treated with estradiol. Immunoprecipitates of uterine Tyr(P) IRS-1 contained both p85, the regulatory subunit of phosphatidylinositol (PI) 3-kinase, and PI 3-kinase catalytic activity. Estradiol also stimulated binding of IRS-1 and PI 3-kinase to the IGF-1R. Depletion of IRS-1 from uterine extracts reduced PI 3-kinase associated with the receptor, which suggests that binding of the enzyme to IGF-1R occurs primarily in a complex that also contains IRS-1. Following treatment with estradiol, formation of Tyr(P) IGF-1R, Tyr(P) IRS-1, and the p85.IRS-1 complex was very weak in the uterus of IGF-1(m/m) mice, which are severely deficient in IGF-1. This indicated that most, if not all, of the estradiol-stimulated Tyr phosphorylation of uterine IRS-1 originates from ligand activation of IGF-1R kinase. IRS-2 was also Tyr-phosphorylated in the normal uterus and bound more IGF-1R and p85 in response to estradiol; however, a marked decrease in levels of uterine IRS-2 occurred 12-24 h after treatment with estradiol. Since IRS-2 was present in IGF-1R precipitates and a recombinant form of IGF-1 (long R3 IGF-1) stimulated formation of Tyr(P) IRS-2, hormonal activation of this docking protein probably occurs through the IGF-1R. In summary, our findings show that estrogen activation of uterine IGF-1R kinase results in enhanced binding of p85 (PI 3-kinase) to IRS-1 and IRS-2. The formation of one or both of these complexes may be important for the potent mitogenic action of this steroid. That estradiol stimulated a decrease of IRS-2, but not of IRS-1, suggests that these docking proteins have different roles in hormone-induced signaling in the uterus. JF - The Journal of biological chemistry AU - Richards, R G AU - Walker, M P AU - Sebastian, J AU - DiAugustine, R P AD - Hormones and Cancer Group, Laboratory of Molecular Carcinogenesis, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 1998/05/08/ PY - 1998 DA - 1998 May 08 SP - 11962 EP - 11969 VL - 273 IS - 19 SN - 0021-9258, 0021-9258 KW - Adaptor Proteins, Signal Transducing KW - 0 KW - GRB2 Adaptor Protein KW - Grb2 protein, mouse KW - Insulin Receptor Substrate Proteins KW - Intracellular Signaling Peptides and Proteins KW - Irs1 protein, mouse KW - Irs2 protein, mouse KW - Phosphoproteins KW - Proteins KW - Phosphotyrosine KW - 21820-51-9 KW - Estradiol KW - 4TI98Z838E KW - Insulin-Like Growth Factor I KW - 67763-96-6 KW - Phosphatidylinositol 3-Kinases KW - EC 2.7.1.- KW - Receptor Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - Receptor, IGF Type 1 KW - Protein Tyrosine Phosphatase, Non-Receptor Type 1 KW - EC 3.1.3.48 KW - Protein Tyrosine Phosphatase, Non-Receptor Type 11 KW - Protein Tyrosine Phosphatase, Non-Receptor Type 6 KW - Protein Tyrosine Phosphatases KW - Ptpn11 protein, mouse KW - Ptpn6 protein, mouse KW - SH2 Domain-Containing Protein Tyrosine Phosphatases KW - Index Medicus KW - Animals KW - Insulin-Like Growth Factor I -- deficiency KW - Protein Tyrosine Phosphatases -- metabolism KW - Phosphatidylinositol 3-Kinases -- metabolism KW - Phosphotyrosine -- metabolism KW - Mice KW - Receptor Protein-Tyrosine Kinases -- metabolism KW - Proteins -- metabolism KW - src Homology Domains KW - Signal Transduction KW - Female KW - Cell Division KW - Uterus -- metabolism KW - Receptor, IGF Type 1 -- metabolism KW - Estradiol -- pharmacology KW - Phosphoproteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79836035?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Insulin-like+growth+factor-1+%28IGF-1%29+receptor-insulin+receptor+substrate+complexes+in+the+uterus.+Altered+signaling+response+to+estradiol+in+the+IGF-1%28m%2Fm%29+mouse.&rft.au=Richards%2C+R+G%3BWalker%2C+M+P%3BSebastian%2C+J%3BDiAugustine%2C+R+P&rft.aulast=Richards&rft.aufirst=R&rft.date=1998-05-08&rft.volume=273&rft.issue=19&rft.spage=11962&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 - 1998-06-05 N1 - Date created - 1998-06-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutation of an active site residue of tryptophan synthase (beta-serine 377) alters cofactor chemistry. AN - 79832356; 9565551 AB - To better understand how an enzyme controls cofactor chemistry, we have changed a tryptophan synthase residue that interacts with the pyridine nitrogen of the pyridoxal phosphate cofactor from a neutral Ser (beta-Ser377) to a negatively charged Asp or Glu. The spectroscopic properties of the mutant enzymes are altered and become similar to those of tryptophanase and aspartate aminotransferase, enzymes in which an Asp residue interacts with the pyridine nitrogen of pyridoxal phosphate. The absorption spectrum of each mutant enzyme undergoes a pH-dependent change (pKa approximately 7.7) from a form with a protonated internal aldimine nitrogen (lambdamax = 416 nm) to a deprotonated form (lambdamax = 336 nm), whereas the absorption spectra of the wild type tryptophan synthase beta2 subunit and alpha2 beta2 complex are pH-independent. The reaction of the S377D alpha2 beta2 complex with L-serine, L-tryptophan, and other substrates results in the accumulation of pronounced absorption bands (lambdamax = 498-510 nm) ascribed to quinonoid intermediates. We propose that the engineered Asp or Glu residue changes the cofactor chemistry by stabilizing the protonated pyridine nitrogen of pyridoxal phosphate, reducing the pKa of the internal aldimine nitrogen and promoting formation of quinonoid intermediates. JF - The Journal of biological chemistry AU - Jhee, K H AU - Yang, L H AU - Ahmed, S A AU - McPhie, P AU - Rowlett, R AU - Miles, E W AD - National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/05/08/ PY - 1998 DA - 1998 May 08 SP - 11417 EP - 11422 VL - 273 IS - 19 SN - 0021-9258, 0021-9258 KW - Bacterial Proteins KW - 0 KW - Glutamates KW - Macromolecular Substances KW - Schiff Bases KW - Aspartic Acid KW - 30KYC7MIAI KW - Serine KW - 452VLY9402 KW - Pyridoxal Phosphate KW - 5V5IOJ8338 KW - Tryptophan KW - 8DUH1N11BX KW - Tryptophan Synthase KW - EC 4.2.1.20 KW - Index Medicus KW - Hydrogen-Ion Concentration KW - Tryptophan -- chemistry KW - Aspartic Acid -- chemistry KW - Binding Sites KW - Structure-Activity Relationship KW - Mutagenesis, Site-Directed KW - Bacterial Proteins -- chemistry KW - Spectrum Analysis KW - Glutamates -- chemistry KW - Pyridoxal Phosphate -- metabolism KW - Tryptophan Synthase -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79832356?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Mutation+of+an+active+site+residue+of+tryptophan+synthase+%28beta-serine+377%29+alters+cofactor+chemistry.&rft.au=Jhee%2C+K+H%3BYang%2C+L+H%3BAhmed%2C+S+A%3BMcPhie%2C+P%3BRowlett%2C+R%3BMiles%2C+E+W&rft.aulast=Jhee&rft.aufirst=K&rft.date=1998-05-08&rft.volume=273&rft.issue=19&rft.spage=11417&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 - 1998-06-05 N1 - Date created - 1998-06-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Psychomotor slowing, negative symptoms and dopamine receptor availability--an IBZM SPECT study in neuroleptic-treated and drug-free schizophrenic patients. AN - 79943790; 9633833 AB - Anhedonia and psychomotor slowing in schizophrenia have been attributed to a dysfunction of dopaminergic neurotransmission. To differentiate between disease and drug-induced negative symptoms, we examined eight drug-free and eight neuroleptic-treated schizophrenic patients. Positive and negative symptoms and extrapyramidal side effects were assessed using standardized rating scales (PSAS, AMDP, SANS). 'Reaction time' and 'motor speed' were measured using a computer-aided system and striatal dopamine D2/D3 receptor availability was assessed using [I-123]IBZM SPECT. Psychomotor reaction time, parkinsonism, affective flattening and avolition were increased in treated patients relative to the untreated cohort and were negatively correlated with dopamine D2/D3 receptor availability. Significant positive correlations were found between parkinsonism and affective flattening and between psychomotor slowing and avolition. Positive symptoms were not significantly associated with striatal IBZM binding. These findings support the hypothesis that neuroleptic-induced dopamine D2/D3 blockade in the striatum can mimic certain negative symptoms, such as affective flattening and avolition, and indicates that psychomotor testing may be helpful in differentiating between disease and drug-induced negative symptoms. JF - Schizophrenia research AU - Heinz, A AU - Knable, M B AU - Coppola, R AU - Gorey, J G AU - Jones, D W AU - Lee, K S AU - Weinberger, D R AD - Clinical Brain Disorders Branch, NIMH, NIMH Neuroscience Center, Center at St. Elizabeths, Washington, DC 20032, USA. Y1 - 1998/05/04/ PY - 1998 DA - 1998 May 04 SP - 19 EP - 26 VL - 31 IS - 1 SN - 0920-9964, 0920-9964 KW - Antipsychotic Agents KW - 0 KW - Benzamides KW - Dopamine Antagonists KW - Pyrrolidines KW - Receptors, Dopamine KW - 3-iodo-2-hydroxy-6-methoxy-N-((1-ethyl-2-pyrrolidinyl)methyl)benzamide KW - 84226-06-2 KW - Haloperidol KW - J6292F8L3D KW - Risperidone KW - L6UH7ZF8HC KW - Index Medicus KW - Acute Disease KW - Humans KW - Adult KW - Middle Aged KW - Brain -- metabolism KW - Brain -- diagnostic imaging KW - Reaction Time KW - Receptors, Dopamine -- drug effects KW - Haloperidol -- adverse effects KW - Psychomotor Disorders -- diagnosis KW - Tomography, Emission-Computed, Single-Photon KW - Schizophrenia -- drug therapy KW - Risperidone -- adverse effects KW - Antipsychotic Agents -- adverse effects KW - Schizophrenia -- complications KW - Psychomotor Disorders -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79943790?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Schizophrenia+research&rft.atitle=Psychomotor+slowing%2C+negative+symptoms+and+dopamine+receptor+availability--an+IBZM+SPECT+study+in+neuroleptic-treated+and+drug-free+schizophrenic+patients.&rft.au=Heinz%2C+A%3BKnable%2C+M+B%3BCoppola%2C+R%3BGorey%2C+J+G%3BJones%2C+D+W%3BLee%2C+K+S%3BWeinberger%2C+D+R&rft.aulast=Heinz&rft.aufirst=A&rft.date=1998-05-04&rft.volume=31&rft.issue=1&rft.spage=19&rft.isbn=&rft.btitle=&rft.title=Schizophrenia+research&rft.issn=09209964&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-09-14 N1 - Date created - 1998-09-14 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Schizophr Res 1998 Nov 9;34(1-2):121 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A trial of dextromethorphan in parkinsonian patients with motor response complications. AN - 85406657; pmid-9613730 AB - The effects of the NMDA antagonist dextromethorphan (DM) on levodopa-associated dyskinesias and motor fluctuations were studied in patients with advanced Parkinson's disease. During initial open-label dose escalation, 6 of 18 patients reported a beneficial effect at their individually determined optimal DM dose (range, 60-120 mg/day). The 12 remaining patients either experienced reversible side effects, particularly mild drowsiness, or decreased levodopa efficacy, and were therefore excluded from the study. The six responders entered the double-blind, placebo-controlled, crossover study with two 2-week arms separated by 1 week wash-out. On the last day of each arm, motor ratings were performed every 20 minutes for 8 consecutive hours. In addition, motor complications and Activities of Daily Living (ADL) were assessed using the Unified Parkinson's Disease Rating Scale (UPDRS) and patient diaries. With DM, dyskinesias improved by 25% according to physician's ratings and by 40% according to UPDRS interviews, without compromising the anti-Parkinson effect of levodopa. Motor fluctuations and ADL scores also improved significantly. Although the narrow therapeutic index of DM limits its clinical usefulness, these findings support the view that drugs acting to inhibit glutamatergic transmission at the NMDA receptor can ameliorate levodopa-associated motor complications. JF - Movement disorders : official journal of the Movement Disorder Society AU - Verhagen Metman, L AU - Blanchet, P J AU - van den Munckhof, P AU - Del Dotto, P AU - Natté, R AU - Chase, T N AD - Experimental Therapeutics Branch, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Maryland 20892-1406, USA. Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 414 EP - 417 VL - 13 IS - 3 SN - 0885-3185, 0885-3185 KW - Index Medicus KW - National Library of Medicine KW - Double-Blind Method KW - Dyskinesia, Drug-Induced -- drug therapy KW - Dose-Response Relationship, Drug KW - Humans KW - Dyskinesia, Drug-Induced -- diagnosis KW - Aged KW - Dextromethorphan -- therapeutic use KW - Parkinson Disease -- drug therapy KW - Parkinson Disease -- diagnosis KW - Drug Therapy, Combination KW - Dextromethorphan -- adverse effects KW - Neurologic Examination -- drug effects KW - Activities of Daily Living -- classification KW - Cross-Over Studies KW - Middle Aged KW - Male KW - Female KW - Antiparkinson Agents -- adverse effects KW - Motor Skills -- drug effects KW - N-Methylaspartate -- antagonists & inhibitors KW - Carbidopa -- adverse effects KW - Antiparkinson Agents -- therapeutic use KW - Carbidopa -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85406657?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Movement+disorders+%3A+official+journal+of+the+Movement+Disorder+Society&rft.atitle=A+trial+of+dextromethorphan+in+parkinsonian+patients+with+motor+response+complications.&rft.au=Verhagen+Metman%2C+L%3BBlanchet%2C+P+J%3Bvan+den+Munckhof%2C+P%3BDel+Dotto%2C+P%3BNatt%C3%A9%2C+R%3BChase%2C+T+N&rft.aulast=Verhagen+Metman&rft.aufirst=L&rft.date=1998-05-01&rft.volume=13&rft.issue=3&rft.spage=414&rft.isbn=&rft.btitle=&rft.title=Movement+disorders+%3A+official+journal+of+the+Movement+Disorder+Society&rft.issn=08853185&rft_id=info:doi/ LA - English DB - ComDisDome N1 - Date revised - 2008-01-14 N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - The role of dendrites in auditory coincidence detection. AN - 85231130; pmid-9607764 AB - Coincidence-detector neurons in the auditory brainstem of mammals and birds use interaural time differences to localize sounds. Each neuron receives many narrow-band inputs from both ears and compares the time of arrival of the inputs with an accuracy of 10-100 micros. Neurons that receive low-frequency auditory inputs (up to about 2 kHz) have bipolar dendrites, and each dendrite receives inputs from only one ear. Using a simple model that mimics the essence of the known electrophysiology and geometry of these cells, we show here that dendrites improve the coincidence-detection properties of the cells. The biophysical mechanism for this improvement is based on the nonlinear summation of excitatory inputs in each of the dendrites and the use of each dendrite as a current sink for inputs to the other dendrite. This is a rare case in which the contribution of dendrites to the known computation of a neuron may be understood. Our results show that, in these neurons, the cell morphology and the spatial distribution of the inputs enrich the computational power of these neurons beyond that expected from 'point neurons' (model neurons lacking dendrites). JF - Nature AU - Agmon-Snir, H AU - Carr, C E AU - Rinzel, J AD - Mathematical Research Branch, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA. PY - 1998 SP - 268 EP - 272 VL - 393 IS - 6682 SN - 0028-0836, 0028-0836 KW - Chickens KW - Support, U.S. Gov't, P.H.S. KW - Auditory Pathways KW - Animal KW - Brain Stem KW - Action Potentials KW - Support, Non-U.S. Gov't KW - Dendrites KW - Models, Neurological KW - Hearing KW - Auditory Perception UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85231130?accountid=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=Nature&rft.atitle=The+role+of+dendrites+in+auditory+coincidence+detection.&rft.au=Agmon-Snir%2C+H%3BCarr%2C+C+E%3BRinzel%2C+J&rft.aulast=Agmon-Snir&rft.aufirst=H&rft.date=1998-05-01&rft.volume=393&rft.issue=6682&rft.spage=268&rft.isbn=&rft.btitle=&rft.title=Nature&rft.issn=00280836&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Association of unconventional myosin MYO15 mutations with human nonsyndromic deafness DFNB3. AN - 85225910; pmid-9603736 AB - DFNB3, a locus for nonsyndromic sensorineural recessive deafness, maps to a 3-centimorgan interval on human chromosome 17p11.2, a region that shows conserved synteny with mouse shaker-2. A human unconventional myosin gene, MYO15, was identified by combining functional and positional cloning approaches in searching for shaker-2 and DFNB3. MYO15 has at least 50 exons spanning 36 kilobases. Sequence analyses of these exons in affected individuals from three unrelated DFNB3 families revealed two missense mutations and one nonsense mutation that cosegregated with congenital recessive deafness. JF - Science AU - Wang, A AU - Liang, Y AU - Fridell, R A AU - Probst, F J AU - Wilcox, E R AU - Touchman, J W AU - Morton, C C AU - Morell, R J AU - Noben-Trauth, K AU - Camper, S A AU - Friedman, Thomas B AD - Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, MD 20850, USA.; National Institute on Deafness and Other Communication Disorders PY - 1998 SP - 1447 EP - 1451 VL - 280 IS - 5368 SN - 0036-8075, 0036-8075 KW - Pedigree KW - Cochlea KW - Animals KW - Chromosomes, Human, Pair 17 KW - Exons KW - Humans KW - Myosins KW - Brain KW - Gene Expression KW - Mice KW - Amino Acid Sequence KW - Cosmids KW - Sequence Analysis, DNA KW - Chromosome Mapping KW - Research Support, U.S. Gov't, P.H.S. KW - Deafness KW - Sequence Alignment KW - Research Support, U.S. Gov't, Non-P.H.S. KW - Molecular Sequence Data KW - Point Mutation KW - Mutation KW - Genes, Recessive KW - Female KW - Male UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85225910?accountid=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=Science&rft.atitle=Association+of+unconventional+myosin+MYO15+mutations+with+human+nonsyndromic+deafness+DFNB3.&rft.au=Wang%2C+A%3BLiang%2C+Y%3BFridell%2C+R+A%3BProbst%2C+F+J%3BWilcox%2C+E+R%3BTouchman%2C+J+W%3BMorton%2C+C+C%3BMorell%2C+R+J%3BNoben-Trauth%2C+K%3BCamper%2C+S+A%3BFriedman%2C+Thomas+B&rft.aulast=Wang&rft.aufirst=A&rft.date=1998-05-01&rft.volume=280&rft.issue=5368&rft.spage=1447&rft.isbn=&rft.btitle=&rft.title=Science&rft.issn=00368075&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Correction of deafness in shaker-2 mice by an unconventional myosin in a BAC transgene. AN - 85225450; pmid-9603735 AB - The shaker-2 mouse mutation, the homolog of human DFNB3, causes deafness and circling behavior. A bacterial artificial chromosome (BAC) transgene from the shaker-2 critical region corrected the vestibular defects, deafness, and inner ear morphology of shaker-2 mice. An unconventional myosin gene, Myo15, was discovered by DNA sequencing of this BAC. Shaker-2 mice were found to have an amino acid substitution at a highly conserved position within the motor domain of this myosin. Auditory hair cells of shaker-2 mice have very short stereocilia and a long actin-containing protrusion extending from their basal end. This histopathology suggests that Myo15 is necessary for actin organization in the hair cells of the cochlea. JF - Science AU - Probst, F J AU - Fridell, R A AU - Raphael, Y AU - Saunders, T L AU - Wang, A AU - Liang, Y AU - Morell, R J AU - Touchman, J W AU - Lyons, R H AU - Noben-Trauth, K AU - Friedman, Thomas B AU - Camper, S A AD - Department of Human Genetics, 4701 MSRB III, University of Michigan, 1500 West Medical Center Drive, Ann Arbor, MI 48109, USA.; National Institute on Deafness and Other Communication Disorders PY - 1998 SP - 1444 EP - 1447 VL - 280 IS - 5368 SN - 0036-8075, 0036-8075 KW - Labyrinth KW - Support, U.S. Gov't, P.H.S. KW - Hair Cells KW - Human KW - Transgenes KW - Myosins KW - Animal KW - Brain KW - Mice KW - Amino Acid Sequence KW - Mice, Transgenic KW - Binding Sites KW - Phenotype KW - Deafness KW - Mice, Mutant Strains KW - Chromosomes, Bacterial KW - Liver KW - Genetic Complementation Test KW - Mice, Inbred C57BL KW - Point Mutation KW - Male KW - Female UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85225450?accountid=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=Science&rft.atitle=Correction+of+deafness+in+shaker-2+mice+by+an+unconventional+myosin+in+a+BAC+transgene.&rft.au=Probst%2C+F+J%3BFridell%2C+R+A%3BRaphael%2C+Y%3BSaunders%2C+T+L%3BWang%2C+A%3BLiang%2C+Y%3BMorell%2C+R+J%3BTouchman%2C+J+W%3BLyons%2C+R+H%3BNoben-Trauth%2C+K%3BFriedman%2C+Thomas+B%3BCamper%2C+S+A&rft.aulast=Probst&rft.aufirst=F&rft.date=1998-05-01&rft.volume=280&rft.issue=5368&rft.spage=1444&rft.isbn=&rft.btitle=&rft.title=Science&rft.issn=00368075&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Development of the mouse inner ear and origin of its sensory organs. AN - 85219243; pmid-9547240 AB - The molecular mechanisms dictating the morphogenesis and differentiation of the mammalian inner ear are largely unknown. To better elucidate the normal development of this organ, two approaches were taken. First, the membranous labyrinths of mouse inner ears ranging from 10.25 to 17 d postcoitum (dpc) were filled with paint to reveal their gross development. Particular attention was focused on the developing utricle, saccule, and cochlea. Second, we used bone morphogenetic protein 4 (BMP4) and lunatic fringe (Fng) as molecular markers to identify the origin of the sensory structures. Our data showed that BMP4 was an early marker for the superior, lateral, and posterior cristae, whereas Fng served as an early marker for the macula utriculi, macula sacculi, and the sensory portion of the cochlea. The posterior crista was the first organ to appear at 11.5 dpc and was followed by the superior crista, the lateral crista, and the macula utriculi at 12 dpc. The macula sacculi and the cochlea were present at 12 dpc but became distinguishable from each other by 13 dpc. Based on the gene expression patterns, the anterior and lateral cristae may share a common origin. Similarly, three sensory organs, the macula utriculi, macula sacculi, and cochlea, seem to arise from a single region of the otocyst. JF - The Journal of Neuroscience AU - Morsli, H AU - Choo, D AU - Ryan, A AU - Johnson, R AU - Wu, Doris Kar-Wah AD - National Institute on Deafness and Other Communication Disorders, Rockville, Maryland 20850, USA.; National Institute on Deafness and Other Communication Disorders PY - 1998 SP - 3327 EP - 3335 VL - 18 IS - 9 SN - 0270-6474, 0270-6474 KW - Labyrinth KW - Support, U.S. Gov't, P.H.S. KW - Sense Organs KW - DNA-Binding Proteins KW - Morphogenesis KW - Animal KW - Cell Differentiation KW - Mice KW - Nerve Growth Factors KW - Fetal Proteins KW - Transcription Factors KW - Embryo and Fetal Development KW - Bone Morphogenetic Proteins KW - Neurotrophin 3 KW - Gene Expression Regulation, Developmental KW - Biological Markers UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85219243?accountid=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=Development+of+the+mouse+inner+ear+and+origin+of+its+sensory+organs.&rft.au=Morsli%2C+H%3BChoo%2C+D%3BRyan%2C+A%3BJohnson%2C+R%3BWu%2C+Doris+Kar-Wah&rft.aulast=Morsli&rft.aufirst=H&rft.date=1998-05-01&rft.volume=18&rft.issue=9&rft.spage=3327&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 - Role of wild-type p53 in the enhancement of camptothecin cytotoxicity against human prostate tumor cells. AN - 80027208; 9673414 AB - The role of wild-type human p53 protein in enhancing camptothecin cytotoxicity was examined by infecting human prostate PC3 cells with adenovirus expressing human wild-type p53 gene (Adwtp53). The prostate PC3 cells are null for p53 gene. Infection induced the synthesis of both wtp53, and WAF1 (p21) proteins, resulting in growth arrest of PC3 cells. In the presence of camptothecin, an inhibitor of topoisomerase 1, significant increases in both p53 and p21 proteins were detected in Adwtp53-infected PC3 cells. While Adwtp53 and camptothecin, as single agents, caused apoptosis and cell death, combinations of camptothecin and Adwtp53 were better in inducing apoptosis and cell death in PC3 cells. In contrast, cisplatin neither stabilized p53 and p21 proteins nor enhanced DNA fragmentation when combined with Adwtp53 in PC3 cells, indicating specificity for camptothecin. These observations suggest that introduction of wild-type p53 gene with topoisomerase I inhibitors may offer a clinical advantage for the treatment of prostate tumors containing mut53 or null for p53 gene. JF - Anticancer research AU - Arah, I N AU - Song, K AU - Seth, P AU - Cowan, K H AU - Sinha, B K AD - Department of Developmental Therapeutics, National Cancer Institute, NIH, Bethesda, Maryland 20982, USA. PY - 1998 SP - 1845 EP - 1849 VL - 18 IS - 3A SN - 0250-7005, 0250-7005 KW - CDKN1A protein, human KW - 0 KW - Cyclin-Dependent Kinase Inhibitor p21 KW - Cyclins KW - Enzyme Inhibitors KW - Recombinant Proteins KW - Tumor Suppressor Protein p53 KW - Cisplatin KW - Q20Q21Q62J KW - Camptothecin KW - XT3Z54Z28A KW - Index Medicus KW - Adenoviridae KW - Cyclins -- biosynthesis KW - Recombinant Proteins -- biosynthesis KW - Dose-Response Relationship, Drug KW - Humans KW - Cell Death -- drug effects KW - Gene Expression Regulation, Neoplastic -- drug effects KW - Tumor Cells, Cultured KW - Transfection KW - Cisplatin -- toxicity KW - Genetic Vectors KW - Kinetics KW - Apoptosis -- drug effects KW - Enzyme Inhibitors -- metabolism KW - Male KW - Tumor Suppressor Protein p53 -- biosynthesis KW - Prostatic Neoplasms -- pathology KW - Genes, p53 KW - Camptothecin -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80027208?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Anticancer+research&rft.atitle=Role+of+wild-type+p53+in+the+enhancement+of+camptothecin+cytotoxicity+against+human+prostate+tumor+cells.&rft.au=Arah%2C+I+N%3BSong%2C+K%3BSeth%2C+P%3BCowan%2C+K+H%3BSinha%2C+B+K&rft.aulast=Arah&rft.aufirst=I&rft.date=1998-05-01&rft.volume=18&rft.issue=3A&rft.spage=1845&rft.isbn=&rft.btitle=&rft.title=Anticancer+research&rft.issn=02507005&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-08-10 N1 - Date created - 1998-08-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interaction between glucocorticoids and corticotropin releasing hormone (CRH) in the regulation of the pituitary CRH receptor in vivo in the rat. AN - 80004174; 9663650 AB - Acute stress causes biphasic changes in corticotropin releasing hormone (CRH) receptor mRNA expression with an early decrease followed by an increase. However, in the absence of glucocorticoids in adrenalectomized rats, stress results in prolonged CRH receptor (CRH-R) mRNA loss, suggesting that interactions between glucocorticoids and hypothalamic factors are critical for regulation of CRH receptor mRNA. To address this question, CRH binding, type-1 CRH-R mRNA, POMC mRNA and POMC hnRNA expression were measured by binding autoradiography and in situ hybridization in pituitaries from intact and adrenalectomized rats. CRH-R mRNA decreased by 59% 5 h after injection of corticosterone (10 mg s.c.) and returned to basal levels by 18 h, a time when plasma corticosterone concentrations were still elevated, and CRH binding and POMC hnRNA were significantly reduced. Elevations in plasma corticosterone in the range of acute stress by injection of 2 mg s.c. caused CRH-R mRNA expression to return to near basal values by 6 h, after a 52% and 39% decrease at 2 h and 4 h. More transient changes were seen after a single injection of CRH (1 microg), with a 44% decrease in CRH-R mRNA and a 175% increase in POMC hnRNA by 2 h, returning to basal values by 4 h. The transient effect of CRH was not due to clearance of CRH from the circulation or receptor desensitization since CRH receptor mRNA expression also recovered after injection of a higher dose (10 microg) or repeated injections of CRH which caused sustained increases in plasma CRH and pituitary POMC hnRNA levels. CRH injection in adrenalectomized rats decreased CRH-R mRNA for up to 6 h, suggesting that glucocorticoids are permissive for the recovery of CRH-R mRNA. Supporting this hypothesis, simultaneous injection of corticosterone and CRH restored CRH-R mRNA expression by 4 h, and increased CRH binding 4 h and 6 h after injection. The data show that interaction between CRH and glucocorticoids counteracts individual inhibitory effects of these regulators alone, and that such effects are likely to contribute to the regulatory pattern of pituitary CRH receptors during acute stress. JF - Journal of neuroendocrinology AU - Ochedalski, T AU - Rabadan-Diehl, C AU - Aguilera, G AD - Section on Endocrine Physiology, Developmental Endocrinology Branch, National Institute of Child Health and Human Development, Bethesda, MD, USA. Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 363 EP - 369 VL - 10 IS - 5 SN - 0953-8194, 0953-8194 KW - Glucocorticoids KW - 0 KW - RNA, Messenger KW - Receptors, Corticotropin-Releasing Hormone KW - RNA KW - 63231-63-0 KW - Pro-Opiomelanocortin KW - 66796-54-1 KW - Corticotropin-Releasing Hormone KW - 9015-71-8 KW - Corticosterone KW - W980KJ009P KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Drug Interactions KW - RNA, Messenger -- metabolism KW - RNA -- metabolism KW - Cell Nucleus -- metabolism KW - Pro-Opiomelanocortin -- genetics KW - Corticosterone -- pharmacology KW - Male KW - Pro-Opiomelanocortin -- metabolism KW - Receptors, Corticotropin-Releasing Hormone -- metabolism KW - Receptors, Corticotropin-Releasing Hormone -- drug effects KW - Receptors, Corticotropin-Releasing Hormone -- genetics KW - Pituitary Gland -- metabolism KW - Corticotropin-Releasing Hormone -- pharmacology KW - Glucocorticoids -- pharmacology KW - Pituitary Gland -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80004174?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+neuroendocrinology&rft.atitle=Interaction+between+glucocorticoids+and+corticotropin+releasing+hormone+%28CRH%29+in+the+regulation+of+the+pituitary+CRH+receptor+in+vivo+in+the+rat.&rft.au=Ochedalski%2C+T%3BRabadan-Diehl%2C+C%3BAguilera%2C+G&rft.aulast=Ochedalski&rft.aufirst=T&rft.date=1998-05-01&rft.volume=10&rft.issue=5&rft.spage=363&rft.isbn=&rft.btitle=&rft.title=Journal+of+neuroendocrinology&rft.issn=09538194&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-09-18 N1 - Date created - 1998-09-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The pathogenesis of squamous cell cancer: lessons learned from studies of skin carcinogenesis. AN - 79983248; 9651822 AB - This study used the induction of squamous cell carcinomas on mouse skin as an experimental model to evaluate molecular and biochemical changes that contribute to the neoplastic phenotype. The study was facilitated by the development of keratinocyte cell culture assays that reproduce each stage of the carcinogenesis process, by discoveries of stage-specific genetic and epigenetic changes and by application of pharmacological and molecular tools that modify each step. An early event in the transformation of keratinocytes involves mutation and activation of the rasHa gene, producing a benign tumor. The phenotypic consequences of ras mutations are mediated by activation of the epidermal growth factor receptor (EGFR), upregulation of protein kinase C (PKC) alpha and AP-1 mediated transcriptional activity and inactivation of PKC delta through tyrosine phosphorylation. These changes in benign tumors are manifested by hyperproliferation (EGFR), aberrant expression of keratinocyte genes (PKC alpha and AP-1) and delayed terminal differentiation (PKC delta). Accumulated chromosomal abnormalities, multifocal phenotypic changes and alterations in gene expression are associated with premalignant progression. Upregulation of the fos gene and AP-1 transcriptional activity causes malignant conversion of benign keratinocytes. In the absence of c-fos, benign tumor cells fail to upregulate secreted angiogenic and proteolytic factors and this may prevent malignant conversion. These pathways provide targets for preventive strategies to interrupt the process of carcinogenesis prior to the evolution of the fully malignant tumor. JF - Journal of dermatological science AU - Yuspa, S H AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4335, USA. Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 1 EP - 7 VL - 17 IS - 1 SN - 0923-1811, 0923-1811 KW - Index Medicus KW - Animals KW - Precancerous Conditions -- physiopathology KW - Papilloma -- etiology KW - Humans KW - Disease Progression KW - Papilloma -- metabolism KW - Carcinoma, Squamous Cell -- etiology KW - Skin Neoplasms -- etiology KW - Skin Neoplasms -- therapy KW - Carcinoma, Squamous Cell -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79983248?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+dermatological+science&rft.atitle=The+pathogenesis+of+squamous+cell+cancer%3A+lessons+learned+from+studies+of+skin+carcinogenesis.&rft.au=Yuspa%2C+S+H&rft.aulast=Yuspa&rft.aufirst=S&rft.date=1998-05-01&rft.volume=17&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Journal+of+dermatological+science&rft.issn=09231811&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-09-18 N1 - Date created - 1998-09-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - 2,3,7,8-Tetrachlorodibenzo-p-dioxin plasma levels in Seveso 20 years after the accident. AN - 79978456; 9520360 AB - In 1976, near Seveso, Italy, an industrial accident caused the release of large quantities of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) into the atmosphere, resulting in the highest levels of the toxicant ever recorded in humans. The contaminated area was divided into three zones (A, B, R) corresponding to decreasing TCDD levels in soil, and cohort including all residents was enumerated. The population of the surrounding noncontaminated area (non-ABR) was chosen as referent population. Two decades after the accident. plasma TCDD levels were measured in 62 subjects randomly sampled from the highest exposed zones (A and B) and 59 subjects from non-ABR, frequency matched for age, gender, and cigarette smoking status. Subjects living in the exposed areas have persistently elevated plasma TCDD levels (range = 1.2-89.9 ppt; geometric mean = 53.2 and 11.0 ppt for Zone A and Zone B, respectively). Levels significantly decrease by distance from the accident site (p = 0.0001), down to general population values (4.9 ppt) in non-ABR, thus validating the original zone classification based on environmental measurements. Women have higher TCDD levels than men in the entire study area (p = 0.0003 in Zone B; p = 0.007 in non-ABR). This gender difference persists after adjustment for location within the zone, consumption of meat derived from locally raised animals, age, body mass index, and smoking. There is no evidence for a gender difference in exposure, so variation in metabolism or elimination due to body fat or hormone-related factors may explain this finding. Elevated TCDD levels in women may contribute to adverse reproductive, developmental, and cancer outcomes. JF - Environmental health perspectives AU - Landi, M T AU - Consonni, D AU - Patterson, D G AU - Needham, L L AU - Lucier, G AU - Brambilla, P AU - Cazzaniga, M A AU - Mocarelli, P AU - Pesatori, A C AU - Bertazzi, P A AU - Caporaso, N E AD - Genetic Epidemiology Branch, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 273 EP - 277 VL - 106 IS - 5 SN - 0091-6765, 0091-6765 KW - Environmental Pollutants KW - 0 KW - Polychlorinated Dibenzodioxins KW - 1,2,3,4-tetrachlorodibenzodioxin KW - HF5S8P28CC KW - Index Medicus KW - Meat KW - Demography KW - Sex Characteristics KW - Humans KW - Middle Aged KW - Diet KW - Aging -- blood KW - Male KW - Italy KW - Female KW - Multivariate Analysis KW - Polychlorinated Dibenzodioxins -- analogs & derivatives KW - Polychlorinated Dibenzodioxins -- blood KW - Environmental Pollutants -- blood KW - Accidents, Occupational UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79978456?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=2%2C3%2C7%2C8-Tetrachlorodibenzo-p-dioxin+plasma+levels+in+Seveso+20+years+after+the+accident.&rft.au=Landi%2C+M+T%3BConsonni%2C+D%3BPatterson%2C+D+G%3BNeedham%2C+L+L%3BLucier%2C+G%3BBrambilla%2C+P%3BCazzaniga%2C+M+A%3BMocarelli%2C+P%3BPesatori%2C+A+C%3BBertazzi%2C+P+A%3BCaporaso%2C+N+E&rft.aulast=Landi&rft.aufirst=M&rft.date=1998-05-01&rft.volume=106&rft.issue=5&rft.spage=273&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 - 1998-09-02 N1 - Date created - 1998-09-02 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Int Arch Occup Environ Health. 1979 Mar 7;43(1):1-15 [107126] Teratog Carcinog Mutagen. 1997-1998;17(4-5):225-40 [9508732] J Natl Cancer Inst. 1986 Feb;76(2):229-34 [3456061] JAMA. 1986 Nov 21;256(19):2683-6 [3490589] J Occup Med. 1987 May;29(5):422-9 [2439670] J Natl Cancer Inst. 1987 Oct;79(4):693-9 [3116310] Carcinogenesis. 1988 Sep;9(9):1677-9 [3409472] J Occup Med. 1989 Feb;31(2):121-3 [2709162] Hum Toxicol. 1989 May;8(3):173-203 [2663703] Helv Chir Acta. 1989 Apr;55(6):861-8 [2753726] Int Arch Occup Environ Health. 1990;62(2):139-57 [2139014] N Engl J Med. 1991 Jan 24;324(4):212-8 [1985242] Cancer Res. 1991 Mar 1;51(5):1391-7 [1671757] J Toxicol Environ Health. 1991 Apr;32(4):357-66 [1826746] Lancet. 1991 Oct 19;338(8773):959-64 [1681339] Lancet. 1991 Oct 26;338(8774):1027-32 [1681353] Drug Metab Dispos. 1993 Jan-Feb;21(1):43-9 [8095225] Epidemiology. 1993 Sep;4(5):398-406 [8399687] Am J Epidemiol. 1994 Feb 1;139(3):272-81 [8116602] Eur J Pharmacol. 1995 May 26;293(1):1-40 [7545581] Cancer Epidemiol Biomarkers Prev. 1995 Jul-Aug;4(5):529-33 [7549810] J Toxicol Environ Health. 1996 Mar;47(4):363-78 [8600289] J Toxicol Environ Health. 1996 Feb 23;47(3):209-20 [8604146] J Biol Chem. 1996 May 3;271(18):10533-7 [8631852] Cancer Causes Control. 1996 May;7(3):312-21 [8734824] Lancet. 1996 Aug 10;348(9024):409 [8709758] Occup Environ Med. 1996 Sep;53(9):606-12 [8882118] Am J Ind Med. 1996 Dec;30(6):647-54 [8914711] Epidemiology. 1997 Nov;8(6):646-52 [9345664] Nature. 1982 Nov 18;300(5889):271-3 [7144882] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Predictors of mortality in bacteremic cancer patients: retrospective analysis of 64 deaths occurring among 262 bacteremic episodes. AN - 79941087; 9629885 AB - A total of 262 bacteremic episodes were observed in cancer patients in a single cancer institution during the last 7 years, and the recorded outcome was death in 65. The 65 patients who died (24.8% overall mortality) were divided retrospectively into two subgroups: (a) those who died of underlying disease with bacteremia (45 cases, 16.9% crude mortality) and (b) those who died of bacteremia (20 patients, 7.7% attributable mortality). Comparison of several risk factors in subgroups of patients who achieved a cure (197 cases) and of those who died and whose deaths were attributable (20 cases) revealed six risk factors that were associated with attributable mortality: (1) chemotherapy-induced neutropenia (P < 0.03), (2) Acinetobacter/Stenotrophomonas spp. bacteremias (P < 0.001), (3) liver failure (P < 0.001), (4) inappropriate therapy (P < 0.0001), (5) organ complications (P < 0.003) and (6) multiresistant organisms (P < 0.001). Enterococci and Pseudomonas aeruginosa, surprisingly, were found more frequently in those who died of an underlying disease with bacteremia than among patients who were cured (17.6% vs 7.6%, P < 0.05 and 29.1% vs 13.8%, P < 0.02). Those who died of infection had higher numbers of positive blood cultures, with 2.05 per episode, than did those who died of underlying disease with bacteremia (1.82) or those who were cured (1.51). Other risk factors, such as underlying disease, type of chemotherapy, origin of bacteremia, age, and catheters did not predict either overall or attributable mortality within the study group. JF - Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer AU - Spanik, S AU - Sufliarsky, J AU - Mardiak, J AU - Sorkovska, D AU - Trupl, J AU - Kunova, A AU - Kukuckova, E AU - Rusnakova, V AU - Demitrovicova, A AU - Pichna, P AU - Krupova, I AU - Kralovicova, K AU - Mateićka, F AU - West, D AU - Krcmery, V AD - Department of Medicine and Microbiology, National Cancer Institute, Bratislava, Slovakia. Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 291 EP - 294 VL - 6 IS - 3 SN - 0941-4355, 0941-4355 KW - Antineoplastic Agents KW - 0 KW - Index Medicus KW - Neutropenia -- mortality KW - Humans KW - Retrospective Studies KW - Aged KW - Bacteria -- isolation & purification KW - Neutropenia -- chemically induced KW - Antineoplastic Agents -- adverse effects KW - Risk Factors KW - Adult KW - Antibiotic Prophylaxis KW - Middle Aged KW - Female KW - Male KW - Neoplasms -- drug therapy KW - Bacteremia -- mortality KW - Neoplasms -- mortality KW - Opportunistic Infections -- mortality KW - Cause of Death UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79941087?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Supportive+care+in+cancer+%3A+official+journal+of+the+Multinational+Association+of+Supportive+Care+in+Cancer&rft.atitle=Predictors+of+mortality+in+bacteremic+cancer+patients%3A+retrospective+analysis+of+64+deaths+occurring+among+262+bacteremic+episodes.&rft.au=Spanik%2C+S%3BSufliarsky%2C+J%3BMardiak%2C+J%3BSorkovska%2C+D%3BTrupl%2C+J%3BKunova%2C+A%3BKukuckova%2C+E%3BRusnakova%2C+V%3BDemitrovicova%2C+A%3BPichna%2C+P%3BKrupova%2C+I%3BKralovicova%2C+K%3BMatei%C4%87ka%2C+F%3BWest%2C+D%3BKrcmery%2C+V&rft.aulast=Spanik&rft.aufirst=S&rft.date=1998-05-01&rft.volume=6&rft.issue=3&rft.spage=291&rft.isbn=&rft.btitle=&rft.title=Supportive+care+in+cancer+%3A+official+journal+of+the+Multinational+Association+of+Supportive+Care+in+Cancer&rft.issn=09414355&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-08-24 N1 - Date created - 1998-08-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Synergistic neurotoxic effects of combined treatments with cytokines in murine primary mixed neuron/glia cultures. AN - 79939388; 9626992 AB - Activation of brain glial cells with the bacterial endotoxin lipopolysaccharide (LPS), the HIV-1 coat protein gp120, or beta-amyloid-derived peptides, stimulates the expression of several cytokines, including tumor necrosis factor-alpha (TNFalpha), interleukin-1 (IL-1) and IL-6. and nitric oxide (NO) which have been proposed as causes of neurodegeneration in the brain. In the present study, the neurotoxic effects of several cytokines, alone or in various combinations, and the correlations of the release of lactate dehydrogenase, the loss of neurons, and the secretion of NO in brain neuronal cell injury were investigated in murine primary mixed neuronal/glial cell cultures. A specific combination of cytokines, i.e., IL-1 (1 ng/ml)+ TNFalpha (10 ng/ml)/interferon-gamma (IFNgamma) (200 u/ml), induced a dramatic neuronal cell injury in the neuron/glia cultures, and its cytotoxic profile was very similar to that seen with the LPS/IFNgamma-induced neuron injury. This indicates that among the many toxic immune mediators secreted in response to LPS, IL-1 and TNFalpha can mimic LPS as the triggering signals and primary mediators for glia-mediated neuron injury in the presence of IFNgamma. This study provides new insights about the cytotoxic mechanism(s) for cytokine-mediated neuron injury. JF - Journal of neuroimmunology AU - Jeohn, G H AU - Kong, L Y AU - Wilson, B AU - Hudson, P AU - Hong, J S AD - Neuropharmacology Section, Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. Y1 - 1998/05/01/ PY - 1998 DA - 1998 May 01 SP - 1 EP - 10 VL - 85 IS - 1 SN - 0165-5728, 0165-5728 KW - Cytokines KW - 0 KW - Drug Combinations KW - Enzyme Inhibitors KW - Interleukin-1 KW - Lipopolysaccharides KW - Neurotoxins KW - Tumor Necrosis Factor-alpha KW - Nitric Oxide KW - 31C4KY9ESH KW - Interferon-gamma KW - 82115-62-6 KW - L-Lactate Dehydrogenase KW - EC 1.1.1.27 KW - NG-Nitroarginine Methyl Ester KW - V55S2QJN2X KW - Index Medicus KW - AIDS/HIV KW - Animals KW - Coculture Techniques KW - Interleukin-1 -- pharmacology KW - NG-Nitroarginine Methyl Ester -- pharmacology KW - Lipopolysaccharides -- pharmacology KW - Tumor Necrosis Factor-alpha -- pharmacology KW - Nitric Oxide -- metabolism KW - Interferon-gamma -- pharmacology KW - Mice KW - Mice, Inbred Strains KW - Enzyme Inhibitors -- pharmacology KW - Drug Synergism KW - L-Lactate Dehydrogenase -- metabolism KW - Neuroglia -- metabolism KW - Neurons -- metabolism KW - Cytokines -- pharmacology KW - Neurons -- drug effects KW - Neurotoxins -- pharmacology KW - Neuroglia -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79939388?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neuroimmunology&rft.atitle=Synergistic+neurotoxic+effects+of+combined+treatments+with+cytokines+in+murine+primary+mixed+neuron%2Fglia+cultures.&rft.au=Jeohn%2C+G+H%3BKong%2C+L+Y%3BWilson%2C+B%3BHudson%2C+P%3BHong%2C+J+S&rft.aulast=Jeohn&rft.aufirst=G&rft.date=1998-05-01&rft.volume=85&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Journal+of+neuroimmunology&rft.issn=01655728&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-07-07 N1 - Date created - 1998-07-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of long-term gastric acid suppressive therapy on serum vitamin B12 levels in patients with Zollinger-Ellison syndrome. AN - 79938123; 9626024 AB - Long-term treatment with H(+)-K(+)-adenotriphosphatase (ATPase) inhibitors, such as omeprazole or lansoprazole, for severe gastroesophageal reflux disease is now widely used. Whether such treatment will result in vitamin B12 deficiency is controversial. We studied whether long-term treatment with omeprazole alters serum vitamin B12 levels in patients with Zollinger-Ellison syndrome. In 131 consecutive patients treated with either omeprazole (n = 111) or histamine H2-receptor antagonists (n = 20), serum vitamin B12 and folate levels and complete blood counts were determined after acid secretion had been controlled for at least 6 months. These studies were repeated yearly. Serum vitamin B12 and folate levels were correlated with the type of antisecretory drug and the extent of inhibition of acid secretion. The mean duration of omeprazole treatment was 4.5 years, and for H2-receptor antagonists 10 years. Vitamin B12 levels, but not serum folate levels or any hematological parameter, were significantly (P = 0.03) lower in patients treated with omeprazole, especially those with omeprazole-induced sustained hyposecretion (P = 0.0014) or complete achlorhydria (P < 0.0001). In 68 patients with two determinations at least 5 years apart, vitamin B12 levels decreased significantly (30%; P = 0.001) only in patients rendered achlorhydric. The duration of omeprazole treatment was inversely correlated with vitamin B12 levels (P = 0.013), but not folate levels. Eight patients (6%) developed subnormal B12 levels during follow-up. Long-term omeprazole treatment leads to significant decreases in serum vitamin B12 but not folate levels. These results suggest patients with Zollinger-Ellison syndrome treated with H(+)-K(+)-ATPase inhibitors should have serum vitamin B12 levels monitored. Furthermore, these results raise the possibility that other patients treated chronically with H(+)-K(+)-ATPase inhibitors may develop B12 deficiency. JF - The American journal of medicine AU - Termanini, B AU - Gibril, F AU - Sutliff, V E AU - Yu, F AU - Venzon, D J AU - Jensen, R T AD - Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 422 EP - 430 VL - 104 IS - 5 SN - 0002-9343, 0002-9343 KW - Anti-Ulcer Agents KW - 0 KW - Folic Acid KW - 935E97BOY8 KW - Adenosine Triphosphatases KW - EC 3.6.1.- KW - Omeprazole KW - KG60484QX9 KW - Vitamin B 12 KW - P6YC3EG204 KW - Abridged Index Medicus KW - Index Medicus KW - Humans KW - Folic Acid -- blood KW - Drug Monitoring KW - Adult KW - Aged KW - Vitamin B 12 -- blood KW - Middle Aged KW - Follow-Up Studies KW - Adolescent KW - Time Factors KW - Male KW - Female KW - Vitamin B 12 Deficiency -- blood KW - Anti-Ulcer Agents -- adverse effects KW - Zollinger-Ellison Syndrome -- drug therapy KW - Omeprazole -- adverse effects KW - Adenosine Triphosphatases -- antagonists & inhibitors KW - Vitamin B 12 Deficiency -- chemically induced KW - Achlorhydria -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79938123?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+of+medicine&rft.atitle=Effect+of+long-term+gastric+acid+suppressive+therapy+on+serum+vitamin+B12+levels+in+patients+with+Zollinger-Ellison+syndrome.&rft.au=Termanini%2C+B%3BGibril%2C+F%3BSutliff%2C+V+E%3BYu%2C+F%3BVenzon%2C+D+J%3BJensen%2C+R+T&rft.aulast=Termanini&rft.aufirst=B&rft.date=1998-05-01&rft.volume=104&rft.issue=5&rft.spage=422&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+medicine&rft.issn=00029343&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-06-25 N1 - Date created - 1998-06-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transfection of interleukin-12 cDNAs into tumor cells induces cytotoxic immune responses against native tumor: implications for tumor vaccination. AN - 79927210; 9622098 AB - Interleukin-12 (IL-12) is a heterodimeric cytokine that is central to the development of T helper 1-dependent cellular immunity. Although this cytokine has potential therapeutic application as an antineoplastic agent, the systemic infusion of IL-12 has led to toxic fatalities; hence, restriction of expression of IL-12 to the microenvironment of target tumor cells has obvious appeal. In this study, we examined whether tumor cells that were liposome-transfected with IL-12 could enhance the induction of cytolytic lymphocyte immunity to the native tumor. The plasmid expression vector that we used has several useful features including replication to high copy number as an episome and a polycistronic message enabling the production of both the p35 and p40 subunits of IL-12 without alternative splicing; up to 3 ng/mL/10(6)/48 hours of IL-12 was produced following transfection. Tumor cells transfected with IL-12 were superior to untransfected cells in the induction of lymphocyte-mediated cytolysis. IL-12 transfectants induced a heterogeneous population of natural killer, lymphokine activated killer, and cytolytic T lymphocytes, the latter of which exhibited tumor-specific activity. Our studies suggest that liposome-mediated transfection of tumor cells with an episomal, high copy number plasmid vector expressing both IL-12 subunits is a promising approach to cancer vaccination, a strategy that could be implemented ex vivo in treating malignancies such as metastatic ovarian cancer. JF - Cancer gene therapy AU - Hoshino, T AU - Jiang, Y Z AU - Dunn, D AU - Paul, D AU - Qazilbash, M AU - Cowan, K AU - Wang, J AU - Barrett, J AU - Liu, J AD - Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. PY - 1998 SP - 150 EP - 157 VL - 5 IS - 3 SN - 0929-1903, 0929-1903 KW - Cancer Vaccines KW - 0 KW - DNA, Complementary KW - Interleukin-12 KW - 187348-17-0 KW - Index Medicus KW - Lymphocytes -- immunology KW - Tumor Cells, Cultured KW - Transfection KW - Humans KW - Genetic Vectors KW - Dependovirus -- genetics KW - Enzyme-Linked Immunosorbent Assay KW - Cytotoxicity, Immunologic KW - Cancer Vaccines -- administration & dosage KW - Cancer Vaccines -- immunology KW - Interleukin-12 -- biosynthesis KW - Interleukin-12 -- genetics KW - Interleukin-12 -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79927210?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+gene+therapy&rft.atitle=Transfection+of+interleukin-12+cDNAs+into+tumor+cells+induces+cytotoxic+immune+responses+against+native+tumor%3A+implications+for+tumor+vaccination.&rft.au=Hoshino%2C+T%3BJiang%2C+Y+Z%3BDunn%2C+D%3BPaul%2C+D%3BQazilbash%2C+M%3BCowan%2C+K%3BWang%2C+J%3BBarrett%2C+J%3BLiu%2C+J&rft.aulast=Hoshino&rft.aufirst=T&rft.date=1998-05-01&rft.volume=5&rft.issue=3&rft.spage=150&rft.isbn=&rft.btitle=&rft.title=Cancer+gene+therapy&rft.issn=09291903&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-08-05 N1 - Date created - 1998-08-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Neural activation during acute capsaicin-evoked pain and allodynia assessed with PET. AN - 79923309; 9619195 AB - The PET H2 15O-bolus method was used to image regional brain activity in normal human subjects during intense pain induced by intradermal injection of capsaicin and during post-capsaicin mechanical allodynia (the perception of pain from a normally non-painful stimulus). Images of regional cerebral blood flow were acquired during six conditions: (i) rest; (ii) light brushing of the forearm; (iii) forearm intradermal injection of capsaicin, (iv) and (v) the waning phases of capsaicin pain; and (vi) allodynia. Allodynia was produced by light brushing adjacent to the capsaicin injection site after ongoing pain from the capsaicin injection had completely subsided. Capsaicin treatment produced activation in many discrete brain regions which we classified as subserving four main functions: sensation-perception (primary somatosensory cortex, thalamus and insula); attention (anterior cingulate cortex); descending pain control (periaqueductal grey); and an extensive network related to sensory-motor integration (supplementary motor cortex, bilateral putamen and insula, anterior lobe and vermis of the cerebellum and superior colliculus). Comparison of the noxious and non-noxious stimuli yielded several new insights into neural organization of pain and tactile sensations. Capsaicin pain, which had no concomitant tactile component, produced little or no activation in secondary somatosensory cortex (SII), whereas light brushing produced a prominent activation of SII, suggesting a differential sensitivity of SII to tactile versus painful stimuli. The cerebellar vermis was strongly activated by capsaicin, whereas light brush and experimental allodynia produced little or no activation, suggesting a selective association with C-fibre stimulation and nociceptive second-order spinal neurons. The experimental allodynia activated a network that partially overlapped those activated by both pain and light brush alone. Unlike capsaicin-induced pain, allodynia was characterized by bilateral activation of inferior prefrontal cortex, suggesting that prefrontal responses to pain are context dependent. JF - Brain : a journal of neurology AU - Iadarola, M J AU - Berman, K F AU - Zeffiro, T A AU - Byas-Smith, M G AU - Gracely, R H AU - Max, M B AU - Bennett, G J AD - Pain and Neurosensory Mechanisms Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892-4410, USA. Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 931 EP - 947 VL - 121 ( Pt 5) SN - 0006-8950, 0006-8950 KW - Capsaicin KW - S07O44R1ZM KW - Abridged Index Medicus KW - Index Medicus KW - Acute Disease KW - Dose-Response Relationship, Drug KW - Cerebrovascular Circulation -- drug effects KW - Humans KW - Perception -- physiology KW - Evaluation Studies as Topic KW - Stress, Mechanical KW - Adult KW - Injections, Subcutaneous KW - Middle Aged KW - Image Processing, Computer-Assisted KW - Female KW - Male KW - Capsaicin -- toxicity KW - Tomography, Emission-Computed KW - Neuralgia -- chemically induced KW - Neuralgia -- diagnostic imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79923309?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain+%3A+a+journal+of+neurology&rft.atitle=Neural+activation+during+acute+capsaicin-evoked+pain+and+allodynia+assessed+with+PET.&rft.au=Iadarola%2C+M+J%3BBerman%2C+K+F%3BZeffiro%2C+T+A%3BByas-Smith%2C+M+G%3BGracely%2C+R+H%3BMax%2C+M+B%3BBennett%2C+G+J&rft.aulast=Iadarola&rft.aufirst=M&rft.date=1998-05-01&rft.volume=121+%28+Pt+5%29&rft.issue=&rft.spage=931&rft.isbn=&rft.btitle=&rft.title=Brain+%3A+a+journal+of+neurology&rft.issn=00068950&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-06-23 N1 - Date created - 1998-06-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The effect of static magnetic fields on the photohemolysis of human erythrocytes by ketoprofen. AN - 79911557; 9613243 AB - Ultraviolet irradiation (lambda > 300 nm) of the nonsteroidal anti-inflammatory agent ketoprofen (KP, 3-benzoyl-alpha-methylbenzoacetic acid) in aqueous solution, pH 7.4, results in heterolytic decarboxylation of the drug to give 3-ethylbenzophenone (EtBP). Ketoprofen caused the photohemolysis of human erythrocytes probably as a result of lipid peroxidation. Application of a static magnetic field (250-1500 G) during UV (> 300 nm) irradiation of KP and erythrocytes significantly decreased the time required for photohemolysis. This observation suggests that KP-induced photohemolysis involves the initial generation of a triplet radical pair derived from the reaction of triplet state KP (or 3-EtBP) with erythrocyte component(s) probably lipids. The magnetic field increases the concentration and/or lifetime of free radicals that escape from the radical pair so that the critical radical concentration needed to initiate membrane damage and cause cell lysis is reached sooner. Spin-trapping studies with 2,6-dibromo-1-nitrosobenzene-4-sulfonate confirmed that the application of an external static magnetic field increased the concentration of radicals released during the photolysis of either KP or 3-EtBP dissolved in organized media such as sodium dodecylsulfate micelles. JF - Photochemistry and photobiology AU - Chignell, C F AU - Sik, R H AD - Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. chignell@niehs.nih.gov Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 591 EP - 595 VL - 67 IS - 5 SN - 0031-8655, 0031-8655 KW - Anti-Inflammatory Agents, Non-Steroidal KW - 0 KW - Ketoprofen KW - 90Y4QC304K KW - Index Medicus KW - Photochemistry KW - Hemolysis -- drug effects KW - Ultraviolet Rays KW - Humans KW - Hemolysis -- radiation effects KW - Erythrocytes -- drug effects KW - Electromagnetic Fields KW - Erythrocytes -- radiation effects KW - Anti-Inflammatory Agents, Non-Steroidal -- adverse effects KW - Ketoprofen -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79911557?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Photochemistry+and+photobiology&rft.atitle=The+effect+of+static+magnetic+fields+on+the+photohemolysis+of+human+erythrocytes+by+ketoprofen.&rft.au=Chignell%2C+C+F%3BSik%2C+R+H&rft.aulast=Chignell&rft.aufirst=C&rft.date=1998-05-01&rft.volume=67&rft.issue=5&rft.spage=591&rft.isbn=&rft.btitle=&rft.title=Photochemistry+and+photobiology&rft.issn=00318655&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-06-24 N1 - Date created - 1998-06-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Spontaneous neoplasm incidences in Fischer 344 rats and B6C3F1 mice in two-year carcinogenicity studies: a National Toxicology Program update. AN - 79910076; 9608650 AB - Spontaneous neoplasm rates were determined for control Fischer 344 (F344) rats and B6C3F1 mice from 2-yr rodent carcinogenicity studies carried out by the National Toxicology Program (NTP). The most frequently occurring neoplasms in untreated male F344 rats were testicular adenoma (89.1%), mononuclear cell leukemia (50.5%), adrenal gland pheochromocytoma (31.9%), and pituitary gland neoplasms (30.4%). For untreated female F344 rats, the most frequently occurring neoplasms were pituitary gland neoplasms (54.2%), mammary gland fibroadenoma (41.2%), and mononuclear cell leukemia (28.1%). The most frequently occurring neoplasms in untreated male B6C3F1 mice were liver adenoma/carcinoma (42.2%), lung adenoma/carcinoma (20.5%), and malignant lymphoma (8.3%). For untreated female B6C3F1 mice, the most frequently occurring neoplasms were liver adenoma/carcinoma (23.6%), malignant lymphoma (20.9%), and pituitary gland adenoma/carcinoma (14.8%). The tumor rates observed in feeding study (untreated) and inhalation study (chamber) control rats were generally similar. The major exceptions were pituitary gland tumors and testicular adenoma in male F344 rats. The overall incidence of testicular adenoma was much lower in chamber controls (69.4%) than in feeding study controls (89.1%), whereas pituitary gland neoplasm showed the opposite trend (60.7% vs 30.4%). The most likely explanation for this difference is related to the individual housing of chamber controls and the group housing of feeding study controls. Differences in diagnostic criteria may influence reported tumor rates. To ensure consistency and comparability of tumor diagnosis from study to study, the NTP uses rigorous histopathology quality assurance and peer review procedures. Biological factors such as body weight may also affect tumor incidence. For example, increased body weights are associated with increased incidences of certain site-specific neoplasms, especially pituitary gland and mammary gland neoplasms in rats and liver tumors in mice. The presence of Helicobacter hepaticus has been associated with an increased incidence of liver neoplasms in male B6C3F1 mice. Other factors that may produce differences in control tumor rates from study to study include diet, environmental factors, genetic drift, study duration, and survival differences. The NTP database provides historical control data that may be useful in the evaluation of possible chemically related changes in tumor incidence. However, it is essential that the study being evaluated be comparable to those in the NTP database with respect to those factors that are known to influence tumor occurrence. JF - Toxicologic pathology AU - Haseman, J K AU - Hailey, J R AU - Morris, R W AD - Biostatistics Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. PY - 1998 SP - 428 EP - 441 VL - 26 IS - 3 SN - 0192-6233, 0192-6233 KW - Index Medicus KW - Rats KW - Body Weight KW - Animals KW - Survival Rate KW - Mice KW - Male KW - Female KW - Neoplasms -- veterinary KW - Mice, Inbred Strains KW - Rats, Inbred F344 KW - Neoplasms -- pathology KW - Rodent Diseases -- epidemiology KW - Neoplasms -- epidemiology KW - Rodent Diseases -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79910076?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicologic+pathology&rft.atitle=Spontaneous+neoplasm+incidences+in+Fischer+344+rats+and+B6C3F1+mice+in+two-year+carcinogenicity+studies%3A+a+National+Toxicology+Program+update.&rft.au=Haseman%2C+J+K%3BHailey%2C+J+R%3BMorris%2C+R+W&rft.aulast=Haseman&rft.aufirst=J&rft.date=1998-05-01&rft.volume=26&rft.issue=3&rft.spage=428&rft.isbn=&rft.btitle=&rft.title=Toxicologic+pathology&rft.issn=01926233&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-08-12 N1 - Date created - 1998-08-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - p53 mutations in cyclophosphamide-associated bladder cancer. AN - 79908839; 9610789 AB - Cyclophosphamide is a known bladder carcinogen, with cumulative dose directly related to increased risk. There is no consensus, however, on which major cyclophosphamide metabolite (i.e., acrolein or phosphoramide mustard) drives bladder carcinogenesis. We examined 19 cyclophosphamide-related bladder tumors to test the hypothesis that they might contain somatic mutations in the p53 tumor suppressor gene that could link a specific metabolite to the etiology of these cancers. Forty-three % (9 of 19) of the cases had a mutation in p53, with a predominance at G:C bp (7 of 9, 77%), a preference for non-CpG sites (6 of 7, 86%), and frequent G:C-->A:T transitions (5 of 7, 71%). The p53 mutation spectrum of these cyclophosphamide-associated bladder cancers differed significantly from patterns reported for sporadic (P = 0.020), smoking-related (0.043), and schistosomiasis-linked (P = 0.002) tumors but not arylamine-associated neoplasms (P = 0.860). Differences between the cyclophosphamide and arylamine-associated spectra included an unusual degree of clustering of exon 6 mutations (43% versus 17%, respectively) and an absence of multiple mutations in the former. Notably lacking in our series were G:C-->T:A transversions, the principal mutation associated with acrolein. Instead, the mutation spectrum matches the phosphoramide mustard adduction sequences determined by a repetitive primer-extension assay (P = 0.024), indicating that this metabolite might be a key mutagen in cyclophosphamide-related bladder cancer. JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology AU - Khan, M A AU - Travis, L B AU - Lynch, C F AU - Soini, Y AU - Hruszkewycz, A M AU - Delgado, R M AU - Holowaty, E J AU - van Leeuwen, F E AU - Glimelius, B AU - Stovall, M AU - Boice, J D AU - Tarone, R E AU - Bennett, W P AD - Laboratory of Human Carcinogenesis, Radiation Epidemiology Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 397 EP - 403 VL - 7 IS - 5 SN - 1055-9965, 1055-9965 KW - Antineoplastic Agents, Alkylating KW - 0 KW - Cyclophosphamide KW - 8N3DW7272P KW - Index Medicus KW - Humans KW - DNA Mutational Analysis KW - Lymphoma, Non-Hodgkin -- complications KW - Adult KW - Case-Control Studies KW - Aged KW - Middle Aged KW - Male KW - Female KW - Genes, p53 -- drug effects KW - Urinary Bladder Neoplasms -- secondary KW - Urinary Bladder Neoplasms -- genetics KW - Mutation -- genetics KW - Antineoplastic Agents, Alkylating -- adverse effects KW - Urinary Bladder Neoplasms -- chemically induced KW - Cyclophosphamide -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79908839?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=p53+mutations+in+cyclophosphamide-associated+bladder+cancer.&rft.au=Khan%2C+M+A%3BTravis%2C+L+B%3BLynch%2C+C+F%3BSoini%2C+Y%3BHruszkewycz%2C+A+M%3BDelgado%2C+R+M%3BHolowaty%2C+E+J%3Bvan+Leeuwen%2C+F+E%3BGlimelius%2C+B%3BStovall%2C+M%3BBoice%2C+J+D%3BTarone%2C+R+E%3BBennett%2C+W+P&rft.aulast=Khan&rft.aufirst=M&rft.date=1998-05-01&rft.volume=7&rft.issue=5&rft.spage=397&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 - 1999-01-12 N1 - Date created - 1999-01-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Glycine modulates the toxicity of benzyl acetate in F344 rats. AN - 79908384; 9608646 AB - The influence of supplemental glycine on benzyl acetate (BA; a compound metabolized via the hippurate pathway)-induced toxicity was investigated. Groups of male F344 rats were fed NIH-07 diet containing 0, 20,000, 35,000, or 50,000 ppm BA for up to 28 days. Two additional groups were fed NIH-07 diet with 50,000 ppm BA and 27,000 ppm glycine or 50,000 ppm BA 32,000 ppm L-alanine; supplemental glycine and L-alanine were equimolar. The L-alanine group served as an amino nitrogen control. A third group was fed NIH-07 diet with 32,000 ppm L-alanine and served as an untreated isonitrogenous control BA caused increase in mortality, body weight loss, the incidence of abnormal neurobehavioral signs such as ataxia and convulsions, along with astrocyte hypertrophy and neuronal necrosis in the cerebellum, hippocampus, and pyriform cortex of the brain. These effects were reduced significantly by supplementation with glycine but not with L-alanine. These results suggest that the neurodegeneration induced by BA is mediated by a depletion of the glycine pool and the subsequent excitotoxicity. JF - Toxicologic pathology AU - Abdo, K M AU - Wenk, M L AU - Harry, G J AU - Mahler, J AU - Goehl, T J AU - Irwin, R D AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. abdok@niehs.nih.gov PY - 1998 SP - 395 EP - 402 VL - 26 IS - 3 SN - 0192-6233, 0192-6233 KW - Air Pollutants, Occupational KW - 0 KW - Benzyl Compounds KW - benzyl acetate KW - 0ECG3V79ZJ KW - Glycine KW - TE7660XO1C KW - Index Medicus KW - Seizures -- chemically induced KW - Animals KW - Ataxia -- chemically induced KW - Dose-Response Relationship, Drug KW - Brain -- drug effects KW - Air Pollutants, Occupational -- adverse effects KW - Hypertrophy -- prevention & control KW - Seizures -- prevention & control KW - Rats KW - Rats, Inbred F344 KW - Necrosis KW - Survival Rate KW - Brain -- pathology KW - Weight Loss -- drug effects KW - Dietary Supplements KW - Hypertrophy -- chemically induced KW - Ataxia -- prevention & control KW - Male KW - Organ Size -- drug effects KW - Neurodegenerative Diseases -- chemically induced KW - Benzyl Compounds -- adverse effects KW - Glycine -- pharmacology KW - Neurodegenerative Diseases -- pathology KW - Neurodegenerative Diseases -- mortality KW - Neurodegenerative Diseases -- prevention & control KW - Glycine -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79908384?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicologic+pathology&rft.atitle=Glycine+modulates+the+toxicity+of+benzyl+acetate+in+F344+rats.&rft.au=Abdo%2C+K+M%3BWenk%2C+M+L%3BHarry%2C+G+J%3BMahler%2C+J%3BGoehl%2C+T+J%3BIrwin%2C+R+D&rft.aulast=Abdo&rft.aufirst=K&rft.date=1998-05-01&rft.volume=26&rft.issue=3&rft.spage=395&rft.isbn=&rft.btitle=&rft.title=Toxicologic+pathology&rft.issn=01926233&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-08-12 N1 - Date created - 1998-08-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dopamine biosynthesis is selectively abolished in substantia nigra/ventral tegmental area but not in hypothalamic neurons in mice with targeted disruption of the Nurr1 gene. AN - 79903327; 9608532 AB - To ascertain the function of an orphan nuclear receptor Nurr1, a transcription factor belonging to a large gene family that includes receptors for steroids, retinoids, and thyroid hormone, we generated Nurr1-null mice by homologous recombination. Mice, heterozygous for a single mutated Nurr1 allele, appear normal, whereas mice homozygous for the null allele die within 24 h after birth. Dopamine (DA) was absent in the substantia nigra (SN) and ventral tegmental area (VTA) of Nurr1-null mice, consistent with absent tyrosine hydroxylase (TH), L-aromatic amino acid decarboxylase, and other DA neuron markers. TH immunoreactivity and mRNA expression in hypothalamic, olfactory, and lower brain stem regions were unaffected. L-Dihydroxyphenylalanine treatments, whether given to the pregnant dams or to the newborns, failed to rescue the Nurr1-null mice. We were unable to discern differences between null and wild-type mice in the cellularity, presence of neurons, or axonal projections to the SN and VTA. These findings provide evidence for a new mechanism of DA depletion in vivo and suggest a unique role for Nurr1 in fetal development and/or postnatal survival. JF - Molecular and cellular neurosciences AU - Castillo, S O AU - Baffi, J S AU - Palkovits, M AU - Goldstein, D S AU - Kopin, I J AU - Witta, J AU - Magnuson, M A AU - Nikodem, V M AD - National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-1766, USA. Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 36 EP - 46 VL - 11 IS - 1-2 SN - 1044-7431, 1044-7431 KW - Biomarkers KW - 0 KW - DNA-Binding Proteins KW - Nr4a2 protein, mouse KW - Nuclear Receptor Subfamily 4, Group A, Member 2 KW - RNA, Messenger KW - Transcription Factors KW - Levodopa KW - 46627O600J KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Animals KW - Exons KW - RNA, Messenger -- analysis KW - Mice KW - Pregnancy KW - Phenotype KW - Levodopa -- pharmacology KW - Brain Chemistry -- genetics KW - Heterozygote KW - Mice, Inbred C57BL KW - Mice, Neurologic Mutants KW - Female KW - Mutagenesis, Insertional KW - Substantia Nigra -- metabolism KW - Neurons -- metabolism KW - Dopamine -- deficiency KW - Ventral Tegmental Area -- pathology KW - Substantia Nigra -- pathology KW - Hypothalamus -- metabolism KW - Dopamine -- physiology KW - Dopamine -- biosynthesis KW - Ventral Tegmental Area -- metabolism KW - Transcription Factors -- deficiency KW - Transcription Factors -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79903327?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+neurosciences&rft.atitle=Dopamine+biosynthesis+is+selectively+abolished+in+substantia+nigra%2Fventral+tegmental+area+but+not+in+hypothalamic+neurons+in+mice+with+targeted+disruption+of+the+Nurr1+gene.&rft.au=Castillo%2C+S+O%3BBaffi%2C+J+S%3BPalkovits%2C+M%3BGoldstein%2C+D+S%3BKopin%2C+I+J%3BWitta%2C+J%3BMagnuson%2C+M+A%3BNikodem%2C+V+M&rft.aulast=Castillo&rft.aufirst=S&rft.date=1998-05-01&rft.volume=11&rft.issue=1-2&rft.spage=36&rft.isbn=&rft.btitle=&rft.title=Molecular+and+cellular+neurosciences&rft.issn=10447431&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-08-07 N1 - Date created - 1998-08-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Reduction in transforming growth factor-beta type II receptor in mouse lung carcinogenesis. AN - 79900353; 9609100 AB - Transforming growth factor-beta (TGF-beta) is a growth modulator that inhibits the proliferation of many epithelial cells through interaction with its receptors, the type I and type II receptors (TGF-beta RI and RII) by activating their serine/threonine kinase activities. Loss of growth inhibition by TGF-beta is thought to contribute to the development of many types of tumors. To examine the roles of TGF-beta1, -beta2, and -beta3 and TGF-beta RI and RII in chemically induced mouse lung tumorigenesis, we used immunohistochemical and in situ hybridization analyses to measure the expression of their proteins and mRNAs in A/J mice treated with the carcinogen urethane to induce lung adenomas. Immunostaining for the TGF-beta ligands and receptors was detected in the epithelia of the bronchioles of untreated and treated A/J mice at similar levels. Immunostaining for the TGF-beta ligands and receptors was also detected in adenomas by 2 mo. While immunostaining for TGF-beta1, -beta2, and -beta3 and TGF-beta RI in adenomas was detected at levels comparable to those in bronchioles, immunostaining for TGF-beta RII was less intense in adenomas than in bronchioles. Decreased immunostaining for TGF-beta RII in adenomas persisted for at least 8 mo after exposure to urethane, whereas immunostaining for TGF-beta1, -beta2, and -beta3 and TGF-beta RI persisted at levels comparable to those in normal bronchioles. In situ hybridization studies conducted with TGF-beta receptor riboprobes showed a corresponding reduction in expression of TGF-beta RII mRNA but not of TGF-beta RI mRNA in adenomas compared with expression in bronchioles. Expression of TGF-beta RII mRNA was also examined in non-tumorigenic and tumorigenic mouse lung cells; expression of TGF-beta RII mRNA was lower in the tumorigenic cells derived from urethane-induced lung tumors. These data suggest that a decrease in expression of TGF-beta RII may contribute to autonomous cell growth and may play an important role in mouse lung carcinogenesis induced by urethane. JF - Molecular carcinogenesis AU - Jakowlew, S B AU - Moody, T W AU - You, L AU - Mariano, J M AD - Department of Cell and Cancer Biology, Medicine Branch, National Cancer Institute, Rockville, Maryland 20850, USA. Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 46 EP - 56 VL - 22 IS - 1 SN - 0899-1987, 0899-1987 KW - Carcinogens KW - 0 KW - RNA, Messenger KW - Receptors, Transforming Growth Factor beta KW - Transforming Growth Factor beta KW - Urethane KW - 3IN71E75Z5 KW - TGF-beta type I receptor KW - EC 2.7.1.11 KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - Activin Receptors, Type I KW - EC 2.7.11.30 KW - transforming growth factor-beta type II receptor KW - Index Medicus KW - Animals KW - Protein-Serine-Threonine Kinases -- metabolism KW - Carcinogens -- toxicity KW - Mice KW - RNA, Messenger -- biosynthesis KW - Protein-Serine-Threonine Kinases -- biosynthesis KW - Mice, Inbred A KW - Polymerase Chain Reaction KW - Down-Regulation KW - Epithelial Cells KW - Urethane -- toxicity KW - Cell Line KW - Female KW - Cell Division KW - Transforming Growth Factor beta -- biosynthesis KW - Lung -- immunology KW - Lung Neoplasms -- immunology KW - Lung -- drug effects KW - Transcription, Genetic KW - Receptors, Transforming Growth Factor beta -- biosynthesis KW - Lung -- metabolism KW - Cell Transformation, Neoplastic KW - Lung Neoplasms -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79900353?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+carcinogenesis&rft.atitle=Reduction+in+transforming+growth+factor-beta+type+II+receptor+in+mouse+lung+carcinogenesis.&rft.au=Jakowlew%2C+S+B%3BMoody%2C+T+W%3BYou%2C+L%3BMariano%2C+J+M&rft.aulast=Jakowlew&rft.aufirst=S&rft.date=1998-05-01&rft.volume=22&rft.issue=1&rft.spage=46&rft.isbn=&rft.btitle=&rft.title=Molecular+carcinogenesis&rft.issn=08991987&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-06-16 N1 - Date created - 1998-06-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Specific vanilloid responses in C6 rat glioma cells. AN - 79900088; 9602075 AB - Capsaicin and its ultrapotent analog resiniferatoxin (RTX) act through specific vanilloid receptors on sensory neurons. Here, we describe specific vanilloid responses in rat C6 glioma cells. Capsaicin and RTX stimulated 45Ca uptake in a similar fashion to that found for cultured rat dorsal root ganglion neurons (DRGs); this response was antagonized by the antagonists capsazepine and ruthenium red. As in DRGs, pretreatment of C6 cells with capsaicin or RTX produced desensitization to subsequent stimulation of 45Ca uptake. The potency for desensitization by RTX in the C6 cells corresponded to that for 45Ca uptake, whereas in DRGs it occurred at significantly lower concentrations corresponding to that for the high affinity [3H]RTX binding site. Consistent with this difference, in C6 cells we were unable to detect [3H]RTX binding. These characteristics suggest the presence of C-type but not R-type vanilloid receptors on C6 cells. After 2 day treatment, capsaicin but not RTX inhibited the proliferation and altered the differentiation of the cells and produced apoptosis. In the long term experiments, capsazepine, instead of antagonizing the effect of capsaicin, acted as an agonist. Moreover, capsazepine displayed these effects with higher potency than that of capsaicin. The different potencies and structure activity relations suggest a distinct mechanism for these long-term vanilloid effects. Our finding that C6 cells can respond directly to capsaicin necessitates a reevaluation of the in vivo pathway of response to vanilloids, and highlights the importance of the neuron-glial network. Copyright 1998 Elsevier Science B.V. JF - Brain research. Molecular brain research AU - Bíró, T AU - Brodie, C AU - Modarres, S AU - Lewin, N E AU - Acs, P AU - Blumberg, P M AD - Molecular Mechanisms of Tumor Promotion Section, Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 89 EP - 98 VL - 56 IS - 1-2 SN - 0169-328X, 0169-328X KW - Calcium Radioisotopes KW - 0 KW - Diterpenes KW - Neurotoxins KW - Receptors, Drug KW - resiniferatoxin KW - A5O6P1UL4I KW - capsazepine KW - LFW48MY844 KW - Capsaicin KW - S07O44R1ZM KW - Index Medicus KW - Rats KW - Diterpenes -- pharmacology KW - Calcium Radioisotopes -- metabolism KW - Animals KW - Tumor Cells, Cultured KW - Cell Division -- drug effects KW - Neurotoxins -- pharmacology KW - Diterpenes -- antagonists & inhibitors KW - Cell Differentiation -- drug effects KW - Capsaicin -- analogs & derivatives KW - Capsaicin -- antagonists & inhibitors KW - Capsaicin -- pharmacology KW - Receptors, Drug -- metabolism KW - Glioma -- metabolism KW - Receptors, Drug -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79900088?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain+research.+Molecular+brain+research&rft.atitle=Specific+vanilloid+responses+in+C6+rat+glioma+cells.&rft.au=B%C3%ADr%C3%B3%2C+T%3BBrodie%2C+C%3BModarres%2C+S%3BLewin%2C+N+E%3BAcs%2C+P%3BBlumberg%2C+P+M&rft.aulast=B%C3%ADr%C3%B3&rft.aufirst=T&rft.date=1998-05-01&rft.volume=56&rft.issue=1-2&rft.spage=89&rft.isbn=&rft.btitle=&rft.title=Brain+research.+Molecular+brain+research&rft.issn=0169328X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-01-14 N1 - Date created - 1999-01-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Amyloid precursor protein modulates the interaction of nerve growth factor with p75 receptor and potentiates its activation of trkA phosphorylation. AN - 79897039; 9602092 AB - We have recently shown that the secreted form of amyloid precursor protein (APPs) potentiates the neurotrophic actions of nerve growth factor (NGF). The combined presence of NGF and APPs in low concentrations resulted in a synergistic potentiation of NGF neuritogenic activity on PC12 cells. Therefore, the effect of APPs on NGF receptor-binding has been examined. In the presence of APPs, the apparent affinity of NGF's low affinity binding site increased by a factor of 2.5. In addition, a 2- to 2.5-fold decrease in the number of sites was observed, although APPs did not compete with NGF for the same binding sites. These effects of APPs were not caused by direct interaction with NGF itself. In addition, APPs synergistically potentiated the tyrosine phosphorylation of trkA due to NGF. These results suggest that an increased affinity of p75 for NGF may underlie the potentiation of neurotrophic actions of NGF by APPs, and that increase may be caused by an indirect interaction between APPs and p75. Copyright 1998 Elsevier Science B.V. JF - Brain research. Molecular brain research AU - Akar, C A AU - Wallace, W C AD - Laboratory of Cellular and Molecular Biology, National Institute on Aging, Gerontology Research Center, 4940 Eastern Ave., Baltimore, MD 21224, USA. Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 125 EP - 132 VL - 56 IS - 1-2 SN - 0169-328X, 0169-328X KW - Amyloid beta-Protein Precursor KW - 0 KW - Nerve Growth Factors KW - Proto-Oncogene Proteins KW - Receptor, Nerve Growth Factor KW - Receptors, Nerve Growth Factor KW - Receptor Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - Receptor, trkA KW - Index Medicus KW - Rats KW - Animals KW - Protein Binding -- drug effects KW - Humans KW - Kidney -- cytology KW - Enzyme Activation -- drug effects KW - Drug Synergism KW - Cell Line KW - Phosphorylation -- drug effects KW - Binding Sites KW - Receptors, Nerve Growth Factor -- physiology KW - Nerve Growth Factors -- metabolism KW - Proto-Oncogene Proteins -- metabolism KW - Amyloid beta-Protein Precursor -- secretion KW - Amyloid beta-Protein Precursor -- physiology KW - Amyloid beta-Protein Precursor -- metabolism KW - Receptor Protein-Tyrosine Kinases -- metabolism KW - Receptors, Nerve Growth Factor -- metabolism KW - Nerve Growth Factors -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79897039?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain+research.+Molecular+brain+research&rft.atitle=Amyloid+precursor+protein+modulates+the+interaction+of+nerve+growth+factor+with+p75+receptor+and+potentiates+its+activation+of+trkA+phosphorylation.&rft.au=Akar%2C+C+A%3BWallace%2C+W+C&rft.aulast=Akar&rft.aufirst=C&rft.date=1998-05-01&rft.volume=56&rft.issue=1-2&rft.spage=125&rft.isbn=&rft.btitle=&rft.title=Brain+research.+Molecular+brain+research&rft.issn=0169328X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-01-14 N1 - Date created - 1999-01-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of L-NMMA and fluid loading on TNF-induced cardiovascular dysfunction in dogs. AN - 79893613; 9603114 AB - We investigated the effects of N(omega)-monomethyl-L-arginine (L-NMMA) and fluid loading on tumor necrosis factor (TNF)-induced cardiovascular dysfunction in awake dogs. L-NMMA (40 mg x kg(-1) given intravenously over a period of 10 min, and followed by dosing at 40 mg x kg(-1) x h(-1) for 6 h) and TNF (20 or 45 microg x kg(-1) given intravenously for 20 min), given alone or in combination, significantly decreased stroke volume, cardiac index, oxygen delivery, and left-ventricular (LV) function plots over a period of 6 h. Of note was that the cardiac-depressant effects of TNF and L-NMMA given together were significantly less than additive. Thus, the combination was beneficial (or significantly less harmful to cardiac performance than expected), possibly because L-NMMA augmented cardiac preload as shown by significant increases in both pulmonary capillary wedge pressure (PCWP) and central venous pressure (CVP). Fluid challenges at 6 h (Ringer's solution at 80 ml x kg(-1) given over a period of 30 min) also significantly increased PCWP and CVP, and abolished the beneficial preload effect of L-NMMA on cardiac performance. Thus, after fluid loading, the cardiac-depressant effects of TNF and L-NMMA given together became equal to the sum of those produced by TNF and L-NMMA given separately. Although L-NMMA significantly decreased serum nitrite/nitrate levels, TNF did not increase these end products of nitric oxide (NO) production relative to controls. Therefore, after preload abnormalities were eliminated with fluid loading, L-NMMA had no beneficial effect on TNF-induced cardiac depression, and TNF did not increase end products of NO production. These findings are not consistent with NO being the mechanism of TNF-induced acute cardiac depression. JF - American journal of respiratory and critical care medicine AU - Quezado, Z M AU - Karzai, W AU - Danner, R L AU - Freeman, B D AU - Yan, L AU - Eichacker, P Q AU - Banks, S M AU - Cobb, J P AU - Cunnion, R E AU - Quezado, M J AU - Sevransky, J E AU - Natanson, C AD - Critical Care Medicine Department, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 1397 EP - 1405 VL - 157 IS - 5 Pt 1 SN - 1073-449X, 1073-449X KW - Enzyme Inhibitors KW - 0 KW - Isotonic Solutions KW - Tumor Necrosis Factor-alpha KW - omega-N-Methylarginine KW - 27JT06E6GR KW - Ringer's solution KW - 8026-10-6 KW - Abridged Index Medicus KW - Index Medicus KW - Hemodynamics -- drug effects KW - Animals KW - Venous Pressure -- drug effects KW - Infusions, Intravenous KW - Pulmonary Wedge Pressure -- drug effects KW - Isotonic Solutions -- administration & dosage KW - Dogs KW - Hypotension -- chemically induced KW - Tumor Necrosis Factor-alpha -- toxicity KW - Enzyme Inhibitors -- pharmacology KW - omega-N-Methylarginine -- pharmacology KW - Ventricular Dysfunction, Left -- physiopathology KW - Water-Electrolyte Balance KW - Hypotension -- physiopathology KW - Ventricular Dysfunction, Left -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79893613?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+respiratory+and+critical+care+medicine&rft.atitle=Effects+of+L-NMMA+and+fluid+loading+on+TNF-induced+cardiovascular+dysfunction+in+dogs.&rft.au=Quezado%2C+Z+M%3BKarzai%2C+W%3BDanner%2C+R+L%3BFreeman%2C+B+D%3BYan%2C+L%3BEichacker%2C+P+Q%3BBanks%2C+S+M%3BCobb%2C+J+P%3BCunnion%2C+R+E%3BQuezado%2C+M+J%3BSevransky%2C+J+E%3BNatanson%2C+C&rft.aulast=Quezado&rft.aufirst=Z&rft.date=1998-05-01&rft.volume=157&rft.issue=5+Pt+1&rft.spage=1397&rft.isbn=&rft.btitle=&rft.title=American+journal+of+respiratory+and+critical+care+medicine&rft.issn=1073449X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-06-16 N1 - Date created - 1998-06-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Plasmodium gallinaceum: differential killing of some mosquito stages of the parasite by insect defensin. AN - 79890083; 9603495 AB - We examined several insect antimicrobial peptides to study their effect on Plasmodium gallinaceum zygotes, ookinetes, oocysts, and sporozoites. Only two insect defensins-Aeschna cyanea (dragon fly) and Phormia terranovae (flesh fly)-had a profound toxic effect on the oocysts in Aedes aegypti and on isolated sporozoites. The defensins affected the oocysts in a time-dependent manner. Injecting the peptide into the hemolymph 1 or 2 days after an infectious blood meal had no significant effect on prevalence of infection or relative oocyst density per mosquito. When injected 3 days after parasite ingestion, the relative oocyst density was significantly reduced. Injection on day 4 or later damaged the developing oocysts, although the oocysts density per mosquito was not significantly different when examined on day 8. The oocysts were swollen or had extensive internal vacuolization. The peptides had no detectable effect on the early stages of the parasite: the zygotes and ookinetes tested in vitro. Both the defensins were highly toxic to isolated sporozoites in vitro as indicated by disruption of the membrane permeability barrier, a change in morphology, and loss of motility. In contrast to the toxicity of cecropin and magainin for mosquitoes, defensin, at concentrations that kill parasites, is not toxic to mosquitoes, suggesting that defensin should be studied further as a potential molecule to block sporogonic development of Plasmodium. JF - Experimental parasitology AU - Shahabuddin, M AU - Fields, I AU - Bulet, P AU - Hoffmann, J A AU - Miller, L H AD - Medical Entomology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. shahabuddin@nih.gov Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 103 EP - 112 VL - 89 IS - 1 SN - 0014-4894, 0014-4894 KW - Anti-Infective Agents KW - 0 KW - Blood Proteins KW - Defensins KW - Index Medicus KW - Animals KW - Chickens KW - Insects -- chemistry KW - Zygote -- drug effects KW - Diptera -- chemistry KW - Insect Vectors -- parasitology KW - Plasmodium gallinaceum -- growth & development KW - Aedes -- parasitology KW - Anti-Infective Agents -- pharmacology KW - Plasmodium gallinaceum -- drug effects KW - Blood Proteins -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79890083?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+parasitology&rft.atitle=Plasmodium+gallinaceum%3A+differential+killing+of+some+mosquito+stages+of+the+parasite+by+insect+defensin.&rft.au=Shahabuddin%2C+M%3BFields%2C+I%3BBulet%2C+P%3BHoffmann%2C+J+A%3BMiller%2C+L+H&rft.aulast=Shahabuddin&rft.aufirst=M&rft.date=1998-05-01&rft.volume=89&rft.issue=1&rft.spage=103&rft.isbn=&rft.btitle=&rft.title=Experimental+parasitology&rft.issn=00144894&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-06-02 N1 - Date created - 1998-06-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - JC virusType 2: definition of subtypes based on DNA sequence analysis of ten complete genomes. AN - 79888950; 9603329 AB - Five major genotypes of JC virus (JCV) have been defined based on nucleotide differences in the VP1 gene of the DNA sequence. These types are probably a result of virus evolution in geographically isolated population groups. One of the first genotypes identified, Type 2, was found to represent strains of Asian origin. In order to further define the spectrum within Type 2 strains, the entire 5.1 kb genome of nine urinary strains of JCV was amplified by PCR with one pair of primers. These urine samples were obtained in the USA (California and New Mexico) from three European Americans, three Native Americans, two African Americans and one Hispanic American. The complete genome of an Asian JCV strain (Tokyo-1) isolated from progressive multifocal leukoencephalopathy (PML) brain in Japan was also sequenced. Here, we report the analysis of these ten DNA sequences and their deduced protein translations. Two phylogenetically distinct subtypes of Type 2 were found, 2A and 2B, which differ from each other by 0.8-1.1% of the coding region sequence. A 215 bp product amplified with primers in the VP1 gene contains enough sequence information to distinguish the major types and subtypes of JCV and is suitable for application in viral epidemiological studies. The investigation of these genomic variations is of special interest because JCV Type 2 strains are found at a significantly higher frequency in brain tissue of patients with PML than would be predicted from their excretion in a control population. JF - The Journal of general virology AU - Agostini, H T AU - Shishido-Hara, Y AU - Baumhefner, R W AU - Singer, E J AU - Ryschkewitsch, C F AU - Stoner, G L AD - Neurotoxicology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-4126, USA. Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 1143 EP - 1151 VL - 79 ( Pt 5) SN - 0022-1317, 0022-1317 KW - Capsid Proteins KW - 0 KW - DNA, Viral KW - VP1 protein, polyomavirus KW - Index Medicus KW - Regulatory Sequences, Nucleic Acid KW - Genetic Variation KW - Base Sequence KW - Humans KW - Adult KW - Point Mutation KW - Molecular Sequence Data KW - Aged KW - Middle Aged KW - Male KW - Female KW - Tumor Virus Infections -- virology KW - JC Virus -- genetics KW - JC Virus -- classification KW - Capsid -- genetics KW - Papillomavirus Infections -- virology KW - Genome, Viral KW - Sequence Analysis, DNA UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79888950?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+general+virology&rft.atitle=JC+virusType+2%3A+definition+of+subtypes+based+on+DNA+sequence+analysis+of+ten+complete+genomes.&rft.au=Agostini%2C+H+T%3BShishido-Hara%2C+Y%3BBaumhefner%2C+R+W%3BSinger%2C+E+J%3BRyschkewitsch%2C+C+F%3BStoner%2C+G+L&rft.aulast=Agostini&rft.aufirst=H&rft.date=1998-05-01&rft.volume=79+%28+Pt+5%29&rft.issue=&rft.spage=1143&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+general+virology&rft.issn=00221317&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-06-15 N1 - Date created - 1998-06-15 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF015529; GENBANK; AF015536; AF015535; AF015534; AF015533; AF015532; AF015531; AF030085; AF015530; AF015684 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Activity-dependent neurotrophic factor: structure-activity relationships of femtomolar-acting peptides. AN - 79886286; 9580606 AB - Activity-dependent neurotrophic factor (ADNF) is a glia-derived protein that is neuroprotective at femtomolar concentrations. A 14-amino acid peptide of ADNF (ADNF-14) has been reported that protects cultured neurons from multiple neurotoxins. Structure-activity relationships of peptides related to ADNF-14 now have been determined. A 9-amino acid core peptide (ADNF-9) has been identified that has greater potency and a broader effective concentration range (10(-16) to 10(-13) M) than ADNF or ADNF-14 in preventing cell death associated with tetrodotoxin treatment of cerebral cortical cultures. Deletions or conservative amino acid substitutions to ADNF-9 resulted in reduced potency, narrower effective concentration range and/or decreased efficacy. Removal of the N-terminal serine or the COOH-terminal isoleucine-proline-alanine from ADNF-9 produced a significant reduction in survival-promoting activity. Comparative studies of ADNF-9 action in mixed (glia plus neurons) vs. glia-depleted neuronal cultures indicated that ADNF-9 can act directly on neurons, although the potency of the peptide was 10,000-fold greater in mixed cultures. Kinetic studies showed that exposure to ADNF-9 for only 2 hr was sufficient to produce a 4-day protection against the cell-killing action of tetrodotoxin. Treatment with bafilomycin A1 (an inhibitor of receptor-mediated endocytosis) for 2 hr prevented the ADNF- and ADNF-9-mediated neuroprotection. ADNF-9, like ADNF-14, was neuroprotective against N-methyl-D-aspartate and the beta-amyloid peptide (amino acids 25-35), and had a much broader range of effective concentrations than ADNF-14. These studies identify ADNF-9 as an attractive lead compound for the development of therapeutic agents against neurodegenerative diseases. JF - The Journal of pharmacology and experimental therapeutics AU - Brenneman, D E AU - Hauser, J AU - Neale, E AU - Rubinraut, S AU - Fridkin, M AU - Davidson, A AU - Gozes, I AD - Section on Developmental and Molecular Pharmacology, National Institute for Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 619 EP - 627 VL - 285 IS - 2 SN - 0022-3565, 0022-3565 KW - Nerve Tissue Proteins KW - 0 KW - Neuroprotective Agents KW - Index Medicus KW - Rats KW - Animals KW - Cerebral Cortex -- drug effects KW - Dose-Response Relationship, Drug KW - Cells, Cultured KW - Structure-Activity Relationship KW - Nerve Tissue Proteins -- pharmacology KW - Neuroprotective Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79886286?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Activity-dependent+neurotrophic+factor%3A+structure-activity+relationships+of+femtomolar-acting+peptides.&rft.au=Brenneman%2C+D+E%3BHauser%2C+J%3BNeale%2C+E%3BRubinraut%2C+S%3BFridkin%2C+M%3BDavidson%2C+A%3BGozes%2C+I&rft.aulast=Brenneman&rft.aufirst=D&rft.date=1998-05-01&rft.volume=285&rft.issue=2&rft.spage=619&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 - 1998-06-08 N1 - Date created - 1998-06-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Levodopa therapy: consequences of the nonphysiologic replacement of dopamine. AN - 79884378; 9591518 AB - Normal motor function is dependent on the highly regulated synthesis and release of the transmitter dopamine by neurons projecting from the substantia nigra to the corpus striatum. Parkinson's disease involves the progressive degeneration of these neurons. Its core symptoms are a direct consequence of a striatal insufficiency of intrasynaptic dopamine. Levodopa, the standard of care for the treatment of PD, acts after its conversion to dopamine by restoring striatal dopaminergic transmission. However, there are significant differences between the normally functioning dopamine system and the restoration of function provided by standard levodopa treatment. Increasing clinical and preclinical evidence suggests that the intermittent stimulation of dopamine receptors resulting from current therapeutic regimens contributes to the response complications that ultimately affect most parkinsonian patients. It now appears that chronic nonphysiologic stimulation of dopaminergic receptors on striatal GABAergic neurons activates characteristic signaling pathways, leading to a potentiation of the synaptic efficacy of adjacent glutamatergic receptors of the N-methyl-D-aspartate (NMDA) subtype. As a result, function of these GABAergic efferent neurons changes in ways that favor the appearance of motor complications. Conceivably, use of dopaminomimetic replacement strategies that provide more continuous dopamine receptor stimulation will act to prevent or alleviate these disabling complications. A number of promising approaches to achieving this goal are now under development. JF - Neurology AU - Chase, T N AD - Experimental Therapeutics Branch, National Institute of Neurological and Communicative Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-1406, USA. Y1 - 1998/05// PY - 1998 DA - May 1998 SP - S17 EP - S25 VL - 50 IS - 5 Suppl 5 SN - 0028-3878, 0028-3878 KW - Antiparkinson Agents KW - 0 KW - Catechol O-Methyltransferase Inhibitors KW - Delayed-Action Preparations KW - Dopamine Agents KW - Enzyme Inhibitors KW - Levodopa KW - 46627O600J KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Delayed-Action Preparations -- therapeutic use KW - Enzyme Inhibitors -- therapeutic use KW - Humans KW - Disease Models, Animal KW - Dyskinesia, Drug-Induced -- etiology KW - Antiparkinson Agents -- adverse effects KW - Dopamine Agents -- therapeutic use KW - Parkinson Disease -- metabolism KW - Levodopa -- therapeutic use KW - Antiparkinson Agents -- therapeutic use KW - Dopamine Agents -- adverse effects KW - Levodopa -- adverse effects KW - Parkinson Disease -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79884378?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurology&rft.atitle=Levodopa+therapy%3A+consequences+of+the+nonphysiologic+replacement+of+dopamine.&rft.au=Chase%2C+T+N&rft.aulast=Chase&rft.aufirst=T&rft.date=1998-05-01&rft.volume=50&rft.issue=5+Suppl+5&rft.spage=S17&rft.isbn=&rft.btitle=&rft.title=Neurology&rft.issn=00283878&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-06-09 N1 - Date created - 1998-06-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Amantadine as treatment for dyskinesias and motor fluctuations in Parkinson's disease. AN - 79880205; 9595981 AB - To determine the effects of the N-methyl-D-aspartate (NMDA) antagonist amantadine on levodopa-associated dyskinesias and motor fluctuations in Parkinson's disease (PD). NMDA receptor blockade can ameliorate levodopa-induced dyskinesias in primates and PD patients. Amantadine, a well-tolerated and modestly effective antiparkinsonian agent, was recently found to possess NMDA antagonistic properties. Eighteen patients with advanced PD participated in a double-blind, placebo-controlled, cross-over study. At the end of each 3-week treatment arm, parkinsonian and dyskinesia scores were obtained during a steady-state intravenous levodopa infusion. Motor fluctuations and dyskinesias were also documented with patient-kept diaries and Unified Parkinson's Disease Rating Scale (UPDRS) interviews. In the 14 patients completing this trial, amantadine reduced dyskinesia severity by 60% (p = 0.001) compared to placebo, without altering the antiparkinsonian effect of levodopa. Motor fluctuations occurring with patients' regular oral levodopa regimen also improved according to UPDRS and patient-kept diaries. These findings suggest that amantadine given as adjuvant to levodopa can markedly improve motor response complications and support the view that hyperfunction of NMDA receptors contributes to the pathogenesis of levodopa-associated motor complications. JF - Neurology AU - Verhagen Metman, L AU - Del Dotto, P AU - van den Munckhof, P AU - Fang, J AU - Mouradian, M M AU - Chase, T N AD - Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-1406, USA. Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 1323 EP - 1326 VL - 50 IS - 5 SN - 0028-3878, 0028-3878 KW - Antiparkinson Agents KW - 0 KW - Excitatory Amino Acid Antagonists KW - Receptors, N-Methyl-D-Aspartate KW - Levodopa KW - 46627O600J KW - Amantadine KW - BF4C9Z1J53 KW - Abridged Index Medicus KW - Index Medicus KW - Double-Blind Method KW - Logistic Models KW - Humans KW - Adult KW - Treatment Outcome KW - Cross-Over Studies KW - Aged KW - Motor Activity -- drug effects KW - Middle Aged KW - Levodopa -- adverse effects KW - Male KW - Female KW - Dyskinesia, Drug-Induced -- drug therapy KW - Amantadine -- therapeutic use KW - Excitatory Amino Acid Antagonists -- therapeutic use KW - Receptors, N-Methyl-D-Aspartate -- antagonists & inhibitors KW - Antiparkinson Agents -- therapeutic use KW - Parkinson Disease -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79880205?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurology&rft.atitle=Amantadine+as+treatment+for+dyskinesias+and+motor+fluctuations+in+Parkinson%27s+disease.&rft.au=Verhagen+Metman%2C+L%3BDel+Dotto%2C+P%3Bvan+den+Munckhof%2C+P%3BFang%2C+J%3BMouradian%2C+M+M%3BChase%2C+T+N&rft.aulast=Verhagen+Metman&rft.aufirst=L&rft.date=1998-05-01&rft.volume=50&rft.issue=5&rft.spage=1323&rft.isbn=&rft.btitle=&rft.title=Neurology&rft.issn=00283878&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-06-08 N1 - Date created - 1998-06-08 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Neurology. 1998 May;50(5):1211-2 [9595964] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Simultaneous binding of heparin and platelet factor-4 to platelets: further insights into the mechanism of heparin-induced thrombocytopenia. AN - 79878550; 9590145 AB - Heparin-induced thrombocytopenia (HIT) is mediated by antibody against complexes of platelet factor-4 (PF4) and heparin. Although it has been assumed that these complexes bind to platelets and provide a target for the antibody, this has never been demonstrated. Furthermore, there is evidence suggesting that heparin-PF4 complexes do not bind to platelets. We have analyzed the effect of each ligand on the platelet binding of the other. We particularly focused on the result when heparin and PF4 are in equimolar concentration because we had previously shown that this was the condition under which HIT-IgG increased on the platelet surface. We found that when the molar concentration of PF4 approximates or exceeds that of heparin, the ligands bind simultaneously to the cells and HIT-IgG binds also. However, when heparin is in molar excess, both PF4 binding and HIT-IgG binding are diminished. Our data are consistent with the hypothesis that heparin-PF4 complexes bind via their heparin component to heparin binding sites on the platelet membrane rather than by their PF4 component to PF4 sites. The conditions promoting the binding of the complexes also lead to binding of HIT-IgG. JF - American journal of hematology AU - Horne, M K AU - Hutchison, K J AD - Clinical Pathology Department, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 24 EP - 30 VL - 58 IS - 1 SN - 0361-8609, 0361-8609 KW - Immunoglobulin G KW - 0 KW - Ligands KW - Platelet Factor 4 KW - 37270-94-3 KW - Heparin KW - 9005-49-6 KW - Index Medicus KW - Swine KW - Osmolar Concentration KW - Animals KW - Immunoglobulin G -- metabolism KW - Time Factors KW - Platelet Factor 4 -- metabolism KW - Thrombocytopenia -- chemically induced KW - Heparin -- metabolism KW - Thrombocytopenia -- blood KW - Blood Platelets -- metabolism KW - Heparin -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79878550?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+hematology&rft.atitle=Simultaneous+binding+of+heparin+and+platelet+factor-4+to+platelets%3A+further+insights+into+the+mechanism+of+heparin-induced+thrombocytopenia.&rft.au=Horne%2C+M+K%3BHutchison%2C+K+J&rft.aulast=Horne&rft.aufirst=M&rft.date=1998-05-01&rft.volume=58&rft.issue=1&rft.spage=24&rft.isbn=&rft.btitle=&rft.title=American+journal+of+hematology&rft.issn=03618609&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-06-04 N1 - Date created - 1998-06-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Rhabdomyosarcomas and radiation hypersensitivity in a mouse model of Gorlin syndrome. AN - 79872834; 9585239 AB - Gorlin (or nevoid basal cell carcinoma) syndrome is characterized by a variety of clinical problems including generalized overgrowth of the body, cysts, developmental abnormalities of the skeleton and a predisposition to benign and malignant tumors. The syndrome results from germline mutations of the human homolog of the drosophila segment polarity gene patched (ptc). Here we report that mice heterozygous for ptc develop many of the features characteristic of Gorlin syndrome and that they exhibit a high incidence of rhabdomyosarcomas (RMS), the most common soft-tissue sarcoma in children. The downstream signalling partner of ptc, gli1, was overexpressed in all RMSs analyzed, indicating that abnormal signalling of the ptc-gli1 pathway may be common for the various tumors associated with the syndrome. igf2, implicated in the formation of RMSs, was also overexpressed, suggesting cross-talk between the ptc and igf2 pathways in tumorigenesis. Developmental defects in Gorlin syndrome resemble those induced by ionizing radiation. We show that ptc heterozygous mice exhibit increased incidence of radiation-induced teratogenesis. This suggests a role for ptc in the response to ionizing radiation and provides a model for both the systemic (developmental) and stochastic (cancer) abnormalities observed in Gorlin syndrome. JF - Nature medicine AU - Hahn, H AU - Wojnowski, L AU - Zimmer, A M AU - Hall, J AU - Miller, G AU - Zimmer, A AD - Section on Genetics, National Institute of Mental Health, Bethesda, MD 20892, USA. Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 619 EP - 622 VL - 4 IS - 5 SN - 1078-8956, 1078-8956 KW - Cesium Radioisotopes KW - 0 KW - Intracellular Signaling Peptides and Proteins KW - Membrane Proteins KW - Oncogene Proteins KW - Patched Receptors KW - Patched-1 Receptor KW - Ptch1 protein, mouse KW - Receptors, Cell Surface KW - Trans-Activators KW - Transcription Factors KW - Zinc Finger Protein GLI1 KW - Index Medicus KW - Animals KW - Disease Models, Animal KW - Embryo, Mammalian -- radiation effects KW - Oncogene Proteins -- genetics KW - Mice KW - Dose-Response Relationship, Radiation KW - Transcription Factors -- genetics KW - Transcription Factors -- biosynthesis KW - Oncogene Proteins -- biosynthesis KW - Heterozygote KW - Molecular Sequence Data KW - Crosses, Genetic KW - Rhabdomyosarcoma -- genetics KW - Basal Cell Nevus Syndrome -- complications KW - Rhabdomyosarcoma -- complications KW - Membrane Proteins -- genetics KW - Basal Cell Nevus Syndrome -- genetics KW - Mutation KW - Radiation Tolerance -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79872834?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+medicine&rft.atitle=Rhabdomyosarcomas+and+radiation+hypersensitivity+in+a+mouse+model+of+Gorlin+syndrome.&rft.au=Hahn%2C+H%3BWojnowski%2C+L%3BZimmer%2C+A+M%3BHall%2C+J%3BMiller%2C+G%3BZimmer%2C+A&rft.aulast=Hahn&rft.aufirst=H&rft.date=1998-05-01&rft.volume=4&rft.issue=5&rft.spage=619&rft.isbn=&rft.btitle=&rft.title=Nature+medicine&rft.issn=10788956&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-05-29 N1 - Date created - 1998-05-29 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - W65013; GENBANK N1 - SuppNotes - Comment In: Nat Med. 1998 May;4(5):559-60 [9585226] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Laboratory and diagnostic testing in child and adolescent psychiatry: a review of the past 10 years. AN - 79871377; 9585646 AB - To review in a critical fashion the literature of the past decade covering diagnostic and laboratory testing in the field of child and adolescent psychiatry. A computerized search of articles published during the past decade was made, and selected articles are presented. Because of the paucity of articles specifically relating to minors, selected articles from adult psychiatry are cited. With a few notable exceptions, few controlled studies on the specificity and sensitivity of any laboratory test for any specific disorder of behavior presenting in children have been conducted in children and adolescents. A high index of suspicion will remain the clinician's best ally in utilizing laboratory measures in the assessment of psychopathology. Nonetheless, studies have appeared that will guide the clinician as to what tests are not clinically useful. Indications and the lack of indications for specific laboratory studies are an integral part of the knowledge base that child psychiatrists must have. Much more empirical data will need to be collected prospectively to inform the field and to move the judicious use of the laboratory from an art to a science. JF - Journal of the American Academy of Child and Adolescent Psychiatry AU - Zametkin, A J AU - Ernst, M AU - Silver, R AD - National Institute of Mental Health, NIH, Bethesda, MD 20892, USA. zametkin@box-z.nih.gov Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 464 EP - 472 VL - 37 IS - 5 SN - 0890-8567, 0890-8567 KW - Psychotropic Drugs KW - 0 KW - Index Medicus KW - Mental Disorders -- diagnosis KW - Mental Disorders -- drug therapy KW - Humans KW - Adult KW - Psychotropic Drugs -- pharmacokinetics KW - Mental Disorders -- etiology KW - Child KW - Psychotropic Drugs -- adverse effects KW - Psychotropic Drugs -- administration & dosage KW - Adolescent KW - Diagnostic Tests, Routine KW - Adolescent Psychiatry -- education KW - Child Psychiatry -- education UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79871377?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+American+Academy+of+Child+and+Adolescent+Psychiatry&rft.atitle=Laboratory+and+diagnostic+testing+in+child+and+adolescent+psychiatry%3A+a+review+of+the+past+10+years.&rft.au=Zametkin%2C+A+J%3BErnst%2C+M%3BSilver%2C+R&rft.aulast=Zametkin&rft.aufirst=A&rft.date=1998-05-01&rft.volume=37&rft.issue=5&rft.spage=464&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+American+Academy+of+Child+and+Adolescent+Psychiatry&rft.issn=08908567&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-06-11 N1 - Date created - 1998-06-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The GDPAL region of the pre-S1 envelope protein is important for morphogenesis of woodchuck hepatitis virus. AN - 79869859; 9581699 AB - The pre-S envelope protein of duck hepatitis B virus (DHBV) contains a region, Asp-Asp-Pro-Leu-Leu (DDPLL), that is specifically required for virus assembly and secretion (Lenhoff and Summers, J Virol 1994;68:4565-4571). We found that amino acids 201 to 205 of the pre-S envelope protein of woodchuck hepatitis virus (WHV) form a conserved amino acid cluster, Gly-Asp-Pro-Ala-Leu (GDPAL), which resembles the DDPLL sequence of DHBV. To determine whether the GDPAL region was functionally equivalent to the DDPLL region, we deleted this region from the pre-S protein of WHV or mutated individual amino acids within the region. The mutant DNA was transfected into human hepatoma cell line Huh7, and the medium was assayed for virion production by immunoprecipitation and Southern blot analysis. We found that an in-frame deletion of this small region inhibited virion formation, suggesting that the GDPAL region of the pre-S envelope protein was required for virus assembly and/or secretion of WHV. Individual replacement of alanine 204, leucine 205, or serine 206 with other amino acid residues did not affect virus production. However, substitution of either aspartic acid 202 with valine or proline 203 with leucine dramatically inhibited WHV production. Furthermore, the GDPAL mutants were individually tested for their abilities to complement a pre-S1 defective genome. The results showed that the GDPAL region functioned as part of the pre-S1 protein but was not required to function as part of the pre-S2 protein. JF - Hepatology (Baltimore, Md.) AU - Yu, M AU - Emerson, S U AU - Cote, P AU - Shapiro, M AU - Purcell, R H AD - Hepatitis Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 1408 EP - 1414 VL - 27 IS - 5 SN - 0270-9139, 0270-9139 KW - DNA, Viral KW - 0 KW - Protein Precursors KW - RNA, Viral KW - Viral Envelope Proteins KW - Index Medicus KW - Virus Replication KW - Humans KW - Protein Precursors -- physiology KW - Morphogenesis KW - Amino Acid Sequence KW - Structure-Activity Relationship KW - Mutagenesis, Site-Directed KW - Sequence Alignment KW - Genetic Complementation Test KW - Molecular Sequence Data KW - RNA, Viral -- metabolism KW - Cell Line KW - DNA, Viral -- metabolism KW - Hepatitis B Virus, Woodchuck -- genetics KW - Viral Envelope Proteins -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79869859?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Hepatology+%28Baltimore%2C+Md.%29&rft.atitle=The+GDPAL+region+of+the+pre-S1+envelope+protein+is+important+for+morphogenesis+of+woodchuck+hepatitis+virus.&rft.au=Yu%2C+M%3BEmerson%2C+S+U%3BCote%2C+P%3BShapiro%2C+M%3BPurcell%2C+R+H&rft.aulast=Yu&rft.aufirst=M&rft.date=1998-05-01&rft.volume=27&rft.issue=5&rft.spage=1408&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 - 1998-05-19 N1 - Date created - 1998-05-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Changes in expression of 15-lipoxygenase and prostaglandin-H synthase during differentiation of human tracheobronchial epithelial cells. AN - 79845185; 9569236 AB - The purpose of our studies was to examine differentiation-dependent expression of 15-lipoxygenase (15-LO) and prostaglandin H synthase (PGHS) isoforms in cultured normal human tracheobronchial epithelial cells. In the presence of retinoic acid (RA) the cultures differentiated into a mucociliary epithelium. When cultured in RA-depleted media, the cultures differentiated into a squamous epithelium. In the absence of RA the cultures did not express 15-LO or either of the PGHS isoforms. The PGHS-1 isoform was not expressed in RA-sufficient cultures, but both PGHS-2 messenger RNA (mRNA) and protein were strongly expressed, and prostaglandin E2 (PGE2) was produced during the predifferentiation phase. No PGHS-2 expression or PGE2 could be detected in fully differentiated mucociliary cultures. 15-LO showed the opposite expression pattern: neither mRNA nor protein were detected during the predifferentiation stage, but both were strongly expressed once mucous differentiation had occurred. Cytosolic phospholipase A2 protein was expressed throughout all stages of growth and differentiation. The cultures generated no 15-LO metabolites when incubated with 10 microM to 50 microM arachidonic acid (AA) and stimulated with ionophore. However, lysates prepared from such cultures generated 15-hydroxyeicosatetraenoic acid (15-HETE) and 12-HETE from AA, indicating that the cells contained active enzyme. When cultures expressing 15-LO protein were incubated with 10 microM linoleic acid (LA) instead of AA, and were stimulated with ionophore, they generated 13-hydroxy-9,11-octadecadienoic acid. LA rather than AA appeared to be the preferred substrate for the 15-LO enzyme. Our studies indicated that the expression of 15-LO and PGHS-2 is differentiation dependent in airway epithelial cells. JF - American journal of respiratory cell and molecular biology AU - Hill, E M AU - Eling, T AU - Nettesheim, P AD - Laboratories of Molecular Carcinogenesis and Pulmonary Pathobiology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA. Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 662 EP - 669 VL - 18 IS - 5 SN - 1044-1549, 1044-1549 KW - Antithrombins KW - 0 KW - Hydroxyeicosatetraenoic Acids KW - Isoenzymes KW - Linoleic Acids KW - Retinoids KW - Arachidonic Acid KW - 27YG812J1I KW - 13-hydroxy-9,11-octadecadienoic acid KW - 5204-88-6 KW - 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid KW - 59985-28-3 KW - 15-hydroxy-5,8,11,13-eicosatetraenoic acid KW - 73945-47-8 KW - Linoleic Acid KW - 9KJL21T0QJ KW - Arachidonate 15-Lipoxygenase KW - EC 1.13.11.33 KW - Prostaglandin-Endoperoxide Synthases KW - EC 1.14.99.1 KW - Phospholipases A KW - EC 3.1.1.32 KW - Phospholipases A2 KW - EC 3.1.1.4 KW - Index Medicus KW - 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid -- genetics KW - Linoleic Acids -- genetics KW - Arachidonic Acid -- pharmacology KW - Cytosol -- enzymology KW - Humans KW - Cell Differentiation -- genetics KW - Retinoids -- pharmacology KW - Chromatography, High Pressure Liquid KW - Antithrombins -- genetics KW - Hydroxyeicosatetraenoic Acids -- genetics KW - Phospholipases A -- genetics KW - Cells, Cultured KW - Gene Expression Regulation, Enzymologic -- drug effects KW - Cilia -- enzymology KW - Gene Expression Regulation, Enzymologic -- physiology KW - Mucous Membrane -- cytology KW - Linoleic Acid -- pharmacology KW - Isoenzymes -- analysis KW - Epithelial Cells -- cytology KW - Epithelial Cells -- enzymology KW - Bronchi -- cytology KW - Arachidonate 15-Lipoxygenase -- genetics KW - Prostaglandin-Endoperoxide Synthases -- genetics KW - Prostaglandin-Endoperoxide Synthases -- analysis KW - Trachea -- cytology KW - Arachidonate 15-Lipoxygenase -- analysis KW - Isoenzymes -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79845185?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+respiratory+cell+and+molecular+biology&rft.atitle=Changes+in+expression+of+15-lipoxygenase+and+prostaglandin-H+synthase+during+differentiation+of+human+tracheobronchial+epithelial+cells.&rft.au=Hill%2C+E+M%3BEling%2C+T%3BNettesheim%2C+P&rft.aulast=Hill&rft.aufirst=E&rft.date=1998-05-01&rft.volume=18&rft.issue=5&rft.spage=662&rft.isbn=&rft.btitle=&rft.title=American+journal+of+respiratory+cell+and+molecular+biology&rft.issn=10441549&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-06-04 N1 - Date created - 1998-06-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dissociation kinetics of RecA protein-three-stranded DNA complexes reveals a low fidelity of RecA-assisted recognition of homology. AN - 79840204; 9571054 AB - We determined that the incorporation of one mismatch into RecA mediated synaptic complexes between oligonucleotide single-stranded DNAs and target duplex DNAs destabilizes the complex by 0.8 to 1.9 kcal/mol. This finding supports our previous result, that RecA binding per se can significantly decrease the loss in free energy associated with mismatch incorporation even in the absence of ATP hydrolysis. We show that the specificity is mostly driven by the dissociation process. We found that the relative destabilization induced by different mismatches depends on their position. Thus, while there is a good correlation between the ranking order of mismatches at the 5' end of synaptic complexes and mismatches in heteroduplexes (D-loops), there is no correlation between the ranking order for mismatches at the 3' end and mismatches in various DNA structures. This difference between the 5' and 3' ends of synaptic complexes agrees well with the established 5' to 3' polarity of the strand exchange promoted by RecA protein. The lack of a correlation between mismatches at the 3' end of synaptic complexes and mismatches in D-loops suggests the intermediate is probably not a canonical protein-free D-loop. Copyright 1998 Academic Press Limited. JF - Journal of molecular biology AU - Malkov, V A AU - Camerini-Otero, R D AD - Genetics and Biochemistry Branch, National Institutes of Health (NIDDK), Building 10 Room 9D15, Bethesda, MD, 20892, USA. Y1 - 1998/05/01/ PY - 1998 DA - 1998 May 01 SP - 317 EP - 330 VL - 278 IS - 2 SN - 0022-2836, 0022-2836 KW - Nucleic Acid Heteroduplexes KW - 0 KW - Oligonucleotides KW - DNA KW - 9007-49-2 KW - Rec A Recombinases KW - EC 2.7.7.- KW - Index Medicus KW - Plasmids -- metabolism KW - Kinetics KW - Oligonucleotides -- metabolism KW - Nucleic Acid Conformation KW - Mutagenesis KW - Rec A Recombinases -- genetics KW - DNA -- metabolism KW - Rec A Recombinases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79840204?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+molecular+biology&rft.atitle=Dissociation+kinetics+of+RecA+protein-three-stranded+DNA+complexes+reveals+a+low+fidelity+of+RecA-assisted+recognition+of+homology.&rft.au=Malkov%2C+V+A%3BCamerini-Otero%2C+R+D&rft.aulast=Malkov&rft.aufirst=V&rft.date=1998-05-01&rft.volume=278&rft.issue=2&rft.spage=317&rft.isbn=&rft.btitle=&rft.title=Journal+of+molecular+biology&rft.issn=00222836&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-06-30 N1 - Date created - 1998-06-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetic changes associated with primary Merkel cell carcinoma. AN - 79834798; 9576574 AB - Merkel cell carcinoma (MCC) is a malignant tumor of the skin with a well-established neuroendocrine phenotype but an unknown histogenetic origin. Cytogenetic and molecular studies have shown evidence for genetic changes on the distal portion of chromosome 1p in different tumors with well-established neuroendocrine origins, specifically neuroblastomas, malignant melanomas, and pheochromocytomas. Involvement of chromosome 1 in MCC recently has been demonstrated by cytogenetic analysis and analysis of loss of heterozygosity (LOH) in metastatic tumor tissue. We performed analysis of LOH of the distal portion of chromosome 1p in paraffin material of 10 primary MCCs after tissue microdissection, using the polymorphic markers D1S160, D1S243, D1S468, D1S1646, and D1S1598. Seven of 10 analyzed MCCs shared a distal deletion involving 1p35-36. None of the cases showed 1p involvement proximal to 1p35. The findings are similar to those described for malignant melanoma, pheochromocytoma, and neuroblastoma, tumors known to originate from neural crest cells. In conjunction with previous cytogenetic data, we conclude that Merkel cell carcinogenesis shares pathogenetic mechanisms with other neoplasms of neural crest derivation. JF - American journal of clinical pathology AU - Vortmeyer, A O AU - Merino, M J AU - Böni, R AU - Liotta, L A AU - Cavazzana, A AU - Zhuang, Z AD - Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 565 EP - 570 VL - 109 IS - 5 SN - 0002-9173, 0002-9173 KW - Abridged Index Medicus KW - Index Medicus KW - Chromosomes, Human, Pair 1 KW - Loss of Heterozygosity KW - Polymorphism, Genetic KW - Aged, 80 and over KW - Humans KW - Aged KW - Middle Aged KW - Male KW - Female KW - Gene Deletion KW - Skin Neoplasms -- genetics KW - Carcinoma, Merkel Cell -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79834798?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+clinical+pathology&rft.atitle=Genetic+changes+associated+with+primary+Merkel+cell+carcinoma.&rft.au=Vortmeyer%2C+A+O%3BMerino%2C+M+J%3BB%C3%B6ni%2C+R%3BLiotta%2C+L+A%3BCavazzana%2C+A%3BZhuang%2C+Z&rft.aulast=Vortmeyer&rft.aufirst=A&rft.date=1998-05-01&rft.volume=109&rft.issue=5&rft.spage=565&rft.isbn=&rft.btitle=&rft.title=American+journal+of+clinical+pathology&rft.issn=00029173&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-05-14 N1 - Date created - 1998-05-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Impaired aquaporin and urea transporter expression in rats with adriamycin-induced nephrotic syndrome. AN - 79834760; 9573539 AB - Nephrotic syndrome is associated with abnormal regulation of renal water excretion. To investigate the role of collecting duct water channels and solute transporters in this process, we have carried out semiquantitative immunoblotting of kidney tissues from rats with adriamycin-induced nephrotic syndrome. These experiments demonstrated that adriamycin-induced nephrotic syndrome is associated with marked decreases in expression of aquaporin-2, aquaporin-3, aquaporin-4, and the vasopressin-regulated urea transporter in renal inner medulla, indicative of a suppression of the capacity for water and urea absorption by the inner medullary collecting duct. In contrast, expression of the alpha(1)-subunit of the Na,K-ATPase in the inner medulla was unaltered. Light and electron microscopy of perfusion-fixed kidneys demonstrated that the collecting ducts are morphologically normal and unobstructed. Inner medullary expression of the descending limb water channel, aquaporin-1, was not significantly altered, pointing to a selective effect on the collecting duct. Aquaporin-2 and aquaporin-3 expression was also markedly diminished in the renal cortex, indicating that the effect is not limited to the inner medullary collecting duct. Differential centrifugation studies and immunocytochemistry in inner medullary thin sections demonstrated increased targeting of aquaporin-2 to the plasma membrane, consistent with the expected short-term action of vasopressin on aquaporin-2 trafficking. The extensive down-regulation of aquaporin and urea transporter expression may represent an appropriate renal response to the extracellular volume expansion observed in nephrotic syndrome, but may occur at the expense of decreased urinary concentrating and diluting capacity. JF - Kidney international AU - Fernández-Llama, P AU - Andrews, P AU - Nielsen, S AU - Ecelbarger, C A AU - Knepper, M A AD - Laboratory of Kidney and Electrolyte Metabolism, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda Maryland, USA. Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 1244 EP - 1253 VL - 53 IS - 5 SN - 0085-2538, 0085-2538 KW - Aqp1 protein, rat KW - 0 KW - Aqp2 protein, rat KW - Aqp3 protein, rat KW - Aqp4 protein, rat KW - Aquaporin 2 KW - Aquaporin 4 KW - Aquaporin 6 KW - Aquaporins KW - Carrier Proteins KW - HSP70 Heat-Shock Proteins KW - Ion Channels KW - Membrane Glycoproteins KW - Membrane Transport Proteins KW - urea transporter KW - Aquaporin 1 KW - 146410-94-8 KW - Aquaporin 3 KW - 158801-98-0 KW - Doxorubicin KW - 80168379AG KW - Urea KW - 8W8T17847W KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - Adenylyl Cyclases KW - EC 4.6.1.1 KW - Index Medicus KW - Urea -- metabolism KW - Kidney Tubules, Collecting -- metabolism KW - Animals KW - HSP70 Heat-Shock Proteins -- metabolism KW - Kidney Medulla -- ultrastructure KW - Adenylyl Cyclases -- metabolism KW - Doxorubicin -- toxicity KW - Kidney Tubules, Collecting -- ultrastructure KW - Rats KW - Rats, Sprague-Dawley KW - Kidney Medulla -- metabolism KW - GTP-Binding Proteins -- metabolism KW - Microscopy, Electron KW - Immunohistochemistry KW - Male KW - Carrier Proteins -- metabolism KW - Nephrotic Syndrome -- metabolism KW - Nephrotic Syndrome -- chemically induced KW - Membrane Glycoproteins -- metabolism KW - Ion Channels -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79834760?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Impaired+aquaporin+and+urea+transporter+expression+in+rats+with+adriamycin-induced+nephrotic+syndrome.&rft.au=Fern%C3%A1ndez-Llama%2C+P%3BAndrews%2C+P%3BNielsen%2C+S%3BEcelbarger%2C+C+A%3BKnepper%2C+M+A&rft.aulast=Fern%C3%A1ndez-Llama&rft.aufirst=P&rft.date=1998-05-01&rft.volume=53&rft.issue=5&rft.spage=1244&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 - 1998-06-30 N1 - Date created - 1998-06-30 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Kidney Int. 1998 May;53(5):1417-8 [9573561] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Proteolytic inactivation of MAP-kinase-kinase by anthrax lethal factor. AN - 79827136; 9563949 AB - Anthrax lethal toxin, produced by the bacterium Bacillus anthracis, is the major cause of death in animals infected with anthrax. One component of this toxin, lethal factor (LF), is suspected to be a metalloprotease, but no physiological substrates have been identified. Here it is shown that LF is a protease that cleaves the amino terminus of mitogen-activated protein kinase kinases 1 and 2 (MAPKK1 and MAPKK2) and that this cleavage inactivates MAPKK1 and inhibits the MAPK signal transduction pathway. The identification of a cleavage site for LF may facilitate the development of LF inhibitors. JF - Science (New York, N.Y.) AU - Duesbery, N S AU - Webb, C P AU - Leppla, S H AU - Gordon, V M AU - Klimpel, K R AU - Copeland, T D AU - Ahn, N G AU - Oskarsson, M K AU - Fukasawa, K AU - Paull, K D AU - Vande Woude, G F AD - Advanced BioScience Laboratories-Basic Research Program, National Cancer Institute-Frederick Cancer Research and Development Center, Post Office Box B, Frederick, MD 21702. Y1 - 1998/05/01/ PY - 1998 DA - 1998 May 01 SP - 734 EP - 737 VL - 280 IS - 5364 SN - 0036-8075, 0036-8075 KW - Antigens, Bacterial KW - 0 KW - Bacterial Toxins KW - Enzyme Inhibitors KW - Myelin Basic Protein KW - Recombinant Fusion Proteins KW - anthrax toxin KW - MAP2K2 protein, human KW - EC 2.7.1.- KW - Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - Calcium-Calmodulin-Dependent Protein Kinases KW - EC 2.7.11.17 KW - MAP Kinase Kinase 1 KW - EC 2.7.12.2 KW - MAP Kinase Kinase 2 KW - MAP2K1 protein, human KW - Map2k1 protein, mouse KW - Mitogen-Activated Protein Kinase Kinases KW - Metalloendopeptidases KW - EC 3.4.24.- KW - Index Medicus KW - Animals KW - Calcium-Calmodulin-Dependent Protein Kinases -- metabolism KW - Enzyme Activation KW - Humans KW - Enzyme Inhibitors -- toxicity KW - Oocytes -- physiology KW - Mice KW - Binding Sites KW - Recombinant Fusion Proteins -- metabolism KW - Metalloendopeptidases -- toxicity KW - Xenopus laevis KW - Phosphorylation KW - Calcium-Calmodulin-Dependent Protein Kinases -- antagonists & inhibitors KW - Myelin Basic Protein -- metabolism KW - Cell Line, Transformed KW - Metalloendopeptidases -- metabolism KW - Signal Transduction KW - Sequence Deletion KW - Protein-Serine-Threonine Kinases -- chemistry KW - Protein-Serine-Threonine Kinases -- metabolism KW - Protein-Serine-Threonine Kinases -- genetics KW - Protein-Tyrosine Kinases -- metabolism KW - Protein-Serine-Threonine Kinases -- antagonists & inhibitors KW - Protein-Tyrosine Kinases -- antagonists & inhibitors KW - Protein-Tyrosine Kinases -- genetics KW - Bacterial Toxins -- metabolism KW - Bacterial Toxins -- toxicity KW - Bacillus anthracis -- enzymology KW - Protein-Tyrosine Kinases -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79827136?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Proteolytic+inactivation+of+MAP-kinase-kinase+by+anthrax+lethal+factor.&rft.au=Duesbery%2C+N+S%3BWebb%2C+C+P%3BLeppla%2C+S+H%3BGordon%2C+V+M%3BKlimpel%2C+K+R%3BCopeland%2C+T+D%3BAhn%2C+N+G%3BOskarsson%2C+M+K%3BFukasawa%2C+K%3BPaull%2C+K+D%3BVande+Woude%2C+G+F&rft.aulast=Duesbery&rft.aufirst=N&rft.date=1998-05-01&rft.volume=280&rft.issue=5364&rft.spage=734&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 - 1998-05-18 N1 - Date created - 1998-05-18 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Science. 1998 Jun 12;280(5370):1671, 1673-4 [9660700] Science. 1998 May 1;280(5364):676 [9599144] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Site-directed mutations in the vnd/NK-2 homeodomain. Basis of variations in structure and sequence-specific DNA binding. AN - 79822095; 9556579 AB - Secondary structures, DNA binding properties, and thermal denaturation behavior of six site-directed mutant homeodomains encoded by the vnd/NK-2 gene from Drosophila melanogaster are described. Three single site H52R, Y54M, and T56W mutations, two double site H52R/T56W and Y54M/T56W mutations, and one triple site H52R/Y54M/T56W mutation were investigated. These positions were chosen based on their variability across homeodomains displaying differences in secondary structure and DNA binding specificity. Multidimensional NMR, electrophoretic mobility shift assays, and circular dichroism spectropolarimetry studies were carried out on recombinant 80-amino acid residue proteins containing the homeodomain. Position 56, but more importantly position 56 in combination with position 52, plays an important role in determining the length of the recognition helix. The H52R mutation alone does not affect the length of this helix but does increase the thermal stability. Introduction of site mutations at positions 52 and 56 in vnd/NK-2 does not modify their high affinity binding to the 18-base pair DNA fragment containing the vnd/NK-2 consensus binding sequence, CAAGTG. Site mutations involving position 54 (Y54M, Y54M/T56W, and H52R/Y54M/T56W) all show a decrease of 1 order of magnitude in their binding affinity. The roles in structure and sequence specificity of individual atom-atom interactions are described. JF - The Journal of biological chemistry AU - Weiler, S AU - Gruschus, J M AU - Tsao, D H AU - Yu, L AU - Wang, L H AU - Nirenberg, M AU - Ferretti, J A AD - Laboratory of Biophysical Chemistry, NHLBI, National Institutes of Health, Bethesda, Maryland 20892-0380, USA. Y1 - 1998/05/01/ PY - 1998 DA - 1998 May 01 SP - 10994 EP - 11000 VL - 273 IS - 18 SN - 0021-9258, 0021-9258 KW - DNA-Binding Proteins KW - 0 KW - Drosophila Proteins KW - Homeodomain Proteins KW - Transcription Factors KW - vnd protein, Drosophila KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Animals KW - Protein Structure, Secondary KW - Drosophila melanogaster KW - Molecular Sequence Data KW - Circular Dichroism KW - Amino Acid Sequence KW - Protein Binding KW - Magnetic Resonance Spectroscopy KW - Homeodomain Proteins -- genetics KW - DNA-Binding Proteins -- chemistry KW - Homeodomain Proteins -- metabolism KW - DNA-Binding Proteins -- genetics KW - Homeodomain Proteins -- chemistry KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79822095?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Site-directed+mutations+in+the+vnd%2FNK-2+homeodomain.+Basis+of+variations+in+structure+and+sequence-specific+DNA+binding.&rft.au=Weiler%2C+S%3BGruschus%2C+J+M%3BTsao%2C+D+H%3BYu%2C+L%3BWang%2C+L+H%3BNirenberg%2C+M%3BFerretti%2C+J+A&rft.aulast=Weiler&rft.aufirst=S&rft.date=1998-05-01&rft.volume=273&rft.issue=18&rft.spage=10994&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 - 1998-06-02 N1 - Date created - 1998-06-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The N-terminal domain of IkappaB alpha masks the nuclear localization signal(s) of p50 and c-Rel homodimers. AN - 79820089; 9566883 AB - Members of the Rel/NF-kappaB family of transcription factors are related to each other over a region of about 300 amino acids called the Rel Homology Domain (RHD), which governs DNA binding, dimerization, and binding to inhibitor. At the C-terminal end of the RHD, each protein has a nuclear localization signal (NLS). The crystal structures of the p50 and RelA family members show that the RHD consists of two regions: an N-terminal section which contains some of the DNA contacts and a C-terminal section which contains the remaining DNA contacts and controls dimerization. In unstimulated cells, the homo- or heterodimeric Rel/NF-kappaB proteins are cytoplasmic by virtue of binding to an inhibitor protein (IkappaB) which somehow masks the NLS of each member of the dimer. The IkappaB proteins consist of an ankyrin-repeat-containing domain that is required for binding to dimers and N- and C-terminal domains that are dispensable for binding to most dimers. In this study, we examined the interaction between IkappaB alpha and Rel family homodimers by mutational analysis. We show that (i) the dimerization regions of p50, RelA, and c-Rel are sufficient for binding to IkappaB alpha, (ii) the NLSs of RelA and c-Rel are not required for binding to IkappaB alpha but do stabilize the interaction, (iii) the NLS of p50 is required for binding to IkappaB alpha, (iv) only certain residues within the p50 NLS are required for binding, and (v) in a p50-IkappaB alpha complex or a c-Rel-IkappaB alpha complex, the N terminus of IkappaB alpha either directly or indirectly masks one or both of the dimer NLSs. JF - Molecular and cellular biology AU - Latimer, M AU - Ernst, M K AU - Dunn, L L AU - Drutskaya, M AU - Rice, N R AD - Molecular Basis of Carcinogenesis Laboratory, ABL-Basic Research Program, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland 21701, USA. Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 2640 EP - 2649 VL - 18 IS - 5 SN - 0270-7306, 0270-7306 KW - DNA-Binding Proteins KW - 0 KW - I-kappa B Proteins KW - NF-kappa B KW - NF-kappa B p50 Subunit KW - NFKBIA protein, human KW - Nuclear Localization Signals KW - Proto-Oncogene Proteins KW - Proto-Oncogene Proteins c-rel KW - NF-KappaB Inhibitor alpha KW - 139874-52-5 KW - Index Medicus KW - Cytoplasm -- metabolism KW - Humans KW - Dimerization KW - Cell Compartmentation KW - Protein Binding KW - Mutation KW - Binding Sites KW - Proto-Oncogene Proteins -- metabolism KW - NF-kappa B -- genetics KW - NF-kappa B -- metabolism KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79820089?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+and+cellular+biology&rft.atitle=The+N-terminal+domain+of+IkappaB+alpha+masks+the+nuclear+localization+signal%28s%29+of+p50+and+c-Rel+homodimers.&rft.au=Latimer%2C+M%3BErnst%2C+M+K%3BDunn%2C+L+L%3BDrutskaya%2C+M%3BRice%2C+N+R&rft.aulast=Latimer&rft.aufirst=M&rft.date=1998-05-01&rft.volume=18&rft.issue=5&rft.spage=2640&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 - 1998-05-21 N1 - Date created - 1998-05-21 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Science. 1986 Oct 17;234(4774):364-8 [2876518] Nature. 1998 Jan 22;391(6665):410-3 [9450761] Mol Cell Biol. 1992 Sep;12(9):4067-75 [1508203] Genes Dev. 1992 Oct;6(10):1899-913 [1340770] Cell. 1992 Oct 16;71(2):243-53 [1423592] J Virol. 1993 Feb;67(2):832-42 [8419648] Mol Biol Cell. 1992 Dec;3(12):1339-52 [1493333] EMBO J. 1993 Jul;12(7):2781-8 [8334994] Proc Natl Acad Sci U S A. 1993 Oct 1;90(19):8962-6 [8415639] J Biol Chem. 1993 Oct 25;268(30):22703-9 [8226780] Gene Expr. 1993;3(2):135-50 [8268718] Proc Natl Acad Sci U S A. 1994 Jun 7;91(12):5350-4 [8202491] Mol Cell Biol. 1995 Feb;15(2):872-82 [7823953] Nature. 1995 Jan 26;373(6512):303-10 [7530332] Nature. 1995 Jan 26;373(6512):311-7 [7830764] Cell. 1995 Feb 24;80(4):573-82 [7867065] Science. 1995 Mar 10;267(5203):1485-8 [7878466] Mol Cell Biol. 1995 May;15(5):2809-18 [7739562] Mol Cell Biol. 1995 Jul;15(7):3627-34 [7791770] Adv Cancer Res. 1995;66:255-92 [7793317] EMBO J. 1995 Jun 15;14(12):2876-83 [7796813] Genes Dev. 1995 Jul 1;9(13):1586-97 [7628694] Mol Cell Biol. 1995 Oct;15(10):5339-45 [7565683] Proc Natl Acad Sci U S A. 1995 Oct 24;92(22):10242-6 [7479760] Mol Cell Biol. 1996 Mar;16(3):1103-14 [8622655] J Virol. 1996 May;70(5):3176-88 [8627798] Annu Rev Immunol. 1996;14:649-83 [8717528] J Virol. 1997 Apr;71(4):3161-7 [9060679] EMBO J. 1997 Mar 17;16(6):1413-26 [9135156] Nat Struct Biol. 1998 Jan;5(1):67-73 [9437432] Proc Natl Acad Sci U S A. 1992 May 15;89(10):4333-7 [1533932] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of matrix in an early postentry step in the human immunodeficiency virus type 1 life cycle. AN - 79810983; 9557701 AB - The matrix protein of human immunodeficiency virus type 1 (HIV-1) has been reported to play a crucial role in the targeting of the Gag polyprotein precursor to the plasma membrane and in the incorporation of viral envelope glycoproteins into budding virions. In this report, we present evidence that mutation of a highly conserved Leu at matrix amino acid 20 blocks or markedly delays virus replication in a range of cell types, including T-cell lines, primary human peripheral blood mononuclear cells, and monocyte-derived macrophages. These mutations do not impair virus assembly and release, RNA encapsidation, or envelope glycoprotein incorporation into virions but rather cause significant defects in an early step in the virus life cycle, as measured by single-cycle infectivity assays and the analysis of viral DNA synthesis early postinfection. This infectivity defect is independent of the type of envelope glycoprotein carried on mutant virions; similar results are obtained in pseudotyping experiments using wild-type or truncated HIV-1 envelope glycoproteins, the amphotropic murine leukemia virus envelope, or the vesicular stomatitis G protein. Intriguingly, matrix residue 20 mutations also increase the apparent binding of Gag to membrane, accelerate the kinetics of Gag processing, and induce defects in endogenous reverse transcriptase activity without affecting virion density or morphology. These results help elucidate the function of matrix in HIV-1 replication. JF - Journal of virology AU - Kiernan, R E AU - Ono, A AU - Englund, G AU - Freed, E O AD - Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-0460, USA. Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 4116 EP - 4126 VL - 72 IS - 5 SN - 0022-538X, 0022-538X KW - DNA, Viral KW - 0 KW - Gene Products, gag KW - HIV Envelope Protein gp41 KW - RNA, Viral KW - Viral Envelope Proteins KW - Viral Matrix Proteins KW - HIV Reverse Transcriptase KW - EC 2.7.7.49 KW - Index Medicus KW - AIDS/HIV KW - Virion KW - HeLa Cells KW - Humans KW - HIV Envelope Protein gp41 -- metabolism KW - Jurkat Cells KW - Amino Acid Sequence KW - Gene Products, gag -- metabolism KW - Mutagenesis, Site-Directed KW - DNA, Viral -- biosynthesis KW - Tumor Cells, Cultured KW - HIV Envelope Protein gp41 -- genetics KW - HIV Reverse Transcriptase -- metabolism KW - Molecular Sequence Data KW - Viral Envelope Proteins -- metabolism KW - Cell Membrane -- metabolism KW - RNA, Viral -- metabolism KW - HIV-1 -- metabolism KW - HIV-1 -- genetics KW - Viral Matrix Proteins -- genetics KW - Virus Replication -- physiology KW - HIV-1 -- physiology KW - Viral Matrix Proteins -- physiology KW - HIV-1 -- ultrastructure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79810983?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Role+of+matrix+in+an+early+postentry+step+in+the+human+immunodeficiency+virus+type+1+life+cycle.&rft.au=Kiernan%2C+R+E%3BOno%2C+A%3BEnglund%2C+G%3BFreed%2C+E+O&rft.aulast=Kiernan&rft.aufirst=R&rft.date=1998-05-01&rft.volume=72&rft.issue=5&rft.spage=4116&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 - 1998-05-20 N1 - Date created - 1998-05-20 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: EMBO J. 1996 Nov 1;15(21):5783-8 [8918455] J Virol. 1996 Dec;70(12):8540-8 [8970978] Proc Natl Acad Sci U S A. 1996 Apr 2;93(7):3099-104 [8610175] J Virol. 1996 May;70(5):2809-24 [8627755] J Virol. 1996 May;70(5):2963-73 [8627772] J Virol. 1996 Jun;70(6):3551-60 [8648689] J Virol. 1996 Aug;70(8):5297-305 [8764040] Virology. 1973 Dec;56(2):549-64 [4127970] J Mol Biol. 1982 Apr 15;156(3):609-31 [6288961] Virology. 1983 Oct 30;130(2):415-26 [6196908] J Virol. 1984 Mar;49(3):909-17 [6608006] J Virol. 1996 Dec;70(12):8645-52 [8970990] J Virol. 1996 Dec;70(12):8701-9 [8970997] Cell. 1997 Jan 24;88(2):171-3; discussion 173-4 [9008157] Virology. 1997 Feb 17;228(2):294-306 [9123837] J Virol. 1997 Jun;71(6):4409-18 [9151831] J Virol. 1997 Jul;71(7):5382-90 [9188609] J Virol. 1997 Aug;71(8):5871-7 [9223476] J Virol. 1997 Sep;71(9):6582-92 [9261380] J Virol. 1997 Sep;71(9):6973-81 [9261426] EMBO J. 1997 Aug 1;16(15):4531-9 [9303297] AIDS Res Hum Retroviruses. 1990 Jun;6(6):721-30 [2194551] Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):367-71 [8552640] J Virol. 1996 Feb;70(2):1016-26 [8551559] J Virol. 1986 Aug;59(2):284-91 [3016298] Virology. 1987 Jan;156(1):171-6 [3643678] Science. 1988 Jan 29;239(4839):487-91 [2448875] Annu Rev Cell Biol. 1988;4:611-47 [3058168] Proc Natl Acad Sci U S A. 1988 Dec;85(24):9580-4 [2849111] Nature. 1989 Aug 3;340(6232):397-400 [2666861] Proc Natl Acad Sci U S A. 1989 Aug;86(15):5781-5 [2788277] J Virol. 1989 Nov;63(11):4670-5 [2677400] Proc Natl Acad Sci U S A. 1990 Jan;87(2):523-7 [2405382] J Virol. 1991 Jan;65(1):162-9 [1845882] AIDS. 1991 Jun;5(6):617-37 [1652977] AIDS. 1991 Jun;5(6):639-54 [1883539] Proc Natl Acad Sci U S A. 1992 Jan 1;89(1):70-4 [1729720] J Virol. 1992 Apr;66(4):2232-9 [1548759] Virology. 1992 Jul;189(1):167-77 [1604808] J Virol. 1992 Aug;66(8):4893-900 [1378513] J Virol. 1992 Aug;66(8):4966-71 [1629961] J Virol. 1992 Aug;66(8):5067-74 [1378514] J Virol. 1992 Sep;66(9):5667-70 [1501299] J Virol. 1993 Jul;67(7):4264-73 [7685414] Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6125-9 [7687060] J Virol. 1993 Aug;67(8):4945-55 [8331734] J Virol. 1993 Aug;67(8):4972-80 [8331736] J Virol. 1993 Oct;67(10):6322-6 [8371360] J Virol. 1993 Nov;67(11):6387-94 [8411340] Nature. 1993 Oct 14;365(6447):666-9 [8105392] J Virol. 1994 Mar;68(3):1689-96 [8107229] J Virol. 1994 Apr;68(4):2503-12 [8139032] J Virol. 1994 Apr;68(4):2556-69 [8139035] Nature. 1994 May 12;369(6476):107-8 [8192816] Virology. 1994 Jun;201(2):349-55 [8184544] J Virol. 1994 Aug;68(8):5311-20 [8035531] Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):6992-6 [8041734] Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):7311-5 [8041786] J Virol. 1994 Oct;68(10):6644-54 [7521919] Proc Natl Acad Sci U S A. 1994 Sep 27;91(20):9564-8 [7937806] J Virol. 1994 Dec;68(12):8180-7 [7966609] Biochem Biophys Res Commun. 1994 Nov 15;204(3):1031-8 [7980574] J Virol. 1995 Mar;69(3):1984-9 [7853546] Virology. 1995 Feb 1;206(2):935-44 [7531918] Cell. 1995 Feb 10;80(3):379-88 [7859280] J Virol. 1995 May;69(5):2729-36 [7535863] J Virol. 1995 Jun;69(6):3824-30 [7745730] J Virol. 1995 Jun;69(6):3949-54 [7745752] J Virol. 1995 Jul;69(7):4053-9 [7539505] J Virol. 1995 Aug;69(8):5048-56 [7541845] Virology. 1995 Oct 1;212(2):451-7 [7571414] J Virol. 1995 Nov;69(11):6810-8 [7474093] Cell. 1995 Nov 17;83(4):569-76 [7585960] J Virol. 1996 Jan;70(1):341-51 [8523546] Proc Natl Acad Sci U S A. 1996 Oct 29;93(22):12519-24 [8901614] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phylogenetic and functional classification of mitogen- and stress-activated protein kinases. AN - 79809653; 9545468 AB - All currently sequenced stress-activated protein kinases (SAPKs), extracellular signal-regulated kinases (ERKs), and other mitogen-activated protein kinases (MAPKs) were analyzed by sequence alignment, phylogenetic tree construction, and three-dimensional structure modeling in order to classify members of the MAPK family. Based on this analysis the MAPK family was divided into three subgroups (SAPKs, ERKs, and MAPK3) that consist of at least nine subfamilies. Members of a given subfamily were exclusively from animals, plants, or yeast/fungi. A single signature sequence, [LIVM][TS]XX[LIVM]XT[RK][WY]YRXPX[LIVM] [LIVM], was identified that is characteristic for all MAPKs and sufficient to distinguish MAPKs from other members of the protein kinase superfamily. This signature sequence contains the phosphorylation site and is located on loop 12 of the three-dimensional structure of MAPKs. I also identified signature sequences that are characteristic for each of the nine subfamilies of MAPKs. By modeling the three-dimensional structure of three proteins for each MAPK subfamily based on the resolved atomic structures of rat ERK2 and murine p38, it is demonstrated that amino acids conserved in all MAPKs are located primarily in the center of the protein around the catalytic cleft. I conclude that these residues are important for maintaining proper folding into the gross structure common to all MAPKs. On the other hand, amino acids conserved in a given subfamily are located mainly in the periphery of MAPKs, indicating their possible importance for defining interactions with substrates, activators, and inhibitors. Within these subfamily-specific regions, amino acids were identified that represent unique residues occurring in only a single subfamily and their location was mapped in three-dimensional structure models. These unique residues are likely to be crucial for subfamily-specific interactions of MAPKs with substrates, inhibitors, or activators and, therefore, represent excellent targets for site-directed mutagenesis experiments. JF - Journal of molecular evolution AU - Kültz, D AD - Laboratory of Kidney and Electrolyte Metabolism, NHLBI, National Institutes of Health, 10 Center Drive, MSC 1603, Building 10/Room 6N260, Bethesda, MD 20892-1603, USA. kultzd@gwgate.nhlbi.nih.gov Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 571 EP - 588 VL - 46 IS - 5 SN - 0022-2844, 0022-2844 KW - Calcium-Calmodulin-Dependent Protein Kinases KW - EC 2.7.11.17 KW - Index Medicus KW - Rats KW - Animals KW - Sequence Alignment KW - Conserved Sequence KW - Models, Molecular KW - Molecular Sequence Data KW - Mice KW - Amino Acid Sequence KW - Protein Conformation KW - Mutagenesis KW - Phylogeny KW - Calcium-Calmodulin-Dependent Protein Kinases -- physiology KW - Calcium-Calmodulin-Dependent Protein Kinases -- chemistry KW - Calcium-Calmodulin-Dependent Protein Kinases -- classification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79809653?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Phylogenetic+and+functional+classification+of+mitogen-+and+stress-activated+protein+kinases.&rft.au=K%C3%BCltz%2C+D&rft.aulast=K%C3%BCltz&rft.aufirst=D&rft.date=1998-05-01&rft.volume=46&rft.issue=5&rft.spage=571&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 - 1998-05-29 N1 - Date created - 1998-05-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Efficient in vitro repair of 7-hydro-8-oxodeoxyguanosine by human cell extracts: involvement of multiple pathways. AN - 79807250; 9547279 AB - To investigate the repair of oxidative damage in DNA, we have established an in vitro assay utilizing human lymphoblastoid whole cell extracts and plasmid DNA damaged by exposure to methylene blue and visible light. This treatment has been shown to produce predominantly 7-hydro-8-oxodeoxyguanosine (8-oxodG) in double-stranded DNA at low levels of modification. DNA containing 1. 6 lesions per plasmid is substrate for efficient repair synthesis by cell extracts. The incorporation of dGMP is 2.7 +/- 0.5 times greater than the incorporation of dCMP, indicating an average repair patch of 3-4 nucleotides. Damage-specific nicking occurs within 15 min, while resynthesis is slower. The incorporation of dGMP increases linearly, while the incorporation of dCMP exhibits a distinct lag. Extracts from xeroderma pigmentosum (XP) complementation groups A and B exhibit 25 and 40%, respectively, of the incorporation of dCMP compared with normal extracts, but extracts from an XP-D cell line exhibit twice the activity. These data suggest that the efficient repair of 8-oxodG lesions observed in human cell extracts involves more than one pathway of base excision repair. JF - Nucleic acids research AU - Jaiswal, M AU - Lipinski, L J AU - Bohr, V A AU - Mazur, S J AD - Laboratory of Molecular Genetics, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA. Y1 - 1998/05/01/ PY - 1998 DA - 1998 May 01 SP - 2184 EP - 2191 VL - 26 IS - 9 SN - 0305-1048, 0305-1048 KW - Deoxyguanine Nucleotides KW - 0 KW - Radiation-Sensitizing Agents KW - Deoxycytidine Monophosphate KW - 1032-65-1 KW - 2'-deoxyguanosine 5'-phosphate KW - 7EAM4TG712 KW - 8-oxo-7-hydrodeoxyguanosine KW - 88847-89-6 KW - Deoxyguanosine KW - G9481N71RO KW - Methylene Blue KW - T42P99266K KW - Index Medicus KW - DNA Damage KW - Humans KW - Hematopoietic Stem Cells -- cytology KW - Xeroderma Pigmentosum -- metabolism KW - Dose-Response Relationship, Radiation KW - Deoxycytidine Monophosphate -- metabolism KW - Deoxyguanine Nucleotides -- metabolism KW - Cockayne Syndrome -- metabolism KW - Lymphocytes -- radiation effects KW - Light KW - Lymphocytes -- cytology KW - Subcellular Fractions -- metabolism KW - Hematopoietic Stem Cells -- radiation effects KW - Cell Line KW - Cell-Free System KW - DNA Repair -- radiation effects KW - Deoxyguanosine -- metabolism KW - Deoxyguanosine -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79807250?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Efficient+in+vitro+repair+of+7-hydro-8-oxodeoxyguanosine+by+human+cell+extracts%3A+involvement+of+multiple+pathways.&rft.au=Jaiswal%2C+M%3BLipinski%2C+L+J%3BBohr%2C+V+A%3BMazur%2C+S+J&rft.aulast=Jaiswal&rft.aufirst=M&rft.date=1998-05-01&rft.volume=26&rft.issue=9&rft.spage=2184&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 - 1998-06-16 N1 - Date created - 1998-06-16 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Mol Cell Biol. 1989 Sep;9(9):3750-7 [2779565] J Biol Chem. 1997 Oct 24;272(43):27338-44 [9341184] Biochemistry. 1990 Jul 31;29(30):7024-32 [2223758] J Bacteriol. 1991 Jun;173(11):3419-24 [1710617] Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):4690-4 [2052552] Biochemistry. 1992 Jan 14;31(1):106-10 [1731864] Mol Cell Biol. 1992 Apr;12(4):1605-12 [1549115] Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):6866-70 [1495976] Mutat Res. 1992 Sep;275(3-6):331-42 [1383774] Nucleic Acids Res. 1992 Sep 11;20(17):4437-43 [1408745] J Biol Chem. 1993 Mar 5;268(7):4839-47 [8444862] Cancer Res. 1974 Dec;34(12):3318-25 [4371955] J Biol Chem. 1983 Aug 25;258(16):9990-4 [6411709] Arch Biochem Biophys. 1989 Aug 15;273(1):106-11 [2502945] Nature. 1993 Apr 22;362(6422):709-15 [8469282] Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6335-9 [8327515] J Biol Chem. 1993 Sep 15;268(26):19416-21 [8366089] Proc Natl Acad Sci U S A. 1993 Sep 1;90(17):7915-22 [8367443] Proc Natl Acad Sci U S A. 1993 Oct 1;90(19):8901-4 [8415629] Proc Natl Acad Sci U S A. 1993 Nov 15;90(22):10499-503 [8248136] Biochim Biophys Acta. 1994 Jan 18;1217(1):9-15 [8286420] Mol Cell Biol. 1994 Sep;14(9):6187-97 [7915006] Annu Rev Biochem. 1994;63:915-48 [7979257] J Invest Dermatol. 1995 Jan;104(1):68-73 [7798643] Proc Natl Acad Sci U S A. 1995 Jan 31;92(3):719-23 [7846041] Biochemistry. 1995 Apr 18;34(15):5011-7 [7711023] Chem Res Toxicol. 1995 Apr-May;8(3):379-88 [7578924] Nucleic Acids Res. 1996 Apr 15;24(8):1389-94 [8628669] J Biol Chem. 1996 Apr 19;271(16):9573-8 [8621631] EMBO J. 1996 May 1;15(9):2306-12 [8641296] Proc Natl Acad Sci U S A. 1996 May 28;93(11):5197-202 [8643552] Curr Biol. 1996 Aug 1;6(8):968-80 [8805338] Mutat Res. 1996 Dec 2;364(3):183-92 [8960130] Science. 1997 Feb 14;275(5302):990-3 [9020084] Carcinogenesis. 1997 Apr;18(4):605-10 [9111189] Proc Natl Acad Sci U S A. 1997 Apr 29;94(9):4306-11 [9113985] Proc Natl Acad Sci U S A. 1997 Jul 8;94(14):7429-34 [9207108] EMBO J. 1997 Jun 2;16(11):3341-8 [9214649] Proc Natl Acad Sci U S A. 1997 Jul 22;94(15):8010-5 [9223305] Proc Natl Acad Sci U S A. 1997 Jul 22;94(15):8016-20 [9223306] Proc Natl Acad Sci U S A. 1997 Aug 19;94(17):9463-8 [9256505] J Biol Chem. 1997 Aug 8;272(32):19633-6 [9289489] Biochemistry. 1989 Nov 28;28(24):9515-20 [2482074] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The utility of monitoring carcinoembyronic antigen during systemic therapy for advanced colorectal cancer. AN - 79788559; 9538153 AB - To determine if pre-treatment serum carcinoembryonic antigen (CEA) levels or changes in CEA values during treatment have prognostic value, we reviewed five prior fluorouracil/leucovorin-based trials and identified 125 colorectal cancer patients with no prior chemotherapy for metastatic disease in whom CEA values were available. Although pre-treatment serum CEA values did not predict for clinical response or time to progression, serial monitoring of CEA appeared to be useful in patients with an elevated pre-treatment CEA, particularly when a decrease in CEA occurred in concert with radiographic evidence of disease response. The CEA nadir was a strong prognostic variable with respect to time to disease progression. A consistent rise in CEA values over the minimum value signals the need for radiographic re-assessment of the patient's disease status to rule out disease progression. JF - Oncology reports AU - Grem, J L AU - Steinberg, S M AU - Chen, A P AU - McAtee, N AU - Cullen, E AU - Hamilton, J M AU - Allegra, C J AD - NCI-Medicine Branch, NNMC, Building 8, Room 5101, 8901 Wisconsin Ave., Bethesda, MD, 20889-5105, USA. PY - 1998 SP - 559 EP - 567 VL - 5 IS - 3 SN - 1021-335X, 1021-335X KW - Antidotes KW - 0 KW - Antimetabolites, Antineoplastic KW - Carcinoembryonic Antigen KW - Leucovorin KW - Q573I9DVLP KW - Fluorouracil KW - U3P01618RT KW - Index Medicus KW - Sensitivity and Specificity KW - Antidotes -- administration & dosage KW - Humans KW - Leucovorin -- administration & dosage KW - Retrospective Studies KW - Prognosis KW - Clinical Trials as Topic KW - Disease Progression KW - Aged KW - Fluorouracil -- therapeutic use KW - Adult KW - Middle Aged KW - Antimetabolites, Antineoplastic -- therapeutic use KW - Female KW - Male KW - Survival Analysis KW - Rectal Neoplasms -- drug therapy KW - Rectal Neoplasms -- blood KW - Colonic Neoplasms -- drug therapy KW - Rectal Neoplasms -- pathology KW - Carcinoembryonic Antigen -- blood KW - Colonic Neoplasms -- pathology KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Colonic Neoplasms -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79788559?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+reports&rft.atitle=The+utility+of+monitoring+carcinoembyronic+antigen+during+systemic+therapy+for+advanced+colorectal+cancer.&rft.au=Grem%2C+J+L%3BSteinberg%2C+S+M%3BChen%2C+A+P%3BMcAtee%2C+N%3BCullen%2C+E%3BHamilton%2C+J+M%3BAllegra%2C+C+J&rft.aulast=Grem&rft.aufirst=J&rft.date=1998-05-01&rft.volume=5&rft.issue=3&rft.spage=559&rft.isbn=&rft.btitle=&rft.title=Oncology+reports&rft.issn=1021335X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-05-01 N1 - Date created - 1998-05-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The role of transforming growth factor-beta1, -beta2, and -beta3 in androgen-responsive growth of NRP-152 rat prostatic epithelial cells. AN - 79756886; 9525477 AB - We have investigated the role of autocrine/paracrine TGF-beta secretion in the regulation of cell growth by androgens as demonstrated by its inhibition by two androgen response modifiers; the nonsteroidal antiandrogen hydroxyflutamide (OHF), believed to act by inhibiting androgen binding to androgen receptors, or finasteride, an inhibitor of 5alpha-reductase, the enzyme necessary for the conversion of testosterone to 5alpha-dihydrotestosterone (DHT), using the nontumorigenic rat prostatic epithelial cell line NRP-152. Growth of these cells was stimulated three- to sixfold over control by either testosterone or DHT under serum-free culture conditions. This was accompanied by a two- to threefold decrease in the secretion rate of TGF-beta1, -beta2, and -beta3. Finasteride reversed the ability of testosterone but not DHT to stimulate growth and downregulate expression of TGF-beta1, -beta2, and -beta3 in a dose-dependent fashion, suggesting that this activity of testosterone required its conversion to DHT. OHF antagonized the stimulatory effects of DHT on NRP-152 cell growth but could reverse the inhibitory effects of DHT only on TGF-beta2 and TGF-beta3 and not TGF-beta1 secretion. This suggests that either TGF-beta1 regulation by DHT or the androgen antagonism of OHF occurs independent of androgen receptor binding. Neutralizing antibodies to TGF-beta (pantropic and isoform-specific) were able to block the ability of finasteride to antagonize the effects of testosterone nearly completely while only partially inhibiting the antiandrogenic effects of OHF. Thus, the ability of androgens to stimulate growth of NRP-152 cells involves the downregulation of the production of TGF-beta1, -beta2, and -beta3 in addition to other growth-stimulatory mechanisms. JF - Journal of cellular physiology AU - Lucia, M S AU - Sporn, M B AU - Roberts, A B AU - Stewart, L V AU - Danielpour, D AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 184 EP - 192 VL - 175 IS - 2 SN - 0021-9541, 0021-9541 KW - Androgen Antagonists KW - 0 KW - Androgens KW - Antibodies KW - Transforming Growth Factor beta KW - Dihydrotestosterone KW - 08J2K08A3Y KW - hydroxyflutamide KW - 31D90UKP5Y KW - Testosterone KW - 3XMK78S47O KW - Finasteride KW - 57GNO57U7G KW - Flutamide KW - 76W6J0943E KW - Index Medicus KW - Animals KW - Antibodies -- immunology KW - Androgen Antagonists -- pharmacology KW - Finasteride -- pharmacology KW - Testosterone -- antagonists & inhibitors KW - Rats KW - Flutamide -- analogs & derivatives KW - Testosterone -- pharmacology KW - Dihydrotestosterone -- antagonists & inhibitors KW - Down-Regulation -- physiology KW - Dihydrotestosterone -- pharmacology KW - Antibodies -- pharmacology KW - Flutamide -- pharmacology KW - Cell Line KW - Male KW - Prostate -- drug effects KW - Cell Division -- drug effects KW - Androgens -- pharmacology KW - Transforming Growth Factor beta -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79756886?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+role+of+transforming+growth+factor-beta1%2C+-beta2%2C+and+-beta3+in+androgen-responsive+growth+of+NRP-152+rat+prostatic+epithelial+cells.&rft.au=Lucia%2C+M+S%3BSporn%2C+M+B%3BRoberts%2C+A+B%3BStewart%2C+L+V%3BDanielpour%2C+D&rft.aulast=Lucia&rft.aufirst=M&rft.date=1998-05-01&rft.volume=175&rft.issue=2&rft.spage=184&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 - 1998-04-16 N1 - Date created - 1998-04-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - [Frequency of lumbago in a cohort of nursing students]. TT - Frequenza della lombalgia in una coorte di allievi infermieri. AN - 73914734; 9734194 AB - The etiology and frequency of low back pain among health care personnel have been widely studied by means of cross sectional studies. The aim of our study was to calculate low back pain incidence in a prospective cohort of nursing students. A population of 344 subjects (72 males and 272 females) was involved in this investigation. Every student was submitted to a clinical and functional examination of the spine before beginning training and was checked in two following steps by a specific questionnaire for epidemiological studies of spinal disorders in working communities. 197 subjects (57.3%)(41 males and 156 females) completed follow-up. The low back pain incidence was similar at the end of two exposure periods (12.1% and 13.1%). The cumulative incidence was 22.5% throughout the study period. The longitudinal study allowed good control of selection bias and confounding factors; more over it showed that compared to other measurements of occurrence the cumulative incidence was between other occurrence measures, more informative, in our case, than prevalence and incidence rates. A cumulative incidence of low back pain over 20% after only two years of exposure in a young and healthy population of nursing students, requires implementation of ergonomic measures for patient handling tasks. JF - La Medicina del lavoro AU - Baldasseroni, A AU - Tartaglia, R AU - Sgarrella, C AU - Carnevale, F AD - U.O. Igiene e Salute nei Luoghi di Lavoro G. Pieraccini, Azienda Sanitaria di Firenze. PY - 1998 SP - 242 EP - 253 VL - 89 IS - 3 SN - 0025-7818, 0025-7818 KW - Index Medicus KW - Humans KW - Adult KW - Incidence KW - Middle Aged KW - Italy -- epidemiology KW - Longitudinal Studies KW - Male KW - Female KW - Students, Nursing -- statistics & numerical data KW - Low Back Pain -- epidemiology KW - Occupational Diseases -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73914734?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=La+Medicina+del+lavoro&rft.atitle=%5BFrequency+of+lumbago+in+a+cohort+of+nursing+students%5D.&rft.au=Baldasseroni%2C+A%3BTartaglia%2C+R%3BSgarrella%2C+C%3BCarnevale%2C+F&rft.aulast=Baldasseroni&rft.aufirst=A&rft.date=1998-05-01&rft.volume=89&rft.issue=3&rft.spage=242&rft.isbn=&rft.btitle=&rft.title=La+Medicina+del+lavoro&rft.issn=00257818&rft_id=info:doi/ LA - Italian DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-09-21 N1 - Date created - 1998-09-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Rearrangements of archetypal regulatory regions in JC virus genomes from urine. AN - 73855838; 9711540 AB - The regulatory region of progressive multifocal leukoencephalopathy-type JC virus (JCV) is rearranged in each host by a process of deletion and duplication. Of the more than 40 that have been examined, no two regulatory regions have been rearranged identically in the brain. The substrate for this rearrangement appears to be a highly stable archetypal regulatory region excreted in the urine. Its role as the transmissible form of the virus, although inferred, has never been proven. We have now amplified by PCR and cycle-sequenced the regulatory regions from 48 urinary strains of the virus. We find that the urinary form of the regulatory region is not entirely stable. Short deletions and duplications in the range of 2-16 bp were observed in seven of these strains. One of these, an inverted repeat, is a pattern of rearrangement not yet found in the brain. Two others (#208 and 230) showed a 2-bp deletion at position nos. 221 and 222, and an unusual mutation at position no. 219. These two urines were collected in different states of the USA at different times and analysed months apart. It is very unlikely that these unusual changes represent sample contamination or that they arose independently. This finding indicates that archetypal forms of the JCV regulatory region are infectious, despite their relative inactivity in tissue culture. While changes in the archetypal structure can be found, it is clear that rearrangements in the kidney are rare or rarely infectious. JF - Research in virology AU - Agostini, H T AU - Ryschkewitsch, C F AU - Stoner, G L AD - Neurotoxicology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. PY - 1998 SP - 163 EP - 170 VL - 149 IS - 3 SN - 0923-2516, 0923-2516 KW - DNA, Viral KW - 0 KW - Index Medicus KW - AIDS/HIV KW - Leukoencephalopathy, Progressive Multifocal -- virology KW - HIV Infections -- virology KW - HIV Infections -- urine KW - Humans KW - Leukoencephalopathy, Progressive Multifocal -- urine KW - Aged KW - Multiple Sclerosis -- urine KW - Polymerase Chain Reaction KW - Adult KW - Middle Aged KW - Multiple Sclerosis -- virology KW - Female KW - Male KW - Regulatory Sequences, Nucleic Acid KW - Tumor Virus Infections -- virology KW - JC Virus -- genetics KW - Papillomavirus Infections -- urine KW - Tumor Virus Infections -- urine KW - Recombination, Genetic KW - Papillomavirus Infections -- virology KW - DNA, Viral -- urine KW - DNA, Viral -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73855838?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Research+in+virology&rft.atitle=Rearrangements+of+archetypal+regulatory+regions+in+JC+virus+genomes+from+urine.&rft.au=Agostini%2C+H+T%3BRyschkewitsch%2C+C+F%3BStoner%2C+G+L&rft.aulast=Agostini&rft.aufirst=H&rft.date=1998-05-01&rft.volume=149&rft.issue=3&rft.spage=163&rft.isbn=&rft.btitle=&rft.title=Research+in+virology&rft.issn=09232516&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-10-20 N1 - Date created - 1998-10-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The effect of subcutaneous recombinant human erythropoietin (r-HuEPO) on anemia in cancer patients receiving platinum-based chemotherapy. AN - 70041409; 9813972 AB - Advanced cancer is commonly associated with significant anemia which worsens with the administration of cytotoxic drugs. Erythropoietin (EPO) levels in these patients are usually inappropriately low for the degree of anemia. We evaluated the effect of subcutaneous administration of recombinant human erythropoietin (r-HuEPO) on hematologic parameters and transfusion requirements in anemic cancer patients who were receiving platinum-based chemotherapy. Baseline studies included complete hemogram, reticulocyte count, serum iron, TIBC, ferritin and determination of performance status and quality of life (QOL). Twenty-three patients, 13 females, 10 males with mean age 52 years received 150 units/kg of r-HuEPO three times weekly for a minimum of 10 weeks. They also received supplemental iron. Ovarian cancer was the commonest underlying malignancy. Most of the patients received platinum-based combination chemotherapy. Mean duration of r-HuEPO therapy was 12.6 weeks. Average baseline reticulocyte count was 1.8% which increased to 7.0% after one week therapy. Eight patients had normalization of hemoglobin values. Another eight patients improved their hemoglobin by at least 2 g/dl, however, hemoglobin values remained below the normal range. Two patients had only slight increase in hemoglobin but never required blood transfusion. Three patients who were transfusion dependent had decrease in the transfusion requirements. Two patients had no significant benefit. In most patients response was evident within 2 weeks. All responders had improvement in QOL. No significant toxicity was observed. We conclude that r-HuEPO, given subcutaneously, is highly effective in amelioration of anemia and prevention of or reduction in transfusion requirements in cancer patients receiving platinum-based chemotherapy. JF - JPMA. The Journal of the Pakistan Medical Association AU - Malik, I A AU - Khan, Z K AU - Hakimali, A AU - Sabih, M AU - Rehman, G AD - National Cancer Institute, Clifton, Karachi. Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 127 EP - 131 VL - 48 IS - 5 SN - 0030-9982, 0030-9982 KW - Antineoplastic Agents KW - 0 KW - Hemoglobins KW - Recombinant Proteins KW - Erythropoietin KW - 11096-26-7 KW - Ferritins KW - 9007-73-2 KW - Iron KW - E1UOL152H7 KW - Cisplatin KW - Q20Q21Q62J KW - Index Medicus KW - Ferritins -- blood KW - Lung Neoplasms -- complications KW - Humans KW - Lung Neoplasms -- drug therapy KW - Quality of Life KW - Ovarian Neoplasms -- complications KW - Activities of Daily Living KW - Iron -- blood KW - Ovarian Neoplasms -- drug therapy KW - Hemoglobins -- analysis KW - Iron -- administration & dosage KW - Blood Transfusion KW - Injections, Subcutaneous KW - Reticulocyte Count KW - Middle Aged KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Male KW - Female KW - Iron -- therapeutic use KW - Neoplasms -- drug therapy KW - Erythropoietin -- blood KW - Neoplasms -- complications KW - Antineoplastic Agents -- administration & dosage KW - Anemia -- blood KW - Erythropoietin -- administration & dosage KW - Erythropoietin -- therapeutic use KW - Anemia -- drug therapy KW - Anemia -- etiology KW - Cisplatin -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70041409?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=JPMA.+The+Journal+of+the+Pakistan+Medical+Association&rft.atitle=The+effect+of+subcutaneous+recombinant+human+erythropoietin+%28r-HuEPO%29+on+anemia+in+cancer+patients+receiving+platinum-based+chemotherapy.&rft.au=Malik%2C+I+A%3BKhan%2C+Z+K%3BHakimali%2C+A%3BSabih%2C+M%3BRehman%2C+G&rft.aulast=Malik&rft.aufirst=I&rft.date=1998-05-01&rft.volume=48&rft.issue=5&rft.spage=127&rft.isbn=&rft.btitle=&rft.title=JPMA.+The+Journal+of+the+Pakistan+Medical+Association&rft.issn=00309982&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-12-03 N1 - Date created - 1998-12-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of EGb 761 on fatty acid reincorporation during reperfusion following ischemia in the brain of the awake gerbil. AN - 69976099; 9778647 AB - Transient cerebral ischemia (5 min) releases unesterified fatty acids from membrane phospholipids, increasing brain concentrations of fatty acids for up to 1 h following reperfusion. To understand the reported anti-ischemic effect of Ginkgo biloba extract (EGb 761), we monitored its effect on brain fatty acid reincorporation in a gerbil-stroke model. Both common carotid arteries in awake gerbils were occluded for 5 min, followed by 5 min of reperfusion. Animals were infused intravenously with labeled arachidonic (AA) or palmitic acid (Pam), and rates of incorporation of unlabeled fatty acid from the brian acyl-CoA pool were calculated by the model of Robinson et al. (1992), using quantitative autoradiography and biochemical analysis of brain acyl-CoA. Animals were treated for 14 d with 50 or 150 mg/kg/d EGb 761 or vehicle. Ischemia-reperfusion had no effect on the rate of unlabeled Pam incorporation into brain phospholipids from palmitoyl-CoA; this rate also was unaffected by EGb 761. In contrast, ischemia-reperfusion increased the rate of incorporation of unlabeled AA from brain arachidonoyl-CoA by a factor of 2.3-3.3 compared with the control rate; this factor was further augmented to 3.6-5.0 by pretreatment with EGb 761. There is selective reincorporation of AA compared with Pam into brain phospholipids following ischemia. EGb 761 further accelerates AA reincorporation, potentially reducing neurotoxic effects of prolonged exposure of brain to high concentrations of AA and its metabolites. JF - Molecular and chemical neuropathology AU - Rabin, O AU - Drieu, K AU - Grange, E AU - Chang, M C AU - Rapoport, S I AU - Purdon, A D AD - Laboratory of Neurosciences, National Institutes on Aging, National Institutes of Health, Bethesda, MD 20892-1582, USA. Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 79 EP - 101 VL - 34 IS - 1 SN - 1044-7393, 1044-7393 KW - Fatty Acids KW - 0 KW - Flavonoids KW - Membrane Lipids KW - Neuroprotective Agents KW - Phospholipids KW - Plant Extracts KW - Ginkgo biloba extract KW - 19FUJ2C58T KW - Arachidonic Acid KW - 27YG812J1I KW - Palmitic Acid KW - 2V16EO95H1 KW - Index Medicus KW - Gerbillinae KW - Animals KW - Palmitic Acid -- metabolism KW - Wakefulness KW - Male KW - Arachidonic Acid -- metabolism KW - Reperfusion Injury -- metabolism KW - Ischemic Attack, Transient -- metabolism KW - Reperfusion Injury -- prevention & control KW - Plants, Medicinal KW - Brain Chemistry -- drug effects KW - Phospholipids -- metabolism KW - Membrane Lipids -- metabolism KW - Neuroprotective Agents -- therapeutic use KW - Ginkgo biloba -- chemistry KW - Ischemic Attack, Transient -- drug therapy KW - Neuroprotective Agents -- pharmacology KW - Fatty Acids -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69976099?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+chemical+neuropathology&rft.atitle=Effects+of+EGb+761+on+fatty+acid+reincorporation+during+reperfusion+following+ischemia+in+the+brain+of+the+awake+gerbil.&rft.au=Rabin%2C+O%3BDrieu%2C+K%3BGrange%2C+E%3BChang%2C+M+C%3BRapoport%2C+S+I%3BPurdon%2C+A+D&rft.aulast=Rabin&rft.aufirst=O&rft.date=1998-05-01&rft.volume=34&rft.issue=1&rft.spage=79&rft.isbn=&rft.btitle=&rft.title=Molecular+and+chemical+neuropathology&rft.issn=10447393&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-01-04 N1 - Date created - 1999-01-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Complete genome of a JC virus genotype type 6 from the brain of an African American with progressive multifocal leukoencephalopathy. AN - 69196518; 10195251 AB - The major genotypes of the human polyomavirus JC (JCV) include type 1 (European), type 2 (Asian), type 3 (African), and type 4 (United States). Here we report characterization of the complete genome of a genotype obtained from the brain of an African American with systemic lupus erythematosus (SLE) and progressive multifocal leukoencephalopathy (PML). DNA extracted from JCV-infected brain tissue was subjected to whole-genome polymerase chain reaction (PCR) amplification and direct cycle sequencing. Relations to other JCV genotypes and the predicted amino acid sequence were analyzed. This African-American type 6 strain (#601) differs from strains of all other genotypes in about 2% of its DNA sequence. The length of the total coding region of strain #601 is increased to 4855 bp by the insertion of a single nucleotide in the large T-antigen intron. This strain, originally placed with the type 2 group on the basis of its sequence in the VT-intergenic region, is very closely related to strains recently identified in the urine of individuals from Ghana, West Africa. This is the first example of an African JCV genotype identified in the brain of an African-American PML patient. The extent of sequence divergence of JCV type 6 suggests a split of type 6 strains before the separation of types 2 and 3. These findings confirm that distinctive African genotypes of JCV have been maintained in the African-American population and that they are capable of causing PML. JF - Journal of human virology AU - Agostini, H T AU - Ryschkewitsch, C F AU - Stoner, G L AD - Neurotoxicology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. PY - 1998 SP - 267 EP - 272 VL - 1 IS - 4 SN - 1090-9508, 1090-9508 KW - Index Medicus KW - Phylogeny KW - Genotype KW - Base Sequence KW - Humans KW - Adult KW - Molecular Sequence Data KW - African Americans KW - Female KW - Lupus Erythematosus, Systemic -- complications KW - Leukoencephalopathy, Progressive Multifocal -- virology KW - Leukoencephalopathy, Progressive Multifocal -- complications KW - Polyomavirus -- genetics KW - Genome, Viral KW - Brain -- virology KW - Polyomavirus -- isolation & purification KW - Lupus Erythematosus, Systemic -- virology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69196518?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+human+virology&rft.atitle=Complete+genome+of+a+JC+virus+genotype+type+6+from+the+brain+of+an+African+American+with+progressive+multifocal+leukoencephalopathy.&rft.au=Agostini%2C+H+T%3BRyschkewitsch%2C+C+F%3BStoner%2C+G+L&rft.aulast=Agostini&rft.aufirst=H&rft.date=1998-05-01&rft.volume=1&rft.issue=4&rft.spage=267&rft.isbn=&rft.btitle=&rft.title=Journal+of+human+virology&rft.issn=10909508&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-04-29 N1 - Date created - 1999-04-29 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF015538; GENBANK; AF015537 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Telephone Support Groups for HIV-Positive Mothers Whose Children Have Died of AIDS AN - 61445230; 199901455 AB - Describes a telephone support group for human immunodeficiency virus-positive (HIV+) mothers on the East Coast & in the Midwest whose children had died of acquired immune deficiency syndrome (AIDS), 1990-1992. The 12-session support group aimed to help participants counterbalance the impact of grief, confront the reality of death, bring feelings into the open, make use of available resources, acknowledge their own health care needs, find release from guilt & regrets through forgiveness, maintain a sense of inner integration, redefine the self, keep communication channels open in the family, assist the family's other children with their grief, & grant permission to cease grieving. This psychotherapeutic modality is recommended to all social workers involved in the HIV epidemic as a practical & cost-effective means of reaching people who may not be geographically or emotionally able to attend in-person groups. 11 References. M. Greenberg JF - Social Work AU - Wiener, Lori S AD - Pediatric HIV Psychosocial Support Program National Cancer Instit National Instits Health, Bethesda MD wienerl@pbmac.nci.nih.gov Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 279 EP - 285 VL - 43 IS - 3 SN - 0037-8046, 0037-8046 KW - Death KW - Psychotherapy KW - Mothers KW - Acquired Immune Deficiency Syndrome KW - Self Help Groups KW - Children KW - Telephone Communications KW - article KW - 6123: social welfare UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/61445230?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Asocialservices&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Social+Work&rft.atitle=Telephone+Support+Groups+for+HIV-Positive+Mothers+Whose+Children+Have+Died+of+AIDS&rft.au=Wiener%2C+Lori+S&rft.aulast=Wiener&rft.aufirst=Lori&rft.date=1998-05-01&rft.volume=43&rft.issue=3&rft.spage=279&rft.isbn=&rft.btitle=&rft.title=Social+Work&rft.issn=00378046&rft_id=info:doi/ LA - English DB - Social Services Abstracts N1 - Date revised - 2007-05-01 N1 - Last updated - 2016-09-28 N1 - SubjectsTermNotLitGenreText - Acquired Immune Deficiency Syndrome; Mothers; Self Help Groups; Telephone Communications; Children; Death; Psychotherapy ER - TY - JOUR T1 - Dietary habits and stomach cancer in Shanghai, China AN - 17565975; 4352422 AB - Stomach cancer remains the second leading cancer in incidence in Shanghai, China, despite its decline over the past 2 decades. To clarify risk factors for this common malignancy, we conducted a population-based case-control study in Shanghai, China. Included in the study were 1,124 stomach cancer patients (age 20-69) newly diagnosed in 1988-1989 and 1,451 controls randomly selected among Shanghai residents. Usual adult dietary intake was assessed using a comprehensive food frequency questionnaire. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression models. Risks of stomach cancer were inversely associated with high consumption of several food groups, including fresh vegetables and fruits, poultry, eggs, plant oil, and some nutrients, such as protein, fat, fiber and antioxidant vitamins. By contrast, risks increased with increasing consumption of dietary carbohydrates, with odds ratios (ORs) of 1.5 (95% confidence interval [CI] 1.1-2.1) and 1.9 (95% CI 1.3-2.9) in the highest quartile of intake among men (p for trend = 0.02) and women (p = 0.0007), respectively. Similar increases in risk were associated with frequent intake of noodles and bread in both men (p = 0.07) and women (p = 0.05) after further adjustment for fiber consumption. In addition, elevated risks were associated with frequent consumption of preserved, salty or fried foods, and hot soup/porridge, and with irregular meals, speed eating and binge eating. No major differences in risk were seen according to subsite (cardia vs. non-cardia). Our findings add to the evidence that diet plays a major role in stomach cancer risk and suggest the need for further evaluation of risks associated with carbohydrates and starchy foods as well as the mechanisms involved. JF - International Journal of Cancer AU - Ji, B-T AU - Chow, W-H AU - Yang, G AU - McLaughlin, J K AU - Zheng, W AU - Shu, X-O AU - Jin, F AU - Gao, R-N AU - Gao, Y-T AU - Fraumeni, JF Jr AD - National Cancer Institute, 6130 Executive Blvd, EPN 415, Rockville, MD 20852, USA, jib@epndce.nci.nih.gov Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 659 EP - 664 VL - 76 IS - 5 SN - 0020-7136, 0020-7136 KW - China, Shanghai KW - starch KW - stomach KW - Risk Abstracts; Health & Safety Science Abstracts KW - Risk assessment KW - Diets KW - Cancer KW - Public health KW - Carbohydrates KW - H 11000:Diseases/Injuries/Trauma KW - H 12000:Epidemiology and Public Health KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17565975?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+Journal+of+Cancer&rft.atitle=Dietary+habits+and+stomach+cancer+in+Shanghai%2C+China&rft.au=Ji%2C+B-T%3BChow%2C+W-H%3BYang%2C+G%3BMcLaughlin%2C+J+K%3BZheng%2C+W%3BShu%2C+X-O%3BJin%2C+F%3BGao%2C+R-N%3BGao%2C+Y-T%3BFraumeni%2C+JF+Jr&rft.aulast=Ji&rft.aufirst=B-T&rft.date=1998-05-01&rft.volume=76&rft.issue=5&rft.spage=659&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Cancer&rft.issn=00207136&rft_id=info:doi/10.1002%2F%28SICI%291097-0215%2819980529%2976%3A53.3.CO%3B2-M LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Cancer; Diets; Carbohydrates; Public health; Risk assessment DO - http://dx.doi.org/10.1002/(SICI)1097-0215(19980529)76:5<659::AID-IJC8>3.3.CO;2-M ER - TY - JOUR T1 - Evidence that childhood acute lymphoblastic leukemia is associated with an infectious agent linked to hygiene conditions AN - 17094384; 4406834 AB - The incidence of acute lymphoblastic leukemia (ALL) in children has shown temporal and geographic variation during the 20th century, with higher rates in developed nations appearing in the first half of the century, but with persisting low rates in developing nations. We sought to assess the relation of childhood ALL with hygiene conditions, an aspect of socioeconomic development affecting rates of exposure to infectious agents. Infection patterns for hepatitis A virus (HAV), an agent with a fecal-oral route of transmission, were used to indicate hygiene conditions in different populations, with emphasis on instructive United States and Japanese data. A catalytic model was fit to these data, estimating the HAV force of infection and age-specific seroprevalence rates over time. These analyses were used to assess the temporal relationship of changes in HAV infection rates to changes in childhood leukemia mortality and incidence rates. We observed an inverse relationship between HAV infection prevalence and rates of childhood leukemia. Further, decreases in the HAV force of infection in the United States and Japan appear to have preceded increases in childhood leukemia rates. We describe a model based on a putative leukemia-inducing agent with a change in infection rate over time correlated with that of HAV that describes well the temporal trends in childhood leukemia rates for White children in the US and for Japanese children. The data suggest that improved public hygiene conditions, as measured by decreased prevalence of HAV infection, are associated with higher childhood ALL incidence rates. The model that we present supports the plausibility of the hypothesis that decreased childhood exposure to a leukemia-inducing agent associated with hygiene conditions leads to higher rates of ALL in children by increasing the frequency of in utero transmission caused by primary infection during pregnancy (or by increasing the number of individuals infected in early infancy because of lack of protective maternal antibodies). JF - Cancer Causes & Control AU - Smith, MA AU - Simon, R AU - Strickler, H D AU - McQuillan, G AU - Ries, LAG AU - Linet AD - Cancer Therapy Evaluation Program, NCI, Rm. 741, EPN, Bethesda, MD 20892, USA Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 285 EP - 298 VL - 9 IS - 3 SN - 0957-5243, 0957-5243 KW - acute lymphatic leukemia KW - hepatitis A KW - hepatitis A virus KW - man KW - Toxicology Abstracts; Health & Safety Science Abstracts KW - Socioeconomics KW - Children KW - Pregnancy KW - Socio-economic aspects KW - Acute lymphatic leukemia KW - Hygiene KW - X 24240:Miscellaneous KW - H 11000:Diseases/Injuries/Trauma UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17094384?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Causes+%26+Control&rft.atitle=Evidence+that+childhood+acute+lymphoblastic+leukemia+is+associated+with+an+infectious+agent+linked+to+hygiene+conditions&rft.au=Smith%2C+MA%3BSimon%2C+R%3BStrickler%2C+H+D%3BMcQuillan%2C+G%3BRies%2C+LAG%3BLinet&rft.aulast=Smith&rft.aufirst=MA&rft.date=1998-05-01&rft.volume=9&rft.issue=3&rft.spage=285&rft.isbn=&rft.btitle=&rft.title=Cancer+Causes+%26+Control&rft.issn=09575243&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Children; Socioeconomics; Pregnancy; Hygiene; Acute lymphatic leukemia; Socio-economic aspects ER - TY - JOUR T1 - Risk factors for male breast cancer (United States) AN - 17091976; 4406832 AB - The etiology of male breast cancer is obscure, although an excess risk has been associated with Klinefelter syndrome, testicular disorders, benign breast disease including gynecomastia, use of exogenous estrogens, radiation, and a family history of male or female breast cancer. We conducted a case-control study to investigate risk factors further for breast cancer in men. Based on data from the 1986 National (United States) Mortality Followback Survey (NMFS) of almost 20,000 deceased adults (age 25 years or over), we compared information obtained from next-of-kin interviews of 178 men who died of breast cancer with that of 512 male controls who died of other causes. Information was obtained on selected demographic and other factors, including diet, exercise, occupation, height and weight, and use of tobacco and alcohol. Increased risks were found for men who were described by their next-of-kin as very overweight (odds ratio [OR] = 2.3, 95 percent confidence interval [CI] = 1.1-5.0). The risks associated with the three upper quartiles of body mass index (BMI) (wt/ht super(2)) were 1.3, 1.6, and 2.3, respectively, with a significant dose-response relationship (P < 0.01). An excess risk was also associated with limited exercise (OR = 1.3, CI = 0.8-2.0). Consumption of red meat was associated with an increased risk, and consumption of fruits and vegetables with a decreased risk, although the trends were not significant. No association was found for tobacco or alcohol use, but an excess risk was associated with higher levels of socioeconomic status (SES) (OR = 1.8, CI = 1.1-3.0). Our study suggests that obesity increases the risk of male breast cancer, possibly through hormonal mechanisms, while dietary factors, physical activity, and SES indicators also deserve further investigation. JF - Cancer Causes & Control AU - Hsing, A W AU - McLaughlin, J K AU - Cocco, P AU - Chien, HTC AU - Fraumeni, JF Jr AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6130 Executive Blvd., Room 443, Bethesda, MD 20892, USA Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 269 EP - 275 VL - 9 IS - 3 SN - 0957-5243, 0957-5243 KW - USA KW - males KW - obesity KW - physical activity KW - Risk Abstracts KW - Diets KW - Breast cancer KW - Socioeconomics KW - Cancer KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17091976?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Causes+%26+Control&rft.atitle=Risk+factors+for+male+breast+cancer+%28United+States%29&rft.au=Hsing%2C+A+W%3BMcLaughlin%2C+J+K%3BCocco%2C+P%3BChien%2C+HTC%3BFraumeni%2C+JF+Jr&rft.aulast=Hsing&rft.aufirst=A&rft.date=1998-05-01&rft.volume=9&rft.issue=3&rft.spage=269&rft.isbn=&rft.btitle=&rft.title=Cancer+Causes+%26+Control&rft.issn=09575243&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Diets; Socioeconomics; Breast cancer; Cancer ER - TY - JOUR T1 - Fertility problems and breast cancer risk in young women: a case-control study in the United States AN - 17091622; 4406838 AB - Late age at first birth and nulliparity are established risk factors for breast cancer, yet the extent to which fertility problems contribute to these associations remains largely unexplored. Here, we examine self-reported fertility problems as a risk factor for breast cancer in young women. We used a population-based case-control study of 2,173 cases and 1,990 controls aged 20 to 54 years in the United States. Structured in-person interviews were used to elicit detailed information on established and potential breast cancer risk factors. Information was collected on pregnancy details, including difficulties becoming pregnant or maintaining a pregnancy. Self-reported difficulty in becoming pregnant or maintaining a pregnancy was reported by 450 cases and 377 controls. Overall, there was little association between these fertility problems and risk of breast cancer (odds ratio [OR] = 1.05). Parity was associated with a decreased risk of breast cancer in women both with (OR = 0.71) and without (OR = 0.79) fertility problems. There was little evidence of an increased risk of breast cancer with later age at first full-term birth among women without fertility problems, but a relatively strong association among women with fertility problems. Among women with a first full-term birth at age 35 or older, fertility problems were associated with a twofold risk of breast cancer. Analyses of duration of unprotected sexual intercourse prior to first pregnancy as an alternative estimate of infertility produced similar results. JF - Cancer Causes & Control AU - Weiss, HA AU - Troisi, R AU - Rossing, MA AU - Brogan, D AU - Coates, R J AU - Gammon, MD AU - Potischman, N AU - Swanson, CA AU - Brinton, LA AD - Environmental Epidemiology Branch, National Cancer Institute, Executive Plaza North Rm. 443, 6130 Exec. Blvd., Bethesda, MD 20892-7374, USA Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 331 EP - 339 VL - 9 IS - 3 SN - 0957-5243, 0957-5243 KW - USA KW - Risk Abstracts KW - Fertility KW - Statistical analysis KW - Cancer KW - Pregnancy KW - Breast cancer KW - Females KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17091622?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Causes+%26+Control&rft.atitle=Fertility+problems+and+breast+cancer+risk+in+young+women%3A+a+case-control+study+in+the+United+States&rft.au=Weiss%2C+HA%3BTroisi%2C+R%3BRossing%2C+MA%3BBrogan%2C+D%3BCoates%2C+R+J%3BGammon%2C+MD%3BPotischman%2C+N%3BSwanson%2C+CA%3BBrinton%2C+LA&rft.aulast=Weiss&rft.aufirst=HA&rft.date=1998-05-01&rft.volume=9&rft.issue=3&rft.spage=331&rft.isbn=&rft.btitle=&rft.title=Cancer+Causes+%26+Control&rft.issn=09575243&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Pregnancy; Fertility; Breast cancer; Females; Statistical analysis; Cancer ER - TY - JOUR T1 - Molecular properties of ClpAP protease of Escherichia coli: ATP-dependent association of ClpA and ClpP AN - 16553522; 4372875 AB - The ClpAP protease from Escherichia coli consists of the ATP-binding regulatory component, ClpA (subunit M sub(r) 84 165), and the proteolytic component, ClpP (subunit M sub(r) 21 563). Our hydrodynamic studies demonstrate that the predominant forms of these proteins in solution correspond to those observed by electron microscopy. ClpP and proClpP(SA), which in electron micrographs appear to have subunits arranged in rings of seven subunits, were found by ultracentrifugation to have s sub(20,w) values of 12.2 and 13.2 S and molecular weights of 300 000 and 324 000 plus or minus 3000, respectively, indicating that the native form of each consists of two such rings. The two intact rings of ClpP were separated in the presence of greater than or equal to 0.1 M sulfate at low temperatures, suggesting that ring-ring contacts are polar in nature and more easily disrupted than subunit contacts within individual rings. Sedimentation equilibrium analysis indicated that ClpA purified without nucleotide exists as an equilibrium mixture of monomers and dimers with K sub(a) = (1.0 plus or minus 0.2) x 10 super(5) M super(-1) and that, upon addition of MgATP or adenosine 5'-O-(3-thiotriphosphate), ClpA subunits associated to a form with M sub(r) 505 000 plus or minus 5000, consistent with the hexameric structure seen by electron microscopy. Sedimentation velocity and gel-filtration analysis showed that the nucleotide-promoted hexamer of ClpA (s sub(20,w) = 17.2 S) binds tightly to ClpP producing species with s sub(20,w) values of 21 and 27 S (f/f sub(0) = 1.5 and 1.8, respectively), consistent with electron micrographs of ClpAP that show a single tetradecamer of ClpP associated with either one or two ClpA hexamers. Under assay conditions in the presence of ATP and Mg super(2+), the apparent dissociation constant of hexameric ClpA and tetradecameric ClpP was similar to 4 plus or minus 2 nM. By the method of continuous variation, the optimal ratio of ClpA to ClpP in the active complex was 2:1. The specific activities of limiting ClpA and ClpP determined in the presence of an excess of the other component indicated that the second molecule of ClpA provides very little additional activation of ClpP. JF - Biochemistry (Washington) AU - Maurizi, M R AU - Singh, S K AU - Thompson, M W AU - Kessel, M AU - Ginsburg, A AD - Laboratory of Cell Biology, National Cancer Institute, Bldg. 37, Room 1B09, Bethesda, MD 20892, USA Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 7778 EP - 7786 VL - 37 IS - 21 SN - 0006-2960, 0006-2960 KW - ClpA protein KW - ClpP protein KW - Microbiology Abstracts B: Bacteriology KW - Escherichia coli KW - Proteinase KW - J 02728:Enzymes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16553522?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemistry+%28Washington%29&rft.atitle=Molecular+properties+of+ClpAP+protease+of+Escherichia+coli%3A+ATP-dependent+association+of+ClpA+and+ClpP&rft.au=Maurizi%2C+M+R%3BSingh%2C+S+K%3BThompson%2C+M+W%3BKessel%2C+M%3BGinsburg%2C+A&rft.aulast=Maurizi&rft.aufirst=M&rft.date=1998-05-01&rft.volume=37&rft.issue=21&rft.spage=7778&rft.isbn=&rft.btitle=&rft.title=Biochemistry+%28Washington%29&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Proteinase ER - TY - JOUR T1 - Evaluating health risks from groundwater contaminants AN - 16547550; 4374996 AB - A method is proposed to evaluate changes in health risks from ground water drawn from specified locations in the subsurface as a result of the transport of contaminant chemicals from buried waste sites. To evaluate the health risk, a stochastic one-dimensional contaminant transport model is solved with Monte Carlo simulation. The risk at a specified location is equal to the number of times that contaminant concentrations exceed the health standard concentration divided by the number of iterations in the Monte Carlo simulation. The method is used on a simulated aquifer to demonstrate how health risks vary with time and location in the subsurface. JF - Journal of Environmental Engineering AU - Piver, W T AU - Duval, LA AU - Schreifer, JA AD - Nat. Inst. of Envir. Health Sci., Research Triangle Park, NC 27709, USA, piveriehs.nih.gov Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 475 EP - 479 VL - 124 IS - 5 SN - 0733-9372, 0733-9372 KW - Risk Abstracts; Health & Safety Science Abstracts; Pollution Abstracts; Water Resources Abstracts KW - Risk assessment KW - Aquifers KW - Spatial distribution KW - Contamination KW - Environmental health KW - Public health KW - Evaluation KW - Waste disposal sites KW - Monte carlo method KW - Temporal distribution KW - Simulation KW - Stochastic process KW - Risk KW - Chemical wastes KW - Groundwater pollution KW - Model studies KW - P 2000:FRESHWATER POLLUTION KW - SW 0840:Groundwater KW - SW 3030:Effects of pollution KW - R2 23060:Medical and environmental health KW - H 12000:Epidemiology and Public Health KW - P 6000:TOXICOLOGY AND HEALTH UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16547550?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Environmental+Engineering&rft.atitle=Evaluating+health+risks+from+groundwater+contaminants&rft.au=Piver%2C+W+T%3BDuval%2C+LA%3BSchreifer%2C+JA&rft.aulast=Piver&rft.aufirst=W&rft.date=1998-05-01&rft.volume=124&rft.issue=5&rft.spage=475&rft.isbn=&rft.btitle=&rft.title=Journal+of+Environmental+Engineering&rft.issn=07339372&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Aquifers; Risk assessment; Contamination; Spatial distribution; Temporal distribution; Waste disposal sites; Chemical wastes; Simulation; Groundwater pollution; Environmental health; Public health; Stochastic process; Evaluation; Risk; Monte carlo method; Model studies ER - TY - JOUR T1 - The immunogenicity of Haemophilus influenzae type b conjugate vaccines in children born to human immunodeficiency virus-infected women AN - 16525347; 4352055 AB - Background. Immunocompromise caused by HIV-1 infection increases the importance of receipt of routine childhood vaccines to prevent infections such as invasive Haemophilus influenzae type B (Hib) disease. The objectives of the study were to evaluate the immunogenicity of Hib conjugate vaccines among HIV-infected children according to clinical and immunologic disease progression as well as viral load. Methods. The concentration of antibody to polyribosylribitol phosphate (PRP) was measured at similar to 9 and 24 months of age in plasma specimens from children of HIV-infected women enrolled in the Women and Infants Transmission Study. Results. Among 227 children (35 HIV-infected, 192 uninfected) at the 9-month study visit who were known to have received age-appropriate immunization with CRM sub(197) mutant Corynebacterium diphtheriae protein-conjugated Hib vaccine, geometric mean antibody concentrations were lower among HIV-infected children (1.64 mu g/ml) than among uninfected children (2.70 mu g/ml), although the difference was not statistically significant. Anti-PRP antibody concentrations did not vary significantly among these HIV-infected children with predominantly mild-moderate disease progression according to clinical category, immunologic stage or viral load (P greater than or equal to 0.48). The proportion of children with antibody concentrations greater than or equal to 1.0 mu g/ml did not vary significantly according to HIV infection status (73% uninfected, 74% infected) or, if infected, clinical or immunologic disease progression or viral load. Similar results were obtained among 127 children (17 HIV-infected, 110 uninfected) eligible for analysis at the 24-month study visit. Changes in antibody concentrations over time (between 9 and 24 months of age) did not differ significantly among 10 HIV-infected as compared with 72 uninfected children (P = 0.81). Conclusions. These results suggest that HIV-infected children with predominantly mild-moderate disease progression respond reasonably well in terms of a quantitative antibody response to Hib conjugate vaccines during the first 2 years of life. Research to further characterize the immune response to Hib conjugate vaccines and to further delineate the "durability" of anti-PRP antibody concentrations beyond 2 years of life should be pursued. JF - Pediatric Infectious Disease Journal AU - Read, J S AU - Frasch, CE AU - Rich, K AU - Fitzgerald, G A AU - Clemens, J D AU - Pitt, J AU - Pelton, SI AU - Hanson, I C AU - Handelsman, E AU - Diaz, C AU - Fowler, M G AD - Pediatric, Adolescent, and Maternal (PAMA) Branch, National Institute of Child Health and Human Development, National Institutes of Health, Executive Building, Room 4B11F, 6100 Executive Boulevard MSC 7510, Bethesda, MD 20892-7510, USA, jr92o@nih.gov Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 391 EP - 397 VL - 17 IS - 5 SN - 0891-3668, 0891-3668 KW - HIV KW - Haemophilus influenzae type B disease KW - man KW - Virology & AIDS Abstracts; Microbiology Abstracts B: Bacteriology KW - J 02834:Vaccination and immunization KW - V 22003:AIDS: Immunological aspects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16525347?accountid=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=Pediatric+Infectious+Disease+Journal&rft.atitle=The+immunogenicity+of+Haemophilus+influenzae+type+b+conjugate+vaccines+in+children+born+to+human+immunodeficiency+virus-infected+women&rft.au=Read%2C+J+S%3BFrasch%2C+CE%3BRich%2C+K%3BFitzgerald%2C+G+A%3BClemens%2C+J+D%3BPitt%2C+J%3BPelton%2C+SI%3BHanson%2C+I+C%3BHandelsman%2C+E%3BDiaz%2C+C%3BFowler%2C+M+G&rft.aulast=Read&rft.aufirst=J&rft.date=1998-05-01&rft.volume=17&rft.issue=5&rft.spage=391&rft.isbn=&rft.btitle=&rft.title=Pediatric+Infectious+Disease+Journal&rft.issn=08913668&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Mutations affecting the alpha subunit of Bordetella pertussis RNA polymerase suppress growth inhibition conferred by short C-terminal deletions of the response regulator BvgA AN - 16524910; 4358056 AB - The effects of short deletions of the C terminus of the BvgA response regulator protein of the BvgAS two-component system were examined in Bordetella pertussis. When present as a single copy in the chromosome, deletions removing as few as two amino acids conferred a completely Bvg super(-) phenotype. When provided in trans, on the broad-host-range plasmid pRK290, under the control of the native bvgAS promoter, deletions of two or three amino acids conferred a profound growth inhibition which was dependent on the integrity and activity of the wild-type chromosomal bvgAS locus. It is proposed that this phenotype was the result of an inappropriate interaction of the mutant BvgA protein with the RNA polymerase enzyme, specifically the alpha subunit. Mutant strains in which this growth inhibition was relieved were isolated and characterized. Although most of the suppressor mutations affected either the mutant plasmid copy or the wild-type chromosomal bvg locus, three mutations which affected the alpha subunit of B. pertussis RNA polymerase were also isolated. Two of these resulted in increased levels of the alpha subunit, and one caused a substitution of glycine for the aspartic acid residue at position 171, in the N-terminal domain. All three mutations also resulted in a differential phenotype in that expression of fha was essentially normal, but expression of ptx was greatly reduced. JF - Journal of Bacteriology AU - Stibitz, S AD - Division of Bacterial Products, Center for Biologics Evaluation and Research, Food and Drug Administration, 8800 Rockville Pike, Bethesda, MD 20892, USA, stibitz@helix.nih.gov Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 2484 EP - 2492 VL - 180 IS - 9 SN - 0021-9193, 0021-9193 KW - BvgA protein KW - C-terminus KW - DNA-directed RNA polymerase KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - N 14721:RNA polymerases KW - J 02726:RNA and ribosomes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16524910?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Bacteriology&rft.atitle=Mutations+affecting+the+alpha+subunit+of+Bordetella+pertussis+RNA+polymerase+suppress+growth+inhibition+conferred+by+short+C-terminal+deletions+of+the+response+regulator+BvgA&rft.au=Stibitz%2C+S&rft.aulast=Stibitz&rft.aufirst=S&rft.date=1998-05-01&rft.volume=180&rft.issue=9&rft.spage=2484&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=00219193&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Targeting RNase L to human immunodeficiency virus RNA with 2-5A-antisense AN - 16520960; 4331051 AB - In an attempt to develop a lead for the application of 2-5A-antisense to the targeted destruction of human immunodeficiency virus (HIV) RNA, specific target sequences within the HIV mRNAs were identified by analysis of the theoretical secondary structure. 2-5A-antisense chimeras were chosen against a total of 11 different sequences: three in the gag mRNA, three in the rev mRNA and five in the tat mRNA. 2-5A-antisense chimera synthesis was accomplished using solid-phase phosphoramidite chemistry. These chimeras were evaluated for their activity in a cell-free assay system using purified recombinant human RNase L to effect cleavage of super(32)P-labelled RNA transcripts of plasmids derived from HIV NL4-3. This screening revealed that of the three 2-5A-antisense chimeras targeted against gag mRNA, only one had significant HIV RNA cleavage activity, approximately 10-fold-reduced compared to the parent 2-5A tetramer and comparable to that reported for the prototypical 2-5A-anti-PKR chimera, targeted against PKR mRNA. The cleavage activity of this chimera was specific, since a scrambled antisense domain chimera and a chimera without the key 5'-monophosphate moiety were both inactive. The 10 other 2-5A-antisense chimeras against tat and rev had significantly less activity. These results imply that HIV gag RNA, like PKR RNA and a model HIV tat-oligoA-vif RNA, can be cleaved using the 2-5A-antisense approach. The results further imply that not all regions of a potential RNA target are accessible to the 2-5A-antisense approach. JF - Antiviral Chemistry & Chemotherapy AU - Player, M R AU - Maitra, R K AU - Silverman, R H AU - Torrence, P F AD - Section on Biomedical Chemistry, Laboratory of Medicinal Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0805, USA, torrence@helix.nih.gov Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 225 EP - 231 VL - 9 IS - 3 SN - 0956-3202, 0956-3202 KW - Chimeras KW - HIV-1 KW - Human immunodeficiency virus 1 KW - chimeras KW - ribonuclease L KW - Biotechnology and Bioengineering Abstracts; Microbiology Abstracts A: Industrial & Applied Microbiology; Medical and Pharmaceutical Biotechnology Abstracts; Virology & AIDS Abstracts KW - A 01068:Antiviral & viricidal KW - W 30965:Miscellaneous, Reviews KW - V 22004:AIDS: Clinical aspects KW - W3 33380:Antisense UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16520960?accountid=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=Antiviral+Chemistry+%26+Chemotherapy&rft.atitle=Targeting+RNase+L+to+human+immunodeficiency+virus+RNA+with+2-5A-antisense&rft.au=Player%2C+M+R%3BMaitra%2C+R+K%3BSilverman%2C+R+H%3BTorrence%2C+P+F&rft.aulast=Player&rft.aufirst=M&rft.date=1998-05-01&rft.volume=9&rft.issue=3&rft.spage=225&rft.isbn=&rft.btitle=&rft.title=Antiviral+Chemistry+%26+Chemotherapy&rft.issn=09563202&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Maspin gene expression in tumor suppression induced by overexpressing manganese-containing superoxide dismutase cDNA in human breast cancer cells AN - 16517638; 4342357 AB - We have reported the tumor suppressive effects of manganese-containing superoxide dismutase (MnSOD) in human breast cancer cells. In order to understand the molecular mechanism of this anti-tumor effect, we asked whether tumor suppressor gene(s), especially the ones inhibiting tumor invasion and motility, are involved in MnSOD-induced tumor suppression. Maspin is one of the serpin family of protease inhibitors that has been shown to function as a tumor-suppressor in human breast epithelium. In the present study, we demonstrated that maspin expression was up-regulated in human breast cancer MCF-7 cells that overexpress a normal MnSOD gene. The induced maspin transcripts were detected by RT-PCR and Northern blot and identified by sequencing. Maspin gene expression was induced in parallel with the level of exogenous MnSOD protein, which was induced by transfection with varied amounts of cDNA. In order to analyze cell invasion ability, which may be related to the induced maspin gene expression, MnSOD stable transfectants were tested using a matrigel invasion chamber. The invasion ability was reduced to 24% and 36% in the cloned (MCF + SOD) and pooled MnSOD-transfectants (MCF + SODp) respectively, compared with the wild-type MCF-7 cell line. In conclusion, these results suggest that overexpression of a normal MnSOD cDNA in human breast cancer cells up-regulates the gene expression of the protease inhibitor, maspin, which may play a role in the inhibitory function of MnSOD on tumor invasion. JF - Carcinogenesis AU - Li, J-J AU - Colburn, N H AU - Oberley, L W AD - Gene Regulation Section, Laboratory of Biochemical Physiology, National Cancer Institute, NCI-FCRDC, Frederick, MD 21702-1201, USA, Lij@ncifcrf.gov Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 833 EP - 839 VL - 19 IS - 5 SN - 0143-3334, 0143-3334 KW - DNA KW - MCF-7 cells KW - breast carcinoma KW - man KW - manganese KW - maspin KW - Toxicology Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - X 24240:Miscellaneous KW - N 14662:Gene regulation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16517638?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Maspin+gene+expression+in+tumor+suppression+induced+by+overexpressing+manganese-containing+superoxide+dismutase+cDNA+in+human+breast+cancer+cells&rft.au=Li%2C+J-J%3BColburn%2C+N+H%3BOberley%2C+L+W&rft.aulast=Li&rft.aufirst=J-J&rft.date=1998-05-01&rft.volume=19&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 revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Residential wire codes: reproducibility and relation with measured magnetic fields AN - 16499020; 4397079 AB - To investigate the reproducibility of wire codes to characterise residential power line configurations and to determine the extent to which wire codes provide a proxy measure of residential magnetic field strength in a case-control study of childhood leukaemia conducted in nine states within the United States. Misclassification of wire codes was assessed with independent measurements by two technicians for 187 residences. The association between categories of wire code and measured level of magnetic field was evaluated in 858 residences with both a wire code measurement and a 24 hour measurement of the magnetic field in the bedroom. The strength of the association between category of wire code and risk of leukaemia was examined in two regions with different average levels of magnetic field in homes with high categories of wire code. Misclassification of categories of wire code is not a major source of bias in the study. Wire codes provide a proxy measure of exposure to residential magnetic fields. If magnetic fields were a risk factor for leukaemia, however, there would be some attenuation of risk estimates based on wire codes because of misclassification of exposure to magnetic fields at both extremes of the wire code range. The lack of an association between high categories of wire code and risk of leukaemia cannot be explained by a failure of the wire code classification schemes to estimate exposure to magnetic fields in the study area. JF - Occupational and Environmental Medicine AU - Tarone, R E AU - Kaune, W T AU - Linet AU - Hatch, EE AU - Kleinerman, R A AU - Robison, L L AU - Boice, JD Jr AU - Wacholder, S AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, EPN 403, Bethesda, MD 20892, USA Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 333 EP - 339 VL - 55 IS - 5 SN - 1351-0711, 1351-0711 KW - building codes KW - magnetic fields KW - wire codes KW - Health & Safety Science Abstracts KW - H 8000:Radiation Safety/Electrical Safety UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16499020?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthsafetyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Occupational+and+Environmental+Medicine&rft.atitle=Residential+wire+codes%3A+reproducibility+and+relation+with+measured+magnetic+fields&rft.au=Tarone%2C+R+E%3BKaune%2C+W+T%3BLinet%3BHatch%2C+EE%3BKleinerman%2C+R+A%3BRobison%2C+L+L%3BBoice%2C+JD+Jr%3BWacholder%2C+S&rft.aulast=Tarone&rft.aufirst=R&rft.date=1998-05-01&rft.volume=55&rft.issue=5&rft.spage=333&rft.isbn=&rft.btitle=&rft.title=Occupational+and+Environmental+Medicine&rft.issn=13510711&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Phosphorylation destabilizes the amino-terminal domain of enzyme I of the Escherichia coli phosphoenolpyruvate:sugar phosphotransferase system AN - 16470843; 4335543 AB - Thermal stabilities of enzyme I (63 562 M sub(r) subunit), in the Escherichia coli phosphoenolpyruvate (PEP):sugar phosphotransferase system (PTS), and a cloned amino-terminal domain of enzyme I (EIN; 28 346 M sub(r)) were investigated by differential scanning calorimetry (DSC) and far-UV circular dichroism (CD) at pH 7.5. EIN expressed in a Delta pts E. coli strain showed a single, reversible, two-state transition with T sub(m) = 57 degree C and an unfolding enthalpy of similar to 140 kcal/mol. In contrast, monomeric EIN expressed in a wild-type strain (pts super(+)) had two endotherms with T sub(m) approximately equal to 50 and 57 degree C and overall Delta H = 140 kcal/mol and was converted completely to the more stable form after five DSC scans from 10 to 75 degree C (without changes in CD: similar to 58% alpha -helices). Thermal conversion to a more stable form was correlated with dephosphorylation of EIN by mass spectral analysis. Dephospho-enzyme I (monomer reversible reaction dimer) exhibited endotherms for C- and N-terminal domain unfolding with T sub(m) = 41 and 54 degree C, respectively. Thermal unfolding of the C-terminal domain occurred over a broad temperature range ( similar to 30-50 degree C), was scan rate- and concentration-dependent, coincident with a light scattering decrease and Trp residue exposure, and independent of phosphorylation. Reversible thermal unfolding of the nonphosphorylated N-terminal domain was more cooperative, occurring from 50 to 60 degree C. DSC of partially phosphorylated enzyme I indicated that the amino-terminal domain was destabilized by phosphorylation (from T sub(m) = 54 to similar to 48 degree C). A decrease in conformational stability of the amino-terminal domain of enzyme I produced by phosphorylation of the active-site His 189 has the physiological consequence of promoting phosphotransfer to the phosphocarrier protein, HPr. JF - Biochemistry (Washington) AU - Nosworthy, N J AU - Peterkofsky, A AU - Koenig, S AU - Seok, Yeong-Jae AU - Szczepanowski, R H AU - Ginsburg, A AD - National Institutes of Health, Building 3, Room 208, Bethesda, MD 20892-0340, USA, aog@cu.nih.gov Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 6718 EP - 6726 VL - 37 IS - 19 SN - 0006-2960, 0006-2960 KW - enzyme I KW - phosphoenolpyruvate-sugar phosphotransferase KW - Microbiology Abstracts B: Bacteriology KW - J 02728:Enzymes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16470843?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemistry+%28Washington%29&rft.atitle=Phosphorylation+destabilizes+the+amino-terminal+domain+of+enzyme+I+of+the+Escherichia+coli+phosphoenolpyruvate%3Asugar+phosphotransferase+system&rft.au=Nosworthy%2C+N+J%3BPeterkofsky%2C+A%3BKoenig%2C+S%3BSeok%2C+Yeong-Jae%3BSzczepanowski%2C+R+H%3BGinsburg%2C+A&rft.aulast=Nosworthy&rft.aufirst=N&rft.date=1998-05-01&rft.volume=37&rft.issue=19&rft.spage=6718&rft.isbn=&rft.btitle=&rft.title=Biochemistry+%28Washington%29&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Functional analysis of the amino-terminal 8-kDa domain of DNA polymerase beta as revealed by site-directed mutagenesis DNA binding and 5'-deoxyribose phosphate lyase activities AN - 16446226; 4344548 AB - The amino-terminal 8-kDa domain of DNA polymerase beta functions in binding single-stranded DNA (ssDNA), recognition of a 5'-phosphate in gapped DNA structures, and as a 5'-deoxyribose phosphate (dRP) lyase. NMR and x-ray crystal structures of this domain have suggested several residues that may interact with ssDNA or play a role in the dRP lyase reaction. Nine of these residues were altered by site-directed mutagenesis. Each mutant was expressed in Escherichia coli, and the recombinant protein was purified to near homogeneity. CD spectra of these mutant proteins indicated that the alteration did not adversely affect the global protein structure. Single-stranded DNA binding was probed by photochemical cross-linking to oligo(dT) sub(16). Several mutants (F25W, K35A, K60A, and K68A) were impaired in ssDNA binding activity, whereas other mutants (H34G, E71Q, K72A, E75A, and K84A) retained near wild-type binding activity. The 5'-phosphate recognition activity of these mutants was examined by UV cross-linking to a 5-nucleotide gap DNA where the 5' terminus in the gap was either phosphorylated or unphosphorylated. The results indicate that Lys super(35) is involved in 5'-phosphate recognition of DNA polymerase beta . Finally, the dRP lyase activity of these mutants was evaluated using a preincised apurinic/apyrimidinic DNA. Alanine mutants of Lys super(35) and Lys super(60) are significantly reduced in dRP lyase activity, consistent with the lower ssDNA binding activity. More importantly, alanine substitution for Lys super(72) resulted in a greater than 90% loss of dRP lyase activity, without affecting DNA binding. Alanine mutants of Lys super(68) and Lys super(84) had wild-type dRP lyase activity. The triple alanine mutant, K35A/K68A/K72A, was devoid of dRP lyase activity, suggesting that the effects of the alanine substitution at Lys super(72) and Lys super(35) were additive. The results suggest that Lys super(72) is directly involved in formation of a covalent imino intermediate and are consistent with Lys super(72) as the predominant Schiff base nucleophile in the dRP lyase beta -elimination catalytic reaction. JF - Journal of Biological Chemistry AU - Prasad, R AU - Beard, WA AU - Chyan, J Y AU - Maciejewski, M W AU - Mullen, G P AU - Wilson, SH AD - Laboratory of Structural Biology, National Institute of Environmental Health Sciences, 111 T.W. Alexander Drive, Bldg. 101, Rm. B246, Research Triangle Park, NC 27709, USA Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 11121 EP - 11126 VL - 273 IS - 18 SN - 0021-9258, 0021-9258 KW - 5'-Deoxyribose-phosphate lyase KW - 5'-deoxyribose phosphate lyase KW - DNA KW - DNA-directed DNA polymerase beta KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - J 02725:DNA KW - N 14722:DNA polymerases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16446226?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Biological+Chemistry&rft.atitle=Functional+analysis+of+the+amino-terminal+8-kDa+domain+of+DNA+polymerase+beta+as+revealed+by+site-directed+mutagenesis+DNA+binding+and+5%27-deoxyribose+phosphate+lyase+activities&rft.au=Prasad%2C+R%3BBeard%2C+WA%3BChyan%2C+J+Y%3BMaciejewski%2C+M+W%3BMullen%2C+G+P%3BWilson%2C+SH&rft.aulast=Prasad&rft.aufirst=R&rft.date=1998-05-01&rft.volume=273&rft.issue=18&rft.spage=11121&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Enzymatic and structural similarities between the Escherichia coli ATP-dependent proteases, ClpXP and ClpAP AN - 16445139; 4344787 AB - Escherichia coli ClpX, a member of the Clp family of ATPases, has ATP-dependent chaperone activity and is required for specific ATP-dependent proteolytic activities expressed by ClpP. Gel filtration and electron microscopy showed that ClpX subunits (M sub(r) 46,000) associate to form a six-membered ring (M sub(r) similar to 280,000) that is stabilized by binding of ATP or nonhydrolyzable analogs of ATP. ClpP, which is composed of two seven-membered rings stacked face-to-face, interacts with the nucleotide-stabilized hexamer of ClpX to form a complex that could be isolated by gel filtration. Electron micrographs of negatively stained ClpXP preparations showed side views of 1:1 and 2:1 ClpXP complexes in which ClpP was flanked on either one or both sides by a ring of ClpX. Thus, as was seen for ClpAP, a symmetry mismatch exists in the bonding interactions between the seven-membered rings of ClpP and the six-membered rings of ClpX. Competition studies showed that ClpA may have a slightly higher affinity ( similar to 2-fold) for binding to ClpP. Mixed complexes of ClpA, ClpX, and ClpP with the two ATPases bound simultaneously to opposite faces of a single ClpP molecule were seen by electron microscopy. In the presence of ATP or nonhydrolyzable analogs of ATP, ClpXP had nearly the same activity as ClpAP against oligopeptide substrates (> 10,000 min super(-1) /tetradecamer of ClpP). Thus, ClpX and ClpA interactions with ClpP result in structurally analogous complexes and induce similar conformational changes that affect the accessibility and the catalytic efficiency of ClpP active sites. JF - Journal of Biological Chemistry AU - Grimaud, R AU - Kessel, M AU - Beuron, F AU - Steven, A C AU - Maurizi, M R AD - NCI, Natl. Inst. Health, Bldg. 37, 1B07, 37 Convent Dr., MSC 4255, Bethesda, MD 20892-2755, USA Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 12476 EP - 12481 VL - 273 IS - 20 SN - 0021-9258, 0021-9258 KW - ClpAP protein KW - ClpX protein KW - ClpXP protein KW - structure-activity relationships KW - Microbiology Abstracts B: Bacteriology KW - J 02728:Enzymes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16445139?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Biological+Chemistry&rft.atitle=Enzymatic+and+structural+similarities+between+the+Escherichia+coli+ATP-dependent+proteases%2C+ClpXP+and+ClpAP&rft.au=Grimaud%2C+R%3BKessel%2C+M%3BBeuron%2C+F%3BSteven%2C+A+C%3BMaurizi%2C+M+R&rft.aulast=Grimaud&rft.aufirst=R&rft.date=1998-05-01&rft.volume=273&rft.issue=20&rft.spage=12476&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Caffeine-derived N-nitroso compounds. V. Carcinogenicity of mononitrosocaffeidine and dinitrosocaffeidine in bd-ix rats AN - 16439588; 4342370 AB - Mononitrosocaffeidine (MNC) and dinitrosocaffeidine (DNC) are new N-nitroso compounds obtained from in vitro nitrosation of caffeidine, a hydrolysis product of caffeine present in a typically made and widely consumed tea from Kashmir (India), a high incidence area of esophageal and stomach cancer. The chemical synthesis, in vitro metabolic studies and mutagenicity of the compounds has been previously reported. DNC, a nitrosamide is highly mutagenic both with and without metabolic activation whereas MNC, like several other aromatic asymmetric nitrosamines, does not exhibit genotoxic or mutagenic properties. We now report the results of the first carcinogenicity experiments on chronic oral administration of these compounds in BD-IX rats. The acute LD sub(50) of MNC and DNC were about 1300 and 230 mg/kg b.w., respectively. Lung oedema and gastrointestinal haemorrhages were the first symptoms of intoxication observed after 2 days for both the compounds. All three dose groups of MNC treated rats showed localization of tumours in nasal cavity (93.9-100% of all malignant tumours). The tumours were histologically diagnosed as neuroepitheliomas of the olfactory epithelium (neuroblastoma of the bulbus olfactorii) and squamous cell carcinoma of the nasal cavity in the ratio of 3:1. No tumours of the nasal cavity were observed in the untreated controls. DNC, in contrast, induced squamous cell carcinoma of forestomach in 100% animals at low and high doses, of which nearly half the tumours metastasized predominantly into the peritoneum. No forestomach tumours were seen in the untreated controls. The data presented here clearly show the potential for induction of malignant tumours and distinct organ-specificity by MNC and DNC in rats, and support the postulate that a chronic exposure to these compounds may provide a carcinogenic risk for high incidence of gastrointestinal cancers in Kashmir. JF - Carcinogenesis AU - Ivankovic, S AU - Seibel, J AU - Komitowski, D AU - Spiegelhalder, B AU - Preussmann, R AU - Siddiqi, M AD - Chittaranjan National Cancer Institute, 37, S.P.Mukherjee Road, Calcutta-700026, India, cncinst@giasc101.vsnl.net.in Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 933 EP - 937 VL - 19 IS - 5 SN - 0143-3334, 0143-3334 KW - dinitrosocaffeidine KW - mononitrosocaffeidine KW - rats KW - Toxicology Abstracts KW - X 24120:Food, additives & contaminants KW - X 24200:Nitrosamines & related compounds UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16439588?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Caffeine-derived+N-nitroso+compounds.+V.+Carcinogenicity+of+mononitrosocaffeidine+and+dinitrosocaffeidine+in+bd-ix+rats&rft.au=Ivankovic%2C+S%3BSeibel%2C+J%3BKomitowski%2C+D%3BSpiegelhalder%2C+B%3BPreussmann%2C+R%3BSiddiqi%2C+M&rft.aulast=Ivankovic&rft.aufirst=S&rft.date=1998-05-01&rft.volume=19&rft.issue=5&rft.spage=933&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - The multifaceted roles of nitric oxide in cancer AN - 16436359; 4342342 AB - The roles of nitric oxide (NO) in numerous disease states have generated considerable discussion over the past several years. NO has been labeled as the causative agent in different pathophysiological mechanisms, yet appears to protect against various chemical species such as those generated under oxidative stress. Similarly, NO appears to exert a dichotomy of effects within the multistage model of cancer. Chronic inflammation can lead to the production of chemical intermediates, among them NO, which in turn can mediate damage to DNA. Yet, NO also appears to be critical for the tumoricidal activity of the immune system. Furthermore, NO can also have a multitude of effects on other aspects of tumor biology, including angiogenesis and metastasis. This report will discuss how the chemistry of NO may impact the initiation and progression stages of cancer. JF - Carcinogenesis AU - Wink, DA AU - Vodovotz, Y AU - Laval, J AU - Laval, F AU - Dewhirst, M W AU - Mitchell, J B AD - Radiation Biology Branch, National Cancer Institute, Bldg. 10, Room B3-B69, Bethesda, MD 20892, USA Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 711 EP - 721 VL - 19 IS - 5 SN - 0143-3334, 0143-3334 KW - Toxicology Abstracts KW - X 24250:Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16436359?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=The+multifaceted+roles+of+nitric+oxide+in+cancer&rft.au=Wink%2C+DA%3BVodovotz%2C+Y%3BLaval%2C+J%3BLaval%2C+F%3BDewhirst%2C+M+W%3BMitchell%2C+J+B&rft.aulast=Wink&rft.aufirst=DA&rft.date=1998-05-01&rft.volume=19&rft.issue=5&rft.spage=711&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Apparent role of hydroxyl radicals in oxidative brain injury induced by sodium nitroprusside AN - 16436327; 4331468 AB - Sodium nitroprusside (disodium nitroferricyanide) has been suggested to cause cytotoxicity through either the release of cyanide and/or nitric oxide. The present study investigated a possible mechanism that after a brief release of nitric oxide, iron moiety of breakdown products of sodium nitroprusside could cause a long lasting oxidative stress, such as hydroxyl radical generation, lipid peroxidation and cytotoxicity. Intranigral administration of sodium nitroprusside (0-16.8 nmol) to rats induced an acute increase in lipid peroxidation in the substantia nigra and a chronic dopamine depletion in the caudate nucleus. Photodegraded (nitric oxide-exhausted) sodium nitroprusside, however, still produced lipid peroxidation and neurotoxicity in the midbrain. Moreover, non-iron containing nitric oxide-donor compounds, such as S-nitroso-N-acetylpenicillamine, did not cause oxidative brain injury in vivo suggesting that nitric oxide may not mediate neurotoxicity induced by sodium nitroprusside. Additional in vitro studies demonstrated that both freshly prepared (nitric oxide donor) and photodegraded (nitric oxide-exhausted) sodium nitroprusside generated hydroxyl radicals in the presence of ascorbate and also increased lipid peroxidation in brain homogenates. These pro-oxidative effects of sodium nitroprusside were blocked by nitric oxide, S-nitroso-N-acetylpenicillamine, oxyhemoglobin, and deferoxamine (iron chelator). The present results suggest that iron moiety, rather than nitric oxide, may mediate the pro-oxidative properties of sodium nitroprusside. With this new information in mind, the misuse of sodium nitroprusside as a selective nitric oxide donor in both basic and clinical uses should be urgently addressed. JF - Free Radical Biology & Medicine AU - Rauhala, P AU - Khaldi, A AU - Mohanakumar, K P AU - Chiueh, C C AD - LCS, National Institute of Mental Health, NIH, Bldg. 10, Rm. 3D-41, Bethesda, MD 20892-1264, USA Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 1065 EP - 1073 VL - 24 IS - 7-8 SN - 0891-5849, 0891-5849 KW - nitric oxide KW - nitroprusside KW - sodium nitroprusside KW - CSA Neurosciences Abstracts; Toxicology Abstracts KW - N3 11104:Mammals (except primates) KW - X 24240:Miscellaneous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16436327?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Free+Radical+Biology+%26+Medicine&rft.atitle=Apparent+role+of+hydroxyl+radicals+in+oxidative+brain+injury+induced+by+sodium+nitroprusside&rft.au=Rauhala%2C+P%3BKhaldi%2C+A%3BMohanakumar%2C+K+P%3BChiueh%2C+C+C&rft.aulast=Rauhala&rft.aufirst=P&rft.date=1998-05-01&rft.volume=24&rft.issue=7-8&rft.spage=1065&rft.isbn=&rft.btitle=&rft.title=Free+Radical+Biology+%26+Medicine&rft.issn=08915849&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - An RNA pseudoknot as the molecular switch for translation of the repZ-gene encoding the replication initiator of IncI alpha plasmid ColIb-P9 AN - 16430545; 4339040 AB - Translation initiation of the repZ gene encoding the replication initiator of plasmid ColIb-P9 is not only negatively regulated by the action of the antisense Inc RNA encoded in the leader region, but is also coupled to the translation and termination of a transcribed leader sequence, repY, a positive regulatory element for repZ gene expression. This translational coupling depends on base pairing between two complementary sequences, 5'-rGGCG-3' and 5'-rCGCC-3', which are located upstream of and in the middle of repY, respectively, and have the potential to form a pseudoknot with the stem-loop structure I. Another stem-loop called structure III near the 3'-end of repY sequesters both the 5'-rCGCC-3' sequence and the repZ ribosome-binding site. Here we show that the RepZ mRNA leader sequence synthesized in vitro indeed contains several stem-loop structures including structures I and III, but not the pseudoknot. However, disruption of structure III, without changing the repZ ribosome-binding site, by means of base substitution and deletion induces base pairing between the two short complementary sequences distantly separated, resulting in the formation of a pseudoknot. When the pseudoknot is allowed to form in vivo due to the same mutations, a maximum level of repZ expression is obtained comparable to one observed in the absence of Inc RNA. These results strengthen our previously proposed model that the pseudoknot induced by the translation and termination of the repY reading frame functions as the molecular switch for translational initiation of the repZ gene. JF - Journal of Biological Chemistry AU - Asano, K AU - Mizobuchi, K AD - Lab. Eukaryotic Gene Regulation, NICHD, Natl. Institutes Health, Bethesda, MD 20892, USA Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 11815 EP - 11825 VL - 273 IS - 19 SN - 0021-9258, 0021-9258 KW - plasmid ColIb-P9 KW - pseudoknots KW - psudoknots KW - repY regulatory element KW - repZ gene KW - translation initiation KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - J 02760:Plasmids KW - N 14430:Translation initiation, elongation & termination UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16430545?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Biological+Chemistry&rft.atitle=An+RNA+pseudoknot+as+the+molecular+switch+for+translation+of+the+repZ-gene+encoding+the+replication+initiator+of+IncI+alpha+plasmid+ColIb-P9&rft.au=Asano%2C+K%3BMizobuchi%2C+K&rft.aulast=Asano&rft.aufirst=K&rft.date=1998-05-01&rft.volume=273&rft.issue=19&rft.spage=11815&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Characterization of an MDR1 retroviral bicistronic vector for correction of X-linked severe combined immunodeficiency AN - 16416014; 4324765 AB - X-linked severe combined immunodeficiency (XSCID) is a hereditary disorder characterized by severe T cell lymphopenia and abnormal B cell function. The disease is caused by mutations in IL2RG, the gene encoding the interleukin-2 receptor common gamma chain ( gamma c) shared by several interleukin receptors. A Harvey retroviral bicistronic vector containing an IL2RG cDNA and cDNA encoding the multidrug transporter (MDR1) was constructed to investigate the correction of XSCID. Translation of the MDR1 cDNA is achieved from an internal ribosome entry site (IRES). Mouse fibroblasts transfected or transduced with the vector expressed both membrane proteins as detected with specific monoclonal antibodies by fluorescence activated cell sorting. Two human XSCID B cell lines were transduced using a filter concentration method in combination with phosphate depletion. Significant expression of both proteins was detected by Western blot analysis. This construct might be particularly useful if high expression of gamma c is required, as might be achievable through in vivo selection for drug resistance of recipient lymphocytes. JF - Gene Therapy AU - Kleiman, SE AU - Pastan, I AU - Puck, J M AU - Gottesman, M M AD - Laboratory of Cell Biology, Division of Basic Sciences, National Institutes of Health, Building 37, Room 1A09, 37 Convent Drive MSC4255, Bethesda, MD 20892-4255, USA Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 671 EP - 676 VL - 5 IS - 5 SN - 0969-7128, 0969-7128 KW - Mdr-1 protein KW - bicistronic vectors KW - interleukin 2 receptors KW - mice KW - multidrug resistance KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - W3 33181:Gene therapy vectors KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16416014?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Gene+Therapy&rft.atitle=Characterization+of+an+MDR1+retroviral+bicistronic+vector+for+correction+of+X-linked+severe+combined+immunodeficiency&rft.au=Kleiman%2C+SE%3BPastan%2C+I%3BPuck%2C+J+M%3BGottesman%2C+M+M&rft.aulast=Kleiman&rft.aufirst=SE&rft.date=1998-05-01&rft.volume=5&rft.issue=5&rft.spage=671&rft.isbn=&rft.btitle=&rft.title=Gene+Therapy&rft.issn=09697128&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Research toward vaccines against malaria AN - 16415938; 4311197 AB - Malaria is one of the major causes of disease and death between the Tropic of Cancer and Tropic of Capricorn. Plasmodium falciparum has an especially profound impact on infants and children in sub-Saharan Africa, where its effect on health is increasing as chloroquine resistance spreads across the continent. We believe that vaccination against P. falciparum is the intervention with the greatest potential to reduce malaria-associated severe morbidity and mortality in areas with the most intense transmission and that it may do so without necessarily preventing blood stage infection. Malaria vaccines also would be the optimal method for preventing malaria in travelers to countries where malaria is transmitted. Such vaccines will have to entirely prevent the development of any clinical manifestations of infection with P. falciparum and of the second most common human malaria parasite, P. vivax. This will require preventing blood stage infection. Infants and young children at risk from P. falciparum in Africa and nonimmune travelers to areas endemic for P. falciparum and P. vivax represent the extremes of target groups in whom malaria vaccines would be useful. Even in countries where the overall numbers of afflicted individuals are not as great as in Africa, malaria wreaks its havoc in many epidemiologic settings and population groups, dramatically undermines the productivity of workers, and drains national budgets. From the Amazon basin to the Indian subcontinent, Southeast Asia, and Oceania, malaria is often a major national public health problem. In these settings, vaccines offer the greatest potential for reducing malaria's debilitating effects. The spread of drug-resistant P. falciparum and the recent emergence and spread of chloroquine-resistant P. vivax have created an increasing urgency for effective malaria vaccines. JF - Nature Medicine AU - Miller, L H AU - Hoffman, S L AD - Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA, louis_miller@nih.gov Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 520 EP - 524 VL - 4 IS - 5 SN - 1078-8956, 1078-8956 KW - Plasmodium falciparum KW - Plasmodium vivax KW - Biotechnology and Bioengineering Abstracts; Immunology Abstracts; Microbiology Abstracts C: Algology, Mycology & Protozoology; Medical and Pharmaceutical Biotechnology Abstracts KW - W3 33365:Vaccines (other) KW - K 03086:Immunology & vaccination KW - F 06807:Active immunization KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16415938?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+Medicine&rft.atitle=Research+toward+vaccines+against+malaria&rft.au=Miller%2C+L+H%3BHoffman%2C+S+L&rft.aulast=Miller&rft.aufirst=L&rft.date=1998-05-01&rft.volume=4&rft.issue=5&rft.spage=520&rft.isbn=&rft.btitle=&rft.title=Nature+Medicine&rft.issn=10788956&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Efficacy of multiple administrations of a recombinant adenovirus expressing wild-type p53 in an immune-competent mouse tumor model AN - 16410546; 4324757 AB - Infection of Renca cells in vitro with a recombinant adenovirus expressing a marker gene beta -galactosidase resulted in high level of the transgene expression. Renca tumors grown in Balb/C mice were also infectable with this recombinant adenovirus. The transgene expression in the tumors lasted for about 7 days, however, administration of another dose of Ad- beta gal, on day 7 produced beta -galactosidase expression. To investigate the effect of antibodies to adenovirus, animals were injected with multiple doses of adenovirus to produce neutralizing antibodies. To these animals Renca cells were injected and tumors formed. Interestingly, when Ad beta -gal was administered into these tumors, a high level of transgene expression was still observed. We next explored the utility of a recombinant adenovirus expressing p53 (AdWTp53) in the Renca tumor model. Renca cells when exposed to an adenovirus expressing p53 (AdWTp53) produced a high level of p53 protein, a p53-inducible gene p21/WAF1/Cip1 and underwent apoptosis. A single injection of AdWTp53 (10 super(9) plaque forming units) resulted in significant inhibition of tumor growth. However, multiple administrations (four doses of 2.5 x 10 super(8) plaque forming units) of AdWTp53 were needed for tumor cures. Mixing uninfected and AdWTp53-infected cells showed a bystander effect of AdWTp53-infected Renca cells. Based on these results we believe that an appropriate dose scheduling of AdWTp53 can be efficacious for cancer gene therapy in immune-competent tumor-bearing animals. JF - Gene Therapy AU - Li, Z AU - Rakkar, A AU - Katayose, Y AU - Kim, M AU - Shanmugam, N AU - Srivastava, S AU - Moul, J W AU - McLeod, D G AU - Cowan, KH AU - Seth, P AD - Medicine Branch, National Cancer Institute, National Institutes of Health, Building 10, Room 12N226, Bethesda, MD 20892, USA Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 605 EP - 613 VL - 5 IS - 5 SN - 0969-7128, 0969-7128 KW - Adenovirus KW - beta -galactosidase KW - mice KW - p53 protein KW - Biotechnology and Bioengineering Abstracts; Genetics Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - G 07397:Rodentia (mice) KW - W 30965:Miscellaneous, Reviews KW - W3 33180:Gene based (protocols, clinical trials, and animal models) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16410546?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Gene+Therapy&rft.atitle=Efficacy+of+multiple+administrations+of+a+recombinant+adenovirus+expressing+wild-type+p53+in+an+immune-competent+mouse+tumor+model&rft.au=Li%2C+Z%3BRakkar%2C+A%3BKatayose%2C+Y%3BKim%2C+M%3BShanmugam%2C+N%3BSrivastava%2C+S%3BMoul%2C+J+W%3BMcLeod%2C+D+G%3BCowan%2C+KH%3BSeth%2C+P&rft.aulast=Li&rft.aufirst=Z&rft.date=1998-05-01&rft.volume=5&rft.issue=5&rft.spage=605&rft.isbn=&rft.btitle=&rft.title=Gene+Therapy&rft.issn=09697128&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Generation of polyclonal rabbit antisera to mouse melanoma associated antigens using gene gun immunization AN - 16404929; 4313935 AB - Lymphocytes from patients with melanoma have been used to clone melanoma associated antigens which are, for the most part, nonmutated melanocyte tissue differentiation antigens. To establish a mouse model for the use of these `self' antigens as targets for anti-tumor immune responses, we have employed the mouse homologues of the human melanoma antigens Tyrosinase, Tyrosinase Related Protein-1 (TRP-1), gp100, and MART-1. We sought to generate antisera against these proteins for use in the construction of experimental recombinant and synthetic anti-cancer vaccines, and for use in biologic studies. Using genes cloned from the B16 mouse melanoma or from murine melanocytes, we immunized rabbits with plasmid DNAs coated onto microscopic gold beads that were then delivered using a hand-held, helium-driven `gene gun'. This strategy enabled us to generate polyclonal rabbit sera containing antibodies that specifically recognized each antigen, as measured by immunostaining of vaccinia virus infected cells. The sera that we generated specifically for TRP-1, gp100, and MART-1 recognized extracts of the spontaneous murine melanoma, B16. The identities of the recognized proteins was confirmed by Western blot analysis. The titers and specificities of these antisera were determined using ELISA. Interestingly, serum samples generated against murine MART-1 and gp100 developed antibodies that were cross-reactive with the corresponding human homologues. Recognition of human gp100 and murine Tyrosinase appeared to be dependent upon conformational epitopes since specificity was lost upon denaturation of the antigens. These anti-sera may be useful in the detection, purification and characterization of the mouse homologues of recently cloned human tumor associated antigens and may enable the establishment of an animal model of the immune consequences of vaccination against `self' antigens. JF - Journal of Immunological Methods AU - Surman AU - Irvine, K R AU - Shulman, E P AU - Allweis, T M AU - Rosenberg, SA AU - Restifo, N P AD - Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA Y1 - 1998/05/01/ PY - 1998 DA - 1998 May 01 SP - 51 EP - 62 PB - Elsevier Science B.V. VL - 214 IS - 1-2 SN - 0022-1759, 0022-1759 KW - MART-1 antigen KW - glycoprotein gp100 KW - tyrosinase related protein 1 KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - W3 33375:Antibodies KW - F 06711:Monoclonal antibodies, hybridomas, antigens and antisera KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16404929?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Immunological+Methods&rft.atitle=Generation+of+polyclonal+rabbit+antisera+to+mouse+melanoma+associated+antigens+using+gene+gun+immunization&rft.au=Surman%3BIrvine%2C+K+R%3BShulman%2C+E+P%3BAllweis%2C+T+M%3BRosenberg%2C+SA%3BRestifo%2C+N+P&rft.aulast=Surman&rft.aufirst=&rft.date=1998-05-01&rft.volume=214&rft.issue=1-2&rft.spage=51&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immunological+Methods&rft.issn=00221759&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Synthesis and Characterization of Lipooligosaccharide-Based Conjugates as Vaccine Candidates for Moraxella (Branhamella) catarrhalis AN - 16387220; 4307565 AB - Moraxella (Branhamella) catarrhalis is an important cause of otitis media and sinusitis in children and of lower respiratory tract infections in adults. Lipooligosaccharide (LOS) is a major surface antigen of the bacterium and elicits bactericidal antibodies. Treatment of the LOS from strain ATCC 25238 with anhydrous hydrazine reduced its toxicity 20,000-fold, as assayed in the Limulus amebocyte lysate (LAL) test. The detoxified LOS (dLOS) was coupled to tetanus toxoid (TT) or high-molecular-weight proteins (HMP) from nontypeable Haemophilus influenzae through a linker of adipic acid dihydrazide to form dLOS-TT or dLOS-HMP. The molar ratios of dLOS to TT and HMP conjugates were 19:1 and 31:1, respectively. The antigenicity of the two conjugates was similar to that of the LOS, as determined by double immunodiffusion. Subcutaneous or intramuscular injection of both conjugates elicited a 50- to 100-fold rise in the geometric mean of immunoglobulin G (IgG) to the homologous LOS in mice after three injections and a 350- to 700-fold rise of anti-LOS IgG in rabbits after two injections. The immunogenicity of the conjugate was enhanced by formulation with monophosphoryl lipid A plus trehalose dimycolate. In rabbits, conjugate-induced antisera had complement-mediated bactericidal activity against the homologous strain and heterologous strains of M. catarrhalis. These results indicate that a detoxified LOS-protein conjugate is a candidate for immunization against M. catarrhalis diseases. JF - Infection and Immunity AU - Gu, Xin-Xing AU - Chen, Jing AU - Barenkamp, S J AU - Robbins, J B AU - Tsai, Chao-Ming AU - Lim, D J AU - Battey, J AD - NIDCD, NIH, 5 Research Court, 2A31, Rockville, MD 20850, USA, xgu@pop.nidcd.nih.gov Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 1891 EP - 1897 VL - 66 IS - 5 SN - 0019-9567, 0019-9567 KW - Moraxella catarrhalis KW - children KW - lipooligosaccharides KW - man KW - monophosphoryl lipid A KW - Immunology Abstracts; Microbiology Abstracts B: Bacteriology KW - J 02834:Vaccination and immunization KW - F 06807:Active immunization UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16387220?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Infection+and+Immunity&rft.atitle=Synthesis+and+Characterization+of+Lipooligosaccharide-Based+Conjugates+as+Vaccine+Candidates+for+Moraxella+%28Branhamella%29+catarrhalis&rft.au=Gu%2C+Xin-Xing%3BChen%2C+Jing%3BBarenkamp%2C+S+J%3BRobbins%2C+J+B%3BTsai%2C+Chao-Ming%3BLim%2C+D+J%3BBattey%2C+J&rft.aulast=Gu&rft.aufirst=Xin-Xing&rft.date=1998-05-01&rft.volume=66&rft.issue=5&rft.spage=1891&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - The ClpXP and ClpAP proteases degrade proteins with carboxy-terminal peptide tails added by the SsrA-tagging system AN - 16349489; 4316731 AB - Interruption of translation in Escherichia coli can lead to the addition of an 11-residue carboxy-terminal peptide tail to the nascent chain. This modification is mediated by SsrA RNA (also called 10Sa RNA and tmRNA) and marks the tagged polypeptide for proteolysis. Degradation in vivo of lambda repressor amino-terminal domain variants bearing this carboxy-terminal SsrA peptide tag is shown here to depend on the cytoplasmic proteases ClpXP and ClpAP. Degradation in vitro of SsrA-tagged substrates was reproduced with purified components and required a substrate with a wild-type SsrA tail, the presence of both ClpP and either ClpA or ClpX, and ATP. Clp-dependent proteolysis accounts for most degradation of SsrA-tagged amino-domain substrates at 32 degree C, but additional proteases contribute to the degradation of some of these SsrA-tagged substrates at 39 degree C. The existence of multiple cytoplasmic proteases that function in SsrA quality-control surveillance suggests that the SsrA tag is designed to serve as a relatively promiscuous signal for proteolysis. Having diverse degradation systems able to recognize this tag may increase degradation capacity, permit degradation of a wide variety of different tagged proteins, or allow SsrA-tagged proteins to be degraded under different growth conditions. JF - Genes & Development AU - Gottesman, S AU - Roche, E AU - Zhou, YanNing AU - Sauer, R T AD - Laboratory of Molecular Biology, National Cancer Institute, Bethesda, MD 20892, USA, susang@helix.nih.gov Y1 - 1998/05/01/ PY - 1998 DA - 1998 May 01 SP - 1338 EP - 1347 VL - 12 IS - 9 SN - 0890-9369, 0890-9369 KW - ClpAP protein KW - ClpXP protein KW - protein degradation KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - J 02728:Enzymes KW - N 14400:General UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16349489?accountid=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=Genes+%26+Development&rft.atitle=The+ClpXP+and+ClpAP+proteases+degrade+proteins+with+carboxy-terminal+peptide+tails+added+by+the+SsrA-tagging+system&rft.au=Gottesman%2C+S%3BRoche%2C+E%3BZhou%2C+YanNing%3BSauer%2C+R+T&rft.aulast=Gottesman&rft.aufirst=S&rft.date=1998-05-01&rft.volume=12&rft.issue=9&rft.spage=1338&rft.isbn=&rft.btitle=&rft.title=Genes+%26+Development&rft.issn=08909369&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Genetic uncoupling of the dsRNA-binding and RNA cleavage activities of the Escherichia coli endoribonuclease RNase III - the effect of dsRNA binding on gene expression AN - 16347403; 4315626 AB - RNase III, a double-stranded RNA-specific endonuclease, is proposed to be one of Escherichia coli's global regulators because of its ability to affect the expression of a large number of unrelated genes by influencing post-transcriptional control of mRNA stability or mRNA translational efficiency. Here, we describe the phenotypes of bacteria carrying point mutations in rnc, the gene encoding RNase III. The substrate recognition and RNA-processing properties of mutant proteins were analysed in vivo by measuring expression from known RNase III-modulated genes and in vitro from the proteins' binding and cleavage activities on known double-stranded RNA substrates. Our results show that although the point mutation rnc70 exhibited all the usual rnc null-like phenotypes, unlike other mutations, it was dominant over the wild-type allele. Multicopy expression of rnc70 could suppress a lethal phenotype of the wild-type rnc allele in a certain genetic background; it could also inhibit the RNase III-mediated activation of lambda N gene translation by competing for the RNA-binding site of the wild-type endonuclease. The mutant protein failed to cleave the standard RNase III substrates in vitro but exhibited an affinity for double-stranded RNA when passed through poly(rI):poly(rC) columns. Filter binding and gel-shift assays with purified Rnc70 showed that the mutant protein binds to known RNase III mRNA substrates in a site-specific manner. In vitro processing reactions with purified enzyme and labelled RNA showed that the in vivo dominant effect of the mutant enzyme over the wild-type was not necessarily caused by formation of mixed dimers. Thus, the rnc70 mutation generates a mutant RNase III with impaired endonucleolytic activity but without blocking its ability to recognize and bind double-stranded RNA substrates. JF - Molecular Microbiology AU - Dasgupta, S AU - Fernandez, L AU - Kameyama, L AU - Inada, T AU - Nakamura, Y AU - Pappas, A AU - Court, D L AD - Gene Regulation and Chromosome Biology Laboratory, ABL-Basic Research Program, NCI-FCRDC, PO Box B, Frederick, MD 21702, USA, court@ncifcrf.gov Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 629 EP - 640 VL - 28 IS - 3 SN - 0950-382X, 0950-382X KW - RNA KW - point mutation KW - rnc gene KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - J 02726:RNA and ribosomes KW - N 14711:RNases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16347403?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+Microbiology&rft.atitle=Genetic+uncoupling+of+the+dsRNA-binding+and+RNA+cleavage+activities+of+the+Escherichia+coli+endoribonuclease+RNase+III+-+the+effect+of+dsRNA+binding+on+gene+expression&rft.au=Dasgupta%2C+S%3BFernandez%2C+L%3BKameyama%2C+L%3BInada%2C+T%3BNakamura%2C+Y%3BPappas%2C+A%3BCourt%2C+D+L&rft.aulast=Dasgupta&rft.aufirst=S&rft.date=1998-05-01&rft.volume=28&rft.issue=3&rft.spage=629&rft.isbn=&rft.btitle=&rft.title=Molecular+Microbiology&rft.issn=0950382X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Antisense depletion of RI alpha subunit of protein kinase A induces apoptosis and growth arrest in human breast cancer cells AN - 1496897241; 16923064 AB - In recent years, several laboratories have explored the possibility of using antisense oligodeoxynucleotides for specific manipulation of gene expression leading to cancer treatment. The enhanced expression of the RI alpha subunit of cyclic AMP-dependent protein kinase type I (PKA-I) has been correlated with cancer cell growth. In the present study, the effects of an antisense oligodeoxynucleotide targeted against RI alpha subunit of PKA-I on growth inhibition and apoptosis in MDA-MB-231 human breast cancer cells were investigated. The growth inhibitory effects of RI alpha antisense oligodeoxynucleotide correlated with a decrease in the RI alpha mRNA and protein levels. The growth inhibition was accompanied by changes in the cell cycle phase distribution, cell morpbology, cleavage of poly (ADP-ribose) polymerase (PARP), and appearance of apoptotic nuclei. By comparison, mismatched control oligodeoxynucleotide had no effect. On the basis of these results, it can be suggested that the RI alpha antisense oligodeoxynucleotide, which efficiently depletes the growth stimulatory RI alpha and induces apoptosis/differentiation, could be used as a therapeutic agent for breast cancer treatment. JF - Breast Cancer Research and Treatment AU - Srivastava, Rakesh K AU - Srivastava, Aparna R AU - Park, Yun Gyu AU - Agrawal, Sudhir AU - Cho-Chung, Yoon S AD - Cellular Biochemistry Section, Laboratory of Tumor and Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 97 EP - 107 PB - Springer Science+Business Media, Van Godewijckstraat 30 Dordrecht 3311 GX Netherlands VL - 49 IS - 2 SN - 0167-6806, 0167-6806 KW - Biotechnology and Bioengineering Abstracts KW - Antisense oligonucleotides KW - W 30915:Pharmaceuticals & Vaccines UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1496897241?accountid=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=Breast+Cancer+Research+and+Treatment&rft.atitle=Antisense+depletion+of+RI+alpha+subunit+of+protein+kinase+A+induces+apoptosis+and+growth+arrest+in+human+breast+cancer+cells&rft.au=Srivastava%2C+Rakesh+K%3BSrivastava%2C+Aparna+R%3BPark%2C+Yun+Gyu%3BAgrawal%2C+Sudhir%3BCho-Chung%2C+Yoon+S&rft.aulast=Srivastava&rft.aufirst=Rakesh&rft.date=1998-05-01&rft.volume=49&rft.issue=2&rft.spage=97&rft.isbn=&rft.btitle=&rft.title=Breast+Cancer+Research+and+Treatment&rft.issn=01676806&rft_id=info:doi/10.1023%2FA%3A1005905723550 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2014-02-01 N1 - Last updated - 2014-02-11 N1 - SubjectsTermNotLitGenreText - Antisense oligonucleotides DO - http://dx.doi.org/10.1023/A:1005905723550 ER - TY - JOUR T1 - Identification of amino acid residues associated with modulation of flavin-containing monooxygenase (FMO) activity by imipramine: structure/function studies with FMO1 from pig and rabbit. AN - 79822717; 9558327 AB - The activity of the flavin-containing monooxygenase (FMO) can be modulated by a number of nitrogen-containing compounds in a manner that is both isoform and modulator-dependent. We now show that the direction (activation or inhibition) and extent of modulation can also be dependent on substrate concentration. Imipramine activates methimazole metabolism catalyzed by rabbit FMO1 or FMO2 at methimazole concentrations greater than 50 or 100 microM, respectively, and inhibits at lower methimazole concentrations. The extent of the activation increases as the substrate concentration increases, and the extent of inhibition increases as the substrate concentration decreases. With either inhibition or activation, the magnitude of the effect shows a similar, direct dependency on imipramine concentration. In contrast, imipramine inhibits the metabolism of methimazole catalyzed by pig FMO1 at all substrate concentrations. The structural basis for this unique ortholog difference between the responses of rabbit and pig FMO1 to imipramine was studied by random chimeragenesis and site-directed mutagenesis. Results with chimeras indicated that modulation of FMO1 activity by imipramine is controlled to a great extent by two areas of the FMO primary structure (residues 381-432 and 433-465). Four amino acids in these regions (positions 381, 400, 420 and 433) and one additional residue (position 186) were identified by site-directed mutagenesis as primary determinants of the imipramine response. When the residues at these positions in rabbit FMO1 are exchanged for the corresponding residues of pig FMO1, a mutant with the functional properties of pig FMO1 is produced. Our results suggest that the response of FMO1 to imipramine involves a distribution between two sites that is regulated by structural features that do not alter the overall binding. The inhibition observed, although it appears to be competitive, likely does not involve competition for a binding site since alteration of imipramine metabolism has no effect on the parameters of methimazole metabolism. JF - Biochemistry AU - Wyatt, M K AU - Overby, L H AU - Lawton, M P AU - Philpot, R M AD - Molecular Pharmacology Section, Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1998/04/28/ PY - 1998 DA - 1998 Apr 28 SP - 5930 EP - 5938 VL - 37 IS - 17 SN - 0006-2960, 0006-2960 KW - Amino Acids KW - 0 KW - Recombinant Fusion Proteins KW - Methimazole KW - 554Z48XN5E KW - Oxygenases KW - EC 1.13.- KW - dimethylaniline monooxygenase (N-oxide forming) KW - EC 1.14.13.8 KW - Imipramine KW - OGG85SX4E4 KW - Index Medicus KW - Swine KW - Animals KW - Recombinant Fusion Proteins -- biosynthesis KW - Genetic Vectors -- biosynthesis KW - Rabbits KW - Enzyme Activation -- genetics KW - Recombinant Fusion Proteins -- chemistry KW - Structure-Activity Relationship KW - Mutagenesis, Site-Directed KW - Methimazole -- metabolism KW - Amino Acid Substitution -- genetics KW - Enzyme Activation -- drug effects KW - Catalysis KW - Oxygenases -- biosynthesis KW - Oxygenases -- metabolism KW - Amino Acids -- chemistry KW - Amino Acids -- genetics KW - Imipramine -- pharmacology KW - Oxygenases -- genetics KW - Imipramine -- metabolism KW - Amino Acids -- metabolism KW - Oxygenases -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79822717?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemistry&rft.atitle=Identification+of+amino+acid+residues+associated+with+modulation+of+flavin-containing+monooxygenase+%28FMO%29+activity+by+imipramine%3A+structure%2Ffunction+studies+with+FMO1+from+pig+and+rabbit.&rft.au=Wyatt%2C+M+K%3BOverby%2C+L+H%3BLawton%2C+M+P%3BPhilpot%2C+R+M&rft.aulast=Wyatt&rft.aufirst=M&rft.date=1998-04-28&rft.volume=37&rft.issue=17&rft.spage=5930&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-05-20 N1 - Date created - 1998-05-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Iron-dependent oxidation, ubiquitination, and degradation of iron regulatory protein 2: implications for degradation of oxidized proteins. AN - 79821850; 9560204 AB - The ability of iron to catalyze formation of reactive oxygen species significantly contributes to its toxicity in cells and animals. Iron uptake and distribution is regulated tightly in mammalian cells, in part by iron regulatory protein 2 (IRP2), a protein that is degraded efficiently by the proteasome in iron-replete cells. Here, we demonstrate that IRP2 is oxidized and ubiquitinated in cells before degradation. Moreover, iron-dependent oxidation converts IRP2 into a substrate for ubiquitination in vitro. A regulatory pathway is described in which excess iron is sensed by its ability to catalyze site-specific oxidations in IRP2, oxidized IRP2 is ubiquitinated, and ubiquitinated IRP2 subsequently is degraded by the proteasome. Selective targeting and removal of oxidatively modified proteins may contribute to the turnover of many proteins that are degraded by the proteasome. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Iwai, K AU - Drake, S K AU - Wehr, N B AU - Weissman, A M AU - LaVaute, T AU - Minato, N AU - Klausner, R D AU - Levine, R L AU - Rouault, T A AD - Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-5430, USA. Y1 - 1998/04/28/ PY - 1998 DA - 1998 Apr 28 SP - 4924 EP - 4928 VL - 95 IS - 9 SN - 0027-8424, 0027-8424 KW - Iron-Regulatory Proteins KW - 0 KW - Iron-Sulfur Proteins KW - Multienzyme Complexes KW - RNA-Binding Proteins KW - Recombinant Proteins KW - Ubiquitins KW - Iron KW - E1UOL152H7 KW - Cysteine Endopeptidases KW - EC 3.4.22.- KW - Proteasome Endopeptidase Complex KW - EC 3.4.25.1 KW - Iron Regulatory Protein 2 KW - EC 4.2.1.3 KW - Index Medicus KW - Oxidation-Reduction KW - Animals KW - Ubiquitins -- metabolism KW - COS Cells KW - Recombinant Proteins -- metabolism KW - Iron -- metabolism KW - Cell-Free System KW - Multienzyme Complexes -- metabolism KW - RNA-Binding Proteins -- metabolism KW - Cysteine Endopeptidases -- metabolism KW - Iron-Sulfur Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79821850?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Iron-dependent+oxidation%2C+ubiquitination%2C+and+degradation+of+iron+regulatory+protein+2%3A+implications+for+degradation+of+oxidized+proteins.&rft.au=Iwai%2C+K%3BDrake%2C+S+K%3BWehr%2C+N+B%3BWeissman%2C+A+M%3BLaVaute%2C+T%3BMinato%2C+N%3BKlausner%2C+R+D%3BLevine%2C+R+L%3BRouault%2C+T+A&rft.aulast=Iwai&rft.aufirst=K&rft.date=1998-04-28&rft.volume=95&rft.issue=9&rft.spage=4924&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 - 1998-06-04 N1 - Date created - 1998-06-04 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Biol Chem. 1985 Dec 15;260(29):15394-7 [2866184] J Biol Chem. 1997 Sep 5;272(36):22642-7 [9278421] Arch Biochem Biophys. 1991 Sep;289(2):371-5 [1680314] Cell. 1993 Jan 15;72(1):19-28 [8380757] Annu Rev Biochem. 1993;62:797-821 [8352601] J Biol Chem. 1994 Jan 28;269(4):2405-10 [8300566] Methods Enzymol. 1994;233:346-57 [8015469] Science. 1994 Sep 2;265(5177):1454-8 [8073290] Cell. 1994 Sep 9;78(5):761-71 [8087844] Cell. 1994 Oct 7;79(1):13-21 [7923371] J Biol Chem. 1994 Dec 9;269(49):30904-10 [7983023] Science. 1995 May 5;268(5211):726-31 [7732382] Genes Dev. 1995 Jul 1;9(13):1586-97 [7628694] J Biol Chem. 1995 Sep 15;270(37):21645-51 [7665579] Curr Biol. 1995 Aug 1;5(8):854-8 [7583140] J Biol Chem. 1995 Oct 13;270(41):24209-15 [7592626] EMBO J. 1995 Nov 1;14(21):5350-7 [7489724] Cell. 1996 Mar 22;84(6):853-62 [8601309] J Biol Chem. 1996 Apr 12;271(15):8709-13 [8621503] J Biol Chem. 1996 Jun 28;271(26):15504-9 [8663134] Proc Natl Acad Sci U S A. 1996 Aug 6;93(16):8175-82 [8710843] Annu Rev Biochem. 1996;65:801-47 [8811196] Annu Rev Genet. 1996;30:405-39 [8982460] Immunol Today. 1997 Apr;18(4):189-98 [9136456] J Biol Chem. 1997 Aug 15;272(33):20313-6 [9252331] Arch Biochem Biophys. 1990 Apr;278(1):26-34 [1969723] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Corticosterone attenuates zinc-induced neurotoxicity in primary hippocampal cultures. AN - 79873639; 9593952 AB - Primary hippocampal cultures derived from newborn rats were exposed to zinc chloride at 50, 75, 100, 150 and 200 microM concentrations. Neuronal injury was assessed morphologically and by the lactate dehydrogenase (LDH) efflux assay. Zinc exposure increased LDH efflux in a concentration-dependent manner. Exposure to 100 microM zinc for 24 h resulted in beading of neurites and swelling of neuronal soma. When cultures were co-exposed to zinc at 100 microM and corticosterone in the range of 10-5 to 10-7 M, degeneration of neurons caused by zinc was attenuated. Our study suggests that corticosterone can protect neurons from zinc-induced neurotoxicity at low doses. Copyright 1998 Elsevier Science B.V. JF - Brain research AU - Sunanda AU - Rao, B S AU - Raju, T R AD - Department of Neurophysiology, National Institute of Mental Health and Neuro Sciences, Bangalore 560 029, India. Y1 - 1998/04/27/ PY - 1998 DA - 1998 Apr 27 SP - 295 EP - 298 VL - 791 IS - 1-2 SN - 0006-8993, 0006-8993 KW - Neuroprotective Agents KW - 0 KW - Neurotoxins KW - L-Lactate Dehydrogenase KW - EC 1.1.1.27 KW - Zinc KW - J41CSQ7QDS KW - Corticosterone KW - W980KJ009P KW - Index Medicus KW - Rats KW - Animals, Newborn KW - Animals KW - Analysis of Variance KW - Cells, Cultured KW - Rats, Wistar KW - L-Lactate Dehydrogenase -- metabolism KW - Zinc -- antagonists & inhibitors KW - Neurons -- drug effects KW - Hippocampus -- cytology KW - Neurons -- enzymology KW - Hippocampus -- enzymology KW - Corticosterone -- pharmacology KW - Neurotoxins -- antagonists & inhibitors KW - Neuroprotective Agents -- pharmacology KW - Hippocampus -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79873639?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Corticosterone+attenuates+zinc-induced+neurotoxicity+in+primary+hippocampal+cultures.&rft.au=Sunanda%3BRao%2C+B+S%3BRaju%2C+T+R&rft.aulast=Sunanda&rft.aufirst=&rft.date=1998-04-27&rft.volume=791&rft.issue=1-2&rft.spage=295&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 - 1998-08-03 N1 - Date created - 1998-08-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Polyamine-like actions of aminoglycosides and aminoglycoside derivatives at NMDA receptors. AN - 79983093; 9653898 AB - Recent pharmacological studies indicate that aminoglycoside-induced hearing loss may be an excitotoxic process modulated by a polyamine-like activation of cochlear NMDA receptors. Aminoglycoside antibiotics are constituted by a series of glycosidically linked aminocyclitols and aminosugars. We report here on the actions of these individual aminocyclitols and aminosugars on wild type NMDA receptors from rat brain. Compared to the parent molecules, neither aminocyclitols (e.g., 2-deoxystreptamine, streptamine, and streptidine) nor aminosugars (e.g., D-glucosamine and kanosamine) were effective at enhancing [3H]dizocilpine ([3H]MK-801) binding or inhibiting [3H]ifenprodil at NMDA receptors. Moreover, the appropriate combinations of aminosugars and aminocyclitols did not reconstitute the activity of the parent aminoglycoside at NMDA receptors. These data indicate that the polyamine-like actions of aminoglycosides are attributable to the conformation of the parent molecule rather than a particular amine containing constituent. Thus, it may be possible to synthesize or isolate aminoglycoside antibiotics devoid of ototoxicity. JF - European journal of pharmacology AU - Segal, J A AU - Skolnick, P AD - Laboratory of Neuroscience, NIDDK, National Institutes of Health, Bethesda, MD 20892, USA. segalj@lilly.com Y1 - 1998/04/24/ PY - 1998 DA - 1998 Apr 24 SP - 311 EP - 317 VL - 347 IS - 2-3 SN - 0014-2999, 0014-2999 KW - Adrenergic alpha-Antagonists KW - 0 KW - Anti-Bacterial Agents KW - Excitatory Amino Acid Antagonists KW - Piperidines KW - Polyamines KW - Receptors, N-Methyl-D-Aspartate KW - Neomycin KW - 1404-04-2 KW - Spermine KW - 2FZ7Y3VOQX KW - Kanamycin KW - 59-01-8 KW - Dizocilpine Maleate KW - 6LR8C1B66Q KW - ifenprodil KW - R8OE3P6O5S KW - Index Medicus KW - Animals KW - Dizocilpine Maleate -- metabolism KW - Drug Interactions KW - Dose-Response Relationship, Drug KW - Piperidines -- metabolism KW - Neomycin -- pharmacology KW - Excitatory Amino Acid Antagonists -- pharmacology KW - Kanamycin -- pharmacology KW - Rats KW - Rats, Sprague-Dawley KW - Spermine -- pharmacology KW - In Vitro Techniques KW - Carbohydrate Sequence KW - Molecular Sequence Data KW - Male KW - Adrenergic alpha-Antagonists -- pharmacology KW - Polyamines -- pharmacology KW - Receptors, N-Methyl-D-Aspartate -- drug effects KW - Anti-Bacterial Agents -- pharmacology KW - Polyamines -- metabolism KW - Receptors, N-Methyl-D-Aspartate -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79983093?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Polyamine-like+actions+of+aminoglycosides+and+aminoglycoside+derivatives+at+NMDA+receptors.&rft.au=Segal%2C+J+A%3BSkolnick%2C+P&rft.aulast=Segal&rft.aufirst=J&rft.date=1998-04-24&rft.volume=347&rft.issue=2-3&rft.spage=311&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 - 1998-09-17 N1 - Date created - 1998-09-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of accessory proteins on T4 DNA polymerase replication fidelity. AN - 79840996; 9571039 AB - The influence of replication accessory proteins on the fidelity of T4 DNA polymerase has been examined. Steady-state kinetic measurements showed that exonuclease-deficient T4 DNA polymerase, alone or with clamp loaders gp44/gp62 and polymerase clamp gp45, displays decreased binding affinity for incorrect as compared to correct dNTPs and a deceased kcat for misinsertion as compared to correct insertion. Kinetic constants were similar with and without accessory proteins, indicating that accessory proteins had little effect on misinsertion. They also had little effect on the Km value for extension of a T.T mismatch. However, the kcat value for T.T mismatch extension was fivefold higher in the presence of the clamp loader and clamp proteins. Thus, in the absence of proofreading, these accessory proteins may promote stable misincorporation. The kinetic analysis is supported by error rate determinations during gap-filling synthesis, which require both misinsertion and mispair extension. For some mispairs, the accuracy of exonuclease-deficient polymerase alone is similar to that in the presence of clamp loader, clamp and single-stranded DNA binding protein (gp32). However, exonuclease-deficient holoenzyme complex is actually less accurate than the polymerase alone for some base substitutions. We suggest that gp45 promotes extension of mismatches by tethering the polymerase to DNA, a process that may be relevant to replication past lesions or other blocks to DNA synthesis. The error rate for one-nucleotide deletions in homopolymeric runs was similar for the polymerase with or without its accessory proteins. This implies that strand misalignment errors arise during highly processive replication. Thus, either unpaired bases can migrate through the run while the DNA polymerase is bound to the template-primer, or the DNA polymerase dissociates from the DNA to allow misalignment but remains tethered to the template through interactions with the clamp. Finally, the T4 replication accessory proteins reduced by >/=10-fold the rate at which exonuclease-deficient T4 DNA polymerase generated deletions of larger numbers of nucleotides, indicating that these proteins influence replication fidelity for other than single base mutations. Copyright 1998 Academic Press Limited. JF - Journal of molecular biology AU - Kroutil, L C AU - Frey, M W AU - Kaboord, B F AU - Kunkel, T A AU - Benkovic, S J AD - Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1998/04/24/ PY - 1998 DA - 1998 Apr 24 SP - 135 EP - 146 VL - 278 IS - 1 SN - 0022-2836, 0022-2836 KW - DNA, Viral KW - 0 KW - DNA-Binding Proteins KW - Oligodeoxyribonucleotides KW - Trans-Activators KW - Viral Proteins KW - gene 43 protein, Enterobacteria phage T4 KW - gene 44 protein, Enterobacteria phage T4 KW - gene 45 protein, Enterobacteria phage T4 KW - gp32 protein, Enterobacteria phage T4 KW - gp62 protein, bacteriophage T4 KW - DNA-Directed DNA Polymerase KW - EC 2.7.7.7 KW - Index Medicus KW - Frameshift Mutation KW - DNA, Viral -- biosynthesis KW - Base Sequence KW - Kinetics KW - Molecular Sequence Data KW - Mutagenesis KW - Trans-Activators -- metabolism KW - Bacteriophage T4 -- metabolism KW - Viral Proteins -- metabolism KW - DNA Replication KW - DNA-Directed DNA Polymerase -- metabolism KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79840996?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+molecular+biology&rft.atitle=Effect+of+accessory+proteins+on+T4+DNA+polymerase+replication+fidelity.&rft.au=Kroutil%2C+L+C%3BFrey%2C+M+W%3BKaboord%2C+B+F%3BKunkel%2C+T+A%3BBenkovic%2C+S+J&rft.aulast=Kroutil&rft.aufirst=L&rft.date=1998-04-24&rft.volume=278&rft.issue=1&rft.spage=135&rft.isbn=&rft.btitle=&rft.title=Journal+of+molecular+biology&rft.issn=00222836&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-06-25 N1 - Date created - 1998-06-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Delineation of the regions of interleukin-2 (IL-2) receptor beta chain important for association of Jak1 and Jak3. Jak1-independent functional recruitment of Jak3 to Il-2Rbeta. AN - 79818923; 9553136 AB - Interleukin-2 (IL-2) induces heterodimerization of the IL-2 receptor beta (IL-2Rbeta) and gammac chains of its receptor and activates the Janus family tyrosine kinases, Jak1 and Jak3. Whereas Jak1 associates with IL-2Rbeta, Jak3 associates primarily with gammac but also with IL-2Rbeta. We analyzed four IL-2Rbeta mutations that diminish IL-2-induced proliferation and found that each also decreased IL-2-induced signal transducer and activator of transcription (STAT) activation. For this reason, and because the mutations were in the IL-2Rbeta membrane-proximal region, we investigated and found that each mutation diminished IL-2Rbeta association with both Jak1 and Jak3. This suggested that these Jaks might interact with the same region of IL-2Rbeta; however, certain IL-2Rbeta internal deletions and C-terminal truncations differentially affected the association of Jak1 and Jak3. Interestingly, just as Jak1-IL-2Rbeta association is Jak3-independent and functionally important, we show that Jak3-IL-2Rbeta association is Jak1-independent and implicate this association as being important for IL-2-induced Stat5 activation. Moreover, Jak1 and Jak3 could associate only in the presence of IL-2Rbeta, suggesting that these kinases can simultaneously bind to IL-2Rbeta. Thus, our data not only demonstrate that somewhat more distal as well as membrane-proximal cytoplasmic regions of a type I cytokine receptor are important for Jak kinase association but also suggest that two IL-2Rbeta-Jak kinase interactions are important for IL-2 signaling. JF - The Journal of biological chemistry AU - Zhu, M H AU - Berry, J A AU - Russell, S M AU - Leonard, W J AD - Laboratory of Molecular Immunology, NHLBI, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/04/24/ PY - 1998 DA - 1998 Apr 24 SP - 10719 EP - 10725 VL - 273 IS - 17 SN - 0021-9258, 0021-9258 KW - DNA-Binding Proteins KW - 0 KW - Interleukin-2 KW - Milk Proteins KW - Receptors, Interleukin-2 KW - STAT5 Transcription Factor KW - Trans-Activators KW - Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - JAK1 protein, human KW - EC 2.7.10.2 KW - JAK3 protein, human KW - Jak1 protein, mouse KW - Jak3 protein, mouse KW - Janus Kinase 1 KW - Janus Kinase 3 KW - Index Medicus KW - Trans-Activators -- metabolism KW - Animals KW - Interleukin-2 -- metabolism KW - COS Cells KW - HeLa Cells KW - Humans KW - Mice KW - Protein Binding KW - Mutagenesis, Site-Directed KW - Signal Transduction KW - DNA-Binding Proteins -- metabolism KW - Receptors, Interleukin-2 -- metabolism KW - Protein-Tyrosine Kinases -- metabolism KW - Receptors, Interleukin-2 -- genetics KW - Receptors, Interleukin-2 -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79818923?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Delineation+of+the+regions+of+interleukin-2+%28IL-2%29+receptor+beta+chain+important+for+association+of+Jak1+and+Jak3.+Jak1-independent+functional+recruitment+of+Jak3+to+Il-2Rbeta.&rft.au=Zhu%2C+M+H%3BBerry%2C+J+A%3BRussell%2C+S+M%3BLeonard%2C+W+J&rft.aulast=Zhu&rft.aufirst=M&rft.date=1998-04-24&rft.volume=273&rft.issue=17&rft.spage=10719&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 - 1998-05-22 N1 - Date created - 1998-05-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Human P2Y1 receptor: molecular modeling and site-directed mutagenesis as tools to identify agonist and antagonist recognition sites. AN - 79820512; 9554879 AB - The molecular basis for recognition by human P2Y1 receptors of the novel, competitive antagonist 2'-deoxy-N6-methyladenosine 3', 5'-bisphosphate (MRS 2179) was probed using site-directed mutagenesis and molecular modeling. The potency of this antagonist was measured in mutant receptors in which key residues in the transmembrane helical domains (TMs) 3, 5, 6, and 7 were replaced by Ala or other amino acids. The capacity of MRS 2179 to block stimulation of phospholipase C promoted by 2-methylthioadenosine 5'-diphosphate (2-MeSADP) was lost in P2Y1 receptors having F226A, K280A, or Q307A mutations, indicating that these residues are critical for the binding of the antagonist molecule. Mutation of the residues His132, Thr222, and Tyr136 had an intermediate effect on the capacity of MRS 2179 to block the P2Y1 receptor. These positions therefore appear to have a modulatory role in recognition of this antagonist. F131A, H277A, T221A, R310K, or S317A mutant receptors exhibited an apparent affinity for MRS 2179 that was similar to that observed with the wild-type receptor. Thus, Phe131, Thr221, His277, and Ser317 are not essential for antagonist recognition. A computer-generated model of the human P2Y1 receptor was built and analyzed to help interpret these results. The model was derived through primary sequence comparison, secondary structure prediction, and three-dimensional homology building, using rhodopsin as a template, and was consistent with data obtained from mutagenesis studies. We have introduced a "cross-docking" procedure to obtain energetically refined 3D structures of the ligand-receptor complexes. Cross-docking simulates the reorganization of the native receptor structure induced by a ligand. A putative nucleotide binding site was localized and used to predict which residues are likely to be in proximity to agonists and antagonists. According to our model TM6 and TM7 are close to the adenine ring, TM3 and TM6 are close to the ribose moiety, and TM3, TM6, and TM7 are near the triphosphate chain. JF - Journal of medicinal chemistry AU - Moro, S AU - Guo, D AU - Camaioni, E AU - Boyer, J L AU - Harden, T K AU - Jacobson, K A AD - Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0810, USA. Y1 - 1998/04/23/ PY - 1998 DA - 1998 Apr 23 SP - 1456 EP - 1466 VL - 41 IS - 9 SN - 0022-2623, 0022-2623 KW - Enzyme Inhibitors KW - 0 KW - Ligands KW - N(6)-methyl-2'-deoxyadenosine 3',5'-diphosphate KW - P2RY1 protein, human KW - Purinergic P2 Receptor Agonists KW - Purinergic P2 Receptor Antagonists KW - Receptors, Purinergic P2 KW - Receptors, Purinergic P2Y1 KW - Adenosine Diphosphate KW - 61D2G4IYVH KW - Type C Phospholipases KW - EC 3.1.4.- KW - Index Medicus KW - Animals KW - Protein Structure, Secondary KW - Type C Phospholipases -- antagonists & inhibitors KW - COS Cells KW - Humans KW - Receptors, Purinergic P2 -- chemistry KW - Enzyme Inhibitors -- chemistry KW - Amino Acid Sequence KW - Receptors, Purinergic P2 -- genetics KW - Molecular Sequence Data KW - Point Mutation KW - Enzyme Inhibitors -- pharmacology KW - Enzyme-Linked Immunosorbent Assay KW - Enzyme Inhibitors -- metabolism KW - Protein Conformation KW - Mutagenesis, Site-Directed KW - Adenosine Diphosphate -- analogs & derivatives KW - Models, Molecular KW - Adenosine Diphosphate -- chemistry KW - Adenosine Diphosphate -- pharmacology KW - Adenosine Diphosphate -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79820512?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+medicinal+chemistry&rft.atitle=Human+P2Y1+receptor%3A+molecular+modeling+and+site-directed+mutagenesis+as+tools+to+identify+agonist+and+antagonist+recognition+sites.&rft.au=Moro%2C+S%3BGuo%2C+D%3BCamaioni%2C+E%3BBoyer%2C+J+L%3BHarden%2C+T+K%3BJacobson%2C+K+A&rft.aulast=Moro&rft.aufirst=S&rft.date=1998-04-23&rft.volume=41&rft.issue=9&rft.spage=1456&rft.isbn=&rft.btitle=&rft.title=Journal+of+medicinal+chemistry&rft.issn=00222623&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-05-21 N1 - Date created - 1998-05-21 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7 [271968] J Mol Biol. 1981 Jan 5;145(1):215-50 [7265198] J Mol Biol. 1982 May 5;157(1):105-32 [7108955] Mol Cell Biol. 1983 Feb;3(2):280-9 [6300662] Biochem J. 1983 May 15;212(2):473-82 [6309146] EMBO J. 1982;1(12):1635-40 [6765200] Methods Enzymol. 1987;152:684-704 [3657593] Biochem J. 1988 Jun 1;252(2):583-93 [2843174] Nature. 1993 Apr 22;362(6422):770-2 [8469290] FEBS Lett. 1993 Jun 14;324(2):219-25 [8508924] J Med Chem. 1993 Nov 26;36(24):3937-46 [8254622] Pharmacol Rev. 1994 Jun;46(2):143-56 [7938164] J Biol Chem. 1995 Mar 3;270(9):4185-8 [7876172] J Biol Chem. 1995 Jun 9;270(23):13987-97 [7775460] Biochem Pharmacol. 1996 Feb 23;51(4):545-55 [8619901] Br J Pharmacol. 1996 May;118(1):167-73 [8733591] Drug Des Discov. 1995 Nov;13(2):133-54 [8872457] Mol Pharmacol. 1997 Sep;52(3):499-507 [9281613] Nature. 1997 Sep 11;389(6647):203-6 [9296501] J Med Chem. 1997 Nov 21;40(24):3871-86 [9397168] J Med Chem. 1998 Jan 15;41(2):183-90 [9457242] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cross-talk between protein kinase C-alpha (PKC-alpha) and -delta (PKC-delta): PKC-alpha elevates the PKC-delta protein level, altering its mRNA transcription and degradation. AN - 79812693; 9548940 AB - Studies utilizing the overexpression of individual isoforms indicated that both PKC-alpha and -delta promote a number of biological effects, including inhibition of DNA synthesis associated with rearrangements of the actin cytoskeleton in the murine B-cell lymphoma (Baf3), differentiation of the murine promyelocyte line 32D, and activation of MAP kinase in CHO fibroblasts. We postulated that these results reflect some form of cross-regulation between PKC-alpha and -delta rather than their functional redundancy. In this report, we show that overexpression of PKC-alpha in Baf3 and 32D leads to an elevation of the endogenous PKC-delta mRNA and protein levels. The elevated steady-state PKC-delta mRNA level results from a combination of increased PKC-delta transcription and mRNA stability. Upregulation of PKC-delta mRNA by PKC-alpha occurs even after a selective depletion of the PKC-delta protein. In addition, phorbol ester-induced elevation of PKC-delta mRNA and protein levels can be prevented by the PKC inhibitor GF109203X, an indication of the requirement for PKC kinase activity. Inhibition of new protein synthesis by cycloheximide showed that upregulation of PKC-delta mRNA, as opposed to delayed downregulation of the PKC-delta protein, is primarily responsible for the accumulation of this isoform by PKC-alpha. In parental Baf3 and 32D cells and PKC-alpha overexpressers, PKC-alpha and PKC-delta are uniquely involved in cross-regulation, while PKC-epsilon, PKC-eta, and PKC-mu are not. JF - Biochemistry AU - Romanova, L Y AU - Alexandrov, I A AU - Nordan, R P AU - Blagosklonny, M V AU - Mushinski, J F AD - Laboratory of Genetics and Medicine Branch, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1998/04/21/ PY - 1998 DA - 1998 Apr 21 SP - 5558 EP - 5565 VL - 37 IS - 16 SN - 0006-2960, 0006-2960 KW - Indoles KW - 0 KW - Isoenzymes KW - Maleimides KW - RNA, Messenger KW - Prkcd protein, mouse KW - EC 2.7.1.- KW - Prkca protein, mouse KW - EC 2.7.11.13 KW - Protein Kinase C KW - Protein Kinase C-alpha KW - Protein Kinase C-delta KW - bisindolylmaleimide I KW - L79H6N0V6C KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - Enzyme Stability -- genetics KW - Up-Regulation -- genetics KW - Mice KW - Enzyme Activation -- genetics KW - Lymphoma, B-Cell KW - Tumor Cells, Cultured KW - Up-Regulation -- drug effects KW - Enzyme Activation -- drug effects KW - Leukemia, Promyelocytic, Acute KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Enzyme Stability -- drug effects KW - Indoles -- pharmacology KW - Maleimides -- pharmacology KW - Protein Kinase C -- metabolism KW - Transcription, Genetic -- drug effects KW - RNA, Messenger -- metabolism KW - Isoenzymes -- physiology KW - Isoenzymes -- biosynthesis KW - Protein Kinase C -- genetics KW - Protein Kinase C -- biosynthesis KW - Protein Kinase C -- physiology KW - Isoenzymes -- genetics KW - Isoenzymes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79812693?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cross-talk+between+protein+kinase+C-alpha+%28PKC-alpha%29+and+-delta+%28PKC-delta%29%3A+PKC-alpha+elevates+the+PKC-delta+protein+level%2C+altering+its+mRNA+transcription+and+degradation.&rft.au=Romanova%2C+L+Y%3BAlexandrov%2C+I+A%3BNordan%2C+R+P%3BBlagosklonny%2C+M+V%3BMushinski%2C+J+F&rft.aulast=Romanova&rft.aufirst=L&rft.date=1998-04-21&rft.volume=37&rft.issue=16&rft.spage=5558&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-05-14 N1 - Date created - 1998-05-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - BSE: the final resting place. AN - 79964269; 9643681 JF - Lancet (London, England) AU - Brown, P AD - Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892, USA. Y1 - 1998/04/18/ PY - 1998 DA - 1998 Apr 18 SP - 1146 EP - 1147 VL - 351 IS - 9110 SN - 0140-6736, 0140-6736 KW - Hazardous Waste KW - 0 KW - Medical Waste KW - Abridged Index Medicus KW - Index Medicus KW - United States KW - Animals KW - Cattle KW - Risk Factors KW - Humans KW - Ireland KW - Hazardous Waste -- legislation & jurisprudence KW - Creutzfeldt-Jakob Syndrome -- transmission KW - Prion Diseases -- prevention & control KW - Encephalopathy, Bovine Spongiform -- transmission KW - Medical Waste -- legislation & jurisprudence KW - Prion Diseases -- transmission KW - Creutzfeldt-Jakob Syndrome -- prevention & control KW - Encephalopathy, Bovine Spongiform -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79964269?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Lancet+%28London%2C+England%29&rft.atitle=BSE%3A+the+final+resting+place.&rft.au=Brown%2C+P&rft.aulast=Brown&rft.aufirst=P&rft.date=1998-04-18&rft.volume=351&rft.issue=9110&rft.spage=1146&rft.isbn=&rft.btitle=&rft.title=Lancet+%28London%2C+England%29&rft.issn=01406736&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-07-01 N1 - Date created - 1998-07-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Recognition of core binding sites by bacteriophage integrases. AN - 79839431; 9571022 AB - Bacteriophage integrases promote recombination between DNA molecules that carry attachment sites. They are members of a large and widely distributed family of site-specific recombinases with diverse biological roles. The integrases of phages lambda and HK022 are closely related members of this family, but neither protein efficiently recombines the attachment sites of the other phage. The nucleotides responsible for this specificity difference are located close to the points of recombinational strand exchange, within an integrase binding motif called the extended core binding site. There are four imperfectly repeated copies of this motif in each set of phage attachment sites, but only two, B' and C, contain major specificity determinants. When these specificity determinants were replaced by the corresponding nucleotides from a site with the alternative specificity, the resulting mutant was recombined by both integrases. Thus, the determinants act by impeding recombination promoted by the non-cognate integrase. We found that identical nucleotide substitutions within different core site copies had different effects on recombination, suggesting that integrase does not recognize each of the extended core binding sites in the same way. Finally, substitution at several positions in lambda integrase with the corresponding HK022-specific amino acids prevents recombination of lambda attachment sites, and this defect can be suppressed in an allele-specific manner by appropriate substitutions of HK022-specific nucleotides in the extended core binding sites. Copyright 1998 Academic Press Limited. JF - Journal of molecular biology AU - Dorgai, L AU - Sloan, S AU - Weisberg, R A AD - Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, Bethesda, MD 20892, USA. Y1 - 1998/04/17/ PY - 1998 DA - 1998 Apr 17 SP - 1059 EP - 1070 VL - 277 IS - 5 SN - 0022-2836, 0022-2836 KW - Viral Proteins KW - 0 KW - Integrases KW - EC 2.7.7.- KW - Index Medicus KW - Coliphages -- enzymology KW - Sequence Alignment KW - Plasmids -- genetics KW - Recombination, Genetic -- genetics KW - Molecular Sequence Data KW - Viral Proteins -- metabolism KW - Amino Acid Sequence KW - Mutagenesis -- genetics KW - Binding Sites -- genetics KW - Bacteriophages -- enzymology KW - Integrases -- chemistry KW - Integrases -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79839431?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+molecular+biology&rft.atitle=Recognition+of+core+binding+sites+by+bacteriophage+integrases.&rft.au=Dorgai%2C+L%3BSloan%2C+S%3BWeisberg%2C+R+A&rft.aulast=Dorgai&rft.aufirst=L&rft.date=1998-04-17&rft.volume=277&rft.issue=5&rft.spage=1059&rft.isbn=&rft.btitle=&rft.title=Journal+of+molecular+biology&rft.issn=00222836&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-06-19 N1 - Date created - 1998-06-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transforming G protein-coupled receptors block insulin and ras-induced adipocytic differentiation in 3T3-L1 cells: evidence for a PKC and MAP kinase independent pathway. AN - 79837969; 9571194 AB - We have used the expression of muscarinic m1 receptors in the preadipocytic 3T3-L1 cell line for dissecting the nature of the G protein-linked pathways governing adipocytic differentiation, a complex process controlled by many stimuli and their downstream targets. 3T3-L1 cells can be differentiated by insulin or by ras oncogenes, and MAP kinase has been implicated in this process. However, m1 stimulation failed to induce differentiation of 3T3-L1 cells. Furthermore, it prevented insulin or v-ras-induced adipocytic differentiation, utilizing a protein kinase C-independent pathway. m1 stimulation did not alter the phosphorylation state of the insulin receptor substrates IRS-1 and SHC, nor the recruitment of Grb-2. Interestingly, whereas m1 receptors potently activated MAP kinase, another differentiation-inhibitor, TNF alpha, did not affect it. These results suggest that the control of adipocytic differentiation can occur utilizing a biochemical route independent of protein kinase C, and acting downstream, or independently from the Ras-MAP kinase pathway. JF - Biochemical and biophysical research communications AU - Crespo, P AU - Font de Mora, J AU - Aaronson, D S AU - Santos, E AU - Gutkind, J S AD - Molecular Signaling Unit, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892, USA. crespop@medi.unican.es Y1 - 1998/04/17/ PY - 1998 DA - 1998 Apr 17 SP - 554 EP - 561 VL - 245 IS - 2 SN - 0006-291X, 0006-291X KW - Adaptor Proteins, Signal Transducing KW - 0 KW - Adaptor Proteins, Vesicular Transport KW - GRB2 Adaptor Protein KW - Grb2 protein, mouse KW - Indoles KW - Insulin KW - Insulin Receptor Substrate Proteins KW - Irs1 protein, mouse KW - Maleimides KW - Phosphoproteins KW - Proteins KW - Receptors, Muscarinic KW - Shc Signaling Adaptor Proteins KW - Shc1 protein, mouse KW - Src Homology 2 Domain-Containing, Transforming Protein 1 KW - Tumor Necrosis Factor-alpha KW - Carbachol KW - 8Y164V895Y KW - Protein Kinase C KW - EC 2.7.11.13 KW - Calcium-Calmodulin-Dependent Protein Kinases KW - EC 2.7.11.17 KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - ras Proteins KW - EC 3.6.5.2 KW - bisindolylmaleimide I KW - L79H6N0V6C KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - 3T3 Cells KW - Animals KW - Tumor Necrosis Factor-alpha -- pharmacology KW - Mice KW - Histocytochemistry KW - Proteins -- metabolism KW - Signal Transduction -- physiology KW - Phosphorylation KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Indoles -- pharmacology KW - Protein Kinase C -- physiology KW - Calcium-Calmodulin-Dependent Protein Kinases -- physiology KW - Carbachol -- pharmacology KW - Maleimides -- pharmacology KW - Phosphoproteins -- metabolism KW - Cell Differentiation -- physiology KW - GTP-Binding Proteins -- metabolism KW - Insulin -- pharmacology KW - Adipocytes -- metabolism KW - ras Proteins -- pharmacology KW - Receptors, Muscarinic -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79837969?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Transforming+G+protein-coupled+receptors+block+insulin+and+ras-induced+adipocytic+differentiation+in+3T3-L1+cells%3A+evidence+for+a+PKC+and+MAP+kinase+independent+pathway.&rft.au=Crespo%2C+P%3BFont+de+Mora%2C+J%3BAaronson%2C+D+S%3BSantos%2C+E%3BGutkind%2C+J+S&rft.aulast=Crespo&rft.aufirst=P&rft.date=1998-04-17&rft.volume=245&rft.issue=2&rft.spage=554&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 - 1998-06-02 N1 - Date created - 1998-06-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular cloning of the helodermin and exendin-4 cDNAs in the lizard. Relationship to vasoactive intestinal polypeptide/pituitary adenylate cyclase activating polypeptide and glucagon-like peptide 1 and evidence against the existence of mammalian homologues. AN - 79809920; 9545315 AB - Helodermin and exendin-4, two peptides isolated from the salivary gland of the Gila monster, Heloderma suspectum, are approximately 50% homologous to vasoactive intestinal peptide (VIP) and glucagon-like peptide-1 (GLP-1), respectively, and interact with the mammalian receptors for VIP and GLP-1 with equal or higher affinity and efficacy. Immunohistochemical studies suggested the presence of helodermin-like peptides in mammals. To determine whether helodermin and exendin-4 are present in mammals and their evolutionary relationship to VIP and GLP-1, their cDNAs were first cloned from Gila monster salivary gland. Northern blots and reverse transcription-polymerase chain reaction of multiple Gila monster tissues identified approximately 500-base pair transcripts only from salivary gland. Both helodermin and exendin-4 full-length cDNAs were approximately 500 base pairs long, and they encoded precursor proteins containing the entire amino acid sequence of helodermin and exendin-4, as well as a 44- or 45-amino acid N-terminal extension peptide, respectively, having approximately 60% homology. The size and structural organization of these cDNAs indicated that they were closely related to one another but markedly different from known cDNAs for the VIP/GLP-1 peptide family previously identified in both lower and higher evolved species. Cloning of the Gila monster VIP/peptide histidine isoleucine, pituitary adenylate cyclase activating polypeptide, and glucagon/GLP-1 cDNAs and Southern blotting of Gila monster DNA demonstrate the coexistence of separate genes for these peptides and suggests, along with the restricted salivary gland expression, that helodermin and exendin-4 coevolved to serve a separate specialized function. Probing of a variety of rat and human tissues on Northern blots, human and rat Southern blots, and genomic and cDNA libraries with either helodermin- or exendin-4-specific cDNAs failed to identify evidence for mammalian homologues. These data indicate that helodermin and exendin-4 are not the precursors to VIP and GLP-1 and that they belong to a separate peptide family encoded by separate genes. Furthermore, the existence of as yet undiscovered mammalian homologues to helodermin and exendin-4 seems unlikely. JF - The Journal of biological chemistry AU - Pohl, M AU - Wank, S A AD - Digestive Diseases Branch, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/04/17/ PY - 1998 DA - 1998 Apr 17 SP - 9778 EP - 9784 VL - 273 IS - 16 SN - 0021-9258, 0021-9258 KW - ADCYAP1 protein, human KW - 0 KW - Adcyap1 protein, rat KW - DNA Primers KW - DNA, Complementary KW - Neuropeptides KW - Peptide Fragments KW - Peptides KW - Pituitary Adenylate Cyclase-Activating Polypeptide KW - Protein Precursors KW - Recombinant Proteins KW - Venoms KW - glucagon-like peptide 1 (7-36) KW - 107444-51-9 KW - Vasoactive Intestinal Peptide KW - 37221-79-7 KW - Glucagon-Like Peptides KW - 62340-29-8 KW - heliodermin KW - 89468-62-2 KW - Glucagon-Like Peptide 1 KW - 89750-14-1 KW - Glucagon KW - 9007-92-5 KW - exenatide KW - 9P1872D4OL KW - Index Medicus KW - Animals KW - Recombinant Proteins -- biosynthesis KW - Mammals KW - Humans KW - Lizards KW - Amino Acid Sequence KW - Cloning, Molecular KW - Rats KW - Polymerase Chain Reaction KW - Base Sequence KW - Chickens KW - Peptide Fragments -- chemistry KW - Sequence Alignment KW - Trout KW - Protein Precursors -- chemistry KW - Molecular Sequence Data KW - Recombinant Proteins -- chemistry KW - Sequence Homology, Amino Acid KW - Vasoactive Intestinal Peptide -- chemistry KW - Peptides -- metabolism KW - Peptides -- chemistry KW - Peptides -- genetics KW - Neuropeptides -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79809920?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Molecular+cloning+of+the+helodermin+and+exendin-4+cDNAs+in+the+lizard.+Relationship+to+vasoactive+intestinal+polypeptide%2Fpituitary+adenylate+cyclase+activating+polypeptide+and+glucagon-like+peptide+1+and+evidence+against+the+existence+of+mammalian+homologues.&rft.au=Pohl%2C+M%3BWank%2C+S+A&rft.aulast=Pohl&rft.aufirst=M&rft.date=1998-04-17&rft.volume=273&rft.issue=16&rft.spage=9778&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 - 1998-05-21 N1 - Date created - 1998-05-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characterization of V3 loop-Pseudomonas exotoxin chimeras. Candidate vaccines for human immunodeficiency virus-1. AN - 79809524; 9545339 AB - To develop a candidate vaccine for human immunodeficiency virus, type 1 (HIV-1), chimeric proteins were constructed by inserting sequences derived from the V3 loop of gp120 into a nontoxic form of Pseudomonas exotoxin (PE). Inserts of 14 or 26 amino acids, constrained by a disulfide bond, were introduced between domains II and III of PE. V3 loop-toxin proteins expressed in Escherichia coli and corresponding to either MN (subtype B) or Thai (subtype E) strains, were recognized by strain-specific monoclonal anti-gp120 antibodies. When loop sequences were introduced into an enzymatically active form of the toxin, there was no loss of toxin-mediated cell killing, suggesting that these sequences were co-transported to the cytosol. Sera from rabbits injected with nontoxic PE-V3 loop chimeras were reactive for strain-specific gp120s in Western blots, immunocapture assays, enzyme-linked immunosorbent assays, and neutralized HIV-1 infectivity. Since toxin vectors were designed to receive oligonucleotide duplexes encoding any V3 loop sequence, this approach should allow for the production of V3 loop-toxin chimeras corresponding to multiple HIV isolates. JF - The Journal of biological chemistry AU - FitzGerald, D J AU - Fryling, C M AU - McKee, M L AU - Vennari, J C AU - Wrin, T AU - Cromwell, M E AU - Daugherty, A L AU - Mrsny, R J AD - Biotherapy Section, Laboratory of Molecular Biology, Division of Basic Science, NCI, National Institutes of Health, Bethesda, Maryland 20892-4255, USA. Y1 - 1998/04/17/ PY - 1998 DA - 1998 Apr 17 SP - 9951 EP - 9958 VL - 273 IS - 16 SN - 0021-9258, 0021-9258 KW - AIDS Vaccines KW - 0 KW - Bacterial Toxins KW - Exotoxins KW - HIV Antibodies KW - HIV Envelope Protein gp120 KW - Recombinant Fusion Proteins KW - Vaccines, Synthetic 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 - AIDS/HIV KW - Animals KW - Recombinant Fusion Proteins -- immunology KW - Humans KW - Rabbits KW - Amino Acid Sequence KW - Recombinant Fusion Proteins -- toxicity KW - Recombinant Fusion Proteins -- chemistry KW - Tumor Cells, Cultured KW - Acquired Immunodeficiency Syndrome -- blood KW - Cell Survival -- drug effects KW - HIV Antibodies -- blood KW - HIV Antibodies -- immunology KW - Acquired Immunodeficiency Syndrome -- immunology KW - Neutralization Tests KW - Escherichia coli KW - Molecular Sequence Data KW - Enzyme-Linked Immunosorbent Assay KW - Carcinoma, Squamous Cell KW - Protein Conformation KW - HIV-1 -- isolation & purification KW - HIV Envelope Protein gp120 -- chemistry KW - Exotoxins -- chemistry KW - Exotoxins -- immunology KW - HIV Envelope Protein gp120 -- immunology KW - Exotoxins -- toxicity KW - HIV Envelope Protein gp120 -- toxicity KW - Pseudomonas aeruginosa KW - HIV-1 -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79809524?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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+V3+loop-Pseudomonas+exotoxin+chimeras.+Candidate+vaccines+for+human+immunodeficiency+virus-1.&rft.au=FitzGerald%2C+D+J%3BFryling%2C+C+M%3BMcKee%2C+M+L%3BVennari%2C+J+C%3BWrin%2C+T%3BCromwell%2C+M+E%3BDaugherty%2C+A+L%3BMrsny%2C+R+J&rft.aulast=FitzGerald&rft.aufirst=D&rft.date=1998-04-17&rft.volume=273&rft.issue=16&rft.spage=9951&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 - 1998-05-21 N1 - Date created - 1998-05-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of transcriptional repressor ICER in cyclic AMP-mediated attenuation of cytokine gene expression in human thymocytes. AN - 79804862; 9545284 AB - Proliferating human medullary thymocytes can exhibit characteristic T helper cell type 1 cytokine responses exemplified by the immediate early expression of interleukin-2, interferon-gamma, tumor necrosis factor-alpha, and lymphotoxin-beta. Here we report that cAMP-mediated attenuation of the transcription of T helper-1-specific cytokine genes in human medullary thymocytes correlates with the induction of the cAMP-mediated transcriptional repressor ICER (inducible cAMP early repressor). We show that ICER binds specifically to several NFAT/AP-1 (nuclear factor of activated T cells/activating protein-1) composite DNA sites essential for the activation of the interleukin (IL)-2 promoter as well as to a homologous DNA motif present in the proximal segment of the interferon-gamma promoter. In the presence of the minimal NFAT DNA-binding domain, which is sufficient for both DNA binding and AP-1 complex formation, ICER and NFAT form NFAT/ICER ternary complexes on several NFAT/AP-1 DNA composite sites previously identified as essential for the expression of the immunoregulatory cytokines such as IL-2, IL-4, granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor-alpha. In extracts prepared from human medullary thymocytes treated with forskolin and ionomycin, these composite sites bind endogenously expressed ICER either singly or in complexes. Moreover, in Jurkat cells, ectopically expressed ICER represses transcription from NFAT-mediated, phorbol ester/ionophore-activated IL-2, granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor-alpha promoters. We present evidence that ICER interactions with NFAT/AP-1 composite DNA sites correlate with its ability to repress transcription. These findings provide further insight into the mechanisms involved in cAMP-mediated transcriptional attenuation of cytokine expression. JF - The Journal of biological chemistry AU - Bodor, J AU - Habener, J F AD - Laboratory of Molecular Endocrinology, Massachusetts General Hospital, Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts 02114, USA. Bodorj@exchange.nih.gov Y1 - 1998/04/17/ PY - 1998 DA - 1998 Apr 17 SP - 9544 EP - 9551 VL - 273 IS - 16 SN - 0021-9258, 0021-9258 KW - Cytokines KW - 0 KW - DNA-Binding Proteins KW - Interleukin-2 KW - LTB protein, human KW - Lymphotoxin-alpha KW - Lymphotoxin-beta KW - Membrane Proteins KW - NFATC Transcription Factors KW - Nuclear Proteins KW - RNA, Messenger KW - Recombinant Proteins KW - Repressor Proteins KW - Transcription Factor AP-1 KW - Transcription Factors KW - Tumor Necrosis Factor-alpha KW - Cyclic AMP Response Element Modulator KW - 135844-64-3 KW - Ionomycin KW - 56092-81-0 KW - Interferon-gamma KW - 82115-62-6 KW - Cyclic AMP KW - E0399OZS9N KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Lymphotoxin-alpha -- biosynthesis KW - Transcription, Genetic -- drug effects KW - Recombinant Proteins -- biosynthesis KW - Transcription Factors -- metabolism KW - Transcription Factor AP-1 -- metabolism KW - Cell Nucleus -- metabolism KW - Humans KW - Interferon-gamma -- biosynthesis KW - Interleukin-2 -- biosynthesis KW - Tumor Necrosis Factor-alpha -- biosynthesis KW - Ionomycin -- pharmacology KW - RNA, Messenger -- biosynthesis KW - Binding Sites KW - Child, Preschool KW - Infant KW - Lymphocyte Activation KW - Base Sequence KW - Cells, Cultured KW - Membrane Proteins -- biosynthesis KW - Molecular Sequence Data KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Thymus Gland -- immunology KW - Cytokines -- genetics KW - Gene Expression Regulation -- immunology KW - Cytokines -- biosynthesis KW - Repressor Proteins -- metabolism KW - Cyclic AMP -- metabolism KW - T-Lymphocytes -- drug effects KW - Thymus Gland -- drug effects KW - T-Lymphocytes -- immunology KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79804862?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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+transcriptional+repressor+ICER+in+cyclic+AMP-mediated+attenuation+of+cytokine+gene+expression+in+human+thymocytes.&rft.au=Bodor%2C+J%3BHabener%2C+J+F&rft.aulast=Bodor&rft.aufirst=J&rft.date=1998-04-17&rft.volume=273&rft.issue=16&rft.spage=9544&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 - 1998-05-21 N1 - Date created - 1998-05-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Acquired salivary dysfunction. Drugs and radiation. AN - 79892306; 9599303 AB - When considering the effects of drugs on salivary glands, a distinction should be drawn between the complaint of oral dryness (xerostomia), a symptom, and measurable secretory hypofunction, a sign. In general, the symptom of xerostomia is often not accompanied by objective reductions in salivary output, and xerostomia is not a reliable indicator of secretory hypofunction. Whereas therapeutic pharmaceutical side effects represent the most prominent cause of xerostomia, with over 500 drugs associated with this symptom, only a small number of drugs have been demonstrated to reduce salivary output substantially. There are examples in which drugs with a high prevalence of xerostomia complaints do not affect secretory function. The mechanisms responsible for this discrepancy between subjective and objective findings have not been fully identified. It is hypothesized that alterations in systemic or mucosal hydration may play a role. Of the drugs with true salivary hypofunctional actions, most have direct anticholinergic properties. In almost all cases, the salivary effects of pharmaceuticals are not permanent, and function returns to pretreatment levels when the medication is stopped. By contrast, the effects of irradiation on the salivary glands are permanent when exposures exceed 50 Gy. About 40,000 individuals per year receive irradiation that involves the salivary glands (by external beam or internal sources--radon implants and 1311) for treatment of cancers of the head and neck region. Although these radiation effects have been recognized as a significant clinical problem for more than 80 years, the specific mechanisms responsible for radiation-induced salivary gland dysfunction are still not understood. With the exception of studies documenting the secretory functional deficits following head and neck irradiation, limited studies have been done in humans. The majority of experimental work has been done in rodents. A variety of mechanisms, including mitotic and interphase cell death, direct DNA damage or effects of secondary metabolites, damage to progenitor cells, or altered gene expression, have all been proposed to explain the salivary epithelial cell death observed. Recent experimental studies with models of radiation-induced salivary damage in rats and a human salivary cell line suggest that the small percentage of surviving epithelial cells are capable of performing functions such as signal transduction and ion transport normally. Apoptotic cell death following irradiation has not been a prominent feature in these model systems. The effects of head and neck radiation on the salivary glands and oral cavity continue to present multiple significant clinical problems both during and after radiotherapy. In recent years, there has been some progress in minimizing these effects through more careful shielding and pretreatment planning. Additionally, there are preliminary results from a clinical trial suggesting that the use of a secretagogue, pilocarpine HCl, given during the course of radiotherapy, may reduce the secretory hypofunctional effects. A multicenter trial is now underway to test this hypothesis. There is still a real need to develop more effective treatments for this condition. JF - Annals of the New York Academy of Sciences AU - Fox, P C AD - Clinical Investigations Section, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892-1190, USA. pfox@yoda.nidr.nih.gov Y1 - 1998/04/15/ PY - 1998 DA - 1998 Apr 15 SP - 132 EP - 137 VL - 842 SN - 0077-8923, 0077-8923 KW - Index Medicus KW - Xerostomia -- etiology KW - Salivary Glands -- radiation effects KW - Salivary Glands -- physiopathology KW - Animals KW - Salivary Glands -- drug effects KW - Xerostomia -- chemically induced KW - Humans KW - Cranial Irradiation -- adverse effects KW - Salivation -- radiation effects KW - Salivation -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79892306?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Acquired+salivary+dysfunction.+Drugs+and+radiation.&rft.au=Fox%2C+P+C&rft.aulast=Fox&rft.aufirst=P&rft.date=1998-04-15&rft.volume=842&rft.issue=&rft.spage=132&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 - 1998-06-18 N1 - Date created - 1998-06-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Two North American families with hereditary papillary renal carcinoma and identical novel mutations in the MET proto-oncogene. AN - 79817356; 9563489 AB - Hereditary papillary renal carcinoma (HPRC) is a newly recognized inherited disorder characterized by a predisposition to develop multiple bilateral papillary renal carcinomas. Individuals affected with HPRC have been shown to have germ-line mutations in the tyrosine kinase domain of the MET proto-oncogene. We identified a novel mutation in exon 16 of the MET gene in two large North American HPRC families. The H1112R MET mutation segregated with the disease, was not present in 320 normal chromosomes, and caused malignant transformation of NIH 3T3 cells. By examining individuals with the H1112R mutation, we determined the age-dependent penetrance of this mutation and identified additional nonrenal malignancies that occurred in mutation carriers. Affected members of the two families shared the same haplotype within and immediately distal to the MET gene, suggesting a founder effect. The identification of the H1112R mutation will facilitate predictive testing in HPRC and guide future studies of the MET gene in human neoplasia. JF - Cancer research AU - Schmidt, L AU - Junker, K AU - Weirich, G AU - Glenn, G AU - Choyke, P AU - Lubensky, I AU - Zhuang, Z AU - Jeffers, M AU - Vande Woude, G AU - Neumann, H AU - Walther, M AU - Linehan, W M AU - Zbar, B AD - Intramural Research Support Program, Science Applications International Corporation-Frederick, National Cancer Institute-Frederick Cancer Research & Development Center, Maryland 21702, USA. Y1 - 1998/04/15/ PY - 1998 DA - 1998 Apr 15 SP - 1719 EP - 1722 VL - 58 IS - 8 SN - 0008-5472, 0008-5472 KW - Proto-Oncogene Proteins c-met KW - EC 2.7.10.1 KW - Index Medicus KW - Pedigree KW - North America KW - 3T3 Cells KW - Animals KW - Humans KW - Aged KW - Amino Acid Sequence KW - Mice KW - Mice, Nude KW - Base Sequence KW - Penetrance KW - Transfection KW - Adult KW - Molecular Sequence Data KW - Carcinogenicity Tests KW - Middle Aged KW - Neoplasms, Multiple Primary -- genetics KW - Female KW - Male KW - Kidney Neoplasms -- genetics KW - Proto-Oncogene Proteins c-met -- genetics KW - Mutation KW - Carcinoma, Papillary -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79817356?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Two+North+American+families+with+hereditary+papillary+renal+carcinoma+and+identical+novel+mutations+in+the+MET+proto-oncogene.&rft.au=Schmidt%2C+L%3BJunker%2C+K%3BWeirich%2C+G%3BGlenn%2C+G%3BChoyke%2C+P%3BLubensky%2C+I%3BZhuang%2C+Z%3BJeffers%2C+M%3BVande+Woude%2C+G%3BNeumann%2C+H%3BWalther%2C+M%3BLinehan%2C+W+M%3BZbar%2C+B&rft.aulast=Schmidt&rft.aufirst=L&rft.date=1998-04-15&rft.volume=58&rft.issue=8&rft.spage=1719&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-05-21 N1 - Date created - 1998-05-21 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - J02958; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Association of elevated mutagenesis in the spleen with genetic susceptibility to induced plasmacytoma development in mice. AN - 79816905; 9563470 AB - Using the phage lambdaLIZ-based transgenic in vivo mutagenesis assay, mean mutant rates were determined in the spleen of mice exposed to sustained oxidative stress and were found to be increased approximately 3-fold in plasmacytoma-susceptible BALB/c and C.D2-Idh1-Pep3 mice, but not in plasmacytoma-resistant DBA/2N mice. This finding suggests a correlation between the genetic susceptibility to inflammation-induced peritoneal plasmacytomagenesis and the phenotype of increased mutagenesis in lymphoid tissues, raising the possibility that plasmacytoma resistance genes may inhibit tumor development by minimizing oxidative mutagenesis in B cells. JF - Cancer research AU - Felix, K AU - Kelliher, K AU - Bornkamm, G W AU - Janz, S AD - Laboratory of Genetics, DBS, National Cancer Institute, NIH, Bethesda, Maryland 20892-4255, USA. felixk@dc37a.nci.nih.gov Y1 - 1998/04/15/ PY - 1998 DA - 1998 Apr 15 SP - 1616 EP - 1619 VL - 58 IS - 8 SN - 0008-5472, 0008-5472 KW - Carcinogens KW - 0 KW - Terpenes KW - pristane KW - 26HZV48DT1 KW - Buthionine Sulfoximine KW - 5072-26-4 KW - Glutathione KW - GAN16C9B8O KW - Index Medicus KW - Mice, Inbred Strains KW - Carcinogens -- pharmacology KW - Animals KW - Disease Susceptibility KW - Glutathione -- metabolism KW - Mice KW - Terpenes -- pharmacology KW - Buthionine Sulfoximine -- pharmacology KW - Mice, Inbred BALB C KW - Plasmacytoma -- genetics KW - Plasmacytoma -- chemically induced KW - Spleen -- pathology KW - Oxidative Stress -- genetics KW - Mutagenesis -- genetics KW - Spleen -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79816905?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Association+of+elevated+mutagenesis+in+the+spleen+with+genetic+susceptibility+to+induced+plasmacytoma+development+in+mice.&rft.au=Felix%2C+K%3BKelliher%2C+K%3BBornkamm%2C+G+W%3BJanz%2C+S&rft.aulast=Felix&rft.aufirst=K&rft.date=1998-04-15&rft.volume=58&rft.issue=8&rft.spage=1616&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 - 1998-05-21 N1 - Date created - 1998-05-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - p53-dependent and -independent regulation of the death receptor KILLER/DR5 gene expression in response to genotoxic stress and tumor necrosis factor alpha. AN - 79816678; 9563466 AB - The death receptor (DR) KILLER/DR5 gene has recently been identified as a doxorubicin-regulated transcript that was also induced by exogenous wild-type p53 in p53-negative cells. KILLER/DR5 gene encodes a DR containing cell surface protein that is highly homologous to DR4, another DR of the tumor necrosis factor (TNF) receptor family. Both DR4 and KILLER/DR5 independently bind to their specific ligand TRAIL and engage the caspase cascade to induce apoptosis. TRID (also known as TRAIL-R3) is an antiapoptotic decoy receptor that lacks the cytoplasmic death domain and competes with KILLER/DR5 and DR4 for binding to TRAIL. In this study, we demonstrate that the DR KILLER/DR5 gene is regulated in a p53-dependent and -independent manner during genotoxic and nongenotoxic stress-induced apoptosis. Just like other p53-regulated genes, ionizing radiation induction of KILLER/DR5 occurs in p53 wild-type cells, whereas methyl methanesulfonate regulation of KILLER/DR5 occurs in a p53-dependent and -independent manner. However, unlike other p53-regulated genes, KILLER/DR5 is not regulated following UV irradiation. TNF-alpha, a nongenotoxic cytokine, also induced the expression of KILLER/DR5 in a number of cancer cell lines, irrespective of p53 status. TNF-alpha did not alter the KILLER/DR5 mRNA stability, suggesting that the TNF-alpha regulation of KILLER/DRS expression appears transcriptional. We also provide evidence that KILLER/DR5 is regulated in a trigger and cell type-specific manner and that its induction by TNF-alpha, p53, or DNA damage is not the consequence of apoptosis induced by these agents. Unlike KILLER/DR5, none of the other KILLER/DR5 family members, including DR4, TRID, or the ligand TRAIL, displayed genotoxic stress or TNF-alpha regulation in a p53 transcription-dependent manner. Thus, KILLER/DR5 appears a bona fide downstream target of p53 that is also regulated in a cell type-specific, trigger-dependent, and p53-independent manner. JF - Cancer research AU - Sheikh, M S AU - Burns, T F AU - Huang, Y AU - Wu, G S AU - Amundson, S AU - Brooks, K S AU - Fornace, A J AU - el-Deiry, W S AD - Basic Research Laboratory, Division of Basic Sciences, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. mssheikh@box-m.nih.gov Y1 - 1998/04/15/ PY - 1998 DA - 1998 Apr 15 SP - 1593 EP - 1598 VL - 58 IS - 8 SN - 0008-5472, 0008-5472 KW - Apoptosis Regulatory Proteins KW - 0 KW - GPI-Linked Proteins KW - Membrane Glycoproteins KW - RNA, Messenger KW - Receptors, TNF-Related Apoptosis-Inducing Ligand KW - Receptors, Tumor Necrosis Factor KW - Receptors, Tumor Necrosis Factor, Member 10c KW - TNF-Related Apoptosis-Inducing Ligand KW - TNFRSF10A protein, human KW - TNFRSF10B protein, human KW - TNFRSF10C protein, human KW - TNFSF10 protein, human KW - Tumor Necrosis Factor Decoy Receptors KW - Tumor Necrosis Factor-alpha KW - Tumor Suppressor Protein p53 KW - Doxorubicin KW - 80168379AG KW - Methyl Methanesulfonate KW - AT5C31J09G KW - Index Medicus KW - Immunoblotting KW - Ultraviolet Rays KW - Blotting, Northern KW - Tumor Cells, Cultured -- drug effects KW - Dose-Response Relationship, Drug KW - Humans KW - RNA, Messenger -- analysis KW - Tumor Cells, Cultured -- radiation effects KW - Methyl Methanesulfonate -- pharmacology KW - Doxorubicin -- pharmacology KW - Transfection KW - Time Factors KW - Membrane Glycoproteins -- metabolism KW - Radiation, Ionizing KW - Tumor Suppressor Protein p53 -- physiology KW - Apoptosis KW - Tumor Necrosis Factor-alpha -- pharmacology KW - Gene Expression Regulation, Neoplastic -- radiation effects KW - Receptors, Tumor Necrosis Factor -- metabolism KW - Tumor Necrosis Factor-alpha -- metabolism KW - Gene Expression Regulation, Neoplastic -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79816678?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=p53-dependent+and+-independent+regulation+of+the+death+receptor+KILLER%2FDR5+gene+expression+in+response+to+genotoxic+stress+and+tumor+necrosis+factor+alpha.&rft.au=Sheikh%2C+M+S%3BBurns%2C+T+F%3BHuang%2C+Y%3BWu%2C+G+S%3BAmundson%2C+S%3BBrooks%2C+K+S%3BFornace%2C+A+J%3Bel-Deiry%2C+W+S&rft.aulast=Sheikh&rft.aufirst=M&rft.date=1998-04-15&rft.volume=58&rft.issue=8&rft.spage=1593&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 - 1998-05-21 N1 - Date created - 1998-05-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A subtractive PCR-based cDNA library made from fetal thymic stromal cells AN - 16413031; 4313926 AB - We describe our initial approach to clone and characterize genes expressed preferentially in thymic stromal cells, in an attempt to generate molecular reagents to study the role of these cells in thymopoiesis and thymic function. Thymic stromal cells were prepared from fetal thymic organ cultures by treating them with 2-deoxyguanosine and depleting the remaining hematopoietic cells with anti-CD45 antibody. A cDNA library was then prepared after subtraction and amplification by PCR. The cloned inserts were sequenced and compared for homology with known genes in the data base. Unidentified cDNAs were then examined for expression in normal and SCID thymus and in a set of SV40-transformed thymic epithelial cell lines, by Northern blotting and a dot blot assay. In this report we describe the development of the library and present a general description of the genes identified from the initial 249 cDNAs sequenced. Among these, a relatively high percentage (55%) do not show any homology to previously identified genes. Several genes with a limited expression pattern were selected for further study. JF - Journal of Immunological Methods AU - Kim, M G AU - Chen, C AU - Flomerfelt, F AU - Germain, R N AU - Schwartz, R H AD - Laboratory of Cellular and Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA Y1 - 1998/04/15/ PY - 1998 DA - 1998 Apr 15 SP - 163 EP - 176 PB - Elsevier Science B.V. VL - 213 IS - 2 SN - 0022-1759, 0022-1759 KW - 2-deoxyguanosine KW - CD45 antigen KW - Polymerase chain reaction KW - SV40 KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - F 06713:Physicochemical methods KW - W3 33243:Molecular methods KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16413031?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Immunological+Methods&rft.atitle=A+subtractive+PCR-based+cDNA+library+made+from+fetal+thymic+stromal+cells&rft.au=Kim%2C+M+G%3BChen%2C+C%3BFlomerfelt%2C+F%3BGermain%2C+R+N%3BSchwartz%2C+R+H&rft.aulast=Kim&rft.aufirst=M&rft.date=1998-04-15&rft.volume=213&rft.issue=2&rft.spage=163&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immunological+Methods&rft.issn=00221759&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Effect of mutating the regulatory phosphoserine and conserved threonine on the activity of the expressed catalytic domain of Acanthamoeba myosin I heavy chain kinase. AN - 79801262; 9539704 AB - Phosphorylation of Ser-627 is both necessary and sufficient for full activity of the expressed 35-kDa catalytic domain of myosin I heavy chain kinase (MIHCK). Ser-627 lies in the variable loop between highly conserved residues DFG and APE at a position at which a phosphorylated Ser/Thr also occurs in many other Ser/Thr protein kinases. The variable loop of MIHCK contains two other hydroxyamino acids: Thr-631, which is conserved in almost all Ser/Thr kinases, and Thr-632, which is not conserved. We determined the effects on the kinase activity of the expressed catalytic domain of mutating Ser-627, Thr-631, and Thr-632 individually to Ala, Asp, and Glu. The S627A mutant was substantially less active than wild type (wt), with a lower kcat and higher Km for both peptide substrate and ATP, but was more active than unphosphorylated wt. The S627D and S627E mutants were also less active than phosphorylated wt, i.e., acidic amino acids cannot substitute for phospho-Ser-627. The activity of the T631A mutant was as low as that of the S627A mutant, whereas the T632A mutant was as active as phosphorylated wt, indicating that highly conserved Thr-631, although not phosphorylated, is essential for catalytic activity. Asp and Glu substitutions for Thr-631 and Thr-632 were inhibitory to various degrees. Molecular modeling indicated that Thr-631 can hydrogen bond with conserved residue Asp-591 in the catalytic loop and that similar interactions are possible for other kinases whose activities also are regulated by phosphorylation in the variable loop. Thus, this conserved Thr residue may be essential for the activities of other Ser/Thr protein kinases as well as for the activity of MIHCK. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Szczepanowska, J AU - Ramachandran, U AU - Herring, C J AU - Gruschus, J M AU - Qin, J AU - Korn, E D AU - Brzeska, H AD - Laboratory of Cell Biology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1998/04/14/ PY - 1998 DA - 1998 Apr 14 SP - 4146 EP - 4151 VL - 95 IS - 8 SN - 0027-8424, 0027-8424 KW - Protozoan Proteins KW - 0 KW - Recombinant Proteins KW - Phosphoserine KW - 17885-08-4 KW - Threonine KW - 2ZD004190S KW - Calcium-Calmodulin-Dependent Protein Kinases KW - EC 2.7.11.17 KW - myosin-heavy-chain kinase KW - EC 2.7.11.7 KW - Index Medicus KW - Animals KW - Spodoptera KW - Models, Molecular KW - Amino Acid Sequence KW - Binding Sites KW - Mutagenesis, Site-Directed KW - Sequence Alignment KW - Conserved Sequence KW - Transfection KW - Recombinant Proteins -- metabolism KW - Kinetics KW - Molecular Sequence Data KW - Point Mutation KW - Recombinant Proteins -- chemistry KW - Sequence Homology, Amino Acid KW - Cell Line KW - Calcium-Calmodulin-Dependent Protein Kinases -- metabolism KW - Protein Structure, Secondary KW - Acanthamoeba -- enzymology KW - Calcium-Calmodulin-Dependent Protein Kinases -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79801262?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Effect+of+mutating+the+regulatory+phosphoserine+and+conserved+threonine+on+the+activity+of+the+expressed+catalytic+domain+of+Acanthamoeba+myosin+I+heavy+chain+kinase.&rft.au=Szczepanowska%2C+J%3BRamachandran%2C+U%3BHerring%2C+C+J%3BGruschus%2C+J+M%3BQin%2C+J%3BKorn%2C+E+D%3BBrzeska%2C+H&rft.aulast=Szczepanowska&rft.aufirst=J&rft.date=1998-04-14&rft.volume=95&rft.issue=8&rft.spage=4146&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 - 1998-05-13 N1 - Date created - 1998-05-13 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Biol Chem. 1973 Jul 10;248(13):4691-7 [4268864] J Biol Chem. 1996 Jul 19;271(29):16983-6 [8707782] J Biol Chem. 1996 Oct 25;271(43):27044-8 [8900194] J Biol Chem. 1996 Oct 25;271(43):27049-55 [8900195] J Biol Chem. 1996 Oct 25;271(43):27056-62 [8900196] J Biol Chem. 1996 Dec 13;271(50):31787-90 [8943216] Eur J Biochem. 1996 Dec 1;242(2):171-85 [8973630] EMBO J. 1996 Dec 16;15(24):6810-21 [9003756] Mol Cell Biol. 1997 Mar;17(3):1129-43 [9032240] Proc Natl Acad Sci U S A. 1997 Feb 18;94(4):1092-5 [9037011] J Biol Chem. 1997 Mar 21;272(12):7586-94 [9065412] J Biol Chem. 1997 Apr 18;272(16):10514-21 [9099695] Proc Natl Acad Sci U S A. 1997 Aug 5;94(16):8503-8 [9238006] J Biol Chem. 1984 Mar 10;259(5):3224-9 [6321501] Science. 1988 Jul 1;241(4861):42-52 [3291115] J Biol Chem. 1989 Nov 15;264(32):19340-8 [2530230] J Biol Chem. 1990 Mar 5;265(7):3591-4 [2154483] J Biol Chem. 1990 Sep 25;265(27):16138-44 [2168881] J Biol Chem. 1992 Mar 5;267(7):4949-56 [1311323] Annu Rev Cell Biol. 1992;8:429-62 [1335745] Biochemistry. 1993 Mar 9;32(9):2154-61 [8443157] Mol Cell Biol. 1993 Apr;13(4):2332-41 [8455615] J Biol Chem. 1993 Aug 25;268(24):17995-8001 [8394357] Protein Sci. 1993 Oct;2(10):1559-73 [8251932] Nature. 1994 Feb 24;367(6465):704-11 [8107865] Protein Sci. 1994 Feb;3(2):176-87 [8003955] Structure. 1994 May 15;2(5):345-55 [8081750] Biochemistry. 1995 Feb 28;34(8):2447-54 [7873523] EMBO J. 1995 Mar 1;14(5):1015-23 [7889932] FASEB J. 1995 May;9(8):576-96 [7768349] J Biol Chem. 1995 Jul 7;270(27):15984-92 [7608157] Nature. 1995 Jul 27;376(6538):313-20 [7630397] Structure. 1995 May 15;3(5):467-82 [7663944] J Biol Chem. 1995 Sep 8;270(36):21121-8 [7673144] Proteins. 1995 Aug;22(4):378-91 [7479711] J Biol Chem. 1995 Nov 17;270(46):27969-76 [7499274] Cell. 1996 Apr 19;85(2):149-58 [8612268] Nat Struct Biol. 1996 Aug;3(8):696-700 [8756328] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Brefeldin A-inhibited guanine nucleotide-exchange activity of Sec7 domain from yeast Sec7 with yeast and mammalian ADP ribosylation factors. AN - 79800398; 9539714 AB - The Saccharomyces cerevisiae Sec7 protein (ySec7p), which is an important component of the yeast secretory pathway, contains a sequence of approximately 200 amino acids referred to as a Sec7 domain. Similar Sec7 domain sequences have been recognized in several guanine nucleotide-exchange proteins (GEPs) for ADP ribosylation factors (ARFs). ARFs are approximately 20-kDa GTPases that regulate intracellular vesicular membrane trafficking and activate phospholipase D. GEPs activate ARFs by catalyzing the replacement of bound GDP with GTP. We, therefore, undertook to determine whether a Sec7 domain itself could catalyze nucleotide exchange on ARF and found that it exhibited brefeldin A (BFA)-inhibitable ARF GEP activity. BFA is known to inhibit ARF GEP activity in Golgi membranes, thereby causing reversible apparent dissolution of the Golgi complex in many cells. The His6-tagged Sec7 domain from ySec7p (rySec7d) synthesized in Escherichia coli enhanced binding of guanosine 5'-[gamma-[35S]thio]triphosphate by recombinant yeast ARF1 (ryARF1) and ryARF2 but not by ryARF3. The effects of rySec7d on ryARF2 were inhibited by BFA in a concentration-dependent manner but not by inactive analogues of BFA (B-17, B-27, and B-36). rySec7d also promoted BFA-sensitive guanosine 5'-[gamma-thio]triphosphate binding by nonmyristoylated recombinant human ARF1 (rhARF1), rhARF5, and rhARF6, although the effect on rhARF6 was very small. These results are consistent with the conclusion that the yeast Sec7 domain itself contains the elements necessary for ARF GEP activity and its inhibition by BFA. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Sata, M AU - Donaldson, J G AU - Moss, J AU - Vaughan, M AD - Pulmonary-Critical Care Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1998/04/14/ PY - 1998 DA - 1998 Apr 14 SP - 4204 EP - 4208 VL - 95 IS - 8 SN - 0027-8424, 0027-8424 KW - Carrier Proteins KW - 0 KW - Cyclopentanes KW - DNA Primers KW - Fungal Proteins KW - Guanine Nucleotide Exchange Factors KW - Recombinant Proteins KW - Sec7 guanine nucleotide exchange factors KW - NAD KW - 0U46U6E8UK KW - Brefeldin A KW - 20350-15-6 KW - Guanosine 5'-O-(3-Thiotriphosphate) KW - 37589-80-3 KW - Cholera Toxin KW - 9012-63-9 KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - ADP-Ribosylation Factor 1 KW - EC 3.6.5.2 KW - ADP-Ribosylation Factors KW - Index Medicus KW - Recombinant Proteins -- drug effects KW - Carrier Proteins -- metabolism KW - Humans KW - Cholera Toxin -- pharmacology KW - Sequence Tagged Sites KW - Cloning, Molecular KW - NAD -- metabolism KW - Polymerase Chain Reaction KW - Recombinant Proteins -- metabolism KW - Kinetics KW - Guanosine 5'-O-(3-Thiotriphosphate) -- metabolism KW - Fungal Proteins -- metabolism KW - Cyclopentanes -- pharmacology KW - Saccharomyces cerevisiae -- metabolism KW - GTP-Binding Proteins -- metabolism KW - Fungal Proteins -- drug effects KW - GTP-Binding Proteins -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79800398?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Brefeldin+A-inhibited+guanine+nucleotide-exchange+activity+of+Sec7+domain+from+yeast+Sec7+with+yeast+and+mammalian+ADP+ribosylation+factors.&rft.au=Sata%2C+M%3BDonaldson%2C+J+G%3BMoss%2C+J%3BVaughan%2C+M&rft.aulast=Sata&rft.aufirst=M&rft.date=1998-04-14&rft.volume=95&rft.issue=8&rft.spage=4204&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 - 1998-05-13 N1 - Date created - 1998-05-13 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cell. 1989 Mar 10;56(5):801-13 [2647301] J Biol Chem. 1998 Jan 2;273(1):23-7 [9417041] EMBO J. 1989 Sep;8(9):2695-702 [2684655] Proc Natl Acad Sci U S A. 1990 Feb;87(3):1238-42 [2105501] Mol Cell Biol. 1990 Dec;10(12):6690-9 [2123295] J Cell Biol. 1991 Jan;112(1):27-37 [1986005] J Biol Chem. 1991 Feb 15;266(5):2772-7 [1993656] Cell. 1991 Nov 1;67(3):449-51 [1934055] Nature. 1992 Jan 9;355(6356):173-5 [1729652] Biochim Biophys Acta. 1992 Aug 17;1132(1):75-8 [1511013] Nature. 1992 Nov 26;360(6402):350-2 [1448151] J Biol Chem. 1993 Mar 5;268(7):4863-72 [8444865] Cell. 1993 Dec 17;75(6):1137-44 [8261513] Science. 1994 Jan 28;263(5146):523-6 [8290961] Nature. 1994 Mar 3;368(6466):32-8 [7906398] Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3063-6 [8159707] Cell. 1994 Jul 1;77(7):1051-62 [8020095] J Biol Chem. 1994 Aug 19;269(33):20931-7 [8063710] Nature. 1994 Nov 3;372(6501):55-63 [7969419] Proc Natl Acad Sci U S A. 1994 Nov 22;91(24):11718-22 [7972129] Curr Opin Cell Biol. 1994 Aug;6(4):527-32 [7986529] J Cell Biol. 1995 Mar;128(6):1003-17 [7896867] Mol Cell Biochem. 1994 Sep;138(1-2):157-66 [7898460] Mol Cell Biol. 1996 Jul;16(7):3275-84 [8668142] Cell. 1996 Jul 26;86(2):233-42 [8706128] J Biol Chem. 1996 Sep 6;271(36):21767-74 [8702973] Nature. 1996 Dec 5;384(6608):479-81 [8945477] Nature. 1996 Dec 5;384(6608):481-4 [8945478] J Biol Chem. 1984 May 25;259(10):6228-34 [6327671] J Biol Chem. 1986 Aug 25;261(24):11398-403 [2426273] J Biol Chem. 1988 Aug 25;263(24):11711-7 [3042778] Proc Natl Acad Sci U S A. 1997 Mar 4;94(5):1745-8 [9050849] Science. 1997 Mar 28;275(5308):1927-30 [9072969] EMBO J. 1997 Sep 1;16(17):5445-54 [9312003] J Cell Biol. 1997 Oct 6;139(1):49-61 [9314528] Proc Natl Acad Sci U S A. 1997 Nov 25;94(24):12926-31 [9371777] Cold Spring Harb Symp Quant Biol. 1988;53 Pt 2:629-36 [3151179] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mechanisms of replication-deficient vaccinia virus/T7 RNA polymerase hybrid expression: effect of T7 RNA polymerase levels and alpha-amanitin. AN - 79829826; 9568032 AB - Components of the eukaryotic vaccinia virus/T7 RNA polymerase hybrid expression system were assessed using recombinant and nonrecombinant forms of modified vaccinia Ankara (MVA), a replication-deficient vaccinia virus strain. Recombinant MVA virus expressing T7 RNA polymerase (Wyatt, L. S., Moss, B., and Rozenblatt, S. (1995). Virology 210, 202-205) stimulated high levels of expression from a T7 promoter-chloramphenicol acetyltransferase (CAT) reporter. Most, but not all, of the virally induced expression was T7 RNA polymerase and T7 promoter dependent, with no viral enhancement of translation of T7 transcripts. The efficacy of supplying T7 RNA polymerase expression from nonviral sources was evaluated using a self-amplifying T7 RNA polymerase autogene or an inducible T7 RNA polymerase expression vector. The latter modes yielded CAT activity dependent on T7 RNA polymerase expression; however, expression required viral factors independent of T7 RNA polymerase and did not reach that attained using the recombinant virus. In further experiments, MVA-induced T7 RNA polymerase expression was upregulated by alpha-amanitin, an inhibitor of eukaryotic polymerases. This indicates that MVA/T7 RNA polymerase hybrid expression may be rendered still more efficient by ameliorating transcriptional interference due to an alpha-amanitin-sensitive eukaryotic factor(s). JF - Virology AU - Engleka, K A AU - Lewis, E W AU - Howard, B H AD - Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-2753, USA. engleka1@jeflin.tju.edu Y1 - 1998/04/10/ PY - 1998 DA - 1998 Apr 10 SP - 331 EP - 339 VL - 243 IS - 2 SN - 0042-6822, 0042-6822 KW - Amanitins KW - 0 KW - Enzyme Inhibitors KW - Viral Proteins KW - Chloramphenicol O-Acetyltransferase KW - EC 2.3.1.28 KW - bacteriophage T7 RNA polymerase KW - EC 2.7.7.- KW - DNA-Directed RNA Polymerases KW - EC 2.7.7.6 KW - Index Medicus KW - Virus Replication KW - Chloramphenicol O-Acetyltransferase -- genetics KW - Promoter Regions, Genetic KW - HeLa Cells KW - Humans KW - Enzyme Induction KW - Enzyme Inhibitors -- metabolism KW - Vaccinia virus -- genetics KW - Vaccinia virus -- enzymology KW - Defective Viruses -- genetics KW - Vaccinia virus -- physiology KW - Genetic Vectors KW - DNA-Directed RNA Polymerases -- metabolism KW - Gene Expression KW - Defective Viruses -- enzymology KW - Amanitins -- metabolism KW - Amanitins -- genetics KW - Defective Viruses -- physiology KW - DNA-Directed RNA Polymerases -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79829826?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mechanisms+of+replication-deficient+vaccinia+virus%2FT7+RNA+polymerase+hybrid+expression%3A+effect+of+T7+RNA+polymerase+levels+and+alpha-amanitin.&rft.au=Engleka%2C+K+A%3BLewis%2C+E+W%3BHoward%2C+B+H&rft.aulast=Engleka&rft.aufirst=K&rft.date=1998-04-10&rft.volume=243&rft.issue=2&rft.spage=331&rft.isbn=&rft.btitle=&rft.title=Virology&rft.issn=00426822&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-05-27 N1 - Date created - 1998-05-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cryo-crystallography of a true substrate, indole-3-glycerol phosphate, bound to a mutant (alphaD60N) tryptophan synthase alpha2beta2 complex reveals the correct orientation of active site alphaGlu49. AN - 79795555; 9535826 AB - The reversible cleavage of indole-3-glycerol by the alpha-subunit of tryptophan synthase has been proposed to be catalyzed by alphaGlu49 and alphaAsp60. Although previous x-ray crystallographic structures of the tryptophan synthase alpha2beta2 complex showed an interaction between the carboxylate of alphaAsp60 and the bound inhibitor indole-3-propanol phosphate, the carboxylate of alphaGlu49 was too distant to play its proposed role. To clarify the structural and functional roles of alphaGlu49, we have determined crystal structures of a mutant (alphaD60N) alpha2beta2 complex in the presence and absence of the true substrate, indole-3-glycerol phosphate. The enzyme in the crystal cleaves indole-3-glycerol phosphate very slowly at room temperature but not under cryo-conditions of 95 K. The structure of the complex with the true substrate obtained by cryo-crystallography reveals that indole-3-glycerol phosphate and indole-3-propanol phosphate have similar binding modes but different torsion angles. Most importantly, the side chain of alphaGlu49 interacts with 3-hydroxyl group of indole-3-glycerol phosphate as proposed. The movement of the side chain of alphaGlu49 into an extended conformation upon binding the true substrate provides evidence for an induced fit mechanism. Our results demonstrate how cryo-crystallography and mutagenesis can provide insight into enzyme mechanism. JF - The Journal of biological chemistry AU - Rhee, S AU - Miles, E W AU - Davies, D R AD - Laboratory of Molecular Biology, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/04/10/ PY - 1998 DA - 1998 Apr 10 SP - 8553 EP - 8555 VL - 273 IS - 15 SN - 0021-9258, 0021-9258 KW - Glycerophosphates KW - 0 KW - Macromolecular Substances KW - Recombinant Proteins KW - indoleglycerol phosphate KW - 4220-97-7 KW - Tryptophan Synthase KW - EC 4.2.1.20 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Recombinant Proteins -- isolation & purification KW - Recombinant Proteins -- metabolism KW - Models, Molecular KW - Point Mutation KW - Molecular Sequence Data KW - Crystallography, X-Ray KW - Amino Acid Sequence KW - Recombinant Proteins -- chemistry KW - Binding Sites KW - Tryptophan Synthase -- isolation & purification KW - Tryptophan Synthase -- metabolism KW - Tryptophan Synthase -- chemistry KW - Glycerophosphates -- chemistry KW - Glycerophosphates -- metabolism KW - Protein Conformation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79795555?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Cryo-crystallography+of+a+true+substrate%2C+indole-3-glycerol+phosphate%2C+bound+to+a+mutant+%28alphaD60N%29+tryptophan+synthase+alpha2beta2+complex+reveals+the+correct+orientation+of+active+site+alphaGlu49.&rft.au=Rhee%2C+S%3BMiles%2C+E+W%3BDavies%2C+D+R&rft.aulast=Rhee&rft.aufirst=S&rft.date=1998-04-10&rft.volume=273&rft.issue=15&rft.spage=8553&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 - 1998-05-14 N1 - Date created - 1998-05-14 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - 1A5A; PDB; 1A5B N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Catalysis by phospholipase C delta1 requires that Ca2+ bind to the catalytic domain, but not the C2 domain. AN - 79790603; 9538021 AB - The hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) by phosphoinositide-specific phospholipase C (PLC) is absolutely dependent on Ca2+. The PH domain truncated catalytic core of rat phospholipase C delta1 (PLC-delta1) has Ca2+ binding sites in its catalytic and C2 domains, and potential Ca2+ binding sites in two EF-hands. A catalytically inactive PLC-delta1 catalytic core bound with low affinity to PIP2-containing vesicles in the presence of Ca2+. A mutant PLC-delta1 has been engineered which lacks the C2 domain Ca2+ binding site and the surrounding loops known as the jaws. Isothermal calorimetric titration showed four Ca2+ ions bind to the wild-type PLC-delta1 catalytic core in solution but only one binds to the C2 domain jaws deletion mutant. The activity and Ca2+ dependence of wild-type and mutant phospholipase Cs were determined using substrate incorporated in detergent micelles and in large unilamellar vesicles. The activities of wild-type and mutant were identical to each other in both assay systems. Wild-type and the C2 jaws deletion mutant of PLC have Hill coefficients of 1.12-1.16 with respect to [Ca2+]. We conclude that a single Ca2+ bound to the catalytic domain is entirely responsible for the Ca2+ dependence of the basal activity of PLC-delta1. JF - Biochemistry AU - Grobler, J A AU - Hurley, J H AD - Laboratory of Molecular Biology, National Institute of Diabetes, Digestive, and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0580, USA. Y1 - 1998/04/07/ PY - 1998 DA - 1998 Apr 07 SP - 5020 EP - 5028 VL - 37 IS - 14 SN - 0006-2960, 0006-2960 KW - Isoenzymes KW - 0 KW - Recombinant Proteins KW - Type C Phospholipases KW - EC 3.1.4.- KW - Phospholipase C delta KW - EC 3.1.4.11 KW - Plcd1 protein, rat KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Rats KW - Animals KW - Chromatography, Gel KW - Recombinant Proteins -- metabolism KW - Kinetics KW - Molecular Sequence Data KW - Calorimetry KW - Amino Acid Sequence KW - Recombinant Proteins -- chemistry KW - Recombinant Proteins -- genetics KW - Protein Binding KW - Hydrolysis KW - Mutagenesis KW - Catalysis KW - Isoenzymes -- chemistry KW - Calcium -- metabolism KW - Type C Phospholipases -- chemistry KW - Type C Phospholipases -- genetics KW - Isoenzymes -- genetics KW - Isoenzymes -- metabolism KW - Type C Phospholipases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79790603?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Catalysis+by+phospholipase+C+delta1+requires+that+Ca2%2B+bind+to+the+catalytic+domain%2C+but+not+the+C2+domain.&rft.au=Grobler%2C+J+A%3BHurley%2C+J+H&rft.aulast=Grobler&rft.aufirst=J&rft.date=1998-04-07&rft.volume=37&rft.issue=14&rft.spage=5020&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-05-14 N1 - Date created - 1998-05-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Immunotoxins for targeted cancer therapy. AN - 1859323924; 10837618 AB - Immunotoxins constitute a new modality for the treatment of cancer, since they target cells displaying specific surface-receptors or antigens. Immunotoxins contain a ligand such as a growth factor, monoclonal antibody, or fragment of an antibody which is connected to a protein toxin. After the ligand subunit binds to the surface of the target cell, the molecule internalizes and the toxin kills the cell. Bacterial toxins which have been targeted to cancer cells include Pseudomonas exotoxin and diphtheria toxin, which are well suited to forming recombinant single-chain or double-chain fusion toxins. Plant toxins include ricin, abrin, pokeweed antiviral protein, saporin and gelonin, and have generally been connected to ligands by disulfide-bond chemistry. Immunotoxins have been produced to target hematologic malignancies and solid tumors via a wide variety of growth factor receptors and antigens. Challenges facing the clinical application of immunotoxins are discussed. JF - Advanced drug delivery reviews AU - Pastan AU - Kreitman AD - Laboratory of Molecular Biology, Division of Cancer Biology, National Cancer Institute, National Institutes of Health, 37/4E16, 37 Convent Drive MSC 4255, Bethesda, MD 20892, USA Y1 - 1998/04/06/ PY - 1998 DA - 1998 Apr 06 SP - 53 EP - 88 VL - 31 IS - 1-2 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859323924?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Advanced+drug+delivery+reviews&rft.atitle=Immunotoxins+for+targeted+cancer+therapy.&rft.au=Pastan%3BKreitman&rft.aulast=Pastan&rft.aufirst=&rft.date=1998-04-06&rft.volume=31&rft.issue=1-2&rft.spage=53&rft.isbn=&rft.btitle=&rft.title=Advanced+drug+delivery+reviews&rft.issn=1872-8294&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2000-06-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Lack of carcinogenicity of cadmium chloride in female Syrian hamsters. AN - 80029671; 9674965 AB - Cadmium is very effective at inducing necrosis within the ovaries of rodents, and the Syrian hamster appears particularly sensitive. The extent of cadmium-induced necrosis depends on the stage of the estrous cycle and is most pronounced when injected on the day prior to ovulation (proestrous). In male rodents cadmium induces a similar necrosis within the testes, which given sufficient time can lead to the development of testicular tumors. In this study we tested the hypothesis that cadmium-induced ovarian necrosis could eventually lead to tumor formation. In sexually mature groups of female Syrian hamsters (> 8 weeks old; n = 50-59), the estrous cycle was determined by visual inspection of vaginal discharge for four consecutive cycles. The animals were then given cadmium (0, 30, 40 and 50 micromol/kg) subcutaneously as a single injection in the dorsal thoracic midline on cycle day 4 (proestrous). Based on prior work, these doses are sufficient to induce extensive acute ovarian damage. Animals were then observed over the next 78 weeks. Although survival and body weight were reduced by cadmium, treatment with the metal did not result in an enhanced incidence of tumors at any site including the ovaries. Non-neoplastic lesions such as amyloidosis and pancreatic hepatocytes were linked to cadmium exposure. These results indicate that the association of cadmium-induced testicular necrosis with tumor development seen in males does not occur in the Syrian hamster ovaries. JF - Toxicology AU - Waalkes, M P AU - Rehm, S AD - Laboratory of Comparative Carcinogenesis, Division of Basic Sciences, National Cancer Institute, Frederick Cancer Research and Development Center, Frederick, MD 21702, USA. Y1 - 1998/04/03/ PY - 1998 DA - 1998 Apr 03 SP - 173 EP - 178 VL - 126 IS - 3 SN - 0300-483X, 0300-483X KW - Carcinogens KW - 0 KW - Cadmium Chloride KW - J6K4F9V3BA KW - Index Medicus KW - Pancreas -- pathology KW - Animals KW - Liver -- pathology KW - Dose-Response Relationship, Drug KW - Amyloidosis -- chemically induced KW - Pancreas -- drug effects KW - Necrosis KW - Estrus KW - Liver -- drug effects KW - Body Weight -- drug effects KW - Injections, Subcutaneous KW - Mesocricetus KW - Female KW - Cricetinae KW - Cadmium Chloride -- administration & dosage KW - Carcinogens -- administration & dosage KW - Ovary -- pathology KW - Ovary -- drug effects KW - Cadmium Chloride -- toxicity KW - Carcinogens -- toxicity KW - Ovarian Neoplasms -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80029671?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology&rft.atitle=Lack+of+carcinogenicity+of+cadmium+chloride+in+female+Syrian+hamsters.&rft.au=Waalkes%2C+M+P%3BRehm%2C+S&rft.aulast=Waalkes&rft.aufirst=M&rft.date=1998-04-03&rft.volume=126&rft.issue=3&rft.spage=173&rft.isbn=&rft.btitle=&rft.title=Toxicology&rft.issn=0300483X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-08-06 N1 - Date created - 1998-08-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of mutations in the polymerase domain on the polymerase, RNase H and strand transfer activities of human immunodeficiency virus type 1 reverse transcriptase. AN - 79785029; 9533880 AB - Based on structural analyses and on the behavior of mutants, we suggest that the polymerase domain of HIV-1 reverse transcriptase (RT) plays a critical role in holding and appropriately positioning the template-primer both at the polymerase active site and at the RNase H active site. For RT to successfully copy the viral RNA genome, RNase H must cleave the RNA with absolute precision. We believe that a combination of the structure of the template-primer and its precise positioning are responsible for the specific cleavages RNase H makes. We have proposed that resistance of HIV-1 RT to nucleoside analogs involves a subtle repositioning of the template-primer. This hypothesis is based on both structural and biochemical analyses. Mutations that confer resistance to nucleoside analogs do not cluster at the polymerase active site; however, they are in positions where they could alter the interaction between RT and the template-primer. If, as we have hypothesized, the polymerase domain is primarily responsible for positioning the template-primer and RNase H cleavage depends on this positioning, it should be possible to use RNase H cleavage to monitor at least some of the major changes in the position of the template-primer. We have used three assays (polymerase, RNase H, and strand transfer) to investigate the effects of mutations in the polymerase domain, including mutations that confer resistance to nucleotide analogs, on HIV-1 RT. All three assays involve RNA sequences derived from the viral genome. The data show that alterations in the polymerase domain, in particular, mutations that are in positions that would be expected to alter the interaction of RT with the template-primer, can alter both the efficiency and specificity of RNase H cleavage. These results are discussed in light of the structure of HIV-1 RT. Copyright 1998 Academic Press Limited. JF - Journal of molecular biology AU - Gao, H Q AU - Boyer, P L AU - Arnold, E AU - Hughes, S H AD - ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Frederick, MD 21702-1201, USA. Y1 - 1998/04/03/ PY - 1998 DA - 1998 Apr 03 SP - 559 EP - 572 VL - 277 IS - 3 SN - 0022-2836, 0022-2836 KW - RNA KW - 63231-63-0 KW - HIV Reverse Transcriptase KW - EC 2.7.7.49 KW - Ribonuclease H KW - EC 3.1.26.4 KW - Index Medicus KW - AIDS/HIV KW - Base Sequence KW - Models, Molecular KW - Humans KW - Molecular Sequence Data KW - Structure-Activity Relationship KW - Protein Conformation KW - Binding Sites KW - HIV Reverse Transcriptase -- genetics KW - RNA -- metabolism KW - HIV Reverse Transcriptase -- metabolism KW - HIV-1 -- enzymology KW - HIV Reverse Transcriptase -- chemistry KW - Ribonuclease H -- metabolism KW - Mutagenesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79785029?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+molecular+biology&rft.atitle=Effects+of+mutations+in+the+polymerase+domain+on+the+polymerase%2C+RNase+H+and+strand+transfer+activities+of+human+immunodeficiency+virus+type+1+reverse+transcriptase.&rft.au=Gao%2C+H+Q%3BBoyer%2C+P+L%3BArnold%2C+E%3BHughes%2C+S+H&rft.aulast=Gao&rft.aufirst=H&rft.date=1998-04-03&rft.volume=277&rft.issue=3&rft.spage=559&rft.isbn=&rft.btitle=&rft.title=Journal+of+molecular+biology&rft.issn=00222836&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-05-21 N1 - Date created - 1998-05-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The solution structure of a fungal AREA protein-DNA complex: an alternative binding mode for the basic carboxyl tail of GATA factors. AN - 79782532; 9533883 AB - The solution structure of a complex between the DNA binding domain of a fungal GATA factor and a 13 base-pair oligonucleotide containing its physiologically relevant CGATAG target sequence has been determined by multidimensional nuclear magnetic resonance spectroscopy. The AREA DNA binding domain, from Aspergillus nidulans, possesses a single Cys2-Cys2 zinc finger module and a basic C-terminal tail, which recognize the CGATAG element via an extensive network of hydrophobic interactions with the bases in the major groove and numerous non-specific contacts along the sugar-phosphate backbone. The zinc finger core of the AREA DNA binding domain has the same global fold as that of the C-terminal DNA binding domain of chicken GATA-1. In contrast to the complex with the DNA binding domain of GATA-1 in which the basic C-terminal tail wraps around the DNA and lies in the minor groove, the structure of complex with the AREA DNA binding domain reveals that the C-terminal tail of the fungal domain runs parallel with the sugar phosphate backbone along the edge of the minor groove. This difference is principally attributed to amino acid substitutions at two positions of the AREA DNA binding domain (Val55, Asn62) relative to that of GATA-1 (Gly55, Lys62). The impact of the different C-terminal tail binding modes on the affinity and specificity of GATA factors is discussed. Copyright 1998 Academic Press Limited. JF - Journal of molecular biology AU - Starich, M R AU - Wikström, M AU - Arst, H N AU - Clore, G M AU - Gronenborn, A M AD - National Institute of Diabetes and Digestive Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0520, USA. Y1 - 1998/04/03/ PY - 1998 DA - 1998 Apr 03 SP - 605 EP - 620 VL - 277 IS - 3 SN - 0022-2836, 0022-2836 KW - AreA protein, Aspergillus nidulans KW - 0 KW - DNA-Binding Proteins KW - Erythroid-Specific DNA-Binding Factors KW - Fungal Proteins KW - GATA1 Transcription Factor KW - GATA1 protein, human KW - Solutions KW - Transcription Factors KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Models, Molecular KW - Humans KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Sequence Homology, Amino Acid KW - Nucleic Acid Conformation KW - Protein Conformation KW - Mutagenesis KW - Binding Sites KW - Fungal Proteins -- chemistry KW - Fungal Proteins -- metabolism KW - DNA-Binding Proteins -- chemistry KW - Transcription Factors -- metabolism KW - DNA -- metabolism KW - Transcription Factors -- chemistry KW - DNA-Binding Proteins -- genetics KW - DNA -- chemistry KW - Aspergillus nidulans -- chemistry KW - Zinc Fingers KW - Fungal Proteins -- genetics KW - Transcription Factors -- genetics KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79782532?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+molecular+biology&rft.atitle=The+solution+structure+of+a+fungal+AREA+protein-DNA+complex%3A+an+alternative+binding+mode+for+the+basic+carboxyl+tail+of+GATA+factors.&rft.au=Starich%2C+M+R%3BWikstr%C3%B6m%2C+M%3BArst%2C+H+N%3BClore%2C+G+M%3BGronenborn%2C+A+M&rft.aulast=Starich&rft.aufirst=M&rft.date=1998-04-03&rft.volume=277&rft.issue=3&rft.spage=605&rft.isbn=&rft.btitle=&rft.title=Journal+of+molecular+biology&rft.issn=00222836&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-05-21 N1 - Date created - 1998-05-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The solution structure of the Leu22-->Val mutant AREA DNA binding domain complexed with a TGATAG core element defines a role for hydrophobic packing in the determination of specificity. AN - 79782315; 9533884 AB - The seemingly innocuous leucine-to-valine mutation at position 22 of the AREA DNA binding domain results in dramatic changes in the in vivo expression profile of genes controlled by this GATA transcription factor. This is associated with a preference of the Leu22-->Val mutant for TGATAG sites over (A/C)GATAG sites. Quantitative gel retardation assays confirm this observation and show that the Leu22-->Val mutant AREA DNA binding domain has a approximately 30-fold lower affinity than the wild-type domain for a 13 base-pair oligonucleotide containing the wild-type CGATAG target. To gain insight into the measured affinity data and further explore sequence specificity of the AREA protein, the solution structure of a complex between the Leu22-->Val mutant AREA DNA binding domain and a 13 base-pair oligonucleotide containing its physiologically relevant TGATAG target sequence has been determined by multidimensional nuclear magnetic resonance spectroscopy. Comparison of this structure with that of the wild-type AREA DNA binding domain complexed to its cognate CGATAG target site shows how subtle changes in amino acid side-chain length and hydrophobic packing can affect affinity and specificity for GATA-containing sequences, and how changes in DNA sequence can be compensated for by changes in protein sequence. Copyright 1998 Academic Press Limited. JF - Journal of molecular biology AU - Starich, M R AU - Wikström, M AU - Schumacher, S AU - Arst, H N AU - Gronenborn, A M AU - Clore, G M AD - Laboratory of Chemical Physics, Building 5, National Institute of Diabetes and Digestive and Kidney Diseases National Institutes of Health, Bethesda, MD 20892-0520, USA. Y1 - 1998/04/03/ PY - 1998 DA - 1998 Apr 03 SP - 621 EP - 634 VL - 277 IS - 3 SN - 0022-2836, 0022-2836 KW - AreA protein, Aspergillus nidulans KW - 0 KW - DNA-Binding Proteins KW - Fungal Proteins KW - Solutions KW - Transcription Factors KW - DNA KW - 9007-49-2 KW - Leucine KW - GMW67QNF9C KW - Valine KW - HG18B9YRS7 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Models, Molecular KW - Nucleic Acid Conformation KW - Protein Conformation KW - Binding Sites KW - Aspergillus nidulans -- metabolism KW - DNA-Binding Proteins -- chemistry KW - Transcription Factors -- metabolism KW - DNA -- metabolism KW - Leucine -- genetics KW - DNA-Binding Proteins -- genetics KW - Leucine -- chemistry KW - Valine -- genetics KW - Fungal Proteins -- genetics KW - Transcription Factors -- genetics KW - Fungal Proteins -- chemistry KW - Fungal Proteins -- metabolism KW - Aspergillus nidulans -- genetics KW - Leucine -- metabolism KW - Transcription Factors -- chemistry KW - Aspergillus nidulans -- chemistry KW - DNA -- chemistry KW - Zinc Fingers KW - Valine -- metabolism KW - Valine -- chemistry KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79782315?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+molecular+biology&rft.atitle=The+solution+structure+of+the+Leu22--%26gt%3BVal+mutant+AREA+DNA+binding+domain+complexed+with+a+TGATAG+core+element+defines+a+role+for+hydrophobic+packing+in+the+determination+of+specificity.&rft.au=Starich%2C+M+R%3BWikstr%C3%B6m%2C+M%3BSchumacher%2C+S%3BArst%2C+H+N%3BGronenborn%2C+A+M%3BClore%2C+G+M&rft.aulast=Starich&rft.aufirst=M&rft.date=1998-04-03&rft.volume=277&rft.issue=3&rft.spage=621&rft.isbn=&rft.btitle=&rft.title=Journal+of+molecular+biology&rft.issn=00222836&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-05-21 N1 - Date created - 1998-05-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Enzymatic hydrolysis of organic cyclic carbonates. AN - 79766133; 9525873 AB - Ethylene carbonate, a cyclic organic carbonate widely used industrially, is toxic when metabolically converted to ethylene glycol. A rat liver enzyme active in catalyzing the ring opening has been purified to electrophoretic homogeneity and found to be active in the hydrolysis of ethylene, vinylene, and propylene carbonates to CO2 and the respective glycols. Neither thiocarbonates nor open chain carbonates served as substrate nor did a variety of esters, lactams, lactones, and related heterocycles. The enzyme was active, however, with imides and appears to be identical to rat liver imidase. The identification was confirmed by copurification of enzyme activities, by similarities in the pattern of inhibition, and by the reactivity with a polyclonal antibody directed against the enzyme purified here. JF - The Journal of biological chemistry AU - Yang, Y L AU - Ramaswamy, S G AU - Jakoby, W B AD - Laboratory of Biochemistry and Metabolism, NIDDK, National Institutes of Health, Bethesda, Maryland 20892-1812, USA. Y1 - 1998/04/03/ PY - 1998 DA - 1998 Apr 03 SP - 7814 EP - 7817 VL - 273 IS - 14 SN - 0021-9258, 0021-9258 KW - Dioxolanes KW - 0 KW - Amidohydrolases KW - EC 3.5.- KW - dihydropyrimidinase KW - EC 3.5.2.2 KW - ethylene carbonate KW - RGJ96TB7R7 KW - Index Medicus KW - Rats KW - Oxidation-Reduction KW - Animals KW - Substrate Specificity KW - Hydrolysis KW - Amidohydrolases -- metabolism KW - Dioxolanes -- chemistry KW - Dioxolanes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79766133?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Enzymatic+hydrolysis+of+organic+cyclic+carbonates.&rft.au=Yang%2C+Y+L%3BRamaswamy%2C+S+G%3BJakoby%2C+W+B&rft.aulast=Yang&rft.aufirst=Y&rft.date=1998-04-03&rft.volume=273&rft.issue=14&rft.spage=7814&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 - 1998-05-07 N1 - Date created - 1998-05-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Serotonin transporter messenger RNA in the developing rat brain: early expression in serotonergic neurons and transient expression in non-serotonergic neurons. AN - 85264721; pmid-9502257 AB - Serotonin has been shown to affect the development of the mammalian nervous system. The serotonin transporter is a major factor in regulating extracellular serotonin levels. Using in situ hybridization histochemistry the rat serotonin transporter messenger RNA was localized during embryogenesis, the first four weeks postnatally and adulthood. Three general classes of serotonin transporter messenger RNA expression patterns were observed: (i) early detection with continued expression through adult age, (ii) transient expression colocalized with vesicular monoamine transporter 2 messenger RNA but with no detectable tryptophan hydroxylase immunoreactivity, and (iii) transient expression in the apparent absence of both vesicular monoamine transporter 2 messenger RNA and tryptophan hydroxylase immunoreactivity. For example, hybridization for serotonin transporter messenger RNA was strong in serotonin cell body-containing areas beginning early in gestation, and remained intense through adulthood. Immunoreactivity for tryptophan hydroxylase, the rate-limiting enzyme in serotonin synthesis, was completely overlapping with the presence of serotonin transporter messenger RNA in raphe nuclei postnatally. Sensory relay systems including the ventrobasal nucleus (somatosensory), lateral and medial geniculate nuclei (visual and auditory, respectively) as well as trigeminal, cochlear and solitary nuclei were representative of the second class of observations. In general, the limbic system expressed serotonin transporter messenger RNA in the third pattern with various limbic structures differing in the timing of expression. Septum, olfactory areas and the developing hippocampus contained serotonin transporter messenger RNA early in the developing brain. Other regions such as cingulate and frontopolar cortex exhibited hybridization peri- and postnatally, respectively. Several hypothalamic nuclei and pituitary transiently expressed serotonin transporter messenger RNA either postnatally or perinatally, respectively. If the observed patterns correlate with functional protein expression, distinct classes of serotonin transporter messenger RNA expression may reflect different functional roles for the serotonin transporter and serotonin, itself. Since the serotonin transporter is a target for a number of addictive substances including cocaine and amphetamine derivatives as well as antidepressants, transient expression of the serotonin transporter might suggest a window of vulnerability of associated cells to fetal drug exposure. Re-uptake, storage and re-release from non-serotonergic neurons might serve as a feedback mechanism from target neurons to serotonergic neurons. Alternatively, the transient expression of serotonin transporter messenger RNA may reflect critical periods important for tight regulation of extracellular serotonin in several brain regions, and may indicate previously unappreciated roles for serotonin as a developmental cue. JF - Neuroscience AU - Hansson, S R AU - Mezey, E AU - Hoffman, B J AD - Unit on Molecular Pharmacology, Laboratory of Cellular and Molecular Regulation, National Institute of Mental Health, Bethesda, MD 20892, USA. PY - 1998 SP - 1185 EP - 1201 VL - 83 IS - 4 SN - 0306-4522, 0306-4522 KW - Pituitary Gland KW - Carrier Proteins KW - Membrane Glycoproteins KW - Aging KW - Animal KW - Brain KW - Transcription, Genetic KW - Organ Specificity KW - Membrane Proteins KW - Serotonin KW - RNA Probes KW - Pineal Gland KW - Pregnancy KW - RNA, Messenger KW - Rats KW - Animals, Newborn KW - Rats, Sprague-Dawley KW - Tryptophan Hydroxylase KW - Neurons KW - Embryo and Fetal Development KW - Female KW - Gene Expression Regulation, Developmental UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85264721?accountid=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&rft.atitle=Serotonin+transporter+messenger+RNA+in+the+developing+rat+brain%3A+early+expression+in+serotonergic+neurons+and+transient+expression+in+non-serotonergic+neurons.&rft.au=Hansson%2C+S+R%3BMezey%2C+E%3BHoffman%2C+B+J&rft.aulast=Hansson&rft.aufirst=S&rft.date=1998-04-01&rft.volume=83&rft.issue=4&rft.spage=1185&rft.isbn=&rft.btitle=&rft.title=Neuroscience&rft.issn=03064522&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Respiratory tract carcinogenesis by mineral fibres and dusts: models and mechanisms. AN - 80041271; 9689803 AB - Experimental pathology studies in respiratory carcinogenesis by mineral fibres and dusts are reviewed. Animal models, analogous to the corresponding human pathology, were developed for carcinogenesis by polycyclic aromatic hydrocarbons carried on mineral particles, by N-nitroso compounds, by asbestos fibres and by crystalline silica (quartz). Species and organ susceptibility factors determine marked differences in the carcinogenic response to silica in different species and target organs, suggesting possible pathogenetic mechanisms, such as the role of surface oxygen radicals and the induction of related enzymes. Cellular models have been effectively used to study the induction of toxicity and neoplastic transformation by mineral fibres and dusts. Cell culture models have been developed for respiratory epithelial cells and for their transformation. These include not only models for the laryngotracheobronchial columnar epithelium, but also for the alveolar type II epithelium and its transformation by silica. Recent studies on simian virus (SV)40 carcinogenesis in animal and cellular models and on the detection of SV40-like sequences in the deoxyribonucleic acid of human tumours point to the need for much further research on the role of interactions of viral, chemical and physical factors in human respiratory carcinogenesis. JF - Monaldi archives for chest disease = Archivio Monaldi per le malattie del torace AU - Saffiotti, U AD - Laboratory of Experimental Pathology, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1998/04// PY - 1998 DA - April 1998 SP - 160 EP - 167 VL - 53 IS - 2 SN - 1122-0643, 1122-0643 KW - Mineral Fibers KW - 0 KW - Asbestos KW - 1332-21-4 KW - Quartz KW - 14808-60-7 KW - Index Medicus KW - Sensitivity and Specificity KW - Rats KW - Animals KW - Cells, Cultured KW - Humans KW - Disease Models, Animal KW - Mice KW - Cricetinae KW - Mineral Fibers -- adverse effects KW - Respiratory Tract Neoplasms -- etiology KW - Cell Transformation, Neoplastic -- chemically induced KW - Quartz -- adverse effects KW - Asbestos -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80041271?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Monaldi+archives+for+chest+disease+%3D+Archivio+Monaldi+per+le+malattie+del+torace&rft.atitle=Respiratory+tract+carcinogenesis+by+mineral+fibres+and+dusts%3A+models+and+mechanisms.&rft.au=Saffiotti%2C+U&rft.aulast=Saffiotti&rft.aufirst=U&rft.date=1998-04-01&rft.volume=53&rft.issue=2&rft.spage=160&rft.isbn=&rft.btitle=&rft.title=Monaldi+archives+for+chest+disease+%3D+Archivio+Monaldi+per+le+malattie+del+torace&rft.issn=11220643&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-08-26 N1 - Date created - 1998-08-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - NIH-supported intervention trials in osteoporosis. AN - 80004646; 9666216 JF - Aging (Milan, Italy) AU - McGowan, J A AD - National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, Maryland, USA. Y1 - 1998/04// PY - 1998 DA - April 1998 SP - 160 VL - 10 IS - 2 SN - 0394-9532, 0394-9532 KW - Vitamin D KW - 1406-16-2 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - United States KW - Randomized Controlled Trials as Topic KW - Humans KW - Aged KW - Calcium -- administration & dosage KW - Vitamin D -- administration & dosage KW - Cardiovascular Diseases -- prevention & control KW - Estrogen Replacement Therapy -- adverse effects KW - Risk Factors KW - National Institutes of Health (U.S.) KW - Cohort Studies KW - Breast Neoplasms -- etiology KW - Breast Neoplasms -- prevention & control KW - Middle Aged KW - Diet KW - Colorectal Neoplasms -- prevention & control KW - Female KW - Research Support as Topic KW - Osteoporosis -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80004646?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Aging+%28Milan%2C+Italy%29&rft.atitle=NIH-supported+intervention+trials+in+osteoporosis.&rft.au=McGowan%2C+J+A&rft.aulast=McGowan&rft.aufirst=J&rft.date=1998-04-01&rft.volume=10&rft.issue=2&rft.spage=160&rft.isbn=&rft.btitle=&rft.title=Aging+%28Milan%2C+Italy%29&rft.issn=03949532&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-10-20 N1 - Date created - 1998-10-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inhibition of EGF-dependent mitogenesis by prostaglandin E2 in Syrian hamster embryo fibroblasts. AN - 79984048; 9654400 AB - Lipid metabolism can play an important role in the development and progression of human cancers. We have used Syrian hamster embryo (SHE) fibroblasts as a model system to study how lipid metabolites can alter cell proliferation and apoptosis. For example, the linoleic acid metabolite 13(S)-HpODE enhances EGF-dependent growth by inhibiting de-phosphorylation of the EGFR which leads to activation of the MAP kinase pathway. In contrast, the arachidonic acid metabolite, PGE2, inhibits EGF-dependent mitogenesis and the expression of the proto-oncogenes c-myc, c-jun, and jun-B. In this study, we have investigated the mechanism by which PGE2 attenuates these responses by studying the EGF signaling cascade in SHE cells. PGE2 pretreatment caused a concentration-dependent decrease in EGF-dependent phosphorylation of MAP kinase and a corresponding inhibition of EGF-stimulated MAP kinase activity. Pretreatment of the SHE cells with PGE2 had little effect on the magnitude of EGF-dependent receptor auto-phosphorylation and the phosphorylation of GAP suggesting a down-stream target. Treatment of cells with forskolin and EGF causes similar inhibition of MAP kinase phosphorylation as observed with PGE2 and EGF. Since PGE2 elevates cAMP in these cells, it may act by altering cAMP accumulation. Raf-1 activity can be inhibited by a cAMP-dependent process. Raf-1 activity, measured by phosphorylation of Mek-1, was attenuated by the addition of PGE2. To determine if inhibition of Raf-1 activity causes inhibition of the MAP kinase pathway, cells were concomitantly incubated with PGE2 and EGF. Inhibition of MAP kinase phosphorylation was observed. From these data, we propose that in SHE cells PGE2 increases cAMP levels, which in turn causes inhibition of Raf-1 activity. The MAP kinase pathway is thus downregulated which decreases mitogenesis and proto-oncogene expression. This study demonstrates that an arachidonic acid metabolite can modulate phosphorylation and activity of key signal transduction proteins in a growth factor mitogenic pathway. JF - Prostaglandins, leukotrienes, and essential fatty acids AU - Hsi, L C AU - Eling, T E AD - National Institute of Environmental Health Sciences, Laboratory of Molecular Carcinogenesis, Eicosanoid Biochemistry Section, Research Triangle Park, NC 27709, USA. Y1 - 1998/04// PY - 1998 DA - April 1998 SP - 271 EP - 281 VL - 58 IS - 4 SN - 0952-3278, 0952-3278 KW - GTPase-Activating Proteins KW - 0 KW - Oxytocics KW - Proteins KW - Colforsin KW - 1F7A44V6OU KW - Epidermal Growth Factor KW - 62229-50-9 KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - Proto-Oncogene Proteins c-raf KW - EC 2.7.11.1 KW - Calcium-Calmodulin-Dependent Protein Kinases KW - EC 2.7.11.17 KW - Dinoprostone KW - K7Q1JQR04M KW - Index Medicus KW - Animals KW - Calcium-Calmodulin-Dependent Protein Kinases -- metabolism KW - Receptor, Epidermal Growth Factor -- metabolism KW - Dose-Response Relationship, Drug KW - Cell Division -- drug effects KW - Proto-Oncogene Proteins c-raf -- metabolism KW - Proteins -- metabolism KW - Phosphorylation -- drug effects KW - Colforsin -- pharmacology KW - Embryo, Mammalian -- cytology KW - Proto-Oncogene Proteins c-raf -- drug effects KW - Mesocricetus KW - Embryo, Mammalian -- drug effects KW - Cell Line KW - Cricetinae KW - Oxytocics -- administration & dosage KW - Fibroblasts -- drug effects KW - Dinoprostone -- pharmacology KW - Oxytocics -- pharmacology KW - Mitosis -- drug effects KW - Fibroblasts -- cytology KW - Epidermal Growth Factor -- pharmacology KW - Dinoprostone -- administration & dosage KW - Fibroblasts -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79984048?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Prostaglandins%2C+leukotrienes%2C+and+essential+fatty+acids&rft.atitle=Inhibition+of+EGF-dependent+mitogenesis+by+prostaglandin+E2+in+Syrian+hamster+embryo+fibroblasts.&rft.au=Hsi%2C+L+C%3BEling%2C+T+E&rft.aulast=Hsi&rft.aufirst=L&rft.date=1998-04-01&rft.volume=58&rft.issue=4&rft.spage=271&rft.isbn=&rft.btitle=&rft.title=Prostaglandins%2C+leukotrienes%2C+and+essential+fatty+acids&rft.issn=09523278&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-09-08 N1 - Date created - 1998-09-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Heterocyclic amine content in beef cooked by different methods to varying degrees of doneness and gravy made from meat drippings. AN - 79973462; 9651044 AB - Meats cooked at high temperatures sometimes contain heterocyclic amines (HCAs) that are known mutagens and animal carcinogens, but their carcinogenic potential in humans has not been established. To investigate the association between HCAs and cancer, sources of exposure to these compounds need to be determined. Beef is the most frequently consumed meat in the United States and for this study we determined HCA values in beef samples cooked in ways to represent US cooking practices, the results of which can be used in epidemiological studies to estimate HCA exposure from dietary questionnaires. We measured five HCAs [2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)] in different types of cooked beef using solid-phase extraction and HPLC. Steak and hamburger patties were pan-fried, oven-broiled, and grilled/barbecued to four levels of doneness (rare, medium, well done or very well done), while beef roasts were oven cooked to three levels of doneness (rare, medium or well done). The measured values of the specific HCAs varied with the cut of beef, cooking method, and doneness level. In general, MeIQx content increased with doneness under each cooking condition for steak and hamburger patties, up to 8.2 ng/g. PhIP was the predominant HCA produced in steak (1.9 to 30 ng/g), but was formed only in very well done fried or grilled hamburger. DiMeIQx was found in trace levels in pan-fried steaks only, while IQ and MeIQ were not detectable in any of the samples. Roast beef did not contain any of the HCAs, but the gravy made from the drippings from well done roasts had 2 ng/g of PhIP and 7 ng/g of MeIQx. Epidemiological studies need to consider the type of meat, cooking method and degree of doneness/surface browning in survey questions to adequately assess an individual's exposure to HCAs. JF - Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association AU - Sinha, R AU - Rothman, N AU - Salmon, C P AU - Knize, M G AU - Brown, E D AU - Swanson, C A AU - Rhodes, D AU - Rossi, S AU - Felton, J S AU - Levander, O A AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD 20892, USA. Y1 - 1998/04// PY - 1998 DA - April 1998 SP - 279 EP - 287 VL - 36 IS - 4 SN - 0278-6915, 0278-6915 KW - Heterocyclic Compounds KW - 0 KW - Index Medicus KW - Animals KW - Cattle KW - Temperature KW - Chromatography, High Pressure Liquid KW - Heterocyclic Compounds -- analysis KW - Cooking KW - Meat -- analysis KW - Meat Products -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79973462?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Heterocyclic+amine+content+in+beef+cooked+by+different+methods+to+varying+degrees+of+doneness+and+gravy+made+from+meat+drippings.&rft.au=Sinha%2C+R%3BRothman%2C+N%3BSalmon%2C+C+P%3BKnize%2C+M+G%3BBrown%2C+E+D%3BSwanson%2C+C+A%3BRhodes%2C+D%3BRossi%2C+S%3BFelton%2C+J+S%3BLevander%2C+O+A&rft.aulast=Sinha&rft.aufirst=R&rft.date=1998-04-01&rft.volume=36&rft.issue=4&rft.spage=279&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 - 1998-07-10 N1 - Date created - 1998-07-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Recombinant adenovirus encoding gp100 modulates experimental melanin-protein induced uveitis (EMIU). AN - 79972359; 9650089 AB - Experimental melanin-protein induced uveitis (EMIU) is a T-cell mediated autoimmune uveitis induced by immunization with bovine uveal melanin protein. Gp100, a melanocyte lineage-specific protein, is identified as a human melanoma antigen. A recombinant adenovirus construct encoding gp100 (Ad2CMV-gp100) has been used as a vaccine for cancer therapy. This study examines the effect of Ad2CMV-gp100 on EMIU. To induce EMIU, rats were injected intraperitoneally on day 7 before immunization with ad2CMV-gp100, control adenovirus encoding LacZ (Ad2CMV-LacZ), or no virus. On day 21 after immunization, the right eye was processed for histology and the left eye was analysed for cytokines by quantitative reverse transcriptase-polymerase chain reaction. Western blot analysis showed that uveal melanin-protein contains gp100. In three independent experiments, ocular inflammation was significantly suppressed, and expression of ocular IL-12p40 mRNA was much lower in the rats which received Ad2CMV-gp100 before immunization than in those that received Ad2CMV-LacZ or no virus. No abnormalities developed in rats which received Ad2CMV-gp100 or Ad2CMV-LacZ alone. Therefore, Ad2CMV-gp100 injection prevents the development of EMIU, at least in part, through cytokine regulation. JF - Journal of autoimmunity AU - Chan, C C AU - Li, Y AU - Sun, B AU - Li, Q AU - Matteson, D M AU - Shen, D F AU - Nussenblatt, R B AU - Zhai, Y AD - Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892-1858, USA. ccc@helix.nih.gov Y1 - 1998/04// PY - 1998 DA - April 1998 SP - 111 EP - 118 VL - 11 IS - 2 SN - 0896-8411, 0896-8411 KW - Cytokines KW - 0 KW - Eye Proteins KW - Membrane Glycoproteins KW - Neoplasm Proteins KW - PMEL protein, human KW - RNA, Messenger KW - Recombinant Proteins KW - gp100 Melanoma Antigen KW - Interleukin-12 KW - 187348-17-0 KW - Index Medicus KW - Specific Pathogen-Free Organisms KW - Animals KW - Rats, Inbred Lew KW - Choroid -- chemistry KW - Humans KW - T-Lymphocytes, Cytotoxic -- immunology KW - Recombinant Proteins -- genetics KW - Immunization Schedule KW - RNA, Messenger -- genetics KW - RNA, Messenger -- biosynthesis KW - Cytokines -- analysis KW - Rats KW - Cattle KW - Recombinant Proteins -- immunology KW - Gene Expression Regulation KW - Recombinant Proteins -- administration & dosage KW - Female KW - Uveitis -- prevention & control KW - Autoimmune Diseases -- prevention & control KW - Eye Proteins -- toxicity KW - Genetic Vectors -- administration & dosage KW - Defective Viruses -- genetics KW - Neoplasm Proteins -- immunology KW - Autoimmune Diseases -- etiology KW - Uveitis -- immunology KW - Desensitization, Immunologic KW - Uveitis -- etiology KW - Adenoviridae -- genetics KW - Membrane Glycoproteins -- toxicity KW - Eye Proteins -- immunology KW - Interleukin-12 -- biosynthesis KW - Neoplasm Proteins -- toxicity KW - Eye Proteins -- genetics KW - Neoplasm Proteins -- genetics KW - Genetic Vectors -- genetics KW - Eye Proteins -- biosynthesis KW - Interleukin-12 -- genetics KW - Membrane Glycoproteins -- immunology KW - Membrane Glycoproteins -- genetics KW - Autoimmune Diseases -- immunology KW - Eye Proteins -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79972359?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+autoimmunity&rft.atitle=Recombinant+adenovirus+encoding+gp100+modulates+experimental+melanin-protein+induced+uveitis+%28EMIU%29.&rft.au=Chan%2C+C+C%3BLi%2C+Y%3BSun%2C+B%3BLi%2C+Q%3BMatteson%2C+D+M%3BShen%2C+D+F%3BNussenblatt%2C+R+B%3BZhai%2C+Y&rft.aulast=Chan&rft.aufirst=C&rft.date=1998-04-01&rft.volume=11&rft.issue=2&rft.spage=111&rft.isbn=&rft.btitle=&rft.title=Journal+of+autoimmunity&rft.issn=08968411&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-10-22 N1 - Date created - 1998-10-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Heterocyclic amine content of pork products cooked by different methods and to varying degrees of doneness. AN - 79970326; 9651045 AB - Heterocyclic amines (HCAs) are known mutagens and animal carcinogens produced in meats cooked at high temperature. As pork is the second most frequently consumed meat in the United States, five predominant HCAs [2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3,4,8-trimethylimidazo[4.5-f]quinoxaline (DiMeIQx) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)] were measured in various pork products, cooked by different techniques and to varying doneness levels. Pork chops and ham slices were pan-fried and oven-broiled; bacon was pan-fried, oven-broiled or microwaved; hot dogs were pan-fried, oven-broiled, grilled/barbecued or boiled; sausage links and patties were pan-fried. All the products were cooked to three levels of doneness: just until done, well done or very well done. HCA type and level varied substantially by pork product, cooking method and doneness level. The highest PhIP levels were found in well done and very well done oven-broiled bacon; for very well done 30.3 and 4.0 ng per gram of meat of PhIP and MeIQx, respectively. Pan-fried very well done sausage patties contained 5.4 ng of MeIQx per gram of meat, while sausage links contained 1.3 ng per gram of meat. MeIQx was formed in well done and very well done pan-fried but not broiled pork chops. Hot dogs or ham slices had low or undetectable levels of HCAs. These results demonstrate that epidemiological studies investigating the relationship between HCA intake and cancer risk need to incorporate type of meat, cooking method and degree of doneness/surface browning into questions to assess adequately an individual's HCA exposure. JF - Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association AU - Sinha, R AU - Knize, M G AU - Salmon, C P AU - Brown, E D AU - Rhodes, D AU - Felton, J S AU - Levander, O A AU - Rothman, N AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD 20892, USA. Y1 - 1998/04// PY - 1998 DA - April 1998 SP - 289 EP - 297 VL - 36 IS - 4 SN - 0278-6915, 0278-6915 KW - Heterocyclic Compounds KW - 0 KW - Index Medicus KW - Swine KW - Animals KW - Temperature KW - Chromatography, High Pressure Liquid KW - Heterocyclic Compounds -- analysis KW - Cooking KW - Meat -- analysis KW - Meat Products -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79970326?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Heterocyclic+amine+content+of+pork+products+cooked+by+different+methods+and+to+varying+degrees+of+doneness.&rft.au=Sinha%2C+R%3BKnize%2C+M+G%3BSalmon%2C+C+P%3BBrown%2C+E+D%3BRhodes%2C+D%3BFelton%2C+J+S%3BLevander%2C+O+A%3BRothman%2C+N&rft.aulast=Sinha&rft.aufirst=R&rft.date=1998-04-01&rft.volume=36&rft.issue=4&rft.spage=289&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 - 1998-07-10 N1 - Date created - 1998-07-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The genetic effects of environmental lead. AN - 79953087; 9637233 AB - This article reviews the effects of lead on genetic systems in the context of lead's various other toxic effects and its abundance and distribution in the environment. Lead is perhaps the longest used and best recognized toxic environmental chemical, yet it continued be used recklessly until only very recently. Lead is thus a lesson in the limitations and strengths of science, human conscience and common sense. Lead has been tested and found to be capable of eliciting a positive response in an extraordinarily wide range of biological and biochemical tests; among them tests for enzyme inhibition, fidelity of DNA synthesis, mutation, chromosome aberrations, cancer and birth defects. It reacts or complexes with many biomolecules and adversely affects the reproductive, nervous, gastrointestinal, immune, renal, cardiovascular, skeletal, muscular and hematopoietic systems as well as developmental processes. It is likely that lead is a selective agent that continues to act on and influence the genetic structure and future evolution of exposed plant and animal populations. JF - Mutation research AU - Johnson, F M AD - Toxicology Operations Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1998/04// PY - 1998 DA - April 1998 SP - 123 EP - 140 VL - 410 IS - 2 SN - 0027-5107, 0027-5107 KW - Environmental Pollutants KW - 0 KW - Water Pollutants, Chemical KW - Lead KW - 2P299V784P KW - Index Medicus KW - Animals KW - Water Pollutants, Chemical -- toxicity KW - Humans KW - Lead Poisoning -- etiology KW - Environmental Exposure -- adverse effects KW - Lead -- adverse effects KW - Genetic Diseases, Inborn -- genetics KW - Genetic Diseases, Inborn -- chemically induced KW - Environmental Pollutants -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79953087?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+research&rft.atitle=The+genetic+effects+of+environmental+lead.&rft.au=Johnson%2C+F+M&rft.aulast=Johnson&rft.aufirst=F&rft.date=1998-04-01&rft.volume=410&rft.issue=2&rft.spage=123&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 - 1998-07-02 N1 - Date created - 1998-07-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Anthralin stimulates keratinocyte-derived proinflammatory cytokines via generation of reactive oxygen species. AN - 79932746; 9628260 AB - Topical application of anthralin, used in the treatment of psoriasis, is often accompanied by severe skin inflammation, presumably due to free radical products of the drug. The role of inflammatory cytokines and their induction by anthralin-derived reactive oxygen species were studied in cultures of normal human keratinocytes (NHKs). Anthralin was added to cultures of NHKs in the presence or absence of various antioxidants, including superoxide dismutase, tetramethylthiourea, N-acetylcysteine and vitamin E and relative changes in cytokine secretion and in the number of mRNA transcripts were examined. In addition, NHKs were either treated with neutralizing antibodies to tumor necrosis factor (TNF)-alpha or transfected with a CAT-linked IL-8 promoter to establish the direct effects of anthralin on chemokine synthesis. Anthralin, at concentrations between 5 microM and 25 microM, caused a marked increase in granulocyte macrophage-colony stimulating factor (GM-CSF), interleukin (IL)-6, IL-8 and TNFalpha synthesis that was selectively inhibited by specific antioxidants. Furthermore, anthralin induced chemokine secretion without the need of primary cytokines. Taken together, these studies suggest that oxygen radicals generated from anthralin are responsible for the induction of inflammatory cytokines which, in turn contributes to their dermal toxicity. JF - Inflammation research : official journal of the European Histamine Research Society ... [et al.] AU - Lange, R W AU - Hayden, P J AU - Chignell, C F AU - Luster, M I AD - Environmental Immunology Section, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC 27709, USA. lange+@pitt.edu Y1 - 1998/04// PY - 1998 DA - April 1998 SP - 174 EP - 181 VL - 47 IS - 4 SN - 1023-3830, 1023-3830 KW - Anti-Inflammatory Agents KW - 0 KW - Antibodies KW - Antioxidants KW - Cytokines KW - Interleukin-6 KW - Interleukin-8 KW - RNA, Messenger KW - Reactive Oxygen Species KW - Tumor Necrosis Factor-alpha KW - Vitamin E KW - 1406-18-4 KW - Granulocyte-Macrophage Colony-Stimulating Factor KW - 83869-56-1 KW - Superoxide Dismutase KW - EC 1.15.1.1 KW - Thiourea KW - GYV9AM2QAG KW - tetramethylthiourea KW - J6T67A1P72 KW - Anthralin KW - U8CJK0JH5M KW - Acetylcysteine KW - WYQ7N0BPYC KW - Index Medicus KW - Transcription, Genetic -- drug effects KW - Dose-Response Relationship, Drug KW - Humans KW - Tumor Necrosis Factor-alpha -- biosynthesis KW - Acetylcysteine -- pharmacology KW - Thiourea -- analogs & derivatives KW - Granulocyte-Macrophage Colony-Stimulating Factor -- biosynthesis KW - Superoxide Dismutase -- pharmacology KW - Interleukin-8 -- biosynthesis KW - RNA, Messenger -- metabolism KW - Transfection KW - Cells, Cultured KW - Thiourea -- pharmacology KW - Antibodies -- pharmacology KW - Vitamin E -- pharmacology KW - Interleukin-6 -- biosynthesis KW - Administration, Topical KW - Reactive Oxygen Species -- metabolism KW - Antioxidants -- pharmacology KW - Keratinocytes -- drug effects KW - Cytokines -- biosynthesis KW - Keratinocytes -- metabolism KW - Anthralin -- pharmacology KW - Anti-Inflammatory Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79932746?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Inflammation+research+%3A+official+journal+of+the+European+Histamine+Research+Society+...+%5Bet+al.%5D&rft.atitle=Anthralin+stimulates+keratinocyte-derived+proinflammatory+cytokines+via+generation+of+reactive+oxygen+species.&rft.au=Lange%2C+R+W%3BHayden%2C+P+J%3BChignell%2C+C+F%3BLuster%2C+M+I&rft.aulast=Lange&rft.aufirst=R&rft.date=1998-04-01&rft.volume=47&rft.issue=4&rft.spage=174&rft.isbn=&rft.btitle=&rft.title=Inflammation+research+%3A+official+journal+of+the+European+Histamine+Research+Society+...+%5Bet+al.%5D&rft.issn=10233830&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-09-25 N1 - Date created - 1998-09-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CONF T1 - Introduction and summary of the 13th meeting of the Scientific Group on Methodologies for the Safety Evaluation of Chemicals (SGOMSEC): alternative testing methodologies. AN - 79898356; 9599686 AB - A workshop on alternative toxicological testing methodologies was convened by the Scientific Group on Methodologies for the Safety Evaluation of Chemicals (SGOMSEC) 26-31 January 1997 in Ispra, Italy, at the European Centre for the Validation of Alternative Methods. The purpose of the workshop was to assess the current status of alternative testing methodologies available to evaluate adverse human health and environmental effects of chemicals. Another objective of the workshop was to identify and recommend research needed to fill knowledge gaps that would lead to new test methodologies. Four work groups were established to address conceptual issues, acute toxicity, organ toxicity, and ecotoxicology. A joint workshop report was prepared for each topic and included recommendations for the development and use of alternative methods. Participants concluded that alternative methods and approaches are available that can be incorporated into tiered strategies for toxicological assessments. Use of these methods will reduce the numbers of animals required, and in some instances reduce animal pain and distress. It was recommended that future efforts to develop test methods should emphasize mechanism-based methods that can provide improved predictions of toxicity. Continued international cooperation was encouraged to facilitate future progress in the development of alternative toxicological testing methods. These methods will provide for improvements in human health protection, environmental protection, and animal welfare. JF - Environmental health perspectives AU - Stokes, W S AU - Marafante, E Y1 - 1998/04// PY - 1998 DA - April 1998 SP - 405 EP - 412 VL - 106 Suppl 2 KW - Environmental Pollutants KW - 0 KW - Index Medicus KW - Animals KW - Public Health KW - Humans KW - Animal Testing Alternatives KW - Animal Welfare KW - Toxicity Tests -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79898356?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&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=Introduction+and+summary+of+the+13th+meeting+of+the+Scientific+Group+on+Methodologies+for+the+Safety+Evaluation+of+Chemicals+%28SGOMSEC%29%3A+alternative+testing+methodologies.&rft.au=Stokes%2C+W+S%3BMarafante%2C+E&rft.aulast=Stokes&rft.aufirst=W&rft.date=1998-04-01&rft.volume=106+Suppl+2&rft.issue=&rft.spage=405&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 - 1998-07-16 N1 - Date created - 1998-07-16 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Environ Health Perspect. 1998 Apr;106 Suppl 2:441-51 [9599690] Fundam Appl Toxicol. 1992 Feb;18(2):200-10 [1534777] Environ Health Perspect. 1998 Apr;106 Suppl 2:413-8 [9599687] Environ Health Perspect. 1998 Apr;106 Suppl 2:419-25 [9599688] Environ Health Perspect. 1998 Apr;106 Suppl 2:427-39 [9599689] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A selective historical review of congener-specific human tissue measurements as sensitive and specific biomarkers of exposure to dioxins and related compounds. AN - 79897846; 9599725 AB - Estimating internal exposure or dose of dioxins and related chemicals such as dibenzofurans and dioxinlike polychlorinated biphenyls is relatively straightforward in laboratory animals because a known dose is given and the amount absorbed can be measured. In wildlife, direct tissue measurement and measurement of environmental samples have both recently been used to estimate exposure. Until recently, human studies used only indirect indicators such as skin lesions to qualitatively estimate exposure to these chlorinated organic compounds. Environmental measurements have also sometimes been used to estimate human exposure. Dioxins in human tissue were not measured until the 1970s, when 2,3,7,8-tetrachlorodibenzo-p-dioxin was measured in mothers' milk; congener-specific measurement of dioxins and dibenzofurans in tissues (blood, milk, and adipose tissue) of the general population and exposed workers was first performed in the United States in the 1980s. Measurement in a sensitive and specific fashion of the 17 toxic dioxin and dibenzofuran congeners currently found in human tissue from industrial countries began in the 1980s. The use of known chemical standards, capillary columns, high resolution gas chromatography and mass spectrometry (GC-MS) has now become relatively common. GC-MS analysis of blood is currently accepted as the gold standard for estimating human exposure to dioxins. However, analyses are still costly and time consuming, and worldwide there are few qualified laboratories. There is currently a lack of knowledge concerning kinetics at higher and lower exposure levels for most of the toxic dioxin congeners and of levels in target tissues of concern. JF - Environmental health perspectives AU - Schecter, A AD - Department of Preventive Medicine, State University of New York Health Science Center-Syracuse, Binghamton, USA. schecter@niehs.nih.gov Y1 - 1998/04// PY - 1998 DA - April 1998 SP - 737 EP - 742 VL - 106 Suppl 2 SN - 0091-6765, 0091-6765 KW - Benzofurans KW - 0 KW - Biomarkers KW - Dioxins KW - Index Medicus KW - Sensitivity and Specificity KW - Mass Spectrometry KW - Chromatography, Gas KW - Dose-Response Relationship, Drug KW - Humans KW - Risk Assessment KW - Dioxins -- analysis KW - Environmental Exposure KW - Benzofurans -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79897846?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+health+perspectives&rft.atitle=A+selective+historical+review+of+congener-specific+human+tissue+measurements+as+sensitive+and+specific+biomarkers+of+exposure+to+dioxins+and+related+compounds.&rft.au=Schecter%2C+A&rft.aulast=Schecter&rft.aufirst=A&rft.date=1998-04-01&rft.volume=106+Suppl+2&rft.issue=&rft.spage=737&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 - 1998-07-16 N1 - Date created - 1998-07-16 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Toxicol Appl Pharmacol. 1971 Nov;20(3):396-403 [5132781] Toxicol Appl Pharmacol. 1992 May;114(1):97-107 [1585378] Toxicol Appl Pharmacol. 1978 Nov;46(2):279-303 [734660] Br J Cancer. 1979 Jun;39(6):711-7 [444410] Anal Chem. 1980 Aug;52(9):1497-500 [6774628] Br J Cancer. 1981 Feb;43(2):169-76 [7470379] J Occup Med. 1992 Jul;34(7):702-7 [1494962] Arch Environ Contam Toxicol. 1993 May;24(4):504-12 [8507107] Anal Biochem. 1993 May 15;211(1):102-12 [8323021] Epidemiology. 1993 Sep;4(5):398-406 [8399687] J Toxicol Environ Health. 1994 Apr;41(4):481-8 [8145287] Environ Health Perspect. 1994 Jan;102 Suppl 1:135-47 [8187703] Environ Health Perspect. 1994 Jan;102 Suppl 1:149-58 [8187704] Environ Health Perspect. 1994 Jan;102 Suppl 1:159-71 [8187705] Pediatr Res. 1994 Oct;36(4):468-73 [7816522] Anal Biochem. 1994 Oct;222(1):217-23 [7856852] Am J Public Health. 1995 Apr;85(4):516-22 [7702115] Early Hum Dev. 1995 Apr 14;41(2):111-27 [7601016] Am J Epidemiol. 1995 Dec 1;142(11):1165-75 [7485063] J Toxicol Environ Health. 1996 Mar;47(4):363-78 [8600289] J Toxicol Environ Health. 1996 Feb 23;47(3):209-20 [8604146] Am J Ind Med. 1996 Dec;30(6):647-54 [8914711] Environ Res. 1984 Feb;33(1):261-8 [6692811] Rocz Panstw Zakl Hig. 1984;35(4):297-301 [6522993] Environ Health Perspect. 1985 May;60:241-54 [3928350] Am J Ind Med. 1986;9(4):305-21 [3706306] JAMA. 1988 Mar 18;259(11):1661-7 [3343772] Toxicol Appl Pharmacol. 1988 Mar 30;93(1):22-30 [3353999] Environ Res. 1988 Dec;47(2):112-28 [3263267] J Toxicol Environ Health. 1989;27(2):165-71 [2733058] Int Arch Occup Environ Health. 1990;62(2):139-57 [2139014] N Engl J Med. 1991 Jan 24;324(4):212-8 [1985242] Lancet. 1991 Oct 19;338(8773):959-64 [1681339] Lancet. 1991 Oct 26;338(8774):1027-32 [1681353] Toxicol Appl Pharmacol. 1992 May;114(1):108-17 [1585363] Toxicol Appl Pharmacol. 1992 May;114(1):118-26 [1585364] Environ Health Perspect. 1973 Sep;5:27-35 [4752911] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evaluation and validation issues in the development of transgenic mouse carcinogenicity bioassays. AN - 79896872; 9599694 AB - Transgenic mouse models have emerged as plausible alternatives to long-term bioassays for carcinogenicity. Three transgenic lines evaluated to date have shown a clear capability to discriminate between carcinogens and noncarcinogens, using long-term bioassay results as the standard. The data also suggest that the transgenic lines will not fully duplicate long-term bioassay results. It is proposed that these models do not respond to chemicals that have induced highly restricted species or strain-specific tumor responses in mice or rats. Rather, the value of the transgenic models is predicated on a preferential response to transspecies carcinogens (i.e., those positive in both rats and mice, often including tumors in the same tissues). Thus, although results in transgenic models may not be completely concordant with long-term bioassays, the data can be used effectively in chemical and drug safety assessments. Further, it is proposed that validation of the models is readily achievable via ongoing studies. Validation of any alternative model is best achieved by sufficient mechanistic understanding of the model to reasonably predict the outcome of bioassays conducted in the models and use all available information on the drug or chemical. This goal can now be met with the transgenic mouse lines. JF - Environmental health perspectives AU - Tennant, R W AD - Laboratory of Environmental Carcinogenesis and Mutagenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. tennant@niehs.nih.gov Y1 - 1998/04// PY - 1998 DA - April 1998 SP - 473 EP - 476 VL - 106 Suppl 2 SN - 0091-6765, 0091-6765 KW - Index Medicus KW - Animals KW - Reproducibility of Results KW - Animal Welfare KW - Mice KW - Models, Biological KW - Animal Testing Alternatives KW - Carcinogenicity Tests -- methods KW - Mice, Transgenic UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79896872?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Evaluation+and+validation+issues+in+the+development+of+transgenic+mouse+carcinogenicity+bioassays.&rft.au=Tennant%2C+R+W&rft.aulast=Tennant&rft.aufirst=R&rft.date=1998-04-01&rft.volume=106+Suppl+2&rft.issue=&rft.spage=473&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 - 1998-07-16 N1 - Date created - 1998-07-16 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Science. 1987 May 22;236(4804):933-41 [3554512] Prog Exp Tumor Res. 1964;4:207-50 [14150247] Mutagenesis. 1990 Mar;5(2):191-7 [2188074] Proc Natl Acad Sci U S A. 1990 Dec;87(23):9178-82 [2251261] Prog Exp Tumor Res. 1991;33:1-20 [2028021] Nature. 1992 Mar 19;356(6366):215-21 [1552940] Mutat Res. 1993 Mar;286(1):111-8 [7678907] Carcinogenesis. 1993 Jul;14(7):1335-41 [8330346] Environ Health Perspect. 1993 Apr;100:307-15 [8354178] Nat Genet. 1993 Nov;5(3):225-9 [8275085] Mol Carcinog. 1994 Mar;9(3):143-54 [7908201] Oncogene. 1994 Dec;9(12):3731-6 [7970733] Environ Mol Mutagen. 1995;25(4):302-13 [7607185] Toxicology. 1995 Aug 25;101(3):125-56 [7676462] Prog Clin Biol Res. 1995;391:223-35 [8532720] Environ Health Perspect. 1995 Oct;103(10):942-50 [8529591] Hum Exp Toxicol. 1996 Mar;15(3):183-202 [8839204] Carcinogenesis. 1996 Nov;17(11):2455-61 [8968063] Cell. 1990 May 4;61(3):407-17 [2185890] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Animal models of human response to dioxins. AN - 79895455; 9599728 AB - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is the most potent member of a class of chlorinated hydrocarbons that interact with the aryl hydrocarbon receptor (AhR). TCDD and dioxinlike compounds are environmentally and biologically stable and as a result, human exposure is chronic and widespread. Studies of highly exposed human populations show that dioxins produce developmental effects, chloracne, and an increase in all cancers and suggest that they may also alter immune and endocrine function. In contrast, the health effects of low-level environmental exposure have not been established. Experimental animal models can enhance the understanding of the effects of low-level dioxin exposure, particularly when there is evidence that humans respond similarly to the animal models. Although there are species differences in pharmacokinetics, experimental animal models demonstrate AhR-dependent health effects that are similar to those found in exposed human populations. Comparisons of biochemical changes show that humans and animal models have similar degrees of sensitivity to dioxin-induced effects. The information gained from animal models is important for developing mechanistic models of dioxin toxicity and critical for assessing the risks to human populations under different circumstances of exposure. JF - Environmental health perspectives AU - Grassman, J A AU - Masten, S A AU - Walker, N J AU - Lucier, G W AD - Laboratory of Computational Biology and Risk Analysis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA. grassman@niehs.nih.gov Y1 - 1998/04// PY - 1998 DA - April 1998 SP - 761 EP - 775 VL - 106 Suppl 2 SN - 0091-6765, 0091-6765 KW - Dioxins KW - 0 KW - Polychlorinated Dibenzodioxins KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Index Medicus KW - Animals KW - Dose-Response Relationship, Drug KW - Humans KW - Gene Expression KW - Cytochrome P-450 Enzyme System -- drug effects KW - Risk Assessment KW - Dioxins -- adverse effects KW - Dioxins -- pharmacokinetics KW - Polychlorinated Dibenzodioxins -- pharmacokinetics KW - Polychlorinated Dibenzodioxins -- adverse effects KW - Disease Models, Animal KW - Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79895455?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Animal+models+of+human+response+to+dioxins.&rft.au=Grassman%2C+J+A%3BMasten%2C+S+A%3BWalker%2C+N+J%3BLucier%2C+G+W&rft.aulast=Grassman&rft.aufirst=J&rft.date=1998-04-01&rft.volume=106+Suppl+2&rft.issue=&rft.spage=761&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 - 1998-07-16 N1 - Date created - 1998-07-16 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Am J Public Health. 1994 Mar;84(3):415-21 [8129058] Am J Public Health. 1994 Mar;84(3):439-45 [8129062] Environ Health Perspect. 1993 Nov;101(6):504-8 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[8790407] Fundam Appl Toxicol. 1996 Jan;29(1):40-7 [8838638] J Toxicol Environ Health. 1977 Oct;3(3):451-64 [926199] Toxicol Appl Pharmacol. 1978 Nov;46(2):279-303 [734660] Arch Toxicol Suppl. 1980;4:163-5 [6933896] Cancer Res. 1980 Oct;40(10):3616-20 [6108157] Annu Rev Pharmacol Toxicol. 1982;22:517-54 [6282188] Cancer Res. 1982 Dec;42(12):5030-7 [6291746] Am J Ind Med. 1984;5(1-2):81-115 [6230932] Mol Pharmacol. 1984 Jan;25(1):185-91 [6708934] Eur J Biochem. 1985 Mar 1;147(2):429-35 [2982617] Toxicol Appl Pharmacol. 1985 Feb;77(2):251-9 [2579474] Toxicol Appl Pharmacol. 1985 Mar 15;77(3):434-43 [2579475] Toxicol Appl Pharmacol. 1985 Jun 15;79(1):99-111 [4049410] Cancer Res. 1986 Feb;46(2):999-1004 [3079671] Cancer Res. 1986 Mar;46(3):1030-7 [3002608] Drug Metab Dispos. 1986 Jan-Feb;14(1):34-40 [2868862] J Steroid Biochem. 1986 Jan;24(1):353-6 [3009986] JAMA. 1986 Nov 21;256(19):2687-95 [2877102] Annu Rev Biochem. 1987;56:881-914 [3039909] Toxicol Appl Pharmacol. 1987 Sep 15;90(2):206-16 [3629596] Mol Pharmacol. 1987 Nov;32(5):572-8 [3119985] Toxicol Appl Pharmacol. 1988 Apr;93(2):231-46 [3358261] Environ Health Perspect. 1987 Dec;76:79-87 [2834196] Hepatology. 1989 Jan;9(1):126-38 [2642290] Neurotoxicol Teratol. 1989 Jan-Feb;11(1):13-9 [2725437] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - JC virus excreted by multiple sclerosis patients and paired controls from Hungary. AN - 79893253; 9599332 AB - JC virus (JCV), a human polyomavirus, is the agent of the demyelinating disease progressive multifocal leukoencephalopathy (PML). JCV exists in four main genotypes in the USA. Type 1, including subtypes Type 1A and Type 1B, makes up about 64% of strains in the USA and is thought to be of European origin. Type 2 is found in Asia, and Type 3 in Africa. A fourth type is found only in the USA. In general, these genotypes differ in 1-2.5% of their DNA sequence. Thirty MS patients and 30 paired controls from Budapest were studied. The clinical course of MS was mainly secondary progressive, and patients were stable at the time of testing. Most of the controls were relatives of the probands: a spouse, parent, or child. Overall, 25 of 60 (42%) of the urines tested positive for JCV by PCR. These included 13 of 30 MS patients, and 12 of 30 controls. Genotyping in the VPI gene showed all 25 JCV strains to be Type 1. Among the MS patients, seven were Type 1A and six were Type 1B. Among the controls, nine were Type 1A and three were Type 1B. In five pairs of MS patients and controls, both were positive for JCV by PCR. Two of these were husband/wife pairs of which one pair was matched for subtype (both Type 1A), and the other was not. Two of them were mother/daughter pairs, and both were matched for subtype (both Type 1B). These findings demonstrate that JCV Type 1 predominates among Hungarians, and suggest that parent/child pairs can be used to trace JCV transmission within the MS family. JF - Multiple sclerosis (Houndmills, Basingstoke, England) AU - Stoner, G L AU - Agostini, H T AU - Ryschkewitsch, C F AU - Komoly, S AD - Neurotoxicology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/04// PY - 1998 DA - April 1998 SP - 45 EP - 48 VL - 4 IS - 2 SN - 1352-4585, 1352-4585 KW - DNA, Viral KW - 0 KW - Index Medicus KW - Genotype KW - Genetic Variation KW - Hungary KW - DNA, Viral -- analysis KW - Humans KW - Adult KW - Middle Aged KW - DNA, Viral -- urine KW - Male KW - Female KW - Multiple Sclerosis -- urine KW - JC Virus -- genetics KW - Multiple Sclerosis -- virology KW - JC Virus -- isolation & purification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79893253?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Multiple+sclerosis+%28Houndmills%2C+Basingstoke%2C+England%29&rft.atitle=JC+virus+excreted+by+multiple+sclerosis+patients+and+paired+controls+from+Hungary.&rft.au=Stoner%2C+G+L%3BAgostini%2C+H+T%3BRyschkewitsch%2C+C+F%3BKomoly%2C+S&rft.aulast=Stoner&rft.aufirst=G&rft.date=1998-04-01&rft.volume=4&rft.issue=2&rft.spage=45&rft.isbn=&rft.btitle=&rft.title=Multiple+sclerosis+%28Houndmills%2C+Basingstoke%2C+England%29&rft.issn=13524585&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-07-10 N1 - Date created - 1998-07-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A human vascular endothelial cell model to study angiogenesis and tumorigenesis. AN - 79888138; 9600354 AB - Endothelial cell biology has recently been the subject of considerable interest in thrombosis and cancer research. However, the successful establishment of immortalized human endothelial cells which retain differentiated cell characteristics has been rare. We have successfully established immortalized human umbilical vein endothelial cells (HUVECs) by human papilloma virus (HPV)-16 E6-E7. HPV-16 E6, E7 and E6-E7 were successfully introduced into HUVEC cells. Both E6 and E7 cultures had an extended lifespan but eventually underwent senescence. E6-E7 cultures 4-5-2G, however, acquired an indefinite lifespan in culture but did not undergo malignant conversion. Telomerase activity was not detected in either E6 or E7 cultures; however, telomerase was detected in E6-E7 4-5-2G cells. The cells exhibited a 'cobblestone' morphology and developed a capillary-like tube structure upon reaching confluence. The 4-5-2G line expressed Factor VIII related antigen and took up DiI-Ac-LDL as markers of endothelial origin. The line expressed integrin subunits (alpha(v)beta3, alph(v)beta5, beta1, alpha2, alpha3, beta4 and alpha6) consistent with an endothelial origin. The higher passage of 4-5-2G line showed a similar intensity of integrin immunostaining to that of primary HUVECS. Subsequent infection of these immortal cells with the Kirsten murine sarcoma virus which contains an activated K-ras oncogene induced morphological transformation that led to the acquisition of invasion capability and neoplastic properties. Telomerase was also detected in the tumorigenic v-Ki-ras transformed cell line. These cell lines should be useful for studies of the molecular mechanisms underlying normal and neoplastic endothelial cell proliferation and migration, and might also provide an in vitro model for development of pharmacologic and gene therapy for cardiovascular thrombosis and cancer. JF - Carcinogenesis AU - Rhim, J S AU - Tsai, W P AU - Chen, Z Q AU - Chen, Z AU - Van Waes, C AU - Burger, A M AU - Lautenberger, J A AD - Laboratory of Biochemical Physiology, National Cancer Institute, Frederick, MD 21702, USA. rhimi@fcrfv1.ncifcrf.gov Y1 - 1998/04// PY - 1998 DA - April 1998 SP - 673 EP - 681 VL - 19 IS - 4 SN - 0143-3334, 0143-3334 KW - DNA, Viral KW - 0 KW - E6 protein, Human papillomavirus type 16 KW - Integrins KW - Oncogene Proteins, Viral KW - Papillomavirus E7 Proteins KW - Repressor Proteins KW - oncogene protein E7, Human papillomavirus type 16 KW - Index Medicus KW - Karyotyping KW - Papillomaviridae -- physiology KW - Humans KW - Oncogene Proteins, Viral -- physiology KW - Genes, ras KW - Cell Aging KW - Chromosome Aberrations KW - Oncogene Proteins, Viral -- genetics KW - Cell Line, Transformed KW - Integrins -- metabolism KW - DNA, Viral -- genetics KW - Cell Transformation, Neoplastic KW - Cell Transformation, Viral KW - Neoplasms -- pathology KW - Neoplasms -- blood supply KW - Endothelium, Vascular -- pathology KW - Models, Biological UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79888138?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+human+vascular+endothelial+cell+model+to+study+angiogenesis+and+tumorigenesis.&rft.au=Rhim%2C+J+S%3BTsai%2C+W+P%3BChen%2C+Z+Q%3BChen%2C+Z%3BVan+Waes%2C+C%3BBurger%2C+A+M%3BLautenberger%2C+J+A&rft.aulast=Rhim&rft.aufirst=J&rft.date=1998-04-01&rft.volume=19&rft.issue=4&rft.spage=673&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-06-04 N1 - Date created - 1998-06-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of retinoid analogues on mammary cancer in transgenic mice with c-neu breast cancer oncogene. AN - 79881069; 9598873 AB - Breast cancer is one of the most common cancers and is a leading cause of mortality in women. The TG.NK transgenic mouse line expresses the c-neu breast cancer oncogene under the control of an MMTV promoter and appears to be a useful animal model for evaluation of intervention strategies to delay/prevent breast cancer. Fiber-rich nonpurified diet (NTP-2000), as compared to a purified diet (AIN-76A), has previously been shown to significantly delay the development of mammary cancer in the TG.NK model. Four-week old hemizygous TG.NK female mice with MMTV/c-neu oncogene were fed NTP-2000 diet containing the retinoid analogue 4-hydroxyphenyl retinamide (4-HPR) at 5 mM/kg or an arotinoid Ro 40-8757 at 2 and 3 mmol/kg for 26 weeks. The 4-HPR at 5 mmol/kg diet delayed the development of palpable tumors up to 24 weeks, but by 26 weeks, the incidence was not significantly different from the NTP-2000 diet control group. However, the 4-HPR diet markedly decreased the average weight of the tumors at 26 weeks. The 4-HPR diet also caused a significant increase in body weight without an increase in food consumption. Arotinoid Ro-40-8757 at both doses inhibited the development of mammary tumors for the duration of the study. However, the Ro 40-8757 at 3 mmol/kg appeared to be toxic as indicated by a significant depression of the average body weight with alopecia and skin scaling in some mice. Our observations with TG.NK transgenic mouse and fiber-rich diet (NTP-2000) indicate that the arotinoid Ro 40-8757 has a markedly higher inhibitory effect on the development of mammary cancer than 4-HPR. Studies to evaluate genetic changes and expression of hormonal receptors and growth factors associated with the inhibition of mammary cancer development by the retinoid analogues are in progress. JF - Breast cancer research and treatment AU - Rao, G N AU - Ney, E AU - Herbert, R A AD - Environmental Toxicology Program, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 1998/04// PY - 1998 DA - April 1998 SP - 265 EP - 271 VL - 48 IS - 3 SN - 0167-6806, 0167-6806 KW - Anticarcinogenic Agents KW - 0 KW - Morpholines KW - Retinoids KW - Fenretinide KW - 187EJ7QEXL KW - mofarotene KW - 8K3CVY8F8V KW - Index Medicus KW - Animals KW - Retinoids -- therapeutic use KW - Morpholines -- therapeutic use KW - Genes, erbB-2 -- genetics KW - Mice KW - Mice, Transgenic KW - Female KW - Fenretinide -- therapeutic use KW - Anticarcinogenic Agents -- therapeutic use KW - Mammary Neoplasms, Animal -- genetics KW - Mammary Neoplasms, Animal -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79881069?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Breast+cancer+research+and+treatment&rft.atitle=Effect+of+retinoid+analogues+on+mammary+cancer+in+transgenic+mice+with+c-neu+breast+cancer+oncogene.&rft.au=Rao%2C+G+N%3BNey%2C+E%3BHerbert%2C+R+A&rft.aulast=Rao&rft.aufirst=G&rft.date=1998-04-01&rft.volume=48&rft.issue=3&rft.spage=265&rft.isbn=&rft.btitle=&rft.title=Breast+cancer+research+and+treatment&rft.issn=01676806&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-08-13 N1 - Date created - 1998-08-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of lead on cytoskeletal proteins expressed in E14 mesencephalic primary cultures. AN - 79875419; 9596558 AB - Several lines of evidence indicated that Pb exposure in vivo and in vitro altered neurite morphology in central and peripheral neurons. The present report shows that neurite length in mesencephalic primary cultures, consisting of neurons and glia, was decreased by Pb exposure when serum factors, presumably essential for glial functions, were absent in the culture medium. We studied whether a serum factor might control the mechanisms involved in the uptake and accumulation of Pb and its effect on cytoskeleton proteins. The total amount of Pb taken up in cell cultures was measured by atomic absorption spectroscopy and appeared to be down-regulated by a non-albumin-like serum component. In presence of serum, Pb exposure failed to alter cytoskeletal proteins. Instead, in serum-free neurobasal medium, Pb uptake failed to reach saturation within 6 h. Western blot analysis showed that the tau, 280 kDa MAP-2b, 70 kDa MAP-2c and GAP-43 protein bands were decreased 24 h after a 3 h exposure to 3 or 6 microM Pb in absence of serum. However, if cultures were maintained in serum-containing media after a 3 h Pb exposure without serum, the immunoblots did not differ from those of controls. It can be inferred that a serum factor prevents cytoskeletal protein alterations by Pb. In serum free medium, Pb that is primarily scavenged by the metallothionein I/II isoforms present in glial cells, may bind to thiol residues of proteins involved in either oxidative stress response or transcriptional regulation of cytoskeletal proteins. JF - Neurochemistry international AU - Scortegagna, M AU - Chikhale, E AU - Hanbauer, I AD - Laboratory of Molecular Immunology, NHLBI, Bethesda, MD 20892-1674, USA. Y1 - 1998/04// PY - 1998 DA - April 1998 SP - 353 EP - 359 VL - 32 IS - 4 SN - 0197-0186, 0197-0186 KW - Cytoskeletal Proteins KW - 0 KW - GAP-43 Protein KW - Microtubule-Associated Proteins KW - Tubulin KW - tau Proteins KW - Lead KW - 2P299V784P KW - Index Medicus KW - Rats KW - GAP-43 Protein -- metabolism KW - Animals KW - tau Proteins -- metabolism KW - Rats, Sprague-Dawley KW - Microtubule-Associated Proteins -- metabolism KW - Blotting, Western KW - Cells, Cultured KW - Tubulin -- metabolism KW - Spectrophotometry, Atomic KW - Female KW - Pregnancy KW - Mesencephalon -- metabolism KW - Mesencephalon -- drug effects KW - Lead -- toxicity KW - Cytoskeletal Proteins -- metabolism KW - Lead -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79875419?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurochemistry+international&rft.atitle=Effect+of+lead+on+cytoskeletal+proteins+expressed+in+E14+mesencephalic+primary+cultures.&rft.au=Scortegagna%2C+M%3BChikhale%2C+E%3BHanbauer%2C+I&rft.aulast=Scortegagna&rft.aufirst=M&rft.date=1998-04-01&rft.volume=32&rft.issue=4&rft.spage=353&rft.isbn=&rft.btitle=&rft.title=Neurochemistry+international&rft.issn=01970186&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-07-29 N1 - Date created - 1998-07-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Induction of transgene expression in Tg.AC(v-Ha-ras) transgenic mice concomitant with DNA hypomethylation. AN - 79870064; 9585254 AB - Tg.AC transgenic mice have a transgene composed of a zeta-globin transcriptional control region, a v-Ha-ras coding region, and a simian virus 40 3' polyadenylation signal sequence. Induced ectopic expression of the transgene by chemical treatment or full-skin-thickness wounding leads to the development of skin papillomas. Reverse transcription-polymerase chain reaction assays and protein blotting indicated that the transgene was expressed 16-28 d after full-skin-thickness surgical wounding. Normal unwounded skin did not express the transgene. DNA blotting indicated that the position of the transgene remained stable during wound-induced tumorigenesis. Concomitant with the v-Ha-ras mRNA and protein expression was the hypomethylation of specific MspI/HpaII sites within the transgene. These results are consistent with the hypothesis that hypomethylation is required for the induced and sustained expression of the Tg.AC v-Ha-ras transgene in spontaneous and induced tumors in Tg.AC mice. JF - Molecular carcinogenesis AU - Cannon, R E AU - Spalding, J W AU - Virgil, K M AU - Faircloth, R S AU - Humble, M C AU - Lacks, G D AU - Tennant, R W AD - Laboratory of Environmental Carcinogenesis and Mutagenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1998/04// PY - 1998 DA - April 1998 SP - 244 EP - 250 VL - 21 IS - 4 SN - 0899-1987, 0899-1987 KW - Globins KW - 9004-22-2 KW - Oncogene Protein p21(ras) KW - EC 3.6.5.2 KW - Index Medicus KW - Polymerase Chain Reaction KW - Animals KW - Simian virus 40 -- genetics KW - Globins -- genetics KW - Transcription, Genetic KW - Mice KW - Mice, Transgenic KW - Wounds and Injuries -- complications KW - Female KW - Skin -- injuries KW - Oncogene Protein p21(ras) -- genetics KW - Oncogene Protein p21(ras) -- biosynthesis KW - Skin Neoplasms -- etiology KW - Transgenes KW - Wound Healing -- genetics KW - Papilloma -- genetics KW - Genes, ras KW - Skin Neoplasms -- genetics KW - DNA Methylation KW - Papilloma -- etiology KW - Gene Expression Regulation KW - Oncogene Protein p21(ras) -- physiology KW - Cell Transformation, Neoplastic -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79870064?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+carcinogenesis&rft.atitle=Induction+of+transgene+expression+in+Tg.AC%28v-Ha-ras%29+transgenic+mice+concomitant+with+DNA+hypomethylation.&rft.au=Cannon%2C+R+E%3BSpalding%2C+J+W%3BVirgil%2C+K+M%3BFaircloth%2C+R+S%3BHumble%2C+M+C%3BLacks%2C+G+D%3BTennant%2C+R+W&rft.aulast=Cannon&rft.aufirst=R&rft.date=1998-04-01&rft.volume=21&rft.issue=4&rft.spage=244&rft.isbn=&rft.btitle=&rft.title=Molecular+carcinogenesis&rft.issn=08991987&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-05-20 N1 - Date created - 1998-05-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular genetic dissection of mouse unconventional myosin-VA: head region mutations. AN - 79845554; 9560408 AB - The mouse dilute (d) locus encodes unconventional myosin-VA (MyoVA). Mice carrying null alleles of dilute have a lightened coat color and die from a neurological disorder resembling ataxia and opisthotonus within three weeks of birth. Immunological and ultrastructural studies suggest that MyoVA is involved in the transport of melanosomes in melanocytes and smooth endoplasmic reticulum in cerebellar Purkinje cells. In studies described here, we have used an RT-PCR-based sequencing approach to identify the mutations responsible for 17 viable dilute alleles that vary in their effects on coat color and the nervous system. Seven of these mutations mapped to the MyoVA motor domain and are reported here. Crystallographic modeling and mutant expression studies were used to predict how these mutations might affect motor domain function and to attempt to correlate these effects with the mutant phenotype. JF - Genetics AU - Huang, J D AU - Cope, M J AU - Mermall, V AU - Strobel, M C AU - Kendrick-Jones, J AU - Russell, L B AU - Mooseker, M S AU - Copeland, N G AU - Jenkins, N A AD - ABL-Basic Research Program, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland 21702, USA. Y1 - 1998/04// PY - 1998 DA - April 1998 SP - 1951 EP - 1961 VL - 148 IS - 4 SN - 0016-6731, 0016-6731 KW - Intermediate Filament Proteins KW - 0 KW - Myo5a protein, mouse KW - Myosin Type V KW - EC 3.6.1.- KW - Myosin Heavy Chains KW - EC 3.6.4.1 KW - Index Medicus KW - Animals KW - Hair Color -- genetics KW - Alleles KW - Models, Molecular KW - Gene Expression KW - Mice KW - Crystallography, X-Ray KW - Male KW - Female KW - Intermediate Filament Proteins -- genetics KW - Intermediate Filament Proteins -- chemistry KW - Mutagenesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79845554?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Molecular+genetic+dissection+of+mouse+unconventional+myosin-VA%3A+head+region+mutations.&rft.au=Huang%2C+J+D%3BCope%2C+M+J%3BMermall%2C+V%3BStrobel%2C+M+C%3BKendrick-Jones%2C+J%3BRussell%2C+L+B%3BMooseker%2C+M+S%3BCopeland%2C+N+G%3BJenkins%2C+N+A&rft.aulast=Huang&rft.aufirst=J&rft.date=1998-04-01&rft.volume=148&rft.issue=4&rft.spage=1951&rft.isbn=&rft.btitle=&rft.title=Genetics&rft.issn=00166731&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-06-26 N1 - Date created - 1998-06-26 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nature. 1970 Aug 15;227(5259):680-5 [5432063] Genetics. 1998 Apr;148(4):1963-72 [9560409] Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350-4 [388439] Proc Natl Acad Sci U S A. 1984 Apr;81(7):1991-5 [6326095] Mol Cell Biol. 1990 Feb;10(2):501-9 [2300051] Nature. 1991 Feb 21;349(6311):709-13 [1996138] Circulation. 1992 Aug;86(2):345-52 [1638703] J Cell Biol. 1992 Dec;119(6):1541-57 [1469047] Proc Natl Acad Sci U S A. 1993 May 1;90(9):3993-7 [8483915] Mutat Res. 1993 Jul;297(1):3-38 [7686271] Science. 1993 Jul 2;261(5117):50-8 [8316857] Science. 1993 Jul 2;261(5117):58-65 [8316858] J Exp Zool. 1993 Sep 15;267(1):33-9 [8376949] Cell. 1993 Oct 8;75(1):13-23 [8402892] Nature. 1994 Mar 24;368(6469):306-12 [8127365] J Cell Biol. 1994 Oct;127(2):425-40 [7929586] Nature. 1995 Mar 2;374(6517):60-1 [7870171] Nature. 1995 Mar 2;374(6517):62-4 [7870172] Proc Natl Acad Sci U S A. 1995 Apr 25;92(9):3864-8 [7731997] Curr Opin Cell Biol. 1995 Feb;7(1):82-8 [7755993] EMBO J. 1995 May 15;14(10):2326-32 [7774591] Biochemistry. 1995 Jul 18;34(28):8960-72 [7619795] Biochemistry. 1995 Jul 18;34(28):8973-81 [7619796] Nat Genet. 1995 Dec;11(4):369-75 [7493015] Biochemistry. 1996 Apr 30;35(17):5404-17 [8611530] Curr Opin Cell Biol. 1996 Feb;8(1):97-105 [8791411] Brain Res. 1996 Apr 1;714(1-2):226-30 [8861629] Neurosci Lett. 1996 Sep 13;215(3):169-72 [8899740] Am J Hum Genet. 1996 Nov;59(5):1074-83 [8900236] Proc Natl Acad Sci U S A. 1996 Dec 10;93(25):14554-8 [8962090] J Cell Sci. 1997 Feb;110 ( Pt 4):439-49 [9067596] Genetics. 1997 Feb;145(2):435-43 [9071596] J Cell Sci. 1997 Apr;110 ( Pt 7):847-59 [9133672] Nat Genet. 1997 Jun;16(2):188-90 [9171832] Nat Genet. 1997 Jun;16(2):191-3 [9171833] Mutat Res. 1971 Jan;11(1):107-23 [5556347] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Relationship of binge drinking to alcohol dependence, other psychiatric disorders, and behavioral problems in an American Indian tribe. AN - 79844565; 9581662 AB - The hypothesis that binge drinking is a benign behavior not associated with alcohol dependence, other psychiatric disorders, or problem areas, in American Indians, was tested in a sample of 582 adult Southwestern American Indian males and females in large multigenerational pedigrees. All information was obtained from semistructured psychiatric interviews that were independently blind-rated for DSM-III-R diagnoses. Three main outcome measures were used: the relationship between binge drinking and (1) alcohol dependence and other psychiatric disorders, (2) substance abuse treatment, and (3) four behavioral problem categories-violence/lawlessness, physical, social, and work. Binge drinking and alcohol dependence were strongly associated. Most binge drinkers were diagnosed as alcohol dependent. However, when controlling for alcohol dependence and other covariates, binge drinking was independently associated with an increase in odds for positive diagnoses for multiple psychiatric disorders, and for social, work, physical, and violence/lawlessness behavioral problems. In sum, binge drinking was found to be a common and severe problem with deleterious consequences in multiple domains of functioning. Assessment instruments should be designed to elicit information on binge patterns of drinking and strategies devised to provide appropriate treatment. JF - Alcoholism, clinical and experimental research AU - Robin, R W AU - Long, J C AU - Rasmussen, J K AU - Albaugh, B AU - Goldman, D AD - Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, Maryland, USA. Y1 - 1998/04// PY - 1998 DA - April 1998 SP - 518 EP - 523 VL - 22 IS - 2 SN - 0145-6008, 0145-6008 KW - Ethanol KW - 3K9958V90M KW - Index Medicus KW - Psychiatric Status Rating Scales KW - Ethanol -- poisoning KW - Social Problems -- statistics & numerical data KW - Humans KW - Adult KW - Social Problems -- psychology KW - Southwestern United States KW - Male KW - Female KW - Comorbidity KW - Social Behavior Disorders -- epidemiology KW - Alcoholic Intoxication -- psychology KW - Alcoholic Intoxication -- epidemiology KW - Social Behavior Disorders -- psychology KW - Alcoholism -- epidemiology KW - Mental Disorders -- epidemiology KW - Mental Disorders -- psychology KW - Indians, North American -- psychology KW - Indians, North American -- statistics & numerical data KW - Alcoholism -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79844565?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Alcoholism%2C+clinical+and+experimental+research&rft.atitle=Relationship+of+binge+drinking+to+alcohol+dependence%2C+other+psychiatric+disorders%2C+and+behavioral+problems+in+an+American+Indian+tribe.&rft.au=Robin%2C+R+W%3BLong%2C+J+C%3BRasmussen%2C+J+K%3BAlbaugh%2C+B%3BGoldman%2C+D&rft.aulast=Robin&rft.aufirst=R&rft.date=1998-04-01&rft.volume=22&rft.issue=2&rft.spage=518&rft.isbn=&rft.btitle=&rft.title=Alcoholism%2C+clinical+and+experimental+research&rft.issn=01456008&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-07-20 N1 - Date created - 1998-07-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Posttranslational inhibition of Ty1 retrotransposition by nucleotide excision repair/transcription factor TFIIH subunits Ssl2p and Rad3p. AN - 79840811; 9560391 AB - rtt4-1 (regulator of Ty transposition) is a cellular mutation that permits a high level of spontaneous Ty1 retrotransposition in Saccharomyces cerevisiae. The RTT4 gene is allelic with SSL2 (RAD25), which encodes a DNA helicase present in basal transcription (TFIIH) and nucleotide excision repair (NER) complexes. The ssl2-rtt (rtt4-1) mutation stimulates Ty1 retrotransposition, but does not alter Ty1 target site preferences, or increase cDNA or mitotic recombination. In addition to ssl2-rtt, the ssl2-dead and SSL2-1 mutations stimulate Ty1 transposition without altering the level of Ty1 RNA or proteins. However, the level of Ty1 cDNA markedly increases in the ssl2 mutants. Like SSL2, certain mutations in another NER/TFIIH DNA helicase encoded by RAD3 stimulate Ty1 transposition. Although Ssl2p and Rad3p are required for NER, inhibition of Ty1 transposition is independent of Ssl2p and Rad3p NER functions. Our work suggests that NER/TFIIH subunits antagonize Ty1 transposition posttranslationally by inhibiting reverse transcription or destabilizing Ty1 cDNA. JF - Genetics AU - Lee, B S AU - Lichtenstein, C P AU - Faiola, B AU - Rinckel, L A AU - Wysock, W AU - Curcio, M J AU - Garfinkel, D J AD - Gene Regulation and Chromosome Biology Laboratory, Advanced BioScience Laboratories-Basic Research Program, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland 21702-1201, USA. Y1 - 1998/04// PY - 1998 DA - April 1998 SP - 1743 EP - 1761 VL - 148 IS - 4 SN - 0016-6731, 0016-6731 KW - DNA Transposable Elements KW - 0 KW - DNA, Complementary KW - Fungal Proteins KW - Retroelements KW - SSL2 protein, S cerevisiae KW - Saccharomyces cerevisiae Proteins KW - TAF6 protein, S cerevisiae KW - TATA-Binding Protein Associated Factors KW - Transcription Factor TFIID KW - Transcription Factors KW - Transcription Factors, TFII KW - Transcription Factor TFIIH KW - 148710-81-0 KW - Alcohol Oxidoreductases KW - EC 1.1.- KW - HIS4 protein, S cerevisiae KW - EC 1.1.1.23 KW - Aminohydrolases KW - EC 3.5.4.- KW - Adenosine Triphosphatases KW - EC 3.6.1.- KW - Pyrophosphatases KW - Rad3 protein, S cerevisiae KW - DNA Helicases KW - EC 3.6.4.- KW - Index Medicus KW - DNA Helicases -- metabolism KW - Adenosine Triphosphatases -- metabolism KW - Fungal Proteins -- genetics KW - Mutagenesis KW - Chromosomes, Fungal KW - Alleles KW - Fungal Proteins -- metabolism KW - Recombination, Genetic KW - DNA Helicases -- genetics KW - Adenosine Triphosphatases -- genetics KW - Protein Biosynthesis KW - DNA Repair KW - Transcription Factors -- metabolism KW - Transcription Factors -- chemistry KW - Gene Expression Regulation KW - Transcription Factors -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79840811?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Posttranslational+inhibition+of+Ty1+retrotransposition+by+nucleotide+excision+repair%2Ftranscription+factor+TFIIH+subunits+Ssl2p+and+Rad3p.&rft.au=Lee%2C+B+S%3BLichtenstein%2C+C+P%3BFaiola%2C+B%3BRinckel%2C+L+A%3BWysock%2C+W%3BCurcio%2C+M+J%3BGarfinkel%2C+D+J&rft.aulast=Lee&rft.aufirst=B&rft.date=1998-04-01&rft.volume=148&rft.issue=4&rft.spage=1743&rft.isbn=&rft.btitle=&rft.title=Genetics&rft.issn=00166731&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-06-26 N1 - Date created - 1998-06-26 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cell. 1990 Jul 27;62(2):339-52 [2164889] J Biol Chem. 1994 Jan 21;269(3):1852-7 [8294433] J Bacteriol. 1990 Dec;172(12):6620-30 [2174856] Nature. 1994 Jan 6;367(6458):91-4 [8107780] Nature. 1994 Mar 3;368(6466):74-6 [8107888] Nature. 1994 Jun 16;369(6481):578-81 [8202161] Genetics. 1994 Apr;136(4):1245-59 [8013902] Mol Cell Biol. 1994 Oct;14(10):6540-51 [7523854] Genes Dev. 1994 Dec 15;8(24):2974-85 [8001818] Science. 1994 Dec 23;266(5193):2002-6 [7801128] Cell. 1995 Jan 13;80(1):21-8 [7813015] Genetics. 1994 Nov;138(3):587-95 [7851757] Proc Natl Acad Sci U S A. 1995 Jul 3;92(14):6479-83 [7604017] Mol Cell Biol. 1995 Aug;15(8):3998-4008 [7623796] Mol Biol Cell. 1995 May;6(5):611-25 [7545033] Trends Biochem Sci. 1995 Oct;20(10):402-5 [8533152] Genes Dev. 1996 Mar 1;10(5):620-33 [8598291] J Biol Chem. 1996 May 3;271(18):10821-6 [8631896] J Biol Chem. 1996 Apr 12;271(15):8903-10 [8621533] Nature. 1996 Aug 29;382(6594):826-9 [8752279] Curr Biol. 1996 Aug 1;6(8):959-61 [8805314] Science. 1996 Oct 25;274(5287):546, 563-7 [8849441] Genetics. 1996 Mar;142(3):761-76 [8849886] Nature. 1996 Nov 28;384(6607):379-83 [8934527] Genes Dev. 1996 Nov 1;10(21):2657-83 [8946909] Trends Genet. 1996 Nov;12(11):436-8 [8973141] J Virol. 1997 Jul;71(7):5382-90 [9188609] Proc Natl Acad Sci U S A. 1979 Mar;76(3):1035-9 [375221] Gene. 1979 Dec;8(1):121-33 [395029] Cell. 1980 Nov;22(2 Pt 2):427-36 [6256080] Proc Natl Acad Sci U S A. 1981 Apr;78(4):2460-4 [6787605] EMBO J. 1982;1(8):945-51 [6329717] Cell. 1984 Dec;39(3 Pt 2):675-82 [6096019] Mol Gen Genet. 1984;197(2):345-6 [6394957] Cell. 1985 Mar;40(3):491-500 [2982495] Cell. 1985 Sep;42(2):507-17 [2411424] Mol Cell Biol. 1986 Nov;6(11):3575-81 [3025601] Genetics. 1987 Aug;116(4):541-5 [3305158] Proc Natl Acad Sci U S A. 1987 Sep;84(17):6045-9 [2957691] Gene. 1987;57(2-3):267-72 [3319781] Mol Biol Evol. 1985 Nov;2(6):455-68 [2835576] Mol Cell Biol. 1988 Apr;8(4):1432-42 [2837641] Genetics. 1989 May;122(1):19-27 [2659436] Mol Gen Genet. 1989 Sep;218(3):465-74 [2555668] Genetics. 1989 Dec;123(4):655-65 [2558956] Mol Gen Genet. 1990 Jan;220(2):213-21 [2157950] Genes Dev. 1990 Mar;4(3):324-30 [2159935] Genetics. 1988 Jun;119(2):289-301 [2840336] Mol Cell Biol. 1988 Jul;8(7):2964-75 [3043201] Cell. 1988 Sep 23;54(7):955-66 [2843295] Proc Natl Acad Sci U S A. 1991 Feb 1;88(3):936-40 [1846969] Annu Rev Genet. 1990;24:491-518 [1965102] J Virol. 1991 Sep;65(9):4573-81 [1714514] Mol Cell Biol. 1992 Jun;12(6):2813-25 [1317008] Cell. 1992 Jun 12;69(6):1031-42 [1318786] Trends Genet. 1992 Jun;8(6):187-90 [1323152] J Virol. 1992 Oct;66(10):5959-66 [1326652] Proc Natl Acad Sci U S A. 1992 Dec 1;89(23):11416-20 [1333609] Cell. 1992 Dec 11;71(6):925-37 [1458540] Genetics. 1993 Mar;133(3):499-508 [8384143] Cell. 1993 Jun 4;73(5):1007-18 [8388781] Genes Dev. 1993 Nov;7(11):2161-71 [7693549] Cell. 1993 Dec 31;75(7):1379-87 [8269516] Cell. 1990 Aug 24;62(4):777-91 [2167179] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Additional chemotherapy agents improve treatment outcome for children and adults with advanced B-cell lymphomas. AN - 79840435; 9578060 AB - We report the updated results of an intensive treatment protocol for children ( or = 18 years) with advanced B-cell lymphomas. The protocol consists of two chemotherapy regimens: A, consisting of cyclophosphamide, doxorubicin, vincristine and high-dose methotrexate (CODOX-M), and B, consisting of ifosfamide, etoposide, and high-dose cytarabine (IVAC). Both cycles included intrathecal chemotherapy (cytarabine or methotrexate). Patients received a total of four cycles in the following sequence: A, B, A, B. Sixty-six previously untreated patients, enrolled before October 1996, were included in the present analysis. Of these, 55 had Burkitt's or Burkitt's-like lymphoma and 11 had diffuse large B-cell lymphoma. There were 53 males ad 13 females; 40 were children and 26 were adults (age range, 3 to 57 years). To date, 61 patients have achieved a complete response to therapy. Two patients subsequently relapsed, but one of these is a long-term survivor after further therapy and a bone marrow transplant. The event-free survival rate is 85% at I year and beyond. The median potential follow-up period is 48 months (range, 12 to 96 months) for patients remaining in complete remission. Neutropenia occurred in 98% of cycles and infection in 46% of A cycles and 50% of B cycles, but the duration was shortened in B cycles by the administration of granulocyte colony-stimulating factor. Positive blood cultures were observed in 21% of A cycles and 28% of B cycles, and there have been three toxic deaths. These results are better than those achieved with an earlier version of CODOX-M, suggesting that the addition of the IVAC regimen is responsible for the improved results. The similarity of the outcome in children and adults, however, confirms our previous observation that, at least in adults younger than 60 years with Burkitt's or Burkitt's-like lymphomas, treatment with regimens similar to those used in children is warranted. JF - Seminars in oncology AU - Adde, M AU - Shad, A AU - Venzon, D AU - Arndt, C AU - Gootenberg, J AU - Neely, J AU - Nieder, M AU - Owen, W AU - Seibel, N AU - Wilson, W AU - Horak, I D AU - Magrath, I AD - Division of Clinical Sciences, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1998/04// PY - 1998 DA - April 1998 SP - 33 EP - 9; discussion 45-8 VL - 25 IS - 2 Suppl 4 SN - 0093-7754, 0093-7754 KW - Cytarabine KW - 04079A1RDZ KW - Vincristine KW - 5J49Q6B70F KW - Etoposide KW - 6PLQ3CP4P3 KW - Doxorubicin KW - 80168379AG KW - Granulocyte-Macrophage Colony-Stimulating Factor KW - 83869-56-1 KW - Cyclophosphamide KW - 8N3DW7272P KW - Ifosfamide KW - UM20QQM95Y KW - Methotrexate KW - YL5FZ2Y5U1 KW - Index Medicus KW - Cyclophosphamide -- administration & dosage KW - Neoplasm Staging KW - Combined Modality Therapy KW - Humans KW - Vincristine -- administration & dosage KW - Child KW - Doxorubicin -- administration & dosage KW - Cytarabine -- administration & dosage KW - Granulocyte-Macrophage Colony-Stimulating Factor -- therapeutic use KW - Child, Preschool KW - Survival Rate KW - Etoposide -- administration & dosage KW - Adult KW - Middle Aged KW - Adolescent KW - Methotrexate -- administration & dosage KW - Male KW - Female KW - Ifosfamide -- administration & dosage KW - Lymphoma, B-Cell -- drug therapy KW - Lymphoma, B-Cell -- pathology KW - Lymphoma, B-Cell -- radiotherapy KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79840435?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Additional+chemotherapy+agents+improve+treatment+outcome+for+children+and+adults+with+advanced+B-cell+lymphomas.&rft.au=Adde%2C+M%3BShad%2C+A%3BVenzon%2C+D%3BArndt%2C+C%3BGootenberg%2C+J%3BNeely%2C+J%3BNieder%2C+M%3BOwen%2C+W%3BSeibel%2C+N%3BWilson%2C+W%3BHorak%2C+I+D%3BMagrath%2C+I&rft.aulast=Adde&rft.aufirst=M&rft.date=1998-04-01&rft.volume=25&rft.issue=2+Suppl+4&rft.spage=33&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 - 1998-05-12 N1 - Date created - 1998-05-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Aspects of the ultraviolet photobiology of some T-even bacteriophages. AN - 79840391; 9560380 AB - Bacteriophage T4 DNA metabolism is largely insulated from that of its host, although some host functions assist in the repair of T4 DNA damage. Environmental factors sometimes affect survival and mutagenesis after ultraviolet (UV) irradiation of T4, and can affect mutagenesis in many organisms. We therefore tested the effect of certain environmental factors and host genetic defects upon spontaneous and UV-induced mutagenesis and survival in T4 and some related T-even phages. Plating at pH 9 enhances UV resistance in T4 by about 14% compared to pH 7. The host cAMP regulatory system affects host survival after UV irradiation but does not affect T4 survival. Thermal rescue, the increasing survival of irradiated T4 with increasing plating temperature, occurs also in phage T6, but only weakly in phages T2 and RB69; this temperature effect is not altered by supplementing infected cells with additional Holliday resolvase (gp49) early in infection. Phage RB69 turns out to have almost 50% greater UV resistance than T4, but has a genome of about the same size; RB69 is UV-mutable but does not produce r mutants, which are easily seen in T2, T4, and T6. Spontaneous mutagenesis in T4 shows no dependence on medium and little dependence on temperature overall, but mutation rates can increase and probably decrease with temperature at specific sites. UV mutagenesis is not affected by incubating irradiated particles under various conditions before plating, in contrast to phage S13. JF - Genetics AU - Smith, L A AU - Drake, J W AD - Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709-2233, USA. Y1 - 1998/04// PY - 1998 DA - April 1998 SP - 1611 EP - 1618 VL - 148 IS - 4 SN - 0016-6731, 0016-6731 KW - Index Medicus KW - Genotype KW - Hydrogen-Ion Concentration KW - Escherichia coli -- genetics KW - Mutagenesis KW - Ultraviolet Rays KW - T-Phages -- radiation effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79840391?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Aspects+of+the+ultraviolet+photobiology+of+some+T-even+bacteriophages.&rft.au=Smith%2C+L+A%3BDrake%2C+J+W&rft.aulast=Smith&rft.aufirst=L&rft.date=1998-04-01&rft.volume=148&rft.issue=4&rft.spage=1611&rft.isbn=&rft.btitle=&rft.title=Genetics&rft.issn=00166731&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-06-26 N1 - Date created - 1998-06-26 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Genetics. 1987 Mar;115(3):405-17 [3552872] Genetics. 1984 Aug;107(4):505-23 [6745639] Mol Gen Genet. 1989 Feb;215(3):537-42 [2540417] Mol Gen Genet. 1991 May;227(1):144-8 [2046654] Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):7160-4 [1831267] Genetics. 1984 Aug;107(4):525-36 [6745640] Mutat Res. 1984 Nov;129(2):149-52 [6504055] J Bacteriol. 1986 Nov;168(2):936-9 [3096964] Proc Natl Acad Sci U S A. 1992 Feb 15;89(4):1159-63 [1741372] New Biol. 1991 Dec;3(12):1195-205 [1812964] Mutat Res. 1992 Aug;282(4):247-52 [1379686] J Mol Biol. 1994 Jan 21;235(3):807-12 [8289321] Genetics. 1994 Nov;138(3):553-64 [7851754] Cell. 1997 Jun 27;89(7):1087-99 [9215631] Proc Natl Acad Sci U S A. 1997 Jul 22;94(15):8042-6 [9223311] Genetics. 1998 Apr;148(4):1539-50 [9560373] Proc Natl Acad Sci U S A. 1961 Jun 15;47:845-55 [13701658] Genetics. 1946 Nov;31(6):620-40 [17247224] J Bacteriol. 1966 May;91(5):1775-80 [5937237] Genetics. 1970 Jul;65(3):379-90 [4933467] Genetics. 1974 Dec;78(4):989-1014 [4455560] Genetics. 1988 Oct;120(2):329-43 [2974005] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Opposing effects of alpha 1-adrenergic receptor subtypes on Ca2+ and pH homeostasis in rat cardiac myocytes. AN - 79835416; 9575918 AB - We examined the effect of alpha 1-adrenergic receptor (AR) subtypes on contraction, cytosolic Ca2+ concentration ([Ca2+]i), and cytosolic pH (pHi) of rat ventricular myocytes loaded with the Ca2+ indicator indo 1 or the pH indicator carboxyseminaphthorhodafluor-1. Nonselective alpha 1-AR stimulation was effected with phenylephrine plus nadolol. alpha 1-AR subtype stimulation was achieved with alpha 1-AR and chloroethylclonidine (CEC) or with alpha 1-AR and WB-4101. Cells were in bicarbonate buffer with 0.5 mM Ca2+ and were electrically stimulated at 0.5 Hz. Results show that 1) nonselective alpha 1-AR stimulation increased twitch and [Ca2+]i transient amplitudes, myofilament response to Ca2+, and pHi; 2) alpha 1-AR plus CEC increased twitch and [Ca2+]i transient amplitudes and also enhanced myofilament response to Ca2+ via cytosolic alkalinization; 3) alpha 1-AR plus WB-4101 decreased twitch and [Ca2+]i transient amplitudes and also pHi; and 4) cytosolic acidification due to alpha 1-AR plus WB-4101 was abolished by protein kinase C inhibition (staurosporine pretreatment) or downregulation (prolonged exposure to phorbol esters). In summary, the net effects of alpha 1-adrenergic stimulation on contraction, [Ca2+]i, and pHi are due to opposing WB-4101- and CEC-sensitive alpha 1-AR subtype signaling pathways. JF - The American journal of physiology AU - Gambassi, G AU - Spurgeon, H A AU - Ziman, B D AU - Lakatta, E G AU - Capogrossi, M C AD - Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA. Y1 - 1998/04// PY - 1998 DA - April 1998 SP - H1152 EP - H1162 VL - 274 IS - 4 Pt 2 SN - 0002-9513, 0002-9513 KW - Adrenergic alpha-Agonists KW - 0 KW - Adrenergic alpha-Antagonists KW - Dioxanes KW - Drug Combinations KW - Fluorescent Dyes KW - Indoles KW - Receptors, Adrenergic, alpha-1 KW - Phenylephrine KW - 1WS297W6MV KW - chlorethylclonidine KW - 3X825O680H KW - (2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane KW - 613-67-2 KW - Hydrogen KW - 7YNJ3PO35Z KW - Clonidine KW - MN3L5RMN02 KW - indo-1 KW - N18RMK75W1 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Animals KW - Adrenergic alpha-Agonists -- pharmacology KW - Clonidine -- analogs & derivatives KW - Hydrogen-Ion Concentration KW - Myocardial Contraction -- drug effects KW - Rats KW - Rats, Wistar KW - Clonidine -- pharmacology KW - Dioxanes -- pharmacology KW - Drug Synergism KW - Male KW - Phenylephrine -- pharmacology KW - Adrenergic alpha-Antagonists -- pharmacology KW - Calcium -- metabolism KW - Myocardium -- cytology KW - Hydrogen -- metabolism KW - Homeostasis -- physiology KW - Myocardium -- metabolism KW - Receptors, Adrenergic, alpha-1 -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79835416?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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+physiology&rft.atitle=Opposing+effects+of+alpha+1-adrenergic+receptor+subtypes+on+Ca2%2B+and+pH+homeostasis+in+rat+cardiac+myocytes.&rft.au=Gambassi%2C+G%3BSpurgeon%2C+H+A%3BZiman%2C+B+D%3BLakatta%2C+E+G%3BCapogrossi%2C+M+C&rft.aulast=Gambassi&rft.aufirst=G&rft.date=1998-04-01&rft.volume=274&rft.issue=4+Pt+2&rft.spage=H1152&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+physiology&rft.issn=00029513&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-06-02 N1 - Date created - 1998-06-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - An analytic model of pinhole aperture penetration for 3D pinhole SPECT image reconstruction. AN - 79828832; 9572502 AB - Photons penetrate the attenuating material close to the aperture of pinhole collimators in nuclear medicine, broadening the tails of point spread functions (PSFs) and degrading the resolution of planar and SPECT images. An analytic approximation has been developed that models this penetration contribution to the PSF for knife-edge point pinhole apertures. The approximation has the form exp(-gamma r), where r is the distance on the detector surface from the projection of the point source through the pinhole. The rolloff coefficient gamma is a function of the photon energy, point source location and the design parameters of the collimator. There was excellent agreement between measured values of gamma from photon transport simulations of I-131 point sources (364 keV emission only) and theoretical predictions from the analytic formula. Predicted gamma values from the analytic formula averaged 25% greater than measured values from experimental I-131 point source acquisitions. Photon transport simulations were performed that modelled the 364 keV and less abundant 637 and 723 keV emissions and scatter within the scintillation crystal. Measured gamma values from these simulations averaged 12% greater than the experimental values, indicating that about half of the error between the analytic formula and the experimental measurements was due to unmodelled 637 and 723 keV emissions. The remaining error may be due in part to scatter in the pinhole region and backscatter from gamma camera components behind the scintillation crystal. The analytic penetration model was used in designing Metz filters to compensate for penetration blur and these filters were applied to the projection data as part of 3D SPECT image reconstruction. Image resolution and contrast were improved in simulated and experimental I-131 tumour phantom studies. This analytic model of pinhole aperture penetration can be readily incorporated into iterative 3D SPECT pinhole reconstruction algorithms. JF - Physics in medicine and biology AU - Smith, M F AU - Jaszczak, R J AD - Department of Radiology, Duke University Medical Center, Durham, NC, USA. smith@nmdhst.cc.nih.gov Y1 - 1998/04// PY - 1998 DA - April 1998 SP - 761 EP - 775 VL - 43 IS - 4 SN - 0031-9155, 0031-9155 KW - Index Medicus KW - Radiation Protection KW - Photons KW - Humans KW - Phantoms, Imaging KW - Image Processing, Computer-Assisted -- instrumentation KW - Tomography, Emission-Computed, Single-Photon KW - Neoplasms -- diagnostic imaging KW - Models, Theoretical KW - Image Processing, Computer-Assisted -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79828832?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Physics+in+medicine+and+biology&rft.atitle=An+analytic+model+of+pinhole+aperture+penetration+for+3D+pinhole+SPECT+image+reconstruction.&rft.au=Smith%2C+M+F%3BJaszczak%2C+R+J&rft.aulast=Smith&rft.aufirst=M&rft.date=1998-04-01&rft.volume=43&rft.issue=4&rft.spage=761&rft.isbn=&rft.btitle=&rft.title=Physics+in+medicine+and+biology&rft.issn=00319155&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-06-16 N1 - Date created - 1998-06-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - JC virus Type 1 has multiple subtypes: three new complete genomes. AN - 79825122; 9568975 AB - The complete genomes of three new Type 1 strains of JC virus (JCV) from urine have been analysed. These were subtype 1A, subtype 1B and Type 4 as assigned from a short typing fragment in the VP1 gene. They differ from Mad1 (subtype 1A) by less than 1.0% of the DNA sequence. Based on its complete genome, the JCV Type 4 strain falls into a Type 1 subgroup. Type 4, with several Type 3-like sites in the short typing fragment, is a possible recombinant strain. The consensus of Type 1 DNA sequences is distinguished within the coding region from both Type 2 (strain GS/B) and five Type 3 (African and African American) strains at 64 sites. Most mutations are silent, but at 21 positions amino acid changes occur. Our findings define the subtypes of JCV Type 1 and support the validity of genotyping within the short VP1 fragment. JF - The Journal of general virology AU - Agostini, H T AU - Ryschkewitsch, C F AU - Stoner, G L AD - Neurotoxicology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-4126, USA. Y1 - 1998/04// PY - 1998 DA - April 1998 SP - 801 EP - 805 VL - 79 ( Pt 4) SN - 0022-1317, 0022-1317 KW - DNA, Viral KW - 0 KW - Index Medicus KW - Phylogeny KW - Polymerase Chain Reaction KW - Base Sequence KW - Tumor Virus Infections -- virology KW - Humans KW - Urine -- virology KW - Papillomavirus Infections -- virology KW - Molecular Sequence Data KW - Middle Aged KW - Consensus Sequence KW - DNA, Viral -- genetics KW - Male KW - JC Virus -- genetics KW - JC Virus -- classification KW - Genome, Viral KW - JC Virus -- isolation & purification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79825122?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+general+virology&rft.atitle=JC+virus+Type+1+has+multiple+subtypes%3A+three+new+complete+genomes.&rft.au=Agostini%2C+H+T%3BRyschkewitsch%2C+C+F%3BStoner%2C+G+L&rft.aulast=Agostini&rft.aufirst=H&rft.date=1998-04-01&rft.volume=79+%28+Pt+4%29&rft.issue=&rft.spage=801&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+general+virology&rft.issn=00221317&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-05-12 N1 - Date created - 1998-05-12 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF015528; GENBANK; AF015527; AF015526 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Fluoroquinolone antimicrobials: singlet oxygen, superoxide and phototoxicity. AN - 79813911; 9559584 AB - The fluoroquinolone antibacterial agents possess photosensitizing properties that lead to phototoxic responses in both human and animal subjects. The phototoxicity order reported in humans is: fleroxacin > lomefloxacin, pefloxacin >> ciprofloxacin > enoxacin, norfloxacin and ofloxacin. Studies both in vivo and in vitro have related this phototoxicity to the generation of reactive oxygen species including hydrogen peroxide and the hydroxyl radical. We determined the quantum yields of singlet oxygen generation (phi delta) by detection of the singlet oxygen (1O2) luminescence at 1270 nm for several fluoroquinolones, naphthyridines and other structurally related compounds. All the fluoroquinolones examined have low phi delta values ranging from 0.06 to 0.09 in phosphate buffer at pD 7.5. We also determined the 1O2 quenching constants for these compounds and their values were on the order of 10(6) M-1 s-1, except for lomefloxacin whose rate constant was 1.8 x 10(7) M-1 s-1. The phi delta values were significantly decreased in a solvent of lower polarity such as methanol (0.007 300 nm) of superoxide by these antibacterials in dimethylsulfoxide using electron paramagnetic resonance and the spin trap 5,5-dimethyl-1-pyrroline N-oxide. Although there is not a one-to-one correspondence between the relative rates of superoxide generation and the phototoxicity ranking of the fluoroquinolones, the more phototoxic compounds tended to produce superoxide at a faster rate. Nevertheless, the magnitudes of the observed differences do not appear sufficient to explain the range of fluoroquinolone phototoxicity potencies in human and animal subjects in general and the high activity of fleroxacin and lomefloxacin in particular. For these latter drugs the photoinduced loss of the F8 atom as fluoride and the concomitant generation of a highly reactive carbene at C-8 provide a more plausible mechanism for their potent phototoxic and photocarcinogenic properties. JF - Photochemistry and photobiology AU - Martínez, L J AU - Sik, R H AU - Chignell, C F AD - Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA. Y1 - 1998/04// PY - 1998 DA - April 1998 SP - 399 EP - 403 VL - 67 IS - 4 SN - 0031-8655, 0031-8655 KW - Anti-Infective Agents KW - 0 KW - Fluoroquinolones KW - Free Radicals KW - Photosensitizing Agents KW - Quinolones KW - Superoxides KW - 11062-77-4 KW - Singlet Oxygen KW - 17778-80-2 KW - Hydroxyl Radical KW - 3352-57-6 KW - Oxygen KW - S88TT14065 KW - Index Medicus KW - Animals KW - Guinea Pigs KW - Humans KW - Salmonella typhimurium -- drug effects KW - Mice KW - Structure-Activity Relationship KW - Quinolones -- toxicity KW - Photosensitizing Agents -- toxicity KW - Photosensitizing Agents -- chemistry KW - Anti-Infective Agents -- toxicity KW - Quinolones -- chemistry KW - Anti-Infective Agents -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79813911?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Photochemistry+and+photobiology&rft.atitle=Fluoroquinolone+antimicrobials%3A+singlet+oxygen%2C+superoxide+and+phototoxicity.&rft.au=Mart%C3%ADnez%2C+L+J%3BSik%2C+R+H%3BChignell%2C+C+F&rft.aulast=Mart%C3%ADnez&rft.aufirst=L&rft.date=1998-04-01&rft.volume=67&rft.issue=4&rft.spage=399&rft.isbn=&rft.btitle=&rft.title=Photochemistry+and+photobiology&rft.issn=00318655&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-05-21 N1 - Date created - 1998-05-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Activation by diverse xenochemicals of the 51-base pair phenobarbital-responsive enhancer module in the CYP2B10 gene. AN - 79813910; 9547348 AB - By extending previous studies of the phenobarbital (PB)-responsive 132-base pair (bp) enhancer sequence in the CYP2B10 gene, we have delimited a 51-bp enhancer element that is fully inducible by PB in mouse primary hepatocytes. Sixteen structurally unrelated phenobarbital-type inducers activated the 51-bp enhancer element in transient transfection assays. The results thus indicate that most PB-type inducers, if not all inducers, increase the transcription of the CYP2B10 gene by activating this 51-bp element, now designated PB-responsive enhancer module or PBREM. JF - Molecular pharmacology AU - Honkakoski, P AU - Moore, R AU - Washburn, K A AU - Negishi, M AD - Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1998/04// PY - 1998 DA - April 1998 SP - 597 EP - 601 VL - 53 IS - 4 SN - 0026-895X, 0026-895X KW - Pesticides KW - 0 KW - Pyridines KW - Solvents KW - Xenobiotics KW - Camphor KW - 76-22-2 KW - 1,4-bis(2-(3,5-dichloropyridyloxy))benzene KW - 76150-91-9 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Polychlorinated Biphenyls KW - DFC2HB4I0K KW - Steroid Hydroxylases KW - EC 1.14.- KW - Aryl Hydrocarbon Hydroxylases KW - EC 1.14.14.1 KW - Cyp2b10 protein, mouse KW - Cytochrome P450 Family 2 KW - Phenobarbital KW - YQE403BP4D KW - Index Medicus KW - Animals KW - Base Composition KW - Polychlorinated Biphenyls -- pharmacology KW - Liver -- metabolism KW - Mice KW - Pesticides -- pharmacology KW - Enzyme Activation -- genetics KW - Camphor -- pharmacology KW - Liver -- drug effects KW - Enzyme Activation -- drug effects KW - Mice, Inbred C57BL KW - Solvents -- pharmacology KW - Pyridines -- pharmacology KW - Male KW - Phenobarbital -- pharmacology KW - Cytochrome P-450 Enzyme System -- genetics KW - Xenobiotics -- pharmacology KW - Gene Expression Regulation -- drug effects KW - Enhancer Elements, Genetic -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79813910?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Activation+by+diverse+xenochemicals+of+the+51-base+pair+phenobarbital-responsive+enhancer+module+in+the+CYP2B10+gene.&rft.au=Honkakoski%2C+P%3BMoore%2C+R%3BWashburn%2C+K+A%3BNegishi%2C+M&rft.aulast=Honkakoski&rft.aufirst=P&rft.date=1998-04-01&rft.volume=53&rft.issue=4&rft.spage=597&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 - 1998-05-06 N1 - Date created - 1998-05-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The Bacillus subtilis DinR binding site: redefinition of the consensus sequence. AN - 79810358; 9555905 AB - Recently, the DinR protein was established as the cellular repressor of the SOS response in the bacterium Bacillus subtilis. It is believed that DinR functions as the repressor by binding to a consensus sequence located in the promoter region of each SOS gene. The binding site for DinR is believed to be synonymous with the formerly identified Cheo box, a region of 12 bp displaying dyad symmetry (GAAC-N4-GTTC). Electrophoretic mobility shift assays revealed that highly purified DinR does bind to such sites located upstream of the dinA, dinB, dinC, and dinR genes. Furthermore, detailed mutational analysis of the B. subtilis recA operator indicates that some nucleotides are more important than others for maintaining efficient DinR binding. For example, nucleotide substitutions immediately 5' and 3' of the Cheo box as well as those in the N4 region appear to affect DinR binding. This data, combined with computational analyses of potential binding sites in other gram-positive organisms, yields a new consensus (DinR box) of 5'-CGAACRNRYGTTYC-3'. DNA footprint analysis of the B. subtilis dinR and recA DinR boxes revealed that the DinR box is centrally located within a DNA region of 31 bp that is protected from hydroxyl radical cleavage in the presence of DinR. Furthermore, while DinR is predominantly monomeric in solution, it apparently binds to the DinR box in a dimeric state. JF - Journal of bacteriology AU - Winterling, K W AU - Chafin, D AU - Hayes, J J AU - Sun, J AU - Levine, A S AU - Yasbin, R E AU - Woodgate, R AD - Section on DNA Replication, Repair, and Mutagenesis, National Institute of Child Health and Human Development, Bethesda, Maryland 20892-2725, USA. Y1 - 1998/04// PY - 1998 DA - April 1998 SP - 2201 EP - 2211 VL - 180 IS - 8 SN - 0021-9193, 0021-9193 KW - Bacterial Proteins KW - 0 KW - Repressor Proteins KW - dinR protein, Bacillus subtilis KW - 144591-95-7 KW - Hydroxyl Radical KW - 3352-57-6 KW - Rec A Recombinases KW - EC 2.7.7.- KW - beta-Galactosidase KW - EC 3.2.1.23 KW - Index Medicus KW - Rec A Recombinases -- genetics KW - Sequence Homology, Nucleic Acid KW - Models, Molecular KW - Transcription, Genetic KW - Amino Acid Sequence KW - Nucleic Acid Conformation KW - Binding Sites KW - Base Sequence KW - SOS Response (Genetics) -- genetics KW - Sequence Alignment KW - DNA Footprinting KW - Molecular Sequence Data KW - Hydroxyl Radical -- analysis KW - Consensus Sequence KW - beta-Galactosidase -- biosynthesis KW - Bacillus subtilis -- genetics KW - Promoter Regions, Genetic KW - Bacterial Proteins -- metabolism KW - Bacillus subtilis -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79810358?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+Bacillus+subtilis+DinR+binding+site%3A+redefinition+of+the+consensus+sequence.&rft.au=Winterling%2C+K+W%3BChafin%2C+D%3BHayes%2C+J+J%3BSun%2C+J%3BLevine%2C+A+S%3BYasbin%2C+R+E%3BWoodgate%2C+R&rft.aulast=Winterling&rft.aufirst=K&rft.date=1998-04-01&rft.volume=180&rft.issue=8&rft.spage=2201&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 - 1998-05-18 N1 - Date created - 1998-05-18 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Mol Microbiol. 1997 Nov;26(4):643-53 [9427395] Mol Microbiol. 1997 Apr;24(1):141-53 [9140972] Proc Natl Acad Sci U S A. 1984 Mar;81(5):1375-9 [6231641] J Bacteriol. 1985 Jul;163(1):376-84 [3891738] Biochemistry. 1985 May 21;24(11):2812-8 [3896306] Nature. 1987 Apr 30-May 6;326(6116):886-8 [3553960] Proc Natl Acad Sci U S A. 1988 Jul;85(13):4633-7 [3387430] FEBS Lett. 1988 Jul 4;234(1):56-60 [2968919] Biochemistry. 1989 Nov 28;28(24):9521-7 [2611245] J Bacteriol. 1991 Mar;173(5):1696-703 [1847907] Biochimie. 1991 Apr;73(4):449-56 [1911945] J Bacteriol. 1991 Nov;173(22):7084-91 [1657879] Methods Enzymol. 1991;208:103-17 [1779832] Science. 1992 Jan 10;255(5041):203-6 [1553548] J Bacteriol. 1992 May;174(10):3171-6 [1577687] Mol Microbiol. 1992 May;6(10):1263-70 [1640829] Biochimie. 1992 Jul-Aug;74(7-8):755-62 [1391055] Nucleic Acids Res. 1993 Jul 11;21(14):3335-6 [8341617] J Mol Biol. 1994 Aug 26;241(4):507-23 [8057377] Proteins. 1995 Mar;21(3):226-36 [7784426] Mol Microbiol. 1996 Oct;22(1):75-85 [8899710] J Biol Chem. 1996 Dec 27;271(52):33502-8 [8969214] J Bacteriol. 1997 Mar;179(5):1698-703 [9045831] Microbiology. 1997 Mar;143 ( Pt 3):929-36 [9084177] Radiat Res. 1966;:Suppl 6:156+ [5334390] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Isolated hepatic perfusion with tumor necrosis factor and melphalan for unresectable cancers confined to the liver. AN - 79805241; 9552055 AB - To evaluate the efficacy and systemic and regional toxicities of hyperthermic isolated hepatic perfusion (IHP) using tumor necrosis factor (TNF) and melphalan for the treatment of unresectable primary or metastatic cancers confined to the liver. Thirty-four patients (18 men and 16 women; mean age, 49 years) underwent a 60-minute hyperthermic (39.5 degrees to 40.0 degrees C) IHP performed by laparotomy that used TNF 1.0 mg and melphalan 1.5 mg/kg. Perfusion inflow was through the gastroduodenal artery and outflow was from a cannula positioned in an isolated segment of retrohepatic inferior vena cava (IVC). Infrahepatic IVC and portal venous blood flow were shunted to the axillary vein using an external venoveno bypass circuit. Complete vascular isolation of the liver was confirmed by an I-131-labelled human serum albumin monitoring technique. There was no operative mortality. Seventy-five percent of patients had reversible grade III or IV (National Cancer Institute Common Toxicity Criteria) hepatic toxicity with one treatment-related mortality (3%) because of hepatic venoocclusive disease. In 33 assessable patients, the overall response rate was 75% (complete response, one patient [3%]; partial response, 26 patients [72%]). With a median potential follow-up of 15 months, the mean duration of response was 9 months (range, 2 to 30 months). IHP with TNF and melphalan results in significant regression of bulky hepatic cancers confined to the liver in the majority of patients. Based on these initial results, further refinement of this treatment technique is warranted; perhaps by the combination of IHP with other regional treatment strategies to provide long-term control of unresectable cancers confined to liver. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Alexander, H R AU - Bartlett, D L AU - Libutti, S K AU - Fraker, D L AU - Moser, T AU - Rosenberg, S A AD - Surgical Metabolism Section, Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1502, USA. hra@pop.nci.nih.gov Y1 - 1998/04// PY - 1998 DA - April 1998 SP - 1479 EP - 1489 VL - 16 IS - 4 SN - 0732-183X, 0732-183X KW - Antineoplastic Agents, Alkylating KW - 0 KW - Tumor Necrosis Factor-alpha KW - Transaminases KW - EC 2.6.1.- KW - Melphalan KW - Q41OR9510P KW - Index Medicus KW - Transaminases -- metabolism KW - Humans KW - Adult KW - Treatment Outcome KW - Aged KW - Middle Aged KW - Neoplasm Recurrence, Local KW - Male KW - Female KW - Tumor Necrosis Factor-alpha -- administration & dosage KW - Liver Neoplasms -- therapy KW - Melphalan -- administration & dosage KW - Liver Neoplasms -- enzymology KW - Melphalan -- adverse effects KW - Antineoplastic Agents, Alkylating -- adverse effects KW - Tumor Necrosis Factor-alpha -- adverse effects KW - Antineoplastic Agents, Alkylating -- administration & dosage KW - Chemotherapy, Cancer, Regional Perfusion -- methods KW - Liver Neoplasms -- secondary UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79805241?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Isolated+hepatic+perfusion+with+tumor+necrosis+factor+and+melphalan+for+unresectable+cancers+confined+to+the+liver.&rft.au=Alexander%2C+H+R%3BBartlett%2C+D+L%3BLibutti%2C+S+K%3BFraker%2C+D+L%3BMoser%2C+T%3BRosenberg%2C+S+A&rft.aulast=Alexander&rft.aufirst=H&rft.date=1998-04-01&rft.volume=16&rft.issue=4&rft.spage=1479&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 - 1998-05-12 N1 - Date created - 1998-05-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Heart rate variability as an index of cue reactivity in alcoholics. AN - 79800151; 9547935 AB - Autonomic responses follow exposure to conditioned stimuli such as contextual factors associated with alcohol ingestion. Heart rate variability is under autonomic control and may be a measure of such response. Twenty alcoholics and 23 matched social drinkers (all male) were exposed to a neutral cue and then an alcohol cue in identical settings, during which the electrocardiogram of these subjects was recorded. Time and frequency domain parameters of heart rate variability (HRV) were computed by a blind rater. Coefficient of variation of R-R intervals and absolute powers of HRV spectrum (in frequency bands 0.05-0.15 Hz and 0.01-0.05 Hz) following alcohol cue were significantly higher in alcoholics than social drinkers. The mean heart rate (MHR) failed to reflect this difference. HRV paradigm appears more sensitive than MHR to measure cue reactivity. JF - Biological psychiatry AU - Rajan, I AU - Murthy, P J AU - Ramakrishnan, A G AU - Gangadhar, B N AU - Janakiramaiah, N AD - Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, India. Y1 - 1998/04/01/ PY - 1998 DA - 1998 Apr 01 SP - 544 EP - 546 VL - 43 IS - 7 SN - 0006-3223, 0006-3223 KW - Index Medicus KW - Humans KW - Conditioning (Psychology) -- physiology KW - Adult KW - Cues KW - Alcohol Drinking -- physiopathology KW - Autonomic Nervous System -- physiopathology KW - Male KW - Heart Rate -- physiology KW - Alcoholism -- physiopathology KW - Alcoholism -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79800151?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Heart+rate+variability+as+an+index+of+cue+reactivity+in+alcoholics.&rft.au=Rajan%2C+I%3BMurthy%2C+P+J%3BRamakrishnan%2C+A+G%3BGangadhar%2C+B+N%3BJanakiramaiah%2C+N&rft.aulast=Rajan&rft.aufirst=I&rft.date=1998-04-01&rft.volume=43&rft.issue=7&rft.spage=544&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 - 1998-06-08 N1 - Date created - 1998-06-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Alterations in locomotor activity during chronic cocaine administration: effect on dopamine receptors and interaction with opioids. AN - 79794215; 9536022 AB - Chronic cocaine administration can produce tolerance or sensitization to locomotor activating effects, depending on the treatment paradigm. The effects of chronic, continuous cocaine were measured on locomotor activity for 1 hr daily for 7 days. Cocaine produced significant increases in locomotor activity 4 hr after osmotic minipumps were implanted, and an even higher level of activity after 24 hr. This was likely a rapid sensitization to the locomotor activating effects of cocaine, because neither brain nor plasma levels of cocaine were significantly altered over the treatment period. By day 4, activity levels diminished, but remained significantly higher than in saline-treated animals. Twenty-four hr after pump removal, there were no changes in dopamine D1 or D2 receptor binding, or in dopamine-stimulation of adenylyl cyclase activity in either caudate putamen or nucleus accumbens of cocaine-treated animals. Chronic naltrexone produced a slight, nonsignificant decrease in locomotor activity and when combined with cocaine, produced the same pattern of activity as cocaine alone, but with slightly less stimulation on all days. Morphine produced a smaller increase in activity than cocaine that remained constant throughout the treatment week. Cocaine with morphine was additive, producing greater activity and less tolerance than cocaine alone. Thus, continuous cocaine administration produces a rapid sensitization that is lost over the course of the treatment period, yet does not produce any immediate alterations in dopamine receptors or regulation of adenylyl cyclase. The pattern of behavior is not altered by an opioid antagonist, while the sensitization period appears to be prolonged in the presence of an opioid agonist. JF - The Journal of pharmacology and experimental therapeutics AU - Kunko, P M AU - French, D AU - Izenwasser, S AD - Psychobiology Section, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore, Maryland, USA. Y1 - 1998/04// PY - 1998 DA - April 1998 SP - 277 EP - 284 VL - 285 IS - 1 SN - 0022-3565, 0022-3565 KW - Analgesics, Opioid KW - 0 KW - Dopamine Uptake Inhibitors KW - Receptors, Dopamine KW - Adenylyl Cyclases KW - EC 4.6.1.1 KW - Cocaine KW - I5Y540LHVR KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Drug Interactions KW - Dopamine -- pharmacology KW - Enzyme Activation KW - Dose-Response Relationship, Drug KW - Nucleus Accumbens -- enzymology KW - Adenylyl Cyclases -- metabolism KW - Male KW - Receptors, Dopamine -- drug effects KW - Dopamine Uptake Inhibitors -- blood KW - Analgesics, Opioid -- pharmacology KW - Motor Activity -- drug effects KW - Cocaine -- pharmacology KW - Cocaine -- blood KW - Receptors, Dopamine -- metabolism KW - Dopamine Uptake Inhibitors -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79794215?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Alterations+in+locomotor+activity+during+chronic+cocaine+administration%3A+effect+on+dopamine+receptors+and+interaction+with+opioids.&rft.au=Kunko%2C+P+M%3BFrench%2C+D%3BIzenwasser%2C+S&rft.aulast=Kunko&rft.aufirst=P&rft.date=1998-04-01&rft.volume=285&rft.issue=1&rft.spage=277&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 - 1998-05-12 N1 - Date created - 1998-05-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Thapsigargin-induced secretion is dependent on activation of a cholera toxin-sensitive and phosphatidylinositol-3-kinase-regulated phospholipase D in a mast cell line. AN - 79790343; 9536000 AB - Release of secretory granules by rat RBL-2H3 mast cells is mediated primarily through activation of protein kinase C (PKC) and elevation of cytosolic free calcium ([Ca++]I). Here, we show that secretion was also dependent on the activation of a cholera toxin-sensitive phospholipase (PL) D in cells stimulated with thapsigargin. Wortmannin, LY294002, butanol, propranolol and Ro31-7549 inhibited responses to variety of secretagogues in a manner consistent with the notion that secretion was regulated by both PLD and PKC in a phosphatidylinositol-3-kinase-dependent manner. The effects of these inhibitors, however, were especially pronounced in cells activated by thapsigargin. This stimulant induced minimal stimulation of PLC but measurable activation of PLD, as assessed by formation of phosphatidylethanol in the presence of ethanol. The activation of PLD was suppressed by inhibitors of phosphatidylinositol-3-kinase and was dependent on a rise in [Ca++]i because thapsigargin failed to activate PLD and secretion when elevation of [Ca++]i was blocked. Treatment of cells with cholera toxin resulted in selective and similar enhancements in the activation of PLD and secretion by thapsigargin, whereas stimulation of PLC and PLA2 was unaffected. A role for PKC was indicated by the blockade of secretory response to thapsigargin by the PKC inhibitor Ro31-7549 and by the ability of the PKC agonist phorbol-12-myristate-13-acetate to reverse the inhibition of secretion by inhibitors of PLD. Such results suggested that thapsigargin, by causing substantial increases in [Ca++]I, induced secondary signals via PLD and PKC that synergized a calcium signal for secretion. JF - The Journal of pharmacology and experimental therapeutics AU - Cissel, D S AU - Fraundorfer, P F AU - Beaven, M A AD - Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1760, USA. cisseld@gwgate.nhlbi.nih.gov Y1 - 1998/04// PY - 1998 DA - April 1998 SP - 110 EP - 118 VL - 285 IS - 1 SN - 0022-3565, 0022-3565 KW - Adrenergic beta-Antagonists KW - 0 KW - Androstadienes KW - Butanols KW - Chromones KW - Enzyme Inhibitors KW - Morpholines KW - 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one KW - 31M2U1DVID KW - Thapsigargin KW - 67526-95-8 KW - Cholera Toxin KW - 9012-63-9 KW - Propranolol KW - 9Y8NXQ24VQ KW - Phosphatidylinositol 3-Kinases KW - EC 2.7.1.- KW - Phospholipase D KW - EC 3.1.4.4 KW - Calcium KW - SY7Q814VUP KW - wortmannin KW - XVA4O219QW KW - Index Medicus KW - Animals KW - Enzyme Activation KW - Propranolol -- pharmacology KW - Morpholines -- pharmacology KW - Androstadienes -- pharmacology KW - Cholera Toxin -- pharmacology KW - Cells, Cultured -- drug effects KW - Rats KW - Calcium -- metabolism KW - Chromones -- pharmacology KW - Butanols -- pharmacology KW - Adrenergic beta-Antagonists -- pharmacology KW - Female KW - Male KW - Thapsigargin -- pharmacology KW - Phospholipase D -- metabolism KW - Phospholipase D -- drug effects KW - Phosphatidylinositol 3-Kinases -- metabolism KW - Mast Cells -- enzymology KW - Enzyme Inhibitors -- pharmacology KW - Phosphatidylinositol 3-Kinases -- antagonists & inhibitors KW - Mast Cells -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79790343?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Thapsigargin-induced+secretion+is+dependent+on+activation+of+a+cholera+toxin-sensitive+and+phosphatidylinositol-3-kinase-regulated+phospholipase+D+in+a+mast+cell+line.&rft.au=Cissel%2C+D+S%3BFraundorfer%2C+P+F%3BBeaven%2C+M+A&rft.aulast=Cissel&rft.aufirst=D&rft.date=1998-04-01&rft.volume=285&rft.issue=1&rft.spage=110&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 - 1998-05-12 N1 - Date created - 1998-05-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Health hazards of radiation exposure in the context of brain imaging research: special consideration for children. AN - 79786973; 9544683 AB - This review provides information on health and biological effects of low-dose radiation to help institutional review boards and investigators make educated assessments of the risks of low-level radiation exposure involved in research, particularly in children. Studies of low-level radiation exposure with large sample sizes and long follow-up were reviewed. To help interpret the studies, we clarified the measures and measurement strategies of radiation exposure and of health risks. The few large studies of risks of low-level radiation in children have failed to detect an increased incidence of cancer. Most studies of low-level radiation involve adults. The risk of increased rates of cancer after low-level radiation exposure is not supported by population studies of health hazards from exposure to background radiation, radon in homes, radiation in the workplace or radiotherapy. Compared to the frequency of daily spontaneous genetic mutations, the biological effect of low-level radiation at the cellular level seems extremely low. Furthermore, the potentiation of cellular repair mechanisms by low-level radiation may result in a protective effect from subsequent high-level radiation. Studies approved by institutional review boards in the U.S. that involve the exposure of healthy normal children to ionizing radiation were reviewed. Health risks from low-level radiation could not be detected above the "noise" of adverse events of everyday life. In addition, no data were found that demonstrated higher risks with younger age at low-level radiation exposure. JF - Journal of nuclear medicine : official publication, Society of Nuclear Medicine AU - Ernst, M AU - Freed, M E AU - Zametkin, A J AD - Brain Imaging Center, National Institute on Drug Abuse, Baltimore, Maryland 21224, USA. Y1 - 1998/04// PY - 1998 DA - April 1998 SP - 689 EP - 698 VL - 39 IS - 4 SN - 0161-5505, 0161-5505 KW - Radon KW - Q74S4N8N1G KW - Index Medicus KW - Radiation Dosage KW - Risk Factors KW - Humans KW - Environmental Exposure KW - Radiotherapy KW - Child KW - Radon -- adverse effects KW - Radionuclide Imaging KW - Brain -- radiation effects KW - Brain -- diagnostic imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79786973?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+nuclear+medicine+%3A+official+publication%2C+Society+of+Nuclear+Medicine&rft.atitle=Health+hazards+of+radiation+exposure+in+the+context+of+brain+imaging+research%3A+special+consideration+for+children.&rft.au=Ernst%2C+M%3BFreed%2C+M+E%3BZametkin%2C+A+J&rft.aulast=Ernst&rft.aufirst=M&rft.date=1998-04-01&rft.volume=39&rft.issue=4&rft.spage=689&rft.isbn=&rft.btitle=&rft.title=Journal+of+nuclear+medicine+%3A+official+publication%2C+Society+of+Nuclear+Medicine&rft.issn=01615505&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-05-01 N1 - Date created - 1998-05-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Differential selectivity of ligands for the C1a and C1b phorbol ester binding domains of protein kinase Cdelta: possible correlation with tumor-promoting activity. AN - 79776006; 9537243 AB - Protein kinase C (PKC) represents the major, high-affinity receptor for the phorbol esters as well as for a series of structurally diverse natural products. The phorbol esters function by binding to the tandem C1a and C1b domains in PKC, leading to enzyme activation. Although the typical phorbol esters represent the paradigm for tumor promoters in mouse skin, it is now clear that different high affinity ligands for PKC have distinct biological effects. Thus, the daphnane analogue mezerein is a second-stage promoter, the macrolide bryostatin 1 is a partial antagonist, and certain 12-deoxyphorbol 13-monoesters also function as partial antagonists but with a different pattern of activity. The biochemical basis for these differences is an area of active investigation. In this report, we have examined the relative interaction of ligands differing in structure and pattern of biological response with the C1a and C1b domains of PKCdelta. We mutated either or both of the C1 domains of PKCdelta, expressed the constructs in NIH 3T3 cells, and monitored the interaction of the ligands by their ability to induce translocation of the mutated PKCdelta from the cytosol to the particulate fraction. We found that different ligands showed different dependence on the C1a and C1b domains for translocation. Whereas phorbol 12-myristate 13-acetate and the indole alkaloids indolactam and octylindolactam were selectively dependent on the C1b domain, selectivity was not observed for mezerein, for the 12-deoxyphorbol 13-monoesters prostratin or 12-deoxyphorbol 13-phenylacetate, or for the macrocyclic lactone bryostatin 1. Provocatively, the pattern of response corresponds with the activity of the compounds as complete tumor promoters. JF - Cancer research AU - Bögi, K AU - Lorenzo, P S AU - Szállási, Z AU - Acs, P AU - Wagner, G S AU - Blumberg, P M AD - Molecular Mechanisms of Tumor Promotion Section, Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, Maryland 20892-4255, USA. Y1 - 1998/04/01/ PY - 1998 DA - 1998 Apr 01 SP - 1423 EP - 1428 VL - 58 IS - 7 SN - 0008-5472, 0008-5472 KW - Carcinogens KW - 0 KW - Diterpenes KW - Indoles KW - Isoenzymes KW - Lactams KW - Ligands KW - Phorbol Esters KW - Terpenes KW - 7-octylindolactam V KW - 109346-66-9 KW - mezerein KW - 34807-41-5 KW - 12-deoxyphorbolphenylacetate KW - 58821-98-0 KW - prostratin KW - 60857-08-1 KW - indolactam V KW - 8CIY9O1323 KW - Prkcd protein, mouse KW - EC 2.7.1.- KW - Protein Kinase C KW - EC 2.7.11.13 KW - Protein Kinase C-delta KW - Index Medicus KW - Terpenes -- toxicity KW - Animals KW - Mice KW - Binding Sites KW - Mutagenesis, Site-Directed KW - Blotting, Western KW - Lactams -- metabolism KW - Lactams -- toxicity KW - Indoles -- toxicity KW - Terpenes -- metabolism KW - 3T3 Cells -- metabolism KW - Indoles -- metabolism KW - Protein Structure, Tertiary KW - Protein Kinase C -- metabolism KW - Isoenzymes -- chemistry KW - Phorbol Esters -- metabolism KW - Carcinogens -- metabolism KW - Protein Kinase C -- chemistry KW - Carcinogens -- toxicity KW - Phorbol Esters -- toxicity KW - Isoenzymes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79776006?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Differential+selectivity+of+ligands+for+the+C1a+and+C1b+phorbol+ester+binding+domains+of+protein+kinase+Cdelta%3A+possible+correlation+with+tumor-promoting+activity.&rft.au=B%C3%B6gi%2C+K%3BLorenzo%2C+P+S%3BSz%C3%A1ll%C3%A1si%2C+Z%3BAcs%2C+P%3BWagner%2C+G+S%3BBlumberg%2C+P+M&rft.aulast=B%C3%B6gi&rft.aufirst=K&rft.date=1998-04-01&rft.volume=58&rft.issue=7&rft.spage=1423&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 - 1998-04-16 N1 - Date created - 1998-04-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Autophosphorylation in the activation loop is required for full kinase activity in vivo of human and yeast eukaryotic initiation factor 2alpha kinases PKR and GCN2. AN - 79762551; 9528799 AB - The human double-stranded RNA-dependent protein kinase (PKR) is an important component of the interferon response to virus infection. The activation of PKR is accompanied by autophosphorylation at multiple sites, including one in the N-terminal regulatory region (Thr-258) that is required for full kinase activity. Several protein kinases are activated by phosphorylation in the region between kinase subdomains VII and VIII, referred to as the activation loop. We show that Thr-446 and Thr-451 in the PKR activation loop are required in vivo and in vitro for high-level kinase activity. Mutation of either residue to Ala impaired translational control by PKR in yeast cells and COS1 cells and led to tumor formation in mice. These mutations also impaired autophosphorylation and eukaryotic initiation factor 2 subunit alpha (eIF2alpha) phosphorylation by PKR in vitro. Whereas the Ala-446 substitution substantially reduced PKR function, the mutant kinase containing Ala-451 was completely inactive. PKR specifically phosphorylated Thr-446 and Thr-451 in synthetic peptides in vitro, and mass spectrometry analysis of PKR phosphopeptides confirmed that Thr-446 is an autophosphorylation site in vivo. Substitution of Glu-490 in subdomain X of PKR partially restored kinase activity when combined with the Ala-451 mutation. This finding suggests that the interaction between subdomain X and the activation loop, described previously for MAP kinase, is a regulatory feature conserved in PKR. We found that the yeast eIF2alpha kinase GCN2 autophosphorylates at Thr-882 and Thr-887, located in the activation loop at exactly the same positions as Thr-446 and Thr-451 in PKR. Thr-887 was more critically required than was Thr-882 for GCN2 kinase activity, paralleling the relative importance of Thr-446 and Thr-451 in PKR. These results indicate striking similarities between GCN2 and PKR in the importance of autophosphorylation and the conserved Thr residues in the activation loop. JF - Molecular and cellular biology AU - Romano, P R AU - Garcia-Barrio, M T AU - Zhang, X AU - Wang, Q AU - Taylor, D R AU - Zhang, F AU - Herring, C AU - Mathews, M B AU - Qin, J AU - Hinnebusch, A G AD - Laboratory of Eukaryotic Gene Regulation, National Institute of Child Health and Human Development, Bethesda, Maryland 20892, USA. Y1 - 1998/04// PY - 1998 DA - April 1998 SP - 2282 EP - 2297 VL - 18 IS - 4 SN - 0270-7306, 0270-7306 KW - DNA-Binding Proteins KW - 0 KW - Fungal Proteins KW - Peptide Initiation Factors KW - Peptides KW - Saccharomyces cerevisiae Proteins KW - Threonine KW - 2ZD004190S KW - Protein Kinases KW - EC 2.7.- KW - eIF-2 Kinase KW - EC 2.7.11.1 KW - Index Medicus KW - Peptides -- chemical synthesis KW - Protein Biosynthesis KW - 3T3 Cells KW - Animals KW - Mass Spectrometry KW - Threonine -- metabolism KW - COS Cells KW - Neoplasms, Experimental -- etiology KW - Enzyme Activation KW - Humans KW - Peptides -- metabolism KW - Mice, Nude KW - Amino Acid Sequence KW - Mice KW - Binding Sites KW - Mutagenesis, Site-Directed KW - Gene Expression Regulation, Enzymologic KW - Phosphorylation KW - Conserved Sequence KW - Molecular Sequence Data KW - Substrate Specificity KW - Amino Acid Substitution KW - Saccharomyces cerevisiae -- genetics KW - Protein Kinases -- metabolism KW - Peptide Initiation Factors -- metabolism KW - Peptide Initiation Factors -- genetics KW - Fungal Proteins -- metabolism KW - eIF-2 Kinase -- metabolism KW - Protein Kinases -- genetics KW - Saccharomyces cerevisiae -- enzymology KW - Fungal Proteins -- genetics KW - eIF-2 Kinase -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79762551?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Autophosphorylation+in+the+activation+loop+is+required+for+full+kinase+activity+in+vivo+of+human+and+yeast+eukaryotic+initiation+factor+2alpha+kinases+PKR+and+GCN2.&rft.au=Romano%2C+P+R%3BGarcia-Barrio%2C+M+T%3BZhang%2C+X%3BWang%2C+Q%3BTaylor%2C+D+R%3BZhang%2C+F%3BHerring%2C+C%3BMathews%2C+M+B%3BQin%2C+J%3BHinnebusch%2C+A+G&rft.aulast=Romano&rft.aufirst=P&rft.date=1998-04-01&rft.volume=18&rft.issue=4&rft.spage=2282&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 - 1998-05-21 N1 - Date created - 1998-05-21 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Biol Chem. 1979 Jul 25;254(14):6211-4 [221492] Anal Chem. 1997 Oct 1;69(19):3995-4001 [9322436] J Biol Chem. 1987 Nov 15;262(32):15538-44 [3479429] Eur J Biochem. 1989 Jan 2;178(3):581-9 [2912723] Yeast. 1985 Dec;1(2):83-138 [3916863] Mol Cell Biol. 1989 Apr;9(4):1576-86 [2725516] Nucleic Acids Res. 1989 Jun 26;17(12):4895 [2748349] Mol Cell Biol. 1990 Jun;10(6):2820-31 [2188100] Methods Enzymol. 1991;194:477-90 [2005804] Science. 1991 Jul 26;253(5018):407-14 [1862342] Methods Enzymol. 1991;201:110-49 [1943760] Methods Enzymol. 1991;201:21-7 [1719341] Cell. 1992 Feb 7;68(3):585-96 [1739968] EMBO J. 1992 Apr;11(4):1553-62 [1348691] J Biol Chem. 1992 May 25;267(15):10729-36 [1375230] Science. 1992 Sep 18;257(5077):1685-9 [1382315] Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10837-41 [1279695] Mol Cell Biol. 1992 Dec;12(12):5801-15 [1448107] Proc Natl Acad Sci U S A. 1993 Jan 1;90(1):232-6 [7678339] Nature. 1970 Aug 15;227(5259):680-5 [5432063] J Biol Chem. 1978 Oct 25;253(20):7145-8 [212418] Proc Natl Acad Sci U S A. 1993 May 15;90(10):4616-20 [8099443] Proc Natl Acad Sci U S A. 1993 May 15;90(10):4621-5 [8099444] Nature. 1993 Jun 17;363(6430):595-602 [8510751] Mol Cell Biol. 1993 Aug;13(8):4618-31 [8336705] Genes Dev. 1992 Dec;6(12B):2478-90 [1364113] Nature. 1994 Feb 24;367(6465):704-11 [8107865] Gene. 1994 May 27;143(1):21-7 [8200534] Protein Sci. 1994 Feb;3(2):176-87 [8003955] Mol Biol Cell. 1994 Mar;5(3):297-312 [8049522] Mol Cell Biol. 1995 Jan;15(1):365-78 [7799945] Biochemistry. 1995 Feb 28;34(8):2447-54 [7873523] J Biol Chem. 1995 Jun 23;270(25):14843-6 [7797459] J Virol. 1995 Aug;69(8):5195-8 [7541849] Mol Cell Biol. 1995 Aug;15(8):4497-506 [7623840] Proc Natl Acad Sci U S A. 1995 Aug 29;92(18):8283-7 [7545299] Proc Natl Acad Sci U S A. 1995 Oct 10;92(21):9445-9 [7568151] J Biol Chem. 1996 Jan 19;271(3):1756-63 [8576179] Cell. 1996 Apr 19;85(2):149-58 [8612268] J Biol Chem. 1996 Oct 4;271(40):24989-94 [8798780] J Biol Chem. 1996 Oct 11;271(41):25657-63 [8810342] Mol Cell Biol. 1996 Nov;16(11):6295-302 [8887659] J Biol Chem. 1997 Jan 10;272(2):1291-6 [8995434] Mol Cell Biol. 1997 Mar;17(3):1298-313 [9032257] J Biol Chem. 1997 May 9;272(19):12544-50 [9139706] J Biol Chem. 1997 May 30;272(22):14434-41 [9162083] Cell. 1997 Sep 5;90(5):859-69 [9298898] J Biol Chem. 1985 Jul 15;260(14):8237-9 [2409082] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Analysis of the juxtamembrane dileucine motif in the insulin receptor. AN - 79759075; 9528942 AB - Dileucine-containing motifs are involved in trans-Golgi sorting, lysosomal targeting, and internalization. Previously, we have shown that the dileucine motif (EKITLL, residues 982-987) in the juxtamembrane region of the insulin receptor is involved in receptor internalization. Substitution of alanine residues for Leu986 and Leu987 led to a 3- to 5-fold decrease in the ability of the receptors to mediate insulin uptake. In the current study, we show that mutation of the same motif to Met986Ser987, the sequence found in the homologous position in the type I insulin-like growth factor receptor, did not affect insulin uptake. Therefore, we inquired whether the sequence EKITMS as an isolated motif could mediate the targeting of a reporter molecule to endosomes and then lysosomes, as was shown previously with the EKITLL motif of the normal receptor. Chimeric molecules containing Tac antigen fused to different hexapeptide sequences showed distinct patterns of subcellular localization by immunofluorescence microscopy. Tac-EKITLL and Tac-EKITAA were found predominantly in lysosomes and the plasma membrane, respectively. In contrast, Tac-EKITMS was found at the plasma membrane, in the trans-Golgi network, and in endosomes, but only small amounts were found in lysosomes. Thus, the dileucine motif (EKITLL) plays an important role in directing endocytosis of the intact insulin receptor and in mediating efficient endocytosis and lysosomal targeting as an isolated motif. Substitution of AA for LL inhibits endocytosis and lysosomal targeting in both systems. In contrast, substitution of MS for LL permits rapid endocytosis in the intact receptor, but mediates modest endocytosis and very little targeting to lysosomes as an isolated motif. Our observations support the idea that sorting signals are recognized at multiple steps in the cell, and that specific amino acid substitutions may differentially affect each of these sorting steps. JF - Endocrinology AU - Haft, C R AU - De La Luz Sierra, M AU - Hamer, I AU - Carpentier, J L AU - Taylor, S I AD - Diabetes Branch, National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-1829, USA. Y1 - 1998/04// PY - 1998 DA - April 1998 SP - 1618 EP - 1629 VL - 139 IS - 4 SN - 0013-7227, 0013-7227 KW - Antigens, CD3 KW - 0 KW - Insulin KW - Recombinant Fusion Proteins KW - Recombinant Proteins KW - Receptor, Insulin KW - EC 2.7.10.1 KW - Leucine KW - GMW67QNF9C KW - Abridged Index Medicus KW - Index Medicus KW - Antigens, CD3 -- genetics KW - 3T3 Cells KW - Animals KW - HeLa Cells KW - Humans KW - Insulin -- metabolism KW - Amino Acid Sequence KW - Mice KW - Structure-Activity Relationship KW - Mutagenesis KW - Recombinant Fusion Proteins -- metabolism KW - Base Sequence KW - Sequence Alignment KW - Phosphorylation KW - Transfection KW - Molecular Sequence Data KW - Receptor, Insulin -- chemistry KW - Receptor, Insulin -- genetics KW - Sequence Analysis KW - Leucine -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79759075?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Analysis+of+the+juxtamembrane+dileucine+motif+in+the+insulin+receptor.&rft.au=Haft%2C+C+R%3BDe+La+Luz+Sierra%2C+M%3BHamer%2C+I%3BCarpentier%2C+J+L%3BTaylor%2C+S+I&rft.aulast=Haft&rft.aufirst=C&rft.date=1998-04-01&rft.volume=139&rft.issue=4&rft.spage=1618&rft.isbn=&rft.btitle=&rft.title=Endocrinology&rft.issn=00137227&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-04-14 N1 - Date created - 1998-04-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cleavage of the feline calicivirus capsid precursor is mediated by a virus-encoded proteinase. AN - 79757158; 9525628 AB - Feline calicivirus (FCV), a member of the Caliciviridae, produces its major structural protein as a precursor polyprotein from a subgenomic-sized mRNA. In this study, we show that the proteinase responsible for processing this precursor into the mature capsid protein is encoded by the viral genome at the 3'-terminal portion of open reading frame 1 (ORF1). Protein expression studies of either the entire or partial ORF1 indicate that the proteinase is active when expressed either in in vitro translation or in bacterial cells. Site-directed mutagenesis was used to characterize the proteinase Glu-Ala cleavage site in the capsid precursor, utilizing an in vitro cleavage assay in which mutant precursor proteins translated from cDNA clones were used as substrates for trans cleavage by the proteinase. In general, amino acid substitutions in the P1 position (Glu) of the cleavage site were less well tolerated by the proteinase than those in the P1' position (Ala). The precursor cleavage site mutations were introduced into an infectious cDNA clone of the FCV genome, and transfection of RNA derived from these clones into feline kidney cells showed that efficient cleavage of the capsid precursor by the virus-encoded proteinase is a critical determinant in the growth of the virus. JF - Journal of virology AU - Sosnovtsev, S V AU - Sosnovtseva, S A AU - Green, K Y AD - Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/04// PY - 1998 DA - April 1998 SP - 3051 EP - 3059 VL - 72 IS - 4 SN - 0022-538X, 0022-538X KW - DNA, Viral KW - 0 KW - Protein Precursors KW - Endopeptidases KW - EC 3.4.- KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Protein Biosynthesis KW - Animals KW - Base Sequence KW - Protein Precursors -- metabolism KW - Cats KW - Molecular Sequence Data KW - Gene Expression KW - Transcription, Genetic KW - Chromosome Mapping KW - Cell Line KW - Endopeptidases -- genetics KW - Calicivirus, Feline -- enzymology KW - Calicivirus, Feline -- genetics KW - Endopeptidases -- metabolism KW - Capsid -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79757158?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cleavage+of+the+feline+calicivirus+capsid+precursor+is+mediated+by+a+virus-encoded+proteinase.&rft.au=Sosnovtsev%2C+S+V%3BSosnovtseva%2C+S+A%3BGreen%2C+K+Y&rft.aulast=Sosnovtsev&rft.aufirst=S&rft.date=1998-04-01&rft.volume=72&rft.issue=4&rft.spage=3051&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 - 1998-04-17 N1 - Date created - 1998-04-17 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - L40021; GENBANK N1 - SuppNotes - Cited By: Virus Res. 1993 Mar;27(3):219-28 [8488721] J Biol Chem. 1991 Mar 25;266(9):5412-6 [1848550] Virus Res. 1993 Oct;30(1):17-26 [7505513] Nature. 1994 May 5;369(6475):72-6 [8164744] Cell. 1994 Jun 3;77(5):761-71 [7515772] J Virol. 1994 Oct;68(10):6487-95 [8083986] Virology. 1995 Jul 10;210(2):383-90 [7618275] J Virol. 1995 Nov;69(11):7159-68 [7474137] J Virol. 1996 Feb;70(2):1261-5 [8551592] J Gen Virol. 1996 Jan;77 ( Pt 1):123-7 [8558120] J Virol. 1996 Apr;70(4):2605-10 [8642693] J Gen Virol. 1997 May;78 ( Pt 5):1033-40 [9152420] J Virol. 1977 May;22(2):572-6 [559106] Nature. 1978 Aug 10;274(5671):614-5 [672996] Virology. 1978 Aug;89(1):318-21 [687392] Virology. 1979 May;95(1):251-5 [571647] Virus Res. 1988 Aug;11(1):59-72 [3176687] FEBS Lett. 1989 Jan 30;243(2):103-14 [2645167] Arch Virol. 1989;108(1-2):69-79 [2596975] Curr Top Microbiol Immunol. 1990;161:49-87 [2169385] Virus Res. 1990 Nov;17(3):145-60 [2077782] Virology. 1991 Aug;183(2):810-4 [1853578] Virology. 1991 Oct;184(2):677-86 [1887589] J Virol. 1991 Oct;65(10):5440-7 [1716692] Arch Biochem Biophys. 1991 May 1;286(2):402-8 [1654789] Arch Virol. 1992;122(3-4):223-35 [1731695] Biochemistry. 1992 Sep 1;31(34):7862-9 [1510973] Science. 1993 Jan 22;259(5094):516-9 [8380940] Arch Virol. 1990;114(3-4):143-52 [2241572] Annu Rev Microbiol. 1990;44:603-23 [2252396] Virology. 1993 Jul;195(1):51-61 [8391187] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Angiotensin II activates mitogen-activated protein kinase via protein kinase C and Ras/Raf-1 kinase in bovine adrenal glomerulosa cells. AN - 79755320; 9528965 AB - Angiotensin II (Ang II) stimulates growth and mitogenesis in bovine adrenal glomerulosa cells, but little is known about the signaling pathways that mediate these responses. An analysis of the growth-promoting pathways in cultured bovine adrenal glomerulosa cells revealed that Ang II, acting via the AT1 receptor, caused rapid but transient activation of mitogen-activated protein kinase (MAPK), with an ED50 of 10-50 pM. Although neither Ca2+ influx nor Ca2+ release from intracellular stores was sufficient to activate MAPK, Ca2+ appeared to play a permissive role in this response. A major component of Ang II-induced MAPK activation was insensitive to pertussis toxin (PTX), although a minor PTX-sensitive component could not be excluded. Ang II also induced the rapid activation of ras and raf-1 kinase with time-courses that correlated with that of MAPK. Activation of protein kinase C (PKC) by phorbol 12-myristate 13-acetate was sufficient to activate both MAPK and raf-1 kinase. However, whereas PKC depletion had no effect on Ang II-induced raf-1 kinase activation, it attenuated Ang II-induced MAPK activation. Ang II also stimulated a mobility shift of raf-1, reflecting hyperphosphorylation of the kinase. However, unlike its activation, raf-1 hyperphosphorylation was dependent on PKC and its time-course correlated not with activation, but rather with deactivation of the kinase. Taken together, these findings indicate that Ang II stimulates multiple pathways to MAPK activation via PKC and ras/raf-1 kinase in bovine adrenal glomerulosa cells. JF - Endocrinology AU - Tian, Y AU - Smith, R D AU - Balla, T AU - Catt, K J AD - Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/04// PY - 1998 DA - April 1998 SP - 1801 EP - 1809 VL - 139 IS - 4 SN - 0013-7227, 0013-7227 KW - Receptor, Angiotensin, Type 1 KW - 0 KW - Receptor, Angiotensin, Type 2 KW - Receptors, Angiotensin KW - Virulence Factors, Bordetella KW - Angiotensin II KW - 11128-99-7 KW - Egtazic Acid KW - 526U7A2651 KW - Pertussis Toxin KW - EC 2.4.2.31 KW - Proto-Oncogene Proteins c-raf KW - EC 2.7.11.1 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Calcium-Calmodulin-Dependent Protein Kinases KW - EC 2.7.11.17 KW - ras Proteins KW - EC 3.6.5.2 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Calcium KW - SY7Q814VUP KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Calcium -- metabolism KW - Virulence Factors, Bordetella -- pharmacology KW - Cattle KW - Phosphorylation KW - Receptors, Angiotensin -- physiology KW - Kinetics KW - Enzyme Activation -- drug effects KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Egtazic Acid -- pharmacology KW - Protein Kinase C -- metabolism KW - Calcium-Calmodulin-Dependent Protein Kinases -- metabolism KW - Proto-Oncogene Proteins c-raf -- metabolism KW - ras Proteins -- metabolism KW - Zona Glomerulosa -- enzymology KW - Angiotensin II -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79755320?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Angiotensin+II+activates+mitogen-activated+protein+kinase+via+protein+kinase+C+and+Ras%2FRaf-1+kinase+in+bovine+adrenal+glomerulosa+cells.&rft.au=Tian%2C+Y%3BSmith%2C+R+D%3BBalla%2C+T%3BCatt%2C+K+J&rft.aulast=Tian&rft.aufirst=Y&rft.date=1998-04-01&rft.volume=139&rft.issue=4&rft.spage=1801&rft.isbn=&rft.btitle=&rft.title=Endocrinology&rft.issn=00137227&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-04-14 N1 - Date created - 1998-04-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Smaller volume of prefrontal lobe in polysubstance abusers: a magnetic resonance imaging study. AN - 79732314; 9509492 AB - The present study was conducted to test the hypothesis that individuals with substance abuse disorder exhibit structural deficits in the prefrontal cortex. Volumes of the prefrontal lobe in subjects with histories of polysubstance abuse (n = 25) were measured and compared with those in normal volunteers (n = 14), using high-resolution volumetric magnetic resonance imaging (MRI). The research participants were men, 22 to 41 years of age. Polysubstance abusers were abstinent from drugs of abuse (except nicotine) for at least 15 days before MRI scanning. The total volumes of the prefrontal lobe (left and right hemispheres) were significantly smaller in the substance abuse group than in the control group. When the prefrontal lobe was segmented for gray and white matter, the deficit in the substance abusers was seen as significantly smaller volumes of gray but not of white matter. These results indicate that hypoplasia and/or atrophy in the prefrontal cortex accompany substance abuse and suggest that structural deficits in the prefrontal cortex may play an essential role in the neuropathological basis of functional impairments in substance abuse disorder, as demonstrated by functional brain imaging and cognitive studies. JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology AU - Liu, X AU - Matochik, J A AU - Cadet, J L AU - London, E D AD - Neuroscience Branch, National Institute on Drug Abuse, Baltimore, Maryland 21224, USA. Y1 - 1998/04// PY - 1998 DA - April 1998 SP - 243 EP - 252 VL - 18 IS - 4 SN - 0893-133X, 0893-133X KW - Index Medicus KW - Magnetic Resonance Imaging KW - Image Interpretation, Computer-Assisted KW - Humans KW - Adult KW - Observer Variation KW - Time Factors KW - Male KW - Substance-Related Disorders -- pathology KW - Prefrontal Cortex -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79732314?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Smaller+volume+of+prefrontal+lobe+in+polysubstance+abusers%3A+a+magnetic+resonance+imaging+study.&rft.au=Liu%2C+X%3BMatochik%2C+J+A%3BCadet%2C+J+L%3BLondon%2C+E+D&rft.aulast=Liu&rft.aufirst=X&rft.date=1998-04-01&rft.volume=18&rft.issue=4&rft.spage=243&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 - 1998-04-30 N1 - Date created - 1998-04-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Long-term salivary effects of single-dose head and neck irradiation in the rat. AN - 70086553; 9839705 AB - The effect of a single dose of X-irradiation (either 2.5, 5, 7.5, 10 or 15 Gy) to the head and neck region on parotid and submandibular gland function in rats was evaluated for up to 1 year. No animal receiving 15 Gy survived the entire study. Animals receiving > or = 7.5 Gy showed significantly less increase in body weight over time. Average wet weights of both gland types were reduced with as little as 2.5 Gy. Pilocarpine-stimulated parotid salivary flow was diminished significantly at 12 months for each radiation-dose group. Significant salivary flow reductions from submandibular glands were seen at > or = 7.5 Gy at this same time-point. These results show that a single radiation exposure of as low as 2.5 Gy to the head and neck region of rats can cause significant long-term alterations in salivary gland function. JF - Archives of oral biology AU - Nagler, R M AU - Baum, B J AU - Miller, G AU - Fox, P C AD - Gene Therapy and Therapeutics Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892-1190, USA. Y1 - 1998/04// PY - 1998 DA - April 1998 SP - 297 EP - 303 VL - 43 IS - 4 SN - 0003-9969, 0003-9969 KW - Parasympathomimetics KW - 0 KW - Pilocarpine KW - 01MI4Q9DI3 KW - Dentistry KW - Index Medicus KW - Animals KW - Analysis of Variance KW - Pilocarpine -- pharmacology KW - Dose-Response Relationship, Radiation KW - Stimulation, Chemical KW - Rats KW - Secretory Rate -- drug effects KW - Body Weight -- radiation effects KW - Parasympathomimetics -- pharmacology KW - Rats, Wistar KW - Organ Size -- radiation effects KW - Secretory Rate -- radiation effects KW - Time Factors KW - Male KW - Parotid Gland -- anatomy & histology KW - Neck -- radiation effects KW - Submandibular Gland -- anatomy & histology KW - Submandibular Gland -- radiation effects KW - Parotid Gland -- drug effects KW - Parotid Gland -- secretion KW - Submandibular Gland -- drug effects KW - Head -- radiation effects KW - Parotid Gland -- radiation effects KW - Submandibular Gland -- secretion UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70086553?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+oral+biology&rft.atitle=Long-term+salivary+effects+of+single-dose+head+and+neck+irradiation+in+the+rat.&rft.au=Nagler%2C+R+M%3BBaum%2C+B+J%3BMiller%2C+G%3BFox%2C+P+C&rft.aulast=Nagler&rft.aufirst=R&rft.date=1998-04-01&rft.volume=43&rft.issue=4&rft.spage=297&rft.isbn=&rft.btitle=&rft.title=Archives+of+oral+biology&rft.issn=00039969&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-01-22 N1 - Date created - 1999-01-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Analysis of brefeldin A and the prodrug breflate in plasma by gas chromatography with mass selective detection. AN - 69981012; 9777604 AB - Breflate is a water soluble prodrug developed to facilitate parenteral administration of the investigational antineoplastic agent brefeldin A (BFA). Previously, using analytical methods based upon reversed-phase high performance liquid chromatography (HPLC) with low wavelength UV detection or gas chromatography (GC) with electron capture detection following derivatization with heptafluorobutyrylimidazole, it was demonstrated that breflate undergoes rapid and efficient conversion to BFA following bolus i.v. injection in mice and dogs. However, plasma concentrations of the drug and prodrug achieved during the administration of nontoxic doses of breflate to beagle dogs as a 72 h continuous i.v. infusion were undetectable (< 0.1 microgram ml-1) by these methods. The sensitivity and specificity required for therapeutic drug level monitoring were achieved by GC with selected-ion mass spectrometry (MS) detection. Breflate, BFA and 1-eicosanol, the latter added to the sample as an internal standard (IS), were extracted from plasma into tert-butyl methyl ether (TBME) and esterified with trifluoroacetic anhydride. Methanol was added to the reaction mixture to effect the convenient removal of excess reagent as the volatile methyl ester during evaporation of the solvent. The residual material was analyzed directly upon reconstitution by capillary GC with automated splitless injection. Electron-ionization (70 eV) MS detection was performed by sequentially scanning ions at m/z 58, 202 and 325. The lowest concentration of either analyte quantified with acceptable reproducibility, as defined by an inter-day R.S.D. of about 20%, was near 10 ng ml-1 in plasma using a sample volume of 100 microliters. The assay has proven to be sufficiently sensitive, specific and reproducible for the routine analysis of pharmacokinetic specimens acquired during IND (investigational new drug)-directed toxicology studies in dogs. JF - Journal of pharmaceutical and biomedical analysis AU - Phillips, L R AU - Wolfe, T L AU - Malspeis, L AU - Supko, J G AD - Laboratory of Pharmaceutical Chemistry, National Cancer Institute, Frederick, MD 21701, USA. phillips@dtpax.2.ncifcrf.gov Y1 - 1998/04// PY - 1998 DA - April 1998 SP - 1301 EP - 1309 VL - 16 IS - 8 SN - 0731-7085, 0731-7085 KW - Anti-Bacterial Agents KW - 0 KW - Macrolides KW - Prodrugs KW - breflate KW - Brefeldin A KW - 20350-15-6 KW - Index Medicus KW - Sensitivity and Specificity KW - Animals KW - Dogs KW - Mice KW - Male KW - Brefeldin A -- analogs & derivatives KW - Gas Chromatography-Mass Spectrometry -- methods KW - Chromatography, High Pressure Liquid -- methods KW - Anti-Bacterial Agents -- blood KW - Brefeldin A -- pharmacokinetics KW - Prodrugs -- metabolism KW - Anti-Bacterial Agents -- pharmacokinetics KW - Brefeldin A -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69981012?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+pharmaceutical+and+biomedical+analysis&rft.atitle=Analysis+of+brefeldin+A+and+the+prodrug+breflate+in+plasma+by+gas+chromatography+with+mass+selective+detection.&rft.au=Phillips%2C+L+R%3BWolfe%2C+T+L%3BMalspeis%2C+L%3BSupko%2C+J+G&rft.aulast=Phillips&rft.aufirst=L&rft.date=1998-04-01&rft.volume=16&rft.issue=8&rft.spage=1301&rft.isbn=&rft.btitle=&rft.title=Journal+of+pharmaceutical+and+biomedical+analysis&rft.issn=07317085&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-12-24 N1 - Date created - 1998-12-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - How asthma friendly is your school? AN - 215682593; 03813817 AB - Seven questions to determine how a school assists children with asthma are discussed, and resource organizations for parents and school staff are listed. Schools should be smoke-free and should have a policy on asthma treatment and training of staff in asthma treatment. JF - The Journal of School Health AU - National Heart, Lung, and Blood Institute AU - National Asthma Education and Prevention Program AU - School Asthma Education Subcommittee AD - National Heart, Lung, and Blood Institute ; National Asthma Education and Prevention Program Y1 - 1998/04// PY - 1998 DA - Apr 1998 SP - 167 EP - 168 CY - Kent PB - Blackwell Publishing Ltd. VL - 68 IS - 4 SN - 00224391 KW - Physical Fitness And Hygiene KW - Schools KW - Asthma KW - Health care UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/215682593?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthcompleteshell&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+School+Health&rft.atitle=How+asthma+friendly+is+your+school%3F&rft.au=National+Heart%2C+Lung%2C+and+Blood+Institute%3BNational+Asthma+Education+and+Prevention+Program%3BSchool+Asthma+Education+Subcommittee&rft.aulast=National+Heart&rft.aufirst=Lung&rft.date=1998-04-01&rft.volume=68&rft.issue=4&rft.spage=167&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+School+Health&rft.issn=00224391&rft_id=info:doi/ LA - English DB - ProQuest Central; ProQuest Environmental Science Collection N1 - Copyright - Copyright American School Health Association Apr 1998 N1 - Last updated - 2012-02-21 N1 - CODEN - JSHEAZ ER - TY - JOUR T1 - Development and preliminary validation of a forced-choice test of response bias for posttraumatic stress disorder AN - 16548564; 4351706 AB - This article describes the development and preliminary validation of the Morel Emotional Numbing Test for PTSD (MENT), a forced-choice test for detecting response bias in assessments for posttraumatic stress disorder (PTSD). The differences in MENT error rates among four groups of military veterans applying for monetary compensation for combat-related PTSD and two groups of hospitalized military veterans were investigated (N = 102): (a) disability claimants with veritable self-presentations, who were diagnosed with PTSD; (b) disability claimants with veritable self-presentations, who were not diagnosed with PTSD; (c) older disability claimants (age 63 or older) with veritable self-presentations; (d) disability claimants with suspect self-presentations; (e) chemical-dependent inpatients; and (f) schizophrenic inpatients. Veritable versus suspect grouping among disability claimants was determined by examining MMPI-2F-K dissimulation index scores. The results indicated that the suspect group produced more errors on the MENT than the credible groups or the hospitalized patient groups (p < .0001). Clinical decision rules were used to evaluate the relative effectiveness of the MENT to identify malingering in the claimant groups. The overall efficiency or hit rate on the MENT was 95.6%. JF - Journal of Personality Assessment AU - Morel, K R AD - National Institute of Mental Health, Neuropsychiatry Branch, Neuroscience Center at St. Elizabeth's Hospital, 2700 Martin Luther King Jr. Avenue, SE, Washington, DC 20032, USA Y1 - 1998/04// PY - 1998 DA - Apr 1998 SP - 299 EP - 314 VL - 70 IS - 2 SN - 0022-3891, 0022-3891 KW - mental disorders KW - post traumatic stress disorder KW - trauma KW - Health & Safety Science Abstracts KW - Psychology KW - Stress KW - Military KW - Occupational health KW - H 11000:Diseases/Injuries/Trauma KW - H 1000:Occupational Safety and Health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16548564?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthsafetyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Personality+Assessment&rft.atitle=Development+and+preliminary+validation+of+a+forced-choice+test+of+response+bias+for+posttraumatic+stress+disorder&rft.au=Morel%2C+K+R&rft.aulast=Morel&rft.aufirst=K&rft.date=1998-04-01&rft.volume=70&rft.issue=2&rft.spage=299&rft.isbn=&rft.btitle=&rft.title=Journal+of+Personality+Assessment&rft.issn=00223891&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Occupational health; Psychology; Stress; Military ER - TY - JOUR T1 - Oligopeptide permease in Borrelia burgdorferi: Putative peptide-binding components encoded by both chromosomal and plasmid loci AN - 16519342; 4330612 AB - To elucidate the importance of oligopeptide permease for Borrelia burgdorferi, the agent of Lyme disease, a chromosomal locus in B. burgdorferi that encodes homologues of all five subunits of oligopeptide permease has been identified and characterized. B. burgdorferi has multiple copies of the gene encoding the peptide-binding component, OppA; three reside at the chromosomal locus and two are on plasmids. Northern analyses indicate that each oppA gene is independently transcribed, although the three chromosomal oppA genes are also expressed as bi- and tri-cistronic messages. Induction of one of the plasmid-encoded oppA genes was observed following an increase in temperature, which appears to be an important cue for adaptive responses in vivo. The deduced amino acid sequences suggest that all five borrelial OppA homologues are lipoproteins, but the protease-resistance of at least one of them in intact bacteria is inconsistent with outer-surface localization. Insertional inactivation of a plasmid-encoded oppA gene demonstrates that it is not essential for growth in culture. JF - Microbiology AU - Bono, J L AU - Tilly, K AU - Stevenson, B AU - Hogan, D AU - Rosa, P AD - Laboratory of Microbial Structure and Function, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, 903 South Fourth Street, Hamilton, MT 59840, USA, patricia_rosa@nih.gov Y1 - 1998/04// PY - 1998 DA - Apr 1998 SP - 1033 EP - 1044 VL - 144 IS - 4 SN - 1350-0872, 1350-0872 KW - Lyme disease KW - oligopeptide permease KW - oppA gene KW - Biochemistry Abstracts 2: Nucleic Acids; Genetics Abstracts; Microbiology Abstracts B: Bacteriology; Microbiology Abstracts A: Industrial & Applied Microbiology KW - N 14640:Structure & sequence KW - A 01006:Enzymes & cofactors KW - G 07320:Bacterial genetics KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16519342?accountid=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=Microbiology&rft.atitle=Oligopeptide+permease+in+Borrelia+burgdorferi%3A+Putative+peptide-binding+components+encoded+by+both+chromosomal+and+plasmid+loci&rft.au=Bono%2C+J+L%3BTilly%2C+K%3BStevenson%2C+B%3BHogan%2C+D%3BRosa%2C+P&rft.aulast=Bono&rft.aufirst=J&rft.date=1998-04-01&rft.volume=144&rft.issue=4&rft.spage=1033&rft.isbn=&rft.btitle=&rft.title=Microbiology&rft.issn=13500872&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Engineering trimeric fibrous proteins based on bacteriophage T4 adhesins AN - 16517588; 4342206 AB - The adsorption specificity of bacteriophage T4 is determined by genes 12 and 37, encoding the short tail-fibers (STF) and the distal part of the long tail-fibers (LTF), respectively. Both are trimeric proteins with rod domains made up of similar tandem quasi-repeats, similar to 40 amino acids long. Their assembly requires the viral chaperones gp57A and gp38. Here we report that fusing fragments of gp12 and gp37 to another trimeric T4 fibrous protein, fibritin, facilitates correct assembly, thereby by-passing the chaperone requirement. Fibritin is an alpha -helical coiled coil protein whose C-terminal part (fibritin E, comprising the last 120 residues) has recently been solved to atomic resolution. Gp12 fragments of 109 and 70 amino acids, corresponding to three and two quasi-repeats respectively, were fused to the C-terminus of fibritin E. A similar chimera was designed for the last 63 residues of gp37, which contain four copies of the pentapeptide Gly-X-His-X-His and assume a narrow rigid structure in the LTF distal tip. Expressed from plasmids, all three chimeras form soluble trimers that are resistant to dissociation by SDS and digestion by trypsin, indicative of correct folding and oligomerization. JF - Protein Engineering AU - Miroshnikov, KA AU - Marusich, E I AU - Cerritelli, ME AU - Cheng, N AU - Hyde, C C AU - Steven, A C AU - Mesyanzhinov, V V AD - Laboratory of Structural Biology Research, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892-2717, USA, alasdair_steven@nih.gov Y1 - 1998/04// PY - 1998 DA - Apr 1998 SP - 329 EP - 332 VL - 11 IS - 4 SN - 0269-2139, 0269-2139 KW - Fibritin KW - Gene 12 KW - Gene 37 KW - Glycoprotein gp12 KW - Glycoprotein gp37 KW - Glycoprotein gp38 KW - Glycoprotein gp57A KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Virology & AIDS Abstracts KW - V 22032:Viral proteins KW - A 01114:Viruses UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16517588?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologya&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Protein+Engineering&rft.atitle=Engineering+trimeric+fibrous+proteins+based+on+bacteriophage+T4+adhesins&rft.au=Miroshnikov%2C+KA%3BMarusich%2C+E+I%3BCerritelli%2C+ME%3BCheng%2C+N%3BHyde%2C+C+C%3BSteven%2C+A+C%3BMesyanzhinov%2C+V+V&rft.aulast=Miroshnikov&rft.aufirst=KA&rft.date=1998-04-01&rft.volume=11&rft.issue=4&rft.spage=329&rft.isbn=&rft.btitle=&rft.title=Protein+Engineering&rft.issn=02692139&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Burkholderia pseudomallei infection in a Puerto Rican patient with chronic granulomatous disease: Case report and review of occurrences in the Americas AN - 16487443; 4367653 AB - Burkholderia species, notably Burkholderia cepacia and Burkholderia gladioli, are important pathogens in patients with chronic granulomatous disease (CGD). Burkholderia pseudomallei, the causative agent of melioidosis, is endemic in Southeast Asia and northern Australia but is a rare pathogen in other parts of the world. We describe the occurrence of B. pseudomallei infection in a Puerto Rican patient with CGD. This is one of only a small number of documented cases of melioidosis autochthonous to the Americas and is the first reported case of B. pseudomallei infection in a CGD patient from the Americas. We conclude that B. pseudomallei, like B. cepacia and B. gladioli, should be considered a potential pathogen in patients with CGD and that melioidosis should be considered in the differential diagnosis for ill residents of or travelers to Puerto Rico. JF - Clinical Infectious Diseases AU - Dorman, SE AU - Gill, V J AU - Gallin, JI AU - Holland, S M AD - National Institutes of Health, Building 10, Room 11N103, 10 Center Drive, MSC 1886, Bethesda, MD 20892-1886, USA Y1 - 1998/04// PY - 1998 DA - Apr 1998 SP - 889 EP - 894 VL - 26 IS - 4 SN - 1058-4838, 1058-4838 KW - Puerto Rico KW - chronic granulomatous disease KW - man KW - Microbiology Abstracts B: Bacteriology KW - J 02855:Human Bacteriology: Others UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16487443?accountid=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=Clinical+Infectious+Diseases&rft.atitle=Burkholderia+pseudomallei+infection+in+a+Puerto+Rican+patient+with+chronic+granulomatous+disease%3A+Case+report+and+review+of+occurrences+in+the+Americas&rft.au=Dorman%2C+SE%3BGill%2C+V+J%3BGallin%2C+JI%3BHolland%2C+S+M&rft.aulast=Dorman&rft.aufirst=SE&rft.date=1998-04-01&rft.volume=26&rft.issue=4&rft.spage=889&rft.isbn=&rft.btitle=&rft.title=Clinical+Infectious+Diseases&rft.issn=10584838&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Differential immune responses to staphylococcal enterotoxin B mutations in a hydrophobic loop dominating the interface with major histocompatibility complex class II receptors AN - 16480072; 4355559 AB - Bacterial superantigens, such as staphylococcal enterotoxin B (SEB), can trigger acute pathologic effects in humans. A hydrophobic loop on the surface of SEB and other bacterial superantigens, centered around a conserved leucine (L45) residue, is essential for binding to class II major histocompatibility complex molecules. Single residue changes of wild type SEB, designated Q43P, F44P, or L45R, resulted in nonlethal proteins at a dose equivalent to 30 murine LD sub(50) of SEB. Relative to SEB, the mutant proteins did not elevate serum concentrations of proinflammatory cytokines in mice and caused minimal proliferation of human lymphocytes. Anti-SEB titers of mice immunized with Q43P, F44P, L45R, or SEB were similar and protected 77%-100% of animals against a lethal SEB challenge. Levels of toxin-specific IgG1, IgG2a, IgG2b, and IgG3 in mice immunized with SEB, Q43P, or F44P were equivalent, but animals immunized with L45R had significantly elevated levels of IgG2a and IgG2b. Vaccines against staphylococcal superantigens should focus on this critical leucine residue. JF - Journal of Infectious Diseases AU - Woody, MA AU - Krakauer, T AU - Ulrich, R G AU - Stiles, B G AD - Laboratory of Leukocyte Biology, National Cancer Institute - Frederick Cancer Research and Development Center, Bldg. 567, Rm. 210, Frederick, MD 21702-1201, USA, mawoody@mail.ncifcrf.gov Y1 - 1998/04// PY - 1998 DA - Apr 1998 SP - 1013 EP - 1012 VL - 177 IS - 4 SN - 0022-1899, 0022-1899 KW - Staphylococcus KW - class II molecule receptors KW - class II molecules receptors KW - enterotoxin B KW - mice KW - receptors KW - Toxicology Abstracts; Microbiology Abstracts B: Bacteriology; Immunology Abstracts KW - X 24171:Microbial KW - F 06801:Bacteria KW - J 02833:Immune response and immune mechanisms UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16480072?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Infectious+Diseases&rft.atitle=Differential+immune+responses+to+staphylococcal+enterotoxin+B+mutations+in+a+hydrophobic+loop+dominating+the+interface+with+major+histocompatibility+complex+class+II+receptors&rft.au=Woody%2C+MA%3BKrakauer%2C+T%3BUlrich%2C+R+G%3BStiles%2C+B+G&rft.aulast=Woody&rft.aufirst=MA&rft.date=1998-04-01&rft.volume=177&rft.issue=4&rft.spage=1013&rft.isbn=&rft.btitle=&rft.title=Journal+of+Infectious+Diseases&rft.issn=00221899&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Genomics: Re-evaluation of translation machinery evolution AN - 16455894; 4370512 AB - Experiments based on genome sequence analysis have revealed unexpected complexity in the evolution of the translation apparatus, including concerted evolution of Gln-tRNA synthetase and Glu-tRNA super(Gln) amidotransferase, and a novel, class I Lys-tRNA synthetase shared by archaea and spirochaetes. JF - Current Biology AU - Koonin, E V AU - Aravind, L AD - National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA Y1 - 1998/04// PY - 1998 DA - Apr 1998 SP - R266 EP - R269 VL - 8 IS - 8 SN - 0960-9822, 0960-9822 KW - Spirochaetes KW - Spirochetes KW - evolutionary genetics KW - glutamine-tRNA ligase KW - reviews KW - tRNA Lys KW - translation KW - Microbiology Abstracts B: Bacteriology; Genetics Abstracts KW - G 07320:Bacterial genetics KW - J 02740:Genetics and evolution KW - G 07260:Taxonomy, systematics and evolutionary genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16455894?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+Biology&rft.atitle=Genomics%3A+Re-evaluation+of+translation+machinery+evolution&rft.au=Koonin%2C+E+V%3BAravind%2C+L&rft.aulast=Koonin&rft.aufirst=E&rft.date=1998-04-01&rft.volume=8&rft.issue=8&rft.spage=R266&rft.isbn=&rft.btitle=&rft.title=Current+Biology&rft.issn=09609822&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Biology and potential strategies for the treatment of G sub(M2) gangliosidoses AN - 16439887; 4342767 AB - The G sub(M2) gangliosidoses are a group of heritable neurodegenerative disorders caused by excessive accumulation of the ganglioside G sub(M2) owing to deficiency in beta -hexosaminidase activity. Tay-Sachs and Sandhoff diseases have similar clinical phenotypes resulting from a deficiency in human hexosaminidase alpha and beta subunits, respectively. The lack of treatment for G sub(M2) gangliosidoses stimulated interest in developing animal models to understand the molecular mechanisms underlying the various forms of this disease and to test new potential therapies. In this review, we discuss the molecular biology of G sub(M2) gangliosidoses and the different strategies that have been tested in animal models for the treatment of this genetic disorder, including gene transfer and cell engraftment of neural stem cells engineered to express the hexosaminidase isoenzymes. JF - Molecular Medicine Today AU - Chavany, C AU - Jendoubi, M AD - Genetics and Molecular Immunology Section, LI, Bldg 9, Room 1W101, National Institutes of Health, 9 Memorial Drive, Bethesda, MD 20892, USA Y1 - 1998/04// PY - 1998 DA - Apr 1998 SP - 158 EP - 165 VL - 4 IS - 4 SN - 1357-4310, 1357-4310 KW - ganglioside GM2 KW - gangliosidosis KW - reviews KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - W 30965:Miscellaneous, Reviews KW - W3 33000:General topics and reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16439887?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+Medicine+Today&rft.atitle=Biology+and+potential+strategies+for+the+treatment+of+G+sub%28M2%29+gangliosidoses&rft.au=Chavany%2C+C%3BJendoubi%2C+M&rft.aulast=Chavany&rft.aufirst=C&rft.date=1998-04-01&rft.volume=4&rft.issue=4&rft.spage=158&rft.isbn=&rft.btitle=&rft.title=Molecular+Medicine+Today&rft.issn=13574310&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Cooperative breeding and monogamy in prairie voles: influence of the sire and geographical variation AN - 16424442; 4331107 AB - Mammalian monogamy is characterized by pair bonding and a relative absence of sexual dimorphism in body size. Alloparental behaviour is a characteristic of mammalian cooperative breeding systems. Studies of prairie voles, Microtus ochrogaster, from stock captured in a resource-abundant habitat in Illinois have supported the assumption that this species is a monogamous, cooperative breeder, while other studies of prairie voles from a more arid habitat in Kansas have called this assumption into question. We hypothesized that reported differences between these populations represented true intraspecific variation. Patterns of sexual dimorphism in body size, partner preferences and parental contact behaviour were compared in prairie voles from stocks originating in Illinois or Kansas. Both Illinois and Kansas voles showed a strong preference for a familiar partner, which is suggestive of monogamy. Sexual dimorphism in body size was observed in Kansas, but not Illinois voles. Illinois voles displayed significantly higher levels of parental contact behaviour than did voles from Kansas. When animals from Illinois and Kansas were crossed, the expression of parental contact behaviour of the 'hybrid' offspring followed the pattern seen in the population of origin of the sire. Removal of the sire prior to the birth of the litter increased alloparenting in Kansas voles, but removal of the sire was associated with lower levels of alloparenting in Illinois voles. Thus, some traits associated with the social system may show intraspecific variation and can be influenced by the presence or absence of the sire during rearing. JF - Animal Behaviour AU - Roberts, R L AU - Williams, J R AU - Wang, A K AU - Carter, C S AD - Laboratory of Comparative Ethology, National Institute of Child Health and Human Development, NIH Animal Center, P.O. Box 529, Poolesville, MD 20837, USA, robertl@lce.nichd.nih.gov Y1 - 1998/04// PY - 1998 DA - Apr 1998 SP - 1131 EP - 1140 VL - 55 IS - 4 SN - 0003-3472, 0003-3472 KW - Prairie vole KW - USA, Illinois KW - USA, Kansas KW - Ecology Abstracts; Animal Behavior Abstracts KW - Y 25427:Mammals (excluding primates) KW - D 04672:Mammals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16424442?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aecology&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Animal+Behaviour&rft.atitle=Cooperative+breeding+and+monogamy+in+prairie+voles%3A+influence+of+the+sire+and+geographical+variation&rft.au=Roberts%2C+R+L%3BWilliams%2C+J+R%3BWang%2C+A+K%3BCarter%2C+C+S&rft.aulast=Roberts&rft.aufirst=R&rft.date=1998-04-01&rft.volume=55&rft.issue=4&rft.spage=1131&rft.isbn=&rft.btitle=&rft.title=Animal+Behaviour&rft.issn=00033472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Isobutyraldehyde administered by inhalation (whole body exposure) for up to thirteen weeks or two years was a respiratory tract toxicant but was not carcinogenic in F344/N Rats and B6C3F sub(1) mice AN - 16424347; 4312175 AB - Isobutyraldehyde (a chemical structurally related to formaldehyde and used as a flavoring agent) was studied for toxicity and carcinogenicity by exposing male and female F344/N rats and B6C3F sub(1) mice. Animals were exposed to isobutyraldehyde vapors 6 h per day, 5 days per week for up to 13 weeks or 2 years. In the 13-week studies, groups of 10 male and 10 female F344/N rats and B6C3F sub(1) mice were exposed to concentrations of 0, 500, 1000, 2000, 4000, or 8000 ppm. Chemical-related body weight depression and deaths occurred in rats and mice exposed to 4000 and 8000 ppm. Necrosis of the epithelium accompanied with acute inflammatory reaction was observed in the nasal turbinate, larynx, and trachea of rats exposed to 8000 ppm. Exposure of rats to 4000 ppm resulted in metaplasia of the nasal respiratory epithelium, inflammation, degeneration of the olfactory epithelium, and osteodystrophy of the nasal turbinate bone. In the 13-week mouse study, exposure to 8000 ppm or 4000 ppm resulted in necrosis of the epithelium lining of the nasal turbinates. Osteodystrophy of the nasal turbinate bone and squamous metaplasia of the nasal respiratory epithelium were noted in mice exposed 4000 ppm. Degeneration of the olfactory epithelium was noted in males exposed 2000 ppm and in females exposed to 4000 ppm. In the 2-year studies, groups of 50 male and 50 male F344/N rats and B6C3F1 were exposed to concentrations isobutyraldehyde vapors of 0, 500, 1000, or 2000 ppm 6 h per day, 5 days per week. There were no differences in survival rates or mean body weights between exposed groups and control rats. Survival of male mice exposed to 2000 ppm and mean body weights of female mice exposed to 1000 or 2000 ppm were lower than those of the controls. No increase in neoplasm incidence was observed in rats and mice in the 2-year studies that could be attributed to isobutyraldehyde exposure. Chemical-related nonneoplastic lesions were limited to the nose of rats and mice. They included squamous metaplasia of the respiratory epithelium (rats), suppurative inflammation (rats), and olfactory epithelial degeneration (rats and mice) at 1000 and 2000 ppm. JF - Toxicological Sciences AU - Abdo, K M AU - Haseman, J K AU - Nyska, A AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA Y1 - 1998/04// PY - 1998 DA - Apr 1998 SP - 136 EP - 151 VL - 42 IS - 2 SN - 1096-6080, 1096-6080 KW - isobutyraldehyde KW - mice KW - rats KW - Toxicology Abstracts KW - X 24120:Food, additives & contaminants UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16424347?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+Sciences&rft.atitle=Isobutyraldehyde+administered+by+inhalation+%28whole+body+exposure%29+for+up+to+thirteen+weeks+or+two+years+was+a+respiratory+tract+toxicant+but+was+not+carcinogenic+in+F344%2FN+Rats+and+B6C3F+sub%281%29+mice&rft.au=Abdo%2C+K+M%3BHaseman%2C+J+K%3BNyska%2C+A&rft.aulast=Abdo&rft.aufirst=K&rft.date=1998-04-01&rft.volume=42&rft.issue=2&rft.spage=136&rft.isbn=&rft.btitle=&rft.title=Toxicological+Sciences&rft.issn=10966080&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Metabolism and disposition of phenolphthalein in male and female F344 rats and B6C3F1 mice AN - 16424297; 4312168 AB - A recent 2-year carcinogenicity/toxicology study determined that phenolphthalein (PHTH) is a multisite carcinogen in both mice and rats at all doses evaluated. In response to this finding the metabolism and disposition of PHTH has been evaluated in both F344 rats and B6C3F1 mice at a single oral dose of 800 mg/kg. This dose fell within the range previously found to be carcinogenic in rats and mice. Studies were also performed using 1 and 50 mg/kg doses. At 800 mg/kg recovery of [ super(14)C]PHTH after 72 h was near 100% in females but closer to 75% in males. Radioactivity was primarily recovered in the feces in rats (>90%), while mice excreted 30-40% of administered activity in the urine. There was no significant retention of radioactivity in tissues by 72 h and no significant accumulation of radioactivity in any tissue at any time point. Covalent binding to protein in target tissues, bone marrow and ovary, was at or less than the pmol/mg protein range. The major metabolite was PHTH glucuronide. Three minor metabolites were detected. A sulfate conjugate and a hydroxylated metabolite were identified by comparison of retention times and super(1)H NMR and/or mass spectra with synthetic standards. A diglucuronide conjugate was tentatively identified. Biliary elimination was extensive in rats (35% of dose within 6 h); the only product detected in bile was phenolphthalein glucuronide. JF - Toxicological Sciences AU - Griffin, R J AU - Godfrey, V B AU - Burka, L T AD - National Institute of Environmental Health Sciences, National Toxicology Program, Research Triangle Park, NC 27709, USA Y1 - 1998/04// PY - 1998 DA - Apr 1998 SP - 73 EP - 81 VL - 42 IS - 2 SN - 1096-6080, 1096-6080 KW - metabolism KW - mice KW - phenophthalein KW - rats KW - Toxicology Abstracts KW - X 24240:Miscellaneous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16424297?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+Sciences&rft.atitle=Metabolism+and+disposition+of+phenolphthalein+in+male+and+female+F344+rats+and+B6C3F1+mice&rft.au=Griffin%2C+R+J%3BGodfrey%2C+V+B%3BBurka%2C+L+T&rft.aulast=Griffin&rft.aufirst=R&rft.date=1998-04-01&rft.volume=42&rft.issue=2&rft.spage=73&rft.isbn=&rft.btitle=&rft.title=Toxicological+Sciences&rft.issn=10966080&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Antimutator mutants in bacteriophage T4 and Escherichia coli AN - 16419042; 4320339 AB - Antimutators are mutant strains that have reduced mutation rates compared to the corresponding wild-type strain. Their existence, along with mutator mutants that have higher mutation rates compared to the wild-type strain, are powerful evidence that mutation rates are genetically controlled. Compared to mutator mutants, antimutators have a very distinguishing property. Because they prevent normally occurring mutations, they, uniquely, are capable of providing insight into the mechanisms of spontaneous mutations. In this review, antimutator mutants are discussed in bacteriophage T4 and the bacterium Escherichia coli, with regard to their properties, possible mechanisms, and implications for the sources of spontaneous mutations in these two organisms. JF - Genetics AU - Schaaper, R M AD - Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, 111 TW Alexander Dr., Box 12233, Research Triangle Park, NC 27709, USA Y1 - 1998/04// PY - 1998 DA - Apr 1998 SP - 1579 EP - 1585 VL - 148 IS - 4 SN - 0016-6731, 0016-6731 KW - antimutators KW - mutants KW - spontaneous mutation KW - Microbiology Abstracts B: Bacteriology; Virology & AIDS Abstracts; Genetics Abstracts KW - V 22050:Viral genetics including virus reactivation KW - G 07320:Bacterial genetics KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16419042?accountid=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=Genetics&rft.atitle=Antimutator+mutants+in+bacteriophage+T4+and+Escherichia+coli&rft.au=Schaaper%2C+R+M&rft.aulast=Schaaper&rft.aufirst=R&rft.date=1998-04-01&rft.volume=148&rft.issue=4&rft.spage=1579&rft.isbn=&rft.btitle=&rft.title=Genetics&rft.issn=00166731&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - CRE-Palindrome Oligonucleotide as a Transcription Factor Decoy and an Inhibitor of Tumor Growth AN - 16416829; 4310398 AB - A major focus of cellular and molecular research has been to develop means to regulate gene expression in an effort to treat and cure a variety of diseases and abnormal physiologic conditions. The importance of such research has dramatically increased as the Human Genomic Project continues to identify genes at an accelerated pace. Currently, several general methods have been developed to regulate and control gene expression at either the transcriptional or translational steps. This article describes oligonucleotides with high affinity for a target transcription factor that can be introduced into cells as decoy cis-elements to bind the factor and alter gene expression. Specifically, nucleic acid molecules that compete with cAMP response element (CRE) enhancers for binding transcription factors are described. These nucleic acid molecules were shown to function in vitro and in vivo as inhibitors of cancer cell growth, without adversely affecting the growth of noncancerous cells. The CRE-decoy oligonucleotides provide powerful new means of combating cancers by regulating the expression of cAMP-responsive genes. JF - Antisense and Nucleic Acid Drug Development AU - Cho-Chung, Yoon S AD - National Cancer Institute, Building 10, Room 5B05, Bethesda, MD 20892-1750, USA Y1 - 1998/04// PY - 1998 DA - Apr 1998 SP - 167 EP - 170 VL - 8 IS - 2 SN - 1087-2906, 1087-2906 KW - Human Genome Project KW - cAMP response elements KW - cancer KW - cyclic AMP response element KW - gene regulation KW - man KW - oligonucleotides KW - transcription factors KW - Biotechnology and Bioengineering Abstracts; Biochemistry Abstracts 2: Nucleic Acids; Medical and Pharmaceutical Biotechnology Abstracts KW - W3 33385:DNA/RNA KW - N 14250:Biological properties KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16416829?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antisense+and+Nucleic+Acid+Drug+Development&rft.atitle=CRE-Palindrome+Oligonucleotide+as+a+Transcription+Factor+Decoy+and+an+Inhibitor+of+Tumor+Growth&rft.au=Cho-Chung%2C+Yoon+S&rft.aulast=Cho-Chung&rft.aufirst=Yoon&rft.date=1998-04-01&rft.volume=8&rft.issue=2&rft.spage=167&rft.isbn=&rft.btitle=&rft.title=Antisense+and+Nucleic+Acid+Drug+Development&rft.issn=10872906&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Characterization of the bvgR locus of Bordetella pertussis AN - 16416092; 4318178 AB - Bordetella pertussis, the causative agent of whooping cough, produces a wide array of factors that are associated with its ability to cause disease. The expression and regulation of these virulence factors is dependent upon the bvg locus (originally designated the vir locus), which encodes two proteins: BvgA, a 23-kDa cytoplasmic protein, and BvgS, a 135-kDa transmembrane protein. It is proposed that BvgS responds to environmental signals and interacts with BvgA, a transcriptional regulator which upon modification by BvgS binds to specific promoters and activates transcription. An additional class of genes is repressed by the bvg locus. Expression of this class, the bvg-repressed genes (vrgs [for vir-repressed genes]), is reduced under conditions in which expression of the aforementioned bvg-activated virulence factors is maximal; this repression is dependent upon the presence of an intact bvgAS locus. We have previously identified a locus required for regulation of all of the known bvg-repressed genes in B. pertussis. This locus, designated bvgR, maps to a location immediately downstream of bvgAS. We have undertaken deletion and complementation studies, as well as sequence analysis, in order to identify the bvgR open reading frame and identify the cis-acting sequences required for regulated expression of bvgR. Studies utilizing transcriptional fusions of bvgR to the gene encoding alkaline phosphatase have demonstrated that bvgR is activated at the level of transcription and that this activation is dependent upon an intact bvgAS locus. JF - Journal of Bacteriology AU - Merkel, T J AU - Barros, C AU - Stibitz, S AD - OIIB/NIDR/NIH, Building 30, Rm. 303, 30 Convent Dr. MSC 4350, Bethesda, MD 20892-4350, USA, merkel@yoda.nidr.nih.gov Y1 - 1998/04// PY - 1998 DA - Apr 1998 SP - 1682 EP - 1690 VL - 180 IS - 7 KW - BvgA protein KW - BvgS protein KW - bvgR locus KW - nucleotide sequence KW - vir gene KW - virulence factors KW - Genetics Abstracts; Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - N 14640:Structure & sequence KW - G 07320:Bacterial genetics KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16416092?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Bacteriology&rft.atitle=Characterization+of+the+bvgR+locus+of+Bordetella+pertussis&rft.au=Merkel%2C+T+J%3BBarros%2C+C%3BStibitz%2C+S&rft.aulast=Merkel&rft.aufirst=T&rft.date=1998-04-01&rft.volume=180&rft.issue=7&rft.spage=1682&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - The effect of chlorine substitution on the dermal absorption of polychlorinated biphenyls AN - 16412378; 4325845 AB - The fate of selected mono-, di-, tetra-, and hexachlorobiphenyls was investigated following single dermal administration (0.4 mg/kg) to determine the effects of chlorine substitution on the dermal absorption and disposition of polychlorinated biphenyls (PCBs). Single dermal doses of super(14)C-labeled mono-, di-, tetra-, and hexachlorobiphenyls were administered to 1-cm super(2) areas on the backs of F-344 male rats. Unabsorbed radioactivity was removed from the dose site either at euthanasia or 48 h postdose. Distribution of radioactivity in the dose site and selected tissues was determined by serial sacrifice at time points up to 2 weeks. Dermal penetration varied inversely with degree of chlorination and at 48 h ranged from ca. 100% for monochlorobiphenyl to ca. 30% for the hexachlorobiphenyl. Penetration rate constants correlated well with log K sub(ow). PCBs were retained in the epidermis for up to 2 weeks postdose. The data from these studies suggest that systemic absorption of PCBs involves a combination of sequential processes including penetration across the stratum corneum, possibly metabolism in the epidermis and/or dermis, adsorption to proteins, and finally absorption into the systemic circulation. The skin favors the rapid absorption of less chlorinated PCBs, but the relatively rapid metabolism and elimination of these compounds would result in lower body burdens. More highly chlorinated PCBs penetrate less rapidly but remain in the site of exposure and slowly enter the systemic circulation. The dermal absorption of a commercial PCB mixture was modeled, and the results suggest that the net result of the differences in absorbance rates would be a greater body burden of higher chlorinated PCBs relative to those that have a lower chlorine content. JF - Toxicology and Applied Pharmacology AU - Garner, CE AU - Matthews, H B AD - Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, P.O. Box 12233, Research Triangle Park, NC 27709, USA Y1 - 1998/04// PY - 1998 DA - Apr 1998 SP - 150 EP - 158 VL - 149 IS - 2 SN - 0041-008X, 0041-008X KW - PCB KW - absorbance KW - chlorine KW - rats KW - Toxicology Abstracts KW - X 24153:Metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16412378?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+and+Applied+Pharmacology&rft.atitle=The+effect+of+chlorine+substitution+on+the+dermal+absorption+of+polychlorinated+biphenyls&rft.au=Garner%2C+CE%3BMatthews%2C+H+B&rft.aulast=Garner&rft.aufirst=CE&rft.date=1998-04-01&rft.volume=149&rft.issue=2&rft.spage=150&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 revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Non-Antisense Oligonucleotide Approaches for Experimental Treatment of Glioblastoma AN - 16410087; 4310400 AB - Malignant gliomas constitute 40%-50% of all brain tumors, which in themselves cause approximately 2% of all cancer deaths. Astrocytomas, the most common form of brain tumor, are classified by degree of malignancy into three groups: astrocytoma, anaplastic astrocytoma, and glioblastoma multiforme. Glioblastoma multiforme is the most malignant and has an extremely poor prognosis given current available treatments. Cells from such tumors aggressively infiltrate normal tissue, making total surgical removal of tumor impossible, and median survival time from diagnosis is less than 2 years. Thus, development of experimental therapy for glioblastoma, perhaps in combination with more standard chemotherapy, irradiation, or surgery, is warranted. We are taking two approaches to the use of synthetic oligonucleotides in experimental therapy of these tumors. The first approach makes use of synthetic ribozymes delivered to the tumor by continuous infusion with microosmotic minipumps. These studies are being carried out in collaboration with Nigel Davis and Brian Sproat of Innovir Ltd. The experimental model consists of U87MG human glioblastoma cells directly implanted into the striatum of adult athymic rats. Concurrent with tumor inoculation, an indwelling cannula is set in place that allows access to the striatum at or near the site of tumor implantation. Following a period of recovery (usually 24 hours), oligonucleotides are infused continuously for 2 weeks. Animal survival is monitored thereafter. JF - Antisense and Nucleic Acid Drug Development AU - Neckers, L M AU - Kanekal, M AU - Connell, Y AD - Medicine Branch, NCI, NIH, Key West Facility, 9610 Center Drive, Suite 300, Rockville, MD 20850, USA Y1 - 1998/04// PY - 1998 DA - Apr 1998 SP - 177 EP - 179 VL - 8 IS - 2 SN - 1087-2906, 1087-2906 KW - brain carcinoma KW - gioblastoma KW - oigonucleotides KW - oligonucleotides KW - rats KW - Biotechnology and Bioengineering Abstracts; Biochemistry Abstracts 2: Nucleic Acids; Medical and Pharmaceutical Biotechnology Abstracts KW - W3 33385:DNA/RNA KW - N 14250:Biological properties KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16410087?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antisense+and+Nucleic+Acid+Drug+Development&rft.atitle=Non-Antisense+Oligonucleotide+Approaches+for+Experimental+Treatment+of+Glioblastoma&rft.au=Neckers%2C+L+M%3BKanekal%2C+M%3BConnell%2C+Y&rft.aulast=Neckers&rft.aufirst=L&rft.date=1998-04-01&rft.volume=8&rft.issue=2&rft.spage=177&rft.isbn=&rft.btitle=&rft.title=Antisense+and+Nucleic+Acid+Drug+Development&rft.issn=10872906&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Liposomal formulation of a self lymphoma antigen induces potent protective antitumor immunity AN - 16277753; 4294232 AB - We developed a liposome carrier for a model nonimmunogenic, self Ag. This carrier reproducibly converted lymphoma Ig into a potent tumor rejection Ag in mice. A single immunization induced protection against challenges representing 20 to 100 times the minimum lethal dose of parental tumor. This protective effect required minimal amounts of incorporated Ag and IL-2 and elicited specific Abs (compared with free Ag or liposomal control Ig which did not elicit any specific Abs); depletion experiments demonstrated a requirement for effector CD4 super(+) and CD8 super(+) T cells. Head-to-head comparisons, indicating superior potency and induction of specific T cell activation, distinguished liposomal from prototype, carrier-conjugated Ag. These results provide a strategy for formulating weak tumor or other clinically important Ags into vaccines. JF - Journal of Immunology AU - Kwak, L W AU - Pennington, R AU - Boni, L AU - Ochoa, A C AU - Robb, R J AU - Popescu, M C AD - National Cancer Institute, Frederick Cancer Research and Development Center, Bldg. 567, Rm. 205, Frederick, MD 21702, USA Y1 - 1998/04// PY - 1998 DA - Apr 1998 SP - 3637 EP - 3641 VL - 160 IS - 8 SN - 0022-1767, 0022-1767 KW - antigen (tumor-associated) KW - liposomes KW - lymphocytes T KW - lymphoma KW - mice KW - tumors KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - F 06818:Cancer immunotherapy KW - W3 33388:Drug delivery vehicles (liposomes, cochleates, microspheres) KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16277753?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Immunology&rft.atitle=Liposomal+formulation+of+a+self+lymphoma+antigen+induces+potent+protective+antitumor+immunity&rft.au=Kwak%2C+L+W%3BPennington%2C+R%3BBoni%2C+L%3BOchoa%2C+A+C%3BRobb%2C+R+J%3BPopescu%2C+M+C&rft.aulast=Kwak&rft.aufirst=L&rft.date=1998-04-01&rft.volume=160&rft.issue=8&rft.spage=3637&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immunology&rft.issn=00221767&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Locus coeruleus neurons from morphine-treated rats do not show opiate-withdrawal hyperactivity in vitro. AN - 79815154; 9555033 AB - In vitro studies have not consistently demonstrated naloxone-precipitated opiate-withdrawal hyperactivity of locus coeruleus neurons. The reason for this inconsistency may be because partial or complete withdrawal occurred during preparation of the locus coeruleus slice. The aim of the present study was to assay opiate withdrawal-related hyperactivity in neurons recorded from locus coeruleus slices while ensuring the maintenance of dependence until naloxone-precipitated withdrawal. Extracellular recordings were obtained from individual locus coeruleus neurons in slices from morphine-treated and drug-naive rats. Morphine 1 microM was present in all solutions during preparation and recording in slices from morphine-treated rats. The average firing rate of the drug-naive controls was 0.93 Hz (+/-0.04 Hz). Bath application of morphine (1 microM) almost completely suppressed firing in drug-naive controls (0.058 Hz, +/-0.04 Hz, n=12), whereas in solutions containing 1 microM morphine, the firing rate of cells from morphine-treated rats averaged 0.71 Hz (+/-0.05 Hz), indicating considerable, but incomplete tolerance. In the same slices, naloxone increased the average spontaneous firing of locus coeruleus cells to 0.96 Hz (+/-0. 04 Hz). Thus, naloxone did not produce withdrawal hyperactivity, but returned the cells from morphine-treated rats to control rates. We conclude that locus coeruleus cells in locus coeruleus slice preparations from morphine-treated rats did not demonstrate withdrawal-related hyperactivity even when dependence was maintained until naloxone-precipitated withdrawal. Thus, our results do not support a role for adaptations intrinsic to locus coeruleus neurons in withdrawal hyperexcitability, but instead imply the necessity of functional afferent activity. Copyright 1998 Elsevier Science B.V. JF - Brain research AU - Bell, J A AU - Grant, S J AD - Brain Imaging Section, Neuroscience Branch, Intramural Research Program, National Institute on Drug Abuse, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. Y1 - 1998/03/30/ PY - 1998 DA - 1998 Mar 30 SP - 237 EP - 244 VL - 788 IS - 1-2 SN - 0006-8993, 0006-8993 KW - Naloxone KW - 36B82AMQ7N KW - Morphine KW - 76I7G6D29C KW - Index Medicus KW - Rats KW - Naloxone -- pharmacology KW - Evoked Potentials -- drug effects KW - Animals KW - Rats, Sprague-Dawley KW - Basal Metabolism KW - Analysis of Variance KW - In Vitro Techniques KW - Locus Coeruleus -- drug effects KW - Substance Withdrawal Syndrome KW - Morphine -- adverse effects KW - Neurons -- drug effects KW - Locus Coeruleus -- cytology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79815154?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Locus+coeruleus+neurons+from+morphine-treated+rats+do+not+show+opiate-withdrawal+hyperactivity+in+vitro.&rft.au=Bell%2C+J+A%3BGrant%2C+S+J&rft.aulast=Bell&rft.aufirst=J&rft.date=1998-03-30&rft.volume=788&rft.issue=1-2&rft.spage=237&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 - 1998-07-23 N1 - Date created - 1998-07-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Comparative pharmacodynamics of CYP2B induction by DDT, DDE, and DDD in male rat liver and cultured rat hepatocytes. AN - 79781567; 9537282 AB - In this study the pharmacodynamics were characterized of rat hepatic cytochrome P-450 2B (CYP2B) induction by the pesticide DDT [1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane] and its metabolites DDE [1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene], which is bioretained, and DDD [1,1-dichloro-2,2-bis(p-chlorophenyl)ethane], which is metabolized further and therefore less prone to bioaccumulate. DDT, DDE, and DDD were each found to be pure phenobarbital-type cytochrome P-450 inducers in the male F344/NCr rat, causing induction of hepatic CYP2B and CYP3A, but not CYP1A. The ED50 values for CYP2B induction (benzyloxyresorufin O-dealkylation) by DDT, DDE, and DDD were, respectively, 103, 88, and > or = 620 ppm in diet (14 d of exposure). The efficacies (Emax values) for induction of benzyloxyresorufin O-dealkylation by DDT, DDE, and DDD were 24-, 22-, and > or = 1-fold, respectively, compared to control values. The potencies of the three congeners for CYP2B induction appeared also to be similar, with EC50 values (based on total serum DDT equivalents) of 1.5, 1.8, and > or = 0.51 microM, respectively. The EC50 values based on DDT equivalents in hepatic tissue were 15, 16, and > or = 5.9 micromol/kg liver tissue, respectively. In primary cultures of adult rat hepatocytes, DDT, DDE, and DDD each displayed ability to induce total cellular RNA coding for CYP2B (ED50 values of 0.98, 0.83, and > or = 2.7 microM, respectively). These results suggest that DDT, DDE, and DDD each possess a high degree of intrinsic CYP2B-inducing ability for rat liver, despite marked differences in bioretention among the congeners. JF - Journal of toxicology and environmental health. Part A AU - Nims, R W AU - Lubet, R A AU - Fox, S D AU - Jones, C R AU - Thomas, P E AU - Reddy, A B AU - Kocarek, T A AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland, USA. rnims@mabioservices.com Y1 - 1998/03/27/ PY - 1998 DA - 1998 Mar 27 SP - 455 EP - 477 VL - 53 IS - 6 SN - 1528-7394, 1528-7394 KW - Insecticides KW - 0 KW - Dichlorodiphenyl Dichloroethylene KW - 4M7FS82U08 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - DDT KW - CIW5S16655 KW - Mixed Function Oxygenases KW - EC 1.- KW - CYP3A protein, human KW - EC 1.14.14.1 KW - Cytochrome P-450 CYP1A1 KW - Cytochrome P-450 CYP2B1 KW - Cytochrome P-450 CYP3A KW - Dichlorodiphenyldichloroethane KW - V14159DF29 KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Mixed Function Oxygenases -- biosynthesis KW - Cells, Cultured KW - Enzyme Induction KW - Cytochrome P-450 Enzyme System -- biosynthesis KW - Male KW - Cytochrome P-450 CYP1A1 -- biosynthesis KW - Organ Size -- drug effects KW - Dichlorodiphenyldichloroethane -- pharmacology KW - Liver -- anatomy & histology KW - Cytochrome P-450 CYP2B1 -- biosynthesis KW - Liver -- enzymology KW - Liver -- drug effects KW - DDT -- pharmacology KW - Dichlorodiphenyl Dichloroethylene -- pharmacology KW - Insecticides -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79781567?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+toxicology+and+environmental+health.+Part+A&rft.atitle=Comparative+pharmacodynamics+of+CYP2B+induction+by+DDT%2C+DDE%2C+and+DDD+in+male+rat+liver+and+cultured+rat+hepatocytes.&rft.au=Nims%2C+R+W%3BLubet%2C+R+A%3BFox%2C+S+D%3BJones%2C+C+R%3BThomas%2C+P+E%3BReddy%2C+A+B%3BKocarek%2C+T+A&rft.aulast=Nims&rft.aufirst=R&rft.date=1998-03-27&rft.volume=53&rft.issue=6&rft.spage=455&rft.isbn=&rft.btitle=&rft.title=Journal+of+toxicology+and+environmental+health.+Part+A&rft.issn=15287394&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-04-30 N1 - Date created - 1998-04-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Breastfeeding, genetic, obstetric and other risk factors associated with mother-to-child transmission of HIV-1 in Sao Paulo State, Brazil AN - 16511347; 4326230 AB - Objectives: To evaluate the effect of maternal, obstetric, neonatal and post-natal factors on the risk of vertical transmission of HIV-1. Design: Multicentre retrospective cohort study. Setting: Obstetric and paediatric clinics in four cities in Sao Paulo State, Brazil. Main outcome: Child's HIV-1 infection status. Methods: Data were collected by standardized record abstraction and interview on 553 children born to women identified as HIV-1-infected before or at delivery. Paediatric infection was determined by immunoglobulin G anti-HIV-1 tests at age 18 months or by AIDS diagnosis at any age. Multivariate logistic regression was used to assess the effect of potential risk factors on vertical transmission of HIV-1. Results: HIV-1 infection status was determined for 434 children (follow-up rate of 78%); 69 were classified as HIV-1-infected [transmission risk, 16%; 95% confidence interval (CI), 13-20%]. In multivariate analysis, advanced maternal HIV-1 disease [odds ratio (OR), 4.5; 95% CI, 2.1-9.5], ever breastfed (OR, 2.2; 95% CI, 1.2-4.2), child's negative Rhesus blood group (OR, 2.5; 95% CI, 1.2-5.5), third trimester amniocentesis (OR, 4.1; 95% CI, 1.2-13.5) and black racial group (OR, 0.3; 95% CI, 0.1-0.9) were independently and significantly associated with mother-to-child transmission of HIV-1. Transmission was increased marginally with prematurity, more than 10 lifetime sexual partners and prolonged duration of membrane rupture. No association was found between child's HIV-1 infection and mode of delivery or serological evidence of syphilis during pregnancy. Conclusion: These findings support the importance of severity of maternal HIV-1 disease in the risk of vertical transmission of HIV-1, indicate measures to reduce transmission by avoiding amniocentesis and breastfeeding and suggest that race and Rhesus blood type may be markers for genetic susceptibility to infection. JF - AIDS AU - Tess, B H AU - Rodrigues, L C AU - Newell, M-L AU - Dunn, D T AU - Lago, TDG AD - Viral Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, 6130 Executive Blvd., EPN/434, Rockville, MD 20852, USA Y1 - 1998/03/26/ PY - 1998 DA - 1998 Mar 26 SP - 513 EP - 520 VL - 12 IS - 5 SN - 0269-9370, 0269-9370 KW - Brazil KW - Brazil, Sao Paulo KW - HIV-1 KW - breast feeding KW - disease transmission KW - man KW - parent-offspring interactions KW - Risk Abstracts; Virology & AIDS Abstracts KW - V 22006:AIDS: Other aspects KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16511347?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=AIDS&rft.atitle=Breastfeeding%2C+genetic%2C+obstetric+and+other+risk+factors+associated+with+mother-to-child+transmission+of+HIV-1+in+Sao+Paulo+State%2C+Brazil&rft.au=Tess%2C+B+H%3BRodrigues%2C+L+C%3BNewell%2C+M-L%3BDunn%2C+D+T%3BLago%2C+TDG&rft.aulast=Tess&rft.aufirst=B&rft.date=1998-03-26&rft.volume=12&rft.issue=5&rft.spage=513&rft.isbn=&rft.btitle=&rft.title=AIDS&rft.issn=02699370&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - In cortical cultures of trisomy 16 mouse brain the upregulated metallothionein-I/II fails to respond to H2O2 exposure or glutamate receptor stimulation. AN - 79764036; 9518655 AB - To assess whether a defective oxidative defense may contribute to Down's syndrome, we studied the regulation of the metallothionein(MT)-I/II isoforms in primary cultures of cerebral cortex from fetal trisomy 16 mice and their euploid littermates. Western blot analysis showed that MT-I/II was upregulated and the protein carbonyl content was higher in trisomy 16 compared with euploid cultures. Addition of N-acetyl-l-cysteine to the culture medium reduced the increment of MT-I/II in trisomy 16 cortical cells. In euploid, but not trisomic cortical cultures, kainic acid, trans-(+/-)-ACPD, or H2O2 exposure elicited a dose-dependent increase of the MT-I/II immunoblots. In trisomic cells, the MT-I/II immunoblot densities were not increased beyond their elevated basal levels. In contrast, 25 microM Pb induced MT-I/II, to a similar extent, in cortical cultures from euploid and trisomy 16 mice. This suggests that the antioxidant-but not the metal-response element of the MT-I/II promoter was altered by increased oxidative stress. Our data suggest that, in the trisomy 16 mouse, the effects of increased production of reactive oxygen species, due to the increased SOD-1, GluR5, or amyloid precursor protein gene dosage, is exacerbated by an insufficient or missing antioxidant response. Copyright 1998 Elsevier Science B.V. JF - Brain research AU - Scortegagna, M AU - Galdzicki, Z AU - Rapoport, S I AU - Hanbauer, I AD - Laboratory of Molecular Immunology, NHLBI, Bethesda, MD 20892, USA. Y1 - 1998/03/23/ PY - 1998 DA - 1998 Mar 23 SP - 292 EP - 298 VL - 787 IS - 2 SN - 0006-8993, 0006-8993 KW - Excitatory Amino Acid Agonists KW - 0 KW - Free Radical Scavengers KW - Oxidants KW - Receptors, Glutamate KW - Lead KW - 2P299V784P KW - Metallothionein KW - 9038-94-2 KW - Hydrogen Peroxide KW - BBX060AN9V KW - Acetylcysteine KW - WYQ7N0BPYC KW - Index Medicus KW - Animals KW - Astrocytes -- drug effects KW - Acetylcysteine -- pharmacology KW - Mice KW - Stimulation, Chemical KW - Oxidation-Reduction KW - Blotting, Western KW - Mice, Inbred C57BL KW - Lead -- pharmacology KW - Female KW - Free Radical Scavengers -- pharmacology KW - Male KW - Astrocytes -- metabolism KW - Up-Regulation -- physiology KW - Cerebral Cortex -- cytology KW - Metallothionein -- biosynthesis KW - Oxidants -- pharmacology KW - Receptors, Glutamate -- drug effects KW - Cerebral Cortex -- pathology KW - Hydrogen Peroxide -- pharmacology KW - Metallothionein -- drug effects KW - Trisomy -- pathology KW - Excitatory Amino Acid Agonists -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79764036?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=In+cortical+cultures+of+trisomy+16+mouse+brain+the+upregulated+metallothionein-I%2FII+fails+to+respond+to+H2O2+exposure+or+glutamate+receptor+stimulation.&rft.au=Scortegagna%2C+M%3BGaldzicki%2C+Z%3BRapoport%2C+S+I%3BHanbauer%2C+I&rft.aulast=Scortegagna&rft.aufirst=M&rft.date=1998-03-23&rft.volume=787&rft.issue=2&rft.spage=292&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 - 1998-07-10 N1 - Date created - 1998-07-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Visceral abdominal-fat accumulation associated with use of indinavir. AN - 79756655; 9525365 AB - After the addition of the protease inhibitor indinavir to combination drug regimens for HIV-1 infection, some patients have experienced an increase in abdominal girth with symptoms of abdominal fullness, distension, or bloating. We aimed to find out whether this collection of symptoms was associated with changes in abdominal fat and whether such changes were associated with indinavir use. Abdominal computed tomography was used in ten HIV-1-positive patients who had such abdominal symptoms to measure total adipose tissue (TAT) and visceral adipose tissue (VAT) at the umbilicus (L4 vertebral level). The VAT:TAT ratio in the ten cases was compared with that in ten HIV-1-infected patients who had been using indinavir without abdominal symptoms for at least 6 months and ten HIV-1-infected patients who were not using indinavir. The mean VAT:TAT ratios for the three groups-non-users, symptom-free indinavir users, and symptomatic indinavir users-were 0.40 (SD 0.15), 0.59 (0.18), and 0.70 (0.20), respectively (p=0.004). The VAT:TAT ratio correlated with duration of indinavir use (r=0.47, p=0.01). The mean areas of VAT for the three groups were 106 cm2 (SD 72), 141 cm2 (65) and 202 cm2 (93), respectively (p=0.03). The mean body-mass index of the groups was similar, and patients in the two indinavir groups did not gain a significant amount of weight after starting the drug. Serum triglyceride values increased after starting indinavir and correlated with VAT:TAT ratios. Our data suggest that some HIV-1-infected patients on indinavir treatment accumulate intra-abdominal fat that may cause abdominal symptoms. Recent evidence suggests that other HIV-1 protease inhibitors may be associated with changes in body-fat distribution. Larger studies of protease-inhibitor treatment are needed to investigate this association further and to investigate metabolic or endocrine mechanisms that may underlie this phenomenon. JF - Lancet (London, England) AU - Miller, K D AU - Jones, E AU - Yanovski, J A AU - Shankar, R AU - Feuerstein, I AU - Falloon, J AD - Department of Critical Care Medicine, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA. kmiller@atlas.niaid.nih.gov Y1 - 1998/03/21/ PY - 1998 DA - 1998 Mar 21 SP - 871 EP - 875 VL - 351 IS - 9106 SN - 0140-6736, 0140-6736 KW - Anti-HIV Agents KW - 0 KW - Protease Inhibitors KW - Indinavir KW - 5W6YA9PKKH KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Humans KW - Abdomen KW - Adult KW - Tomography, X-Ray Computed KW - HIV Infections -- pathology KW - HIV-1 KW - Radiography, Abdominal KW - Male KW - Protease Inhibitors -- adverse effects KW - Anti-HIV Agents -- adverse effects KW - Body Composition KW - Indinavir -- adverse effects KW - Adipose Tissue -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79756655?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Lancet+%28London%2C+England%29&rft.atitle=Visceral+abdominal-fat+accumulation+associated+with+use+of+indinavir.&rft.au=Miller%2C+K+D%3BJones%2C+E%3BYanovski%2C+J+A%3BShankar%2C+R%3BFeuerstein%2C+I%3BFalloon%2C+J&rft.aulast=Miller&rft.aufirst=K&rft.date=1998-03-21&rft.volume=351&rft.issue=9106&rft.spage=871&rft.isbn=&rft.btitle=&rft.title=Lancet+%28London%2C+England%29&rft.issn=01406736&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-04-10 N1 - Date created - 1998-04-10 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Lancet. 1998 Mar 21;351(9106):847-8 [9525355] Lancet. 1998 Jun 6;351(9117):1735-6 [9734915] Lancet. 1998 Jun 6;351(9117):1736 [9734916] Lancet. 1998 Jun 6;351(9117):1736-7 [9734917] Lancet. 1998 Jul 25;352(9124):320 [9690433] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Immunologic cross-reaction between HIV type 1 p17 and Mycoplasma hyorhinis variable lipoprotein. AN - 79786499; 9546801 AB - Monoclonal antibodies directed against the HIV-1 matrix protein p17 that react with a component present on the surface of HIV-1-infected cells have previously been described. In this study we show that one of these monoclonal antibodies binds to persistently HIV-1-infected cell lines that are coinfected with Mycoplasma hyorhinis, but not to cell lines that are uninfected with mycoplasma. Mycoplasma-infected cells secrete HIV-1 at a higher rate, have a slight increase in cell surface expression of gp120 and gp41, and are less sensitive to immunotoxins than uninfected cells. The anti-p17 antibody binds to a protein of M. hyorhinis grown in cell-free culture. The variable expression and size of the protein among strains is typical of the variable lipoprotein (Vlp) system of M. hyorhinis. Confirmation of the reactivity of the antibody with a Vlp was provided by demonstrating its specific binding to recombinant VlpF expressed in E. coli, and to a synthetic peptide representing the carboxy-terminal region of VlpF, but not to other recombinant Vlp products or peptides. This is a true cross-reaction because the antibody also binds to recombinant p17 expressed in E. coli and the binding is inhibited by the VlpF peptide. These analyses highlight the potential of mycoplasma contamination of tissue culture cell lines to cause anomalous results. With regard to HIV-1, mycoplasma infection of cells results in increased rates of virus secretion, and introduces a potential confounding immunologic cross-reaction as well. The existence of a cell surface form of p17 is unlikely. JF - AIDS research and human retroviruses AU - Pincus, S H AU - Cole, R L AU - Watson-McKown, R AU - Pinter, A AU - Honnen, W AU - Cole, B AU - Wise, K S AD - Laboratory of Microbial Structure and Function, NIAID Rocky Mountain Laboratories, Hamilton, Montana 59840, USA. Y1 - 1998/03/20/ PY - 1998 DA - 1998 Mar 20 SP - 419 EP - 425 VL - 14 IS - 5 SN - 0889-2229, 0889-2229 KW - Antibodies, Monoclonal KW - 0 KW - Bacterial Outer Membrane Proteins KW - Bacterial Proteins KW - Gene Products, gag KW - HIV Antigens KW - Lipoproteins KW - Viral Proteins KW - VlpF protein, Mycoplasma hyorhinis KW - gag Gene Products, Human Immunodeficiency Virus KW - p17 protein, Human Immunodeficiency Virus Type 1 KW - Index Medicus KW - AIDS/HIV KW - Immunoblotting KW - Cells, Cultured KW - Enzyme-Linked Immunosorbent Assay KW - Flow Cytometry KW - Cross Reactions -- immunology KW - HIV-1 -- immunology KW - Lipoproteins -- immunology KW - HIV-1 -- isolation & purification KW - Bacterial Outer Membrane Proteins -- immunology KW - Bacterial Proteins -- immunology KW - Mycoplasma -- growth & development KW - HIV-1 -- growth & development KW - Gene Products, gag -- immunology KW - HIV Antigens -- immunology KW - Mycoplasma -- isolation & purification KW - Mycoplasma -- immunology KW - Antibodies, Monoclonal -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79786499?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Immunologic+cross-reaction+between+HIV+type+1+p17+and+Mycoplasma+hyorhinis+variable+lipoprotein.&rft.au=Pincus%2C+S+H%3BCole%2C+R+L%3BWatson-McKown%2C+R%3BPinter%2C+A%3BHonnen%2C+W%3BCole%2C+B%3BWise%2C+K+S&rft.aulast=Pincus&rft.aufirst=S&rft.date=1998-03-20&rft.volume=14&rft.issue=5&rft.spage=419&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 - 1998-05-14 N1 - Date created - 1998-05-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mammalian DNA topoisomerase I activity and poisoning by camptothecin are inhibited by simian virus 40 large T antigen. AN - 79764431; 9521701 AB - DNA topoisomerase I (top1) is a ubiquitous enzyme that forms reversible DNA single-strand breaks (cleavage complexes) and plays a role in transcription, DNA replication, and repair. Top1 is the target of camptothecins which selectively trap top1 cleavage complexes and represent a novel class of anticancer drugs active against human solid tumors. The present study demonstrates that recombinant large T antigen (T-Ag), a virus encoded helicase with strong affinity for tumor suppressors and cell cycle- and replication-related proteins, suppresses top1 cleavage complexes and top1 catalytic activity. This top1 suppressive activity is probably not due to T-Ag binding to DNA, as a T-Ag truncation mutant containing only the first 246 amino acids and deficient in DNA binding also inhibited top1, and the inhibition was independent of ATP. T-Ag also antagonized and reversed the trapping of top1 cleavage complexes by camptothecin. These results demonstrate a functional interaction between T-Ag and top1: they also suggest the importance of top1-protein interactions for the regulation of DNA replication and modulation of camptothecin activity. JF - Biochemistry AU - Pommier, Y AU - Kohlhagen, G AU - Wu, C AU - Simmons, D T AD - Laboratory of Molecular Pharmacology, National Cancer Institute, Bethesda, Maryland 20892-4255, USA. pommier@nih.gov Y1 - 1998/03/17/ PY - 1998 DA - 1998 Mar 17 SP - 3818 EP - 3823 VL - 37 IS - 11 SN - 0006-2960, 0006-2960 KW - Antigens, Polyomavirus Transforming KW - 0 KW - DNA-Binding Proteins KW - Topoisomerase I Inhibitors KW - DNA Topoisomerases, Type I KW - EC 5.99.1.2 KW - DNA Topoisomerases, Type II KW - EC 5.99.1.3 KW - Camptothecin KW - XT3Z54Z28A KW - Index Medicus KW - Base Sequence KW - Humans KW - DNA Topoisomerases, Type II -- metabolism KW - Molecular Sequence Data KW - Enzyme Activation -- drug effects KW - Electrophoresis, Agar Gel KW - DNA-Binding Proteins -- genetics KW - Sequence Deletion KW - Camptothecin -- antagonists & inhibitors KW - Simian virus 40 -- genetics KW - Camptothecin -- toxicity KW - Antigens, Polyomavirus Transforming -- physiology KW - Antigens, Polyomavirus Transforming -- genetics KW - DNA Topoisomerases, Type I -- genetics KW - Simian virus 40 -- immunology KW - DNA Topoisomerases, Type I -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79764431?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mammalian+DNA+topoisomerase+I+activity+and+poisoning+by+camptothecin+are+inhibited+by+simian+virus+40+large+T+antigen.&rft.au=Pommier%2C+Y%3BKohlhagen%2C+G%3BWu%2C+C%3BSimmons%2C+D+T&rft.aulast=Pommier&rft.aufirst=Y&rft.date=1998-03-17&rft.volume=37&rft.issue=11&rft.spage=3818&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-04-14 N1 - Date created - 1998-04-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Induction of monocyte chemoattractant protein-1 in HIV-1 Tat-stimulated astrocytes and elevation in AIDS dementia. AN - 79735450; 9501225 AB - Activated monocytes release a number of substances, including inflammatory cytokines and eicosanoids, that are highly toxic to cells of the central nervous system. Because monocytic infiltration of the central nervous system closely correlates with HIV-1-associated dementia, it has been suggested that monocyte-derived toxins mediate nervous system damage. In the present study, we show that the HIV-1 transactivator protein Tat significantly increases astrocytic expression and release of monocyte chemoattractant protein-1 (MCP-1). Astrocytic release of beta-chemokines, which are relatively less selective for monocytes, including RANTES, macrophage inflammatory protein-1alpha, and macrophage inflammatory protein-1beta, was not observed. We also show that MCP-1 is expressed in the brains of patients with HIV-1-associated dementia and that, of the beta-chemokines tested, only MCP-1 could be detected in the cerebrospinal fluid of patients with this condition. Together, these data provide a potential link between the presence of HIV-1 in the brain and the monocytic infiltration that may substantially contribute to dementia. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Conant, K AU - Garzino-Demo, A AU - Nath, A AU - McArthur, J C AU - Halliday, W AU - Power, C AU - Gallo, R C AU - Major, E O AD - Laboratory of Molecular Medicine and Neuroscience, National Institute of Neurological Disorders and Stroke, Building 36, Room 5W21, National Institutes of Health, Bethesda, MD 20892, USA. conant@codon.nih.gov Y1 - 1998/03/17/ PY - 1998 DA - 1998 Mar 17 SP - 3117 EP - 3121 VL - 95 IS - 6 SN - 0027-8424, 0027-8424 KW - Chemokine CCL2 KW - 0 KW - Chemokine CCL4 KW - Chemokine CCL5 KW - Gene Products, tat KW - Macrophage Inflammatory Proteins KW - tat Gene Products, Human Immunodeficiency Virus KW - Index Medicus KW - AIDS/HIV KW - Prospective Studies KW - Macrophage Inflammatory Proteins -- analysis KW - Cells, Cultured KW - Humans KW - Adult KW - Middle Aged KW - Brain -- metabolism KW - Monocytes KW - Chemokine CCL5 -- analysis KW - Chemokine CCL2 -- blood KW - AIDS Dementia Complex -- metabolism KW - AIDS Dementia Complex -- cerebrospinal fluid KW - Astrocytes -- drug effects KW - AIDS Dementia Complex -- etiology KW - AIDS Dementia Complex -- blood KW - Chemokine CCL2 -- biosynthesis KW - Gene Products, tat -- pharmacology KW - HIV-1 KW - Chemokine CCL2 -- cerebrospinal fluid UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79735450?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Induction+of+monocyte+chemoattractant+protein-1+in+HIV-1+Tat-stimulated+astrocytes+and+elevation+in+AIDS+dementia.&rft.au=Conant%2C+K%3BGarzino-Demo%2C+A%3BNath%2C+A%3BMcArthur%2C+J+C%3BHalliday%2C+W%3BPower%2C+C%3BGallo%2C+R+C%3BMajor%2C+E+O&rft.aulast=Conant&rft.aufirst=K&rft.date=1998-03-17&rft.volume=95&rft.issue=6&rft.spage=3117&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 - 1998-04-10 N1 - Date created - 1998-04-10 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Immunol. 1994 Sep 1;153(5):2052-63 [8051410] J Virol. 1996 Mar;70(3):1384-9 [8627654] Eur J Immunol. 1995 Jan;25(1):64-8 [7531149] Ann Neurol. 1995 Mar;37(3):373-80 [7695237] Hum Gene Ther. 1995 Feb;6(2):177-84 [7734518] Nature. 1997 Feb 13;385(6617):645-9 [9024664] J Immunol. 1997 Mar 1;158(5):2449-55 [9036996] J Exp Med. 1997 Jul 7;186(1):131-7 [9207007] J Leukoc Biol. 1997 Jul;62(1):34-40 [9225990] J Clin Invest. 1997 Aug 1;100(3):497-502 [9239395] J Biol Chem. 1997 Sep 5;272(36):22385-8 [9278385] Eur J Immunol. 1997 Oct;27(10):2484-9 [9368600] Proc Natl Acad Sci U S A. 1994 Jan 18;91(2):494-8 [8290553] Nature. 1994 Jan 13;367(6459):188-93 [8114918] Ann Neurol. 1983 Mar;13(3):227-31 [6847134] Science. 1986 Jul 11;233(4760):215-9 [3014648] Science. 1986 Sep 5;233(4768):1089-93 [3016903] Proc Natl Acad Sci U S A. 1986 Sep;83(18):7089-93 [3018755] Science. 1988 Feb 5;239(4840):586-92 [3277272] Science. 1990 Apr 20;248(4953):364-7 [2326646] Neurology. 1991 Jun;41(6):778-85 [2046917] Blood. 1991 Aug 15;78(4):1112-6 [1868242] Am J Pathol. 1992 Nov;141(5):1209-16 [1279980] J Virol. 1993 Jan;67(1):277-87 [8416373] FASEB J. 1993 Apr 1;7(6):592-600 [8472896] Ann Neurol. 1993 May;33(5):429-36 [8498818] Ann Neurol. 1993 Jun;33(6):576-82 [8498837] Nature. 1993 Sep 9;365(6442):182-5 [8371761] Exp Hematol. 1996 Feb;24(2):169-75 [8641338] Curr Opin Pediatr. 1995 Dec;7(6):655-62 [8776015] AIDS. 1996 Jul;10(8):843-7 [8828741] Neuroscience. 1996 Sep;74(1):283-92 [8843093] J Infect Dis. 1996 Nov;174(5):1098-101 [8896515] Nat Med. 1996 Nov;2(11):1174-8 [8898734] Science. 1996 Dec 13;274(5294):1917-21 [8943206] Biochem Biophys Res Commun. 1994 Mar 15;199(2):761-6 [7510961] Crit Rev Oral Biol Med. 1995;6(2):109-18 [7548618] Neuropathol Appl Neurobiol. 1995 Jun;21(3):208-17 [7477729] Ann Neurol. 1995 Nov;38(5):755-62 [7486867] J Immunol. 1995 Dec 15;155(12):5769-76 [7499865] Science. 1995 Dec 15;270(5243):1811-5 [8525373] Proc Natl Acad Sci U S A. 1996 Jan 23;93(2):700-4 [8570619] J Immunol. 1996 Apr 15;156(8):3017-23 [8609424] AIDS. 1994 Oct;8(10):1504-6 [7818827] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Carbon dioxide stimulates peroxynitrite-mediated nitration of tyrosine residues and inhibits oxidation of methionine residues of glutamine synthetase: Both modifications mimic effects of adenylylation AN - 16373152; 4257269 AB - The activity of glutamine synthetase (EC 6.3.1.2) from Escherichia coli is regulated by the cyclic adenylylation and deadenylylation of Tyr-397 in each of the enzyme's 12 identical subunits. The nitration of Tyr-397 or of the nearby Tyr-326 by peroxynitrite can convert the unadenylylated enzyme to a form exhibiting regulatory characteristics similar to the form obtained by adenylylation. The adenylylated conformation can also be elicited by the oxidation of surface-exposed methionine residues to methionine sulfoxide. However, the nitration of tyrosine residues and the oxidation of methionine residues are oppositely directed by the presence and absence of CO sub(2.) At physiological concentrations of CO sub(2), pH 7.4, nitration occurs but oxidation of methionine residues is inhibited. Conversely, in the absence of CO sub(2) methionine oxidation is stimulated and nitration of tyrosine is prevented. It was further established that adenylylation of Tyr-397 precludes its nitration by peroxynitrite. Furthermore, nitration of Tyr-326 together with either nitration or adenylylation of Tyr-397 leads to inactivation of the enzyme. These results demonstrate that CO sub(2) can alter the course of peroxynitrite-dependent reactions and serve notice that (i) the reactions have physiological significance only if they are shown to occur at physiological concentrations of CO sub(2) and physiological pH; and (ii) the peroxynitrite-dependent nitration of tyrosine residues or the oxidation of methionine residues of metabolically regulated proteins can seriously compromise their biological function. JF - Proceedings of the National Academy of Sciences, USA AU - Berlett, B AU - Levine, R AU - Stadtman, E AD - Laboratory of Biochemistry, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-0342, erstadtman@nih.gov Y1 - 1998/03/17/ PY - 1998 DA - 1998 Mar 17 SP - 2784 EP - 2789 VL - 95 IS - 6 SN - 0027-8424, 0027-8424 KW - glutamate-ammonia ligase KW - methionine sulfoxide KW - oxidation KW - peroxynitrate KW - Microbiology Abstracts B: Bacteriology KW - J 02728:Enzymes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16373152?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.atitle=Carbon+dioxide+stimulates+peroxynitrite-mediated+nitration+of+tyrosine+residues+and+inhibits+oxidation+of+methionine+residues+of+glutamine+synthetase%3A+Both+modifications+mimic+effects+of+adenylylation&rft.au=Berlett%2C+B%3BLevine%2C+R%3BStadtman%2C+E&rft.aulast=Berlett&rft.aufirst=B&rft.date=1998-03-17&rft.volume=95&rft.issue=6&rft.spage=2784&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - The rpoB mutants destabilizing initiation complexes at stringently controlled promoters behave like 'stringent' RNA polymerases in Escherichia coli AN - 16314522; 4257291 AB - In Escherichia coli, stringently controlled genes are highly transcribed during rapid growth, but 'turned off' under nutrient limiting conditions, a process called the stringent response. To understand how transcriptional initiation at these promoters is coordinately regulated, we analyzed the interactions between RNA polymerase (RNAP) (both wild type and mutants) and four stringently controlled promoters. Our results show that the interactions between RNAP and stringently controlled promoters are intrinsically unstable and can alternate between relatively stable and metastable states. The mutant RNAPs appear to specifically further weaken interactions with these promoters in vitro and behave like 'stringent' RNAPs in the absence of the stringent response in vivo, constituting a novel class of mutant RNAPs. Consistently, these mutant RNAPs also activate the expression of other genes that normally require the response. We propose that the stability of initiation complexes is coupled to the transcription of stringently controlled promoters, and this unique feature coordinates the expression of genes positively and negatively regulated by the stringent response. JF - Proceedings of the National Academy of Sciences, USA AU - Zhou, Y AU - Jin, D AD - Laboratory of Molecular Biology, Building 37, Room 2E14, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, djjin@helix.nih.gov Y1 - 1998/03/17/ PY - 1998 DA - 1998 Mar 17 SP - 2908 EP - 2913 VL - 95 IS - 6 SN - 0027-8424, 0027-8424 KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - N 14721:RNA polymerases KW - J 02726:RNA and ribosomes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16314522?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.atitle=The+rpoB+mutants+destabilizing+initiation+complexes+at+stringently+controlled+promoters+behave+like+%27stringent%27+RNA+polymerases+in+Escherichia+coli&rft.au=Zhou%2C+Y%3BJin%2C+D&rft.aulast=Zhou&rft.aufirst=Y&rft.date=1998-03-17&rft.volume=95&rft.issue=6&rft.spage=2908&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Role of individual N-linked glycosylation sites in the function and intracellular transport of the human alpha folate receptor. AN - 79809737; 9515058 AB - Glycosylation is a structural feature of all three isoforms of the human folate receptor. We have used site-directed mutagenesis to study the role of individual glycosylation sites in the assembly and function of the a isoform of the human folate receptor (alpha(h)FR). Three potential N-linked glycosylation sites in the alpha(h)FR sequence were disrupted by conservative mutation of the S or T residues in the consensus sequence (N-X-S/T) to A or V, respectively. Constructs with the single mutations S(71)-->A (alpha(h)FR(-1)), T(163)-->V (alpha(h)FR(-2)), and S(203)-->A (alpha(h)FR(-3)); the double mutation S(71)--> A/S(203)-->A (alpha(h)FR(-1-3)); and the triple mutation S(71)--> A/S(203)--> A/T(163)--> V (alpha(h)FR(-1-2-3)) were stably transfected into Chinese hamster ovary (CHO) cells. The proteins produced in CHO cells by the mutated cDNAs have apparent molecular weights that are reduced relative to the wild type and are consistent with the loss of carbohydrate residues. The triple mutant, which lacks all three consensus glycosylation sites, yields protein that comigrates with the enzymatically deglycosylated native protein. Determinations of the K(D) for folic acid by Scatchard analyses of the glycosylation mutants indicate that folic acid binding affinity is not significantly affected in the single mutants alpha(h)FR(-1) and alpha(h)FR(-2). However, in the single mutant, alpha(h)FR(-3), and the double mutant, alpha(h)FR(-1-3), folic acid binding affinity is respectively 2.7- and 3.5-fold lower than that in wild type. Deglycosylation by mutation of all three consensus sites (alpha(h)FR(-1-2-3) eliminates both folic acid binding and cell surface expression. In contrast, enzymatic deglycosylation of purified wild-type alpha(h)FR with endoglycosidase F does not significantly affect folate binding affinity. Thus, while carbohydrate residues are not essential for the folate binding activity of the mature folate receptor, at least one of the three core glycosylated residues is necessary for the synthesis of alpha(h)FR in its active conformation. Copyright 1998 Academic Press. JF - Archives of biochemistry and biophysics AU - Roberts, S J AU - Petropavlovskaja, M AU - Chung, K N AU - Knight, C B AU - Elwood, P C AD - Section of Experimental Hematology, Medicine Branch, Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/03/15/ PY - 1998 DA - 1998 Mar 15 SP - 227 EP - 235 VL - 351 IS - 2 SN - 0003-9861, 0003-9861 KW - Carrier Proteins KW - 0 KW - Folate Receptors, GPI-Anchored KW - RNA, Messenger KW - Receptors, Cell Surface KW - Recombinant Proteins KW - Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase KW - EC 3.2.1.96 KW - Index Medicus KW - Animals KW - Humans KW - RNA, Messenger -- analysis KW - Protein Denaturation KW - Glycosylation KW - Recombinant Proteins -- genetics KW - Precipitin Tests KW - Protein Binding -- physiology KW - Consensus Sequence -- genetics KW - Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase -- metabolism KW - Transfection KW - Kinetics KW - CHO Cells KW - Cricetinae KW - Protein Conformation KW - Carrier Proteins -- genetics KW - Carrier Proteins -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79809737?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+biochemistry+and+biophysics&rft.atitle=Role+of+individual+N-linked+glycosylation+sites+in+the+function+and+intracellular+transport+of+the+human+alpha+folate+receptor.&rft.au=Roberts%2C+S+J%3BPetropavlovskaja%2C+M%3BChung%2C+K+N%3BKnight%2C+C+B%3BElwood%2C+P+C&rft.aulast=Roberts&rft.aufirst=S&rft.date=1998-03-15&rft.volume=351&rft.issue=2&rft.spage=227&rft.isbn=&rft.btitle=&rft.title=Archives+of+biochemistry+and+biophysics&rft.issn=00039861&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-04-20 N1 - Date created - 1998-04-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Adenovirus-mediated human immunodeficiency virus-1 Nef expression in human monocytes/macrophages and effect of Nef on downmodulation of Fcgamma receptors and expression of monokines. AN - 79717683; 9490697 AB - To characterize the effect of human immunodeficiency virus-1 (HIV-1) nef expression in human monocytes/macrophage (HMO) and U937 on the levels of FcgammaRs, HLA antigens, and monokines, elutriated HMOs and U937 cells were transfected with an adenovirus-mediated Nef expression system. Nef-expressing cells downmodulated FcgammaRI, FcgammaRII, and upregulated HLA class I molecules. Nef-expressing HMOs, treated with lipopolysaccharide (LPS) or phorbol 12-myristate 13-acetate (PMA), overexpressed tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and IL-10. However, IL-6 was induced by LPS and inhibited by PMA. Additionally, a subpopulation of Nef-expressing HMOs underwent apoptosis. Our data suggest that HIV-1 nef downmodulated FcgammaRs in myeloid cells in a manner similar to that previously reported for its effect on CD4+ in T cells. JF - Blood AU - De, S K AU - Venkateshan, C N AU - Seth, P AU - Gajdusek, D C AU - Gibbs, C J AD - Oral Infection and Immunity Branch, National Institute of Dental Research, the Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892, USA. Y1 - 1998/03/15/ PY - 1998 DA - 1998 Mar 15 SP - 2108 EP - 2117 VL - 91 IS - 6 SN - 0006-4971, 0006-4971 KW - Antigens, CD4 KW - 0 KW - Cation Exchange Resins KW - DNA, Antisense KW - Gene Products, nef KW - HLA Antigens KW - Interleukin-1 KW - Interleukin-6 KW - Lipids KW - Lipofectamine KW - Lipopolysaccharides KW - Monokines KW - Receptors, IgG KW - Receptors, Interleukin-2 KW - Tumor Necrosis Factor-alpha KW - nef Gene Products, Human Immunodeficiency Virus KW - Interleukin-10 KW - 130068-27-8 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Animals KW - Apoptosis KW - Lymphoma, Large B-Cell, Diffuse -- pathology KW - Humans KW - Lipopolysaccharides -- pharmacology KW - Tumor Necrosis Factor-alpha -- genetics KW - Receptors, Interleukin-2 -- genetics KW - HLA Antigens -- biosynthesis KW - Tumor Cells, Cultured KW - Down-Regulation KW - Antigens, CD4 -- genetics KW - Interleukin-6 -- genetics KW - Antigens, CD4 -- biosynthesis KW - Interleukin-1 -- genetics KW - Interleukin-10 -- genetics KW - HLA Antigens -- genetics KW - 3T3 Cells KW - Interleukin-1 -- biosynthesis KW - Receptors, Interleukin-2 -- biosynthesis KW - Tumor Necrosis Factor-alpha -- biosynthesis KW - DNA, Antisense -- genetics KW - Mice KW - Transfection KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Interleukin-10 -- biosynthesis KW - Interleukin-6 -- biosynthesis KW - Receptors, IgG -- biosynthesis KW - HIV-1 -- genetics KW - Gene Products, nef -- physiology KW - Gene Expression Regulation, Viral KW - Monocytes -- metabolism KW - Monokines -- genetics KW - Genetic Vectors -- genetics KW - Monokines -- biosynthesis KW - Genes, nef KW - Receptors, IgG -- genetics KW - Macrophages -- metabolism KW - Adenoviridae -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79717683?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Adenovirus-mediated+human+immunodeficiency+virus-1+Nef+expression+in+human+monocytes%2Fmacrophages+and+effect+of+Nef+on+downmodulation+of+Fcgamma+receptors+and+expression+of+monokines.&rft.au=De%2C+S+K%3BVenkateshan%2C+C+N%3BSeth%2C+P%3BGajdusek%2C+D+C%3BGibbs%2C+C+J&rft.aulast=De&rft.aufirst=S&rft.date=1998-03-15&rft.volume=91&rft.issue=6&rft.spage=2108&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-04-09 N1 - Date created - 1998-04-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Incidence and risk factors for self-reported peptic ulcer disease in the United States AN - 16374302; 4297636 AB - Incidence and risk factors for peptic ulcer disease in the United States have not been well defined. During the 1989 National Health Interview Survey, a population-based sample of 42,392 individuals responded to questions regarding doctor-diagnosed ulcers with confirmation by either an upper gastrointestinal series or endoscopy. Ulcers present during the previous 12 months were considered either incident ulcers if diagnosed during this period or chronic active ulcers if diagnosed more than 12 months before the interview. The incidence of ulcers over the year prior to the interview was 5.27 per 1,000 adults. Whereas incident duodenal ulcer cases represented only 2.4 percent of all persons with a history of duodenal ulcer, the corresponding value for gastric ulcer was 8.7 percent. Risk factors for incident ulcers included increasing age, lower income and educational attainment, and musculoskeletal pain or headache. These were similar to risk factors for chronic active ulcers, except smoking was an additional important risk factor for chronic active ulcers. Thus, incident peptic ulcers are common in the United States but represent a small proportion of persons with a history of ulcer disease. Smoking may be a stronger risk factor for chronic ulcers than for new ulcers. JF - American Journal of Epidemiology AU - Everhart, JE AU - Byrd-Holt, D AU - Sonnenberg, A AD - Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, USA Y1 - 1998/03/15/ PY - 1998 DA - 1998 Mar 15 SP - 529 EP - 536 VL - 147 IS - 6 SN - 0002-9262, 0002-9262 KW - USA KW - man KW - Toxicology Abstracts KW - X 24240:Miscellaneous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16374302?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Journal+of+Epidemiology&rft.atitle=Incidence+and+risk+factors+for+self-reported+peptic+ulcer+disease+in+the+United+States&rft.au=Everhart%2C+JE%3BByrd-Holt%2C+D%3BSonnenberg%2C+A&rft.aulast=Everhart&rft.aufirst=JE&rft.date=1998-03-15&rft.volume=147&rft.issue=6&rft.spage=529&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Epidemiology&rft.issn=00029262&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Transmembrane topology of glucose-6-phosphatase. AN - 79732042; 9497333 AB - Deficiency of microsomal glucose-6-phosphatase (G6Pase), the key enzyme in glucose homeostasis, causes glycogen storage disease type 1a, an autosomal recessive disorder. Characterization of the transmembrane topology of G6Pase should facilitate the identification of amino acid residues contributing to the active site and broaden our understanding of the effects of mutations that cause glycogen storage disease type 1a. Using N- and C-terminal tagged G6Pase, we show that in intact microsomes, the N terminus is resistant to protease digestion, whereas the C terminus is sensitive to such treatment. Our results demonstrate that G6Pase possesses an odd number of transmembrane helices, with its N and C termini facing the endoplasmic reticulum lumen and the cytoplasm, respectively. During catalysis, a phosphoryl-enzyme intermediate is formed, and the phosphoryl acceptor in G6Pase is a His residue. Sequence alignment suggests that mammalian G6Pases, lipid phosphatases, acid phosphatases, and a vanadium-containing chloroperoxidase (whose tertiary structure is known) share a conserved phosphatase motif. Active-site alignment of the vanadium-containing chloroperoxidase and G6Pases predicts that Arg-83, His-119, and His-176 in G6Pase contribute to the active site and that His-176 is the residue that covalently binds the phosphoryl moiety during catalysis. This alignment also predicts that Arg-83, His-119, and His-176 reside on the same side of the endoplasmic reticulum membrane, which is supported by the recently predicted nine-transmembrane helical model for G6Pase. We have previously shown that Arg-83 is involved in positioning the phosphate during catalysis and that His-119 is essential for G6Pase activity. Here we demonstrate that substitution of His-176 with structurally similar or dissimilar amino acids inactivates the enzyme, suggesting that His-176 could be the phosphoryl acceptor in G6Pase during catalysis. JF - The Journal of biological chemistry AU - Pan, C J AU - Lei, K J AU - Annabi, B AU - Hemrika, W AU - Chou, J Y AD - Heritable Disorders Branch, NICHD, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/03/13/ PY - 1998 DA - 1998 Mar 13 SP - 6144 EP - 6148 VL - 273 IS - 11 SN - 0021-9258, 0021-9258 KW - Membrane Proteins KW - 0 KW - Histidine KW - 4QD397987E KW - Glucose-6-Phosphatase KW - EC 3.1.3.9 KW - Trypsin KW - EC 3.4.21.4 KW - Endopeptidase K KW - EC 3.4.21.64 KW - Index Medicus KW - Endopeptidase K -- pharmacology KW - Humans KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Glycogen Storage Disease Type I -- enzymology KW - Trypsin -- pharmacology KW - Sequence Deletion KW - Protein Conformation KW - Mutagenesis KW - Binding Sites KW - Membrane Proteins -- chemistry KW - Glucose-6-Phosphatase -- metabolism KW - Membrane Proteins -- metabolism KW - Glucose-6-Phosphatase -- chemistry KW - Glucose-6-Phosphatase -- drug effects KW - Microsomes -- enzymology KW - Membrane Proteins -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79732042?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Transmembrane+topology+of+glucose-6-phosphatase.&rft.au=Pan%2C+C+J%3BLei%2C+K+J%3BAnnabi%2C+B%3BHemrika%2C+W%3BChou%2C+J+Y&rft.aulast=Pan&rft.aufirst=C&rft.date=1998-03-13&rft.volume=273&rft.issue=11&rft.spage=6144&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 - 1998-04-07 N1 - Date created - 1998-04-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evaluation of the direct genotoxic potential of cadmium in four different rodent cell lines AN - 16489162; 4366720 AB - Cadmium is a toxic environmental contaminant that is carcinogenic in humans and laboratory animals. Although the mechanism underlying cadmium carcinogenesis has not yet been determined experimental evidence suggests that the stress-inducible, metal-binding proteins, metallothioneins, may mediate organ specificity. In the present study, four different rodent cell lines (Chinese hamster ovary cells, rat L6 myoblast cells, rat Clone 9 liver cells, and rat TRL 1215 liver cells) were exposed to 0, 1, 5, 10, 50, or 100 mu M CdCl sub(2) and monitored for evidence of direct DNA damage. A microfiltration assay was used to measure DNA strand breaks and a filter-binding assay was used to measure DNA-protein crosslinks, two lesions that have been associated with cadmium exposure and may mediate genotoxicity of the metal. Although variability in sensitivity to DNA damage was evident between the different cell lines, in all of the cell lines tested, increases in DNA damage were observed only at cadmium doses that completely arrested cell growth. In addition, in three of the four cell lines tested, induction of metallothionein had no substantial protective effect against cadmium-induced cytotoxicity or genotoxicity. While protection against cadmium-induced DNA strand breakage with metallothionein preinduction was observed in the TRL 1215 rat liver cells, metallothionein preinduction did not protect against cadmium-induced DNA-protein crosslinking in that cell line. Taken together, our results support the hypothesis that cadmium is not directly genotoxic. JF - Toxicology AU - Misra, R R AU - Smith, G T AU - Waalkes, M P AD - Inorganic Carcinogenesis Section, Laboratory of Comparative Carcinogenesis, Division of Basic Sciences, Bldg. 538, Room 205E, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, MD 21702-1201, USA Y1 - 1998/03/13/ PY - 1998 DA - 1998 Mar 13 SP - 103 EP - 114 VL - 126 IS - 2 SN - 0300-483X, 0300-483X KW - cell lines KW - Toxicology Abstracts KW - X 24165:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16489162?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology&rft.atitle=Evaluation+of+the+direct+genotoxic+potential+of+cadmium+in+four+different+rodent+cell+lines&rft.au=Misra%2C+R+R%3BSmith%2C+G+T%3BWaalkes%2C+M+P&rft.aulast=Misra&rft.aufirst=R&rft.date=1998-03-13&rft.volume=126&rft.issue=2&rft.spage=103&rft.isbn=&rft.btitle=&rft.title=Toxicology&rft.issn=0300483X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Catalytic mechanism of aldose reductase studied by the combined potentials of quantum mechanics and molecular mechanics. AN - 79788404; 9546197 AB - The catalytic reduction of D-glyceraldehyde to glycerol by aldose reductase has been investigated with the combined potentials of quantum mechanics (QM) and molecular mechanics (MM) to resolve the question of whether Tyr48 or His110 serves as the proton donor during catalysis. Site directed mutagenesis studies favor Tyr48 as the proton donor while the presence of a water channel linking the N delta 1 of His110 to the bulk solvent suggests that His110 is the proton donor. Utilizing the combined potentials of QM and MM, the binding mode of substrate D-glyceraldehyde was investigated by optimizing the local geometry of Asp43, Lys77, Tyr48, His110 and NADPH at the active site of aldose reductase. Reaction pathways for the reduction of D-glyceraldehyde to glycerol were then constructed by treating both Tyr48 and His110 as proton donors. Comparison of energetics obtained from the reaction pathways suggests His110 to be the proton donor. Based on these findings, a reduction mechanism of D-glyceraldehyde to glycerol is described. JF - Biophysical chemistry AU - Lee, Y S AU - Hodoscek, M AU - Brooks, B R AU - Kador, P F AD - National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA. yongslee@helix.nih.gov Y1 - 1998/03/09/ PY - 1998 DA - 1998 Mar 09 SP - 203 EP - 216 VL - 70 IS - 3 SN - 0301-4622, 0301-4622 KW - Protons KW - 0 KW - Aldehyde Reductase KW - EC 1.1.1.21 KW - Index Medicus KW - Quantum Theory KW - Models, Molecular KW - Chemistry, Physical KW - Humans KW - Chemical Phenomena KW - Molecular Conformation KW - Energy Metabolism KW - Catalysis KW - Binding Sites KW - Aldehyde Reductase -- chemistry KW - Aldehyde Reductase -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79788404?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biophysical+chemistry&rft.atitle=Catalytic+mechanism+of+aldose+reductase+studied+by+the+combined+potentials+of+quantum+mechanics+and+molecular+mechanics.&rft.au=Lee%2C+Y+S%3BHodoscek%2C+M%3BBrooks%2C+B+R%3BKador%2C+P+F&rft.aulast=Lee&rft.aufirst=Y&rft.date=1998-03-09&rft.volume=70&rft.issue=3&rft.spage=203&rft.isbn=&rft.btitle=&rft.title=Biophysical+chemistry&rft.issn=03014622&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-05-05 N1 - Date created - 1998-05-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Conditioned release of corticosterone by contextual stimuli associated with cocaine is mediated by corticotropin-releasing factor AN - 16291135; 4276865 AB - Elevated blood concentrations of corticosterone (CORT), an adrenal steroid associated with stress responses, is one of the endocrine correlates of cocaine treatment. Experiment 1 confirmed and extended previous findings that chronic cocaine treatment does not alter corticosteroid responses to cocaine. In Experiment 2, conditioned endocrine effects of cocaine were examined in three groups of rats after 7 consecutive days of treatment. Cocaine-induced conditioning was achieved using a simple contextual design. In group 1 (paired), rats were injected with cocaine (30 mg/kg), then immediately placed into a locomotor activity chamber for 30 min. One hour after the rats were returned to their home cages, they received an injection of saline. In group 2 (unpaired), rats were injected with saline, then immediately placed into a locomotor activity chamber for 30 min. One hour after the rats were returned to their home cages, they received an injection of cocaine (30 mg/kg). Rats in group 3 (control) received only saline injections, but otherwise were treated as animals in the other treatment groups. On the test day (Day 8), all rats were placed immediately into the locomotor apparatus for 30 min prior to collection of a blood sample. Blood CORT concentrations and locomotor activity in the paired group were significantly higher than in the unpaired and control groups. However, pretreatment of the rats in Experiment 3 with the corticotropin-releasing factor (CRF) antagonist, alpha -helical CRF 9-41 (1 mu g, i.c.v.), on the test day, prior to exposure to cocaine-associated contextual cues, attenuated the subsequent conditioned increase in blood CORT concentrations. These data represent the first demonstration of classical conditioning of a steroid hormone response to stimuli associated with a psychoactive drug in rats and suggest that the effect is mediated by endogenous CRF. Because the hypothalamic-pituitary-adrenal (HPA) axis has been implicated in modulating the actions of cocaine, it is plausible that such conditioned increases in CORT release by cocaine-associated cues may further predispose an organism to the reinforcing effects of the drug or enhance the susceptibility to drug-taking behavior. Alternatively, such conditioned effects may be related to the anxiogenic properties of cocaine. Further understanding of the conditioned effects of hormones in the development and expression of addictive behaviors may provide new insights into treatment of drug addiction. JF - Brain Research AU - DeVries, A C AU - Taymans, SE AU - Sundstrom, J M AU - Pert, A AD - Biological Psychiatry Branch, National Institute of Mental Health, Bethesda, MD 20892, USA Y1 - 1998/03/09/ PY - 1998 DA - 1998 Mar 09 SP - 39 EP - 46 PB - Elsevier Science B.V. VL - 786 IS - 1-2 SN - 0006-8993, 0006-8993 KW - hypothalamic-pituitary-adrenal axis KW - rats KW - CSA Neurosciences Abstracts; Toxicology Abstracts KW - N3 11106:Neurobiology of drug abuse KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16291135?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain+Research&rft.atitle=Conditioned+release+of+corticosterone+by+contextual+stimuli+associated+with+cocaine+is+mediated+by+corticotropin-releasing+factor&rft.au=DeVries%2C+A+C%3BTaymans%2C+SE%3BSundstrom%2C+J+M%3BPert%2C+A&rft.aulast=DeVries&rft.aufirst=A&rft.date=1998-03-09&rft.volume=786&rft.issue=1-2&rft.spage=39&rft.isbn=&rft.btitle=&rft.title=Brain+Research&rft.issn=00068993&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Mutations in the contact region between the alpha and beta subunits of tryptophan synthase alter subunit interaction and intersubunit communication. AN - 79716121; 9485448 AB - Interaction between the alpha and beta subunits of tryptophan synthase leads to mutual stabilization of the active conformations and to coordinated control of the activities of the two subunits. To elucidate the roles of specific residues in the interaction site between the alpha and beta subunits, mutant alpha and beta subunits were constructed, and the effects of mutation on subunit interaction and intersubunit communication were determined. Mutation of either alpha subunit Asp56 (alphaD56A) or beta subunit Lys167 (betaK167T), residues that interact in some crystal structures of the tryptophan synthase alpha2beta2 complex, decreases the ability of the alpha subunit to activate the beta subunit and alters the reaction and substrate specificity of the beta subunit. Partial conformational repair is provided by alpha-glycerol 3-phosphate, a ligand that binds to the alpha subunit, or by Cs+ or NH4+, ligands that bind to the beta subunit. Mutation of beta subunit Arg175 (betaR175A), a residue that interacts with alpha subunit Pro57 in some structures, has much smaller effects on activity but results in a 15-fold increase in the apparent Kd for dissociation of the alpha and beta subunits. Replacement of the single tryptophan in the beta subunit by phenylalanine (W177F) has only small effects on activity but increases the apparent subunit dissociation constant approximately 10-fold. The most important conclusions of this investigation are that interaction between alphaAsp56 and betaLys167 is important for intersubunit communication and that mutual stabilization of the active conformations of the two subunits is impaired by mutation of either residue. JF - Biochemistry AU - Rowlett, R AU - Yang, L H AU - Ahmed, S A AU - McPhie, P AU - Jhee, K H AU - Miles, E W AD - Laboratory of Biochemistry and Genetics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/03/03/ PY - 1998 DA - 1998 Mar 03 SP - 2961 EP - 2968 VL - 37 IS - 9 SN - 0006-2960, 0006-2960 KW - Ligands KW - 0 KW - Tryptophan Synthase KW - EC 4.2.1.20 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Kinetics KW - Molecular Sequence Data KW - Circular Dichroism KW - Models, Chemical KW - Crystallography, X-Ray KW - Substrate Specificity KW - Amino Acid Substitution KW - Structure-Activity Relationship KW - Protein Conformation KW - Tryptophan Synthase -- chemistry KW - Tryptophan Synthase -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79716121?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemistry&rft.atitle=Mutations+in+the+contact+region+between+the+alpha+and+beta+subunits+of+tryptophan+synthase+alter+subunit+interaction+and+intersubunit+communication.&rft.au=Rowlett%2C+R%3BYang%2C+L+H%3BAhmed%2C+S+A%3BMcPhie%2C+P%3BJhee%2C+K+H%3BMiles%2C+E+W&rft.aulast=Rowlett&rft.aufirst=R&rft.date=1998-03-03&rft.volume=37&rft.issue=9&rft.spage=2961&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-04-03 N1 - Date created - 1998-04-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Galpha12 requires acylation for its transforming activity. AN - 79713959; 9485474 AB - The alpha subunit of the heterotrimeric G protein G12, harboring a mutation in the GTP binding domain (Q229L), behaves as a potent oncogene in NIH 3T3 cells. This alpha subunit, like most other G protein alpha subunits, undergoes palmitoylation, the reversible posttranslational addition of palmitate to cysteine residues. We investigated the role of palmitoylation of alpha12 in membrane localization and transformation efficiency and whether another lipid modification, myristoylation, could substitute for palmitoylation. NIH 3T3 cells were stably transfected with plasmids that expressed the wild-type alpha12, the constitutively active Q229L (QL) mutant, and mutants in which C11 was changed to S (C11S) and S2 and R6 were changed to G and S, respectively (S2G). Incorporation of [3H]palmitate was found in the endogenous and expressed alpha12 but not in the C11S mutants. Incorporation of [3H]myristate was found only in the S2G mutants. The wild type, QL mutant, and all the acylation mutants were found in the particulate fraction. Cells expressing the nonpalmitoylated C11S,QL mutant did not undergo transformation. The S2G mutation in the nonpalmitoylated C11S,QL mutant restored the transformation efficiency to a greater level than that of the palmitoylated QL mutant as measured by foci formation, growth in soft agar, and growth rate. Palmitoylation was critical for the transformation efficiency of alpha12 but not specifically required because myristoylation could substitute for these functions. JF - Biochemistry AU - Jones, T L AU - Gutkind, J S AD - Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. tlzj@helix.nih.gov Y1 - 1998/03/03/ PY - 1998 DA - 1998 Mar 03 SP - 3196 EP - 3202 VL - 37 IS - 9 SN - 0006-2960, 0006-2960 KW - Proto-Oncogene Proteins KW - 0 KW - Palmitic Acid KW - 2V16EO95H1 KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - GTP-Binding Protein alpha Subunit, Gi2 KW - EC 3.6.5.1 KW - GTP-Binding Protein alpha Subunits, Gi-Go KW - Gnai2 protein, mouse KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Animals KW - 3T3 Cells KW - Transfection KW - Molecular Sequence Data KW - Mice KW - Amino Acid Sequence KW - Cell Membrane -- metabolism KW - Acylation KW - Palmitic Acid -- metabolism KW - GTP-Binding Proteins -- metabolism KW - Proto-Oncogene Proteins -- metabolism KW - Proto-Oncogene Proteins -- genetics KW - GTP-Binding Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79713959?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Galpha12+requires+acylation+for+its+transforming+activity.&rft.au=Jones%2C+T+L%3BGutkind%2C+J+S&rft.aulast=Jones&rft.aufirst=T&rft.date=1998-03-03&rft.volume=37&rft.issue=9&rft.spage=3196&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-04-03 N1 - Date created - 1998-04-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chronic lithium treatment robustly protects neurons in the central nervous system against excitotoxicity by inhibiting N-methyl-D-aspartate receptor-mediated calcium influx. AN - 79710340; 9482940 AB - Lithium is the most commonly used drug for the treatment of manic depressive illness. The precise mechanisms underlying its clinical efficacy remain unknown. We found that long-term exposure to lithium chloride dramatically protects cultured rat cerebellar, cerebral cortical, and hippocampal neurons against glutamate-induced excitotoxicity, which involves apoptosis mediated by N-methyl-D-aspartate (NMDA) receptors. This neuroprotection is long-lasting, occurs at therapeutically relevant concentrations of lithium with an EC50 of approximately 1.3 mM, and requires treatment for 6-7 days for complete protection to occur. In contrast, a 24-h treatment with lithium is ineffective. The protection in cerebellar neurons is specific for glutamate-induced excitotoxicity and can be attributed to inhibition of NMDA receptor-mediated calcium influx measured by 45Ca2+ uptake studies and fura-2 fluorescence microphotometry. The long-term effects of lithium are not caused by down-regulation of NMDA receptor subunit proteins and are unlikely related to its known ability to block inositol monophosphatase activity. Our results suggest that modulation of glutamate receptor hyperactivity represents at least part of the molecular mechanisms by which lithium alters brain function and exerts its clinical efficacy in the treatment for manic depressive illness. These actions of lithium also suggest that abnormality of glutamatergic neurotransmission as a pathogenic mechanism underlying bipolar illness warrants future investigation. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Nonaka, S AU - Hough, C J AU - Chuang, D M AD - Section on Molecular Neurobiology, Biological Psychiatry Branch, National Institute of Mental Health, National Institutes of Health, 10 Center Drive, MSC 1272, Bethesda, MD 20892-1272, USA. Y1 - 1998/03/03/ PY - 1998 DA - 1998 Mar 03 SP - 2642 EP - 2647 VL - 95 IS - 5 SN - 0027-8424, 0027-8424 KW - Chromatin KW - 0 KW - Neurotoxins KW - Receptors, N-Methyl-D-Aspartate KW - Glutamic Acid KW - 3KX376GY7L KW - Dizocilpine Maleate KW - 6LR8C1B66Q KW - 6-Cyano-7-nitroquinoxaline-2,3-dione KW - 6OTE87SCCW KW - Lithium Chloride KW - G4962QA067 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Animals KW - Cerebral Cortex -- cytology KW - Hippocampus -- physiology KW - 6-Cyano-7-nitroquinoxaline-2,3-dione -- pharmacology KW - Chromatin -- physiology KW - Cerebellum -- physiology KW - Cell Survival KW - Dizocilpine Maleate -- pharmacology KW - Rats KW - Rats, Sprague-Dawley KW - Cerebellum -- cytology KW - Cerebral Cortex -- physiology KW - Hippocampus -- cytology KW - Apoptosis -- drug effects KW - Chromatin -- drug effects KW - Embryo, Mammalian KW - DNA Fragmentation KW - Calcium -- metabolism KW - Receptors, N-Methyl-D-Aspartate -- physiology KW - Glutamic Acid -- toxicity KW - Brain -- cytology KW - Receptors, N-Methyl-D-Aspartate -- drug effects KW - Neurons -- drug effects KW - Neurons -- cytology KW - Neurons -- physiology KW - Lithium Chloride -- pharmacology KW - Neurotoxins -- toxicity KW - Brain -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79710340?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Chronic+lithium+treatment+robustly+protects+neurons+in+the+central+nervous+system+against+excitotoxicity+by+inhibiting+N-methyl-D-aspartate+receptor-mediated+calcium+influx.&rft.au=Nonaka%2C+S%3BHough%2C+C+J%3BChuang%2C+D+M&rft.aulast=Nonaka&rft.aufirst=S&rft.date=1998-03-03&rft.volume=95&rft.issue=5&rft.spage=2642&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 - 1998-04-09 N1 - Date created - 1998-04-09 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Trends Pharmacol Sci. 1990 Jun;11(6):254-60 [2166370] Science. 1997 Mar 28;275(5308):1899 [9122692] Br J Psychiatry. 1990 Sep;157:327-30 [1978786] Neuroscience. 1990;39(1):25-32 [1982465] Trends Biochem Sci. 1991 May;16(5):177-81 [1652801] J Clin Psychopharmacol. 1992 Feb;12(1 Suppl):23S-35S [1541715] Mol Pharmacol. 1992 Aug;42(2):210-6 [1355259] Biochim Biophys Acta. 1992 Dec 16;1114(2-3):147-62 [1333807] J Neurobiol. 1992 Nov;23(9):1261-76 [1361523] J Neurochem. 1993 Feb;60(2):652-8 [8380439] Synapse. 1993 Apr;13(4):315-21 [8097597] Life Sci. 1994;55(22):1683-99 [7968248] Trends Neurosci. 1995 Feb;18(2):54-6 [7537406] Neurochem Int. 1995 Jan;26(1):53-8 [7787763] Alcohol Clin Exp Res. 1995 Jun;19(3):721-6 [7573799] Neuron. 1995 Oct;15(4):961-73 [7576644] Nature. 1995 Nov 9;378(6553):182-6 [7477320] J Pharmacol Exp Ther. 1996 Jan;276(1):143-9 [8558424] J Neuropathol Exp Neurol. 1996 Jan;55(1):1-13 [8558164] J Neurosci Res. 1995 Dec;42(5):674-83 [8600300] Proc Natl Acad Sci U S A. 1996 Aug 6;93(16):8455-9 [8710892] Brain Res. 1995 Dec 12;703(1-2):63-71 [8719616] Prog Neurobiol. 1996 Apr;48(6):613-34 [8809910] Funct Neurol. 1996 Jan-Feb;11(1):3-15 [8936453] Proc Natl Acad Sci U S A. 1982 Dec;79(24):7919-23 [6130529] J Immunol Methods. 1983 Dec 16;65(1-2):55-63 [6606682] J Biol Chem. 1985 Mar 25;260(6):3440-50 [3838314] Nature. 1990 Jun 28;345(6278):825-9 [2113617] J Neurochem. 1997 Feb;68(2):469-78 [9003031] Trends Pharmacol Sci. 1990 Sep;11(9):379-87 [2238094] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mice with type 2 and 3 Gaucher disease point mutations generated by a single insertion mutagenesis procedure. AN - 79709194; 9482915 AB - Gaucher disease is caused by mutations in the gene encoding the lysosomal enzyme glucocerebrosidase (GC). Three clinical types of Gaucher disease have been defined according to the presence (type 2 and 3) or absence (type 1) of central nervous system disease and severity of clinical manifestations. The clinical course of the disease correlates with the mutation carried by the GC gene. To produce mice with point mutations that correspond to the clinical types of Gaucher disease, we have devised a highly efficient one-step mutagenesis method-the single insertion mutagenesis procedure (SIMP)-to introduce human disease mutations into the mouse GC gene. By using SIMP, mice were generated carrying either the very severe RecNciI mutation that can cause type 2 disease or the less severe L444P mutation associated with type 3 disease. Mice homozygous for the RecNciI mutation had little GC enzyme activity and accumulated glucosylceramide in brain and liver. In contrast, the mice homozygous for the L444P mutation had higher levels of GC activity and no detectable accumulation of glucosylceramide in brain and liver. Surprisingly, both point mutation mice died within 48 hr of birth, apparently of a compromised epidermal permeability barrier caused by defective glucosylceramide metabolism in the epidermis. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Liu, Y AU - Suzuki, K AU - Reed, J D AU - Grinberg, A AU - Westphal, H AU - Hoffmann, A AU - Döring, T AU - Sandhoff, K AU - Proia, R L AD - Section on Biochemical Genetics, Genetics and Biochemistry Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1998/03/03/ PY - 1998 DA - 1998 Mar 03 SP - 2503 EP - 2508 VL - 95 IS - 5 SN - 0027-8424, 0027-8424 KW - Recombinant Proteins KW - 0 KW - Sphingolipids KW - Glucosylceramidase KW - EC 3.2.1.45 KW - Index Medicus KW - Animals KW - Liver -- pathology KW - Recombinant Proteins -- biosynthesis KW - Humans KW - Skin -- pathology KW - Liver -- metabolism KW - Amino Acid Sequence KW - Brain -- metabolism KW - Mice KW - Mice, Inbred Strains KW - Base Sequence KW - Brain -- pathology KW - Restriction Mapping KW - Recombinant Proteins -- chemistry KW - Sphingolipids -- metabolism KW - Glucosylceramidase -- biosynthesis KW - Gaucher Disease -- genetics KW - Gaucher Disease -- classification KW - Point Mutation KW - Glucosylceramidase -- genetics KW - Glucosylceramidase -- chemistry KW - Gaucher Disease -- pathology KW - Mutagenesis, Insertional UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79709194?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=Mice+with+type+2+and+3+Gaucher+disease+point+mutations+generated+by+a+single+insertion+mutagenesis+procedure.&rft.au=Liu%2C+Y%3BSuzuki%2C+K%3BReed%2C+J+D%3BGrinberg%2C+A%3BWestphal%2C+H%3BHoffmann%2C+A%3BD%C3%B6ring%2C+T%3BSandhoff%2C+K%3BProia%2C+R+L&rft.aulast=Liu&rft.aufirst=Y&rft.date=1998-03-03&rft.volume=95&rft.issue=5&rft.spage=2503&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 - 1998-04-09 N1 - Date created - 1998-04-09 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cell. 1983 May;33(1):25-35 [6380756] Proc Natl Acad Sci U S A. 1995 May 9;92(10):4547-51 [7753840] Nature. 1988 Nov 24;336(6197):348-52 [3194019] Nat Genet. 1995 Oct;11(2):170-6 [7550345] Medicine (Baltimore). 1995 Nov;74(6):305-23 [7500895] Am J Med Genet. 1995 Nov 20;59(3):356-8 [8599361] J Med Genet. 1996 Feb;33(2):132-6 [8929950] J Lipid Res. 1997 Mar;38(3):576-84 [9101438] Hum Mol Genet. 1997 Jun;6(6):887-95 [9175735] Proc Natl Acad Sci U S A. 1997 Jul 22;94(15):8138-43 [9223328] Genome Res. 1997 Oct;7(10):1020-6 [9331372] Pediatr Res. 1997 Nov;42(5):610-4 [9357932] Am J Med Genet. 1997 Nov 28;73(1):41-7 [9375921] Science. 1989 Jun 16;244(4910):1288-92 [2660260] Mol Cell Biol. 1991 Mar;11(3):1402-8 [1996101] Cell. 1991 Mar 22;64(6):1155-61 [2004421] Nature. 1991 Mar 21;350(6315):243-6 [1672446] Mol Cell Biol. 1991 Sep;11(9):4389-97 [1875928] Mol Cell Biol. 1991 Sep;11(9):4509-17 [1875936] Science. 1991 Dec 6;254(5037):1494-7 [1962209] Nature. 1992 Jun 4;357(6377):407-10 [1594045] Semin Dermatol. 1992 Jun;11(2):106-13 [1498013] Pediatr Res. 1992 Oct;32(4):494-8 [1437405] Mol Cell Biol. 1993 Apr;13(4):2134-40 [8455602] Mol Cell Biol. 1993 Jul;13(7):4115-24 [8391633] Mol Cell Biol. 1994 Feb;14(2):1009-16 [8289781] J Biol Chem. 1994 Jan 21;269(3):2283-91 [8294487] Hum Mutat. 1994;3(1):1-11 [8118460] Proc Natl Acad Sci U S A. 1994 Mar 29;91(7):2819-23 [8146196] J Clin Invest. 1994 Apr;93(4):1756-64 [8163674] Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):9975-9 [7937929] J Biol Chem. 1994 Nov 4;269(44):27155-8 [7961620] Biochem Med Metab Biol. 1994 Oct;53(1):16-21 [7857677] Biol Neonate. 1986;49(2):74-80 [3697429] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Isotope exchange studies on the Escherichia coli selenophosphate synthetase mechanism AN - 16362480; 4252767 AB - Selenophosphate synthetase, the Escherichia coli selD gene product, is a 37-kDa protein that catalyzes the synthesis of selenophosphate from ATP and selenide. In the absence of selenide, ATP is converted quantitatively to AMP and two orthophosphates in a very slow partial reaction. A monophosphorylated enzyme derivative containing the gamma -phosphoryl group of ATP has been implicated as an intermediate from the results of positional isotope exchange studies. Conservation of the phosphate bond energy in the final selenophosphate product is indicated by its ability to phosphorylate alcohols and amines to form O- phosphoryl- and N-phosphoryl-derivatives. To further probe the mechanism of action of selenophosphate synthetase, isotope exchange studies with [8- super(14)C]ADP or [8- super(14)C]AMP and unlabeled ATP were carried out, and super(31)P NMR analysis of reaction mixtures enriched in H sub(2) super(18)O was performed. A slow enzyme-catalyzed exchange of ADP with ATP observed in the absence of selenide implies the existence of a phosphorylated enzyme and further supports an intermediary role of ADP in the reaction. Under these conditions ADP is slowly converted to AMP. Incorporation of super(18)O from H sub(2) super(18)O exclusively into orthophosphate in the overall selenide-dependent reaction indicates that the beta -phosphoryl group of the enzyme-bound ADP is attacked by water with liberation of orthophosphate and formation of AMP. Based on these results and the failure of the enzyme to catalyze an exchange of labeled AMP with ATP, the existence of a pyrophosphorylated enzyme intermediate that was postulated earlier can be excluded. JF - Proceedings of the National Academy of Sciences, USA AU - Walker, H AU - Ferretti, J AU - Stadtman, T AD - Laboratory of Biochemistry and Laboratory of Biophysical Chemistry, National Heart, Lung, and Blood Institute, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, tcstadtman@nih.gov Y1 - 1998/03/03/ PY - 1998 DA - 1998 Mar 03 SP - 2180 EP - 2185 VL - 95 IS - 5 SN - 0027-8424, 0027-8424 KW - ATP KW - N-phosphoryl derivatives KW - O-phosphoryl derivatives KW - alcohols KW - amines KW - isotopes KW - orthophosphate KW - se1D gene KW - selenide KW - selenophosphate KW - selenophosphate synthetase KW - Microbiology Abstracts B: Bacteriology KW - J 02728:Enzymes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16362480?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.atitle=Isotope+exchange+studies+on+the+Escherichia+coli+selenophosphate+synthetase+mechanism&rft.au=Walker%2C+H%3BFerretti%2C+J%3BStadtman%2C+T&rft.aulast=Walker&rft.aufirst=H&rft.date=1998-03-03&rft.volume=95&rft.issue=5&rft.spage=2180&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Sequence-specific ligation of DNA using RecA protein AN - 16305573; 4252772 AB - A method is described that allows the sequence-specific ligation of DNA. The method is based on the ability of RecA protein from Escherichia coli to selectively pair oligonucleotides to their homologous sequences at the ends of fragments of duplex DNA. These three-stranded complexes were protected from the action of DNA polymerase. When treated with DNA polymerase, unprotected duplex fragments were converted to fragments with blunt ends, whereas protected fragments retained their cohesive ends. By using conditions that greatly favored ligation of cohesive ends, a second DNA fragment could be selectively ligated to a previously protected fragment of DNA. When this second DNA was a vector, selected fragments were preferentially cloned. The method had sufficient power to be used for the isolation of single-copy genes directly from yeast or human genomic DNA, and potentially could allow the isolation of much longer fragments with greater fidelity than obtainable by using PCR. JF - Proceedings of the National Academy of Sciences, USA AU - Ferrin, L AU - Camerini-Otero, R AD - Genetics and Biochemistry Branch, National Institute of Diabetes, Digestive, and Kidney Disorders, Building 10, Room 9D20, 10 Center Drive, MSC 1810, Bethesda, MD 20892-1810, lancef@bdg10.niddk.nih.gov Y1 - 1998/03/03/ PY - 1998 DA - 1998 Mar 03 SP - 2152 EP - 2157 VL - 95 IS - 5 SN - 0027-8424, 0027-8424 KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - J 02725:DNA KW - J 02727:Amino acids, peptides and proteins KW - N 14940:Nucleic acid-binding proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16305573?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.atitle=Sequence-specific+ligation+of+DNA+using+RecA+protein&rft.au=Ferrin%2C+L%3BCamerini-Otero%2C+R&rft.aulast=Ferrin&rft.aufirst=L&rft.date=1998-03-03&rft.volume=95&rft.issue=5&rft.spage=2152&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Transition phase in the production of recombinant proteins in yeast under the ADH2 promoter: an important step for reproducible manufacturing of a malaria transmission blocking vaccine candidate AN - 856785294; 14295528 AB - TBV25H, a malaria transmission blocking vaccine candidate, has been cloned in Saccharomyces cerevisiae under the control of the glucose repressed ADH2 promoter. Available fermentation procedures for production of this protein have been unsatisfactory, mainly because of irreproducibility. This work presents an efficient and reproducible method for the production of this vaccine candidate by implementing a three-stage fermentation process. During the first (glucose fed-batch) phase, the promoter is repressed and the culture is allowed to grow exponentially. In the second stage, the glucose supply is provided at a slower constant rate. In the third (ethanol consumption) stage, accumulated ethanol is first allowed to be consumed and an external ethanol supplement is then added as required. The promoter is fully derepressed in this phase, and TBV25H is synthesized. The period of glucose limitation was concluded to be essential for reproducibility. It is presumed that during this period, the culture moves gradually from glucose to ethanol utilization, derepressing the promoter, activating recombinant protein biosynthesis and consequently resuming metabolism without the typical diauxic phase of batch cultures. JF - Journal of Industrial Microbiology & Biotechnology AU - Noronha, S B AU - Kaslow, D C AU - Shiloach, J AD - Biotechnology Unit, LCDB, NIDDK, NIH, Bethesda, MD 20892, USA, US Y1 - 1998/03// PY - 1998 DA - Mar 1998 SP - 192 EP - 199 PB - Springer-Verlag, Tiergartenstrasse 17 Heidelberg 69121 Germany VL - 20 IS - 3-4 SN - 1367-5435, 1367-5435 KW - Microbiology Abstracts A: Industrial & Applied Microbiology; ASFA 1: Biological Sciences & Living Resources; ASFA 3: Aquatic Pollution & Environmental Quality; Microbiology Abstracts C: Algology, Mycology & Protozoology; Biotechnology and Bioengineering Abstracts KW - Yeasts KW - Human diseases KW - Protein biosynthesis KW - Fermentation KW - Glucose KW - Disease control KW - Malaria KW - Saccharomyces cerevisiae KW - Batch culture KW - Recombinants KW - Promoters KW - Protein turnover KW - Vaccines KW - Ethanol KW - A 01490:Miscellaneous KW - Q1 08484:Species interactions: parasites and diseases KW - W 30915:Pharmaceuticals & Vaccines KW - Q5 08524:Public health, medicines, dangerous organisms KW - K 03310:Genetics & Taxonomy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/856785294?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aasfaaquaticpollution&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Industrial+Microbiology+%26+Biotechnology&rft.atitle=Transition+phase+in+the+production+of+recombinant+proteins+in+yeast+under+the+ADH2+promoter%3A+an+important+step+for+reproducible+manufacturing+of+a+malaria+transmission+blocking+vaccine+candidate&rft.au=Noronha%2C+S+B%3BKaslow%2C+D+C%3BShiloach%2C+J&rft.aulast=Noronha&rft.aufirst=S&rft.date=1998-03-01&rft.volume=20&rft.issue=3-4&rft.spage=192&rft.isbn=&rft.btitle=&rft.title=Journal+of+Industrial+Microbiology+%26+Biotechnology&rft.issn=13675435&rft_id=info:doi/10.1038%2Fsj.jim.2900507 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2011-03-01 N1 - Last updated - 2015-10-28 N1 - SubjectsTermNotLitGenreText - Yeasts; Recombinants; Promoters; Human diseases; Fermentation; Disease control; Glucose; Malaria; Vaccines; Protein biosynthesis; Protein turnover; Batch culture; Ethanol; Saccharomyces cerevisiae DO - http://dx.doi.org/10.1038/sj.jim.2900507 ER - TY - JOUR T1 - Square-wave action dystonia in Parkinson's disease. AN - 85420469; pmid-9539355 JF - Movement disorders : official journal of the Movement Disorder Society AU - van den Munckhof, P AU - Lenz, F A AU - Chase, T N AD - Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-1406, USA. Y1 - 1998/03// PY - 1998 DA - March 1998 SP - 354 EP - 356 VL - 13 IS - 2 SN - 0885-3185, 0885-3185 KW - Index Medicus KW - National Library of Medicine KW - Carbidopa -- administration & dosage KW - Antiparkinson Agents -- adverse effects KW - Dominance, Cerebral -- physiology KW - Antiparkinson Agents -- administration & dosage KW - Humans KW - Carbidopa -- adverse effects KW - Globus Pallidus -- physiopathology KW - Globus Pallidus -- surgery KW - Drug Combinations KW - Dominance, Cerebral -- drug effects KW - Levodopa -- administration & dosage KW - Neurologic Examination -- drug effects KW - Globus Pallidus -- drug effects KW - Middle Aged KW - Levodopa -- adverse effects KW - Male KW - Dystonia -- surgery KW - Dystonia -- chemically induced KW - Dystonia -- diagnosis KW - Parkinson Disease -- physiopathology KW - Dystonia -- physiopathology KW - Parkinson Disease -- surgery KW - Parkinson Disease -- diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85420469?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Movement+disorders+%3A+official+journal+of+the+Movement+Disorder+Society&rft.atitle=Square-wave+action+dystonia+in+Parkinson%27s+disease.&rft.au=van+den+Munckhof%2C+P%3BLenz%2C+F+A%3BChase%2C+T+N&rft.aulast=van+den+Munckhof&rft.aufirst=P&rft.date=1998-03-01&rft.volume=13&rft.issue=2&rft.spage=354&rft.isbn=&rft.btitle=&rft.title=Movement+disorders+%3A+official+journal+of+the+Movement+Disorder+Society&rft.issn=08853185&rft_id=info:doi/ LA - English DB - ComDisDome N1 - Date revised - 2008-01-14 N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Quantitative and qualitative differences in the verbal learning performance of elderly depressives and healthy controls. AN - 85420208; pmid-9529821 AB - We compared the verbal learning and memory performance of 57 inpatients with unipolar major depression and 30 nondepressed control participants using the California Verbal Learning Test. The effect of age within this elderly sample was also examined, controlling for sex, educational attainment, and estimated level of intelligence. Except for verbal retention, the depressive had deficits in most aspects of performance, including cued and uncued recall and delayed recognition memory. As well, there were interactions between depression effects and age effects on some measures such that depressives' performance declined more rapidly with age than did the performance of controls. The results are discussed in the context of recent contradictory reports about the integrity of learning and memory functions in late-life depression. We conclude that there is consistent evidence, from this and other studies, that elderly depressed inpatients have significant deficits in a range of explicit verbal learning functions. JF - Journal of the International Neuropsychological Society : JINS AU - King, D A AU - Cox, C AU - Lyness, J M AU - Conwell, Y AU - Caine, E D AD - Department of Psychiatry, University of Rochester School of Medicine and Dentistry, UR-NIMH Center for the Study of Psychopathology of the Elderly, NY 14642-8408, USA. Y1 - 1998/03// PY - 1998 DA - March 1998 SP - 115 EP - 126 VL - 4 IS - 2 SN - 1355-6177, 1355-6177 KW - Index Medicus KW - National Library of Medicine KW - Aged, 80 and over KW - Humans KW - Adult KW - Middle Aged KW - Adolescent KW - Female KW - Male KW - Depressive Disorder -- psychology KW - Aged -- psychology KW - Verbal Learning -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85420208?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+International+Neuropsychological+Society+%3A+JINS&rft.atitle=Quantitative+and+qualitative+differences+in+the+verbal+learning+performance+of+elderly+depressives+and+healthy+controls.&rft.au=King%2C+D+A%3BCox%2C+C%3BLyness%2C+J+M%3BConwell%2C+Y%3BCaine%2C+E+D&rft.aulast=King&rft.aufirst=D&rft.date=1998-03-01&rft.volume=4&rft.issue=2&rft.spage=115&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+International+Neuropsychological+Society+%3A+JINS&rft.issn=13556177&rft_id=info:doi/ LA - English DB - ComDisDome N1 - Date revised - 2008-01-14 N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Behavioral phenotype of Smith-Magenis syndrome (del 17p11.2). AN - 85278215; pmid-9613859 AB - Smith-Magenis syndrome (SMS) is a distinct and clinically recognizable multiple congenital anomaly (MCA) and mental retardation syndrome caused by an interstitial deletion of chromosome 17 p11.2. The phenotype of SMS has been well described and includes: a characteristic pattern of physical features; a hoarse, deep voice; speech delay with or without associated hearing loss; signs of peripheral neuropathy; variable levels of mental retardation; and neurobehavioral problems. Although self-injury and sleep disturbance are major problems in SMS, studies are limited on the behavioral phenotype of SMS. This report reviews the current state of knowledge about SMS and presents new data based on syndrome-specific observations by the authors' longitudinal experience working with SMS, specifically related to the behavioral aspects of SMS. This information should have relevance for parents, clinicians, geneticists, and educators involved in the care of individuals with SMS. JF - American Journal of Medical Genetics AU - Smith, A C AU - Dykens, E AU - Greenberg, F AD - Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892-1267, USA. PY - 1998 SP - 179 EP - 185 VL - 81 IS - 2 SN - 0148-7299, 0148-7299 KW - Mental Retardation KW - Phenotype KW - Behavior Therapy KW - Human KW - Syndrome KW - Abnormalities, Multiple KW - Sleep Disorders KW - Child KW - Self-Injurious Behavior KW - Chromosomes, Human, Pair 17 KW - Behavioral Symptoms KW - Gene Deletion UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85278215?accountid=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=Behavioral+phenotype+of+Smith-Magenis+syndrome+%28del+17p11.2%29.&rft.au=Smith%2C+A+C%3BDykens%2C+E%3BGreenberg%2C+F&rft.aulast=Smith&rft.aufirst=A&rft.date=1998-03-01&rft.volume=81&rft.issue=2&rft.spage=179&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 - Coding strategies in monkey V1 and inferior temporal cortices. AN - 85242721; pmid-9497396 AB - We would like to know whether the statistics of neuronal responses vary across cortical areas. We examined stimulus-elicited spike count response distributions in V1 and inferior temporal (IT) cortices of awake monkeys. In both areas, the distribution of spike counts for each stimulus was well described by a Gaussian distribution, with the log of the variance in the spike count linearly related to the log of the mean spike count. Two significant differences in response characteristics were found: both the range of spike counts and the slope of the log(variance) versus log(mean) regression were larger in V1 than in IT. However, neurons in the two areas transmitted approximately the same amount of information about the stimuli and had about the same channel capacity (the maximum possible transmitted information given noise in the responses). These results suggest that neurons in V1 use more variable signals over a larger dynamic range than IT neurons, which use less variable signals over a smaller dynamic range. The two coding strategies are approximately as effective in transmitting information. JF - Journal of Neurophysiology AU - Gershon, E D AU - Wiener, M C AU - Latham, P E AU - Richmond, B J AD - Laboratory of Neuropsychology, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, USA. PY - 1998 SP - 1135 EP - 1144 VL - 79 IS - 3 SN - 0022-3077, 0022-3077 KW - Probability KW - Regression Analysis KW - Neurons KW - Pattern Recognition, Visual KW - Temporal Lobe KW - Animal KW - Normal Distribution KW - Macaca mulatta KW - Electrophysiology KW - Poisson Distribution KW - Wakefulness KW - Brain Mapping UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85242721?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Neurophysiology&rft.atitle=Coding+strategies+in+monkey+V1+and+inferior+temporal+cortices.&rft.au=Gershon%2C+E+D%3BWiener%2C+M+C%3BLatham%2C+P+E%3BRichmond%2C+B+J&rft.aulast=Gershon&rft.aufirst=E&rft.date=1998-03-01&rft.volume=79&rft.issue=3&rft.spage=1135&rft.isbn=&rft.btitle=&rft.title=Journal+of+Neurophysiology&rft.issn=00223077&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Contribution of human prefrontal cortex to delay performance. AN - 85236176; pmid-9555105 AB - Neurological patients with focal lesions in the dorsolateral prefrontal cortex and age-matched control subjects were tested on an auditory version of the delayed-match-to-sample task employing environmental sounds. Subjects had to indicate whether a cue (s/S1) and a subsequent target sound (S2) were identical. On some trials, S1 and S2 were separated by a silent period of 5 sec. On other trials, the 5-sec delay between S1 and S2 was filled with irrelevant tone pips that served as distractors. Behaviorally, frontal patients were impaired by the presence of distractors. Electrophysiologically, patients generated enhanced primary auditory cortex-evoked responses to the tone pips, supporting a failure in inhibitory control of sensory processing after prefrontal damage. Intrahemispheric reductions of neural activity generated in the auditory association cortex and additional intrahemispheric reductions of attention-related frontal activity were also observed in the prefrontal patients. Together, these findings suggest that the dorsolateral prefrontal cortex is crucial for gating distracting information as well as maintaining distributed intrahemispheric neural activity during auditory working memory. JF - Journal of Cognitive Neuroscience AU - Chao, L L AU - Knight, R T AD - National Institute of Mental Health, Laboratory of Brain and Cognition, Bethesda, MD 20892, USA. PY - 1998 SP - 167 EP - 177 VL - 10 IS - 2 SN - 0898-929X, 0898-929X KW - Human KW - Electroencephalography KW - Cues KW - Evoked Potentials, Auditory KW - Aged KW - Acoustic Stimulation KW - Psychomotor Performance KW - Prefrontal Cortex KW - Cerebrovascular Disorders KW - Female KW - Male KW - Reaction Time UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85236176?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Cognitive+Neuroscience&rft.atitle=Contribution+of+human+prefrontal+cortex+to+delay+performance.&rft.au=Chao%2C+L+L%3BKnight%2C+R+T&rft.aulast=Chao&rft.aufirst=L&rft.date=1998-03-01&rft.volume=10&rft.issue=2&rft.spage=167&rft.isbn=&rft.btitle=&rft.title=Journal+of+Cognitive+Neuroscience&rft.issn=0898929X&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Biological evaluation of compounds for their physical dependence potential and abuse liability. XXI. Drug evaluation committee of the college on problems of drug dependence (1997). AN - 80034834; 9686403 JF - NIDA research monograph AU - Jacobson, A E AD - Laboratory of Medicinal Chemistry, National Institutes of Health, Bethesda, MD, USA. Y1 - 1998/03// PY - 1998 DA - March 1998 SP - 346 EP - 362 VL - 178 SN - 1046-9516, 1046-9516 KW - Analgesics KW - 0 KW - Analgesics, Opioid KW - Index Medicus KW - Animals KW - Organizations KW - Analgesics, Opioid -- pharmacology KW - Analgesics -- pharmacology KW - Haplorhini KW - Structure-Activity Relationship KW - Substance-Related Disorders -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80034834?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=NIDA+research+monograph&rft.atitle=Biological+evaluation+of+compounds+for+their+physical+dependence+potential+and+abuse+liability.+XXI.+Drug+evaluation+committee+of+the+college+on+problems+of+drug+dependence+%281997%29.&rft.au=Jacobson%2C+A+E&rft.aulast=Jacobson&rft.aufirst=A&rft.date=1998-03-01&rft.volume=178&rft.issue=&rft.spage=346&rft.isbn=&rft.btitle=&rft.title=NIDA+research+monograph&rft.issn=10469516&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-10-06 N1 - Date created - 1998-10-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CONF T1 - IBC Conference on Engineered Animal Models: Advances and Applications, Washington, DC, USA, 22-23 September 1997. AN - 79959378; 9643963 JF - Transgenic research AU - Wawrousek, E Y1 - 1998/03// PY - 1998 DA - March 1998 SP - 141 EP - 145 VL - 7 IS - 2 KW - Antibodies, Monoclonal KW - 0 KW - Index Medicus KW - Antibodies, Monoclonal -- biosynthesis KW - Animals KW - Humans KW - Carcinogenicity Tests KW - Biological Specimen Banks KW - Mice KW - Mice, Transgenic KW - Genetic Engineering KW - Transgenes KW - Disease Models, Animal KW - Cloning, Organism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79959378?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&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=Transgenic+research&rft.atitle=IBC+Conference+on+Engineered+Animal+Models%3A+Advances+and+Applications%2C+Washington%2C+DC%2C+USA%2C+22-23+September+1997.&rft.au=Wawrousek%2C+E&rft.aulast=Wawrousek&rft.aufirst=E&rft.date=1998-03-01&rft.volume=7&rft.issue=2&rft.spage=141&rft.isbn=&rft.btitle=&rft.title=Transgenic+research&rft.issn=09628819&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-06-24 N1 - Date created - 1998-06-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Diversity of DNA topoisomerases I and inhibitors. AN - 79920915; 9615865 AB - The present review first describes the different type I topoisomerases found in eukaryotic cells: nuclear topoisomerase I (top1), topoisomerase 3 (top3), mitochondrial topoisomerase I and viral topoisomerases I. The second part of the review provides extensive information on the topoisomerase I inhibitors identified to date. These drugs can be grouped in two categories: top1 poisons and top1 suppressors. Both inhibit enzyme catalytic activity but top1 poisons trap the top1 catalytic intermediates ('cleavage complexes') while top1 suppressors prevent or reverse top1 cleavage complexes. The molecular interactions of camptothecin with the top1 cleavage complexes are discussed as well as the mechanisms of selective killing of cancer cells. JF - Biochimie AU - Pommier, Y AD - Laboratory of Molecular Pharmacology, National Cancer Institute, Bethesda, MD 20892-4255, USA. Y1 - 1998/03// PY - 1998 DA - March 1998 SP - 255 EP - 270 VL - 80 IS - 3 SN - 0300-9084, 0300-9084 KW - Antineoplastic Agents KW - 0 KW - Enzyme Inhibitors KW - Topoisomerase I Inhibitors KW - DNA Topoisomerases, Type I KW - EC 5.99.1.2 KW - Index Medicus KW - Animals KW - Humans KW - Enzyme Inhibitors -- pharmacology KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79920915?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochimie&rft.atitle=Diversity+of+DNA+topoisomerases+I+and+inhibitors.&rft.au=Pommier%2C+Y&rft.aulast=Pommier&rft.aufirst=Y&rft.date=1998-03-01&rft.volume=80&rft.issue=3&rft.spage=255&rft.isbn=&rft.btitle=&rft.title=Biochimie&rft.issn=03009084&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-08-07 N1 - Date created - 1998-08-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Delayed auditory feedback during smoking cessation. AN - 79900909; 9604857 AB - Delays between speech production and hearing, delayed auditory feedback (DAF), reduce speech and reading rates. Smoking cessation in heavy smokers causes subjective reports of difficulty in concentration, decrements in cognitive performance, and EEG changes. The purpose of the present study was to determine if tobacco cessation disrupts linguistic processing as modeled by the DAF paradigm. Smokers (n = 14) were tested on 3 d of ad libitum smoking and 3 d no smoking. At each session, they read a word list (24 words) and a story (about 57 words) with and without delay (220 msec). The delay significantly decreased reading speed of the story from 3.4 to 2.9 words per second (wps) and of list from 2.1 to 1.7 wps. However, tobacco cessation had no significant effect on reading speed and no interaction with DAF. Although tobacco withdrawal slows performance on cognitive tasks, linguistic processing modeled by DAF is preserved. DAF may prove useful for the study of other drug classes and drug withdrawal states. JF - Methods and findings in experimental and clinical pharmacology AU - Friedman, A AU - Stanton, J P AU - Gnjidic, M AU - Fant, R V AU - Pickworth, W B AD - National Institute on Drug Abuse, Addiction Research Center, Baltimore, Maryland, USA. Y1 - 1998/03// PY - 1998 DA - March 1998 SP - 147 EP - 153 VL - 20 IS - 2 SN - 0379-0355, 0379-0355 KW - Nicotine KW - 6M3C89ZY6R KW - Index Medicus KW - Humans KW - Nicotine -- adverse effects KW - Adult KW - Substance Withdrawal Syndrome -- physiopathology KW - Auditory Perception -- physiology KW - Smoking Cessation KW - Feedback UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79900909?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Methods+and+findings+in+experimental+and+clinical+pharmacology&rft.atitle=Delayed+auditory+feedback+during+smoking+cessation.&rft.au=Friedman%2C+A%3BStanton%2C+J+P%3BGnjidic%2C+M%3BFant%2C+R+V%3BPickworth%2C+W+B&rft.aulast=Friedman&rft.aufirst=A&rft.date=1998-03-01&rft.volume=20&rft.issue=2&rft.spage=147&rft.isbn=&rft.btitle=&rft.title=Methods+and+findings+in+experimental+and+clinical+pharmacology&rft.issn=03790355&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-07-30 N1 - Date created - 1998-07-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The cloning and characterization of a novel cytochrome P450 family, CYP26, with specificity toward retinoic acid. AN - 79821590; 9564181 AB - A new family of cytochrome P450 enzymes, CYP26, has been cloned and characterized in zebra fish, human, and mouse tissues. CYP26 displays specificity toward retinoic acid and it may function as an important regulator or differentiation and a possible modulator of disease states by controlling retinoid concentration and homeostasis. JF - Nutrition reviews AU - Haque, M AU - Anreola, F AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA. Y1 - 1998/03// PY - 1998 DA - March 1998 SP - 84 EP - 85 VL - 56 IS - 3 SN - 0029-6643, 0029-6643 KW - Tretinoin KW - 5688UTC01R KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Mixed Function Oxygenases KW - EC 1.- KW - Retinoic Acid 4-Hydroxylase KW - EC 1.14.14.1 KW - Index Medicus KW - Animals KW - Humans KW - Cloning, Molecular KW - Mixed Function Oxygenases -- metabolism KW - Cytochrome P-450 Enzyme System -- genetics KW - Tretinoin -- metabolism KW - Cytochrome P-450 Enzyme System -- metabolism KW - Tretinoin -- therapeutic use KW - Mixed Function Oxygenases -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79821590?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nutrition+reviews&rft.atitle=The+cloning+and+characterization+of+a+novel+cytochrome+P450+family%2C+CYP26%2C+with+specificity+toward+retinoic+acid.&rft.au=Haque%2C+M%3BAnreola%2C+F&rft.aulast=Haque&rft.aufirst=M&rft.date=1998-03-01&rft.volume=56&rft.issue=3&rft.spage=84&rft.isbn=&rft.btitle=&rft.title=Nutrition+reviews&rft.issn=00296643&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-05-28 N1 - Date created - 1998-05-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Current management of infectious complications in the injecting drug user. AN - 79818418; 9561947 AB - The diagnosis and management of infectious complications associated with injection drug use (IDU) are among some of the more challenging aspects of working with substance abusing populations. As the population of injection drug users age, we expect the number and severity of these complications to increase. Commonly seen infections, such as bacterial endocarditis and bacterial infections of bones, joints, and soft tissue, are now frequently complicated by concurrent immunodeficiency. Parenterally and sexually transmitted viral hepatitis is responsible for significant IDU morbidity and mortality. The human leukemia/lymphoma virus types I and II are increasing in prevalence in the IDU with uncertain long-term clinical effects. Immune dysfunction has been described in the IDU for decades, but the impact of host immune compromise on the transmission and the course of HIV-1 has yet to be fully appreciated. The integration of the treatment of substance abuse and its concurrent psychiatric disorders with the management of infectious complications, including immunodeficiency, promises to improve patient compliance with possible savings of overall medical costs. JF - Journal of substance abuse treatment AU - Contoreggi, C AU - Rexroad, V E AU - Lange, W R AD - Division of Intramural Research, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA. ccontore@irp.nida.nih.gov PY - 1998 SP - 95 EP - 106 VL - 15 IS - 2 SN - 0740-5472, 0740-5472 KW - Index Medicus KW - AIDS/HIV KW - Humans KW - Infection -- etiology KW - Infection -- therapy KW - Substance Abuse, Intravenous -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79818418?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Current+management+of+infectious+complications+in+the+injecting+drug+user.&rft.au=Contoreggi%2C+C%3BRexroad%2C+V+E%3BLange%2C+W+R&rft.aulast=Contoreggi&rft.aufirst=C&rft.date=1998-03-01&rft.volume=15&rft.issue=2&rft.spage=95&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 - 1998-06-16 N1 - Date created - 1998-06-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Estrogen-dependent gene regulation by an oxidative metabolite of diethylstilbestrol, diethylstilbestrol-4',4"-quinone. AN - 79816846; 9558716 AB - Diethylstilbestrol (DES) is a well-characterized carcinogen in humans and animals although its mechanisms of carcinogenicity are not yet known. While the estrogenic activity of DES is important, there is evidence that oxidative metabolism also plays an important role for its toxicity. DES is oxidatively metabolized in vivo and in vitro to a number of compounds including diethylstilbestrol-4',4"-quinone (DQ), an unstable and reactive intermediate, and Z,Z-dienestrol (ZZ-DIEN). Estrogen receptor (ER) binding assays with mouse uterine cytosol indicate that DES, DQ and ZZ-DIEN have relative binding affinities of 286, 3.6 and 0.3, respectively, relative to estradiol as 100. In addition, DQ binds irreversibly and specifically to ER suggesting that DQ may be biologically active despite its rapid metabolism and lower binding affinity compared to DES. To test this, COS-1 cells were transfected with an estrogen responsive reporter construct containing of VitA2 estrogen response element (ERE) with or without an ER expression vector. In the presence of ER, treatments with DES, DQ and ZZ-DIEN resulted in 11, 10, and 2-fold induction of chloramphenicol acetyltransferase (CAT) activity, respectively. This induction was mediated by estrogen receptor since it was suppressed by pretreatment with a 10-fold excess of the pure antiestrogen ICI 182,780. These data indicate that DQ is a biologically active intermediate that is capable of transactivation of estrogen responsive genes through the ER. Furthermore, the data suggest that the ability of DQ to irreversibly bind ER may result in persistent stimulation of ER. This persistent stimulation may be related to the carcinogenicity of DES. JF - Steroids AU - Chae, K AU - Lindzey, J AU - McLachlan, J A AU - Korach, K S AD - Receptor Biology Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1998/03// PY - 1998 DA - March 1998 SP - 149 EP - 157 VL - 63 IS - 3 SN - 0039-128X, 0039-128X KW - Receptors, Estrogen KW - 0 KW - diethylstilbestrol quinone KW - 5664-37-9 KW - Diethylstilbestrol KW - 731DCA35BT KW - Chloramphenicol O-Acetyltransferase KW - EC 2.3.1.28 KW - Index Medicus KW - Oxidation-Reduction KW - Chloramphenicol O-Acetyltransferase -- genetics KW - Animals KW - COS Cells KW - Transfection KW - Mice KW - Female KW - Chromatography, High Pressure Liquid KW - Diethylstilbestrol -- metabolism KW - Receptors, Estrogen -- genetics KW - Diethylstilbestrol -- pharmacology KW - Gene Expression Regulation -- drug effects KW - Diethylstilbestrol -- analogs & derivatives KW - Receptors, Estrogen -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79816846?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Steroids&rft.atitle=Estrogen-dependent+gene+regulation+by+an+oxidative+metabolite+of+diethylstilbestrol%2C+diethylstilbestrol-4%27%2C4%22-quinone.&rft.au=Chae%2C+K%3BLindzey%2C+J%3BMcLachlan%2C+J+A%3BKorach%2C+K+S&rft.aulast=Chae&rft.aufirst=K&rft.date=1998-03-01&rft.volume=63&rft.issue=3&rft.spage=149&rft.isbn=&rft.btitle=&rft.title=Steroids&rft.issn=0039128X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-05-27 N1 - Date created - 1998-05-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Perchlorate and the thyroid gland. AN - 79807953; 9549759 AB - Perchlorate competitively blocks iodide from entering the thyroid by an effect on the Na+/I- symporter thus preventing the further synthesis of thyroid hormone but has no effect on the iodination process itself. It is concentrated by thyroid tissue in a manner similar to iodide but is not significantly metabolized in the gland or peripherally. What is not settled is whether there are additional perchlorate effects on iodide transport. Perchlorate has a fast turnover in the body and requires frequent daily doses for therapy of thyrotoxicosis. Perchlorate appears to be substantially more effective against large iodide loads than the thionamides, and, with long-term iodide contamination, combined therapy of perchlorate (with < or = 1 g/day) and thionamides is recommended for the more severe cases of thyrotoxicosis that may result from excess iodide or iodide-generating organic compounds, as for example with amiodarone. After approximately 30 days, the perchlorate dosage can be tapered or stopped, continuing with thionamides alone. This markedly increases its safe use. Despite serious side effects during its early use, lower dosages and shorter treatment periods appear to have prevented such reactions in its recent reintroduction, mostly for amiodarone-induced thyroid dysfunction. Perchlorate can also protect against inhibition of thyroid function and the resulting hypothyroidism caused by excess iodide, presumably by reducing the formation of an iodinated inhibitor. The reduction of the iodide pool by perchlorate thus has dual effects--reduction of excess hormone synthesis and hyperthyroidism, on the one hand, and reduction of thyroid inhibitor synthesis and hypothyroidism on the other. Perchlorate remains very useful also as a single dose application in tests measuring the discharge of radioiodide accumulated in the thyroid as a result of many different disruptions in the further metabolism of iodide in the thyroid gland. JF - Pharmacological reviews AU - Wolff, J AD - Laboratory of Biochemical Pharmacology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1998/03// PY - 1998 DA - March 1998 SP - 89 EP - 105 VL - 50 IS - 1 SN - 0031-6997, 0031-6997 KW - Enzyme Inhibitors KW - 0 KW - Iodides KW - Perchlorates KW - Sodium Compounds KW - sodium perchlorate KW - 97F4MTY3VA KW - Iodide Peroxidase KW - EC 1.11.1.8 KW - Amiodarone KW - N3RQ532IUT KW - Index Medicus KW - Iodide Peroxidase -- metabolism KW - Animals KW - Enzyme Inhibitors -- therapeutic use KW - Iodides -- pharmacology KW - Humans KW - Hypothyroidism -- drug therapy KW - Amiodarone -- therapeutic use KW - Enzyme Inhibitors -- chemistry KW - Thyrotoxicosis -- drug therapy KW - Amiodarone -- adverse effects KW - Amiodarone -- chemistry KW - Iodide Peroxidase -- drug effects KW - Amiodarone -- pharmacology KW - Iodides -- metabolism KW - Kinetics KW - Thyrotoxicosis -- chemically induced KW - Sodium Compounds -- therapeutic use KW - Sodium Compounds -- pharmacology KW - Thyroid Gland -- physiology KW - Sodium Compounds -- chemistry KW - Thyroid Gland -- drug effects KW - Sodium Compounds -- metabolism KW - Perchlorates -- adverse effects KW - Perchlorates -- therapeutic use KW - Perchlorates -- chemistry KW - Sodium Compounds -- adverse effects KW - Perchlorates -- pharmacology KW - Perchlorates -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79807953?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pharmacological+reviews&rft.atitle=Perchlorate+and+the+thyroid+gland.&rft.au=Wolff%2C+J&rft.aulast=Wolff&rft.aufirst=J&rft.date=1998-03-01&rft.volume=50&rft.issue=1&rft.spage=89&rft.isbn=&rft.btitle=&rft.title=Pharmacological+reviews&rft.issn=00316997&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-05-11 N1 - Date created - 1998-05-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Toxicity and carcinogenicity studies of oxazepam in the Fischer 344 rat. AN - 79791841; 9538042 AB - Oxazepam and related benzodiazepines are used in the treatment of anxiety. Carcinogenicity studies of oxazepam were performed with the F344 rat because of marked differences in tumor responses observed in NTP studies with B6C3F1 and Swiss-Webster mice compared to the results of Sprague-Dawley rat studies submitted to the FDA by a manufacturer to support registration of the drug. Groups of 50 male and 50 female F344/N rats were fed diets containing 0, 625, 2500, or 5000 ppm oxazepam for up to 105 weeks. A stop-exposure group of 50 males and 50 females received 10,000 ppm oxazepam in diet for 26 weeks, after which animals received control diet. All 5000- and 10, 000-ppm stop-exposure males died before the end of the study. Survival of 2500-ppm males and females was lower than that of controls. Body weight gains of 2500- and 5000-ppm males and females were less than those of controls. Male rats exposed to 2500 ppm had an increased incidence of renal tubule adenoma and hyperplasia. In addition, the incidences of renal tubule adenoma and hyperplasia were increased in the 10,000-ppm stop-exposure group. The incidences of nephropathy in exposed females were greater than those in controls, and the severity of nephropathy increased in exposed males. Epithelial hyperplasia and chronic inflammation of the nonglandular stomach were increased in males given 2500 and 5000 ppm and the incidence of ulcers of the nonglandular stomach in 2500-ppm males was also greater than that in controls. In males exposed to 5000 ppm, mineralization of the glandular stomach and erosion of the duodenum were observed. In females exposed to 2500 ppm, the incidences of epithelial hyperplasia, chronic inflammation, and ulcers of the nonglandular stomach and the incidence of erosion in the glandular stomach were increased. The incidences of centrilobular hepatocyte hypertrophy in males and females given 2500 and 5000 ppm were greater than those in controls. In summary, there was equivocal evidence of carcinogenicity in males based on increased renal tubule adenomas in groups which also had significantly enhanced nephropathy. There was no evidence of carcinogenicity of oxazepam in females given a diet containing 625, 2500, or 5000 ppm for 2 years or 10,000 ppm for 6 months. Copyright 1998 Academic Press. JF - Toxicological sciences : an official journal of the Society of Toxicology AU - Bucher, J R AU - Haseman, J K AU - Herbert, R A AU - Hejtmancik, M AU - Ryan, M J AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, 27709, USA. Y1 - 1998/03// PY - 1998 DA - March 1998 SP - 1 EP - 12 VL - 42 IS - 1 SN - 1096-6080, 1096-6080 KW - Anti-Anxiety Agents KW - 0 KW - Oxazepam KW - 6GOW6DWN2A KW - Index Medicus KW - Animals KW - Liver -- pathology KW - Kidney -- pathology KW - Kidney -- drug effects KW - Rats KW - Rats, Inbred F344 KW - Digestive System -- drug effects KW - Liver -- drug effects KW - Body Weight -- drug effects KW - Toxicity Tests KW - Carcinogenicity Tests KW - Digestive System -- pathology KW - Female KW - Male KW - Survival Analysis KW - Oxazepam -- toxicity KW - Kidney Neoplasms -- chemically induced KW - Adenoma -- chemically induced KW - Anti-Anxiety Agents -- toxicity KW - Oxazepam -- blood KW - Anti-Anxiety Agents -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79791841?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.atitle=Toxicity+and+carcinogenicity+studies+of+oxazepam+in+the+Fischer+344+rat.&rft.au=Bucher%2C+J+R%3BHaseman%2C+J+K%3BHerbert%2C+R+A%3BHejtmancik%2C+M%3BRyan%2C+M+J&rft.aulast=Bucher&rft.aufirst=J&rft.date=1998-03-01&rft.volume=42&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.issn=10966080&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-05-22 N1 - Date created - 1998-05-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Power and sample size for stratified prospective studies using the score method for testing relative risk. AN - 79790120; 9544526 AB - We derive the asymptotic power function of the score test for detecting a common relative risk greater than unity from multiple 2 x 2 tables and formulate methods of sample size determination for use when designing stratified prospective studies. The stratified score test is more efficient than the unstratified test when the latter is unbiased. JF - Biometrics AU - Nam, J M AD - Biostatistics Branch, National Cancer Institute, Rockville, Maryland 20892-7368, USA. jn26r@nih.gov Y1 - 1998/03// PY - 1998 DA - March 1998 SP - 331 EP - 336 VL - 54 IS - 1 SN - 0006-341X, 0006-341X KW - Fungicides, Industrial KW - 0 KW - Thiocarbamates KW - di-allate KW - 77003KI5VJ KW - Index Medicus KW - Animals KW - Biometry KW - Humans KW - Cohort Studies KW - Mice KW - Thiocarbamates -- toxicity KW - Sample Size KW - Lung Neoplasms -- chemically induced KW - Fungicides, Industrial -- toxicity KW - Male KW - Female KW - Carcinogenicity Tests -- statistics & numerical data KW - Risk KW - Prospective Studies UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79790120?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Power+and+sample+size+for+stratified+prospective+studies+using+the+score+method+for+testing+relative+risk.&rft.au=Nam%2C+J+M&rft.aulast=Nam&rft.aufirst=J&rft.date=1998-03-01&rft.volume=54&rft.issue=1&rft.spage=331&rft.isbn=&rft.btitle=&rft.title=Biometrics&rft.issn=0006341X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-05-01 N1 - Date created - 1998-05-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Low genetic variation among killer whales (Orcinus orca) in the eastern north Pacific and genetic differentiation between foraging specialists. AN - 79789340; 9542159 AB - Killer whales from the coastal waters off California through Alaska were compared for genetic variation at three nuclear DNA markers and sequenced for a total of 520 bp from the mitochondrial control region. Two putative sympatric populations that range throughout this region were compared. They can be distinguished by social and foraging behavior and are known as "residents" and "transients". We found low levels of variation within populations compared to other cetacean species. Comparisons between fish (resident) versus marine mammal (transient) foraging specialists indicated highly significant genetic differentiation at both nuclear and mitochondrial loci. This differentiation is at a level consistent with intraspecific variation. A comparison between two parapatric resident populations showed a small but fixed mtDNA haplotype difference. Together these data suggest low levels of genetic dispersal between foraging specialists and a pattern of genetic differentiation consistent with matrifocal population structure and small effective population size. JF - The Journal of heredity AU - Hoelzel, A R AU - Dahlheim, M AU - Stern, S J AD - National Cancer Institute, Laboratory of Viral Carcinogenesis, Frederick, Maryland, USA. PY - 1998 SP - 121 EP - 128 VL - 89 IS - 2 SN - 0022-1503, 0022-1503 KW - DNA Primers KW - 0 KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Phylogeny KW - Animals KW - Tooth -- chemistry KW - Feeding Behavior KW - Polymorphism, Single-Stranded Conformational KW - Skin -- chemistry KW - DNA -- isolation & purification KW - Microsatellite Repeats KW - Alleles KW - Base Sequence KW - DNA -- blood KW - Pacific Ocean KW - Molecular Sequence Data KW - DNA -- chemistry KW - Gene Library KW - Genetic Variation KW - Polymorphism, Genetic KW - Whales -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79789340?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Low+genetic+variation+among+killer+whales+%28Orcinus+orca%29+in+the+eastern+north+Pacific+and+genetic+differentiation+between+foraging+specialists.&rft.au=Hoelzel%2C+A+R%3BDahlheim%2C+M%3BStern%2C+S+J&rft.aulast=Hoelzel&rft.aufirst=A&rft.date=1998-03-01&rft.volume=89&rft.issue=2&rft.spage=121&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 - 1998-05-12 N1 - Date created - 1998-05-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of cadmium exposure on background and anti-5 methylchrysene-1,2-dihydrodiol 3,4-epoxide-induced mutagenesis in the supF gene of pS189 in human Ad293 cells. AN - 79785557; 9544619 AB - Cadmium is a toxic environmental contaminant that is carcinogenic in humans and rodents. Although cadmium has proven to be mutagenic in a variety of assay systems, exactly how cadmium achieves gentoxicity is poorly understood. To define the mechanism(s) underlying the mutagenicity and comutagenicity of cadmium, human Ad293 cells were exposed to subtoxic doses of the metal and transfected with untreated or anti-5-methylchrysene-3,4-dihydrodiol 1,2-epoxide (5-MCDE)-treated pS189 shuttle vector. Alterations in the frequency, types, and distribution of mutations were subsequently assessed in the supF gene of pS189 that was replicated in Ad293 cells and screened in indicator bacteria. Doses of 0.5 and 1 microM CdCl2 increased the mutation frequency of untreated pS189 by approximately 4- and 8-fold, respectively, with no apparent effect on the types of mutations generated. In contrast, host-cell exposure to cadmium had little or no effect on the frequency, types, or distribution of mutations generated with 5-MCDE-treated pS189. These results indicate that cadmium increases mutagenesis of untreated pS189 by affecting a process that is not involved in mutagenesis of the 5-MCDE-treated vector. Although it is not clear exactly how host-cell exposure to cadmium increases background mutagenesis, presumably, the mutagenic effect does not involve cadmium interaction with the cellular machinery used to replicate past bulky DNA lesions. JF - Chemical research in toxicology AU - Misra, R R AU - Page, J E AU - Smith, G T AU - Waalkes, M P AU - Dipple, A AD - Inorganic Carcinogenesis Section, Laboratory of Comparative Carcinogenesis, Division of Basic Sciences, National Cancer Institute, Frederick, Maryland 21702, USA. Y1 - 1998/03// PY - 1998 DA - March 1998 SP - 211 EP - 216 VL - 11 IS - 3 SN - 0893-228X, 0893-228X KW - Carcinogens KW - 0 KW - Chrysenes KW - supF tRNA KW - Cadmium KW - 00BH33GNGH KW - 1,2-dihydroxy-epoxy-1,2,3,4-tetrahydro-5-methylchrysene KW - 81851-68-5 KW - RNA, Transfer KW - 9014-25-9 KW - Index Medicus KW - Base Sequence KW - Transfection -- drug effects KW - Point Mutation -- drug effects KW - Humans KW - Molecular Sequence Data KW - Drug Synergism KW - Cell Line KW - Mutagenesis -- drug effects KW - Chrysenes -- toxicity KW - RNA, Transfer -- genetics KW - Plasmids -- genetics KW - Carcinogens -- toxicity KW - Cadmium -- toxicity KW - Plasmids -- drug effects KW - Genes, Suppressor -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79785557?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Effect+of+cadmium+exposure+on+background+and+anti-5+methylchrysene-1%2C2-dihydrodiol+3%2C4-epoxide-induced+mutagenesis+in+the+supF+gene+of+pS189+in+human+Ad293+cells.&rft.au=Misra%2C+R+R%3BPage%2C+J+E%3BSmith%2C+G+T%3BWaalkes%2C+M+P%3BDipple%2C+A&rft.aulast=Misra&rft.aufirst=R&rft.date=1998-03-01&rft.volume=11&rft.issue=3&rft.spage=211&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 - 1998-05-28 N1 - Date created - 1998-05-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Patterns of Y and X chromosome DNA sequence divergence during the Felidae radiation. AN - 79783664; 9539439 AB - The 37 species of modern cats have evolved from approximately eight phylogenetic lineages within the past 10 to 15 million years. The Felidae family has been described with multiple measures of morphologic and molecular evolutionary methods that serve as a framework for tracking gene divergence during brief evolutionary periods. In this report, we compare the mode and tempo of evolution of noncoding sequences of a large intron within Zfy (783 bp) and Zfx (854 bp), homologous genes located on the felid Y and X chromosomes, respectively. Zfy sequence variation evolves at about twice the rate of Zfx, and both gene intron sequences track feline hierarchical topologies accurately. As homoplasies are infrequent in patterns of nucleotide substitution, the Y chromosome sequence displays a remarkable degree of phylogenetic consistency among cat species and provides a highly informative glimpse of divergence of sex chromosome sequences in Felidae. JF - Genetics AU - Pecon Slattery, J AU - O'Brien, S J AD - Laboratory of Genomic Diversity, Frederick Cancer and Research and Development Center, National Cancer Institute, Maryland 21702, USA. slattery@fcrfv2.ncifcrf.gov Y1 - 1998/03// PY - 1998 DA - March 1998 SP - 1245 EP - 1255 VL - 148 IS - 3 SN - 0016-6731, 0016-6731 KW - DNA-Binding Proteins KW - 0 KW - Kruppel-Like Transcription Factors KW - Transcription Factors KW - zinc finger protein, X-linked KW - Index Medicus KW - Phylogeny KW - Animals KW - Cats -- genetics KW - Introns KW - DNA-Binding Proteins -- genetics KW - Sequence Analysis, DNA KW - Mutagenesis KW - Genetic Variation KW - X Chromosome KW - Carnivora -- genetics KW - Y Chromosome KW - Carnivora -- classification KW - Evolution, Molecular UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79783664?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Patterns+of+Y+and+X+chromosome+DNA+sequence+divergence+during+the+Felidae+radiation.&rft.au=Pecon+Slattery%2C+J%3BO%27Brien%2C+S+J&rft.aulast=Pecon+Slattery&rft.aufirst=J&rft.date=1998-03-01&rft.volume=148&rft.issue=3&rft.spage=1245&rft.isbn=&rft.btitle=&rft.title=Genetics&rft.issn=00166731&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-06-01 N1 - Date created - 1998-06-01 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Mol Biol. 1970 Mar;48(3):443-53 [5420325] J Mol Evol. 1997 Apr;44(4):463-5 [9089087] Cell. 1987 Dec 24;51(6):1091-104 [3690661] Cold Spring Harb Symp Quant Biol. 1987;52:863-7 [3454295] Science. 1989 Jan 6;243(4887):78-80 [2563173] Cell. 1989 Mar 10;56(5):765-70 [2493989] Cell. 1989 Jun 30;57(7):1247-58 [2500252] Nature. 1989 Dec 7;342(6250):708-11 [2512506] Proc Natl Acad Sci U S A. 1990 Mar;87(5):1681-5 [2308929] Science. 1991 Mar 1;251(4997):1030-3 [1998119] J Mol Evol. 1991 Apr;32(4):310-5 [1907665] J Mol Evol. 1992 Jan;34(1):54-61 [1556744] Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7591-5 [1323846] Genomics. 1993 Feb;15(2):317-22 [8449497] Nature. 1993 Apr 22;362(6422):745-7 [8469284] J Mol Evol. 1993 Aug;37(2):160-6 [8411204] Proc Natl Acad Sci U S A. 1994 Jan 18;91(2):827-31 [8290607] J Mol Evol. 1993 Oct;37(4):441-56 [8308912] J Mol Evol. 1994 Sep;39(3):296-305 [7932791] J Mol Evol. 1994 Dec;39(6):569-78 [7807546] J Mol Evol. 1995 Jan;40(1):70-7 [7714913] Bioessays. 1995 Apr;17(4):311-20 [7741724] Mol Biol Evol. 1995 Jul;12(4):690-707 [7544865] Mol Phylogenet Evol. 1996 Dec;6(3):351-65 [8975691] Mol Biol Evol. 1997 Mar;14(3):277-86 [9066795] Nature. 1997 Mar 27;386(6623):388-92 [9121553] Proc Natl Acad Sci U S A. 1978 Nov;75(11):5618-22 [281711] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - T cell-depleted bone marrow transplantation and delayed T cell add-back to control acute GVHD and conserve a graft-versus-leukemia effect. AN - 79782507; 9543057 AB - Thirty-eight patients with hematological malignancies, received T cell-depleted marrow transplants (BMT) and cyclosporine to prevent acute graft-versus-host disease (aGVHD), followed by delayed add-back of donor lymphocytes to prevent leukemia relapse. In 26 patients scheduled for donor T cell add-back of 2 x 10(6) cells/kg on day 30 and 5 x 10(7) cells/kg on day 45 (schedule 1), the overall probability of grade > or = II aGVHD developing was 31.5%, with a 15.5% probability of aGVHD occurring after T cell add-back. In 12 patients receiving 10(7) donor T cells/kg on day 30 (schedule 2), the probability of grade > or = II aGVHD was 100%. The incidence of grade III-IV aGVHD was higher in schedule 2 than in schedule 1 (P=0.02). Of 24 evaluable patients, 10 (46%) developed chronic GVHD which was limited in eight and extensive in two. Current disease-free survival for 18 patients at standard risk for relapse (chronic myeloid leukemia (CML) in chronic or accelerated phase, acute myeloid leukemia in remission) vs 20 patients with more advanced leukemia or multiple myeloma were respectively 72% vs 12% (P < 0.01) with a 29% vs 69% probability of relapse (P=0.08). In 12 CML patients surviving more than 3 months, PCR analysis of the BCR/ABL transcript showed that minimal residual disease after T cell add-back was transient except in two patients who developed hematological relapse. Results indicate that the risk of acute GVHD is low following substantial T cell doses, transfused 45 days after transplant, using cyclosporine prophylaxis. Furthermore a graft-versus-leukemia effect was conserved. JF - Bone marrow transplantation AU - Barrett, A J AU - Mavroudis, D AU - Tisdale, J AU - Molldrem, J AU - Clave, E AU - Dunbar, C AU - Cottler-Fox, M AU - Phang, S AU - Carter, C AU - Okunnieff, P AU - Young, N S AU - Read, E J AD - Bone Marrow Transplant Unit, Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA. Y1 - 1998/03// PY - 1998 DA - March 1998 SP - 543 EP - 551 VL - 21 IS - 6 SN - 0268-3369, 0268-3369 KW - Immunosuppressive Agents KW - 0 KW - Cyclophosphamide KW - 8N3DW7272P KW - Index Medicus KW - Transplantation Conditioning KW - Humans KW - Whole-Body Irradiation KW - Cyclophosphamide -- therapeutic use KW - Cytomegalovirus Infections -- complications KW - Adult KW - Treatment Outcome KW - Incidence KW - Middle Aged KW - Immunosuppressive Agents -- therapeutic use KW - Female KW - Male KW - Secondary Prevention KW - Bone Marrow Transplantation -- methods KW - Leukemia -- therapy KW - Lymphocyte Transfusion KW - T-Lymphocytes -- transplantation KW - Graft vs Host Disease -- epidemiology KW - Leukemia -- complications KW - Graft vs Host Disease -- prevention & control KW - Graft vs Host Reaction UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79782507?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Bone+marrow+transplantation&rft.atitle=T+cell-depleted+bone+marrow+transplantation+and+delayed+T+cell+add-back+to+control+acute+GVHD+and+conserve+a+graft-versus-leukemia+effect.&rft.au=Barrett%2C+A+J%3BMavroudis%2C+D%3BTisdale%2C+J%3BMolldrem%2C+J%3BClave%2C+E%3BDunbar%2C+C%3BCottler-Fox%2C+M%3BPhang%2C+S%3BCarter%2C+C%3BOkunnieff%2C+P%3BYoung%2C+N+S%3BRead%2C+E+J&rft.aulast=Barrett&rft.aufirst=A&rft.date=1998-03-01&rft.volume=21&rft.issue=6&rft.spage=543&rft.isbn=&rft.btitle=&rft.title=Bone+marrow+transplantation&rft.issn=02683369&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-05-27 N1 - Date created - 1998-05-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Melatonin: receptor-mediated events that may affect breast and other steroid hormone-dependent cancers. AN - 79775570; 9537645 AB - Epidemiological studies have suggested a possible link between extremely low frequency electromagnetic fields (EMFs) and increased rates of certain cancers. One cancer that has been postulated to be associated with EMF exposure is breast cancer, for which increased rates have been reported among electricians. These cancer associations are weak, and the link to EMF exposures remains tenuous. Understanding the mechanisms by which EMFs could have biological effects will help in elucidating the risk, if any, from EMFs. One hypothesis that has received considerable attention involves reduction of melatonin levels by EMFs. This hypothesis suggests that loss of melatonin affects a variety of hormonal processes such as estrogen homeostasis and thereby may increase breast cancer rates. Since this theory was first presented, putative melatonin receptors have been cloned, providing new tools with which to examine melatonin's mechanism of action and the melatonin hypothesis. These receptors are found in nuclear and membrane fractions of cells. The nuclear receptors (retinoid Z receptors) are found both in the brain and in non-neural tissues, whereas the membrane-bound receptors are found primarily in neural tissue and have a higher affinity for melatonin. These receptors may control a variety of hormonal and immunological functions, including the release of gonadotropins from the hypothalamus and pituitary and 5-lipoxygenase activity in B lymphocytes. This Working Hypothesis briefly reviews our current knowledge of melatonin receptors and then provides theories on how the inactivation of melatonin receptors may cause cancer and suggests areas of research for addressing this question. JF - Molecular carcinogenesis AU - Baldwin, W S AU - Barrett, J C AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1998/03// PY - 1998 DA - March 1998 SP - 149 EP - 155 VL - 21 IS - 3 SN - 0899-1987, 0899-1987 KW - Receptors, Cell Surface KW - 0 KW - Receptors, Cytoplasmic and Nuclear KW - Receptors, Melatonin KW - Melatonin KW - JL5DK93RCL KW - Index Medicus KW - Humans KW - Receptors, Cytoplasmic and Nuclear -- physiology KW - Melatonin -- physiology KW - Electromagnetic Fields -- adverse effects KW - Breast Neoplasms -- etiology KW - Neoplasms, Hormone-Dependent -- etiology KW - Receptors, Cell Surface -- physiology KW - Breast Neoplasms -- ultrastructure KW - Neoplasms, Hormone-Dependent -- ultrastructure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79775570?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+carcinogenesis&rft.atitle=Melatonin%3A+receptor-mediated+events+that+may+affect+breast+and+other+steroid+hormone-dependent+cancers.&rft.au=Baldwin%2C+W+S%3BBarrett%2C+J+C&rft.aulast=Baldwin&rft.aufirst=W&rft.date=1998-03-01&rft.volume=21&rft.issue=3&rft.spage=149&rft.isbn=&rft.btitle=&rft.title=Molecular+carcinogenesis&rft.issn=08991987&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-04-16 N1 - Date created - 1998-04-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Synergistic effects of 8-chlorocyclic-AMP and retinoic acid on induction of apoptosis in Ewing's sarcoma CHP-100 cells. AN - 79773777; 9533545 AB - The enhanced expression of the regulatory subunit of cyclic AMP (cAMP)-dependent protein kinase type I, RIalpha, has been correlated with cancer cell growth. Retinoic acid (RA) has been shown to play an important role in the regulation of proliferation and differentiation in neoplastic cells. In the present study, the effects of cAMP analogue 8-chlorocyclic-AMP (8-Cl-cAMP) and RA (both singly and combined) on growth inhibition and apoptosis in Ewing's sarcoma CHP-100 cells were evaluated. The inhibitory effects of 8-Cl-cAMP and RA (9-cis-RA, 13-cis-RA, and all-trans-RA) on cell viability were time and dose related. The degree of growth inhibition induced by 9-cis-RA was the greatest among all of the RA analogues (13-cis-RA and all-trans-RA) examined. The combined effects of 8-Cl-cAMP and RA on the induction of growth arrest at the G0-G1 stage of the cell cycle, apoptosis, down-regulation of RIalpha, and cleavage of poly(ADP-ribose) polymerase were synergistic. In conclusion, it is clear that RA and 8-Cl-cAMP act in a synergistic fashion and have potential for combination chemotherapy for the treatment of malignant disease. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Srivastava, R K AU - Srivastava, A R AU - Cho-Chung, Y S AD - Cellular Biochemistry Section, Laboratory of Tumor Immunology and Biology, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1998/03// PY - 1998 DA - March 1998 SP - 755 EP - 761 VL - 4 IS - 3 SN - 1078-0432, 1078-0432 KW - Antineoplastic Agents KW - 0 KW - Nucleosomes KW - 8-Bromo Cyclic Adenosine Monophosphate KW - 23583-48-4 KW - 8-chloro-cyclic adenosine monophosphate KW - 41941-56-4 KW - Tretinoin KW - 5688UTC01R KW - Index Medicus KW - Nucleosomes -- pathology KW - Tumor Cells, Cultured KW - Nucleosomes -- drug effects KW - Cell Survival -- drug effects KW - Bone Neoplasms KW - Humans KW - Cell Division -- drug effects KW - Enzyme-Linked Immunosorbent Assay KW - Sarcoma, Ewing KW - Drug Synergism KW - 8-Bromo Cyclic Adenosine Monophosphate -- analogs & derivatives KW - Apoptosis -- drug effects KW - 8-Bromo Cyclic Adenosine Monophosphate -- toxicity KW - Tretinoin -- toxicity KW - Antineoplastic Agents -- toxicity KW - Cell Cycle -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79773777?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=unknown&rft.jtitle=Mental+Health+and+Social+Inclusion&rft.atitle=Mind+your+language%21&rft.au=Gilfoyle%2C+Sharon+Ann&rft.aulast=Gilfoyle&rft.aufirst=Sharon&rft.date=2017-02-01&rft.volume=21&rft.issue=1&rft.spage=47&rft.isbn=&rft.btitle=&rft.title=Mental+Health+and+Social+Inclusion&rft.issn=20428308&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-05-28 N1 - Date created - 1998-05-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Distinct localization of GLUT-1, -3, and -5 in human monocyte-derived macrophages: effects of cell activation. AN - 79764866; 9530136 AB - We determined subcellular localization of GLUT-1, GLUT-3, and GLUT-5 as human monocytes differentiate into macrophages in culture, and effects of the activating agents N-formyl-methionyl-leucyl-phenylalanine (fMLP) and phorbol myristate acetate (PMA). Western blot analysis demonstrated progressively increased GLUT-1, rapidly decreased GLUT-3, and a delayed increase of GLUT-5 expression during differentiation. Confocal microscopy revealed that each isoform displayed a unique subcellular distribution and cell-activation response. GLUT-1 was localized primarily to the cell surface but was also detected in the perinuclear region in a pattern characteristic of recycling endosomes. GLUT-3 exhibited predominantly a distinct vesicle-like staining but was present only in monocytes. GLUT-5 was found primarily at the cell surface but was detectable intracellularly. Activation with fMLP induced similar GLUT-1 and GLUT-5 redistributions from intracellular compartments toward the cell surface. PMA elicited a similar translocation of GLUT-1, but GLUT-5 was redistributed from the plasma membrane to a distinct intracellular compartment that appeared connected to the cell surface. These results suggest specific subcellular targeting of each transporter isoform and differential regulation of their trafficking pathways in cultured macrophages. JF - The American journal of physiology AU - Malide, D AU - Davies-Hill, T M AU - Levine, M AU - Simpson, I A AD - Experimental Diabetes, Metabolism, and Nutrition Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/03// PY - 1998 DA - March 1998 SP - E516 EP - E526 VL - 274 IS - 3 Pt 1 SN - 0002-9513, 0002-9513 KW - Glucose Transporter Type 1 KW - 0 KW - Glucose Transporter Type 3 KW - Glucose Transporter Type 5 KW - Monosaccharide Transport Proteins KW - Nerve Tissue Proteins KW - SLC2A1 protein, human KW - SLC2A3 protein, human KW - N-Formylmethionine Leucyl-Phenylalanine KW - 59880-97-6 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - N-Formylmethionine Leucyl-Phenylalanine -- pharmacology KW - Microscopy, Confocal KW - Cells, Cultured KW - Humans KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Cell Differentiation KW - Molecular Weight KW - Macrophage Activation -- drug effects KW - Monosaccharide Transport Proteins -- metabolism KW - Monocytes -- cytology KW - Monocytes -- metabolism KW - Monocytes -- drug effects KW - Macrophages -- drug effects KW - Macrophages -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79764866?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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+physiology&rft.atitle=Distinct+localization+of+GLUT-1%2C+-3%2C+and+-5+in+human+monocyte-derived+macrophages%3A+effects+of+cell+activation.&rft.au=Malide%2C+D%3BDavies-Hill%2C+T+M%3BLevine%2C+M%3BSimpson%2C+I+A&rft.aulast=Malide&rft.aufirst=D&rft.date=1998-03-01&rft.volume=274&rft.issue=3+Pt+1&rft.spage=E516&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+physiology&rft.issn=00029513&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-04-24 N1 - Date created - 1998-04-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Adolescent substance abuse: a review of the past 10 years. AN - 79753717; 9519629 AB - To review and synthesize the recent scientific literature on adolescent substance abuse, covering natural history, epidemiology, etiology, comorbidity, assessment, treatment, and prevention, and to highlight areas for future research. Studies of adolescent substance abuse were reviewed with the focus on substance abuse and dependence rather than substance use. There has been a sharp recent resurgence in adolescent drug use. Biological factors, including genetic and temperament characteristics, as well as family environment factors, are emerging as important etiological variables. Comorbidity with other psychiatric disorders, particularly with conduct disorder, is frequent and complicates treatment. New assessment instruments are available for clinical and research use. Among treatment modalities, family-based interventions have received the most study. The past decade has seen growth in the volume and sophistication of research on adolescent substance abuse and in the conceptualization of this problem. Further research is needed, particularly on the significance of comorbid conditions and on individualized and effective treatment approaches. JF - Journal of the American Academy of Child and Adolescent Psychiatry AU - Weinberg, N Z AU - Rahdert, E AU - Colliver, J D AU - Glantz, M D AD - National Institute on Drug Abuse, National Institutes of Health, Rockville, MD, USA. Y1 - 1998/03// PY - 1998 DA - March 1998 SP - 252 EP - 261 VL - 37 IS - 3 SN - 0890-8567, 0890-8567 KW - Index Medicus KW - Substance Abuse Detection KW - Risk Factors KW - Humans KW - Child KW - Adolescent KW - United States -- epidemiology KW - Male KW - Female KW - Comorbidity KW - Substance-Related Disorders -- rehabilitation KW - Substance-Related Disorders -- prevention & control KW - Substance-Related Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79753717?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+American+Academy+of+Child+and+Adolescent+Psychiatry&rft.atitle=Adolescent+substance+abuse%3A+a+review+of+the+past+10+years.&rft.au=Weinberg%2C+N+Z%3BRahdert%2C+E%3BColliver%2C+J+D%3BGlantz%2C+M+D&rft.aulast=Weinberg&rft.aufirst=N&rft.date=1998-03-01&rft.volume=37&rft.issue=3&rft.spage=252&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+American+Academy+of+Child+and+Adolescent+Psychiatry&rft.issn=08908567&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-04-20 N1 - Date created - 1998-04-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Levels and membrane localization of the c-K-ras p21 protein in lungs of mice of different genetic strains and effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and Aroclor 1254. AN - 79752616; 9525281 AB - Mutational activation of the K-ras oncogene often occurs in human and mouse lung adenocarcinomas. Since K-ras p21 functions in trans-membrane signaling, we have investigated whether the amount of this protein in lung cell membranes is a variable that could influence lung tumorigenesis, either due to genetic differences or in response to tumor promoters. The six mouse strains assessed showed little difference in the total lung K-ras p21 after immunoprecipitation and immunoblotting. However, amount of ras p21 in the membrane fraction showed significant differences, with C57BL/6 and BALB/c having 3-5-fold more than NIH Swiss, AKR and DBA mice. Interestingly, a congenic AKR strain having the Ahr(b-1) Ah receptor allele from C57BL/6 mice (designated AKR.B6Ah) had high lung membrane K-ras p21 similar to that of C57BL/6. To test for possible changes related to lung tumor promotion, mice were treated with a promotional dose of TCDD (5 nmol/kg). After 48 h C57BL/6 lungs showed an increase in p21 in both total and membrane fractions. BALB/c, DBA and Swiss mice showed an increase only in membranes. There was no change in the AKR and AKR.B6Ah. Aroclor 1254 (250 mg/kg) caused an increase in membrane/cytosol ratio in Swiss mice. Thus the membrane:cytosol K-ras p21 ratio may be influenced by the Ahr phenotype, and TCDD and PCBs can induce p21 or increase its membrane level in certain strains, but these properties are not fully dependent on Ahr receptor type. In confirmation of the relevance of these findings for the tumor target cell type, the immortalized alveolar type 2 E10 cell line presented K-ras p21 in membrane, and this was increased 4-fold by treatment with 10 nM TCDD. JF - Carcinogenesis AU - Ramakrishna, G AU - Anderson, L M AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, MD 21702, USA. Y1 - 1998/03// PY - 1998 DA - March 1998 SP - 463 EP - 470 VL - 19 IS - 3 SN - 0143-3334, 0143-3334 KW - Aroclors KW - 0 KW - Carcinogens KW - Polychlorinated Dibenzodioxins KW - Chlorodiphenyl (54% Chlorine) KW - 11097-69-1 KW - Proto-Oncogene Proteins p21(ras) KW - EC 3.6.5.2 KW - Index Medicus KW - Animals KW - Cytosol -- metabolism KW - Adenocarcinoma -- chemically induced KW - Cell Membrane -- drug effects KW - Adenocarcinoma -- genetics KW - Mice KW - Mice, Inbred Strains KW - Cells, Cultured KW - Lung Neoplasms -- genetics KW - Cell Membrane -- metabolism KW - Lung Neoplasms -- chemically induced KW - Species Specificity KW - Male KW - Proto-Oncogene Proteins p21(ras) -- metabolism KW - Lung -- cytology KW - Polychlorinated Dibenzodioxins -- toxicity KW - Lung -- drug effects KW - Carcinogens -- toxicity KW - Aroclors -- toxicity KW - Lung -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79752616?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Levels+and+membrane+localization+of+the+c-K-ras+p21+protein+in+lungs+of+mice+of+different+genetic+strains+and+effects+of+2%2C3%2C7%2C8-tetrachlorodibenzo-p-dioxin+%28TCDD%29+and+Aroclor+1254.&rft.au=Ramakrishna%2C+G%3BAnderson%2C+L+M&rft.aulast=Ramakrishna&rft.aufirst=G&rft.date=1998-03-01&rft.volume=19&rft.issue=3&rft.spage=463&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-04-08 N1 - Date created - 1998-04-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pharmacokinetics of fentanyl during hyperthermic, isolated lung perfusion. AN - 79752012; 9521366 AB - Hyperthermic, isolated pulmonary perfusion with tumor necrosis factor is a surgical procedure that isolates the pulmonary vasculature from the systemic circulation in patients with unresectable primary or metastatic disease confined to the chest. High drug levels are delivered to the perfused organ, avoiding systemic toxicity, and preventing loss of active drug through metabolism. The pharmacokinetics of fentanyl are evaluated in three patients while the operative lung is hyperthermic, ventilated, and perfused with an asanguineous solution during nonpulsatile bypass. A loading dose of fentanyl, 1.5 microg/kg to 2.5 microg/kg, was given during the induction of anesthesia followed by a continuous infusion of 150 microg/hr. Results showed no difference in mean plasma fentanyl concentrations before, during, or after bypass and was consistent with clearance values previously reported in healthy adult surgical patients in the absence of an extracorporeal circuit. Adjustments in fentanyl dosing are not required before, during, or after hyperthermic, isolated pulmonary perfusion is established and a steady state of fentanyl is achieved. JF - Southern medical journal AU - Williams, K S AU - Susla, G AU - Temeck, B K AU - Piscitelli, S C AU - Pass, H I AD - Anesthesia Section, Clinical Center Pharmacy, and National Cancer Institute/Surgery Branch, National Institutes of Health, Bethesda, MD 20892-1512, USA. Y1 - 1998/03// PY - 1998 DA - March 1998 SP - 261 EP - 265 VL - 91 IS - 3 SN - 0038-4348, 0038-4348 KW - Anesthetics, Intravenous KW - 0 KW - Fentanyl KW - UF599785JZ KW - Abridged Index Medicus KW - Index Medicus KW - Humans KW - Adult KW - Hemodynamics KW - Middle Aged KW - Fentanyl -- blood KW - Anesthetics, Intravenous -- blood KW - Fentanyl -- pharmacokinetics KW - Hyperthermia, Induced KW - Anesthetics, Intravenous -- pharmacokinetics KW - Lung -- metabolism KW - Chemotherapy, Cancer, Regional Perfusion -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79752012?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Southern+medical+journal&rft.atitle=Pharmacokinetics+of+fentanyl+during+hyperthermic%2C+isolated+lung+perfusion.&rft.au=Williams%2C+K+S%3BSusla%2C+G%3BTemeck%2C+B+K%3BPiscitelli%2C+S+C%3BPass%2C+H+I&rft.aulast=Williams&rft.aufirst=K&rft.date=1998-03-01&rft.volume=91&rft.issue=3&rft.spage=261&rft.isbn=&rft.btitle=&rft.title=Southern+medical+journal&rft.issn=00384348&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-04-02 N1 - Date created - 1998-04-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tolerance and pharmacokinetic interactions of rifabutin and clarithromycin in human immunodeficiency virus-infected volunteers. AN - 79746017; 9517944 AB - This study evaluated the tolerance and potential pharmacokinetic interactions between clarithromycin (500 mg every 12 h) and rifabutin (300 mg daily) in clinically stable human immunodeficiency virus-infected volunteers with CD4 counts of <200 cells/mm3. Thirty-four subjects were randomized equally to either regimen A or regimen B. On days 1 to 14, subjects assigned to regimen A received clarithromycin and subjects assigned to regimen B received rifabutin, and then both groups received both drugs on days 15 to 42. Of the 14 regimen A and the 15 regimen B subjects who started combination therapy, 1 subject in each group prematurely discontinued therapy due to toxicity, but 19 of 29 subjects reported nausea, vomiting, and/or diarrhea. Pharmacokinetic analysis included data for 11 regimen A and 14 regimen B subjects. Steady-state pharmacokinetic parameters for single-agent therapy (day 14) and combination therapy (day 42) were compared. Regimen A resulted in a mean decrease of 44% (P = 0.003) in the clarithromycin area under the plasma concentration-time curve (AUC), while there was a mean increase of 57% (P = 0.004) in the AUC of the clarithromycin metabolite 14-OH-clarithromycin. Regimen B resulted in a mean increase of 99% (P = 0.001) in the rifabutin AUC and a mean increase of 375% (P < 0.001) in the AUC of the rifabutin metabolite 25-O-desacetyl-rifabutin. The usefulness of this combination for prophylaxis of Mycobacterium avium infections is limited by frequent gastrointestinal adverse events. Coadministration of clarithromycin and rifabutin results in significant bidirectional pharmacokinetic interactions. The resulting increase in rifabutin levels may explain the increased frequency of uveitis observed with concomitant use of these drugs. JF - Antimicrobial agents and chemotherapy AU - Hafner, R AU - Bethel, J AU - Power, M AU - Landry, B AU - Banach, M AU - Mole, L AU - Standiford, H C AU - Follansbee, S AU - Kumar, P AU - Raasch, R AU - Cohn, D AU - Mushatt, D AU - Drusano, G AD - Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland 20852-7620, USA. rh23v@nih.gov Y1 - 1998/03// PY - 1998 DA - March 1998 SP - 631 EP - 639 VL - 42 IS - 3 SN - 0066-4804, 0066-4804 KW - Rifabutin KW - 1W306TDA6S KW - Clarithromycin KW - H1250JIK0A KW - Index Medicus KW - AIDS/HIV KW - Drug Interactions KW - Area Under Curve KW - Humans KW - Adult KW - CD4 Lymphocyte Count KW - Male KW - Female KW - Drug Therapy, Combination -- adverse effects KW - Rifabutin -- adverse effects KW - Drug Therapy, Combination -- pharmacokinetics KW - Clarithromycin -- pharmacokinetics KW - Rifabutin -- pharmacokinetics KW - Clarithromycin -- adverse effects KW - Acquired Immunodeficiency Syndrome -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79746017?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antimicrobial+agents+and+chemotherapy&rft.atitle=Tolerance+and+pharmacokinetic+interactions+of+rifabutin+and+clarithromycin+in+human+immunodeficiency+virus-infected+volunteers.&rft.au=Hafner%2C+R%3BBethel%2C+J%3BPower%2C+M%3BLandry%2C+B%3BBanach%2C+M%3BMole%2C+L%3BStandiford%2C+H+C%3BFollansbee%2C+S%3BKumar%2C+P%3BRaasch%2C+R%3BCohn%2C+D%3BMushatt%2C+D%3BDrusano%2C+G&rft.aulast=Hafner&rft.aufirst=R&rft.date=1998-03-01&rft.volume=42&rft.issue=3&rft.spage=631&rft.isbn=&rft.btitle=&rft.title=Antimicrobial+agents+and+chemotherapy&rft.issn=00664804&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-05-12 N1 - Date created - 1998-05-12 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Antimicrob Agents Chemother. 1995 Jun;39(6):1355-60 [7574530] Clin Pharmacokinet. 1995 Feb;28(2):115-25 [7736687] Ann Intern Med. 1996 Mar 15;124(6):573-6 [8597321] Clin Infect Dis. 1996 Apr;22 Suppl 1:S43-7; discussion S47-9 [8785256] N Engl J Med. 1996 Aug 8;335(6):392-8 [8676932] Tuber Lung Dis. 1996 Feb;77(1):19-26 [8733409] J Antimicrob Chemother. 1996 Jun;37 Suppl C:133-42 [8818854] Antimicrob Agents Chemother. 1997 May;41(5):924-6 [9145845] Clin Pharmacol Ther. 1997 May;61(5):554-62 [9164417] Comput Programs Biomed. 1983 Jun;16(3):203-16 [6688572] Antimicrob Agents Chemother. 1985 Oct;28(4):570-5 [4073881] Eur J Clin Pharmacol. 1988;34(6):595-9 [2901960] Xenobiotica. 1989 Jul;19(7):769-80 [2549734] Antimicrob Agents Chemother. 1989 Aug;33(8):1237-41 [2552902] AIDS. 1990 May;4(5):433-41 [2164820] Pharm Res. 1991 Nov;8(11):1434-40 [1665904] Am Rev Respir Dis. 1992 Apr;145(4 Pt 1):856-8 [1532486] J Chromatogr. 1991 Nov 15;571(1-2):199-208 [1839793] J Chemother. 1991 Dec;3(6):357-62 [1840274] Antimicrob Agents Chemother. 1992 Nov;36(11):2413-7 [1336945] J Antimicrob Chemother. 1992 Nov;30(5):643-50 [1493981] Clin Infect Dis. 1993 Jul;17(1):7-20 [8353249] N Engl J Med. 1993 Sep 16;329(12):828-33 [8179648] Drugs. 1993 Aug;46(2):289-312 [7691518] J Clin Pharmacol. 1993 Aug;33(8):719-26 [8408732] N Engl J Med. 1994 Feb 10;330(6):438-9 [8284019] N Engl J Med. 1994 Mar 24;330(12):868 [8114854] Drugs. 1994 Jun;47(6):983-1009 [7521834] Ann Intern Med. 1994 Dec 15;121(12):905-11 [7978715] AIDS Res Hum Retroviruses. 1994 Aug;10(8):913-6 [7811542] J Infect Dis. 1995 Mar;171(3):747-50 [7876634] Drug Metab Dispos. 1994 Nov-Dec;22(6):849-57 [7895601] Antimicrob Agents Chemother. 1994 Dec;38(12):2738-42 [7695255] Ann Pharmacother. 1995 Sep;29(9):906-17 [8547740] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - K-ras point mutation occurs in the early stage of carcinogenesis in lung cancer. AN - 79741433; 9514049 AB - In order to determine the topographical distribution of the K-ras codon 12 mutations in carcinoma and preneoplastic lesions of the lung, selective ultraviolet radiation fractionation, as well as microdissection followed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RELP), was performed. Fourteen of 61 samples amplified (23.0%) had a mutation in the K-ras codon 12. Of 41 adenocarcinoma, 12 samples (29.3%) had a mutation, whereas none of the squamous cell carcinomas had a mutation. One of six large-cell carcinomas, one of three carcinoid tumours and none of three other carcinomas had a mutation. Direct sequencing revealed that K-ras codon 12 of six samples were TGT (Cys), five samples were GTT (Val), two samples were GCT (Ala) and one sample was TTT (Phe). A total of 113 lesions of 13 cases covered by dot were amplified after UV radiation. All of 74 carcinoma lesions had the mutation, and intratumour heterogeneity was not observed. Of 39 non-malignant lesions, one type II cell hyperplasia had the mutation, which suggests that the K-ras mutation occurs in the early stage of carcinogenesis. The lack of intratumour heterogeneity supports the hypothesis. JF - British journal of cancer AU - Sagawa, M AU - Saito, Y AU - Fujimura, S AU - Linnoila, R I AD - Biomarkers and Prevention Research Branch, National Cancer Institute, Rockville, Maryland 20850, USA. Y1 - 1998/03// PY - 1998 DA - March 1998 SP - 720 EP - 723 VL - 77 IS - 5 SN - 0007-0920, 0007-0920 KW - DNA, Neoplasm KW - 0 KW - Index Medicus KW - Polymerase Chain Reaction KW - Hyperplasia KW - Polymorphism, Restriction Fragment Length KW - Humans KW - DNA Mutational Analysis KW - DNA, Neoplasm -- genetics KW - Lung -- pathology KW - Genes, ras KW - Precancerous Conditions -- genetics KW - Lung Diseases -- genetics KW - Point Mutation KW - Carcinoma, Squamous Cell -- genetics KW - Carcinoma, Large Cell -- genetics KW - Lung Neoplasms -- genetics KW - Carcinoid Tumor -- genetics KW - Adenocarcinoma -- genetics KW - Cell Transformation, Neoplastic -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79741433?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=British+journal+of+cancer&rft.atitle=K-ras+point+mutation+occurs+in+the+early+stage+of+carcinogenesis+in+lung+cancer.&rft.au=Sagawa%2C+M%3BSaito%2C+Y%3BFujimura%2C+S%3BLinnoila%2C+R+I&rft.aulast=Sagawa&rft.aufirst=M&rft.date=1998-03-01&rft.volume=77&rft.issue=5&rft.spage=720&rft.isbn=&rft.btitle=&rft.title=British+journal+of+cancer&rft.issn=00070920&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-04-02 N1 - Date created - 1998-04-02 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Am J Pathol. 1995 Jul;147(1):92-101 [7604888] JAMA. 1995 Feb 15;273(7):558-63 [7837389] Cancer Res. 1995 Nov 15;55(22):5133-9 [7585560] Cancer Res. 1996 May 1;56(9):2224-8 [8616876] N Engl J Med. 1988 Sep 1;319(9):525-32 [2841597] Oncogene. 1991 Aug;6(8):1353-62 [1679529] West J Med. 1991 Nov;155(5):505-14 [1815390] Am J Pathol. 1992 Sep;141(3):539-43 [1325739] Oncogene. 1992 Oct;7(10):1989-97 [1408139] J Natl Cancer Inst. 1993 Jul 7;85(13):1058-63 [8515492] Cancer. 1993 Jul 15;72(2):432-8 [8319174] Am J Pathol. 1994 Feb;144(2):303-9 [8311114] Virchows Arch. 1994;424(2):129-34 [7910096] Cancer Res. 1994 Nov 15;54(22):5811-5 [7954406] J Natl Cancer Inst. 1995 Jul 19;87(14):1056-60 [7616596] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Human immunodeficiency virus disease: changing patterns of intraocular inflammation. AN - 79737794; 9512156 AB - To evaluate and put into perspective five articles in this issue of the AMERICAN JOURNAL OF OPHTHALMOLOGY that discuss ocular inflammatory disorders in patients with human immunodeficiency virus (HIV) disease. We drew upon recent observations concerning the effect of HIV disease on the immune system in an attempt to understand the current reports describing intraocular inflammation. Intraocular inflammation appears to be dependent on several factors, including specific antigenic stimuli and the state of the host immune system. During dynamic changes in these factors, conditions may arise that favor inflammatory reactions. Use of antiretroviral therapies is one mechanism that can effect these dynamics. As the immune system equilibrates at one extreme or the other (depletion or reconstitution), conditions favoring inflammation appear to dissipate. Restoration of immune function by the use of combination antiretroviral therapy, including protease inhibitors, may lead to additional cases of transient intraocular inflammation in the future. JF - American journal of ophthalmology AU - Nussenblatt, R B AU - Lane, H C AD - National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. rnq@helix.nih.gov Y1 - 1998/03// PY - 1998 DA - March 1998 SP - 374 EP - 382 VL - 125 IS - 3 SN - 0002-9394, 0002-9394 KW - Anti-HIV Agents KW - 0 KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Drug Therapy, Combination KW - Immune System -- drug effects KW - Eye Infections, Bacterial -- complications KW - Syphilis -- complications KW - Humans KW - Eye Diseases -- etiology KW - Anti-HIV Agents -- adverse effects KW - Eye Diseases -- immunology KW - Uveitis, Posterior -- immunology KW - HIV Infections -- complications KW - Eye Infections, Viral KW - Vitreous Body -- pathology KW - Uveitis, Posterior -- etiology KW - HIV Infections -- immunology KW - Vitreous Body -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79737794?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Human+immunodeficiency+virus+disease%3A+changing+patterns+of+intraocular+inflammation.&rft.au=Nussenblatt%2C+R+B%3BLane%2C+H+C&rft.aulast=Nussenblatt&rft.aufirst=R&rft.date=1998-03-01&rft.volume=125&rft.issue=3&rft.spage=374&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 - 1998-03-24 N1 - Date created - 1998-03-24 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Am J Ophthalmol. 1998 Mar;125(3):411-5 [9512171] Am J Ophthalmol. 1998 Mar;125(3):383-5 [9512157] Comment On: Am J Ophthalmol. 1998 Mar;125(3):411-5 [9512171] Am J Ophthalmol. 1998 Mar;125(3):292-300 [9512145] Am J Ophthalmol. 1998 Mar;125(3):312-24 [9512148] Am J Ophthalmol. 1998 Mar;125(3):301-5 [9512146] Am J Ophthalmol. 1998 Mar;125(3):306-11 [9512147] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Treatment of refractory myositis: a randomized crossover study of two new cytotoxic regimens. AN - 79732352; 9506565 AB - To assess the clinical usefulness of 2 novel therapies for treatment-resistant myositis. Thirty patients with refractory myositis, of whom 25 had an inadequate or no response to previous cytotoxic therapy, were randomized to begin either a combination of weekly oral methotrexate and daily azathioprine (MTX/AZA) or intravenous methotrexate with leucovorin rescue (I.V. MTX) every 2 weeks for 6 months. Crossover to the alternate therapy occurred according to defined rules; evaluations of muscle strength and functional abilities were performed at the beginning, and after 3 and 6 months, of each treatment. Of the 15 patients initially randomized to oral MTX/AZA, 8 improved with oral therapy and 1 improved with I.V. MTX during the crossover period. Of the 15 patients initially randomized to I.V. MTX therapy, 3 improved with the I.V. therapy and 4 with the oral combination during the crossover period. Although the study lacked the power to directly compare both treatments, intention-to-treat analysis showed a trend in favor of those patients who first received oral combination therapy (P = 0.025). There were 0.09 adverse events per patient-month with oral combination therapy and 0.16 per patient-month with I.V. therapy (P = 0.09). Combination oral MTX/AZA may benefit patients with treatment-resistant myositis, including those who previously had inadequate responses to either MTX or AZA alone. I.V. MTX with leucovorin rescue may also benefit some patients with refractory myositis. JF - Arthritis and rheumatism AU - Villalba, L AU - Hicks, J E AU - Adams, E M AU - Sherman, J B AU - Gourley, M F AU - Leff, R L AU - Thornton, B C AU - Burgess, S H AU - Plotz, P H AU - Miller, F W AD - National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1998/03// PY - 1998 DA - March 1998 SP - 392 EP - 399 VL - 41 IS - 3 SN - 0004-3591, 0004-3591 KW - Antimetabolites, Antineoplastic KW - 0 KW - Antirheumatic Agents KW - Azathioprine KW - MRK240IY2L KW - Leucovorin KW - Q573I9DVLP KW - Methotrexate KW - YL5FZ2Y5U1 KW - Abridged Index Medicus KW - Index Medicus KW - Drug Therapy, Combination KW - Administration, Oral KW - Injections, Intravenous KW - Humans KW - Salvage Therapy KW - Adult KW - Cross-Over Studies KW - Aged KW - Middle Aged KW - Male KW - Female KW - Antimetabolites, Antineoplastic -- administration & dosage KW - Azathioprine -- adverse effects KW - Antimetabolites, Antineoplastic -- adverse effects KW - Azathioprine -- therapeutic use KW - Myositis -- drug therapy KW - Methotrexate -- adverse effects KW - Antirheumatic Agents -- administration & dosage KW - Antirheumatic Agents -- adverse effects KW - Methotrexate -- therapeutic use KW - Antimetabolites, Antineoplastic -- therapeutic use KW - Methotrexate -- administration & dosage KW - Antirheumatic Agents -- therapeutic use KW - Leucovorin -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79732352?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Arthritis+and+rheumatism&rft.atitle=Treatment+of+refractory+myositis%3A+a+randomized+crossover+study+of+two+new+cytotoxic+regimens.&rft.au=Villalba%2C+L%3BHicks%2C+J+E%3BAdams%2C+E+M%3BSherman%2C+J+B%3BGourley%2C+M+F%3BLeff%2C+R+L%3BThornton%2C+B+C%3BBurgess%2C+S+H%3BPlotz%2C+P+H%3BMiller%2C+F+W&rft.aulast=Villalba&rft.aufirst=L&rft.date=1998-03-01&rft.volume=41&rft.issue=3&rft.spage=392&rft.isbn=&rft.btitle=&rft.title=Arthritis+and+rheumatism&rft.issn=00043591&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-04-14 N1 - Date created - 1998-04-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Conduct of phase I trials in children with cancer. AN - 79729984; 9508179 AB - Future progress in the care of children with cancer requires appropriate evaluations of promising new agents for pediatric indications, beginning with well-conducted phase I trials. This report summarizes current guidelines for the conduct of pediatric phase I trials and represents a consensus between American and European investigators. The primary objective of pediatric phase I trials is to define safe and appropriate doses and schedules of new agents that can subsequently be used in phase II trials to test for activity against specific childhood malignancies. Prioritization of agents for evaluation in children is critical, since many more investigational agents are evaluated in adult patients than can be systematically evaluated in children. Considerations used in prioritizing agents include activity in xenograft models, novel mechanism of action, favorable drug-resistance profile, and activity observed in adult trials of the agent. Distinctive characteristics of pediatric phase I trials, in comparison to adult phase I trials, include the necessity for multiinstitutional participation and their higher starting dose (typically 80% of the adult maximum-tolerated dose [MTD]), both of which reflect the relative unavailability of appropriate patients. The application of uniform eligibility criteria and standard definitions for MTD and dose-limiting toxicity (DLT) help to assure that pediatric phase I trials are safely conducted and reliably identify appropriate doses and schedules of agents for phase II evaluation. Where possible, pediatric phase I trials also define the pharmacokinetic behavior of new agents in children. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Smith, M AU - Bernstein, M AU - Bleyer, W A AU - Borsi, J D AU - Ho, P AU - Lewis, I J AU - Pearson, A AU - Pein, F AU - Pratt, C AU - Reaman, G AU - Riccardi, R AU - Seibel, N AU - Trueworthy, R AU - Ungerleider, R AU - Vassal, G AU - Vietti, T AD - Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD 20892, USA. smithm@ctep.nci.nih.gov Y1 - 1998/03// PY - 1998 DA - March 1998 SP - 966 EP - 978 VL - 16 IS - 3 SN - 0732-183X, 0732-183X KW - Antineoplastic Agents KW - 0 KW - Index Medicus KW - Infant KW - Humans KW - Guidelines as Topic KW - Child KW - Child, Preschool KW - Antineoplastic Agents -- administration & dosage KW - Clinical Trials, Phase I as Topic -- standards KW - Antineoplastic Agents -- pharmacokinetics KW - Neoplasms -- therapy KW - Antineoplastic Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79729984?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Conduct+of+phase+I+trials+in+children+with+cancer.&rft.au=Smith%2C+M%3BBernstein%2C+M%3BBleyer%2C+W+A%3BBorsi%2C+J+D%3BHo%2C+P%3BLewis%2C+I+J%3BPearson%2C+A%3BPein%2C+F%3BPratt%2C+C%3BReaman%2C+G%3BRiccardi%2C+R%3BSeibel%2C+N%3BTrueworthy%2C+R%3BUngerleider%2C+R%3BVassal%2C+G%3BVietti%2C+T&rft.aulast=Smith&rft.aufirst=M&rft.date=1998-03-01&rft.volume=16&rft.issue=3&rft.spage=966&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 - 1998-03-24 N1 - Date created - 1998-03-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The cytotoxicity of nitroxyl: possible implications for the pathophysiological role of NO. AN - 79729300; 9501920 AB - In addition to the broad repertoire of regulatory functions nitric oxide (NO) serves in mammalian physiology, the L-arginine:NO pathway is also involved in numerous pathophysiological mechanisms. While NO itself may actually protect cells from the toxicity of reactive oxygen radicals in some cases, it has been suggested that reactive nitrogen oxide species formed from nitric oxide synthase (NOS) can be cytotoxic. In addition to NO, the one electron reduction product NO- has been proposed to be formed from NOS. We investigated the potential cytotoxic role of nitroxyl (NO-), using the nitroxyl donor Angelis's salt, (AS; sodium trioxodinitrate, Na2N2O3) as the source of NO-. As was found to be cytotoxic to Chinese hamster V79 lung fibroblast cells over a concentration range of 2-4 mM. The presence of equimolar ferricyanide (Fe(III)-(CN6)3-), which converts NO- to NO, afforded dramatic protection against AS-mediated cytotoxicity. Treatment of V79 cells with L-buthionine sulfoximine to reduce intracellular glutathione markedly enhanced AS cytotoxicity, which suggests that GSH is critical for cellular protection against the toxicity of NO-. Further experiments showed that low molecular weight transition metal complexes associated with the formation of reactive oxygen species are not involved in AS-mediated cytotoxicity since metal chelators had no effect. However, under aerobic conditions, AS was more toxic than under hypoxic conditions, suggesting that oxygen dramatically enhanced AS-mediated cytotoxicity. At a molecular level, AS exposure resulted in DNA double strand breaks in whole cells, and this effect was completely prevented by coincubation of cells with ferricyanide or Tempol. The data in this study suggest that nitroxyl may contribute to the cytotoxicity associated with an enhanced expression of the L-arginine:NO pathway under different biological conditions. JF - Archives of biochemistry and biophysics AU - Wink, D A AU - Feelisch, M AU - Fukuto, J AU - Chistodoulou, D AU - Jourd'heuil, D AU - Grisham, M B AU - Vodovotz, Y AU - Cook, J A AU - Krishna, M AU - DeGraff, W G AU - Kim, S AU - Gamson, J AU - Mitchell, J B AD - Tumor Biology Section, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1998/03/01/ PY - 1998 DA - 1998 Mar 01 SP - 66 EP - 74 VL - 351 IS - 1 SN - 0003-9861, 0003-9861 KW - Cyclic N-Oxides KW - 0 KW - Ferricyanides KW - Free Radical Scavengers KW - Free Radicals KW - Nitrites KW - Nitrogen Oxides KW - Spin Labels KW - hexacyanoferrate III KW - 13408-62-3 KW - oxyhyponitrite KW - 18550-55-5 KW - Nitric Oxide KW - 31C4KY9ESH KW - Buthionine Sulfoximine KW - 5072-26-4 KW - Arginine KW - 94ZLA3W45F KW - Nitric Oxide Synthase KW - EC 1.14.13.39 KW - Glutathione KW - GAN16C9B8O KW - nitroxyl KW - GFQ4MMS07W KW - tempol KW - U78ZX2F65X KW - Index Medicus KW - Animals KW - Nitrites -- pharmacology KW - Arginine -- metabolism KW - Cricetulus KW - DNA Damage KW - Glutathione -- metabolism KW - Fibroblasts KW - Ferricyanides -- pharmacology KW - Lung KW - Cyclic N-Oxides -- pharmacology KW - Buthionine Sulfoximine -- pharmacology KW - Nitric Oxide Synthase -- metabolism KW - Cell Line KW - Cricetinae KW - Cell Death KW - Nitric Oxide -- metabolism KW - Nitrogen Oxides -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79729300?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+biochemistry+and+biophysics&rft.atitle=The+cytotoxicity+of+nitroxyl%3A+possible+implications+for+the+pathophysiological+role+of+NO.&rft.au=Wink%2C+D+A%3BFeelisch%2C+M%3BFukuto%2C+J%3BChistodoulou%2C+D%3BJourd%27heuil%2C+D%3BGrisham%2C+M+B%3BVodovotz%2C+Y%3BCook%2C+J+A%3BKrishna%2C+M%3BDeGraff%2C+W+G%3BKim%2C+S%3BGamson%2C+J%3BMitchell%2C+J+B&rft.aulast=Wink&rft.aufirst=D&rft.date=1998-03-01&rft.volume=351&rft.issue=1&rft.spage=66&rft.isbn=&rft.btitle=&rft.title=Archives+of+biochemistry+and+biophysics&rft.issn=00039861&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-26 N1 - Date created - 1998-03-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phase II trial with dose titration of paclitaxel for the therapy of human immunodeficiency virus-associated Kaposi's sarcoma. AN - 79728804; 9508198 AB - To investigate the antitumor activity and safety of paclitaxel in patients with advanced human immunodeficiency virus (HIV)-associated Kaposi's sarcoma (KS). Twenty-nine patients with advanced HIV-associated KS were enrolled. The patients were overall quite immunosuppressed (median CD4 count, 15 cells/microL). Paclitaxel was initially administered at 135 mg/m2 over 3 hours every 3 weeks without filgrastim support; the dose was increased as tolerated to a maximum of 175 mg/m2. Patients who failed to respond or progressed could then receive filgrastim support or paclitaxel administered over 96 hours. Of 28 assessable patients, 20 had major responses (18 partial responses [PRs], one clinical complete response [CR], and one CR), for a major response rate of 71.4% (95% confidence interval [CI], 51.3% to 86.8%). Each of the five patients with pulmonary KS responded, as did all four assessable patients who had previously received anthracycline therapy for KS. Of six patients who went on to receive a 96-hour infusion of paclitaxel, five had major responses. Neutropenia was the most frequent dose-limiting toxicity; possible novel toxicities included late fevers, late rash, and eosinophilia. Two patients developed an elevated creatinine concentration and one cardiomyopathy. Paclitaxel has substantial activity against advanced HIV-associated KS as a single agent, even in patients with pulmonary involvement or who had previously received anthracyclines. Further research is needed to define the optimal treatment schedule and its role vis-a-vis the other available therapies for this disease. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Welles, L AU - Saville, M W AU - Lietzau, J AU - Pluda, J M AU - Wyvill, K M AU - Feuerstein, I AU - Figg, W D AU - Lush, R AU - Odom, J AU - Wilson, W H AU - Fajardo, M T AU - Humphrey, R W AU - Feigal, E AU - Tuck, D AU - Steinberg, S M AU - Broder, S AU - Yarchoan, R AD - HIV and AIDS Malignancy Branch, National Cancer Institute; the Warren G. Magnuson Clinical Center, Bethesda, MD 20892-1906, USA. Y1 - 1998/03// PY - 1998 DA - March 1998 SP - 1112 EP - 1121 VL - 16 IS - 3 SN - 0732-183X, 0732-183X KW - Antineoplastic Agents, Phytogenic KW - 0 KW - Recombinant Proteins KW - Granulocyte Colony-Stimulating Factor KW - 143011-72-7 KW - Paclitaxel KW - P88XT4IS4D KW - Filgrastim KW - PVI5M0M1GW KW - Index Medicus KW - AIDS/HIV KW - Probability KW - Acquired Immunodeficiency Syndrome -- complications KW - Drug Administration Schedule KW - Granulocyte Colony-Stimulating Factor -- therapeutic use KW - Humans KW - Adult KW - Middle Aged KW - Male KW - Survival Analysis KW - Remission Induction KW - Paclitaxel -- administration & dosage KW - Antineoplastic Agents, Phytogenic -- pharmacokinetics KW - Sarcoma, Kaposi -- drug therapy KW - Paclitaxel -- pharmacokinetics KW - Antineoplastic Agents, Phytogenic -- therapeutic use KW - Paclitaxel -- therapeutic use KW - Antineoplastic Agents, Phytogenic -- administration & dosage KW - Sarcoma, Kaposi -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79728804?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+trial+with+dose+titration+of+paclitaxel+for+the+therapy+of+human+immunodeficiency+virus-associated+Kaposi%27s+sarcoma.&rft.au=Welles%2C+L%3BSaville%2C+M+W%3BLietzau%2C+J%3BPluda%2C+J+M%3BWyvill%2C+K+M%3BFeuerstein%2C+I%3BFigg%2C+W+D%3BLush%2C+R%3BOdom%2C+J%3BWilson%2C+W+H%3BFajardo%2C+M+T%3BHumphrey%2C+R+W%3BFeigal%2C+E%3BTuck%2C+D%3BSteinberg%2C+S+M%3BBroder%2C+S%3BYarchoan%2C+R&rft.aulast=Welles&rft.aufirst=L&rft.date=1998-03-01&rft.volume=16&rft.issue=3&rft.spage=1112&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 - 1998-03-24 N1 - Date created - 1998-03-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Accumulation of a recombinant immunotoxin in a tumor in vivo: fewer than 1000 molecules per cell are sufficient for complete responses. AN - 79728776; 9500458 AB - Recombinant immunotoxins have been shown to cure human tumor xenografts in mice, but their biodistribution to both tumors and normal organs has not been reported. Anti-Tac(Fv)-PE38 is a single-chain recombinant immunotoxin composed of the variable heavy and light domains of the anti-Tac monoclonal antibody that reacts with the primate interleukin 2 (IL2) receptor alpha subunit (IL2R alpha or CD25) fused to a truncated form of Pseudomonas exotoxin (PE). 125I-labeled anti-Tac(Fv)-PE38 was given i.v. to immunodeficient mice each bearing two A431 tumors, one that expresses IL2R alpha (ATAC-4) and one that does not (A431, parental). A single i.v. dose of 4 microg/mouse caused complete regression of the IL2R alpha + tumor. At 6 h, over 6% of the injected dose/g was found in the ATAC-4 tumor, and 2% was in the A431 tumor. Uptake in the ATAC-4 tumor was higher than in any other tissue. Sections of tumor examined by autoradiography indicated that anti-Tac(Fv)-PE38 was distributed throughout the entire tumor, with some portions having higher uptake than others. By subtracting uptake in tumors without receptor (A431) from uptake in receptor-containing tumors (ATAC-4), we calculated that at least 400 molecules/cell specifically bound to IL2R alpha-positive tumor cells at 90 min and 750 molecules/cell bound at 360 min. This is similar to the 400-870 molecules/cell required for >99.9% killing of ATAC-4 cells growing as a monolayer. The results show that solid tumors in mice can be eradicated like cells in tissue culture, and that delivery of less than 1000 molecules/cell is sufficient to cause complete tumor regressions. JF - Cancer research AU - Kreitman, R J AU - Pastan, I AD - Laboratory of Molecular Biology, Division of Cancer Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/03/01/ PY - 1998 DA - 1998 Mar 01 SP - 968 EP - 975 VL - 58 IS - 5 SN - 0008-5472, 0008-5472 KW - Antibodies, Monoclonal KW - 0 KW - Bacterial Toxins KW - Exotoxins KW - Immunotoxins KW - Receptors, Interleukin-2 KW - Recombinant Fusion Proteins KW - Virulence Factors KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - toxA protein, Pseudomonas aeruginosa KW - EC 2.4.2.31 KW - Index Medicus KW - Animals KW - Recombinant Fusion Proteins -- pharmacokinetics KW - Antibodies, Monoclonal -- pharmacokinetics KW - Humans KW - Mice, Nude KW - Mice KW - Recombinant Fusion Proteins -- therapeutic use KW - Antibodies, Monoclonal -- therapeutic use KW - Immunotoxins -- pharmacokinetics KW - Neoplasms, Experimental -- immunology KW - Immunotoxins -- therapeutic use KW - Neoplasms, Experimental -- drug therapy KW - Neoplasms, Experimental -- pathology KW - Exotoxins -- therapeutic use KW - Receptors, Interleukin-2 -- immunology KW - Exotoxins -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79728776?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Accumulation+of+a+recombinant+immunotoxin+in+a+tumor+in+vivo%3A+fewer+than+1000+molecules+per+cell+are+sufficient+for+complete+responses.&rft.au=Kreitman%2C+R+J%3BPastan%2C+I&rft.aulast=Kreitman&rft.aufirst=R&rft.date=1998-03-01&rft.volume=58&rft.issue=5&rft.spage=968&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 - 1998-03-25 N1 - Date created - 1998-03-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Volume of ethanol consumption: effects of different approaches to measurement. AN - 79726968; 9500306 AB - Eight different approaches to measuring alcohol consumption were compared in terms of average daily volume of ethanol intake, selected percentiles of the volume distribution, the proportion of drinkers exceeding a volume-based cutpoint for moderate drinking and the estimated association between volume of intake and alcohol use disorders. Data were drawn from the 1988 National Health Interview Survey and the 1992 National Longitudinal Alcohol Epidemiologic Survey. The eight approaches compared overall and beverage-specific questions, reference periods of varying lengths, and measures based solely on usual intake with those that incorporated different aspects of atypical heavy drinking. Average daily ethanol intake ranged from 0.43 oz based on two questions on current usual frequency and quantity of drinking (assuming 0.5 oz of ethanol per drink) to 0.72 oz based on 21 questions that included usual and heaviest consumption of beer, wine and distilled spirits in the year preceding interview. Estimated volume was highly sensitive to the number and types of questions upon which it was based, and changes in formulation that resulted in relatively small increases in mean volume often were associated with much larger increases in the proportion of drinkers exceeding some specified level of intake and in the estimated association between consumption and alcohol use disorders. These issues should be considered when deciding on the consumption items to be included in alcohol surveys. JF - Journal of studies on alcohol AU - Dawson, D A AD - Division of Biometry and Epidemiology, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland 20892-7003, USA. Y1 - 1998/03// PY - 1998 DA - March 1998 SP - 191 EP - 197 VL - 59 IS - 2 SN - 0096-882X, 0096-882X KW - Index Medicus KW - Sex Factors KW - Humans KW - Reference Standards KW - Aged KW - Longitudinal Studies KW - Cross-Sectional Studies KW - Psychiatric Status Rating Scales KW - Adult KW - Incidence KW - Middle Aged KW - Alcoholic Beverages -- classification KW - Adolescent KW - United States -- epidemiology KW - Female KW - Male KW - Alcoholism -- epidemiology KW - Alcoholism -- diagnosis KW - Alcohol Drinking -- adverse effects KW - Alcohol Drinking -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79726968?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+studies+on+alcohol&rft.atitle=Volume+of+ethanol+consumption%3A+effects+of+different+approaches+to+measurement.&rft.au=Dawson%2C+D+A&rft.aulast=Dawson&rft.aufirst=D&rft.date=1998-03-01&rft.volume=59&rft.issue=2&rft.spage=191&rft.isbn=&rft.btitle=&rft.title=Journal+of+studies+on+alcohol&rft.issn=0096882X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-05-06 N1 - Date created - 1998-05-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Modulation of methylnitrosourea-induced breast cancer in Sprague Dawley rats by dehydroepiandrosterone: dose-dependent inhibition, effects of limited exposure, effects on peroxisomal enzymes, and lack of effects on levels of Ha-Ras mutations. AN - 79726740; 9500451 AB - Dehydroepiandrosterone (DHEA), the major steroid precursor of androgens and estrogens produced in peripheral tissues in primates, is an effective chemopreventive agent in the N-methyl-N-nitrosourea (MNU)-induced rat mammary tumor model. Dietary DHEA (5-600 ppm; 600 mg/kg diet) was administered beginning 1 week before MNU and administered continually throughout the duration of the experiment. The highest dose of DHEA (600 ppm) significantly decreased tumor incidence from 95 to 45% and increased tumor latency and decreased tumor multiplicity from 4.1 to 0.5 tumors/rat. Lower doses of DHEA (5, 24, and 120 ppm) were also effective, decreasing tumor multiplicity by 28, 40, and 55%, respectively, increasing tumor latency in a dose-dependent manner but only minimally affecting final tumor incidence. DHEA in the diet caused a dose-dependent increase in serum levels of DHEA. The 120-ppm dietary dose of DHEA resulted in serum levels of DHEA of approximately 42 pmol/ml levels, similar to those seen in young humans. When we examined whole mounts of mammary glands derived from rats exposed to higher levels of DHEA (600 ppm), we observed a striking increase in lobular development. The doses of DHEA used in these studies (< or =600 ppm) had minimal effects on the induction of fatty acid CoA synthetase, a peroxisome-associated enzyme. In contrast, a dose of 2000 ppm substantially increased levels of peroxisome-associated fatty acid CoA synthetase. The varied and striking efficacy of DHEA was achieved in the absence of any significant effect on body weight gain in the treated rats. Furthermore, tumors from rats treated with MNU alone or rats treated with MNU plus DHEA were examined for the presence of mutations in the Ha-Ras oncogene. There was a slight decrease in the percentage of tumors bearing Ha-Ras mutations in tumors derived from MNU-control rats as contrasted with tumors from MNU-DHEA (120 and 600 ppm)-treated rats. Based on the striking chemopreventive efficacy of continual exposure to DHEA, we examined the effects of more limited exposure to DHEA. Rats were treated with DHEA for a period of 7 weeks immediately before and after MNU injection. Rats were then placed on the control diet for the ensuing 15 weeks. Even this limited exposure to DHEA for a period of 7 weeks profoundly decreased final tumor incidence and multiplicity. Additionally, we examined the effects of intermittent dosing with DHEA. Rats were treated alternatively at 3-week intervals either with diet containing DHEA or with control diet. It was found that this intermittent dosing with DHEA also substantially inhibited the formation of mammary tumors. JF - Cancer research AU - Lubet, R A AU - Gordon, G B AU - Prough, R A AU - Lei, X D AU - You, M AU - Wang, Y AU - Grubbs, C J AU - Steele, V E AU - Kelloff, G J AU - Thomas, C F AU - Moon, R D AD - National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1998/03/01/ PY - 1998 DA - 1998 Mar 01 SP - 921 EP - 926 VL - 58 IS - 5 SN - 0008-5472, 0008-5472 KW - Dehydroepiandrosterone KW - 459AG36T1B KW - Methylnitrosourea KW - 684-93-5 KW - Coenzyme A Ligases KW - EC 6.2.1.- KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Dose-Response Relationship, Drug KW - Cell Division -- drug effects KW - Coenzyme A Ligases -- drug effects KW - Diet KW - Mutation KW - Female KW - Genes, ras KW - Mammary Neoplasms, Animal -- pathology KW - Neoplasms, Experimental -- chemically induced KW - Mammary Neoplasms, Animal -- genetics KW - Dehydroepiandrosterone -- therapeutic use KW - Neoplasms, Experimental -- drug therapy KW - Microbodies -- drug effects KW - Mammary Neoplasms, Animal -- chemically induced KW - Neoplasms, Experimental -- pathology KW - Mammary Neoplasms, Animal -- drug therapy KW - Dehydroepiandrosterone -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79726740?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Modulation+of+methylnitrosourea-induced+breast+cancer+in+Sprague+Dawley+rats+by+dehydroepiandrosterone%3A+dose-dependent+inhibition%2C+effects+of+limited+exposure%2C+effects+on+peroxisomal+enzymes%2C+and+lack+of+effects+on+levels+of+Ha-Ras+mutations.&rft.au=Lubet%2C+R+A%3BGordon%2C+G+B%3BPrough%2C+R+A%3BLei%2C+X+D%3BYou%2C+M%3BWang%2C+Y%3BGrubbs%2C+C+J%3BSteele%2C+V+E%3BKelloff%2C+G+J%3BThomas%2C+C+F%3BMoon%2C+R+D&rft.aulast=Lubet&rft.aufirst=R&rft.date=1998-03-01&rft.volume=58&rft.issue=5&rft.spage=921&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 - 1998-03-25 N1 - Date created - 1998-03-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Open-label trial of oral nalmefene therapy for the pruritus of cholestasis. AN - 79726388; 9500694 AB - The aims of this study were to determine whether long-term oral administration of the opiate antagonist nalmefene is associated with any beneficial effects in patients with pruritus secondary to cholestatic liver disease and to assess the safety of long-term administration of this drug to these patients. Fourteen patients with unrelieved chronic pruritus of cholestasis were studied. Scratching activity, independent of limb movements, was recorded continuously for 24-hour periods before and during treatment with an initial ameliorating dose of nalmefene. Simultaneously, during these periods, visual analogue scores (VASs) of pruritus were recorded every 4 hours while patients were awake. The dose of nalmefene, which initially was 2 mg orally twice daily, was increased during the study, usually until a satisfactory clinical response was achieved. Five patients experienced a transient opioid withdrawal-like reaction that did not preclude continuing with nalmefene therapy. Serum biochemical indices of cholestasis did not change appreciably during treatment. Thirteen patients reported amelioration of the perception of pruritus on nalmefene. In 5 patients, exacerbations of pruritus occurred approximately 4 weeks after an initial ameliorating dose had been reached; these exacerbations were managed by increasing the dose. Baseline mean values for VAS and scratching activity were higher than corresponding means during nalmefene therapy in 13 (P = .002) and 12 (P = .013) patients, respectively. Possible tolerance to nalmefene occurred in 3 patients. Three patients experienced marked exacerbation of pruritus after nalmefene therapy was suddenly discontinued. Blood levels of nalmefene were consistent with normal pharmacokinetics of the drug. These results suggest that nalmefene may have a favorable risk-to-benefit ratio when it is administered orally long-term to patients with the pruritus of cholestasis. JF - Hepatology (Baltimore, Md.) AU - Bergasa, N V AU - Schmitt, J M AU - Talbot, T L AU - Alling, D W AU - Swain, M G AU - Turner, M L AU - Jenkins, J B AU - Jones, E A AD - Liver Diseases Section, Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, USA. Y1 - 1998/03// PY - 1998 DA - March 1998 SP - 679 EP - 684 VL - 27 IS - 3 SN - 0270-9139, 0270-9139 KW - Narcotic Antagonists KW - 0 KW - Naltrexone KW - 5S6W795CQM KW - nalmefene KW - TOV02TDP9I KW - Index Medicus KW - Administration, Oral KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Child KW - Adolescent KW - Pruritus -- drug therapy KW - Narcotic Antagonists -- therapeutic use KW - Naltrexone -- adverse effects KW - Naltrexone -- analogs & derivatives KW - Cholestasis -- drug therapy KW - Naltrexone -- pharmacokinetics KW - Naltrexone -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79726388?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Open-label+trial+of+oral+nalmefene+therapy+for+the+pruritus+of+cholestasis.&rft.au=Bergasa%2C+N+V%3BSchmitt%2C+J+M%3BTalbot%2C+T+L%3BAlling%2C+D+W%3BSwain%2C+M+G%3BTurner%2C+M+L%3BJenkins%2C+J+B%3BJones%2C+E+A&rft.aulast=Bergasa&rft.aufirst=N&rft.date=1998-03-01&rft.volume=27&rft.issue=3&rft.spage=679&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 - 1998-03-19 N1 - Date created - 1998-03-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Development of a murine mutant Ras CD8+ CTL peptide epitope variant that possesses enhanced MHC class I binding and immunogenic properties. AN - 79721420; 9498787 AB - We recently identified a murine mutant Ras p21 CD8+ CTL epitope reflecting residues 4 to 12, containing the mutation of Gly to Val at codon 12, that bound weakly to H-2Kd in vitro and generated a weak primary CTL response in immunized BALB/c mice. Here, we explored the hypothesis that specific modifications to the Ras4-12 peptide sequence can improve MHC binding, leading to enhanced immunogenicity without altering immune specificity. We synthesized Ras4-12 peptides in which Val at residue 12 was replaced with the more dominant H-2Kd C-terminus anchor residue Leu or Ile. In functional H-2Kd binding assays, Ras4-12(L12 or I12) peptide variants competed more effectively than the Ras4-12(V12) peptide. Ras4-12(L12 or I12) peptide variants enhanced both in vitro cytotoxicity and proliferation responses of anti-Ras4-12 CTL compared with the mutant Ras4-12(V12) peptide. Additionally, the Ras4-12(L12) peptide variant induced a quantitatively greater T cell response in vivo compared with that produced by Ras4-12(V12) as determined by IFN-gamma production. Mice immunized with Ras4-12(L12) peptide elicited CD8+ CTL activity specific for target cells presenting the Ras4-12(V12) epitope exogenously and endogenously. Moreover, both anti-Ras4-12(V12)-derived and anti-Ras4-12(L12)-derived CTL lines were similar insofar as their TCR usage and amino acid contact residues in the Ras4-12(V12) peptide. These experiments demonstrate that modifications can be introduced in tumor-specific peptide epitopes to enhance both in vitro and in vivo immunogenicity. The design of oncogene-specific peptide epitope variants as immunogens may accelerate the generation of anti-tumor T cell responses for cancer immunotherapy. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Bristol, J A AU - Schlom, J AU - Abrams, S I AD - Laboratory of Tumor Immunology and Biology, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1998/03/01/ PY - 1998 DA - 1998 Mar 01 SP - 2433 EP - 2441 VL - 160 IS - 5 SN - 0022-1767, 0022-1767 KW - Antigens, CD8 KW - 0 KW - Epitopes KW - H-2 Antigens KW - Peptide Fragments KW - Receptors, Antigen, T-Cell, alpha-beta KW - ras Proteins KW - EC 3.6.5.2 KW - Abridged Index Medicus KW - Index Medicus KW - Amino Acid Substitution -- immunology KW - Animals KW - Receptors, Antigen, T-Cell, alpha-beta -- metabolism KW - Antigens, CD8 -- physiology KW - Genes, ras -- immunology KW - Mice KW - Mice, Inbred BALB C KW - Receptors, Antigen, T-Cell, alpha-beta -- biosynthesis KW - Lymphocyte Activation -- drug effects KW - Amino Acid Substitution -- genetics KW - Injections, Subcutaneous KW - Cytotoxicity, Immunologic -- drug effects KW - Epitope Mapping KW - Cell Line KW - Female KW - ras Proteins -- genetics KW - Epitopes -- genetics KW - Peptide Fragments -- genetics KW - H-2 Antigens -- physiology KW - T-Lymphocytes, Cytotoxic -- immunology KW - T-Lymphocytes, Cytotoxic -- metabolism KW - Peptide Fragments -- immunology KW - Mutagenesis KW - H-2 Antigens -- genetics KW - ras Proteins -- administration & dosage KW - ras Proteins -- immunology KW - Peptide Fragments -- pharmacology KW - ras Proteins -- metabolism KW - Epitopes -- immunology KW - Peptide Fragments -- administration & dosage KW - Epitopes -- metabolism KW - H-2 Antigens -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79721420?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Development+of+a+murine+mutant+Ras+CD8%2B+CTL+peptide+epitope+variant+that+possesses+enhanced+MHC+class+I+binding+and+immunogenic+properties.&rft.au=Bristol%2C+J+A%3BSchlom%2C+J%3BAbrams%2C+S+I&rft.aulast=Bristol&rft.aufirst=J&rft.date=1998-03-01&rft.volume=160&rft.issue=5&rft.spage=2433&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 - 1998-03-18 N1 - Date created - 1998-03-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inhibition of cell proliferation and induction of apoptosis by the retinoid AHPN in human lung carcinoma cells. AN - 79717757; 9490650 AB - In this study, we investigated the effect of the novel retinoid 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid (AHPN/CD437) on the growth of human lung carcinoma cell lines. AHPN inhibits the proliferation of all cell lines tested, irrespective of the lung tumor type, in a concentration- and time-dependent manner. A dramatic reduction in cell number was observed in adenocarcinoma H460 cells, and was shown to be related to an induction of apoptosis. Bromodeoxyuridine (BrdU) incorporation and flow-cytometric analyses indicated that treatment of H460 cells with AHPN induces cell-cycle arrest at the G1 phase. We therefore investigated the effect of AHPN on several regulatory proteins of the G1 phase of the cell-cycle. The cell-cycle arrest induced by AHPN was accompanied by an inhibition of the hyperphosphorylation of the retinoblastoma (Rb) protein, an indication of G1 arrest. Furthermore, two cyclin-dependent kinases, cdk2 and cdk4, which are normally involved in the phosphorylation of Rb, were shown to have decreased activity. In some cell lines, the decrease in cdk activity may be partly related to an increase in p21(WAF1/Cip1) (p21), an inhibitor of cyclin-dependent kinases. No changes were observed in the cyclin-dependent kinase inhibitor p27(Kip1). The observed increase in p53 in response to AHPN could at least to some extent be responsible for the increased levels of p21. The increase in p53 expression was found to be regulated at a post-transcriptional level. Our results suggest that the growth inhibition of certain lung carcinoma cell lines by AHPN is at least partly related to an increase in p21. However, in other cell lines, different mechanisms appear to be involved. The specificity with which AHPN and other retinoids induce growth arrest and p21 expression indicates that the action of AHPN is not mediated by RAR or RXR receptors, but involves a novel signaling pathway. JF - American journal of respiratory cell and molecular biology AU - Adachi, H AU - Preston, G AU - Harvat, B AU - Dawson, M I AU - Jetten, A M AD - Laboratories of Pulmonary Pathobiology and Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, 27709, USA. Y1 - 1998/03// PY - 1998 DA - March 1998 SP - 323 EP - 333 VL - 18 IS - 3 SN - 1044-1549, 1044-1549 KW - CD 437 KW - 0 KW - Proto-Oncogene Proteins KW - Proto-Oncogene Proteins c-bcl-2 KW - Retinoblastoma Protein KW - Retinoids KW - bcl-2-Associated X Protein KW - Index Medicus KW - Proto-Oncogene Proteins c-bcl-2 -- biosynthesis KW - Proto-Oncogene Proteins -- biosynthesis KW - Carcinoma, Non-Small-Cell Lung -- metabolism KW - Tumor Cells, Cultured KW - Carcinoma, Small Cell -- metabolism KW - Humans KW - Retinoblastoma Protein -- metabolism KW - Cell Division -- drug effects KW - Phosphorylation -- drug effects KW - Apoptosis KW - Lung -- drug effects KW - Retinoids -- pharmacology KW - Lung -- pathology KW - Carcinoma -- metabolism KW - Lung Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79717757?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+respiratory+cell+and+molecular+biology&rft.atitle=Inhibition+of+cell+proliferation+and+induction+of+apoptosis+by+the+retinoid+AHPN+in+human+lung+carcinoma+cells.&rft.au=Adachi%2C+H%3BPreston%2C+G%3BHarvat%2C+B%3BDawson%2C+M+I%3BJetten%2C+A+M&rft.aulast=Adachi&rft.aufirst=H&rft.date=1998-03-01&rft.volume=18&rft.issue=3&rft.spage=323&rft.isbn=&rft.btitle=&rft.title=American+journal+of+respiratory+cell+and+molecular+biology&rft.issn=10441549&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-31 N1 - Date created - 1998-03-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Activated T lymphocytes induce degranulation and cytokine production by human mast cells following cell-to-cell contact. AN - 79717040; 9500521 AB - Activated mast cells reside in close apposition to T cells in some inflammatory processes. In this study, we analyzed whether this close physical proximity affects human mast cell degranulation and cytokine release. Thus HMC-1 human mast cells or primary bone marrow-derived human mast cells were cocultured with activated and with resting T cells. Mast cells cocultured with activated T cells released histamine and beta-hexosaminidase and produced tumor necrosis factor alpha (TNF-alpha), an effect that peaked at 20 h. Kinetics of histamine release paralleled the formation of heterotypic aggregates. Separation of the two cell populations with a porous membrane prevented mediator release and TNF-alpha production. Addition of the PI3-kinase inhibitor, wortmannin, inhibited the heterotypic adhesion-associated degranulation but not TNF-alpha production. These data thus indicate a novel pathway through which human mast cells are activated to both release granule-associated mediators and to produce cytokines in association with heterotypic adhesion to activated human T cells. JF - Journal of leukocyte biology AU - Bhattacharyya, S P AU - Drucker, I AU - Reshef, T AU - Kirshenbaum, A S AU - Metcalfe, D D AU - Mekori, Y A AD - The Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-1881, USA. Y1 - 1998/03// PY - 1998 DA - March 1998 SP - 337 EP - 341 VL - 63 IS - 3 SN - 0741-5400, 0741-5400 KW - Androstadienes KW - 0 KW - Antibodies, Monoclonal KW - Antigens, CD3 KW - Cytokines KW - Tumor Necrosis Factor-alpha KW - Phosphatidylinositol 3-Kinases KW - EC 2.7.1.- KW - beta-N-Acetylhexosaminidases KW - EC 3.2.1.52 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - wortmannin KW - XVA4O219QW KW - Index Medicus KW - Coculture Techniques KW - Humans KW - Androstadienes -- pharmacology KW - Antibodies, Monoclonal -- pharmacology KW - Antigens, CD3 -- immunology KW - Bone Marrow Cells KW - beta-N-Acetylhexosaminidases -- metabolism KW - Kinetics KW - Histamine Release KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Cell Adhesion -- drug effects KW - Time Factors KW - Phosphatidylinositol 3-Kinases -- antagonists & inhibitors KW - Antigens, CD3 -- physiology KW - Lymphocyte Activation KW - Mast Cells -- immunology KW - Cytokines -- biosynthesis KW - Cytoplasmic Granules -- immunology KW - Tumor Necrosis Factor-alpha -- biosynthesis KW - T-Lymphocytes -- immunology KW - Mast Cells -- drug effects KW - Cell Communication -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79717040?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+leukocyte+biology&rft.atitle=Activated+T+lymphocytes+induce+degranulation+and+cytokine+production+by+human+mast+cells+following+cell-to-cell+contact.&rft.au=Bhattacharyya%2C+S+P%3BDrucker%2C+I%3BReshef%2C+T%3BKirshenbaum%2C+A+S%3BMetcalfe%2C+D+D%3BMekori%2C+Y+A&rft.aulast=Bhattacharyya&rft.aufirst=S&rft.date=1998-03-01&rft.volume=63&rft.issue=3&rft.spage=337&rft.isbn=&rft.btitle=&rft.title=Journal+of+leukocyte+biology&rft.issn=07415400&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-24 N1 - Date created - 1998-03-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A phase I/II study of the protease inhibitor ritonavir in children with human immunodeficiency virus infection. AN - 79707793; 9480994 AB - Ritonavir, a potent antiretroviral protease inhibitor, has been approved for the treatment of adults and children with human immunodeficiency virus (HIV) infection. In a phase I/II study, we assessed the safety, tolerability, and pharmacokinetic profile of the oral solution of ritonavir in HIV-infected children and studied the preliminary antiviral and clinical effects. HIV-infected children between 6 months and 18 years of age were eligible. Four dose levels of ritonavir oral solution (250, 300, 350, and 400 mg/m given every 12 hours) were evaluated in two age groups (2 years). Ritonavir was administered alone for the first 12 weeks and then in combination with zidovudine and/or didanosine. Clinical and laboratory parameters were monitored every 2 to 4 weeks. A total of 48 children (median age, 7.7 years; range, 0.5 to 14.4 years) were included in this analysis. Dose-related nausea, diarrhea, and abdominal pain were the most common toxicities and resulted in discontinuation of ritonavir in 7 children. Ritonavir was well absorbed at all dose levels, and plasma concentrations reached a peak 2 to 4 hours after a dose. CD4 cells counts increased by a median of 79 cells/mm3 after 4 weeks of monotherapy and were maintained throughout the study. Plasma HIV RNA decreased by 1 to 2 log10 copies/mL within 4 to 8 weeks of ritonavir monotherapy, and this level was sustained in patients enrolled at the highest dose level of 400 mg/m for the 24-week period. The oral solution of ritonavir has potent antiretroviral activity as a single agent and is relatively well tolerated by children when administered alone or in combination with zidovudine or didanosine. JF - Pediatrics AU - Mueller, B U AU - Nelson, R P AU - Sleasman, J AU - Zuckerman, J AU - Heath-Chiozzi, M AU - Steinberg, S M AU - Balis, F M AU - Brouwers, P AU - Hsu, A AU - Saulis, R AU - Sei, S AU - Wood, L V AU - Zeichner, S AU - Katz, T T AU - Higham, C AU - Aker, D AU - Edgerly, M AU - Jarosinski, P AU - Serchuck, L AU - Whitcup, S M AU - Pizzuti, D AU - Pizzo, P A AD - HIV and AIDS Malignancy Branch, National Cancer Institute, Bethesda, Maryland, USA. Y1 - 1998/03// PY - 1998 DA - March 1998 SP - 335 EP - 343 VL - 101 IS - 3 Pt 1 SN - 0031-4005, 0031-4005 KW - Anti-HIV Agents KW - 0 KW - HIV Protease Inhibitors KW - Zidovudine KW - 4B9XT59T7S KW - Didanosine KW - K3GDH6OH08 KW - Ritonavir KW - O3J8G9O825 KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Zidovudine -- therapeutic use KW - Administration, Oral KW - Humans KW - Child KW - CD4 Lymphocyte Count KW - Child, Preschool KW - Viral Load KW - Drug Therapy, Combination KW - Infant KW - Didanosine -- therapeutic use KW - Anti-HIV Agents -- therapeutic use KW - Adolescent KW - Female KW - Male KW - Ritonavir -- therapeutic use KW - Ritonavir -- pharmacokinetics KW - HIV Infections -- drug therapy KW - HIV Protease Inhibitors -- pharmacokinetics KW - HIV Protease Inhibitors -- therapeutic use KW - HIV Protease Inhibitors -- adverse effects KW - Ritonavir -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79707793?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pediatrics&rft.atitle=A+phase+I%2FII+study+of+the+protease+inhibitor+ritonavir+in+children+with+human+immunodeficiency+virus+infection.&rft.au=Mueller%2C+B+U%3BNelson%2C+R+P%3BSleasman%2C+J%3BZuckerman%2C+J%3BHeath-Chiozzi%2C+M%3BSteinberg%2C+S+M%3BBalis%2C+F+M%3BBrouwers%2C+P%3BHsu%2C+A%3BSaulis%2C+R%3BSei%2C+S%3BWood%2C+L+V%3BZeichner%2C+S%3BKatz%2C+T+T%3BHigham%2C+C%3BAker%2C+D%3BEdgerly%2C+M%3BJarosinski%2C+P%3BSerchuck%2C+L%3BWhitcup%2C+S+M%3BPizzuti%2C+D%3BPizzo%2C+P+A&rft.aulast=Mueller&rft.aufirst=B&rft.date=1998-03-01&rft.volume=101&rft.issue=3+Pt+1&rft.spage=335&rft.isbn=&rft.btitle=&rft.title=Pediatrics&rft.issn=00314005&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-10 N1 - Date created - 1998-03-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Construction and characterization of a temperature-sensitive human immunodeficiency virus type 1 reverse transcriptase mutant. AN - 79697840; 9499059 AB - A temperature-sensitive (ts) human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) mutant was generated by charged-cluster-to-alanine mutagenesis. The mutant virus, containing three charged residues within the RT finger domain changed to alanine (K64A, K66A, and D67A), replicated normally at 34.5 but not 39.5 degrees C. Quantitating virus particle production by p24 antigen capture or virion-associated RT activity and virus infectivity by the MAGI cell assay, we found that (i) mutant virions produced at the permissive temperature were indistinguishable from wild-type virus in assays performed at the nonpermissive temperature, suggesting that the ts mutation did not impair early steps in the virus replication cycle and that the mutant RT enzyme was not ts; and (ii) virus particle production in cells transfected with the ts mutant at the nonpermissive temperature was comparable to that of wild-type virus. However, the particle-associated RT activity and infectivity of mutant virions produced at the nonpermissive temperature were greatly reduced when assays were conducted at the permissive temperature. These results are consistent with an irreversible ts event affecting RT that occurs during virus particle production. Radioimmunoprecipitation analyses revealed that both p66 and p51 RT subunits were absent from mutant virions generated at 39.5 degrees C. The presence of normal levels of HIV-1 integrase in mutant particles produced at the nonpermissive temperature was inconsistent with defective Gag-Pol synthesis or Gag-Pol incorporation into progeny virions. Furthermore, wild-type levels of the mutant Pr160(gag-pol) were detected in virions produced at the nonpermissive temperature when the HIV-1 protease was inactivated by site-specific mutagenesis. Taken together, these results are most consistent with a ts defect affecting the degradation or aberrant processing of the mutated RT during its processing/maturation within nascent particles. JF - Journal of virology AU - Huang, M AU - Zensen, R AU - Cho, M AU - Martin, M A AD - Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892, USA. Y1 - 1998/03// PY - 1998 DA - March 1998 SP - 2047 EP - 2054 VL - 72 IS - 3 SN - 0022-538X, 0022-538X KW - Gene Products, gag KW - 0 KW - Protein Precursors KW - gag Gene Products, Human Immunodeficiency Virus KW - pol Gene Products, Human Immunodeficiency Virus KW - pr160 gag-pol precursor protein, Human immunodeficiency virus 1 KW - HIV Reverse Transcriptase KW - EC 2.7.7.49 KW - Alanine KW - OF5P57N2ZX KW - Index Medicus KW - AIDS/HIV KW - Protein Precursors -- metabolism KW - HeLa Cells KW - Protein Precursors -- biosynthesis KW - Humans KW - Temperature KW - Gene Products, gag -- biosynthesis KW - Virion -- metabolism KW - Gene Products, gag -- metabolism KW - Cloning, Molecular KW - HIV Reverse Transcriptase -- genetics KW - HIV-1 -- genetics KW - Alanine -- metabolism KW - HIV Reverse Transcriptase -- metabolism KW - Alanine -- genetics KW - HIV-1 -- enzymology KW - Mutagenesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79697840?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Construction+and+characterization+of+a+temperature-sensitive+human+immunodeficiency+virus+type+1+reverse+transcriptase+mutant.&rft.au=Huang%2C+M%3BZensen%2C+R%3BCho%2C+M%3BMartin%2C+M+A&rft.aulast=Huang&rft.aufirst=M&rft.date=1998-03-01&rft.volume=72&rft.issue=3&rft.spage=2047&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 - 1998-03-12 N1 - Date created - 1998-03-12 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Antimicrob Agents Chemother. 1993 Jun;37(6):1390-2 [8392313] Antimicrob Agents Chemother. 1993 Jun;37(6):1207-13 [8328771] Biochem Pharmacol. 1994 Jan 20;47(2):155-69 [7508227] J Virol. 1994 Apr;68(4):2503-12 [8139032] Proc Natl Acad Sci U S A. 1994 May 10;91(10):4554-8 [8183946] Antimicrob Agents Chemother. 1994 Feb;38(2):275-81 [7514855] Antimicrob Agents Chemother. 1994 Feb;38(2):282-7 [7514856] Proc Natl Acad Sci U S A. 1994 May 24;91(11):4882-6 [7515182] Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):7242-6 [7518928] Curr Opin Biotechnol. 1994 Aug;5(4):414-21 [7520785] J Virol. 1994 Oct;68(10):6782-6 [8084015] J Biol Chem. 1994 Oct 21;269(42):26472-8 [7523408] J Biol Chem. 1994 Nov 11;269(45):28091-7 [7525566] J Biol Chem. 1994 Nov 11;269(45):28118-22 [7525567] J Mol Biol. 1994 Oct 28;243(3):472-83 [7525967] J Virol. 1995 Jan;69(1):597-601 [7983762] Proc Natl Acad Sci U S A. 1995 Feb 14;92(4):1222-6 [7532306] Nucleic Acids Res. 1995 Mar 11;23(5):803-10 [7535923] J Virol. 1995 Nov;69(11):6810-8 [7474093] J Acquir Immune Defic Syndr Hum Retrovirol. 1995;10 Suppl 1:S28-33 [8595505] J Virol. 1996 Jun;70(6):3698-705 [8648704] J Biol Chem. 1996 Mar 1;271(9):4872-8 [8617758] J Biol Chem. 1996 May 24;271(21):12213-20 [8647817] Biochemistry. 1996 Jul 2;35(26):8553-62 [8679616] Science. 1986 Mar 14;231(4743):1289-91 [2418504] Nature. 1987 Jun 25-Jul 1;327(6124):716-7 [2439916] J Virol. 1988 Jan;62(1):139-47 [3257102] EMBO J. 1987 Oct;6(10):3133-7 [2446866] Methods Enzymol. 1987;154:367-82 [3323813] Proc Natl Acad Sci U S A. 1988 Feb;85(4):1218-22 [2448794] Proc Natl Acad Sci U S A. 1988 Dec;85(24):9580-4 [2849111] DNA. 1988 Jul-Aug;7(6):407-16 [2462482] Biochemistry. 1988 Dec 13;27(25):8884-9 [2466481] Proc Natl Acad Sci U S A. 1989 Jul;86(13):4803-7 [2472634] Nature. 1989 Aug 3;340(6232):397-400 [2666861] J Biol Chem. 1989 Aug 25;264(24):13975-8 [2474539] Biochem Biophys Res Commun. 1990 Mar 16;167(2):673-9 [1690991] J Biol Chem. 1990 Jun 5;265(16):8986-8 [1693146] AIDS Res Hum Retroviruses. 1990 Jun;6(6):753-64 [1694680] Proc Natl Acad Sci U S A. 1991 May 15;88(10):4498-502 [2034689] FEBS Lett. 1991 May 6;282(2):231-4 [1709876] Biochemistry. 1991 Jul 2;30(26):6351-6 [1711368] J Virol. 1991 Aug;65(8):4350-8 [2072454] Virology. 1991 Sep;184(1):319-29 [1871974] AIDS. 1991 Jun;5(6):639-54 [1883539] EMBO J. 1991 Dec;10(12):3905-11 [1718745] Virology. 1991 Dec;185(2):661-72 [1683726] J Virol. 1992 Feb;66(2):1031-9 [1370546] J Virol. 1992 Apr;66(4):2232-9 [1548759] Science. 1992 Jun 26;256(5065):1783-90 [1377403] J Virol. 1992 Nov;66(11):6304-13 [1383561] Genetics. 1992 Oct;132(2):337-50 [1427032] J Virol. 1992 Dec;66(12):7533-7 [1279205] J Virol. 1993 Apr;67(4):2266-75 [8445731] Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6320-4 [7687065] J Virol. 1994 Feb;68(2):863-76 [8289389] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - CD4 glycoprotein degradation induced by human immunodeficiency virus type 1 Vpu protein requires the function of proteasomes and the ubiquitin-conjugating pathway. AN - 79696543; 9499087 AB - The human immunodeficiency virus type 1 (HIV-1) vpu gene encodes a type I anchored integral membrane phosphoprotein with two independent functions. First, it regulates virus release from a post-endoplasmic reticulum (ER) compartment by an ion channel activity mediated by its transmembrane anchor. Second, it induces the selective down regulation of host cell receptor proteins (CD4 and major histocompatibility complex class I molecules) in a process involving its phosphorylated cytoplasmic tail. In the present work, we show that the Vpu-induced proteolysis of nascent CD4 can be completely blocked by peptide aldehydes that act as competitive inhibitors of proteasome function and also by lactacystin, which blocks proteasome activity by covalently binding to the catalytic beta subunits of proteasomes. The sensitivity of Vpu-induced CD4 degradation to proteasome inhibitors paralleled the inhibition of proteasome degradation of a model ubiquitinated substrate. Characterization of CD4-associated oligosaccharides indicated that CD4 rescued from Vpu-induced degradation by proteasome inhibitors is exported from the ER to the Golgi complex. This finding suggests that retranslocation of CD4 from the ER to the cytosol may be coupled to its proteasomal degradation. CD4 degradation mediated by Vpu does not require the ER chaperone calnexin and is dependent on an intact ubiquitin-conjugating system. This was demonstrated by inhibition of CD4 degradation (i) in cells expressing a thermally inactivated form of the ubiquitin-activating enzyme E1 or (ii) following expression of a mutant form of ubiquitin (Lys48 mutated to Arg48) known to compromise ubiquitin targeting by interfering with the formation of polyubiquitin complexes. CD4 degradation was also prevented by altering the four Lys residues in its cytosolic domain to Arg, suggesting a role for ubiquitination of one or more of these residues in the process of degradation. The results clearly demonstrate a role for the cytosolic ubiquitin-proteasome pathway in the process of Vpu-induced CD4 degradation. In contrast to other viral proteins (human cytomegalovirus US2 and US11), however, whose translocation of host ER molecules into the cytosol occurs in the presence of proteasome inhibitors, Vpu-targeted CD4 remains in the ER in a transport-competent form when proteasome activity is blocked. JF - Journal of virology AU - Schubert, U AU - Antón, L C AU - Bacík, I AU - Cox, J H AU - Bour, S AU - Bennink, J R AU - Orlowski, M AU - Strebel, K AU - Yewdell, J W AD - Laboratories of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892-0440, USA. Y1 - 1998/03// PY - 1998 DA - March 1998 SP - 2280 EP - 2288 VL - 72 IS - 3 SN - 0022-538X, 0022-538X KW - Antigens, CD4 KW - 0 KW - Calcium-Binding Proteins KW - Cysteine Proteinase Inhibitors KW - Glycoproteins KW - Human Immunodeficiency Virus Proteins KW - Leupeptins KW - Multienzyme Complexes KW - Ubiquitins KW - Viral Regulatory and Accessory Proteins KW - vpu protein, Human immunodeficiency virus 1 KW - lactacystin KW - 133343-34-7 KW - Calnexin KW - 139873-08-8 KW - Cysteine Endopeptidases KW - EC 3.4.22.- KW - Proteasome Endopeptidase Complex KW - EC 3.4.25.1 KW - benzyloxycarbonylleucyl-leucyl-leucine aldehyde KW - RF1P63GW3K KW - Acetylcysteine KW - WYQ7N0BPYC KW - Index Medicus KW - AIDS/HIV KW - Cytosol -- metabolism KW - Acetylcysteine -- analogs & derivatives KW - Enzyme Activation KW - HeLa Cells KW - Humans KW - Acetylcysteine -- pharmacology KW - Mutagenesis KW - Cysteine Proteinase Inhibitors -- pharmacology KW - Leupeptins -- pharmacology KW - Cytoplasm KW - Calcium-Binding Proteins -- genetics KW - Calcium-Binding Proteins -- metabolism KW - Cell Line KW - Multienzyme Complexes -- metabolism KW - HIV-1 -- metabolism KW - Ubiquitins -- metabolism KW - Glycoproteins -- metabolism KW - Cysteine Endopeptidases -- metabolism KW - Antigens, CD4 -- genetics KW - Viral Regulatory and Accessory Proteins -- metabolism KW - Glycoproteins -- genetics KW - Viral Regulatory and Accessory Proteins -- genetics KW - Antigens, CD4 -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79696543?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=CD4+glycoprotein+degradation+induced+by+human+immunodeficiency+virus+type+1+Vpu+protein+requires+the+function+of+proteasomes+and+the+ubiquitin-conjugating+pathway.&rft.au=Schubert%2C+U%3BAnt%C3%B3n%2C+L+C%3BBac%C3%ADk%2C+I%3BCox%2C+J+H%3BBour%2C+S%3BBennink%2C+J+R%3BOrlowski%2C+M%3BStrebel%2C+K%3BYewdell%2C+J+W&rft.aulast=Schubert&rft.aufirst=U&rft.date=1998-03-01&rft.volume=72&rft.issue=3&rft.spage=2280&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 - 1998-03-12 N1 - Date created - 1998-03-12 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Immunol. 1997 Jul 15;159(2):554-64 [9218569] J Immunol. 1985 Feb;134(2):971-6 [3871222] Proc Natl Acad Sci U S A. 1985 Jul;82(13):4539-43 [2989831] Mol Cell Biol. 1985 Dec;5(12):3403-9 [3939316] J Biol Chem. 1987 Mar 15;262(8):3524-7 [3029116] Nature. 1988 Jan 7;331(6151):82-4 [3257544] Nature. 1988 Aug 11;334(6182):532-4 [3043230] Science. 1988 Sep 2;241(4870):1221-3 [3261888] J Virol. 1989 Sep;63(9):3784-91 [2788224] J Virol. 1996 Feb;70(2):809-19 [8551619] Curr Top Microbiol Immunol. 1996;205:19-46 [8575196] Cell. 1996 Mar 8;84(5):769-79 [8625414] J Cell Biol. 1996 Feb;132(3):291-8 [8636208] Biochem J. 1996 Jun 1;316 ( Pt 2):401-7 [8687380] J Biochem. 1996 Mar;119(3):572-6 [8830056] Int J Pept Protein Res. 1996 Apr;47(4):297-310 [8738656] Immunity. 1996 Aug;5(2):103-14 [8769474] Science. 1996 Sep 20;273(5282):1725-8 [8781238] J Virol. 1996 Oct;70(10):7108-15 [8794357] J Biol Chem. 1996 Sep 13;271(37):22791-5 [8798455] Annu Rev Genet. 1995;29:729-54 [8825492] J Biol Chem. 1996 Nov 1;271(44):27280-4 [8910302] J Exp Med. 1988 Oct 1;168(4):1211-24 [2459295] J Virol. 1990 Feb;64(2):621-9 [2404139] Nature. 1990 Jun 14;345(6276):625-8 [2190096] EMBO J. 1990 Sep;9(9):2923-9 [2390975] J Virol. 1990 Nov;64(11):5585-93 [2214026] J Virol. 1991 Dec;65(12):6387-96 [1942241] J Virol. 1992 Jan;66(1):226-34 [1727486] Virology. 1992 Jan;186(1):261-73 [1370128] 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 29;69(5):725-35 [1317266] Biochemistry. 1992 Oct 6;31(39):9421-8 [1356435] J Virol. 1992 Dec;66(12):7193-200 [1433512] Cell. 1992 Dec 11;71(6):963-72 [1333889] Biochemistry. 1993 Feb 16;32(6):1563-72 [8431436] Virology. 1993 Mar;193(1):483-91 [8438583] J Virol. 1993 Jul;67(7):3877-84 [8510209] J Virol. 1993 Aug;67(8):5056-61 [8331740] J Virol. 1993 Dec;67(12):7238-45 [8230446] J Mol Biol. 1994 Feb 11;236(1):16-25 [8107101] Cell. 1994 Mar 11;76(5):853-64 [8124721] J Biol Chem. 1994 Mar 11;269(10):7514-9 [8125971] J Virol. 1994 Apr;68(4):2260-71 [8139011] J Virol. 1994 May;68(5):3092-101 [8151774] J Biol Chem. 1994 Apr 29;269(17):12784-8 [7513695] Trends Biochem Sci. 1994 Mar;19(3):124-8 [8203019] Mol Cell Biol. 1994 Aug;14(8):5501-9 [8035826] Virology. 1994 Oct;204(1):482-6 [8091684] J Immunol. 1995 Jan 15;154(2):511-9 [7814864] J Virol. 1995 Mar;69(3):1510-20 [7853484] Science. 1995 May 5;268(5211):726-31 [7732382] Int J Pept Protein Res. 1995 Jan;45(1):35-43 [7775007] Cell. 1995 Jul 28;82(2):189-92 [7628010] Cell. 1995 Oct 6;83(1):121-7 [7553863] Cell. 1995 Oct 6;83(1):129-35 [7553864] J Virol. 1995 Dec;69(12):7699-711 [7494279] J Biol Chem. 1982 Sep 25;257(18):10766-9 [6955305] Nature. 1996 Dec 5;384(6608):432-8 [8945469] FEBS Lett. 1996 Nov 25;398(1):12-8 [8946945] J Gen Virol. 1997 Mar;78 ( Pt 3):619-25 [9049413] Virology. 1997 Mar 3;229(1):1-11 [9123850] J Exp Med. 1997 Apr 7;185(7):1295-305 [9104816] J Biol Chem. 1997 May 2;272(18):11824-31 [9115240] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Three amino acid substitutions in the L protein of the human parainfluenza virus type 3 cp45 live attenuated vaccine candidate contribute to its temperature-sensitive and attenuation phenotypes. AN - 79694258; 9499025 AB - Studies were initiated to define the genetic basis of the temperature-sensitive (ts), cold adaptation (ca), and attenuation (att) phenotypes of the human parainfluenza virus type 3 (PIV3) cp45 live attenuated vaccine candidate. Genetic data had previously suggested that the L polymerase protein of cp45, which contains three amino acid substitutions at positions 942, 992, and 1558, contributed to its temperature sensitivity (R. Ray, M. S. Galinski, B. R. Heminway, K. Meyer, F. K. Newman, and R. B. Belshe, J. Virol. 70:580-584, 1996; A. Stokes, E. L. Tierney, C. M. Sarris, B. R. Murphy, and S. L. Hall, Virus Res. 30:43-52, 1993). To study the individual and aggregate contributions that these amino acid substitutions make to the ts, att, and ca phenotypes of cp45, seven PIV3 recombinant viruses (three single, three double, and one triple mutant) representing all possible combinations of the three amino acid substitutions were recovered from full-length antigenomic cDNA and analyzed for their ts, att, and ca phenotypes. None of the seven mutant recombinant PIVs was cold adapted. The substitutions at L protein amino acid positions 992 and 1558 each specified a 105-fold reduction in plaque formation in cell culture at 40 degrees C, whereas the substitution at position 942 specified a 300-fold reduction. Thus, each of the three mutations contributes individually to the ts phenotype. The triple recombinant which possesses an L protein with all three mutations was almost as temperature sensitive as cp45, indicating that these mutations are the major contributors to the ts phenotype of cp45. The three individual mutations in the L protein each contributed to restricted replication in the upper or lower respiratory tract of hamsters, and this likely contributes to the observed stability of the ts and att phenotypes of cp45 during replication in vivo. Importantly, the recombinant virus possessing L protein with all three mutations was as restricted in replication as was the cp45 mutant in both the upper and lower respiratory tracts of hamsters, indicating that the L gene of the cp45 virus is a major attenuating component of this candidate vaccine. JF - Journal of virology AU - Skiadopoulos, M H AU - Durbin, A P AU - Tatem, J M AU - Wu, S L AU - Paschalis, M AU - Tao, T AU - Collins, P L AU - Murphy, B R AD - Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland 20892, USA. mskiadopoulos@atlas.niaid.nih.gov Y1 - 1998/03// PY - 1998 DA - March 1998 SP - 1762 EP - 1768 VL - 72 IS - 3 SN - 0022-538X, 0022-538X KW - Vaccines, Attenuated KW - 0 KW - Viral Proteins KW - Viral Vaccines KW - parainfluenza 3 virus, L Protein KW - DNA-Directed RNA Polymerases KW - EC 2.7.7.6 KW - Index Medicus KW - Phenotype KW - Mutagenesis, Site-Directed KW - Animals KW - Viral Plaque Assay KW - Tumor Cells, Cultured KW - Humans KW - Temperature KW - Mesocricetus KW - Macaca mulatta KW - Cell Line KW - Cricetinae KW - Viral Proteins -- genetics KW - Parainfluenza Virus 3, Human -- growth & development KW - Parainfluenza Virus 3, Human -- genetics KW - DNA-Directed RNA Polymerases -- metabolism KW - Viral Proteins -- metabolism KW - Parainfluenza Virus 3, Human -- enzymology KW - DNA-Directed RNA Polymerases -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79694258?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Three+amino+acid+substitutions+in+the+L+protein+of+the+human+parainfluenza+virus+type+3+cp45+live+attenuated+vaccine+candidate+contribute+to+its+temperature-sensitive+and+attenuation+phenotypes.&rft.au=Skiadopoulos%2C+M+H%3BDurbin%2C+A+P%3BTatem%2C+J+M%3BWu%2C+S+L%3BPaschalis%2C+M%3BTao%2C+T%3BCollins%2C+P+L%3BMurphy%2C+B+R&rft.aulast=Skiadopoulos&rft.aufirst=M&rft.date=1998-03-01&rft.volume=72&rft.issue=3&rft.spage=1762&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 - 1998-03-12 N1 - Date created - 1998-03-12 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Virol. 1998 Apr;72(4):2955-61 [9525616] J Virol. 1997 Dec;71(12):8973-82 [9371553] J Med Virol. 1984;13(3):243-9 [6327899] Proc Natl Acad Sci U S A. 1986 Nov;83(21):8122-6 [3095828] J Virol. 1988 Feb;62(2):488-95 [3336068] Virology. 1988 Jun;164(2):487-97 [2835864] Virology. 1988 Aug;165(2):499-510 [2841798] Vaccine. 1990 Oct;8(5):497-502 [2251875] J Virol Methods. 1991 Feb-Mar;31(2-3):161-70 [1650782] Virus Res. 1992 Mar;22(3):173-84 [1320790] Virology. 1992 Nov;191(1):506-10 [1413525] Virus Res. 1992 Sep 1;25(1-2):91-103 [1329377] J Infect Dis. 1993 Apr;167(4):958-62 [8383726] Virology. 1993 Apr;193(2):786-93 [8384756] Virus Res. 1993 Oct;30(1):43-52 [8266719] EMBO J. 1994 Sep 15;13(18):4195-203 [7925265] J Infect Dis. 1995 May;171(5):1107-14 [7751684] Proc Natl Acad Sci U S A. 1995 May 9;92(10):4477-81 [7753828] Virology. 1995 Jun 20;210(1):202-5 [7793072] Virology. 1995 Aug 20;211(2):577-82 [7645261] J Virol. 1995 Oct;69(10):5969-77 [7666501] J Infect Dis. 1995 Dec;172(6):1445-50 [7594701] J Virol. 1996 Jan;70(1):580-4 [8523574] Proc Natl Acad Sci U S A. 1995 Dec 5;92(25):11563-7 [8524804] EMBO J. 1995 Dec 1;14(23):5773-84 [8846771] EMBO J. 1995 Dec 15;14(24):6087-94 [8557028] Virology. 1996 Nov 15;225(2):419-22 [8918930] Virus Genes. 1996;13(3):269-73 [9035372] Genes Cells. 1996 Jun;1(6):569-79 [9078386] J Virol. 1997 Jun;71(6):4272-7 [9151814] J Virol. 1997 Aug;71(8):5814-9 [9223470] Virology. 1997 Jul 21;234(1):74-83 [9234948] Virology. 1997 Sep 1;235(2):323-32 [9281512] J Med Virol. 1982;10(4):235-42 [6298358] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pharmacological therapy. AN - 79619242; 10872480 AB - Collectively sickle cell disease and beta-thalassaemia are the most commonly inherited single-gene defects world-wide and were the first group of diseases for which DNA-based detection strategies were utilized. Although genotypically distinct, these two groups of diseases exhibit several common clinical features: moderate-to-severe haemolytic anaemia, acute and progressive tissue damage, disease- or treatment-related organ failure and premature death. Within the last two decades, a striking improvement in life expectancy in the two patient populations has been observed, by dint of primary and secondary prevention strategies. However, apart from bone marrow transplantation, a generally applicable, specific and non-toxic form of treatment remains unavailable for these disorders. Nonetheless, a greater appreciation of the developmental control of human globin gene expression coupled with observations of the effects of certain classes of agents to 'reverse' erythroid cellular phenotype in in vitro and animal models have led to pharmacological trials to obtain meaningful increases in haemoglobin F production in patients affected by these two severe beta-globin disorders. Contemporary understanding of the quantitative relationship between the abnormal molecules in the red cells (aggregates of sickle haemoglobin) in the sickle cell syndromes and aggregated alpha-globin polypeptides in the beta-thalassemia syndromes, and the extent of the red cell and/or organ involvement, has now enabled investigators to predict how much inhibition of these intracellular pathogenic processes might be necessary to achieve partial or total abrogation of disease manifestations. The results of the Multicenter Study of Hydroxyurea and other controlled trials now bear out these predictions. JF - Bailliere's clinical haematology AU - Rodgers, G P AD - Molecular and Clinical Hematology Branch, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-1822, USA. Y1 - 1998/03// PY - 1998 DA - March 1998 SP - 239 EP - 255 VL - 11 IS - 1 SN - 0950-3536, 0950-3536 KW - Antisickling Agents KW - 0 KW - Fatty Acids KW - Fetal Hemoglobin KW - 9034-63-3 KW - Hydroxyurea KW - X6Q56QN5QC KW - Index Medicus KW - Multicenter Studies as Topic KW - Animals KW - Randomized Controlled Trials as Topic KW - Antisickling Agents -- therapeutic use KW - Fetal Hemoglobin -- physiology KW - Humans KW - Hydroxyurea -- therapeutic use KW - Fetal Hemoglobin -- biosynthesis KW - Child KW - Fatty Acids -- therapeutic use KW - Anemia, Sickle Cell -- drug therapy KW - beta-Thalassemia -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79619242?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Bailliere%27s+clinical+haematology&rft.atitle=Pharmacological+therapy.&rft.au=Rodgers%2C+G+P&rft.aulast=Rodgers&rft.aufirst=G&rft.date=1998-03-01&rft.volume=11&rft.issue=1&rft.spage=239&rft.isbn=&rft.btitle=&rft.title=Bailliere%27s+clinical+haematology&rft.issn=09503536&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-07-14 N1 - Date created - 2000-07-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The incidence of Listeria spp., Salmonella spp., and Clostridium botulinum in smoked fish and shellfish. AN - 73834347; 9708303 AB - The frequency of occurrence of Listeria spp., Salmonella spp., and Clostridium botulinum is samples of smoked finfish and smoked shellfish was analyzed over a 5-year period. Listeria monocytogenes were isolated from 14% of 1,080 samples. For those samples where the smoke process was known, the incidence of L. monocytogenes was higher in cold-smoked than hot-smoked products (51 of 240 cold-smoked compared to 19 of 215 hot-smoked products). Listeria species other than L. monocytogenes were also detected (in 7.2% of cold-smoked and 3.8% of hot-smoked products). The time and temperature smoke processing guidelines are reviewed for a few state authorities. L. monocytogenes was isolated from 15.2% of the 559 samples of foreign origin. There were four countries for which more than 70 samples were analyzed: Canada, Norway, the Philippines, and the United Kingdom. The occurrence of L. monocytogenes in samples from these four countries was 14.3%, 23.7%, 0%, and 16.1%, respectively. The 521 samples originating in the United States were processed by 194 plants. Thirty-seven plants in 13 states produced contaminated product. Salmonella species were isolated from 5 (3.2%) of 156 samples tested for this organism. All positive samples were of foreign origin (4 from the Philippines and 1 from the United Kingdom). No C. botulinum spores were detected in any of the 201 vacuum-packed samples tested for this organism. JF - Journal of food protection AU - Heinitz, M L AU - Johnson, J M AD - U.S. Food and Drug Administration, Minneapolis, Minnesota 55401-1999, USA. gvl@cu.nih.gov Y1 - 1998/03// PY - 1998 DA - March 1998 SP - 318 EP - 323 VL - 61 IS - 3 SN - 0362-028X, 0362-028X KW - Index Medicus KW - Fishes -- microbiology KW - Animals KW - Food Microbiology KW - Cooking -- methods KW - Food Preservation KW - Shellfish -- microbiology KW - Fish Products -- microbiology KW - Salmonella -- isolation & purification KW - Clostridium botulinum -- isolation & purification KW - Listeria -- isolation & purification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73834347?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+food+protection&rft.atitle=The+incidence+of+Listeria+spp.%2C+Salmonella+spp.%2C+and+Clostridium+botulinum+in+smoked+fish+and+shellfish.&rft.au=Heinitz%2C+M+L%3BJohnson%2C+J+M&rft.aulast=Heinitz&rft.aufirst=M&rft.date=1998-03-01&rft.volume=61&rft.issue=3&rft.spage=318&rft.isbn=&rft.btitle=&rft.title=Journal+of+food+protection&rft.issn=0362028X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-09-10 N1 - Date created - 1998-09-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Topical liposome-encapsulated FK506 for the treatment of endotoxin-induced uveitis. AN - 70029206; 9798194 AB - Liposome preparations of FK506 improve the penetration of topically administered drug into the aqueous humor. The purpose of the experiment was to compare topically administered highdose oil-dissolved FK506 (OD-FK506) and low-dose liposome-bound FK506 (LB-506) for the treatment of endotoxin-induced uveitis (EIU). Endotoxin-induced uveitis was produced in female Lewis rats with Salmonella typhimurium endotoxin. Four hours prior to endotoxin injection, one eye received 20 mul eyedrops every four hours containing either high-dose OD-FK506 at 3 mg/ml (N = 20), low-dose LB-FK506 at 0.16 mg/ml (N = 19), prednisolone acetate 1% (N = 20), or empty liposomes (N = 20). Eyes were enucleated 24 hours after endotoxin injection and inflammatory cells were counted on histologic sections by two masked observers. The mean number of infiltrating inflammatory cells per section +/- S.E.M. was 127.8 +/- 20.1, 76.8 +/- 16.7, 75.0 +/- 19.1, and 3.6 +/- 0.4 for animals treated with empty liposomes, LB-FK506, OD-FK506, and prednisolone acetate, respectively. The difference in inflammation between the empty liposome controls and the LB-FK506- and OD-FK506-treated animals was statistically significant (p = 0.03 and p = 0.02, respectively). The difference in inflammation between the high-dose OD-FK506- and low-dose LB-FK506-treated animals was not statistically significant (0 = 0.94). In this study, low-dose LB-FK506 and high-dose (OD-FK506) were both effective in inhibiting EIU. Higher concentrations of LB-FK506 are being developed and should augment the therapeutic effect of topical FK506. JF - Ocular immunology and inflammation AU - Whitcup, S M AU - Pleyer, U AU - Lai, J C AU - Lutz, S AU - Mochizuki, M AU - Chan, C C AD - National Eye Institute, National Institutes of Health, Bethesda, MD 20892-1863, USA. Y1 - 1998/03// PY - 1998 DA - March 1998 SP - 51 EP - 56 VL - 6 IS - 1 SN - 0927-3948, 0927-3948 KW - Drug Carriers KW - 0 KW - Endotoxins KW - Immunosuppressive Agents KW - Liposomes KW - Tacrolimus KW - WM0HAQ4WNM KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred Lew KW - Dose-Response Relationship, Drug KW - Female KW - Administration, Topical KW - Uveitis -- pathology KW - Tacrolimus -- therapeutic use KW - Tacrolimus -- administration & dosage KW - Immunosuppressive Agents -- therapeutic use KW - Uveitis -- drug therapy KW - Uveitis -- chemically induced KW - Immunosuppressive Agents -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70029206?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Ocular+immunology+and+inflammation&rft.atitle=Topical+liposome-encapsulated+FK506+for+the+treatment+of+endotoxin-induced+uveitis.&rft.au=Whitcup%2C+S+M%3BPleyer%2C+U%3BLai%2C+J+C%3BLutz%2C+S%3BMochizuki%2C+M%3BChan%2C+C+C&rft.aulast=Whitcup&rft.aufirst=S&rft.date=1998-03-01&rft.volume=6&rft.issue=1&rft.spage=51&rft.isbn=&rft.btitle=&rft.title=Ocular+immunology+and+inflammation&rft.issn=09273948&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-01-29 N1 - Date created - 1999-01-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Crystallization and preliminary X-ray analysis of tetanus neurotoxin C fragment. AN - 69953381; 9761892 AB - Two crystal forms of recombinant tetanus neurotoxin C fragment have been obtained. The C fragment corresponds to the C-terminal 451 amino-acid residues of tetanus neurotoxin and is the subunit responsible for receptor binding by the toxin. Both forms belong to space group P212121. Form I has unit-cell dimensions of a = 71.3, b = 79.7, c = 94.0 A and produces thin plate crystals. Form II has unit-cell dimensions of a = 67.4, b = 79.7, c = 91.1 A and produces thick rod-shaped crystals. Diffraction data to 2.6 A have been collected from form II crystals. JF - Acta crystallographica. Section D, Biological crystallography AU - Umland, T C AU - Wingert, L AU - Swaminathan, S AU - Schmidt, J J AU - Sax, M AD - Biocrystallography Laboratory, PO Box 12055, VA Medical Center, Pittsburgh, PA 15240, USA. umland@vger.niddk.nih.gov Y1 - 1998/03/01/ PY - 1998 DA - 1998 Mar 01 SP - 273 EP - 275 VL - 54 SN - 0907-4449, 0907-4449 KW - Peptide Fragments KW - 0 KW - Recombinant Proteins KW - Tetanus Toxin KW - tetanospasmin KW - 11032-48-7 KW - Metalloendopeptidases KW - EC 3.4.24.- KW - Index Medicus KW - Crystallization KW - Recombinant Proteins -- isolation & purification KW - Crystallography, X-Ray KW - Recombinant Proteins -- chemistry KW - Tetanus Toxin -- isolation & purification KW - Peptide Fragments -- chemistry KW - Peptide Fragments -- isolation & purification KW - Tetanus Toxin -- chemistry KW - Metalloendopeptidases -- isolation & purification KW - Metalloendopeptidases -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69953381?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Acta+crystallographica.+Section+D%2C+Biological+crystallography&rft.atitle=Crystallization+and+preliminary+X-ray+analysis+of+tetanus+neurotoxin+C+fragment.&rft.au=Umland%2C+T+C%3BWingert%2C+L%3BSwaminathan%2C+S%3BSchmidt%2C+J+J%3BSax%2C+M&rft.aulast=Umland&rft.aufirst=T&rft.date=1998-03-01&rft.volume=54&rft.issue=&rft.spage=273&rft.isbn=&rft.btitle=&rft.title=Acta+crystallographica.+Section+D%2C+Biological+crystallography&rft.issn=09074449&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-11-18 N1 - Date created - 1998-11-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - JC virus type 2B is found more frequently in brain tissue of progressive multifocal leukoencephalopathy patients than in urine from controls. AN - 69194123; 10195243 AB - Previous studies have shown that strains of human polyomavirus JC (JCV) of Asian origin (type 2) are much more highly represented in progressive multifocal leukoencephalopathy (PML) brain than would be expected from their frequency of excretion in urine samples of a comparable control group. The present studies were designed to test whether one subtype of type 2 was preferentially elevated. The statistical relation between JCV subtypes represented in PML brain tissue from 51 probands and those in urine samples from 115 control individuals was examined. The proportion of the JCV subtype 2B in PML brain (36%) was highly significantly increased relative to its occurrence in control urine samples (5.9%; P < .001). Type 1 and its subtypes were not different in the PML brain and control urine cohorts. The number of type 4 strains in PML brains was reduced, although the difference did not reach statistical significance (P = .08). The results predict that the human immunodeficiency virus (HIV)-positive individuals at highest risk of PML infection are those carrying the JCV genotype known as type 2B. Prospective studies will be required to confirm this finding. JF - Journal of human virology AU - Agostini, H T AU - Ryschkewitsch, C F AU - Singer, E J AU - Baumhefner, R W AU - Stoner, G L AD - Neurotoxicology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. PY - 1998 SP - 200 EP - 206 VL - 1 IS - 3 SN - 1090-9508, 1090-9508 KW - Index Medicus KW - AIDS/HIV KW - Genotype KW - California KW - HIV Seropositivity KW - Humans KW - Cohort Studies KW - Adult KW - Maryland KW - Pennsylvania KW - HIV Seronegativity KW - Male KW - Female KW - Leukoencephalopathy, Progressive Multifocal -- virology KW - JC Virus -- genetics KW - Urine -- virology KW - Brain -- virology KW - JC Virus -- isolation & purification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69194123?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+human+virology&rft.atitle=JC+virus+type+2B+is+found+more+frequently+in+brain+tissue+of+progressive+multifocal+leukoencephalopathy+patients+than+in+urine+from+controls.&rft.au=Agostini%2C+H+T%3BRyschkewitsch%2C+C+F%3BSinger%2C+E+J%3BBaumhefner%2C+R+W%3BStoner%2C+G+L&rft.aulast=Agostini&rft.aufirst=H&rft.date=1998-03-01&rft.volume=1&rft.issue=3&rft.spage=200&rft.isbn=&rft.btitle=&rft.title=Journal+of+human+virology&rft.issn=10909508&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-05-06 N1 - Date created - 1999-05-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Why Reading Is Not a Natural Process AN - 58369765; 9900668 AB - The National Institute of Child Health & Human Development's research program on reading development; the roles of phonemic awareness, automaticity, & understanding in developing reading skills; & current refutations to the assertion that reading is a natural process are examined. Although phonemic awareness is necessary for children's development of reading skills, it is contended that acquisition of automaticity in decoding & word recognition is essential for reading comprehension. The findings of contemporary studies that challenge traditional interpretations of instruction in phonemic awareness & reading strategies as unnecessary are reported. In addition to findings that indicate that underdeveloped phonemic & grammatical skills obstruct children's development of reading skills, research has also shown that deficient development of phonemic awareness negatively affects reading acquisition. It is concluded that teachers' confidence in contemporary research is integral to the improvement of reading skills instruction. 13 References. J. W. Parker JF - Educational Leadership AU - Lyon, G Reid AD - National Instit Child Health & Human Development National Instits Health US Dept Health & Human Services, Bldg 6100 Room 4B05 9000 Rockville Pike Bethesda MD 20892 lyonr@exchange.NIH.gov Y1 - 1998/03// PY - 1998 DA - March 1998 SP - 14 EP - 18 VL - 55 IS - 6 SN - 0013-1784, 0013-1784 KW - Phonological Awareness (64970) KW - Reading Instruction (70950) KW - Reading Acquisition (70650) KW - Decoding (Reading) (17600) KW - Word Recognition (98200) KW - article KW - 4116: applied linguistics; reading readiness/acquisition UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/58369765?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Allba&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Educational+Leadership&rft.atitle=Why+Reading+Is+Not+a+Natural+Process&rft.au=Lyon%2C+G+Reid&rft.aulast=Lyon&rft.aufirst=G&rft.date=1998-03-01&rft.volume=55&rft.issue=6&rft.spage=14&rft.isbn=&rft.btitle=&rft.title=Educational+Leadership&rft.issn=00131784&rft_id=info:doi/ LA - English DB - Linguistics and Language Behavior Abstracts (LLBA) N1 - Date revised - 2003-10-01 N1 - Last updated - 2016-09-27 N1 - CODEN - EDLEAW N1 - SubjectsTermNotLitGenreText - Reading Acquisition (70650); Decoding (Reading) (17600); Word Recognition (98200); Phonological Awareness (64970); Reading Instruction (70950) ER - TY - JOUR T1 - Emerging targets for the development of novel antifungal therapeutics AN - 17568495; 4323309 AB - Invasive mycoses have become important causes of morbidity and mortality in immunocompromised patients. New approaches for antifungal therapy are required to meet the challenges imposed by these life-threatening infections. Such approaches are being developed through identification of novel biochemical and molecular targets of pathogenic fungi. JF - Trends in Microbiology AU - Groll, AH AU - De Lucca, AJ AU - Walsh, T J AD - Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute, NIH, Bethesda, MD, USA, twalsh@pbmac.nci.nih.gov Y1 - 1998/03// PY - 1998 DA - Mar 1998 SP - 117 EP - 124 VL - 6 IS - 3 SN - 0966-842X, 0966-842X KW - drug targets KW - Microbiology Abstracts A: Industrial & Applied Microbiology KW - Antifungal agents KW - Reviews KW - A 01067:Antifungal & fungicidal UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17568495?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologya&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Trends+in+Microbiology&rft.atitle=Emerging+targets+for+the+development+of+novel+antifungal+therapeutics&rft.au=Groll%2C+AH%3BDe+Lucca%2C+AJ%3BWalsh%2C+T+J&rft.aulast=Groll&rft.aufirst=AH&rft.date=1998-03-01&rft.volume=6&rft.issue=3&rft.spage=117&rft.isbn=&rft.btitle=&rft.title=Trends+in+Microbiology&rft.issn=0966842X&rft_id=info:doi/10.1016%2FS0966-842X%2897%2901206-7 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Antifungal agents; Reviews DO - http://dx.doi.org/10.1016/S0966-842X(97)01206-7 ER - TY - JOUR T1 - Occupational infection with hepatitis B virus--waging war against an insidious, intractable, intolerable foe AN - 16528160; 4367595 AB - The potential for occupational transmission of bloodborne hepatitis was first identified in the 1940s. The discovery of hepatitis B surface antigen (HBsAg) led to the development of sensitive, specific serological tests for hepatitis B virus infection and immunity and ultimately permitted the characterization of hepatitis B as an important cause of bloodborne hepatitis. Elucidation of the seroepidemiology of hepatitis B virus infection also facilitated quantitation of the magnitude of occupational risk for health care workers contributed by this bloodborne pathogen, and it clearly associated the occupational risk with exposure to blood. JF - Clinical Infectious Diseases AU - Hendersn, D K AD - Warren G. Magnuson Clinical Center, Building 10, Room 2C146, National Institutes of Health, Bethesda, MD 20892, USA Y1 - 1998/03// PY - 1998 DA - Mar 1998 SP - 572 EP - 574 VL - 26 IS - 3 SN - 1058-4838, 1058-4838 KW - disease transmission KW - hepatitis B KW - man KW - Health & Safety Science Abstracts; Virology & AIDS Abstracts KW - H 1000:Occupational Safety and Health KW - V 22122:Symptomatology, pathology & etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16528160?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthsafetyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+Infectious+Diseases&rft.atitle=Occupational+infection+with+hepatitis+B+virus--waging+war+against+an+insidious%2C+intractable%2C+intolerable+foe&rft.au=Hendersn%2C+D+K&rft.aulast=Hendersn&rft.aufirst=D&rft.date=1998-03-01&rft.volume=26&rft.issue=3&rft.spage=572&rft.isbn=&rft.btitle=&rft.title=Clinical+Infectious+Diseases&rft.issn=10584838&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Immunochemical detection and identification of protein adducts of diclofenac in the small intestine of rats: Possible role in allergic reactions AN - 16512875; 4413785 AB - Idiosyncratic adverse drug reactions are unpredictable, target multiple organ systems, and often become life-threatening events. Although the causes of idiosyncratic adverse drug reactions are not known in most cases, evidence suggests that they may be mediated through immunological mechanisms. It is generally thought that for a drug to lead to an immune response, it must first become covalently bound to a carrier protein. Since most drugs are unreactive, it is usually a reactive metabolite that is expected to form covalent adducts. However, it is not clear why more people do not develop immune reactions against drug-protein adducts. One possible explanation is that orally administered drugs may lead to oral tolerance in most individuals through mechanisms similar to that found with orally administered antigens. However, very little is known regarding the interaction of drugs with gut-associated lymphoid tissue of the small intestine, where oral tolerance can develop. As an initial step to test this hypothesis, we have investigated whether diclofenac, a commonly used nonsteroidal antiinflammatory drug, can lead to protein adducts in rat small intestine. Diclofenac was administered to rats by gastric gavage. Immunoblot analysis of small intestine homogenates and isolated enterocyte subcellular fractions with drug-specific antiserum revealed 142-, 130-, 110-, and 55-kDa protein adducts of diclofenac. The 142- and 130-kDa adducts of diclofenac were identified as aminopeptidase N (CD13) and sucrase-isomaltase, respectively, by amino acid sequence analyses and by their reactions with protein-specific antibodies. The adducts were localized by immunohistochemistry and found primarily in the mid-villus and villus-tip enterocytes and also in the dome overlying Peyer's patches. Similar adducts were detected immunochemically in villus-tip enterocytes of animals treated with halothane or acetaminophen. These results show that intestinal protein adducts of drugs can be formed in gut-associated lymphoid tissue where they may lead to the down-regulation of drug-induced allergic reactions in many individuals. JF - Chemical Research in Toxicology AU - Ware, JA AU - Graf, MLM AU - Martin, B M AU - Lustberg, L R AU - Pohl, L R AD - Molecular and Cellular Toxicology Section, NHLBI, NIH, Bldg 10, Rm 8N110, Bethesda, MD 20892-1760, USA Y1 - 1998/03// PY - 1998 DA - Mar 1998 SP - 164 EP - 171 VL - 11 IS - 3 SN - 0893-228X, 0893-228X KW - diclofenac KW - hypersensitivity KW - immunochemistry KW - rats KW - side effects KW - small intestine KW - Toxicology Abstracts KW - X 24117:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16512875?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemical+Research+in+Toxicology&rft.atitle=Immunochemical+detection+and+identification+of+protein+adducts+of+diclofenac+in+the+small+intestine+of+rats%3A+Possible+role+in+allergic+reactions&rft.au=Ware%2C+JA%3BGraf%2C+MLM%3BMartin%2C+B+M%3BLustberg%2C+L+R%3BPohl%2C+L+R&rft.aulast=Ware&rft.aufirst=JA&rft.date=1998-03-01&rft.volume=11&rft.issue=3&rft.spage=164&rft.isbn=&rft.btitle=&rft.title=Chemical+Research+in+Toxicology&rft.issn=0893228X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Mechanisms involved in the intrinsic isoniazid resistance of Mycobacterium avium AN - 16512098; 4298668 AB - Isoniazid (INH), which acts by inhibiting mycolic acid biosynthesis, is very potent against the tuberculous mycobacteria. It is about 100-fold less effective against Mycobacterium avium. This difference has often been attributed to a decreased permeability of the cell wall. We measured the rate of conversion of radiolabelled INH to 4-pyridylmethanol by whole cells and cell-free extracts and estimated the permeability barrier imposed by the cell wall to INH influx in Mycobacterium tuberculosis and M. avium. There was no significant difference in the relative permeability to INH between these two species. However, the total conversion rate in M. tuberculosis was found to be four times greater. Examination of in vitro-generated mutants revealed that the major resistance mechanism for both species is loss of the catalase-peroxidase KatG. Analysis of lipid and protein biosynthetic profiles demonstrated that the molecular target of activated INH was identical for both species. M. avium, however, formed colonies at INH concentrations inhibitory for mycolic acid biosynthesis. These mycolate-deficient M. avium exhibited altered colony morphologies, modified cell wall ultrastructure and were 10-fold more sensitive to treatment with hydrophobic antibiotics, such as rifampin. These findings may significantly impact the design of new therapeutic regimens for the treatment of infections with atypical mycobacteria. JF - Molecular Microbiology AU - Mdluli, K AU - Swanson, J AU - Fischer, E AU - Lee, R E AU - Barry, CE III AD - Tuberculosis Research Unit, National Institutes of Health, National Institutes for Allergy and Infectious Diseases, 903 S. Fourth St., Hamilton, MT 59840, USA, e.clifton_barry@nih.gov Y1 - 1998/03// PY - 1998 DA - Mar 1998 SP - 1223 EP - 1233 VL - 27 IS - 6 SN - 0950-382X, 0950-382X KW - isoniazid KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Microbiology Abstracts B: Bacteriology KW - A 01064:Microbial resistance KW - J 02814:Drug resistance UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16512098?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+Microbiology&rft.atitle=Mechanisms+involved+in+the+intrinsic+isoniazid+resistance+of+Mycobacterium+avium&rft.au=Mdluli%2C+K%3BSwanson%2C+J%3BFischer%2C+E%3BLee%2C+R+E%3BBarry%2C+CE+III&rft.aulast=Mdluli&rft.aufirst=K&rft.date=1998-03-01&rft.volume=27&rft.issue=6&rft.spage=1223&rft.isbn=&rft.btitle=&rft.title=Molecular+Microbiology&rft.issn=0950382X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Mortality and cancer incidence of aircraft maintenance workers exposed to trichloroethylene and other organic solvents and chemicals: extended follow up AN - 16498193; 4397058 AB - To extend the follow up of a cohort of 14 457 aircraft maintenance workers to the end of 1990 to evaluate cancer risks from potential exposure to trichloroethylene and other chemicals. The cohort comprised civilians employed for at least one year between 1952 and 1956, of whom 5727 had died by 31 December 1990. Analyses compared the mortality of the cohort with the general population of Utah and the mortality and cancer incidence of exposed workers with those unexposed to chemicals, while adjusting for age, sex, and calendar time. These findings do not strongly support a causal link with trichloroethylene because the associations were not significant, not clearly dose-related, and inconsistent between men and women. Because findings from experimental investigations and other epidemiological studies on solvents other than trichloroethylene provide some biological plausibility, the suggested links between these chemicals and non-Hodgkin's lymphoma, multiple myeloma, and breast cancer found here deserve further attention. Although this extended follow up cannot rule out a connection between exposures to solvents and some diseases, it seems clear that these workers have not experienced a major increase in cancer mortality or cancer incidence. JF - Occupational and Environmental Medicine AU - Blair, A AU - Hartge, P AU - Stewart, P A AU - McAdams, M AU - Lubin, J AD - Occupational Epidemiology Unit, National Cancer Institute, Executive Plaza North, Room 418, Bethesda, MD 20892-7364, USA Y1 - 1998/03// PY - 1998 DA - Mar 1998 SP - 161 EP - 171 VL - 55 IS - 3 SN - 1351-0711, 1351-0711 KW - aircraft industry KW - trichloroethylene KW - Health & Safety Science Abstracts KW - H 1000:Occupational Safety and Health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16498193?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthsafetyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Occupational+and+Environmental+Medicine&rft.atitle=Mortality+and+cancer+incidence+of+aircraft+maintenance+workers+exposed+to+trichloroethylene+and+other+organic+solvents+and+chemicals%3A+extended+follow+up&rft.au=Blair%2C+A%3BHartge%2C+P%3BStewart%2C+P+A%3BMcAdams%2C+M%3BLubin%2C+J&rft.aulast=Blair&rft.aufirst=A&rft.date=1998-03-01&rft.volume=55&rft.issue=3&rft.spage=161&rft.isbn=&rft.btitle=&rft.title=Occupational+and+Environmental+Medicine&rft.issn=13510711&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Serum hormone levels in relation to reproductive and lifestyle factors in postmenopausal women (United States) AN - 16488263; 4374946 AB - Objectives: Endogenous sex hormones are thought to be involved in breast and endometrial cancers, but few studies have evaluated the relationships between hormones and risk factors for these diseases. Methods: We related serum hormone and sex-hormone binding globulin (SHBG) levels to reproductive and lifestyle risk factors in a cross-sectional study of 125 postmenopausal women in five geographic regions of the United States. Results: The estrogens were associated positively, while SHBG was associated negatively with body mass index (wt/ht super(2)). Estrone, (E1), estrone sulfate, and bioavailable estradiol (BioE2) were inversely associated with height. Androstenedione was positively associated with age at menopause, while androstenedione, E1, estradiol, and BioE2 were inversely associated with age at menarche. Weekly alcohol drinkers had higher hormone levels, and lower SHBG levels than those who abstained. Androstenedione and E1 decreased with increasing levels of nonrecreational activity. Conclusions: Several of these findings support the hypothesis that breast and endometrial cancer risk factors are mediated, in part, through increased endogenous hormone levels. The androstenedione findings are of interest in light of studies relating androstenedione to endometrial and possibly breast cancer. An association of age at menarche with E2, independent of androstenedione, may reflect increased aromatase activity in women with earlier menarche. JF - Cancer Causes & Control AU - Madigan, M P AU - Troisi, R AU - Potischman, N AU - Dorgan, J F AU - Brinton, LA AU - Hoover, R N AD - US National Cancer Institute, Division of Cancer Epidemiology & Genetics, Environmental Epidemiology Branch, EPN 443, Bethesda, MD 20892, USA Y1 - 1998/03// PY - 1998 DA - Mar 1998 SP - 199 EP - 207 VL - 9 IS - 2 SN - 0957-5243, 0957-5243 KW - endometrium KW - estrogens KW - hormones KW - physical activity KW - post-menopause KW - Risk Abstracts KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16488263?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Causes+%26+Control&rft.atitle=Serum+hormone+levels+in+relation+to+reproductive+and+lifestyle+factors+in+postmenopausal+women+%28United+States%29&rft.au=Madigan%2C+M+P%3BTroisi%2C+R%3BPotischman%2C+N%3BDorgan%2C+J+F%3BBrinton%2C+LA%3BHoover%2C+R+N&rft.aulast=Madigan&rft.aufirst=M&rft.date=1998-03-01&rft.volume=9&rft.issue=2&rft.spage=199&rft.isbn=&rft.btitle=&rft.title=Cancer+Causes+%26+Control&rft.issn=09575243&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Neisseria meningitidis producing the Opc adhesin binds epithelial cell proteoglycan receptors AN - 16482038; 4298666 AB - Neisseria meningitidis possesses a repertoire of surface adhesins that promote bacterial adherence to and entry into mammalian cells. Here, we have identified heparan sulphate proteoglycans as epithelial cell receptors for the meningococcal Opc invasin. Binding studies with radiolabelled heparin and heparin affinity chromatography demonstrated that Opc is a heparin binding protein. Subsequent binding experiments with purified super(35)SO sub(4)-labelled epithelial cell proteoglycan receptors and infection assays with epithelial cells that had been treated with heparitinase to remove glycosaminoglycans confirmed that Opc-expressing meningococci exploit host cell-surface proteoglycans to gain access to the epithelial cell interior. Unexpectedly, Opa28-producing meningococci lacking Opc also bound proteoglycans. These bacteria also bound CEA receptors in contrast to the Opc-expressing phenotype, suggesting that Opa28 may possess domains with specificity for different receptors. Opa/Opc-negative meningococci did not bind either proteoglycan or CEA receptors. Using a set of genetically defined mutants with different lipopolysaccharide (LPS) and capsular phenotype, we were able to demonstrate that surface sialic acids interfere with the Opc-proteoglycan receptor interaction. This effect may provide the molecular basis for the reported modulatory effect of capsule and LPS on meningococcal adherence to and entry into various cell types. JF - Molecular Microbiology AU - De Vries, FP AU - Cole, R AU - Dankert, J AU - Frosch, M AU - Van Putten, JPM AD - Rocky Mountain Laboratories, National Institutes for Allergy and Infectious Diseases, National Institutes of Health, 903 South 4th Street, Hamilton, MT 59840, USA, jos_van_putten@nih.gov Y1 - 1998/03// PY - 1998 DA - Mar 1998 SP - 1203 EP - 1212 VL - 27 IS - 6 SN - 0950-382X, 0950-382X KW - Opc protein KW - adhesins KW - proteoglycans KW - Microbiology Abstracts B: Bacteriology KW - J 02848:Nervous system UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16482038?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+Microbiology&rft.atitle=Neisseria+meningitidis+producing+the+Opc+adhesin+binds+epithelial+cell+proteoglycan+receptors&rft.au=De+Vries%2C+FP%3BCole%2C+R%3BDankert%2C+J%3BFrosch%2C+M%3BVan+Putten%2C+JPM&rft.aulast=De+Vries&rft.aufirst=FP&rft.date=1998-03-01&rft.volume=27&rft.issue=6&rft.spage=1203&rft.isbn=&rft.btitle=&rft.title=Molecular+Microbiology&rft.issn=0950382X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Inhibition of acute-, latent-, and chronic-phase human immunodeficiency virus type 1 (HIV-1) replication by a bistriazoloacridone analog that selectively inhibits HIV-1 transcription AN - 16439109; 4343517 AB - Nanomolar concentrations of temacrazine (1,4-bis[3-(6-oxo-6H-v-triazolo[4,5,1-de]acridin-5-yl)amino-propyl ] piperazine) were discovered to inhibit acute human immunodeficiency virus type 1 (HIV-1) infections and suppress the production of virus from chronically and latently infected cells containing integrated proviral DNA. This bistriazoloacridone derivative exerted its mechanism of antiviral action through selective inhibition of HIV-1 transcription during the postintegrative phase of virus replication. Mechanistic studies revealed that temacrazine blocked HIV-1 RNA formation without interference with the transcription of cellular genes or with events associated with the HIV-1 Tat and Rev regulatory proteins. Although temacrazine inhibited the in vitro 3' processing and strand transfer activities of HIV-1 integrase, with a 50% inhibitory concentration of approximately 50 nM, no evidence of an inhibitory effect on the intracellular integration of proviral DNA into the cellular genome during the early phase of infection could be detected. Furthermore, temacrazine did not interfere with virus attachment or fusion to host cells or the enzymatic activities of HIV-1 reverse transcriptase or protease, and the compound was not directly virucidal. Demonstration of in vivo anti-HIV-1 activity by temacrazine identifies bistriazoloacridones as a new class of pharmaceuticals that selectively blocks HIV-1 transcription. JF - Antimicrobial Agents & Chemotherapy AU - Turpin, JA AU - Buckheit, RW Jr AU - Derse, D AU - Hollingshead, M AU - Williamson, K AU - Palamone, C AU - Osterling, M C AU - Hill, SA AU - Graham, L AU - Schaeffer, CA AU - Bu, M AU - Huang, M AU - Cholody, WM AU - Michejda, C J AU - Rice, W G AD - Laboratory of Antiviral Drug Mechanisms, Developmental Therapeutics Program, National Cancer Institute-Frederick Cancer Research and Development Center, SAIC Frederick, Building 431T-B, P.O. Box B, Frederick, MD 21702-1201, USA Y1 - 1998/03// PY - 1998 DA - Mar 1998 SP - 487 EP - 494 VL - 42 IS - 3 SN - 0066-4804, 0066-4804 KW - HIV-1 KW - RNA KW - acquired immune deficiency syndrome KW - antiviral agents KW - human immunodeficiency virus 1 KW - temacrazine KW - transcription KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Virology & AIDS Abstracts KW - V 22002:AIDS: Molecular and in vitro aspects KW - W3 33372:Antiviral agents KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16439109?accountid=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=Antimicrobial+Agents+%26+Chemotherapy&rft.atitle=Inhibition+of+acute-%2C+latent-%2C+and+chronic-phase+human+immunodeficiency+virus+type+1+%28HIV-1%29+replication+by+a+bistriazoloacridone+analog+that+selectively+inhibits+HIV-1+transcription&rft.au=Turpin%2C+JA%3BBuckheit%2C+RW+Jr%3BDerse%2C+D%3BHollingshead%2C+M%3BWilliamson%2C+K%3BPalamone%2C+C%3BOsterling%2C+M+C%3BHill%2C+SA%3BGraham%2C+L%3BSchaeffer%2C+CA%3BBu%2C+M%3BHuang%2C+M%3BCholody%2C+WM%3BMichejda%2C+C+J%3BRice%2C+W+G&rft.aulast=Turpin&rft.aufirst=JA&rft.date=1998-03-01&rft.volume=42&rft.issue=3&rft.spage=487&rft.isbn=&rft.btitle=&rft.title=Antimicrobial+Agents+%26+Chemotherapy&rft.issn=00664804&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Comparison of mutagenesis by O super(6)-methyl- and O super(6)-ethylguanine and O super(4)-methylthymine in Escherichia coli using double-stranded and gapped plasmids AN - 16417091; 4326031 AB - To compare mutagenesis by O super(6)-methylguanine (m super(6)G), O super(4)-methylthymine (m super(4)T) and O super(6)-ethylguanine (e super(6)G), and assess their genotoxicity in Escherichia coli, double-stranded and gapped plasmids were constructed containing a single m super(6)G, e super(6)G or m super(4)T in the initiation codon (ATG) of a lacZ' gene. Modified base induced mutations were scored by the loss of lacZ' activity on X-gal-containing media resulting in formation of white or sectored (mutant) rather than blue (non-mutant) colonies. Genotoxicity experiments with gapped plasmids containing the modified bases indicated that m super(4)T produced a greater number of bacterial colonies than m super(6)G or e super(6)G. m super(4)T was more mutagenic (45% mutant colonies) than m super(6)G (6%) or e super(6)G (11%) in repair competent (w.t.) E. coli when incorporated in double-stranded plasmids. In gapped plasmids, m super(4)T produced 99% mutant colonies (as was observed previously for e super(6)G) in both w.t. E. coli or E. coli deficient in both O super(6)-alkylguanine-DNA alkyltransferases as well as methylation-directed mismatch repair (ada super(-)-ogt super(-)-mutS super(-)). m super(6)G in gapped plasmids produced 62% mutant colonies in w.t. E. coli, but this percentage increased to 94% in the ada super(-)-ogt super(-)-mutS super(-) strain. In double-stranded plasmids both m super(4)T and m super(6)G produced very similar distributions of mutant and non-mutant colonies in the ada super(-)-ogt super(-)-mutS super(-) strain. These observations led to the conclusion that differences in the mutagenicity of m super(6)G and m super(4)T in w.t. E. coli were a result of preferential repair of m super(6)G compared to m super(4)T by alkyltransferase and mismatch repair mechanisms, and did not reflect differences in their respective coding efficiency or their inherent obstructiveness to DNA synthesis as was observed with e super(6)G. The combination of alkyltransferase and mismatch repair was concluded to be primarily responsible for the apparent genotoxicity of m super(6)G compared to m super(4)T in double-stranded plasmids. JF - Carcinogenesis AU - Pauly, G T AU - Hughes, SH AU - Moschel, R C AD - Chemistry of Carcinogenesis Laboratory, ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, PO Box B, Frederick, MD 21702, USA, moschel@ncifcrf.gov Y1 - 1998/03// PY - 1998 DA - Mar 1998 SP - 457 EP - 461 VL - 19 IS - 3 SN - 0143-3334, 0143-3334 KW - ethylguanine KW - methylguanine KW - methylthymine KW - Toxicology Abstracts KW - X 24221:Toxicity testing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16417091?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Comparison+of+mutagenesis+by+O+super%286%29-methyl-+and+O+super%286%29-ethylguanine+and+O+super%284%29-methylthymine+in+Escherichia+coli+using+double-stranded+and+gapped+plasmids&rft.au=Pauly%2C+G+T%3BHughes%2C+SH%3BMoschel%2C+R+C&rft.aulast=Pauly&rft.aufirst=G&rft.date=1998-03-01&rft.volume=19&rft.issue=3&rft.spage=457&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Pharmacodynamic responses of F344 rats to the mouse hepatocarcinogen oxazepam in a 90-day feed study AN - 16415571; 4325811 AB - Oxazepam (Serax) is a widely used benzodiazepine anxiolytic agent and a metabolite of other benzodiazepines such as Valium and Librium. Chronic feeding studies indicated that oxazepam is an hepatocarcinogen in B6C3F1 mice but did not increase hepatic tumors in F344 rats. The present study was performed to compare the hepatic responses of rats with our previous findings in mice to explore the reason(s) for the dramatic differences in tumor response between the two species. Male F344 rats (10 per dose-time group) received diets containing oxazepam at 0, 25, 125, 2500, and 5000 ppm. Hepatocyte labeling indices were measured immunohistochemically by PCNA and BrDU during the last 7 days before sacrifices after 15, 30, 45, and 90 days of dosing. Serum oxazepam was determined by reverse phase HPLC. Results indicated that oxazepam induced significant liver weight increases in a dose-related fashion by 15 days, which remained elevated for the entire study. No important clinical chemistry or pathology changes were noted except those related to hypertrophy. Cell proliferation was significantly increased in a dose-related manner by the 15- and 30-day timepoint in the 2500 and 5000 ppm groups. The most significant finding in the present study of oxazepam was plasma levels of the parent compound. Plasma levels in rats were dramatically lower than in B6C3F1 mice exposed to oxazepam in studies conducted earlier at the same dose levels. These results suggest that the early responses of rats and mice to oxazepam, such as cell proliferation and clinical chemistry parameters, are similar. Our previous studies demonstrated that oxazepam metabolites are excreted in the urine of rats, similar to humans, whereas mice excrete oxazepam metabolites in bile allowing enterohepatic recirculation, which results in high plasma levels of oxazepam. These data indicate that the rat excretes oxazepam kinetically (rate and route) similar to humans, but the mouse produces metabolites similar to humans. JF - Toxicology and Applied Pharmacology AU - Cunningham, M L AU - Bucher, J R AD - National Institute of Environmental Health Sciences, Mail Drop B3-10, P.O. Box 12233, Research Triangle Park, NC 27709, USA, cunning1@niehs.nih.gov Y1 - 1998/03// PY - 1998 DA - Mar 1998 SP - 41 EP - 48 VL - 149 IS - 1 SN - 0041-008X, 0041-008X KW - benzodiazepines KW - oxazepam KW - pharmacokinetics KW - rats KW - Toxicology Abstracts KW - X 24114:Metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16415571?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+and+Applied+Pharmacology&rft.atitle=Pharmacodynamic+responses+of+F344+rats+to+the+mouse+hepatocarcinogen+oxazepam+in+a+90-day+feed+study&rft.au=Cunningham%2C+M+L%3BBucher%2C+J+R&rft.aulast=Cunningham&rft.aufirst=M&rft.date=1998-03-01&rft.volume=149&rft.issue=1&rft.spage=41&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 revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Induction of melanoma antigen-specific cytotoxic T lymphocytes in vitro by stimulation with B7-expressing human melanoma cell lines AN - 16414217; 4315583 AB - Crosslinking of CD28 receptors on resting T lymphocytes by B7 costimulatory molecules expressed by antigen-presenting cells (APCs) plays a critical role in T-cell activation. Human melanomas express major histocompatibility complex (MHC)-restricted tumor-associated antigens that can be recognized by cytotoxic T lymphocytes (CTL), yet they remain poorly immunogenic. One mechanism for the failure of T-cell response is the lack of expression of costimulatory molecules by human melanoma cells. We have transfected the B7-1 gene into three HLA-A2-expressing human melanoma cell lines, and studied their capacity to stimulate primary human T cells. B7-expressing melanoma cells were excellent inducers of T-cell proliferation, cytokine production, and cytolytic activity in allogeneic mixed lymphocyte cultures through a process dependent on the function of the T-cell receptor as well as interactions between B7:CD28, CD2:LFA-3, and LFA-1:ICAM-1. Subset analysis demonstrated that CD4 super(+) T cells or addition of exogenous interleukin-2 was required for the induction of CD8 super(+) CTL. Untransfected parental melanoma cells were inert as APCs in these cultures. Rotating stimulation of T cells with the three B7-expressing cell lines led to the generation of T-cell lines that were cytolytic for HLA-A2 super(+) melanoma cells and other HLA-A2 super(+) targets that were pulsed with HLA-A2-restricted MART-1 peptides. These data demonstrate that expression of B7-1 by human melanoma cells converts them into effective APCs for the in vitro induction of MHC-restricted, melanoma-specific CTL. JF - Journal of Immunotherapy with Emphasis on Tumor Biology AU - Fenton, R G AU - Turcovski-Corrales, S M AU - Taub, D D AD - National Cancer Institute-FCRDC, P.O. Box B, Building 567, Room 207 Frederick, MD 21702, USA Y1 - 1998/03// PY - 1998 DA - Mar 1998 SP - 95 EP - 108 VL - 21 IS - 2 SN - 1053-8550, 1053-8550 KW - A2 determinant KW - double prime B7 antigen KW - histocompatibility antigen HLA KW - man KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - F 06816:Antitumor immune response KW - W3 33350:Cancer vaccines KW - F 06756:Function KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16414217?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Immunotherapy+with+Emphasis+on+Tumor+Biology&rft.atitle=Induction+of+melanoma+antigen-specific+cytotoxic+T+lymphocytes+in+vitro+by+stimulation+with+B7-expressing+human+melanoma+cell+lines&rft.au=Fenton%2C+R+G%3BTurcovski-Corrales%2C+S+M%3BTaub%2C+D+D&rft.aulast=Fenton&rft.aufirst=R&rft.date=1998-03-01&rft.volume=21&rft.issue=2&rft.spage=95&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immunotherapy+with+Emphasis+on+Tumor+Biology&rft.issn=10538550&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - RapA, a novel RNA polymerase-associated protein, is a bacterial homolog of SWI2/SNF2 AN - 16289150; 4295161 AB - We have identified a novel Escherichia coli RNA polymerase (RNAP)-associated protein, an ATPase named RapA. Almost all of this 110-kDa protein in the cell copurifies with RNAP holoenzyme as a 1:1 complex. Purified to homogeneity, RapA also forms a stable complex with RNAP, as if it were a subunit of RNAP. The ATPase activity of RapA is stimulated by binding to RNAP, and thus, RapA and RNAP interact physically as well as functionally. Interestingly, RapA is a homolog of the SWI/SNF family of eukaryotic proteins whose members are involved in transcription activation, nucleosome remodeling, and DNA repair. JF - Journal of Biological Chemistry AU - Sukhodolets, M V AU - Jin, Ding Jun AD - LMB, NCI, Natl. Institutes Health, Bldg. 37, Rm. 2E14, 9000 Rockville Pike, Bethesda, MD 20892, USA Y1 - 1998/03// PY - 1998 DA - Mar 1998 SP - 7018 EP - 7023 VL - 273 IS - 12 SN - 0021-9258, 0021-9258 KW - DNA-directed RNA polymerase-associated protein KW - RapA protein KW - SWI2/SNF2 protein KW - adenosinetriphosphatase KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - N 14721:RNA polymerases KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16289150?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Biological+Chemistry&rft.atitle=RapA%2C+a+novel+RNA+polymerase-associated+protein%2C+is+a+bacterial+homolog+of+SWI2%2FSNF2&rft.au=Sukhodolets%2C+M+V%3BJin%2C+Ding+Jun&rft.aulast=Sukhodolets&rft.aufirst=M&rft.date=1998-03-01&rft.volume=273&rft.issue=12&rft.spage=7018&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Control of ftsZ expression, cell division, and glutamine metabolism in Luria-Bertani medium by the alarmone ppGpp in Escherichia coli AN - 16282992; 4282245 AB - Inactivation of transcription factor sigma super(54), encoded by rpoN (glnF), restores high-temperature growth in Luria-Bertani (LB) medium to strains containing the heat-sensitive cell division mutation ftsZ84. Mutational defects in three other genes involved in general nitrogen control (glnD, glnG, and glnL) also suppress lethal filamentation. Since addition of glutamine to LB medium fully blocks suppression by each mutation, the underlying cause of suppression likely derives from a stringent response to the limitation of glutamine. This model is supported by several observations. The glnL mutation requires RelA-directed synthesis of the nutrient alarmone ppGpp to suppress filamentation. Artificially elevated levels of ppGpp suppress ftsZ84, as do RNA polymerase mutations that reproduce global effects of the ppGpp-induced state. Both the glnF null mutation and an elevated copy number of the relA gene similarly affect transcription from the upstream (pQ) promoters of the ftsQAZ operon, and both of these genetic conditions increase the steady-state level of the FtsZ84 protein. Physiological suppression of ftsZ84 by a high salt concentration was also shown to involve RelA. Additionally, we found that the growth of a glnF or glnD strain on LB medium depends on RelA or supplemental glutamine in the absence of RelA function. These data expand the roles for ppGpp in the regulation of glutamine metabolism and the expression of FtsZ during cell division. JF - Journal of Bacteriology AU - Powell, B S AU - Court, D L AD - Mol. Control and Genet., ABL-Basic Res. Prog., NCI-Frederick Cancer Res. and Dev. Cent., Frederick, MD 21702, USA Y1 - 1998/03// PY - 1998 DA - Mar 1998 SP - 1053 EP - 1062 VL - 180 IS - 5 SN - 0021-9193, 0021-9193 KW - FtsZ protein KW - cell division KW - ftsZ gene KW - gene expression KW - gln gene KW - glutamine KW - Microbiology Abstracts B: Bacteriology KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16282992?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Bacteriology&rft.atitle=Control+of+ftsZ+expression%2C+cell+division%2C+and+glutamine+metabolism+in+Luria-Bertani+medium+by+the+alarmone+ppGpp+in+Escherichia+coli&rft.au=Powell%2C+B+S%3BCourt%2C+D+L&rft.aulast=Powell&rft.aufirst=B&rft.date=1998-03-01&rft.volume=180&rft.issue=5&rft.spage=1053&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=00219193&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Cellular resistance and hypermutability in mismatch repair-deficient human cancer cell lines following treatment with methyl methanesulfonate. AN - 79934579; 9626980 AB - Resistance to the cytotoxic effects of S(N)1 alkylating agents such as N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and N-methyl-N-nitrosourea (MNU) is well established in mismatch repair-defective cells, however, little is known about the cellular response to S(N)2 alkylating agents in these cells. Here we describe the cytotoxic response and the mutagenic response at the hypoxanthine-guanine phosphoribosyl transferase (HPRT) locus to the S(N)2 alkylating agent methyl methanesultfonate (MMS) in human cancer cell lines defective in mismatch repair (MMR). Our findings suggest that cytotoxicity to MMS is mediated through MMR, as indicated by an increased resistance to MMS in MMR-deficient cells. Cells in which specific MMR-gene defects were complemented by chromosome transfer were generally more sensitive to the cytotoxic effects of MMS. Additionally, the induced mutant frequency at HPRT following exposure to MMS is significantly increased in MMR-deficient lines. These findings suggest that resistance to S(N)2 alkylation damage is mediated by MMR genes, and that resistance to such damage in MMR-defective cells correlates with an increase in genomic mutations. The results are consistent with the hypothesis that abasic sites may be substrates for repair involving MMR-gene products in human cells. JF - Mutation research AU - Glaab, W E AU - Risinger, J I AU - Umar, A AU - Barrett, J C AU - Kunkel, T A AU - Tindall, K R AD - Laboratory of Environmental Carcinogenesis and Mutagenesis, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1998/02/26/ PY - 1998 DA - 1998 Feb 26 SP - 197 EP - 207 VL - 398 IS - 1-2 SN - 0027-5107, 0027-5107 KW - Mutagens KW - 0 KW - Nucleic Acid Heteroduplexes KW - Methyl Methanesulfonate KW - AT5C31J09G KW - Index Medicus KW - Tumor Cells, Cultured KW - Humans KW - Mutation KW - Cell Line KW - Methyl Methanesulfonate -- toxicity KW - DNA Repair KW - Mutagens -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79934579?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cellular+resistance+and+hypermutability+in+mismatch+repair-deficient+human+cancer+cell+lines+following+treatment+with+methyl+methanesulfonate.&rft.au=Glaab%2C+W+E%3BRisinger%2C+J+I%3BUmar%2C+A%3BBarrett%2C+J+C%3BKunkel%2C+T+A%3BTindall%2C+K+R&rft.aulast=Glaab&rft.aufirst=W&rft.date=1998-02-26&rft.volume=398&rft.issue=1-2&rft.spage=197&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 - 1998-06-24 N1 - Date created - 1998-06-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Further studies on anti- and proconvulsant effects of inhibitors of nitric oxide synthase in rodents. AN - 79829893; 9570442 AB - We confirmed that the effects of inhibitors of nitric oxide (NO) synthase, such as Nomega-nitro-L-arginine methyl ester and Nomega-nitro-L-arginine, differ depending on several experimental factors. Both compounds but not their less active enantiomers delayed picrotoxin-induced clonus in mice yet increased the incidence of clonus following low-dose picrotoxin. Nomega-nitro-L-arginine methyl ester significantly reduced the latencies of both myoclonus and clonus in older but not younger Sprague-Dawley rats receiving pentylenetetrazol s.c. By contrast, there was no significant change in the latencies for myoclonus and clonus in Wistar rats (older and younger). However, when pentylenetetrazol was administered i.p. rather than s.c., Nomega-nitro-L-arginine methyl ester dramatically increased latencies of convulsive indicators, including tonus, in both Sprague-Dawley and Wistar rats. Nomega-nitro-L-arginine methyl ester also delayed tonus but not myoclonus or clonus in mice, regardless of the systemic route of administration of pentylenetetrazol. Both Nomega-nitro-L-arginine methyl ester and NG-nitro-L-arginine increased the tonic CD50 of pentylenetetrazol in mice and Nomega-nitro-L-arginine methyl ester delayed 4-aminopyridine-induced tonus. However, Nomega-nitro-L-arginine methyl ester reduced the tonic CD50 of both picrotoxin and 4-aminopyridine in mice and failed to suppress tonus following maximal electroshock. Evidently, inhibitors of NO synthase are not universally effective antitonic drugs. JF - European journal of pharmacology AU - Alexander, C B AU - Ellmore, T M AU - Kokate, T G AU - Kirkby, R D AD - Neuronal Excitability Section, Epilepsy Research Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-1408, USA. Y1 - 1998/02/26/ PY - 1998 DA - 1998 Feb 26 SP - 15 EP - 25 VL - 344 IS - 1 SN - 0014-2999, 0014-2999 KW - Anticonvulsants KW - 0 KW - Convulsants KW - Enzyme Inhibitors KW - Picrotoxin KW - 124-87-8 KW - Nitroarginine KW - 2149-70-4 KW - Nitric Oxide Synthase KW - EC 1.14.13.39 KW - NG-Nitroarginine Methyl Ester KW - V55S2QJN2X KW - Pentylenetetrazole KW - WM5Z385K7T KW - Index Medicus KW - Seizures -- chemically induced KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Pentylenetetrazole -- pharmacology KW - Picrotoxin -- pharmacology KW - Rats, Wistar KW - Mice KW - Male KW - Anticonvulsants -- pharmacology KW - NG-Nitroarginine Methyl Ester -- pharmacology KW - Nitric Oxide Synthase -- antagonists & inhibitors KW - Convulsants -- pharmacology KW - Nitroarginine -- pharmacology KW - Enzyme Inhibitors -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79829893?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Further+studies+on+anti-+and+proconvulsant+effects+of+inhibitors+of+nitric+oxide+synthase+in+rodents.&rft.au=Alexander%2C+C+B%3BEllmore%2C+T+M%3BKokate%2C+T+G%3BKirkby%2C+R+D&rft.aulast=Alexander&rft.aufirst=C&rft.date=1998-02-26&rft.volume=344&rft.issue=1&rft.spage=15&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 - 1998-06-09 N1 - Date created - 1998-06-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Apolipoprotein E allelic frequency in elderly smokers. AN - 79734337; 9508061 AB - Susceptibility genes for human diseases (e.g., cancer and atherosclerosis) increase disease risk by altering the metabolic activation of exogenous (e.g., carcinogens) and endogenous (e.g., cholesterol) compounds. The function of these genes, and subsequent risk, can be adversely affected by polymorphisms. This study tests the hypothesis that if specific genetic polymorphisms are related to mortality, then in elderly heavy smokers, there should be a decreased frequency of "at risk" alleles and an increased frequency of "protective" alleles, i.e., a survival effect. One such potential polymorphism is in the apolipoprotein E (apoE) gene, which is involved in cholesterol metabolism, where the epsilon4 allele is associated with an increased risk of coronary artery disease and is under represented in elderly populations. In this study, ApoE variant alleles were determined in 81 living, elderly current smokers (mean age: 72.5; range: 65-94; mean pack-years: 78; range: 13-192) and in 82 younger autopsy donors (mean age: 33; range: 1-58). There was a borderline difference in the apoE 4 allelic frequencies among the groups (11% in the elderly and 18% in the comparable younger group [df = 1; chi(2) = 4.02; P = 0.05]). A significant difference was found for age when stratified as a continuous variable by genotype in the elderly smokers (P = 0.03; mean age for persons with and without epsilon4 was 69.9 and 73.2, respectively). Pack-years of cigarette smokers did not differ by genotype, indicating no selective effect. These results confirm earlier associations for differences in the apoE allelic frequencies in the elderly and extend it to smokers, who generally have increased mortality at younger ages. JF - American journal of medical genetics AU - Bowman, E D AU - Brömeke, B AU - Lensing, W AU - Shields, P G AD - Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892-4255, USA. Y1 - 1998/02/26/ PY - 1998 DA - 1998 Feb 26 SP - 32 EP - 36 VL - 76 IS - 1 SN - 0148-7299, 0148-7299 KW - Apolipoproteins E KW - 0 KW - DNA Primers KW - Index Medicus KW - Coronary Disease -- etiology KW - Gene Frequency KW - Polymorphism, Genetic KW - DNA Primers -- genetics KW - Humans KW - Aged KW - Child KW - Child, Preschool KW - Infant KW - Polymerase Chain Reaction KW - Base Sequence KW - Longevity -- genetics KW - Aged, 80 and over KW - Risk Factors KW - Adult KW - Coronary Disease -- genetics KW - Middle Aged KW - Adolescent KW - Male KW - Female KW - Smoking -- mortality KW - Alleles KW - Smoking -- adverse effects KW - Smoking -- genetics KW - Apolipoproteins E -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79734337?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+medical+genetics&rft.atitle=Apolipoprotein+E+allelic+frequency+in+elderly+smokers.&rft.au=Bowman%2C+E+D%3BBr%C3%B6meke%2C+B%3BLensing%2C+W%3BShields%2C+P+G&rft.aulast=Bowman&rft.aufirst=E&rft.date=1998-02-26&rft.volume=76&rft.issue=1&rft.spage=32&rft.isbn=&rft.btitle=&rft.title=American+journal+of+medical+genetics&rft.issn=01487299&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-04-21 N1 - Date created - 1998-04-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - hSmad5 gene, a human hSmad family member: its full length cDNA, genomic structure, promoter region and mutation analysis in human tumors. AN - 79702574; 9484787 AB - hSmad (mothers against decapentaplegic)-related proteins are important messengers within the Transforming Growth Factor-beta1 (TGF-beta1) superfamily signal transduction pathways. To further characterize a member of this family, we obtained a full length cDNA of the human hSmad5 (hSmad5) gene by rapid amplification of cDNA ends (RACE) and then determined the genomic structure of the gene. There are eight exons and two alternative transcripts; the shorter transcript lacks exon 2. We identified the hSmad5 promoter region from a human genomic YAC clone by obtaining the nucleotide sequence extending 1235 base pairs upstream of the 5' end of the cDNA. We found a CpG island consistent with a promoter region, and we demonstrated promoter activity in a 1232 bp fragment located upstream of the transcription initiation site. To investigate the frequency of somatic hSmad5 mutations in human cancers, we designed intron-based primers to examine coding regions by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis. Neither homozygous deletions or point mutations were found in 40 primary gastric tumors and 51 cell lines derived from diverse types of human cancer including 20 cell lines resistant to the growth inhibitory effects of TGF-beta1. These results suggest that the hSmad5 gene is not commonly mutated and that other genetic alterations mediate the loss of TGF-beta1 responsiveness in human cancers. JF - Oncogene AU - Gemma, A AU - Hagiwara, K AU - Vincent, F AU - Ke, Y AU - Hancock, A R AU - Nagashima, M AU - Bennett, W P AU - Harris, C C AD - Laboratory of Human Carcinogenesis, Division of Basic Sciences, National Cancer Institute, NIH, Bethesda, Maryland 20892-4255, USA. Y1 - 1998/02/19/ PY - 1998 DA - 1998 Feb 19 SP - 951 EP - 956 VL - 16 IS - 7 SN - 0950-9232, 0950-9232 KW - DNA, Complementary KW - 0 KW - DNA, Neoplasm KW - DNA-Binding Proteins KW - Phosphoproteins KW - RNA, Messenger KW - SMAD5 protein, human KW - Smad5 Protein KW - Trans-Activators KW - Index Medicus KW - DNA, Complementary -- genetics KW - Humans KW - Amino Acid Sequence KW - RNA, Messenger -- genetics KW - Base Sequence KW - Promoter Regions, Genetic KW - Genes KW - Tumor Cells, Cultured KW - Sequence Alignment KW - Alternative Splicing KW - Molecular Sequence Data KW - DNA, Neoplasm -- genetics KW - Phosphoproteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79702574?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=hSmad5+gene%2C+a+human+hSmad+family+member%3A+its+full+length+cDNA%2C+genomic+structure%2C+promoter+region+and+mutation+analysis+in+human+tumors.&rft.au=Gemma%2C+A%3BHagiwara%2C+K%3BVincent%2C+F%3BKe%2C+Y%3BHancock%2C+A+R%3BNagashima%2C+M%3BBennett%2C+W+P%3BHarris%2C+C+C&rft.aulast=Gemma&rft.aufirst=A&rft.date=1998-02-19&rft.volume=16&rft.issue=7&rft.spage=951&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-13 N1 - Date created - 1998-03-13 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - U73825; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Intermolecular cleavage by UmuD-like mutagenesis proteins. AN - 79688734; 9465040 AB - The activity of a number of proteins is regulated by self-processing reactions. Elegant examples are the cleavage of the prokaryotic LexA and lambdaCI transcriptional repressors and the UmuD-like mutagenesis proteins. Various studies support the hypothesis that LexA and lambdaCI cleavage reactions are predominantly intramolecular in nature. The recently described crystal structure of the Escherichia coli UmuD' protein (the posttranslational cleavage product of the UmuD protein) suggests, however, that the region of the protein corresponding to the cleavage site is at least 50 A away from the catalytic active site. We considered the possibility, therefore, that the UmuD-like proteins might undergo self-processing that, in contrast to LexA and lambdaCI, occurs via an intermolecular rather than intramolecular reaction. To test this hypothesis, we introduced into E. coli compatible plasmids with mutations at either the cleavage or the catalytic site of three UmuD-like proteins. Cleavage of these proteins only occurs in the presence of both plasmids, indicating that the reaction is indeed intermolecular in nature. Furthermore, this intermolecular reaction is completely dependent upon the multifunctional RecA protein and leads to the restoration of cellular mutagenesis in nonmutable E. coli strains. Intermolecular cleavage of a biotinylated UmuD active site mutant was also observed in vitro in the presence of the wild-type UmuD' protein, indicating that in addition to the intact UmuD protein, the normal cleavage product (UmuD') can also act as a classical enzyme. JF - Proceedings of the National Academy of Sciences of the United States of America AU - McDonald, J P AU - Frank, E G AU - Levine, A S AU - Woodgate, R AD - Section on DNA Replication, Repair, and Mutagenesis, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-2725, USA. Y1 - 1998/02/17/ PY - 1998 DA - 1998 Feb 17 SP - 1478 EP - 1483 VL - 95 IS - 4 SN - 0027-8424, 0027-8424 KW - Bacterial Proteins KW - 0 KW - Escherichia coli Proteins KW - Rec A Recombinases KW - EC 2.7.7.- KW - DNA-Directed DNA Polymerase KW - EC 2.7.7.7 KW - UmuD protein, E coli KW - Index Medicus KW - Protein Processing, Post-Translational KW - Rec A Recombinases -- metabolism KW - Protein Binding KW - Mutagenesis KW - Binding Sites KW - Bacterial Proteins -- metabolism KW - Escherichia coli -- genetics KW - Escherichia coli -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79688734?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Intermolecular+cleavage+by+UmuD-like+mutagenesis+proteins.&rft.au=McDonald%2C+J+P%3BFrank%2C+E+G%3BLevine%2C+A+S%3BWoodgate%2C+R&rft.aulast=McDonald&rft.aufirst=J&rft.date=1998-02-17&rft.volume=95&rft.issue=4&rft.spage=1478&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 - 1998-03-19 N1 - Date created - 1998-03-19 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Biochemistry. 1986 Nov 4;25(22):6866-75 [2948553] Proc Natl Acad Sci U S A. 1985 Jun;82(12):4193-7 [3889923] Proc Natl Acad Sci U S A. 1987 Jun;84(12):3987-91 [3108885] 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] J Mol Biol. 1989 Mar 5;206(1):29-39 [2522996] J Mol Biol. 1989 Dec 5;210(3):439-52 [2693734] J Bacteriol. 1990 Jun;172(6):3030-6 [2188949] Mol Gen Genet. 1990 Nov;224(2):169-76 [2277636] Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2563-7 [2006191] Mol Gen Genet. 1991 Sep;229(1):10-6 [1654503] J Bacteriol. 1992 Nov;174(21):6844-51 [1400235] Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10777-81 [1438275] Cell. 1993 Jun 18;73(6):1165-73 [8513500] J Bacteriol. 1993 Aug;175(16):4943-50 [8349538] J Bacteriol. 1993 Sep;175(17):5411-9 [8366028] Proc Natl Acad Sci U S A. 1993 Sep 1;90(17):8169-73 [8367479] J Bacteriol. 1994 Aug;176(16):5011-21 [8051014] Nature. 1996 Apr 25;380(6576):727-30 [8614470] Science. 1996 Jun 14;272(5268):1644-6 [8658137] J Bacteriol. 1996 Aug;178(15):4400-11 [8755866] Proc Natl Acad Sci U S A. 1996 Sep 17;93(19):10291-6 [8816793] J Mol Biol. 1997 Jul 11;270(2):201-11 [9236122] Nat Struct Biol. 1997 Dec;4(12):979-83 [9406544] Mol Gen Genet. 1982;185(1):43-50 [6211591] Proc Natl Acad Sci U S A. 1984 Mar;81(5):1375-9 [6231641] Gene. 1984 Nov;31(1-3):165-71 [6098521] J Bacteriol. 1987 Feb;169(2):728-34 [3542969] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chimeric papillomavirus virus-like particles elicit antitumor immunity against the E7 oncoprotein in an HPV16 tumor model AN - 16263958; 4242105 AB - Papillomavirus-like particles (VLPs) are a promising prophylactic vaccine candidate to prevent human papillomavirus (HPV) infections and associated epithelial neoplasia. However, they are unlikely to have therapeutic effects because the virion capsid proteins are not detected in the proliferating cells of the infected epithelia or in cervical carcinomas. To increase the number of viral antigen targets for cell-mediated immune responses in a VLP-based vaccine, we have generated stable chimeric VLPs consisting of the L1 major capsid protein plus the entire E7 (11 kDa) or E2 (43 kDa) nonstructural papillomavirus protein fused to the L2 minor capsid protein. The chimeric VLPs are indistinguishable from the parental VLPs in their morphology and in their ability to agglutinate erythrocytes and elicit high titers of neutralizing antibodies. Protection from tumor challenge was tested in C57BL/6 mice by using the tumor cell line TC-1, which expresses HPV16 E7, but not the virion structural proteins. Injection of HPV16 L1/L2-HPV16 E7 chimeric VLPs, but not HPV16 L1/L2 VLPs, protected the mice from tumor challenge, even in the absence of adjuvant. The chimeric VLPs also induced protection against tumor challenge in major histocompatibility class II-deficient mice, but not in beta sub(2)-microglobulin or perforin knockout mice implying that protection was mediated by class I-restricted cytotoxic lymphocytes. These findings raise the possibility that VLPs may generally be efficient vehicles for generating cell-mediated immune responses and that, specifically, chimeric VLPs containing papillomavirus nonstructural proteins may increase the therapeutic potential of VLP-based prophylactic vaccines in humans. JF - Proceedings of the National Academy of Sciences, USA AU - Greenstone, H AU - Nieland, J AU - de Visser, K AU - De Bruijn, M AU - Kirnbauer, R AU - Roden, R AU - Lowy, D AU - Kast, W AU - Schiller, J AD - Laboratory of Cellular Oncology, National Institutes of Health, 36 Convent Drive, MSC 4040, Bethesda, MD 20892-4040 Y1 - 1998/02/17/ PY - 1998 DA - 1998 Feb 17 SP - 1800 EP - 1805 VL - 95 IS - 4 SN - 0027-8424, 0027-8424 KW - double prime E7 protein KW - human papillomavirus 16 KW - mice KW - papillomavirus-like particles KW - Biotechnology and Bioengineering Abstracts; Virology & AIDS Abstracts; Immunology Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - F 06818:Cancer immunotherapy KW - W3 33350:Cancer vaccines KW - V 22114:Human oncogenic viruses KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16263958?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.atitle=Chimeric+papillomavirus+virus-like+particles+elicit+antitumor+immunity+against+the+E7+oncoprotein+in+an+HPV16+tumor+model&rft.au=Greenstone%2C+H%3BNieland%2C+J%3Bde+Visser%2C+K%3BDe+Bruijn%2C+M%3BKirnbauer%2C+R%3BRoden%2C+R%3BLowy%2C+D%3BKast%2C+W%3BSchiller%2C+J&rft.aulast=Greenstone&rft.aufirst=H&rft.date=1998-02-17&rft.volume=95&rft.issue=4&rft.spage=1800&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - SuppNotes - ISSN for electronic version: 1091-6490. ISSN for print version: 0027-8424. N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Mucosal immunization with HIV-1 peptide vaccine induces mucosal and systemic cytotoxic T lymphocytes and protective immunity in mice against intrarectal recombinant HIV-vaccinia challenge AN - 16262747; 4242089 AB - Mucosal tissues are major sites of HIV entry and initial infection. Thus, the induction of a mucosal cytotoxic T lymphocyte (CTL) response is an important feature for an effective HIV vaccine. However, little is known about approaches to induce such a protective CTL response in the mucosa. Here for the first time we show that intrarectal immunization with a synthetic, multideterminant HIV peptide plus cholera toxin adjuvant induced long-lasting, antigen-specific CTL memory in both the inductive (Peyer's patch) and effector (lamina propria) mucosal sites, as well as in systemic sites (spleen), whereas systemic immunization induced specific CTL only in the spleen. Cholera toxin adjuvant, while enhancing the response, was not essential. The CTL recognized target cells either pulsed with HIV peptide or expressing endogenous whole envelope glycoprotein of M sub(r) 160,000 (gp160). Exploring the requirements for CTL induction, we show that mucosal CTL responses are both interleukin 12 and interferon- gamma dependent by using antibody-treated and knock-out mice. Finally, to determine whether a mucosal response is actually protective against local mucosal challenge with virus, we show that intrarectal immunization with the synthetic HIV peptide vaccine protected mice against infection via mucosal challenge with a recombinant vaccinia virus expressing HIV-1IIIB gp160. These studies provide an approach to development of an HIV vaccine that induces CTL immunity in the mucosal and systemic immune systems and protects against mucosal infection with a virus expressing HIV-1 gp160. JF - Proceedings of the National Academy of Sciences, USA AU - Belyakov, I AU - Derby, M AU - Ahlers, J AU - Kelsall, B AU - Earl, P AU - Moss, B AU - Strober, W AU - Berzofsky, J AD - Metabolism Branch, National Cancer Institute, Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, and Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 Y1 - 1998/02/17/ PY - 1998 DA - 1998 Feb 17 SP - 1709 EP - 1714 VL - 95 IS - 4 SN - 0027-8424, 0027-8424 KW - HIV-1 KW - glycoprotein gp160 KW - human immunodeficiency virus 1 KW - mice KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Virology & AIDS Abstracts; Immunology Abstracts KW - W3 33365:Vaccines (other) KW - F 06807:Active immunization KW - V 22003:AIDS: Immunological aspects KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16262747?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.atitle=Mucosal+immunization+with+HIV-1+peptide+vaccine+induces+mucosal+and+systemic+cytotoxic+T+lymphocytes+and+protective+immunity+in+mice+against+intrarectal+recombinant+HIV-vaccinia+challenge&rft.au=Belyakov%2C+I%3BDerby%2C+M%3BAhlers%2C+J%3BKelsall%2C+B%3BEarl%2C+P%3BMoss%2C+B%3BStrober%2C+W%3BBerzofsky%2C+J&rft.aulast=Belyakov&rft.aufirst=I&rft.date=1998-02-17&rft.volume=95&rft.issue=4&rft.spage=1709&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - SuppNotes - ISSN for electronic version: 1091-6490. ISSN for print version: 0027-8424. N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Characterization of functional vanilloid receptors expressed by mast cells. AN - 79678265; 9454764 AB - Capsaicin and its ultrapotent analog resiniferatoxin (RTX) act through specific vanilloid receptors on sensory neurons. The C-type receptor is coupled to 45Ca uptake, whereas the R-type is detectable by [3H]RTX binding. We describe here specific vanilloid responses in murine mast cells (MCs). In the MC lines and in bone marrow-derived mast cells, capsaicin and RTX induced 45Ca uptake similarly to that observed for cultured rat dorsal root ganglion neurons (DRGs). This response was antagonized by the antagonists capsazepine and ruthenium red. As in DRGs, pretreatment of MCs with capsaicin or RTX induced desensitization to subsequent stimulation of 45Ca uptake. The potency for desensitization by RTX in the MCs corresponded to that for 45Ca uptake, whereas in DRGs it occurred at significantly lower concentrations corresponding to that for the high-affinity [3H]RTX binding site. Consistent with this difference, in MCs we were unable to detect [3H]RTX binding. Vanilloids were noncytotoxic to the MCs, in contrast to the DRGs. Although vanilloids did not cause degranulation in MCs, in the P815 clone capsaicin evoked selective interleukin-4 release. We conclude that certain MCs possess vanilloid receptors, but only the C-type that functions as a channel. Our finding that MCs can respond directly to capsaicin necessitates a reevaluation of the in vivo pathway of inflammation in response to vanilloids. JF - Blood AU - Bíró, T AU - Maurer, M AU - Modarres, S AU - Lewin, N E AU - Brodie, C AU - Acs, G AU - Acs, P AU - Paus, R AU - Blumberg, P M AD - Molecular Mechanisms of Tumor Promotion Section, Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA. Y1 - 1998/02/15/ PY - 1998 DA - 1998 Feb 15 SP - 1332 EP - 1340 VL - 91 IS - 4 SN - 0006-4971, 0006-4971 KW - Receptors, Drug KW - 0 KW - Capsaicin KW - S07O44R1ZM KW - Calcium KW - SY7Q814VUP KW - Abridged Index Medicus KW - Index Medicus KW - Rats KW - Calcium -- metabolism KW - Animals KW - Mice KW - Signal Transduction KW - Cell Line KW - Bone Marrow Cells -- metabolism KW - Receptors, Drug -- metabolism KW - Mast Cells -- metabolism KW - Capsaicin -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79678265?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Characterization+of+functional+vanilloid+receptors+expressed+by+mast+cells.&rft.au=B%C3%ADr%C3%B3%2C+T%3BMaurer%2C+M%3BModarres%2C+S%3BLewin%2C+N+E%3BBrodie%2C+C%3BAcs%2C+G%3BAcs%2C+P%3BPaus%2C+R%3BBlumberg%2C+P+M&rft.aulast=B%C3%ADr%C3%B3&rft.aufirst=T&rft.date=1998-02-15&rft.volume=91&rft.issue=4&rft.spage=1332&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-03 N1 - Date created - 1998-03-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutagenesis of a single AT basepair in mice transgenic for PhiX174 am3 cs70 I. Spleen and testis. AN - 79890664; 9600695 AB - Mutations induced in a single AT base pair were studied in spleen and testis by using mice transgenic for PhiX174 am3, cs70 and ethylnitrosourea (ENU) as the mutagen. The transgenic mice were produced on the C57BL6/J background. The line (am54), which carries 50 copies of PhiX per haploid genome integrated in a tandem array, was selected for experimental use and was maintained by random breeding. The animals for mutagenesis studies were produced by mating homozygous am54 males to wildtype C57BL6/J females. Hemizygous male offspring (8 to 10 weeks old) from this cross were injected i.p. with 150 mg ENU per kg and were euthanized 3, 10 or 110 days after treatment. The spontaneous revertant frequency in the spleen was 1.42 x 10(-6) per plaque forming unit (pfu) and in the testis it was 1.41 x 10(-6) per pfu. There was no significant difference between the two tissues. In spleen, it was not until 110 days after ENU treatment that the average revertant frequency among treated animals was significantly higher than the revertant frequency among the control animals. In spleen, the induced frequency of basepair substitutions in the center AT basepair in the am3 nonsense codon was 2 x 10(-6). Also at this post-injection interval the variance of revertant frequencies in the spleen was not different from control variance. In testis, the average revertant frequency 110 days post ENU injection was not significantly different from the control. However, two important observations were made regarding the testis data. First, one animal had a significantly increased revertant frequency 110 days after ENU treatment in comparison to the other four animals in the group that had revertant frequencies equal to or lower than the average control frequency. Second, the variance of revertant frequencies in the testis among the treated animals increased as the post injection period increased. Taken together, these observations may indicate that the revertants formed large clusters in one testis sample. JF - Mutation research AU - Malling, H V AU - Weaver, R P AD - Mammalian Genetics Group, Laboratory of Toxicology, Environmental Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709-2233, USA. malling@niehs.nih.gov Y1 - 1998/02/13/ PY - 1998 DA - 1998 Feb 13 SP - 271 EP - 281 VL - 412 IS - 3 SN - 0027-5107, 0027-5107 KW - Mutagens KW - 0 KW - Adenine KW - JAC85A2161 KW - Ethylnitrosourea KW - P8M1T4190R KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Animals KW - Mice, Inbred C57BL KW - Bacteriophage phi X 174 -- genetics KW - Mice KW - Male KW - Female KW - Mice, Transgenic -- genetics KW - Testis -- drug effects KW - Ethylnitrosourea -- toxicity KW - Mutagens -- toxicity KW - Spleen -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79890664?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mutagenesis+of+a+single+AT+basepair+in+mice+transgenic+for+PhiX174+am3+cs70+I.+Spleen+and+testis.&rft.au=Malling%2C+H+V%3BWeaver%2C+R+P&rft.aulast=Malling&rft.aufirst=H&rft.date=1998-02-13&rft.volume=412&rft.issue=3&rft.spage=271&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 - 1998-06-04 N1 - Date created - 1998-06-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of cdk2 binding sites on the p27Kip1 cyclin-dependent kinase inhibitor. AN - 79709335; 9488039 AB - A cdk2 binding domain on p27Kip1 located within the sequence of amino acids 53-85 was further characterized by generating a series of point mutations within amino acid residues 62-75. Two regions, FDF (residues 62-64) and GXY (residues 72 and 74), were identified within the beta hairpin region of p27Kip1. Mutations within these regions essentially completely inhibited the binding to in vitro translated cdk2 and cdk2/cyclin E complexes formed in vitro or in vivo. The p27Kip1 GST-fusion protein of the point mutation that replaces phenylalanine at residue 64 to alanine (F64A) showed approximately twofold less inhibition of cdk2 kinase activity. The cellular response to the introduction of the F64A mutant form of p27Kip1 was compared to that of p27Kip1 wild type by transfecting HeLa cells with constructs of full length sense and antisense coding sequences. Overexpression of the F64A mutant form of p27Kip1 bound significantly lower levels of cdk2 as compared to wild type and did not affect the cdk2 related kinase activity of the transfected HeLa cells. Overexpression of wild type p27Kip1 resulted in a reduction of the level of cdk2 kinase activity and effectively suppressed the growth of the transfected HeLa cells. JF - Oncogene AU - Kwon, T K AU - Nordin, A A AD - Laboratory of Immunology, Gerontology Research Center, National Institute on Aging, NIH, Baltimore, Maryland 21224, USA. Y1 - 1998/02/12/ PY - 1998 DA - 1998 Feb 12 SP - 755 EP - 762 VL - 16 IS - 6 SN - 0950-9232, 0950-9232 KW - Cdkn1b protein, mouse KW - 0 KW - Cell Cycle Proteins KW - Cyclin E KW - Enzyme Inhibitors KW - Microtubule-Associated Proteins KW - Recombinant Fusion Proteins KW - Tumor Suppressor Proteins KW - Cyclin-Dependent Kinase Inhibitor p27 KW - 147604-94-2 KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - CDC2-CDC28 Kinases KW - EC 2.7.11.22 KW - CDK2 protein, human KW - Cdk2 protein, mouse KW - Cyclin-Dependent Kinase 2 KW - Cyclin-Dependent Kinases KW - Index Medicus KW - Animals KW - HeLa Cells KW - Humans KW - Mice KW - Binding Sites KW - Cyclin E -- metabolism KW - Mutagenesis, Site-Directed KW - Recombinant Fusion Proteins -- metabolism KW - Tumor Cells, Cultured KW - Transfection KW - Recombinant Fusion Proteins -- genetics KW - Cell Division KW - Cyclin-Dependent Kinases -- metabolism KW - Microtubule-Associated Proteins -- metabolism KW - Microtubule-Associated Proteins -- genetics KW - Protein-Serine-Threonine Kinases -- metabolism KW - Cyclin-Dependent Kinases -- antagonists & inhibitors KW - Enzyme Inhibitors -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79709335?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Identification+of+cdk2+binding+sites+on+the+p27Kip1+cyclin-dependent+kinase+inhibitor.&rft.au=Kwon%2C+T+K%3BNordin%2C+A+A&rft.aulast=Kwon&rft.aufirst=T&rft.date=1998-02-12&rft.volume=16&rft.issue=6&rft.spage=755&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-13 N1 - Date created - 1998-03-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Involvement of p85 in p53-dependent apoptotic response to oxidative stress. AN - 79700053; 9490416 AB - Reactive oxygen species have damaging effects on cellular components and so trigger defensive responses by the cell and even programmed cell death, although the mechanisms by which mammalian cells transmit signals in response to oxidative damage are unknown. We report here that the protein p85, a regulator of the signalling protein phosphatidyl-3-OH kinase (PI(3)K), participates in the cell death process that is induced in response to oxidative stress and that this role of p85 in apoptosis does not involve PI(3)K. We show that disruption of p85 by homologous recombination impairs the cellular apoptotic response to oxidative stress. Because the protein p53 is required for cell death induced by oxidative damage, we examined the relation between p85 and p53. Using a chimaeric p53 fusion protein with the oestrogen receptor (p53ER) to supply p53 (p53 is induced upon binding of p53ER to oestradiol) in a p53-deficient cell line, we found that p85 is upregulated by p53 and that its involvement in p53-mediated apoptosis is independent of PI(3)K. We propose that p85 acts as a signal transducer in the cellular response to oxidative stress, mediating cell death regulated by p53. JF - Nature AU - Yin, Y AU - Terauchi, Y AU - Solomon, G G AU - Aizawa, S AU - Rangarajan, P N AU - Yazaki, Y AU - Kadowaki, T AU - Barrett, J C AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 1998/02/12/ PY - 1998 DA - 1998 Feb 12 SP - 707 EP - 710 VL - 391 IS - 6668 SN - 0028-0836, 0028-0836 KW - Androstadienes KW - 0 KW - Antisense Elements (Genetics) KW - Enzyme Inhibitors KW - Recombinant Fusion Proteins KW - Tumor Suppressor Protein p53 KW - Hydrogen Peroxide KW - BBX060AN9V KW - Phosphatidylinositol 3-Kinases KW - EC 2.7.1.- KW - wortmannin KW - XVA4O219QW KW - Index Medicus KW - Animals KW - Fibroblasts -- drug effects KW - Fibroblasts -- enzymology KW - Humans KW - Hydrogen Peroxide -- pharmacology KW - Androstadienes -- pharmacology KW - Fibroblasts -- cytology KW - Mice KW - Recombinant Fusion Proteins -- metabolism KW - Tumor Cells, Cultured KW - Enzyme Inhibitors -- pharmacology KW - Signal Transduction KW - Cell Line KW - Phosphatidylinositol 3-Kinases -- genetics KW - Tumor Suppressor Protein p53 -- physiology KW - Apoptosis KW - Phosphatidylinositol 3-Kinases -- metabolism KW - Oxidative Stress KW - Tumor Suppressor Protein p53 -- genetics KW - Phosphatidylinositol 3-Kinases -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79700053?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature&rft.atitle=Involvement+of+p85+in+p53-dependent+apoptotic+response+to+oxidative+stress.&rft.au=Yin%2C+Y%3BTerauchi%2C+Y%3BSolomon%2C+G+G%3BAizawa%2C+S%3BRangarajan%2C+P+N%3BYazaki%2C+Y%3BKadowaki%2C+T%3BBarrett%2C+J+C&rft.aulast=Yin&rft.aufirst=Y&rft.date=1998-02-12&rft.volume=391&rft.issue=6668&rft.spage=707&rft.isbn=&rft.btitle=&rft.title=Nature&rft.issn=00280836&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-02 N1 - Date created - 1998-03-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dopamine induces apoptosis through an oxidation-involved SAPK/JNK activation pathway. AN - 79680204; 9452508 AB - Dopamine (DA) is a neurotransmitter, but it also exerts a neurotoxic effect under certain pathological conditions, including age-related neurodegeneration such as Parkinson's disease. By using both the 293 cell line and primary neonatal rat postmitotic striatal neuron cultures, we show here that DA induces apoptosis in a time- and concentration-dependent manner. Concomitant with the apoptosis, DA activates the JNK pathway, including increases in JNK activity, phosphorylation of c-Jun, and subsequent increase in c-Jun protein. This DA-induced JNK activation precedes apoptosis and is persistently sustained during the process of apoptosis. Transient expression of a dominant negative mutant SEK1(Lys --> Arg), an upstream kinase of JNK, prevents both DA-induced JNK activation and apoptosis. A dominant negative c-Jun mutant FLAGDelta169 also reduces DA-induced apoptotic cell death. Anti-oxidants N-acetylcysteine and catalase, which serve as scavengers of reactive oxygen species generated by metabolic DA oxidation, effectively block DA-induced JNK activation and subsequent apoptosis. Thus, our data suggest that DA triggers an apoptotic death program through an oxidative stress-involved JNK activation signaling pathway. Given the fact that the anti-oxidative defense system declines during aging, this molecular event may be implicated in the age-related striatal neuronal cell loss and age-related dopaminergic neurodegenerative disorders, such as Parkinson's and Huntington's diseases. JF - The Journal of biological chemistry AU - Luo, Y AU - Umegaki, H AU - Wang, X AU - Abe, R AU - Roth, G S AD - Molecular Physiology and Genetics Section, Gerontology Research Center, NIA, National Institutes of Health, Baltimore, Maryland 21224, USA. luoyq@helix.nih.gov Y1 - 1998/02/06/ PY - 1998 DA - 1998 Feb 06 SP - 3756 EP - 3764 VL - 273 IS - 6 SN - 0021-9258, 0021-9258 KW - Antioxidants KW - 0 KW - Calcium-Calmodulin-Dependent Protein Kinases KW - EC 2.7.11.17 KW - JNK Mitogen-Activated Protein Kinases KW - EC 2.7.11.24 KW - Mitogen-Activated Protein Kinases KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Rats KW - Oxidation-Reduction KW - Animals KW - Antioxidants -- pharmacology KW - Enzyme Activation KW - Humans KW - Neurons -- cytology KW - Kidney -- cytology KW - Signal Transduction KW - Cell Line KW - Calcium-Calmodulin-Dependent Protein Kinases -- metabolism KW - Apoptosis -- physiology KW - Apoptosis -- drug effects KW - Dopamine -- physiology KW - Dopamine -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79680204?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Dopamine+induces+apoptosis+through+an+oxidation-involved+SAPK%2FJNK+activation+pathway.&rft.au=Luo%2C+Y%3BUmegaki%2C+H%3BWang%2C+X%3BAbe%2C+R%3BRoth%2C+G+S&rft.aulast=Luo&rft.aufirst=Y&rft.date=1998-02-06&rft.volume=273&rft.issue=6&rft.spage=3756&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 - 1998-03-05 N1 - Date created - 1998-03-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transformation suppressor activity of C3G is independent of its CDC25-homology domain. AN - 79700398; 9482107 AB - The guanine nucleotide releasing protein C3G was initially identified as a Crk SH3-binding protein and recently shown to exhibit exchange activity on Rap1 proteins. Overexpression in NIH3T3 cells of a full-length C3G cDNA isolated from human placenta markedly reduced the focus forming activity of cotransfected, malignantly activated, ras oncogenes (5-7-fold). C3G also had a reverting effect on sis-mediated transformation, decreasing the number of c-sis-induced foci by a factor of 5-10-fold. The observed inhibitory effect of C3G on focus-forming activity of Ras and Sis was always higher than that observed with Rap1A, a known target of C3G. The inhibition of focus formation observed in the presence of C3G was not due to toxic effects on cell viability, since transfected C3G cells exhibited the same survival and growth rates as untransfected NIH3T3 cells or cells transfected with plasmid vector alone. Surprisingly, as opposed to Rap1A, which has no effect on Raf-1 oncogene-mediated transformation, C3G also reduced dramatically (6-8-fold) the number of v-raf-induced foci in transfected NIH3T3 cells. The inhibitory effect on Raf-induced transformation suggests that C3G has other functional targets in addition to Rap1. A C3G mutant (C3G deltaCat) lacking the catalytic domain (CDC25-H) but retaining the rest of the N-terminal sequences, including the Crk-binding domain, exhibited similar ability than full length C3G to inhibit focus formation. In contrast, a C3G mutant (C3G Cat), containing the catalytic domain only but lacking the rest of the N-terminal sequences, did not have any inhibitory effect on transformation mediated by the oncogenes tested. The C3G-derived gene products overexpressed in our transfected cell lines localized to the cytoplasm and did not change the basal MAPK or JNK activity of those cell lines nor their ability to activate the kinases in response to agonists. Our results suggest that the N-terminal region of C3G, and not its catalytic domain, may be responsible for the inhibitory effects observed. JF - Oncogene AU - Guerrero, C AU - Fernandez-Medarde, A AU - Rojas, J M AU - Font de Mora, J AU - Esteban, L M AU - Santos, E AD - Laboratory of Cellular and Molecular Biology, NCI, DBS, NIH, Bethesda, Maryland 20892, USA. Y1 - 1998/02/05/ PY - 1998 DA - 1998 Feb 05 SP - 613 EP - 624 VL - 16 IS - 5 SN - 0950-9232, 0950-9232 KW - Cell Cycle Proteins KW - 0 KW - DNA, Complementary KW - Guanine Nucleotide Exchange Factors KW - Platelet-Derived Growth Factor KW - Proteins KW - Proto-Oncogene Proteins KW - Proto-Oncogene Proteins c-sis KW - Retroviridae Proteins, Oncogenic KW - ras Guanine Nucleotide Exchange Factors KW - ras-GRF1 KW - Oncogene Proteins v-raf KW - EC 2.7.11.1 KW - Phosphoprotein Phosphatases KW - EC 3.1.3.16 KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - rap GTP-Binding Proteins KW - EC 3.6.5.2 KW - Index Medicus KW - Animals KW - Peptide Mapping KW - Retroviridae Proteins, Oncogenic -- physiology KW - Humans KW - Proto-Oncogene Proteins -- genetics KW - Platelet-Derived Growth Factor -- physiology KW - Placenta -- chemistry KW - Protein Biosynthesis KW - DNA, Complementary -- genetics KW - Mice KW - GTP-Binding Proteins -- physiology KW - Platelet-Derived Growth Factor -- genetics KW - GTP-Binding Proteins -- genetics KW - Proto-Oncogene Proteins -- physiology KW - Cloning, Molecular KW - Binding Sites KW - Retroviridae Proteins, Oncogenic -- genetics KW - Transfection KW - DNA, Complementary -- metabolism KW - 3T3 Cells -- metabolism KW - Placenta -- metabolism KW - Genes, ras KW - Cell Cycle Proteins -- physiology KW - Phosphoprotein Phosphatases -- physiology KW - Gene Expression Regulation -- physiology KW - Cell Cycle Proteins -- genetics KW - Phosphoprotein Phosphatases -- genetics KW - Proteins -- genetics KW - Proteins -- physiology KW - src Homology Domains KW - Transformation, Genetic -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79700398?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Transformation+suppressor+activity+of+C3G+is+independent+of+its+CDC25-homology+domain.&rft.au=Guerrero%2C+C%3BFernandez-Medarde%2C+A%3BRojas%2C+J+M%3BFont+de+Mora%2C+J%3BEsteban%2C+L+M%3BSantos%2C+E&rft.aulast=Guerrero&rft.aufirst=C&rft.date=1998-02-05&rft.volume=16&rft.issue=5&rft.spage=613&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-09 N1 - Date created - 1998-03-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Plasmodium malariae infection in an asymptomatic 74-year-old Greek woman with splenomegaly. AN - 79672836; 9449730 JF - The New England journal of medicine AU - Vinetz, J M AU - Li, J AU - McCutchan, T F AU - Kaslow, D C AD - Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md 20892, USA. Y1 - 1998/02/05/ PY - 1998 DA - 1998 Feb 05 SP - 367 EP - 371 VL - 338 IS - 6 SN - 0028-4793, 0028-4793 KW - Antibodies, Protozoan KW - 0 KW - Methotrexate KW - YL5FZ2Y5U1 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Lymphoma -- diagnosis KW - Base Sequence KW - Diagnosis, Differential KW - Greece KW - Humans KW - Antibodies, Protozoan -- blood KW - Molecular Sequence Data KW - Lymphoma -- drug therapy KW - Aged KW - Female KW - Splenomegaly -- etiology KW - Methotrexate -- adverse effects KW - Plasmodium malariae -- immunology KW - Plasmodium malariae -- genetics KW - Malaria -- diagnosis KW - Malaria -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79672836?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+New+England+journal+of+medicine&rft.atitle=Plasmodium+malariae+infection+in+an+asymptomatic+74-year-old+Greek+woman+with+splenomegaly.&rft.au=Vinetz%2C+J+M%3BLi%2C+J%3BMcCutchan%2C+T+F%3BKaslow%2C+D+C&rft.aulast=Vinetz&rft.aufirst=J&rft.date=1998-02-05&rft.volume=338&rft.issue=6&rft.spage=367&rft.isbn=&rft.btitle=&rft.title=The+New+England+journal+of+medicine&rft.issn=00284793&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-02-05 N1 - Date created - 1998-02-05 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: N Engl J Med. 2000 Jun 22;342(25):1924 [10877649] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Much ado about not...enough data: high-dose chemotherapy with autologous stem cell rescue for breast cancer. AN - 79683132; 9462677 AB - High-dose chemotherapy with autologous bone marrow or stem cell rescue (HDC/ASCR) has been proposed as a promising treatment strategy for breast cancer. Despite the frequency with which this procedure is performed, the role of HDC/ASCR in the treatment of breast cancer remains undefined. The purpose of this review is to examine the rationale for the procedure, the research progress to date, and the limitations of available data. A literature search of Medline from January 1966 through May 1997, CancerLit from January 1983 through May 1997, and Current Contents through May 1997 identified more than 600 English language papers or abstracts on this topic. Our review focuses on the preclinical and clinical data that explore the concept of chemotherapy dose intensity and the role of dose intensity in treating breast cancer. HDC/ASCR is based on the hypothesis that high-dose chemotherapy will overcome drug resistance, eradicate metastatic disease, and increase the proportion of women with breast cancer who are "cured." To date, results from only one phase 3 trial of HDC/ASCR compared with more conventional therapy have been published. Phase 2 and some phase 3 data on HDC/ASCR in the treatment of high-risk primary breast cancer and metastatic breast cancer are discussed. However, the results are inconclusive. The completion of national and international randomized trials is urgently needed to establish definitively the role of HDC/ASCR in the treatment of breast cancer. JF - Journal of the National Cancer Institute AU - Zujewski, J AU - Nelson, A AU - Abrams, J AD - National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1998/02/04/ PY - 1998 DA - 1998 Feb 04 SP - 200 EP - 209 VL - 90 IS - 3 SN - 0027-8874, 0027-8874 KW - Index Medicus KW - Randomized Controlled Trials as Topic KW - Humans KW - Clinical Trials as Topic KW - Transplantation, Autologous KW - Female KW - Breast Neoplasms -- drug therapy KW - Hematopoietic Stem Cell Transplantation KW - Antineoplastic Combined Chemotherapy Protocols -- administration & dosage KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Breast Neoplasms -- surgery UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79683132?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Much+ado+about+not...enough+data%3A+high-dose+chemotherapy+with+autologous+stem+cell+rescue+for+breast+cancer.&rft.au=Zujewski%2C+J%3BNelson%2C+A%3BAbrams%2C+J&rft.aulast=Zujewski&rft.aufirst=J&rft.date=1998-02-04&rft.volume=90&rft.issue=3&rft.spage=200&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 - 1998-02-17 N1 - Date created - 1998-02-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Unusual insertion element polymorphisms in the promoter and terminator regions of the mucAB-like genes of R471a and R446b. AN - 79790298; 9541650 AB - We have previously identified umu-complementing genes on two incL/M plasmids, R471a and R446b (C. Ho et al., J. Bacteriol., 175 (1993) 5411-5419). Molecular analysis of these genes revealed that they are more structurally and functionally related to mucAB from the incN plasmid pKM101 than to other members of the previously identified Umu-like family. As a consequence, we have termed these new homologs mucAB(R471a) and mucAB(R446b) respectively. Interestingly, while the location of the mucAB-like genes is essentially the same in both R471a and R446b, the regions immediately flanking the mucAB-like genes are highly polymorphic. For example, 5' to mucAB(R471a) we found an insert that appears to be a novel retroelement encoding a putative reverse transcriptase (RT). This RT is related to the reverse transcriptases encoded by group II introns but is embedded in a retron-like context. Immediately 3' to the mucAB(R471a) locus is a putative insertion element of a sparsely-dispersed class not previously reported from enteric bacteria. Both the RT and insertion element are absent in R446b. These observations suggest that the mucAB-like genes from R471a and R446b are located within regions of the R-plasmids that perhaps were once (or still are) mobile genetic elements. Such observations might help explain the distribution of umu-like genes on R-plasmids and bacterial chromosomes. JF - Mutation research AU - Kulaeva, O I AU - Koonin, E V AU - Wootton, J C AU - Levine, A S AU - Woodgate, R AD - Section on DNA Replication, Repair and Mutagenesis, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-2725, USA. Y1 - 1998/02/02/ PY - 1998 DA - 1998 Feb 02 SP - 247 EP - 262 VL - 397 IS - 2 SN - 0027-5107, 0027-5107 KW - Bacterial Proteins KW - 0 KW - DNA Transposable Elements KW - DNA, Bacterial KW - Escherichia coli Proteins KW - mucAB protein, E coli KW - 138186-81-9 KW - RNA-Directed DNA Polymerase KW - EC 2.7.7.49 KW - Aspartic Acid Endopeptidases KW - EC 3.4.23.- KW - signal peptidase II KW - EC 3.4.23.36 KW - Index Medicus KW - Phenotype KW - Base Sequence KW - Aspartic Acid Endopeptidases -- genetics KW - Operon KW - Molecular Sequence Data KW - Escherichia coli -- genetics KW - Amino Acid Sequence KW - Sequence Homology, Amino Acid KW - RNA-Directed DNA Polymerase -- genetics KW - Terminator Regions, Genetic KW - Promoter Regions, Genetic KW - Bacterial Proteins -- genetics KW - Polymorphism, Genetic KW - DNA Transposable Elements -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79790298?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Unusual+insertion+element+polymorphisms+in+the+promoter+and+terminator+regions+of+the+mucAB-like+genes+of+R471a+and+R446b.&rft.au=Kulaeva%2C+O+I%3BKoonin%2C+E+V%3BWootton%2C+J+C%3BLevine%2C+A+S%3BWoodgate%2C+R&rft.aulast=Kulaeva&rft.aufirst=O&rft.date=1998-02-02&rft.volume=397&rft.issue=2&rft.spage=247&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 - 1998-04-22 N1 - Date created - 1998-04-22 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF027768; GENBANK; AF027767 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effortful echolalia. AN - 85420418; pmid-9533994 AB - We report three cases of effortful echolalia in patients with cerebral infarction. The clinical picture of speech disturbance is associated with Type 1 Transcortical Motor Aphasia (TCMA, Goldstein, 1915). The patients always spoke nonfluently with loss of speech initiative, dysarthria, dysprosody, agrammatism, and increased effort and were unable to repeat sentences longer than those containing four or six words. In conversation, they first repeated a few words spoken to them, and then produced self initiated speech. The initial repetition as well as the subsequent self initiated speech, which were realized equally laboriously, can be regarded as mitigated echolalia (Pick, 1924). They were always aware of their own echolalia and tried to control it without effect. These cases demonstrate that neither the ability to repeat nor fluent speech are always necessary for echolalia. The possibility that a lesion in the left medial frontal lobe, including the supplementary motor area, plays an important role in effortful echolalia is discussed. JF - Cortex; a journal devoted to the study of the nervous system and behavior AU - Hadano, K AU - Nakamura, H AU - Hamanaka, T AD - Department of Psychogeriatrics, National Institute of Mental Health (NCNP), Nagoya. hadano@ncnp-k.go.jp Y1 - 1998/02// PY - 1998 DA - February 1998 SP - 67 EP - 82 VL - 34 IS - 1 SN - 0010-9452, 0010-9452 KW - Index Medicus KW - National Library of Medicine KW - Magnetic Resonance Imaging KW - Humans KW - Cerebral Infarction -- pathology KW - Echolalia -- psychology KW - Tomography, X-Ray Computed KW - Memory -- physiology KW - Echolalia -- etiology KW - Aged KW - Echolalia -- pathology KW - Music KW - Middle Aged KW - Neuropsychological Tests KW - Female KW - Male KW - Cerebral Infarction -- complications KW - Cerebral Infarction -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85420418?accountid=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=Cortex%3B+a+journal+devoted+to+the+study+of+the+nervous+system+and+behavior&rft.atitle=Effortful+echolalia.&rft.au=Hadano%2C+K%3BNakamura%2C+H%3BHamanaka%2C+T&rft.aulast=Hadano&rft.aufirst=K&rft.date=1998-02-01&rft.volume=34&rft.issue=1&rft.spage=67&rft.isbn=&rft.btitle=&rft.title=Cortex%3B+a+journal+devoted+to+the+study+of+the+nervous+system+and+behavior&rft.issn=00109452&rft_id=info:doi/ LA - English DB - ComDisDome N1 - Date revised - 2008-01-14 N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Presynaptic localization of G protein isoforms in the efferent nerve terminals of the mammalian cochlea. AN - 85417643; pmid-9508023 AB - Heterotrimeric guanine nucleotide binding proteins (G proteins) are known to be involved in receptor-mediated synaptic activity. In order to determine which G protein isoforms, if any, are involved in synaptic regulation in the organ of Corti, we performed an extensive immunocytochemical screening. We localized a Galpha(q/11) isoform to the efferent nerve terminals using antibodies specific against the alpha subunit of these proteins. The label was observed in the efferent boutons contacting either the outer hair cells or the afferent fibers at the inner spiral bundle. We compared the localization of this isoform to that of the presynaptic protein SNAP-25 in double labeling experiments. Galpha(q/11) immunoreactivity was present predominantly in the cytoplasm of the presynaptic boutons in a region of high density of synaptic vesicles, while SNAP-25 was localized predominantly in the plasma membrane of the boutons. No label for these proteins was found at the afferent synapses, including the presynaptic terminals on hair cells. These results suggest that an isoform of the Gq subfamily of the G proteins might be involved in presynaptic modulation of neurotransmitter release at the cochlear efferents. JF - Hearing research AU - Kurc, M AU - Dodane, V AU - Pinto, D S AU - Kachar, B AD - Section on Structural Cell Biology, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1998/02// PY - 1998 DA - February 1998 SP - 1 EP - 9 VL - 116 IS - 1-2 SN - 0378-5955, 0378-5955 KW - Index Medicus KW - National Library of Medicine KW - Animals KW - Efferent Pathways -- metabolism KW - Guinea Pigs KW - GTP-Binding Proteins -- chemistry KW - Organ of Corti -- metabolism KW - Hair Cells, Auditory -- metabolism KW - Synaptosomal-Associated Protein 25 KW - GTP-Binding Proteins -- metabolism KW - Nerve Tissue Proteins -- metabolism KW - GTP-Binding Proteins -- immunology KW - Immunohistochemistry KW - Male KW - Female KW - Signal Transduction KW - Cochlea -- metabolism KW - Cochlea -- innervation KW - Membrane Proteins KW - Presynaptic Terminals -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85417643?accountid=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=Hearing+research&rft.atitle=Presynaptic+localization+of+G+protein+isoforms+in+the+efferent+nerve+terminals+of+the+mammalian+cochlea.&rft.au=Kurc%2C+M%3BDodane%2C+V%3BPinto%2C+D+S%3BKachar%2C+B&rft.aulast=Kurc&rft.aufirst=M&rft.date=1998-02-01&rft.volume=116&rft.issue=1-2&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Hearing+research&rft.issn=03785955&rft_id=info:doi/ LA - English DB - ComDisDome N1 - Date revised - 2008-01-14 N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Using joint geometry to determine the motion of the cricoarytenoid joint. AN - 85416803; pmid-9479765 AB - Facet surfaces of the cricoarytenoid joints from two cadaver larynges were digitized. The data were used to compute the optimal axis of rotation for each of the joints in the sense that the computed axis minimized the variance of the joint gap over the full range of joint motion. The optimal axis corresponded to a rocking motion of the arytenoid on the corresponding cricoid. This motion was consistent with experimental data from digitized recordings of vocal fold movement. Using the rigid laryngoscopic view, a similarity in vocal process movement, over the range in motion, between the rocking axis and the vertical axis described in the literature was found, resolving the controversy between two conflicting views of motion of the vocal processes. JF - The Journal of the Acoustical Society of America AU - Selbie, W S AU - Zhang, L AU - Levine, W S AU - Ludlow, C L AD - Voice and Speech Section, National Institute on Deafness and Other Communication Disorders, Bethesda, Maryland 20892-1416, USA. Y1 - 1998/02// PY - 1998 DA - February 1998 SP - 1115 EP - 1127 VL - 103 IS - 2 SN - 0001-4966, 0001-4966 KW - Index Medicus KW - National Library of Medicine KW - Humans KW - Aged KW - Female KW - Male KW - Models, Anatomic KW - Cricoid Cartilage -- physiology KW - Arytenoid Cartilage -- physiology KW - Movement -- physiology KW - Joints -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85416803?accountid=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+the+Acoustical+Society+of+America&rft.atitle=Using+joint+geometry+to+determine+the+motion+of+the+cricoarytenoid+joint.&rft.au=Selbie%2C+W+S%3BZhang%2C+L%3BLevine%2C+W+S%3BLudlow%2C+C+L&rft.aulast=Selbie&rft.aufirst=W&rft.date=1998-02-01&rft.volume=103&rft.issue=2&rft.spage=1115&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+the+Acoustical+Society+of+America&rft.issn=00014966&rft_id=info:doi/ LA - English DB - ComDisDome N1 - Date revised - 2008-01-14 N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Endbulb synapses in the anteroventral cochlear nucleus express a specific subset of AMPA-type glutamate receptor subunits. AN - 85220569; pmid-9437035 AB - The anteroventral cochlear nucleus (AVCN) acts as the first relay center in the conduction of auditory information from the ear to the brain, and it probably performs a crucial role in sound localization. Auditory nerve input to the principal neurons of the AVCN, the spherical bushy cells, appears to be mediated by an excitatory amino acid such as glutamate, which acts at a specialized, large synaptic ending called an endbulb of Held. Presumably, endbulb synapses contain some specific combination of glutamate receptors to facilitate rapid neurotransmission of auditory signals. AMPA glutamate receptor composition at the endbulb synapses was examined with both light and electron microscope immunocytochemistry. Electron microscope localization of AMPA receptors was examined with two techniques, preembedding immunoperoxidase and postembedding immunogold, which provide maximum sensitivity and greatest accuracy, respectively. Dense and frequent labeling was seen with the AMPA receptor subunit antibodies GluR2/3 and GluR4, which were colocalized at the endbulb synapses. In contrast, immunolabeling with antibody to GluR2 was low. These data indicate that the major glutamate receptor at this synapse is an AMPA receptor made up mainly of GluR3 and GluR4 subunits. Receptors composed of these subunits display properties, such as calcium permeability and rapid desensitization, that facilitate their specialized functions in auditory information processing. JF - The Journal of Neuroscience AU - Wang, Y X AU - Wenthold, R J AU - Ottersen, O P AU - Petralia, R S AD - National Institute on Deafness and Other Communication Disorders/National Institutes of Health, Bethesda, Maryland 20892, USA. PY - 1998 SP - 1148 EP - 1160 VL - 18 IS - 3 SN - 0270-6474, 0270-6474 KW - Sound Localization KW - Synapses KW - Calcium KW - Support, U.S. Gov't, P.H.S. KW - Animal KW - Cochlear Nucleus KW - Rats KW - Rats, Sprague-Dawley KW - Neurons KW - Receptors, AMPA KW - Microscopy, Immunoelectron KW - Immunohistochemistry KW - Male KW - Immunoenzyme Techniques UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85220569?accountid=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=Endbulb+synapses+in+the+anteroventral+cochlear+nucleus+express+a+specific+subset+of+AMPA-type+glutamate+receptor+subunits.&rft.au=Wang%2C+Y+X%3BWenthold%2C+R+J%3BOttersen%2C+O+P%3BPetralia%2C+R+S&rft.aulast=Wang&rft.aufirst=Y&rft.date=1998-02-01&rft.volume=18&rft.issue=3&rft.spage=1148&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 - Validating new toxicology tests for regulatory acceptance. AN - 79943612; 9629594 AB - Before a new or revised toxicology test is considered acceptable for safety evaluation of new substances, the test users and the industrial and regulatory decision makers must feel comfortable with it, and the decisions it supports. Comfort with, and the acceptance of, a new test comes after knowing that it has been validated for its proposed use. The validation process is designed to determine the operational characteristics of a test, that is, its reliability and relevance, in addition to its strengths and limitations. The reliability of a test is measured by its reproducibility. Its relevance is judged by its mechanistic relationship to the health effects of concern, and its ability to predict or identify those effects. The U.S. government has recently formed the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) to work with federal agencies and test developers to coordinate the evaluation and adoption of new test methods. The ICCVAM will provide guidance to agencies and other stakeholders on criteria and processes for development, validation, and acceptance of tests; coordinate technical reviews of proposed new tests of interagency interest; facilitate information sharing among agencies; and serve as an interagency resource and communications link with parties outside of the federal government on matters of test method validation. JF - Regulatory toxicology and pharmacology : RTP AU - Zeiger, E AU - Stokes, W S AD - Environmental Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. zeiger@niehs.nih.gov Y1 - 1998/02// PY - 1998 DA - February 1998 SP - 32 EP - 37 VL - 27 IS - 1 Pt 1 SN - 0273-2300, 0273-2300 KW - Index Medicus KW - United States KW - Evaluation Studies as Topic KW - Animals KW - Reproducibility of Results KW - Forecasting KW - Toxicity Tests -- trends KW - Toxicology -- legislation & jurisprudence KW - Toxicology -- organization & administration KW - Toxicity Tests -- standards UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79943612?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Regulatory+toxicology+and+pharmacology+%3A+RTP&rft.atitle=Validating+new+toxicology+tests+for+regulatory+acceptance.&rft.au=Zeiger%2C+E%3BStokes%2C+W+S&rft.aulast=Zeiger&rft.aufirst=E&rft.date=1998-02-01&rft.volume=27&rft.issue=1+Pt+1&rft.spage=32&rft.isbn=&rft.btitle=&rft.title=Regulatory+toxicology+and+pharmacology+%3A+RTP&rft.issn=02732300&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-08-13 N1 - Date created - 1998-08-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dose-dependent prevention of sugar cataracts in galactose-fed dogs by the aldose reductase inhibitor M79175. AN - 79933482; 9533847 AB - Sugar cataracts rapidly develop in dogs fed a diet containing 30% galactose. While studies on the formation and progression of these sugar cataracts suggest that they are osmotic in nature and are linked to aldose reductase, sugar cataract formation in the dog to date has not been completely prevented by the administration of aldose reductase inhibitors sorbinil and M79175. To demonstrate that the formation and progression of sugar cataracts in galactose-fed dogs can be dose-dependently inhibited by the administration of aldose reductase inhibitors, 9-month old male beagles were placed on diet containing 30% galactose with/without 10 or 16 mg kg-1 day-1 of M79175 for up to 39 months. Cataract progression in all dogs was followed by periodic slit lamp examination and documented by retroillumination photography. Although large variations in cataract formation and progression were observed, all dogs fed a 30% galactose diet for 39 months developed cataracts. Lens changes were significantly less in galactose-fed dogs treated with either 10 or 16 mg kg-1 M79175 and no cataract formation was observed in 3 of 6 galactose-fed dogs treated with 16 mg kg-1 M79175. These observations confirm that aldose reductase plays a key role in initiating cataract formation in galactose-fed dogs and that cataract formation can be prevented by adequate inhibition of aldose reductase. Copyright 1998 Academic Press Limited. JF - Experimental eye research AU - Sato, S AU - Mori, K AU - Wyman, M AU - Kador, P F AD - Laboratory of Ocular Therapeutics, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892-1850, USA. Y1 - 1998/02// PY - 1998 DA - February 1998 SP - 217 EP - 222 VL - 66 IS - 2 SN - 0014-4835, 0014-4835 KW - Dietary Carbohydrates KW - 0 KW - Enzyme Inhibitors KW - Imidazoles KW - Imidazolidines KW - M 79175 KW - 82319-87-7 KW - Aldehyde Reductase KW - EC 1.1.1.21 KW - Galactose KW - X2RN3Q8DNE KW - Index Medicus KW - Animals KW - Dietary Carbohydrates -- toxicity KW - Dose-Response Relationship, Drug KW - Dogs KW - Male KW - Imidazoles -- pharmacology KW - Galactose -- administration & dosage KW - Cataract -- chemically induced KW - Enzyme Inhibitors -- pharmacology KW - Galactose -- toxicity KW - Aldehyde Reductase -- antagonists & inhibitors KW - Aldehyde Reductase -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79933482?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Traumatic+Stress&rft.atitle=International+tourists%E2%80%99+reactions+to+a+natural+disaster%3A+Experiences+of+the+2015+earthquake+in+Nepal+among+Israeli+travelers&rft.au=Itzhaky%2C+Haya%3BKissil%2C+Karni%3BWeiss%E2%80%90Dagan%2C+Shlomit&rft.aulast=Itzhaky&rft.aufirst=Haya&rft.date=2016-12-01&rft.volume=29&rft.issue=6&rft.spage=522&rft.isbn=&rft.btitle=&rft.title=Journal+of+Traumatic+Stress&rft.issn=08949867&rft_id=info:doi/10.1002%2Fjts.22136 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-06-24 N1 - Date created - 1998-06-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Endocrine effects of nicotine administration, tobacco and other drug withdrawal in humans. AN - 79927354; 9621394 AB - The focus of this manuscript is on the effects of smoking and tobacco withdrawal on the hypothalamic-pituitary axis (HPA). A variety of studies have shown that nicotine administered intravenously or through intense cigarette smoking can induce changes in hormones associated with the HPA. Administration of, and abrupt cessation from, other drugs of abuse has also been shown to affect levels of these hormones. Additionally, many of the symptoms of stress and tobacco withdrawal overlap suggesting that the hormonal changes seen during periods of stress may be observed during tobacco abstinence. These findings led to a study of the effects of tobacco withdrawal on plasma ACTH, cortisol, and prolactin levels. The results indicated tobacco cessation caused small and transient effects on plasma hormone levels which were not significantly influenced by nicotine replacement and were not related to other signs of withdrawal. JF - Psychoneuroendocrinology AU - Pickworth, W B AU - Fant, R V AD - National Institute on Drug Abuse, Addiction Research Center, Baltimore, MD 21224, USA. wpickwo@irp.nida.nih.gov Y1 - 1998/02// PY - 1998 DA - February 1998 SP - 131 EP - 141 VL - 23 IS - 2 SN - 0306-4530, 0306-4530 KW - Nicotinic Agonists KW - 0 KW - Nicotine KW - 6M3C89ZY6R KW - Index Medicus KW - Hypothalamo-Hypophyseal System -- drug effects KW - Animals KW - Humans KW - Smoking -- physiopathology KW - Substance Withdrawal Syndrome -- physiopathology KW - Nicotine -- pharmacology KW - Endocrine Glands -- drug effects KW - Smoking Cessation KW - Nicotinic Agonists -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79927354?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psychoneuroendocrinology&rft.atitle=Endocrine+effects+of+nicotine+administration%2C+tobacco+and+other+drug+withdrawal+in+humans.&rft.au=Pickworth%2C+W+B%3BFant%2C+R+V&rft.aulast=Pickworth&rft.aufirst=W&rft.date=1998-02-01&rft.volume=23&rft.issue=2&rft.spage=131&rft.isbn=&rft.btitle=&rft.title=Psychoneuroendocrinology&rft.issn=03064530&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-08-26 N1 - Date created - 1998-08-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ifenprodil blocks the excitatory effects of the opioid peptide dynorphin 1-17 on NMDA receptor-mediated currents in the CA3 region of the guinea pig hippocampus. AN - 79831943; 9571650 AB - This study found that dynorphin had a biphasic concentration response relationship on N-methyl-D-aspartate (NMDA) receptor-mediated currents in the CA3 region of the guinea pig hippocampal slice. A previous study demonstrated that the inhibitory effect was mediated by a kappa 2 opioid receptor. In the present study, the polyamine site antagonist ifenprodil converted dynorphin's biphasic concentration response relationship to a monophasic inhibitory curve. The polyamine diethylenetriamine also blocked dynorphin's excitatory actions. The combination of dynorphin 1-17 and naloxone produced neurotoxicity, presumably as a result of dynorphin's excitatory actions on NMDA receptors. In addition, the release of endogenous dynorphin from mossy fibers in the presence of naloxone injured the cells. Ifenprodil prevented the neurotoxicity of both applied and released dynorphin. These findings suggest that dynorphin acts at a polyamine site to produce its excitatory effects and, further, suggest that dynorphin may mediate some neuropathologies through its interaction at this site. JF - Neuropeptides AU - Caudle, R M AU - Dubner, R AD - Pain and Neurosensory Mechanisms Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892, USA. Robert Caudle@NIH.GOV Y1 - 1998/02// PY - 1998 DA - February 1998 SP - 87 EP - 95 VL - 32 IS - 1 SN - 0143-4179, 0143-4179 KW - Excitatory Amino Acid Antagonists KW - 0 KW - Narcotic Antagonists KW - Piperidines KW - Polyamines KW - Receptors, N-Methyl-D-Aspartate KW - diethylenetriamine KW - 03K6SX4V2J KW - Naloxone KW - 36B82AMQ7N KW - Dynorphins KW - 74913-18-1 KW - ifenprodil KW - R8OE3P6O5S KW - Index Medicus KW - Naloxone -- pharmacology KW - Animals KW - Polyamines -- pharmacology KW - Electric Conductivity KW - Guinea Pigs KW - Electric Stimulation KW - Narcotic Antagonists -- pharmacology KW - Male KW - Binding Sites KW - Piperidines -- pharmacology KW - Receptors, N-Methyl-D-Aspartate -- physiology KW - Hippocampus -- physiology KW - Receptors, N-Methyl-D-Aspartate -- drug effects KW - Receptors, N-Methyl-D-Aspartate -- antagonists & inhibitors KW - Excitatory Amino Acid Antagonists -- pharmacology KW - Dynorphins -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79831943?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuropeptides&rft.atitle=Ifenprodil+blocks+the+excitatory+effects+of+the+opioid+peptide+dynorphin+1-17+on+NMDA+receptor-mediated+currents+in+the+CA3+region+of+the+guinea+pig+hippocampus.&rft.au=Caudle%2C+R+M%3BDubner%2C+R&rft.aulast=Caudle&rft.aufirst=R&rft.date=1998-02-01&rft.volume=32&rft.issue=1&rft.spage=87&rft.isbn=&rft.btitle=&rft.title=Neuropeptides&rft.issn=01434179&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-06-11 N1 - Date created - 1998-06-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetic influences in antisocial personality and drug use disorders. AN - 79831494; 9571383 AB - While an association between antisocial personality disorder (APD) and substance use disorder (SUD) has been frequently observed, the causes of the comorbidity remain unclear. Adoption and twin studies have found evidence of both genetic and environmental influences in APD and SUD. Therefore, comorbidity between APD and SUD may be the result of shared genetic influences, shared environmental influences, or a combination of the two. However, only a limited number of adoption and twin studies have addressed this issue and the results have not been conclusive. In future studies, a distinction should be made between alcohol and drug abuse and between juvenile and adult APD symptoms. Twin samples of adequate size would allow use of structural equation analytical methods for estimation of the relative magnitude of genetic and environmental influences shared between the two conditions, as well as influences contributing to each specifically. Results would be highly relevant for the clinical setting as well as for efforts to identify the genes involved in either trait. JF - Drug and alcohol dependence AU - van den Bree, M B AU - Svikis, D S AU - Pickens, R W AD - Intramural Research Program, National Institute on Drug Abuse, Baltimore, Maryland 21224, USA. mvandenb@irp.nida.nih.gov Y1 - 1998/02/01/ PY - 1998 DA - 1998 Feb 01 SP - 177 EP - 187 VL - 49 IS - 3 SN - 0376-8716, 0376-8716 KW - Index Medicus KW - Environment KW - Humans KW - Adult KW - Twin Studies as Topic KW - Adoption KW - Research Design KW - Family Health KW - Comorbidity KW - Antisocial Personality Disorder -- epidemiology KW - Antisocial Personality Disorder -- genetics KW - Substance-Related Disorders -- genetics KW - Substance-Related Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79831494?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Genetic+influences+in+antisocial+personality+and+drug+use+disorders.&rft.au=van+den+Bree%2C+M+B%3BSvikis%2C+D+S%3BPickens%2C+R+W&rft.aulast=van+den+Bree&rft.aufirst=M&rft.date=1998-02-01&rft.volume=49&rft.issue=3&rft.spage=177&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 - 1998-08-06 N1 - Date created - 1998-08-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - New delta-opioid antagonists as pharmacological probes. AN - 79808768; 9550939 JF - Trends in pharmacological sciences AU - Bryant, S D AU - Salvadori, S AU - Cooper, P S AU - Lazarus, L H AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 22709, USA. Y1 - 1998/02// PY - 1998 DA - February 1998 SP - 42 EP - 46 VL - 19 IS - 2 SN - 0165-6147, 0165-6147 KW - Ligands KW - 0 KW - Narcotic Antagonists KW - Oligopeptides KW - Receptors, Opioid, delta KW - Receptors, Opioid, kappa KW - Receptors, Opioid, mu KW - Tetrahydroisoquinolines KW - tyrosyl-1,2,3,4-tetrahydro-3-isoquinolinecarbonyl-phenylalanyl-phenylalanine KW - 146369-65-5 KW - Index Medicus KW - Receptors, Opioid, mu -- antagonists & inhibitors KW - Receptors, Opioid, kappa -- antagonists & inhibitors KW - Oligopeptides -- pharmacology KW - Opioid-Related Disorders -- genetics KW - Molecular Conformation KW - Drug Design KW - Cloning, Molecular KW - Receptors, Opioid, delta -- antagonists & inhibitors KW - Receptors, Opioid, delta -- genetics KW - Narcotic Antagonists -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79808768?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=New+delta-opioid+antagonists+as+pharmacological+probes.&rft.au=Bryant%2C+S+D%3BSalvadori%2C+S%3BCooper%2C+P+S%3BLazarus%2C+L+H&rft.aulast=Bryant&rft.aufirst=S&rft.date=1998-02-01&rft.volume=19&rft.issue=2&rft.spage=42&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 - 1998-05-07 N1 - Date created - 1998-05-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular modeling of cytochrome P450 2B1: mode of membrane insertion and substrate specificity. AN - 79779255; 9535274 AB - A molecular model of a mammalian membrane-bound cytochrome P450, rat P450 2B1, was constructed in order to elucidate its mode of attachment to the endoplasmic reticulum and the structural basis of substrate specificity. The model was primarily derived from the structure of P450BM-3, which as a class II P450 is the most functionally similar P450 of known structure. However, model development was also guided by the conserved core regions of P450cam and P450terp. To optimally align the P450 2B1 and P450BM-3 sequences, multiple alignment was performed using sequences of five P450s in the II family, followed by minor adjustments on the basis of secondary structure predictions. The resulting P450 2B1 homology model structure was refined by molecular dynamics heating, equilibration, simulation, and energy minimization. The model suggests that the F-G loop serves as both a hydrophobic membrane anchor and entrance channel for hydrophobic substrates from the membrane to the P450 active site. To assess the mode of substrate binding, benzphetamine, testosterone, and benzo[a]pyrene were docked into the active site. The hydrophobic substrate-binding pocket is consistent with the preferences of this P450 toward hydrophobic substrates, while the presence of an acidic Glu-105 in this pocket is consistent with the preference of this P450 for the cationic substrate benzphetamine. This model is thus consistent with several known experimental properties of this P450, such as membrane attachment and substrate selectivity. JF - Journal of protein chemistry AU - Dai, R AU - Pincus, M R AU - Friedman, F K AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1998/02// PY - 1998 DA - February 1998 SP - 121 EP - 129 VL - 17 IS - 2 SN - 0277-8033, 0277-8033 KW - Membrane Proteins KW - 0 KW - Benzphetamine KW - 0M3S43XK27 KW - Benzo(a)pyrene KW - 3417WMA06D KW - Testosterone KW - 3XMK78S47O KW - Cytochrome P-450 CYP2B1 KW - EC 1.14.14.1 KW - Index Medicus KW - Rats KW - Animals KW - Protein Structure, Secondary KW - Testosterone -- metabolism KW - Models, Molecular KW - Molecular Sequence Data KW - Benzphetamine -- metabolism KW - Amino Acid Sequence KW - Substrate Specificity KW - Sequence Homology, Amino Acid KW - Binding Sites KW - Benzo(a)pyrene -- metabolism KW - Membrane Proteins -- chemistry KW - Membrane Proteins -- metabolism KW - Cytochrome P-450 CYP2B1 -- metabolism KW - Cytochrome P-450 CYP2B1 -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79779255?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+protein+chemistry&rft.atitle=Molecular+modeling+of+cytochrome+P450+2B1%3A+mode+of+membrane+insertion+and+substrate+specificity.&rft.au=Dai%2C+R%3BPincus%2C+M+R%3BFriedman%2C+F+K&rft.aulast=Dai&rft.aufirst=R&rft.date=1998-02-01&rft.volume=17&rft.issue=2&rft.spage=121&rft.isbn=&rft.btitle=&rft.title=Journal+of+protein+chemistry&rft.issn=02778033&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-05-18 N1 - Date created - 1998-05-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The U.S. National Toxicology Program evaluation of transgenic mice as predictive models for identifying carcinogens. AN - 79778494; 9539007 AB - National Institute of Environmental Health Sciences researchers have invested considerable effort in exploring the utility of transgenic mice to detect carcinogens and study mechanisms of carcinogenesis. Work has assessed several mouse models genetically altered to enhance their expression of chemically induced tumors. Results with the p53def (hemizygous for the tumor-suppressor gene) and the Tg.AC (carrier of an activated H-ras oncogene) mice have been used as a basis for a proposed new strategy for identifying chemical carcinogens and assessing risk. The U.S. National Toxicology Program is conducting a series of studies with these two transgenic strains to further examine their strengths and weaknesses for identification of documented rodent and human carcinogens and to explore their ability to provide information concerning the effective dosimetry for target organ mutation. JF - Environmental health perspectives AU - Eastin, W C AD - Experimental Toxicology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. eastin@niehs.nih.gov Y1 - 1998/02// PY - 1998 DA - February 1998 SP - 81 EP - 84 VL - 106 Suppl 1 SN - 0091-6765, 0091-6765 KW - Index Medicus KW - Animals KW - Genes, p53 -- physiology KW - Humans KW - Genes, ras -- physiology KW - Mice KW - Carcinogenicity Tests KW - Mice, Transgenic UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79778494?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+health+perspectives&rft.atitle=The+U.S.+National+Toxicology+Program+evaluation+of+transgenic+mice+as+predictive+models+for+identifying+carcinogens.&rft.au=Eastin%2C+W+C&rft.aulast=Eastin&rft.aufirst=W&rft.date=1998-02-01&rft.volume=106+Suppl+1&rft.issue=&rft.spage=81&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 - 1998-04-23 N1 - Date created - 1998-04-23 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1990 Dec;87(23):9178-82 [2251261] Nature. 1992 Mar 19;356(6366):215-21 [1552940] Environ Health Perspect. 1993 Apr;100:307-15 [8354178] Mutat Res. 1996 Sep;365(1-3):119-27 [8898993] Carcinogenesis. 1996 Feb;17(2):177-84 [8625435] Environ Health Perspect. 1996 Jan;104(1):84-8 [8834866] Environ Health Perspect. 1995 Oct;103(10):942-50 [8529591] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Carcinogenesis studies of tetrahydrofuran vapors in rats and mice. AN - 79761024; 9520354 AB - Tetrahydrofuran (THF) is a widely used industrial solvent and was selected for carcinogenesis studies by the National Toxicology Program (NTP) because of its potential for widespread occupational exposure in humans and a lack of information on animal toxicity and carcinogenicity. Groups of 50 male and 50 female F344/N rats and B6C3F1 mice were exposed to 0, 200, 600, or 1800 ppm THF by inhalation, 6 h per day, 5 days per week, for 105 weeks. Survival and mean body weights of male and female rats exposed to THF were comparable to that of the controls. No clinical findings or nonneoplastic lesions related to THF exposure were observed in male or female rats. The incidences of renal tubule epithelial adenoma or carcinoma (combined) in exposed male rats occurred with a positive trend, and in males exposed to 600 and 1800 ppm exceeded the historical range for controls in 2-year NTP inhalation studies. There were no other neoplastic lesions related to THF exposure observed in male or female rats. After week 36, the survival of male mice exposed to 1800 ppm was significantly lower than that of the controls. Mean body weights of male and female mice exposed to THF were similar to those of the controls throughout the study. Male mice exposed to 1800 ppm were observed in a state of narcosis during and up to 1 h after the exposure periods. Nonneoplastic lesions related to THF exposure were not observed in male or female mice. The neoplastic lesions related to THF exposure were seen in female mice only. In female mice exposed to 1800 ppm, the incidences of hepatocellular neoplasms were significantly greater than those in the controls. In conclusion, there was some evidence of carcinogenic activity of THF in male F344/N rats due to increased incidences of adenoma or carcinoma (combined) of the kidney at the 600 and 1800 ppm exposure levels. There was clear evidence of carcinogenic activity in female B6C3F1 mice based on increased incidences of hepatocellular neoplasms at the 1800 ppm exposure level. THF was not carcinogenic in female rats or male mice exposed at 200, 600, or 1800 ppm. Copyright 1998 Academic Press. JF - Toxicological sciences : an official journal of the Society of Toxicology AU - Chhabra, R S AU - Herbert, R A AU - Roycroft, J H AU - Chou, B AU - Miller, R A AU - Renne, R A AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1998/02// PY - 1998 DA - February 1998 SP - 183 EP - 188 VL - 41 IS - 2 SN - 1096-6080, 1096-6080 KW - Furans KW - 0 KW - Solvents KW - tetrahydrofuran KW - 3N8FZZ6PY4 KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Kidney Neoplasms -- chemically induced KW - Liver Neoplasms -- chemically induced KW - Carcinogenicity Tests KW - Volatilization KW - Mice KW - Male KW - Female KW - Solvents -- toxicity KW - Furans -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79761024?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.atitle=Carcinogenesis+studies+of+tetrahydrofuran+vapors+in+rats+and+mice.&rft.au=Chhabra%2C+R+S%3BHerbert%2C+R+A%3BRoycroft%2C+J+H%3BChou%2C+B%3BMiller%2C+R+A%3BRenne%2C+R+A&rft.aulast=Chhabra&rft.aufirst=R&rft.date=1998-02-01&rft.volume=41&rft.issue=2&rft.spage=183&rft.isbn=&rft.btitle=&rft.title=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.issn=10966080&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-05-28 N1 - Date created - 1998-05-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - CD40 ligand and IFN-gamma synergistically restore IL-12 production in HIV-infected patients. AN - 79750265; 9521075 AB - IL-12 production in HIV-infected (HIV+) individuals is severely impaired after stimulation by bacterial products or T cell-dependent stimuli. Because CD40-CD40 ligand (CD40L) interactions are the major mechanism involved in the T cell-dependent activation of antigen-presenting cells, we investigated whether this pathway was functional in HIV+ donors. CD40 expression was increased on freshly isolated monocytes from HIV+ individuals compared to HIV donors. However, equivalent CD40 expression was obtained in the two groups after cytokine stimulation. Since CD40 expression was intact in HIV+ donors' cells, we determined whether IL-12 production could be restored by providing exogenous T cell-dependent stimuli, CD40L and IFN-gamma, at the time of bacterial stimulation. IL-12 production was not altered by CD40L alone, was increased by IFN-gamma, and was synergistically restored to normal values by IFN-gamma + CD40L. This combination was more efficient for enhancing IL-12 production than granulocyte-macrophage colony-stimulating factor + CD40L or neutralizing anti-IL-10 antibody + CD40L. CD40L did not affect IL-10 production, whereas IFN-gamma significantly decreased it. This study demonstrates that the defect in IL-12 production by leukocytes from HIV+ donors can be overcome in vitro if the interacting cells are provided with the right T cell-dependent co-stimuli. JF - European journal of immunology AU - Chougnet, C AU - Thomas, E AU - Landay, A L AU - Kessler, H A AU - Buchbinder, S AU - Scheer, S AU - Shearer, G M AD - Experimental Immunology Branch, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1998/02// PY - 1998 DA - February 1998 SP - 646 EP - 656 VL - 28 IS - 2 SN - 0014-2980, 0014-2980 KW - Antibodies KW - 0 KW - Antigens, CD40 KW - Interleukin-1 KW - Ligands KW - Membrane Glycoproteins KW - Recombinant Proteins KW - CD40 Ligand KW - 147205-72-9 KW - Interleukin-12 KW - 187348-17-0 KW - Interferon-gamma KW - 82115-62-6 KW - Index Medicus KW - AIDS/HIV KW - Recombinant Proteins -- pharmacology KW - Interleukin-1 -- immunology KW - Humans KW - HIV Seronegativity -- immunology KW - Blood Donors KW - HIV Seropositivity -- immunology KW - Lymphocyte Activation KW - Interleukin-1 -- metabolism KW - Antibodies -- pharmacology KW - Monocytes -- metabolism KW - Adult KW - Leukocytes, Mononuclear -- metabolism KW - Drug Synergism KW - T-Lymphocytes -- immunology KW - Antigens, CD40 -- biosynthesis KW - Membrane Glycoproteins -- physiology KW - Interleukin-12 -- biosynthesis KW - HIV Infections -- immunology KW - Interferon-gamma -- pharmacology KW - Antigens, CD40 -- metabolism KW - Membrane Glycoproteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79750265?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+Social+Work&rft.atitle=The+challenges+of+realising+social+justice+in+21+%26lt%3Bsup%26gt%3Bst%26lt%3B%2Fsup%26gt%3B+century+social+work&rft.au=Dominelli%2C+Lena%3BIoakimidis%2C+Vasilios&rft.aulast=Dominelli&rft.aufirst=Lena&rft.date=2016-11-01&rft.volume=59&rft.issue=6&rft.spage=693&rft.isbn=&rft.btitle=&rft.title=International+Social+Work&rft.issn=00208728&rft_id=info:doi/10.1177%2F0020872816665981 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-31 N1 - Date created - 1998-03-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phase II trial of topotecan administered as 72-hour continuous infusion in children with refractory solid tumors: a collaborative Pediatric Branch, National Cancer Institute, and Children's Cancer Group Study. AN - 79746244; 9516923 AB - The antitumor activity of topotecan administered as a 72-h continuous i.v. infusion was evaluated in children with refractory neuroblastoma and sarcomas of soft tissue and bone. We also attempted to increase the dose intensity of topotecan by including an intrapatient dose escalation in the trial design. Ninety-three children (85 eligible and evaluable for response) with recurrent or refractory neuroblastoma, osteosarcoma, Ewing's sarcoma/peripheral neuroectodermal tumor, rhabdomyosarcoma, or other soft-tissue sarcomas received topotecan administered as a 72-h i.v. infusion every 21 days. The initial dose was 1.0 mg/m2/day, with subsequent intrapatient dose escalation to 1.3 mg/m2/day for those patients who did not experience dose-limiting toxicity after their first cycle of topotecan. There was one complete response in a patient with neuroblastoma (n = 26) and one partial response in a patient with Ewing's sarcoma/peripheral neuroectodermal tumor (n = 25). No complete or partial responses were observed in 17 patients with osteosarcoma, 15 patients with rhabdomyosarcoma, or 2 patients with other soft-tissue sarcomas; however, 8 patients had prolonged (15-48 weeks) stable disease while receiving topotecan. Topotecan was well tolerated. The most commonly observed toxicities were myelosuppression (dose-limiting) and nausea and vomiting. Intrapatient dose escalations were performed in 68% of the patients who received more than one cycle of topotecan, and 1.3 mg/m2/day was tolerated by 79% of the patients who received the higher dose and were evaluable for hematological toxicity. In conclusion, topotecan administered as a 72-h continuous infusion every 21 days is inactive (objective response rate, < 20%) in children with refractory or recurrent neuroblastoma and sarcomas of soft tissue or bone. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Blaney, S M AU - Needle, M N AU - Gillespie, A AU - Sato, J K AU - Reaman, G H AU - Berg, S L AU - Adamson, P C AU - Krailo, M D AU - Bleyer, W A AU - Poplack, D G AU - Balis, F M AD - Pediatric Branch, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1998/02// PY - 1998 DA - February 1998 SP - 357 EP - 360 VL - 4 IS - 2 SN - 1078-0432, 1078-0432 KW - Antineoplastic Agents KW - 0 KW - Topotecan KW - 7M7YKX2N15 KW - Index Medicus KW - Osteosarcoma -- drug therapy KW - Drug Administration Schedule KW - Infusions, Intravenous KW - Dose-Response Relationship, Drug KW - Humans KW - Soft Tissue Neoplasms -- drug therapy KW - Child KW - Sarcoma, Ewing -- drug therapy KW - Child, Preschool KW - Infant KW - Neuroblastoma -- drug therapy KW - Adult KW - Bone Neoplasms -- drug therapy KW - Rhabdomyosarcoma -- drug therapy KW - Adolescent KW - Neuroectodermal Tumors, Primitive, Peripheral -- drug therapy KW - Female KW - Male KW - Topotecan -- adverse effects KW - Neoplasms -- drug therapy KW - Antineoplastic Agents -- therapeutic use KW - Topotecan -- therapeutic use KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79746244?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=Phase+II+trial+of+topotecan+administered+as+72-hour+continuous+infusion+in+children+with+refractory+solid+tumors%3A+a+collaborative+Pediatric+Branch%2C+National+Cancer+Institute%2C+and+Children%27s+Cancer+Group+Study.&rft.au=Blaney%2C+S+M%3BNeedle%2C+M+N%3BGillespie%2C+A%3BSato%2C+J+K%3BReaman%2C+G+H%3BBerg%2C+S+L%3BAdamson%2C+P+C%3BKrailo%2C+M+D%3BBleyer%2C+W+A%3BPoplack%2C+D+G%3BBalis%2C+F+M&rft.aulast=Blaney&rft.aufirst=S&rft.date=1998-02-01&rft.volume=4&rft.issue=2&rft.spage=357&rft.isbn=&rft.btitle=&rft.title=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10780432&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-04-09 N1 - Date created - 1998-04-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Carbon disulfide neurotoxicity in rats: I. Introduction and study design. AN - 79722977; 9498224 JF - Neurotoxicology AU - Sills, R C AU - Morgan, D L AU - Harry, G J AD - Environmental Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, N.C. 27709, USA. Y1 - 1998/02// PY - 1998 DA - February 1998 SP - 83 EP - 87 VL - 19 IS - 1 SN - 0161-813X, 0161-813X KW - Carbon Disulfide KW - S54S8B99E8 KW - Index Medicus KW - Rats KW - Body Weight KW - Neurophysiology -- methods KW - Animals KW - Rats, Inbred F344 KW - Drug Administration Schedule KW - Administration, Inhalation KW - Male KW - Female KW - Carbon Disulfide -- toxicity KW - Nervous System -- drug effects KW - Research Design KW - Carbon Disulfide -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79722977?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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&rft.atitle=Carbon+disulfide+neurotoxicity+in+rats%3A+I.+Introduction+and+study+design.&rft.au=Sills%2C+R+C%3BMorgan%2C+D+L%3BHarry%2C+G+J&rft.aulast=Sills&rft.aufirst=R&rft.date=1998-02-01&rft.volume=19&rft.issue=1&rft.spage=83&rft.isbn=&rft.btitle=&rft.title=Neurotoxicology&rft.issn=0161813X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-04-21 N1 - Date created - 1998-04-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Human glutathione S-transferase P1 polymorphisms: relationship to lung tissue enzyme activity and population frequency distribution. AN - 79721271; 9498276 AB - The association between glutathione S-transferase (GST) activity as measured by 1-chloro-2,4-dinitrobenzene (CDNB) conjugation and genotype at exon 5 and exon 6 of the human GSTP1 gene was investigated in normal lung tissue obtained from 34 surgical patients. These samples were genotyped for previously identified polymorphisms in exon 5 (Ile105Val) and exon 6 (Ala114Val) by PCR-RFLP and direct sequencing. GST enzyme activity was significantly lower among individuals with the 105 Val allele. Homozygous Ile/Ile samples (n = 18) had a mean cytosolic CDNB conjugating activity of 74.9 +/- 3.8 nmol/mg per min; heterozygotes (n = 13) had a mean specific activity of 62.1 +/- 4.2 nmol/mg per min and homozygous Val/Val (n = 3) had a mean specific activity of 52.5 +/- 4.5 nmol/mg per min. The CDNB conjugating activity measured for the Ile/Ile genotype group was significantly different from that observed in the Ile/Val group (P = 0.03), and from Ile/Val and Val/Val genotypes combined (P = 0.009). Mean GST activity values were consistently lower in individuals with genotypes containing the 105 valine allele, regardless of smoking exposure. Genotypes at codon 114 were also assessed but the mean GST activity was not significantly lower in individuals with the 114 valine allele. A new haplotype, present in two samples who were homozygous 105Ile and had a 114Val, was identified and proposed as GSTP1*D. Frequencies of the exon 5 and exon 6 polymorphisms were determined in samples obtained from European-Americans, African-Americans and Taiwanese. The differences observed were highly significant suggesting the possibility of GSTP1 genotype-associated, ethnic differences in cancer susceptibility and chemotherapeutic response. JF - Carcinogenesis AU - Watson, M A AU - Stewart, R K AU - Smith, G B AU - Massey, T E AU - Bell, D A AD - Laboratory of Computational Biology and Risk Assessment, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1998/02// PY - 1998 DA - February 1998 SP - 275 EP - 280 VL - 19 IS - 2 SN - 0143-3334, 0143-3334 KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Index Medicus KW - Genotype KW - Polymerase Chain Reaction KW - African Continental Ancestry Group -- genetics KW - Polymorphism, Restriction Fragment Length KW - Polymorphism, Genetic KW - Humans KW - Taiwan -- epidemiology KW - United States -- epidemiology KW - European Continental Ancestry Group -- genetics KW - Asian Continental Ancestry Group -- genetics KW - Polymorphism, Single-Stranded Conformational KW - Continental Population Groups -- genetics KW - Gene Frequency KW - Glutathione Transferase -- metabolism KW - Lung -- enzymology KW - Glutathione Transferase -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79721271?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Human+glutathione+S-transferase+P1+polymorphisms%3A+relationship+to+lung+tissue+enzyme+activity+and+population+frequency+distribution.&rft.au=Watson%2C+M+A%3BStewart%2C+R+K%3BSmith%2C+G+B%3BMassey%2C+T+E%3BBell%2C+D+A&rft.aulast=Watson&rft.aufirst=M&rft.date=1998-02-01&rft.volume=19&rft.issue=2&rft.spage=275&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-24 N1 - Date created - 1998-03-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tetravinyl-tetramethylcyclo-tetrasiloxane (tetravinyl D4) is a mutagen in Rat2lambda lacI fibroblasts. AN - 79719855; 9498283 AB - Small fragments of silicone gels injected intraperitoneally have been used to induce plasmacytomas in genetically susceptible mice. Silicone oils, in contrast to silicone gels, are apparently not tumorigenic in the mouse plasmacytoma system. The reason for this difference as well as the mechanism of silicone gel-induced plasmacytoma development is poorly understood. We chose to examine the possibility that low molecular wt silicone compounds such as siloxanes, leaking from the complex silicone gel matrix into the surrounding tissue, may be mutagenic. We postulate that this mutagenicity may be a critical determinant of the plasmacytoma inducing potency of silicone gels. Six siloxane compounds, either linear or cyclic di-, tri-, or tetrasiloxanes substituted with methyl or vinyl moieties, were selected as model compounds to study mutagenicity in Rat2lambda lacI fibroblasts in vitro. Using phage lambda-derived lacI/lacZ genes as target/reporter genes to quantitate mutagenesis, and gamma-cyclodextrin as vehicle to effectively deliver siloxanes, we found that exposure to 50 microM of tetravinyl-tetramethylcyclo-tetrasiloxane (tetravinyl D4) resulted in a modest 1.7-fold increase of mutant frequencies over controls in Rat2lambda lacI cells. In related toxicity experiments, tetravinyl D4 was shown to perturb lipid membranes leading to a loss of cytosolic glutathione (GSH), which by itself resulted in a 1.5-fold increased mutant rate in Rat2lambda lacI cells. We conclude that certain siloxanes may act as direct mutagens in mammalian cells. In addition, siloxane-induced mutagenicity may be enhanced by the depletion of intracellular GSH caused by the interaction of lipophilic siloxanes with cell membranes. JF - Carcinogenesis AU - Felix, K AU - Lin, S AU - Bornkamm, G W AU - Janz, S AD - Laboratory of Genetics, DBS, NCI, NIH, Bethesda, MD 20892, USA. felixk@dc37a.nci.nih.gov Y1 - 1998/02// PY - 1998 DA - February 1998 SP - 315 EP - 320 VL - 19 IS - 2 SN - 0143-3334, 0143-3334 KW - Heterocyclic Compounds KW - 0 KW - Mutagens KW - Siloxanes KW - tetravinyl-tetramethylcyclo-tetrasiloxane KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Index Medicus KW - Rats KW - Glutathione Transferase -- physiology KW - Fibroblasts -- drug effects KW - Animals KW - Mutagenicity Tests KW - Cells, Cultured KW - Lac Operon KW - Siloxanes -- pharmacology KW - Heterocyclic Compounds -- pharmacology KW - Mutagens -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79719855?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Tetravinyl-tetramethylcyclo-tetrasiloxane+%28tetravinyl+D4%29+is+a+mutagen+in+Rat2lambda+lacI+fibroblasts.&rft.au=Felix%2C+K%3BLin%2C+S%3BBornkamm%2C+G+W%3BJanz%2C+S&rft.aulast=Felix&rft.aufirst=K&rft.date=1998-02-01&rft.volume=19&rft.issue=2&rft.spage=315&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-24 N1 - Date created - 1998-03-24 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Carcinogenesis. 1999 Aug;20(8):1653-4 [10426824] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Isolation of recombinant secretory proteins by limited induction and quantitative harvest. AN - 79715123; 9494711 JF - BioTechniques AU - Rosenberg, H F AD - Laboratory of Host Defenses, NIAID/NIH, Bethesda, MD 20892, USA. Y1 - 1998/02// PY - 1998 DA - February 1998 SP - 188 EP - 90, 192 VL - 24 IS - 2 SN - 0736-6205, 0736-6205 KW - Bacterial Proteins KW - 0 KW - Neurotoxins KW - Oligopeptides KW - Peptides KW - Protein Sorting Signals KW - Recombinant Proteins KW - Isopropyl Thiogalactoside KW - 367-93-1 KW - FLAG peptide KW - 98849-88-8 KW - Eosinophil-Derived Neurotoxin KW - EC 3.1.- KW - Ribonucleases KW - Index Medicus KW - Periplasm -- chemistry KW - Bacterial Proteins -- genetics KW - Protein Sorting Signals -- genetics KW - Plasmids -- genetics KW - Neurotoxins -- genetics KW - Peptides -- immunology KW - Bacterial Proteins -- isolation & purification KW - Peptides -- genetics KW - Isopropyl Thiogalactoside -- pharmacology KW - Ribonucleases -- metabolism KW - Recombinant Proteins -- isolation & purification KW - Recombinant Proteins -- secretion KW - Escherichia coli -- genetics KW - Gene Expression Regulation -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79715123?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Isolation+of+recombinant+secretory+proteins+by+limited+induction+and+quantitative+harvest.&rft.au=Rosenberg%2C+H+F&rft.aulast=Rosenberg&rft.aufirst=H&rft.date=1998-02-01&rft.volume=24&rft.issue=2&rft.spage=188&rft.isbn=&rft.btitle=&rft.title=BioTechniques&rft.issn=07366205&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-04-10 N1 - Date created - 1998-04-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Skeletal muscle-specific immunotoxin for the treatment of focal muscle spasm. AN - 79707660; 9484377 AB - Intramuscular injection of botulinum toxin type A (BTX) is used to treat many disorders characterized by muscular spasms. The utility of BTX, however, is limited by its short duration of action, the development of resistance after repeated injections, and cross-reactivity with autonomic neurons. To overcome these limitations, we engineered an immunotoxin (ITX) to damage skeletal muscle fibers selectively by chemically linking a monoclonal antibody against the nicotinic acetylcholine receptor to the toxin ricin. In vitro, the ITX was 20,000-fold more toxic to myotubes than myoblasts, consistent with the degree of acetylcholine receptor expression. The gastrocnemius muscles of 30 rats were unilaterally injected with a series of protein toxins at various concentrations and examined histopathologically 7 and 30 days later. ITX produced destructive myopathic changes at a dose 300-fold less than the maximum tolerated dose. Assessment of rat muscle strength after unilateral gastrocnemius injections showed that ITX was more effective and had a longer duration of action than BTX. ITXs may have potential for the treatment of involuntary muscle spasms. JF - Neurology AU - Hott, J S AU - Dalakas, M C AU - Sung, C AU - Hallett, M AU - Youle, R J AD - Biochemistry Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1998/02// PY - 1998 DA - February 1998 SP - 485 EP - 491 VL - 50 IS - 2 SN - 0028-3878, 0028-3878 KW - Antibodies, Monoclonal KW - 0 KW - Immunotoxins KW - Muscle Proteins KW - Receptors, Nicotinic KW - Ricin KW - 9009-86-3 KW - Botulinum Toxins, Type A KW - EC 3.4.24.69 KW - Abridged Index Medicus KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Protein Engineering KW - Cell Survival -- drug effects KW - Botulinum Toxins, Type A -- toxicity KW - Mice KW - Receptors, Nicotinic -- immunology KW - Mice, Inbred BALB C KW - Muscle Proteins -- biosynthesis KW - Female KW - Muscular Diseases -- drug therapy KW - Muscle, Skeletal -- pathology KW - Ricin -- toxicity KW - Muscle, Skeletal -- cytology KW - Immunotoxins -- toxicity KW - Ricin -- therapeutic use KW - Immunotoxins -- therapeutic use KW - Spasm -- drug therapy KW - Muscle, Skeletal -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79707660?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurology&rft.atitle=Skeletal+muscle-specific+immunotoxin+for+the+treatment+of+focal+muscle+spasm.&rft.au=Hott%2C+J+S%3BDalakas%2C+M+C%3BSung%2C+C%3BHallett%2C+M%3BYoule%2C+R+J&rft.aulast=Hott&rft.aufirst=J&rft.date=1998-02-01&rft.volume=50&rft.issue=2&rft.spage=485&rft.isbn=&rft.btitle=&rft.title=Neurology&rft.issn=00283878&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-16 N1 - Date created - 1998-03-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Multiple regions of ligand discrimination revealed by analysis of chimeric parathyroid hormone 2 (PTH2) and PTH/PTH-related peptide (PTHrP) receptors. AN - 79701425; 9482662 AB - PTH and PTH-related peptide (PTHrP) bind to the PTH/PTHrP receptor and stimulate cAMP accumulation with similar efficacy. Only PTH activates the PTH2 receptor. To examine the structural basis for this selectivity, we analyzed receptor chimeras in which the amino terminus and third extracellular domains of the two receptors were interchanged. All chimeric receptors bound radiolabeled PTH with high affinity. Transfer of the PTH2 receptor amino terminus to the PTH/PTHrP receptor eliminated high-affinity PTHrP binding and significantly decreased activation by PTHrP. A PTH/PTHrP receptor N terminus modified by deletion of the nonhomologous E2 domain transferred weak PTHrP interaction to the PTH2 receptor. Introduction of the PTH2 receptor third extracellular loop into the PTH/PTHrP receptor increased the EC50 for PTH and PTHrP, while preserving high-affinity PTH binding and eliminating high-affinity PTHrP binding. Similarly, transfer of the PTH/PTHrP receptor third extracellular loop preserved high-affinity PTH binding by the PTH2 receptor but decreased its activation. Return of Gln440 and Arg394, corresponding residues in the PTH/PTHrP and PTH2 receptor third extracellular loops, to the parent residue restored function of these receptors. Simultaneous interchange of wild-type amino termini and third extracellular loops eliminated agonist activation but not binding for both receptors. Function was restored by elimination of the E2 domain in the receptor with a PTH/PTHrP receptor N terminus and return of Gln440/Arg394 to the parent sequence in both receptors. These data suggest that the amino terminus and third extracellular loop of the PTH2 and PTH/PTHrP receptors interact similarly with PTH, and that both domains contribute to differential interaction with PTHrP. JF - Molecular endocrinology (Baltimore, Md.) AU - Clark, J A AU - Bonner, T I AU - Kim, A S AU - Usdin, T B AD - Section on Genetics, National Institute of Mental Health, Bethesda, Maryland 20892-4090, USA. janet@codon.nih.gov Y1 - 1998/02// PY - 1998 DA - February 1998 SP - 193 EP - 206 VL - 12 IS - 2 SN - 0888-8809, 0888-8809 KW - Ligands KW - 0 KW - Receptor, Parathyroid Hormone, Type 1 KW - Receptor, Parathyroid Hormone, Type 2 KW - Receptors, Parathyroid Hormone KW - Recombinant Fusion Proteins KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Animals KW - COS Cells KW - Amino Acid Substitution -- genetics KW - Humans KW - Protein Binding -- genetics KW - Binding Sites -- genetics KW - Protein Structure, Tertiary KW - Recombinant Fusion Proteins -- metabolism KW - Receptors, Parathyroid Hormone -- genetics KW - Receptors, Parathyroid Hormone -- analysis KW - Receptors, Parathyroid Hormone -- chemistry KW - Recombinant Fusion Proteins -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79701425?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Multiple+regions+of+ligand+discrimination+revealed+by+analysis+of+chimeric+parathyroid+hormone+2+%28PTH2%29+and+PTH%2FPTH-related+peptide+%28PTHrP%29+receptors.&rft.au=Clark%2C+J+A%3BBonner%2C+T+I%3BKim%2C+A+S%3BUsdin%2C+T+B&rft.aulast=Clark&rft.aufirst=J&rft.date=1998-02-01&rft.volume=12&rft.issue=2&rft.spage=193&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 - 1998-03-30 N1 - Date created - 1998-03-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A pilot study of 2-chloro-2'-deoxyadenosine in the treatment of systemic lupus erythematosus-associated glomerulonephritis. AN - 79700393; 9485092 AB - To determine the safety and tolerability, as well as the clinical and immunologic effects, of 2-chloro-2'-deoxyadenosine (2-CdA) in patients with systemic lupus erythematosus-associated glomerulonephritis. In a phase I study, 12 patients with proliferative lupus nephritis received 2-CdA either in weekly escalating intravenous treatments (0.15 mg/kg/week x 4, 0.1875 mg/kg/week x 4, 0.225 mg/kg/week x 4; n = 5) or in a continuous 7-day infusion (0.05 mg/kg/day; n = 7). Safety, renal improvement, and immunologic effects were evaluated for 12 months. Patients treated with 2-CdA showed peripheral lymphocyte depletion without a significant reduction in neutrophil, monocyte, or platelet numbers or hematocrit levels. Naive and memory T cells were decreased, as were lymphocytes with markers of early and late activation. Peripheral B cell depletion was not associated with significant decreases in serum immunoglobulin levels. Continuous infusion induced better clinical responses than weekly infusions, as evidenced by 1) the percentage of patients showing complete response (43% versus 0%), 2) the percentage with at least 50% reduction in proteinuria (43% versus 20%), 3) the percentage with at least a 50% reduction in urinary dysmorphic red cells (57% versus 0%), and 4) the percentage in whom cellular casts disappeared (43% versus 0%). Several infections occurred; these responded to standard antibiotic therapy. In this pilot study, 2-CdA was safely administered to 12 patients with lupus nephritis. It induced prolonged reductions in lymphocyte populations and may be efficacious in selected patients with lupus nephritis when administered as a continuous infusion. JF - Arthritis and rheumatism AU - Davis, J C AU - Austin, H AU - Boumpas, D AU - Fleisher, T A AU - Yarboro, C AU - Larson, A AU - Balow, J AU - Klippel, J H AU - Scott, D AD - National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/02// PY - 1998 DA - February 1998 SP - 335 EP - 343 VL - 41 IS - 2 SN - 0004-3591, 0004-3591 KW - Cytokines KW - 0 KW - Immunosuppressive Agents KW - Cladribine KW - 47M74X9YT5 KW - Abridged Index Medicus KW - Index Medicus KW - Gene Expression -- drug effects KW - Cytokines -- genetics KW - Humans KW - Adult KW - Kidney -- drug effects KW - Pilot Projects KW - Middle Aged KW - Cytokines -- antagonists & inhibitors KW - Male KW - Female KW - Lupus Nephritis -- physiopathology KW - Cladribine -- adverse effects KW - Lupus Nephritis -- drug therapy KW - Cladribine -- therapeutic use KW - Lupus Nephritis -- immunology KW - Immunosuppressive Agents -- therapeutic use KW - Immunosuppressive Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79700393?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Arthritis+and+rheumatism&rft.atitle=A+pilot+study+of+2-chloro-2%27-deoxyadenosine+in+the+treatment+of+systemic+lupus+erythematosus-associated+glomerulonephritis.&rft.au=Davis%2C+J+C%3BAustin%2C+H%3BBoumpas%2C+D%3BFleisher%2C+T+A%3BYarboro%2C+C%3BLarson%2C+A%3BBalow%2C+J%3BKlippel%2C+J+H%3BScott%2C+D&rft.aulast=Davis&rft.aufirst=J&rft.date=1998-02-01&rft.volume=41&rft.issue=2&rft.spage=335&rft.isbn=&rft.btitle=&rft.title=Arthritis+and+rheumatism&rft.issn=00043591&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-19 N1 - Date created - 1998-03-19 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Arthritis Rheum. 1998 Sep;41(9):1704-5 [9751108] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Human endometrial stromal cells generate uncombined alpha-subunit from human chorionic gonadotropin, which can synergize with progesterone to induce decidualization. AN - 79695745; 9467577 AB - During the secretory phase of the menstrual cycle, endometrial stromal cells differentiate into decidual cells, which play a crucial role in implantation and maintenance of pregnancy. In this and our previous study, we demonstrate that glycoprotein hormone free alpha-subunit potentiates progesterone-mediated decidualization of human endometrial stromal cells in vitro. Although addition of intact hCG to cultures resulted in stimulatory activity, its potency was 20-fold less than that of alpha-subunit. However, in the present study we show that decidualizing endometrial cells actively generate uncombined alpha-subunit by dissociating hCG. The amount of dissociated alpha-subunit could fully account for the stimulatory activity observed with hCG. Active dissociation of hCG was dependent on the presence of endometrial cells and did not occur in conditioned medium, excluding involvement of a stable secreted factor such as a protease. In addition to dissociated alpha- and beta-subunits, minor amounts of beta-core and alpha-fragments were detected as degradation products during active dissociation. We also observed an increase in beta-immunoreactivity that coeluted with hCG on size-exclusion gel chromatography, indicating that a portion of the still dimeric hCG may have been nicked in the dissociation process. However, using an assay with specificity for nicked hCG, we showed that dissociation of hCG was not produced from a pool of preexisting nicked hCG. These findings more firmly establish the concept that gonadotropin hormone free alpha-subunit plays a role in the regulation of human endometrial cell differentiation. In addition, identification of the various products formed by incubation of hCG with decidualizing cells yielded insight into the mechanism of hCG degradation, and may explain some activity previously ascribed to hCG. JF - The Journal of clinical endocrinology and metabolism AU - Nemansky, M AU - Moy, E AU - Lyons, C D AU - Yu, I AU - Blithe, D L AD - Unit of Glycobiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/02// PY - 1998 DA - February 1998 SP - 575 EP - 581 VL - 83 IS - 2 SN - 0021-972X, 0021-972X KW - Chorionic Gonadotropin KW - 0 KW - Culture Media, Conditioned KW - Glycoprotein Hormones, alpha Subunit KW - Progesterone KW - 4G7DS2Q64Y KW - Prolactin KW - 9002-62-4 KW - Abridged Index Medicus KW - Index Medicus KW - Prolactin -- biosynthesis KW - Ovulation KW - Chorionic Gonadotropin -- pharmacology KW - Cells, Cultured KW - Kinetics KW - Humans KW - Adult KW - Middle Aged KW - Drug Synergism KW - Female KW - Glycoprotein Hormones, alpha Subunit -- metabolism KW - Progesterone -- pharmacology KW - Decidua -- physiology KW - Glycoprotein Hormones, alpha Subunit -- pharmacology KW - Stromal Cells -- metabolism KW - Decidua -- drug effects KW - Endometrium -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79695745?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+clinical+endocrinology+and+metabolism&rft.atitle=Human+endometrial+stromal+cells+generate+uncombined+alpha-subunit+from+human+chorionic+gonadotropin%2C+which+can+synergize+with+progesterone+to+induce+decidualization.&rft.au=Nemansky%2C+M%3BMoy%2C+E%3BLyons%2C+C+D%3BYu%2C+I%3BBlithe%2C+D+L&rft.aulast=Nemansky&rft.aufirst=M&rft.date=1998-02-01&rft.volume=83&rft.issue=2&rft.spage=575&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+clinical+endocrinology+and+metabolism&rft.issn=0021972X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-02-27 N1 - Date created - 1998-02-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Case series: spectrum of neuroleptic-induced movement disorders and extrapyramidal side effects in childhood-onset schizophrenia. AN - 79695446; 9473920 AB - Neuroleptic-treated pediatric patients with childhood-onset schizophrenia (COS) are at risk for developing extrapyramidal side effects and involuntary movement disorders. A preliminary examination of the incidence of withdrawal dyskinesias (WD), tardive dyskinesia (TD), and extrapyramidal side effects in these patients is presented. Thirty-four COS patients (mean age +/- SD, 14.2 +/- 2.1 years) were examined for TD using the Abnormal Involuntary Movements Scale and for extrapyramidal side effects using the Simpson-Angus Neurologic Rating Scale, after a 14- to 28-day drug-free period (n = 33), at week 6 of treatment and 2 to 4 years after completion of the study (n = 14). The mean (+/-SD) number of months of prior neuroleptic exposure for the group was 22.4 (15.0) months. Seventeen (50%) of 34 patients were noted to have either WD or TD at some point during their participation in the studies. The majority of patients experienced WD that were mainly in the orofacial region, transient in nature, and diminished with haloperidol and clozapine. Patients with TD/WD had greater levels of premorbid impairment (p = .02), increased severity of positive symptoms of schizophrenia (p < .01), and a trend toward more months of neuroleptic exposure (p = .10, one-tailed). A high proportion of COS patients were found to have TD/WD. The majority of these abnormal movements were not severe and generally improved over time. TD/WD in COS appears to be associated with greater premorbid impairment, severity of illness, and duration of neuroleptic exposure. J. Am. Acad. JF - Journal of the American Academy of Child and Adolescent Psychiatry AU - Kumra, S AU - Jacobsen, L K AU - Lenane, M AU - Smith, A AU - Lee, P AU - Malanga, C J AU - Karp, B I AU - Hamburger, S AU - Rapoport, J L AD - Child Psychiatry Branch, National Institute of Mental Health, Bethesda, MD 20892-1600, USA. Y1 - 1998/02// PY - 1998 DA - February 1998 SP - 221 EP - 227 VL - 37 IS - 2 SN - 0890-8567, 0890-8567 KW - Antipsychotic Agents KW - 0 KW - Index Medicus KW - Cross-Sectional Studies KW - Substance Withdrawal Syndrome KW - Prospective Studies KW - Humans KW - Chi-Square Distribution KW - Child KW - Adolescent KW - Male KW - Female KW - Dyskinesia, Drug-Induced KW - Schizophrenia, Childhood -- drug therapy KW - Antipsychotic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79695446?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+American+Academy+of+Child+and+Adolescent+Psychiatry&rft.atitle=Case+series%3A+spectrum+of+neuroleptic-induced+movement+disorders+and+extrapyramidal+side+effects+in+childhood-onset+schizophrenia.&rft.au=Kumra%2C+S%3BJacobsen%2C+L+K%3BLenane%2C+M%3BSmith%2C+A%3BLee%2C+P%3BMalanga%2C+C+J%3BKarp%2C+B+I%3BHamburger%2C+S%3BRapoport%2C+J+L&rft.aulast=Kumra&rft.aufirst=S&rft.date=1998-02-01&rft.volume=37&rft.issue=2&rft.spage=221&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+American+Academy+of+Child+and+Adolescent+Psychiatry&rft.issn=08908567&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-05-05 N1 - Date created - 1998-05-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Neuroprotection by S-nitrosoglutathione of brain dopamine neurons from oxidative stress. AN - 79692884; 9472981 AB - The proposed anti- and pro-oxidant effects of nitric oxide (NO) derivatives, such as S-nitrosoglutathione (GSNO) and peroxynitrite, were investigated in the rat nigrostriatal dopaminergic system. Intranigral infusion of freshly prepared GSNO (0-16.8 nmol, i.n.) prevented iron-induced (4.2 nmol, i.n.) oxidative stress and nigral injury, reflected by a decrease in striatal dopamine levels. This neuroprotective effect of GSNO was verified by ex vivo imaging of brain dopamine uptake sites using 125I-labeled RTI-55. In addition, in vitro data indicate that GSNO concentration-dependently inhibited iron-evoked hydroxyl radical generation and brain lipid peroxidation. In this iron-induced oxidant stress model, GSNO was approximately 100-fold more potent than the antioxidant glutathione (GSH). Light-exposed, NO-exhausted GSNO produced neither antioxidative nor neuroprotective effects, which indicates that NO may mediate at least part of GSNO's effects. Moreover, GSNO completely (and GSH only partially) inhibited the weak pro-oxidant effect of peroxynitrite, which produced little injury to nigral neurons in vivo. This study provides relevant in vivo evidence suggesting that nanomol GSNO can protect brain dopamine neurons from iron-induced oxidative stress and degeneration. In conclusion, S-nitrosylation of GSH by NO and oxygen may be part of the antioxidative cellular defense system. JF - FASEB journal : official publication of the Federation of American Societies for Experimental Biology AU - Rauhala, P AU - Lin, A M AU - Chiueh, C C AD - Unit on Neurodegeneration and Neuroprotection, Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, Maryland 20892-1264, USA. Y1 - 1998/02// PY - 1998 DA - February 1998 SP - 165 EP - 173 VL - 12 IS - 2 SN - 0892-6638, 0892-6638 KW - Ferrous Compounds KW - 0 KW - Iodine Radioisotopes KW - Neuroprotective Agents KW - Nitrates KW - Nitroso Compounds KW - Oxidants KW - peroxynitric acid KW - 26404-66-0 KW - monoferrous acid citrate KW - 33KM3X4QQW KW - 2beta-carbomethoxy-3beta-(4-iodophenyl)tropane KW - 4H1Z7121WS KW - S-Nitrosoglutathione KW - 57564-91-7 KW - Glutathione KW - GAN16C9B8O KW - Cocaine KW - I5Y540LHVR KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Ferrous Compounds -- toxicity KW - Cocaine -- analogs & derivatives KW - Nitrates -- toxicity KW - Oxidants -- toxicity KW - Cocaine -- pharmacokinetics KW - Autoradiography KW - Infusions, Parenteral KW - Male KW - Nitroso Compounds -- administration & dosage KW - Neurons -- drug effects KW - Neuroprotective Agents -- administration & dosage KW - Lipid Peroxidation -- drug effects KW - Substantia Nigra -- drug effects KW - Dopamine -- metabolism KW - Glutathione -- administration & dosage KW - Glutathione -- pharmacology KW - Neurons -- pathology KW - Neuroprotective Agents -- pharmacology KW - Substantia Nigra -- pathology KW - Oxidative Stress -- drug effects KW - Neurons -- physiology KW - Nitroso Compounds -- pharmacology KW - Substantia Nigra -- physiology KW - Glutathione -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79692884?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=FASEB+journal+%3A+official+publication+of+the+Federation+of+American+Societies+for+Experimental+Biology&rft.atitle=Neuroprotection+by+S-nitrosoglutathione+of+brain+dopamine+neurons+from+oxidative+stress.&rft.au=Rauhala%2C+P%3BLin%2C+A+M%3BChiueh%2C+C+C&rft.aulast=Rauhala&rft.aufirst=P&rft.date=1998-02-01&rft.volume=12&rft.issue=2&rft.spage=165&rft.isbn=&rft.btitle=&rft.title=FASEB+journal+%3A+official+publication+of+the+Federation+of+American+Societies+for+Experimental+Biology&rft.issn=08926638&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-02-27 N1 - Date created - 1998-02-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Modulation of fluorouracil cytotoxicity by interferon-alpha and -gamma. AN - 79690252; 9463483 AB - Because interferons (IFN)-alpha and -gamma individually have increased fluorouracil (FUra) cytotoxicity in several in vitro models, we studied the effects of FUra combined with IFN-alpha + gamma in HT29 colon cancer cells. A 96-hr exposure to IFN-alpha (500 units/ml) plus IFN-gamma (10 units/ml) and a 72-hr exposure to 0. 25-1 microM FUra (hr 24-96) inhibited cell growth and colony formation in an additive or more-than-additive fashion. When cells were exposed to IFN-alpha + gamma and FUra, free FdUMP levels became detectable, whereas [3H]FUra-RNA incorporation decreased. Exposure to IFN-alpha + gamma, FUra, or the combination decreased dTTP pools to 58%, 43%, and 17% of control, respectively. A marked increase in the dATP to dTTP ratio was seen with FUra with or without IFN-alpha + gamma. Thymidylate synthase catalytic activity was reduced to 28% and 24% of control with FUra with or without IFN-alpha + gamma, suggesting that the enhanced dTTP depletion must be due to another mechanism. FUra-mediated thymidylate synthase inhibition was accompanied by a 124-fold increase in total deoxyuridylate immunoreactivity and a 31-fold increase in dUTP pools, but the addition of IFN-alpha + gamma attenuated the accumulation. Treatment with IFN-alpha + gamma and FUra individually interfered with nascent DNA chain elongation, whereas the three-drug combination produced the most striking effects. IFN-alpha + gamma plus FUra produced the greatest amount of single-strand breaks in nascent DNA and dramatically decreased net DNA synthesis. IFN-alpha + gamma with or without FUra produced double-strand breaks in parental DNA. These results suggest that dTTP depletion, dATP/dTTP imbalance, pronounced inhibition of DNA synthesis, and damage to nascent and parental DNA contribute to the enhanced cytotoxicity with the triple combination. JF - Molecular pharmacology AU - Ismail, A AU - Van Groeningen, C J AU - Hardcastle, A AU - Ren, Q AU - Aherne, G W AU - Geoffroy, F AU - Allegra, C J AU - Grem, J L AD - National Cancer Institute-Navy Medical Oncology Branch, National Naval Medical Center, Bethesda, Maryland 20889, USA. Y1 - 1998/02// PY - 1998 DA - February 1998 SP - 252 EP - 261 VL - 53 IS - 2 SN - 0026-895X, 0026-895X KW - DNA, Neoplasm KW - 0 KW - Interferon-alpha KW - RNA, Neoplasm KW - Thymine Nucleotides KW - Interferon-gamma KW - 82115-62-6 KW - thymidine 5'-triphosphate KW - QOP4K539MU KW - Fluorouracil KW - U3P01618RT KW - Index Medicus KW - RNA, Neoplasm -- biosynthesis KW - Drug Interactions KW - Drug Administration Schedule KW - Thymine Nucleotides -- metabolism KW - Tumor Cells, Cultured -- drug effects KW - Humans KW - DNA, Neoplasm -- biosynthesis KW - DNA Fragmentation KW - DNA Repair -- drug effects KW - Fluorouracil -- administration & dosage KW - Interferon-alpha -- administration & dosage KW - Interferon-gamma -- administration & dosage KW - Fluorouracil -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79690252?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Modulation+of+fluorouracil+cytotoxicity+by+interferon-alpha+and+-gamma.&rft.au=Ismail%2C+A%3BVan+Groeningen%2C+C+J%3BHardcastle%2C+A%3BRen%2C+Q%3BAherne%2C+G+W%3BGeoffroy%2C+F%3BAllegra%2C+C+J%3BGrem%2C+J+L&rft.aulast=Ismail&rft.aufirst=A&rft.date=1998-02-01&rft.volume=53&rft.issue=2&rft.spage=252&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 - 1998-03-10 N1 - Date created - 1998-03-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A review of alcohol clearance in humans. AN - 79688693; 9476961 AB - The level of blood or brain alcohol is considered to influence alcohol ingestion by causing subjective perceptions or neural activations that are reinforcing or rewarding. Alcohol-dependent people may try to maintain some desired tissue level, drinking to replace the millimolar levels that were cleared from the blood by metabolism. The biomedical literature describes many approaches to understanding the role of blood alcohol levels in human physiology and behavior, and this review examines some of the published results. They include the general kinetics of intake and removal of beverage alcohol as well as the characteristics of many different catalysts that can interact with alcohol. Because ingested alcohol creates blood levels that are a 1000-fold greater than those normally experienced during abstinence, ethanol may impose itself as an alternate substrate for the many oxidoreductases that act physiologically on other endogenous alcohols. Many enzymes that can act on millimolar ethanol have been isolated, and their structural genes are sequenced. Unfortunately, the genetic sequence does not indicate the physiological material upon which the translated gene product may act. In a sense, the set of enzymes with catalytic sites occupied by millimolar ethanol during alcohol drinking might constructively be regarded as "orphan gene products" whose physiological role remains to be clarified. This review is designed to indicate some of what is known, what is not known, and what needs to be known to improve the interpretations regarding adaptations to beverage alcohol and the ability of millimolar levels of alcohol to diminish dysphoria. The dysphoria may be influenced by ethanol, by ethanol metabolites, or by altered metabolism of currently unspecified endogenous substrates. A major challenge is to evaluate the multiple alternative variables within a context that stimulates curiosity and encourages quantitative tests of the relative contribution of each variable to the overall physiology of an individual. JF - Alcohol (Fayetteville, N.Y.) AU - Lands, W E AD - National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892-7003, USA. wlands@willco.niaaa.nih.gov Y1 - 1998/02// PY - 1998 DA - February 1998 SP - 147 EP - 160 VL - 15 IS - 2 SN - 0741-8329, 0741-8329 KW - Ethanol KW - 3K9958V90M KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Alcohol Dehydrogenase KW - EC 1.1.1.1 KW - Catalase KW - EC 1.11.1.6 KW - Aldehyde Dehydrogenase KW - EC 1.2.1.3 KW - Index Medicus KW - Catalase -- metabolism KW - Animals KW - Kinetics KW - Humans KW - Alcoholism KW - Metabolic Clearance Rate KW - Cytochrome P-450 Enzyme System -- metabolism KW - Alcohol Dehydrogenase -- metabolism KW - Aldehyde Dehydrogenase -- metabolism KW - Ethanol -- blood KW - Ethanol -- pharmacokinetics KW - Ethanol -- administration & dosage KW - Ethanol -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79688693?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Alcohol+%28Fayetteville%2C+N.Y.%29&rft.atitle=A+review+of+alcohol+clearance+in+humans.&rft.au=Lands%2C+W+E&rft.aulast=Lands&rft.aufirst=W&rft.date=1998-02-01&rft.volume=15&rft.issue=2&rft.spage=147&rft.isbn=&rft.btitle=&rft.title=Alcohol+%28Fayetteville%2C+N.Y.%29&rft.issn=07418329&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-06 N1 - Date created - 1998-03-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Vinblastine for recurrent Hodgkin's disease following autologous bone marrow transplant. AN - 79685327; 9469345 AB - Bone marrow transplant (BMT) can cure recurrent Hodgkin's disease, but more than half of patients will progress and require additional treatment. When this occurs, there are no curative options and palliative therapy is usually indicated. In such patients, we have routinely used long-term vinblastine therapy because of its relatively low toxicity and high activity. We retrospectively reviewed the charts of all patients with Hodgkin's disease who relapsed after autologous BMT since 1991. Of 23 patients, 16 received vinblastine; we also include our index case, who began vinblastine following relapse in 1987. Patients received vinblastine 4 to 6 mg/m2 every 1 to 2 weeks, and continued until evidence of disease progression. The 17 patients in this report had a median age of 31 years, performance status of 2, had received a median of three prior regimens, and 12 (71%) patients were advanced stage. Ten (59%) patients had objective responses, of which two (12%) were complete (CR) and eight (47%) were partial (PR). Two additional patients without measurable disease clinically improved for more than 6 months, and 1 patient had stable disease for more than 18 months. With a median follow-up of 20.4 months, the median event-free (EFS) and overall survival were 8.3 and 38.8 months, respectively. The two complete responders remain in remission at 4.6+ and 9+ years. Vinblastine was well tolerated with 3% of cycles associated with fever and neutropenia, and no cumulative or chronic toxicity. Vinblastine provides effective palliation with low toxicity in recurrent Hodgkin's disease following transplant. These results suggest that long-term vinblastine therapy may be potentially curative and should be considered as initial therapy for such patients. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Little, R AU - Wittes, R E AU - Longo, D L AU - Wilson, W H AD - Medicine Branch, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1998/02// PY - 1998 DA - February 1998 SP - 584 EP - 588 VL - 16 IS - 2 SN - 0732-183X, 0732-183X KW - Antineoplastic Agents, Phytogenic KW - 0 KW - Vinblastine KW - 5V9KLZ54CY KW - Index Medicus KW - Disease-Free Survival KW - Survival Rate KW - Combined Modality Therapy KW - Humans KW - Adult KW - Retrospective Studies KW - Middle Aged KW - Transplantation, Autologous KW - Recurrence KW - Male KW - Female KW - Vinblastine -- therapeutic use KW - Antineoplastic Agents, Phytogenic -- adverse effects KW - Antineoplastic Agents, Phytogenic -- therapeutic use KW - Vinblastine -- adverse effects KW - Hodgkin Disease -- therapy KW - Hodgkin Disease -- mortality KW - Bone Marrow Transplantation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79685327?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Vinblastine+for+recurrent+Hodgkin%27s+disease+following+autologous+bone+marrow+transplant.&rft.au=Little%2C+R%3BWittes%2C+R+E%3BLongo%2C+D+L%3BWilson%2C+W+H&rft.aulast=Little&rft.aufirst=R&rft.date=1998-02-01&rft.volume=16&rft.issue=2&rft.spage=584&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.issn=0732183X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-02 N1 - Date created - 1998-03-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A T cell-independent antitumor response in mice with bone marrow cells retrovirally transduced with an antibody/Fc-gamma chain chimeric receptor gene recognizing a human ovarian cancer antigen. AN - 79683783; 9461189 AB - In order to treat common cancers with immunotherapy, chimeric receptors have been developed that combine the tumor specificity of antibodies with T-cell effector functions. Previously, we demonstrated that T cells transduced with a chimeric receptor gene against human ovarian cancer were able to recognize ovarian cancer cells in vitro and in vivo. We now report that recipients of bone marrow cells transduced with these genes exhibited significant antitumor activity in vivo. Moreover, in vivo depletion of T cells in reconstituted mice did not affect antitumor activity, suggesting that other immune cells expressing the chimeric receptor gene may play an important role in tumor rejection. JF - Nature medicine AU - Wang, G AU - Chopra, R K AU - Royal, R E AU - Yang, J C AU - Rosenberg, S A AU - Hwu, P AD - Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/02// PY - 1998 DA - February 1998 SP - 168 EP - 172 VL - 4 IS - 2 SN - 1078-8956, 1078-8956 KW - Antibodies, Monoclonal KW - 0 KW - Cytokines KW - Immunoglobulin Variable Region KW - Receptors, Antigen, T-Cell KW - Recombinant Fusion Proteins KW - Index Medicus KW - Radiation Dosage KW - Animals KW - Antibodies, Monoclonal -- genetics KW - Ovarian Neoplasms -- genetics KW - Humans KW - Neoplasms, Experimental -- genetics KW - Cytokines -- metabolism KW - Mice KW - Immunotherapy -- methods KW - Neoplasms, Experimental -- immunology KW - Mice, Inbred C57BL KW - Retroviridae -- genetics KW - T-Lymphocytes -- immunology KW - Female KW - Recombinant Fusion Proteins -- genetics KW - Recombinant Fusion Proteins -- pharmacology KW - Hematopoietic Stem Cells -- virology KW - Receptors, Antigen, T-Cell -- genetics KW - Hematopoietic Stem Cell Transplantation -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79683783?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+medicine&rft.atitle=A+T+cell-independent+antitumor+response+in+mice+with+bone+marrow+cells+retrovirally+transduced+with+an+antibody%2FFc-gamma+chain+chimeric+receptor+gene+recognizing+a+human+ovarian+cancer+antigen.&rft.au=Wang%2C+G%3BChopra%2C+R+K%3BRoyal%2C+R+E%3BYang%2C+J+C%3BRosenberg%2C+S+A%3BHwu%2C+P&rft.aulast=Wang&rft.aufirst=G&rft.date=1998-02-01&rft.volume=4&rft.issue=2&rft.spage=168&rft.isbn=&rft.btitle=&rft.title=Nature+medicine&rft.issn=10788956&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-02-23 N1 - Date created - 1998-02-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phase I study of paclitaxel as a radiation sensitizer in the treatment of mesothelioma and non-small-cell lung cancer. AN - 79683647; 9469352 AB - To determine the maximum-tolerated dose (MTD) and dose-limiting toxicities of paclitaxel with concurrent thoracic irradiation in patients with malignant pleural mesothelioma and locally advanced non-small-cell lung cancer (NSCLC) using a 120-hour continuous infusion regimen. A secondary objective was to assess the effect of paclitaxel on the cell cycle through serial tumor biopsies. Paclitaxel was administered as a 120-hour (5-day) continuous infusion repeated every 3 weeks during the course of radiation therapy. The starting dose of paclitaxel was 90 mg/m2. Doses were escalated at 15-mg/m2 increments in successive cohorts of three patients. In NSCLC patients, radiation was delivered to the primary tumor and regional lymph nodes for a total tumor dose of 6,120 cGy. In mesothelioma patients, hemithoracic irradiation was delivered as the initial treatment field with a conedown to the tumor volume for a total dose of 5,760 to 6,300 cGy. Tumor biopsies were obtained, if possible, before and during paclitaxel treatment. Thirty patients were entered onto this study through three dose levels (from 90 mg/m2 to 120 mg/m2). The MTD was determined to be 105 mg/m2. The dose-limiting toxicity was grade 4 neutropenia (two patients). Grade 2 gastrointestinal (GI) toxicity (nausea and vomiting) was also observed at 120 mg/m2. Three of 30 patients developed a hypersensitivity reaction. Six patients had grade 2 lung injury manifested by a persistent cough that required antitussives. Five patients underwent tumor biopsies. None of the patients showed a significant block of cells in mitosis (G2/M) after paclitaxel infusion. The MTD of paclitaxel, when administered as a 120-hour continuous infusion with concurrent radiotherapy, was determined to be 105 mg/m2. The dose-limiting toxicity was neutropenia. Continuous infusion paclitaxel administered with large field irradiation of the lung is well tolerated and deserves continued evaluation. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Herscher, L L AU - Hahn, S M AU - Kroog, G AU - Pass, H AU - Temeck, B AU - Goldspiel, B AU - Cook, J AU - Mitchell, J B AU - Liebmann, J AD - Radiation Oncology Branch, Division of Cancer Treatment, National Cancer Institute, Bethesda, MD 20892, USA. herscher@box-h.nih.gov Y1 - 1998/02// PY - 1998 DA - February 1998 SP - 635 EP - 641 VL - 16 IS - 2 SN - 0732-183X, 0732-183X KW - Radiation-Sensitizing Agents KW - 0 KW - Paclitaxel KW - P88XT4IS4D KW - Index Medicus KW - Infusions, Intravenous KW - Radiotherapy Dosage KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Male KW - Female KW - Paclitaxel -- administration & dosage KW - Paclitaxel -- adverse effects KW - Lung Neoplasms -- radiotherapy KW - Mesothelioma -- radiotherapy KW - Pleural Neoplasms -- radiotherapy KW - Radiation-Sensitizing Agents -- adverse effects KW - Radiation-Sensitizing Agents -- administration & dosage KW - Carcinoma, Non-Small-Cell Lung -- radiotherapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79683647?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+paclitaxel+as+a+radiation+sensitizer+in+the+treatment+of+mesothelioma+and+non-small-cell+lung+cancer.&rft.au=Herscher%2C+L+L%3BHahn%2C+S+M%3BKroog%2C+G%3BPass%2C+H%3BTemeck%2C+B%3BGoldspiel%2C+B%3BCook%2C+J%3BMitchell%2C+J+B%3BLiebmann%2C+J&rft.aulast=Herscher&rft.aufirst=L&rft.date=1998-02-01&rft.volume=16&rft.issue=2&rft.spage=635&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 - 1998-03-02 N1 - Date created - 1998-03-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of p53 and apoptosis in sensitization of cis-diamminedichloroplatinum antitumor activity by interleukin-1 in ovarian carcinoma cells. AN - 79682871; 9458352 AB - We have previously reported that interleukin-1 (IL-1 ) sensitized cisplatin cytotoxicity against human ovarian NIH:OVCAR-3 tumor cells. We have further examined inter-actions of IL-1 with cisplatin in these ovarian cells. Treatment of cells with either IL-1 or CDDP or combinations resulted in a significant accumulation of cells in G1 phase and a concomitant decrease in the S phase of the cell cycle. IL-1 and CDDP treatment induced p53 protein in NIH:OVCAR-3 tumor cells. CDDP and IL-1 treatment decreased the steady-state expression of c-myc RNA and induced significant degradation of the genomic DNA into internucleosomal sized DNA fragments which was further increased in the presence of both agents in these cells. Taken together, these studies suggest that IL-1 may kill ovarian NIH:OVCAR-3 tumor cells by inducing a blockade at G1/S of the cell cycle, down-regulating c-myc gene and inducing p53-dependent apoptosis. The synergistic interactions of IL-1 with CDDP may involve the enhancement of p53-dependent apoptosis. JF - International journal of oncology AU - Song, K AU - Fukushima, P AU - Seth, P AU - Sinha, B K AD - Developmental Therapeutics Department, Medicine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1998/02// PY - 1998 DA - February 1998 SP - 299 EP - 304 VL - 12 IS - 2 SN - 1019-6439, 1019-6439 KW - Interleukin-1 KW - 0 KW - Tumor Suppressor Protein p53 KW - Cisplatin KW - Q20Q21Q62J KW - Index Medicus KW - Gene Expression -- drug effects KW - DNA Fragmentation -- genetics KW - Down-Regulation KW - Tumor Cells, Cultured -- drug effects KW - Humans KW - In Vitro Techniques KW - Enzyme-Linked Immunosorbent Assay KW - Genes, myc -- drug effects KW - Drug Synergism KW - Genes, myc -- genetics KW - Female KW - Cell Cycle -- drug effects KW - Cisplatin -- therapeutic use KW - Interleukin-1 -- pharmacology KW - Ovarian Neoplasms -- genetics KW - Ovarian Neoplasms -- pathology KW - Apoptosis -- physiology KW - Tumor Suppressor Protein p53 -- drug effects KW - Apoptosis -- drug effects KW - Interleukin-1 -- therapeutic use KW - Cisplatin -- pharmacology KW - Tumor Suppressor Protein p53 -- metabolism KW - Ovarian Neoplasms -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79682871?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+journal+of+oncology&rft.atitle=Role+of+p53+and+apoptosis+in+sensitization+of+cis-diamminedichloroplatinum+antitumor+activity+by+interleukin-1+in+ovarian+carcinoma+cells.&rft.au=Song%2C+K%3BFukushima%2C+P%3BSeth%2C+P%3BSinha%2C+B+K&rft.aulast=Song&rft.aufirst=K&rft.date=1998-02-01&rft.volume=12&rft.issue=2&rft.spage=299&rft.isbn=&rft.btitle=&rft.title=International+journal+of+oncology&rft.issn=10196439&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-03-01 N1 - Date created - 2001-02-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetic alterations in the development of mammary and prostate cancer in the C3(1)/Tag transgenic mouse model. AN - 79682040; 9458374 AB - We have generated a transgenic mouse model in which female mice develop ductal mammary adenocarcinomas and male mice develop prostatic adenocarcinomas by using a transgene containing the hormone-responsive rat prostatic steroid binding protein 5' flanking region C3(1) fused to the simian virus 40 (SV40) large T antigen. We have identified some genetic alterations during mammary and prostate tumor progression: (i) p53 is functionally inactivated during mammary cancer development without p53 mutations; (ii) Alterations in apoptosis during mammary tumor progression are p53 and bcl-2 independent; (iii) Ha-ras mutations occur early in the development of prostate cancer. This unique animal model offers the opportunity to study multistep tumorigenesis in these organs. JF - International journal of oncology AU - Yoshidome, K AU - Shibata, M A AU - Maroulakou, I G AU - Liu, M L AU - Jorcyk, C L AU - Gold, L G AU - Welch, V N AU - Green, J E AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, National Institutes of Health, Building 41, Room C629, 9000 Rockville Pike, Bethesda, MD 20892, USA. Y1 - 1998/02// PY - 1998 DA - February 1998 SP - 449 EP - 453 VL - 12 IS - 2 SN - 1019-6439, 1019-6439 KW - Index Medicus KW - Animals KW - Disease Models, Animal KW - Mice KW - Mice, Transgenic KW - Rats KW - Phenotype KW - Apoptosis -- genetics KW - Genes, ras -- genetics KW - Genes, bcl-2 -- genetics KW - Genes, p53 -- genetics KW - Mutation KW - Female KW - Male KW - Breast Neoplasms -- genetics KW - Mammary Neoplasms, Animal -- genetics KW - Prostatic Neoplasms -- genetics KW - Adenocarcinoma -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79682040?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Nervous+and+Mental+Disease&rft.atitle=Risk+factors+for+posttraumatic+stress+symptoms+among+avalanche+survivors%3A+A+16-year+follow-up&rft.au=Thordardottir%2C+Edda+Bjork%3BHansdottir%2C+Ingunn%3BShipherd%2C+Jillian+C.%3BValdimarsdottir%2C+Unnur+Anna%3BResnick%2C+Heidi%3BElklit%2C+Ask%3BGudmundsdottir%2C+Ragnhildur%3BGudmundsdottir%2C+Berglind&rft.aulast=Thordardottir&rft.aufirst=Edda&rft.date=2016-04-01&rft.volume=204&rft.issue=4&rft.spage=298&rft.isbn=&rft.btitle=&rft.title=Journal+of+Nervous+and+Mental+Disease&rft.issn=00223018&rft_id=info:doi/10.1097%2FNMD.0000000000000475 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-03-01 N1 - Date created - 2001-02-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutation of polyadenylation signals generates murine retroviruses that produce fused virus-cell RNA transcripts at high frequency. AN - 79678775; 9454719 AB - Retroviruses act as insertional mutagens and can also capture cellular sequences through a mechanism which initially requires the generation of RNA transcripts which fail to cleave and polyadenylate correctly. The correct termination of retroviral transcripts at the 3' LTR R/U5 junction is primarily dependent on the canonical AAUAAA polyadenylation signal, so we have analyzed the effect of mutating the polyadenylation signal sequences on the properties of a selectable murine retroviral vector. Mutation of consensus polyadenylation signal sequences in the 5' and/or 3' proviral LTRs demonstrated that a UA to GG change generated larger sized virus-specific RNA, consistent with loss of normal polyadenylation. Cell clones infected with viruses generated by proviral constructs containing this mutation in the 5' LTR express either normal-length or elongated viral RNA. Fused transcripts contained the mutant polyadenylation signal, while sequence analysis was consistent with the hypothesis that premature 5' to 3' primer strand transfer was responsible for the high frequency (80%) of wild-type polyadenylation. Cells infected by viruses from constructs mutated in both 5' and 3' proviral LTRs expressed poly(A)+ viral RNA between 0.3 and 3 kb larger than normal virus in 100% of infected clones, and sequence analysis of clones derived from either infected rodent or human cells confirmed that these transcripts contained both viral and adjacent cellular sequences. While mutant virus exhibits no increased ability to alter cell phenotypes, the read-through transcripts contain both unique and repetitive cell-derived sequences and can easily be recovered using PCR techniques, suggesting that these viruses may serve as effective tools for rapidly cloning cellular sequences and generating random genomic markers for gene mapping. Copyright 1998 Academic Press. JF - Virology AU - Zhang, Q Y AU - Clausen, P A AU - Yatsula, B A AU - Calothy, G AU - Blair, D G AD - Division of Basic Sciences, NCI-FCRDC, Frederick, Maryland, 21702-1201, USA. Y1 - 1998/02/01/ PY - 1998 DA - 1998 Feb 01 SP - 80 EP - 93 VL - 241 IS - 1 SN - 0042-6822, 0042-6822 KW - RNA, Viral KW - 0 KW - Poly A KW - 24937-83-5 KW - RNA KW - 63231-63-0 KW - Ribonucleases KW - EC 3.1.- KW - Index Medicus KW - 3T3 Cells KW - Animals KW - HeLa Cells KW - Humans KW - Mice KW - Ribonucleases -- metabolism KW - Binding Sites KW - Mutagenesis KW - Rats KW - Base Sequence KW - RNA -- metabolism KW - Molecular Sequence Data KW - Proviruses -- genetics KW - Repetitive Sequences, Nucleic Acid KW - RNA, Viral -- metabolism KW - Cell Line KW - Poly A -- genetics KW - Moloney murine leukemia virus -- genetics KW - Virus Integration KW - Poly A -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79678775?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mutation+of+polyadenylation+signals+generates+murine+retroviruses+that+produce+fused+virus-cell+RNA+transcripts+at+high+frequency.&rft.au=Zhang%2C+Q+Y%3BClausen%2C+P+A%3BYatsula%2C+B+A%3BCalothy%2C+G%3BBlair%2C+D+G&rft.aulast=Zhang&rft.aufirst=Q&rft.date=1998-02-01&rft.volume=241&rft.issue=1&rft.spage=80&rft.isbn=&rft.btitle=&rft.title=Virology&rft.issn=00426822&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-02-26 N1 - Date created - 1998-02-26 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF014457; GENBANK; AF014450; AF014452; AF014451; AF014454; AF014453; AF014456; AF014455 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of ferrous iron chelator 2,2'-dipyridyl in preventing delayed vasospasm in a primate model of subarachnoid hemorrhage. AN - 79671933; 9452239 AB - Oxyhemoglobin (HbO2) causes vasospasm after subarachnoid hemorrhage (SAH). The most likely spasmogenic component of HbO2 is iron. Various iron chelators, such as deferoxamine, have prevented vasospasm in vivo with limited success. However, only chelators of iron in the ferric state have been studied in animal models of vasospasm after SAH. Because free radical formation requires the ferrous (Fe++) moiety and Fe++ is a potent binder of the vasodilator nitric oxide, the authors hypothesized that iron in the ferrous state causes vasospasm and that chelators of Fe++, such as 2,2'-dipyridyl, may prevent vasospasm. This study was undertaken to investigate the influence of 2,2'-dipyridyl on vasospasm after induction of SAH in a primate model. Twelve cynomolgus monkeys were randomly divided into two groups and then both groups underwent placement of an arterial autologous blood clot in the subarachnoid space around the right middle cerebral artery (MCA). The five animals in the control group received intravenously administered saline and the seven treated animals received intravenously administered chelator (2,2'-dipyridyl) for 14 days. Sequential arteriography for assessment of MCA diameter was performed before and on the 7th day after SAH. Prevention of cerebral vasospasm by means of treatment with continuous intravenous administration of 2,2'-dipyridyl is reported in a primate model of SAH. This result provides insight into the possible mechanism of delayed vasospasm after aneurysmal SAH and provides a potential preventive therapy for it. JF - Journal of neurosurgery AU - Horky, L L AU - Pluta, R M AU - Boock, R J AU - Oldfield, E H AD - Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/02// PY - 1998 DA - February 1998 SP - 298 EP - 303 VL - 88 IS - 2 SN - 0022-3085, 0022-3085 KW - Ferrous Compounds KW - 0 KW - Iron Chelating Agents KW - Transferrin KW - 2,2'-Dipyridyl KW - 551W113ZEP KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Liver -- pathology KW - Cerebral Angiography KW - Macaca fascicularis KW - Injections, Intravenous KW - Liver -- drug effects KW - Transferrin -- analysis KW - Time Factors KW - Male KW - Female KW - Ischemic Attack, Transient -- prevention & control KW - Iron Chelating Agents -- therapeutic use KW - Iron Chelating Agents -- adverse effects KW - 2,2'-Dipyridyl -- adverse effects KW - Ferrous Compounds -- antagonists & inhibitors KW - Ischemic Attack, Transient -- diagnostic imaging KW - 2,2'-Dipyridyl -- therapeutic use KW - Subarachnoid Hemorrhage -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79671933?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neurosurgery&rft.atitle=Role+of+ferrous+iron+chelator+2%2C2%27-dipyridyl+in+preventing+delayed+vasospasm+in+a+primate+model+of+subarachnoid+hemorrhage.&rft.au=Horky%2C+L+L%3BPluta%2C+R+M%3BBoock%2C+R+J%3BOldfield%2C+E+H&rft.aulast=Horky&rft.aufirst=L&rft.date=1998-02-01&rft.volume=88&rft.issue=2&rft.spage=298&rft.isbn=&rft.btitle=&rft.title=Journal+of+neurosurgery&rft.issn=00223085&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-02-12 N1 - Date created - 1998-02-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Partial purification and characterization of biological effects of a lipid toxin produced by Mycobacterium ulcerans. AN - 79671465; 9453613 AB - Organisms in the genus Mycobacterium cause a variety of human diseases. One member of the genus, M. ulcerans, causes a necrotizing skin disease called Buruli ulcer. Buruli ulcer is unique among mycobacterial diseases in that the organisms at the site of infection are extracellular and there is little acute inflammatory response. Previous literature reported the presence of a toxin in the culture supernatant of M. ulcerans which causes a cytopathic effect on the mouse fibroblast cell line L929 in which the adherent cells round up and detach from the tissue culture plate. Here we report partial purification of a lipid toxin from the culture supernatant of M. ulcerans which is capable of causing the cytopathic effect on L929 cells. We also show that this cytopathic effect is a result of cytoskeletal rearrangement. The M. ulcerans toxin does not cause cell death but instead arrests cells in the G1 phase of the cell cycle. JF - Infection and immunity AU - George, K M AU - Barker, L P AU - Welty, D M AU - Small, P L AD - Microscopy Branch, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840, USA. katie_george@nih.gov Y1 - 1998/02// PY - 1998 DA - February 1998 SP - 587 EP - 593 VL - 66 IS - 2 SN - 0019-9567, 0019-9567 KW - Bacterial Toxins KW - 0 KW - Lipids KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Animals KW - Cells, Cultured KW - Mice KW - G1 Phase -- drug effects KW - DNA -- biosynthesis KW - Cell Cycle -- drug effects KW - Cytoskeleton -- drug effects KW - Mycobacterium ulcerans -- pathogenicity KW - Lipids -- isolation & purification KW - Bacterial Toxins -- isolation & purification KW - Lipids -- toxicity KW - Bacterial Toxins -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79671465?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Infection+and+immunity&rft.atitle=Partial+purification+and+characterization+of+biological+effects+of+a+lipid+toxin+produced+by+Mycobacterium+ulcerans.&rft.au=George%2C+K+M%3BBarker%2C+L+P%3BWelty%2C+D+M%3BSmall%2C+P+L&rft.aulast=George&rft.aufirst=K&rft.date=1998-02-01&rft.volume=66&rft.issue=2&rft.spage=587&rft.isbn=&rft.btitle=&rft.title=Infection+and+immunity&rft.issn=00199567&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-02-12 N1 - Date created - 1998-02-12 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Clin Microbiol. 1996 Apr;34(4):962-5 [8815117] Infect Immun. 1996 Mar;64(3):683-90 [8641767] Infect Immun. 1997 Apr;65(4):1364-9 [9119475] Infect Immun. 1997 Apr;65(4):1497-504 [9119492] Nature. 1997 Jun 12;387(6634):725-9 [9192900] Nature. 1997 Jun 12;387(6634):729-33 [9192901] Trends Microbiol. 1997 Jul;5(7):282-8 [9234511] J Clin Microbiol. 1998 Apr;36(4):918-25 [9542909] J Biol Chem. 1957 May;226(1):497-509 [13428781] Exp Cell Res. 1988 Jan;174(1):215-29 [3121372] Int J Lepr. 1965 Jul-Sep;33(3):Suppl:698-709 [5322711] Br J Dermatol. 1966 Apr;78(4):187-97 [5910904] Exp Cell Res. 1970 Dec;63(2):309-16 [5530916] Infect Immun. 1974 Jun;9(6):1114-22 [4830529] Proc Natl Acad Sci U S A. 1974 Apr;71(4):1286-90 [4524638] Arch Dermatol. 1974 Nov;110(5):783-8 [4422235] Infect Immun. 1978 Jul;21(1):124-8 [30694] J Infect Dis. 1980 Feb;141(2):218-22 [6245152] J Immunol. 1988 Jan 15;140(2):634-40 [2826597] J Infect Dis. 1988 Mar;157(3):577-80 [2963867] Infect Immun. 1988 May;56(5):1232-6 [3128482] EMBO J. 1989 Apr;8(4):1087-92 [2501082] Clin Exp Immunol. 1990 Apr;80(1):141-8 [2138940] J Gen Microbiol. 1990 Oct;136(10):2001-12 [2269873] Infect Immun. 1991 May;59(5):1755-61 [1850379] Infect Immun. 1991 Aug;59(8):2542-8 [1649796] J Exp Med. 1991 Nov 1;174(5):1031-8 [1940785] J Gen Microbiol. 1992 Jan;138(1):131-7 [1556545] Hosp Pract (Off Ed). 1993 Jan 15;28(1):51-8 [8419415] J Clin Pathol. 1993 Jan;46(1):5-9 [8432888] Ann Clin Lab Sci. 1993 Jul-Aug;23(4):256-66 [8373130] Am J Respir Crit Care Med. 1994 Feb;149(2 Pt 1):510-8 [8306054] J Biol Chem. 1994 Apr 8;269(14):10706-12 [8144660] Infect Immun. 1994 Aug;62(8):3222-9 [8039892] Microb Pathog. 1994 Jun;16(6):401-11 [7830527] Nature. 1995 Jun 8;375(6531):500-3 [7777059] Science. 1995 Sep 1;269(5228):1270-2 [7652575] Biochem J. 1995 Jun 15;308 ( Pt 3):853-8 [8948442] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - N18-RE-105 cells: differentiation and activation of p53 in response to glutamate and adriamycin is blocked by SV40 large T antigen tsA58. AN - 79662864; 9426307 AB - Process extension was induced in cells of the N18-RE-105 neuroblastoma-retinal hybrid line by toxic agents, including glutamate and the p53-inducing anticancer agents adriamycin and etoposide. Both adriamycin and glutamate activated p53 as measured by a plasmid transfection assay. It was therefore hypothesized that SV40 large T antigen, which binds p53, would interfere with cellular differentiation. To test this hypothesis, the temperature-sensitive form of SV40 large T was transduced into N18-RE-105 cells by retroviral infection. SV40 large T-infected cells became de-differentiated, grew in tightly-packed colonies, lost expression of neurofilament, and lost the ability to differentiate in response to glutamate and adriamycin. The de-differentiating effect of SV40 large T antigen may be due to binding and inactivation of cellular proteins, such as p53, p107, p130, p300, and retinoblastoma protein, which are important in cellular growth and differentiation. It is suggested that p53 may play a role in cellular differentiation, perhaps under unusual circumstances involving stress or cytotoxicity. JF - Cell and tissue research AU - Dillon-Carter, O AU - Conejero, C AU - Tornatore, C AU - Poltorak, M AU - Freed, W J AD - Section on Preclinical Neuroscience Neuropsychiatry Branch, NIMH Neuroscience Center at St. Elizabeths, 2700 Martin Luther King Ave., Washington, D.C., 20032, USA. Y1 - 1998/02// PY - 1998 DA - February 1998 SP - 191 EP - 205 VL - 291 IS - 2 SN - 0302-766X, 0302-766X KW - Antigens, Polyomavirus Transforming KW - 0 KW - Antiporters KW - Excitatory Amino Acid Agonists KW - Neurotoxins KW - Tumor Suppressor Protein p53 KW - Homocysteine KW - 0LVT1QZ0BA KW - homocysteic acid KW - 1001-13-4 KW - Glutamic Acid KW - 3KX376GY7L KW - Cystine KW - 48TCX9A1VT KW - Etoposide KW - 6PLQ3CP4P3 KW - alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid KW - 77521-29-0 KW - Doxorubicin KW - 80168379AG KW - Index Medicus KW - Etoposide -- pharmacology KW - Neuroblastoma -- pathology KW - Animals KW - Temperature KW - Neurotoxins -- pharmacology KW - alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid -- pharmacology KW - Mice KW - Retina -- cytology KW - Rats KW - Cystine -- metabolism KW - Rats, Inbred F344 KW - Tumor Cells, Cultured KW - Neurites -- drug effects KW - Apoptosis -- drug effects KW - Hybrid Cells KW - Excitatory Amino Acid Agonists -- pharmacology KW - Homocysteine -- pharmacology KW - Cell Differentiation -- drug effects KW - Homocysteine -- analogs & derivatives KW - Antigens, Polyomavirus Transforming -- pharmacology KW - Neurons -- metabolism KW - Doxorubicin -- pharmacology KW - Neurons -- drug effects KW - Tumor Suppressor Protein p53 -- metabolism KW - Neurons -- ultrastructure KW - Glutamic Acid -- pharmacology KW - Antiporters -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79662864?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+and+tissue+research&rft.atitle=N18-RE-105+cells%3A+differentiation+and+activation+of+p53+in+response+to+glutamate+and+adriamycin+is+blocked+by+SV40+large+T+antigen+tsA58.&rft.au=Dillon-Carter%2C+O%3BConejero%2C+C%3BTornatore%2C+C%3BPoltorak%2C+M%3BFreed%2C+W+J&rft.aulast=Dillon-Carter&rft.aufirst=O&rft.date=1998-02-01&rft.volume=291&rft.issue=2&rft.spage=191&rft.isbn=&rft.btitle=&rft.title=Cell+and+tissue+research&rft.issn=0302766X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-23 N1 - Date created - 1998-03-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - N terminus of Sos1 Ras exchange factor: critical roles for the Dbl and pleckstrin homology domains. AN - 79662103; 9447973 AB - We have studied the functional importance of the N terminus of mouse Sos1 (mSos1), a ubiquitously expressed Ras-specific guanine nucleotide exchange factor whose C-terminal sequences bind Grb-2. Consistent with previous reports, addition of a myristoylation signal to mSos1 (MyrSos1) rendered it transforming for NIH 3T3 cells and deletion of the mSos C terminus (MyrSos1-deltaC) did not interfere with this activity. However, an N-terminally deleted myristoylated mSos1 protein (MyrSos1-deltaN) was transformation defective, although the protein was stable and localized to the membrane. Site-directed mutagenesis was used to examine the role of the Dbl and pleckstrin homology (PH) domains located in the N terminus. When mutations in the PH domain were introduced into two conserved amino acids either singly or together in MyrSos1 or MyrSos1-deltaC, the transforming activity was severely impaired. An analogous reduction in biological activity was seen when a cluster of point mutations was engineered into the Dbl domain. The mitogen-activation protein (MAP) kinase activities induced by the various Dbl and PH mutants of MyrSos1 correlated with their biological activities. When NIH 3T3 cells were transfected with a myristoylated Sos N terminus, their growth response to epidermal growth factor (EGF), platelet-derived growth factor, lysophosphatidic acid or serum was greatly impaired. The dominant inhibitory biological activity of the N terminus correlated with its ability to impair EGF-dependent activation of GTP-Ras and of MAP kinase, as well with the ability of endogenous Sos to form a stable complex with activated EGF receptors. The N terminus with mutations in the Dbl and PH domains was much less inhibitory in these biological and biochemical assays. In contrast to wild-type Sos1, nonmyristoylated versions of Sos1-deltaN and Sos1-deltaC did not form a stable complex with activated EGF receptors. We conclude that the Dbl and PH domains are critical for Sos function and that stable association of Sos with activated EGF receptors requires both the Sos N and C termini. JF - Molecular and cellular biology AU - Qian, X AU - Vass, W C AU - Papageorge, A G AU - Anborgh, P H AU - Lowy, D R AD - Laboratory of Cellular Oncology, Division of Basic Sciences, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1998/02// PY - 1998 DA - February 1998 SP - 771 EP - 778 VL - 18 IS - 2 SN - 0270-7306, 0270-7306 KW - Adaptor Proteins, Signal Transducing KW - 0 KW - Blood Proteins KW - GRB2 Adaptor Protein KW - Grb2 protein, mouse KW - Guanine Nucleotide Exchange Factors KW - Mcf2 protein, mouse KW - Phosphoproteins KW - Proteins KW - Retroviridae Proteins, Oncogenic KW - platelet protein P47 KW - ras Guanine Nucleotide Exchange Factors KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - Calcium-Calmodulin-Dependent Protein Kinases KW - EC 2.7.11.17 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Calcium-Calmodulin-Dependent Protein Kinases -- metabolism KW - Animals KW - 3T3 Cells KW - Receptor, Epidermal Growth Factor -- metabolism KW - Mice KW - Protein Binding KW - Amino Acid Substitution KW - Structure-Activity Relationship KW - Binding Sites KW - Proteins -- chemistry KW - Blood Proteins -- chemistry KW - Retroviridae Proteins, Oncogenic -- chemistry KW - Blood Proteins -- metabolism KW - Retroviridae Proteins, Oncogenic -- metabolism KW - Proteins -- metabolism KW - Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79662103?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=N+terminus+of+Sos1+Ras+exchange+factor%3A+critical+roles+for+the+Dbl+and+pleckstrin+homology+domains.&rft.au=Qian%2C+X%3BVass%2C+W+C%3BPapageorge%2C+A+G%3BAnborgh%2C+P+H%3BLowy%2C+D+R&rft.aulast=Qian&rft.aufirst=X&rft.date=1998-02-01&rft.volume=18&rft.issue=2&rft.spage=771&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 - 1998-02-24 N1 - Date created - 1998-02-24 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cell. 1993 May 7;73(3):611-20 [8490966] Mol Cell Biol. 1997 Dec;17(12):7132-8 [9372945] Annu Rev Biochem. 1993;62:851-91 [8352603] Mol Cell Biol. 1993 Dec;13(12):7718-24 [8246988] J Biol Chem. 1994 Jan 7;269(1):62-5 [8276860] Mol Cell Biol. 1994 Aug;14(8):5192-201 [7518560] Trends Biochem Sci. 1994 Jul;19(7):279-83 [8048167] J Biol Chem. 1994 Aug 19;269(33):21103-9 [8063729] Proc Natl Acad Sci U S A. 1994 Aug 30;91(18):8512-6 [8078913] Cell. 1994 Sep 23;78(6):949-61 [7923364] Biochemistry. 1995 Feb 7;34(5):1475-81 [7849006] Science. 1995 Apr 28;268(5210):576-9 [7725106] Proc Natl Acad Sci U S A. 1983 Aug;80(16):4949-53 [6192445] J Biol Chem. 1989 Apr 5;264(10):5791-8 [2564392] Proc Natl Acad Sci U S A. 1992 Jul 15;89(14):6511-5 [1631150] Science. 1992 Jul 31;257(5070):671-4 [1496380] Nature. 1993 May 6;363(6424):45-51 [8479536] Nature. 1993 May 6;363(6424):85-8 [8479541] Nature. 1993 May 6;363(6424):88-92 [8386805] Cancer Res. 1991 Jan 15;51(2):712-7 [1985788] Cell. 1991 Nov 15;67(4):701-16 [1934068] Mol Cell Biol. 1991 Dec;11(12):6026-33 [1658623] Nature. 1991 Nov 28;354(6351):311-4 [1956381] Science. 1992 Jan 31;255(5044):603-6 [1736363] Nature. 1992 Mar 26;356(6367):340-4 [1372395] J Biol Chem. 1995 May 19;270(20):11707-10 [7744811] Immunity. 1995 May;2(5):451-60 [7538439] J Biol Chem. 1995 Jul 7;270(27):15954-7 [7608150] Nat Genet. 1995 Jul;10(3):294-300 [7670467] Biochem J. 1995 Dec 15;312 ( Pt 3):661-6 [8554502] Bioessays. 1996 Jan;18(1):35-46 [8593162] Curr Opin Cell Biol. 1996 Apr;8(2):197-204 [8791426] Curr Opin Cell Biol. 1996 Apr;8(2):216-22 [8791419] J Biol Chem. 1996 Sep 27;271(39):24300-6 [8798677] Cancer Surv. 1996;27:87-100 [8909796] Oncogene. 1996 Nov 21;13(10):2055-65 [8950972] Curr Opin Genet Dev. 1997 Feb;7(1):75-9 [9024640] EMBO J. 1997 Feb 17;16(4):706-16 [9049300] Prog Biophys Mol Biol. 1996;66(1):1-41 [9107131] EMBO J. 1997 Mar 17;16(6):1351-9 [9135150] FEBS Lett. 1997 Apr 21;407(1):111-5 [9141492] Science. 1993 May 28;260(5112):1338-43 [8493579] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dynamic contact maps of protein structures. AN - 69986692; 9783253 AB - The two-dimensional contact map of interresidue distances is a visual analysis technique for protein structures. We present two standalone software tools designed to be used in combination to increase the versatility of this simple yet powerful technique. First, the program Structer calculates contact maps from three-dimensional molecular structural data. The contact map matrix can then be viewed in the graphical matrix-visualization program Dotter. Instead of using a predefined distance cutoff, we exploit Dotter's dynamic rendering control, allowing interactive exploration at varying distance cutoffs after calculating the matrix once. Structer can use a number of distance measures, can incorporate multiple chains in one contact map, and allows masking of user-defined residue sets. It works either directly with PDB files, or can use the MMDB network API for reading structures. JF - Journal of molecular graphics & modelling AU - Sonnhammer, E L AU - Wootton, J C AD - Computational Biology Branch, National Library of Medicine, National Institutes of Health, Bethesda, Maryland 20894, USA. Y1 - 1998/02// PY - 1998 DA - February 1998 SP - 1 EP - 5, 33 VL - 16 IS - 1 SN - 1093-3263, 1093-3263 KW - Diphtheria Toxin KW - 0 KW - Histocompatibility Antigens Class II KW - Index Medicus KW - Histocompatibility Antigens Class II -- chemistry KW - Diphtheria Toxin -- chemistry KW - Humans KW - Software KW - Computer Simulation KW - Models, Molecular KW - Protein Conformation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69986692?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+graphics+%26+modelling&rft.atitle=Dynamic+contact+maps+of+protein+structures.&rft.au=Sonnhammer%2C+E+L%3BWootton%2C+J+C&rft.aulast=Sonnhammer&rft.aufirst=E&rft.date=1998-02-01&rft.volume=16&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Journal+of+molecular+graphics+%26+modelling&rft.issn=10933263&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-12-30 N1 - Date created - 1998-12-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Sex Differences in Marital and Social Adjustment AN - 60083254; 9905655 AB - A sample of 146 married Japanese men & women, ages 25-85, were interviewed to clarify the relationship between marital adjustment & social adjustment. For the whole sample, the total score of the Short Marital Adjustment Test (SMAT) & its subcategories, dyadic consensus & satisfaction, was significantly correlated with five subcategory scores of the Social Adjustment Scale-II: household adjustment (except the spouse), external family adjustment, work adjustment, social leisure adjustment, & general adjustment. For the men, these correlations were only present for social leisure & general adjustment. Among men, the dyadic consensus scores of the SMAT had stronger correlations with the social adjustment scores; among women, correlations with the marital satisfaction scores were stronger. Thus, marital adjustment may be a part of social adjustment for women, but the two may be discrete for men. 1 Table, 16 References. Adapted from the source document. JF - Journal of Social Psychology AU - Kitamura, Toshinori AU - Aoki, Mitsuka AU - Fujino, Masako AU - Ura, Chiaki AU - Watanabe, Mayumi AU - Watanabe, Kyoko AU - Fujihara, Shigeki AD - Dept Sociocultural Environmental Research NIMH, 1-7-3 Konodai Ichikawa Chiba 272 Japan Y1 - 1998/02// PY - 1998 DA - February 1998 SP - 26 EP - 32 VL - 138 IS - 1 SN - 0022-4545, 0022-4545 KW - Husbands KW - Wives KW - Sex Differences KW - Marriage KW - Marital Satisfaction KW - Adjustment KW - Japan KW - article KW - 1941: the family and socialization; sociology of the family, marriage, & divorce KW - 0312: social psychology; personality & social roles (individual traits, social identity, adjustment, conformism, & deviance) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/60083254?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Asocabs&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Social+Psychology&rft.atitle=Sex+Differences+in+Marital+and+Social+Adjustment&rft.au=Kitamura%2C+Toshinori%3BAoki%2C+Mitsuka%3BFujino%2C+Masako%3BUra%2C+Chiaki%3BWatanabe%2C+Mayumi%3BWatanabe%2C+Kyoko%3BFujihara%2C+Shigeki&rft.aulast=Kitamura&rft.aufirst=Toshinori&rft.date=1998-02-01&rft.volume=138&rft.issue=1&rft.spage=26&rft.isbn=&rft.btitle=&rft.title=Journal+of+Social+Psychology&rft.issn=00224545&rft_id=info:doi/ LA - English DB - Sociological Abstracts N1 - Date revised - 2007-10-30 N1 - Last updated - 2016-09-28 N1 - CODEN - JSPSAG N1 - SubjectsTermNotLitGenreText - Adjustment; Marriage; Sex Differences; Japan; Marital Satisfaction; Husbands; Wives ER - TY - JOUR T1 - In vitro techniques for the assessment of neurotoxicity. AN - 21262698; 11702142 AB - Risk assessment is a process often divided into the following steps: a) hazard identification, b) dose-response assessment, c) exposure assessment, and d) risk characterization. Regulatory toxicity studies usually are aimed at providing data for the first two steps. Human case reports, environmental research, and in vitro studies may also be used to identify or to further characterize a toxic hazard. In this report the strengths and limitations of in vitro techniques are discussed in light of their usefulness to identify neurotoxic hazards, as well as for the subsequent dose-response assessment. Because of the complexity of the nervous system, multiple functions of individual cells, and our limited knowledge of biochemical processes involved in neurotoxicity, it is not known how well any in vitro system would recapitulate the in vivo system. Thus, it would be difficult to design an in vitro test battery to replace in vivo test systems. In vitro systems are well suited to the study of biological processes in a more isolated context and have been most successfully used to elucidate mechanisms of toxicity, identify target cells of neurotoxicity, and delineate the development and intricate cellular changes induced by neurotoxicants. Both biochemical and morphological end points can be used, but many of the end points used can be altered by pharmacological actions as well as toxicity. Therefore, for many of these end points it is difficult or impossible to set a criterion that allows one to differentiate between a pharmacological and a neurotoxic effect. For the process of risk assessment such a discrimination is central. Therefore, end points used to determine potential neurotoxicity of a compound have to be carefully selected and evaluated with respect to their potential to discriminate between an adverse neurotoxic effect and a pharmacologic effect. It is obvious that for in vitro neurotoxicity studies the primary end points that can be used are those affected through specific mechanisms of neurotoxicity. For example, in vitro systems may be useful for certain structurally defined compounds and mechanisms of toxicity, such as organophosphorus compounds and delayed neuropathy, for which target cells and the biochemical processes involved in the neurotoxicity are well known. For other compounds and the different types of neurotoxicity, a mechanism of toxicity needs to be identified first. Once identified, by either in vivo or in vitro methods, a system can be developed to detect and to evaluate predictive ability for the type of in vivo neurotoxicity produced. Therefore, in vitro tests have their greatest potential in providing information on basic mechanistic processes in order to refine specific experimental questions to be addressed in the whole animal. Images Figure 1 JF - Environmental Health Perspectives AU - Harry, G J AU - Billingsley, M AU - Bruinink, A AU - Campbell, I L AU - Classen, W AU - Dorman, D C AU - Galli, C AU - Ray, D AU - Smith, R A AU - Tilson, H A AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA., harry@niehs.nih.gov Y1 - 1998/02// PY - 1998 DA - Feb 1998 SP - 131 EP - 158 PB - US Government Printing Office, Superintendent of Documents, P.O. Box 371954 Pittsburgh PA 15250-7954 USA VL - 106 IS - Suppl 1 SN - 0091-6765, 0091-6765 KW - Risk Abstracts; Pollution Abstracts; CSA Neurosciences Abstracts; Environment Abstracts KW - Risk assessment KW - discrimination KW - Data processing KW - Organophosphorus compounds KW - Biochemistry KW - Toxicity KW - Nervous system KW - Case reports KW - Dose-response effects KW - Neurotoxicity KW - Neuropathy KW - N3 11028:Neuropharmacology & toxicology KW - R2 23050:Environment KW - P 6000:TOXICOLOGY AND HEALTH KW - ENA 02:Toxicology & Environmental Safety UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/21262698?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+Health+Perspectives&rft.atitle=In+vitro+techniques+for+the+assessment+of+neurotoxicity.&rft.au=Harry%2C+G+J%3BBillingsley%2C+M%3BBruinink%2C+A%3BCampbell%2C+I+L%3BClassen%2C+W%3BDorman%2C+D+C%3BGalli%2C+C%3BRay%2C+D%3BSmith%2C+R+A%3BTilson%2C+H+A&rft.aulast=Cao&rft.aufirst=Xing&rft.date=2015-11-01&rft.volume=186&rft.issue=&rft.spage=58&rft.isbn=&rft.btitle=&rft.title=Journal+of+Affective+Disorders&rft.issn=01650327&rft_id=info:doi/10.1016%2Fj.jad.2015.06.058 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-01-01 N1 - Last updated - 2015-03-31 N1 - SubjectsTermNotLitGenreText - Risk assessment; Nervous system; Organophosphorus compounds; Data processing; Case reports; Neurotoxicity; Neuropathy; discrimination; Biochemistry; Dose-response effects; Toxicity ER - TY - JOUR T1 - Reducing Cigarette Sales to Minors in an Urban Setting: Issues and Opportunities for Merchant Intervention AN - 17387378; 4610173 AB - Intervention studies to reduce cigarette sales to minors have been conducted primarily in suburban settings. Little is known about sociocultural factors influencing cigarette sales to minors in urban settings. This study sought to determine sociodemographic and cultural factors that may play a role in cigarette sales and in efforts to reduce sales to minors in urban areas. Merchant education and follow-up surveys were conducted in small local stores in predominantly African-American urban census tracts in Baltimore. The stores had prior evidence of cigarette sales to minors. Merchants reported hostility (66%) and foul language (64%) when they requested youth identification. Youthful-oriented advertising of cigarettes was highly prevalent in all stores and moreso in stores owned and staffed by Asian merchants. Advertising with specific youthful content was predictive (OR = 3.97; 95% CI = 1.70, 9.23; P = .0014) of higher requests for cigarettes from minors. Youth-oriented cigarette advertising is a prevalent environmental risk for urban youth. Differences between Asian and African-American merchants suggest socioethnic factors may be an influential component of illegal sales and educational campaigns to reduce smoking among minors. JF - American Journal of Preventive Medicine AU - Voorhees, C C AU - Yanek, L R AU - Stillman, F A AU - Becker, D M AD - NHLBI/NIH, Division of Epidemiology and Clinical Applications, Prevention and Behavioral Medicine SRG, Rockledge 2, Room 8215, Bethesda, MD 20892-7936, USA Y1 - 1998/02// PY - 1998 DA - Feb 1998 SP - 138 EP - 142 VL - 14 IS - 2 SN - 0749-3797, 0749-3797 KW - African Americans KW - USA, Maryland, Baltimore KW - advertising KW - disease control KW - marketing KW - Health & Safety Science Abstracts KW - Cigarette smoking KW - Adolescents KW - Urban areas KW - H 4000:Food and Drugs UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17387378?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthsafetyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Journal+of+Preventive+Medicine&rft.atitle=Reducing+Cigarette+Sales+to+Minors+in+an+Urban+Setting%3A+Issues+and+Opportunities+for+Merchant+Intervention&rft.au=Voorhees%2C+C+C%3BYanek%2C+L+R%3BStillman%2C+F+A%3BBecker%2C+D+M&rft.aulast=Voorhees&rft.aufirst=C&rft.date=1998-02-01&rft.volume=14&rft.issue=2&rft.spage=138&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Preventive+Medicine&rft.issn=07493797&rft_id=info:doi/10.1016%2FS0749-3797%2897%2900024-X LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Urban areas; Adolescents; Cigarette smoking DO - http://dx.doi.org/10.1016/S0749-3797(97)00024-X ER - TY - JOUR T1 - An Inverse Relation between cagA super(+) Strains of Helicobacter pylori Infection and Risk of Esophageal and Gastric Cardia Adenocarcinoma AN - 17278179; 4493384 AB - Gastric colonization with Helicobacter pylori, especially cagA super(+) strains, is a risk factor for noncardia gastric adenocarcinoma, but its relationship with gastric cardia adenocarcinoma is unclear. Although incidence rates for noncardia gastric adenocarcinoma have declined steadily, paralleling a decline in H. pylori prevalence, rates for adenocarcinomas of esophagus and gastric cardia have sharply increased in industrialized countries in recent decades. To clarify the role of H. pylori infection in these tumors with divergent incidence trends, we analyzed serum IgG antibodies to H. pylori and to a recombinant fragment of CagA by antigen-specific ELISA among 129 patients newly diagnosed with esophageal/gastric cardia adenocarcinoma, 67 patients with noncardia gastric adenocarcinoma, and 224 population controls. Cancer risks were estimated by odds ratios (OR) and 95% confidence intervals (CI) using logistic regression models. Infection with cagA super(+) strains was not significantly related to risk for noncardia gastric cancers (OR, 1.4; CI, 0.7-2.8) but was significantly associated with a reduced risk for esophageal/cardia cancers (OR, 0.4; CI, 0.2-0.8). However, there was little association with cagA super(-) strains of H. pylori for either cancer site (OR, 1.0 and 1.1, respectively). These findings suggest that the effects of H. pylori strains on tumor development vary by anatomical site. Further studies are needed to confirm these results and to assess whether the decreasing prevalence of H. pylori, especially cagA super(+) strains, may be associated with the rising incidence of esophageal/gastric cardia adenocarcinomas in industrialized countries. JF - Cancer Research AU - Chow, W-H AU - Blaser, MJ AU - Blot, W J AU - Gammon, MD AU - Vaughan, T L AU - Risch, HA AU - Perez-Perez, GI AU - Schoenberg, J B AU - Stanford, J L AU - Rotterdam, H AU - West, AB AU - Fraumeni, JF Jr AD - National Cancer Institute, 6130 Executive Boulevard, EPN 418, Rockville, MD 20852, USA Y1 - 1998/02// PY - 1998 DA - Feb 1998 SP - 588 EP - 590 VL - 58 IS - 4 SN - 0008-5472, 0008-5472 KW - cagA protein KW - gastric adenocarcinoma KW - Microbiology Abstracts B: Bacteriology KW - Intestinal microflora KW - Helicobacter pylori KW - Gastrointestinal tract diseases KW - Esophageal carcinoma KW - Carcinoma KW - J 02846:Gastrointestinal tract UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17278179?accountid=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=Cancer+Research&rft.atitle=An+Inverse+Relation+between+cagA+super%28%2B%29+Strains+of+Helicobacter+pylori+Infection+and+Risk+of+Esophageal+and+Gastric+Cardia+Adenocarcinoma&rft.au=Chow%2C+W-H%3BBlaser%2C+MJ%3BBlot%2C+W+J%3BGammon%2C+MD%3BVaughan%2C+T+L%3BRisch%2C+HA%3BPerez-Perez%2C+GI%3BSchoenberg%2C+J+B%3BStanford%2C+J+L%3BRotterdam%2C+H%3BWest%2C+AB%3BFraumeni%2C+JF+Jr&rft.aulast=Chow&rft.aufirst=W-H&rft.date=1998-02-01&rft.volume=58&rft.issue=4&rft.spage=588&rft.isbn=&rft.btitle=&rft.title=Cancer+Research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Helicobacter pylori; Esophageal carcinoma; Intestinal microflora; Carcinoma; Gastrointestinal tract diseases ER - TY - JOUR T1 - Nosocomial catheter-associated Flavobacterium odoratum bacteraemia in cancer patients AN - 16481093; 4287610 JF - Journal of Medical Microbiology AU - Spanik, S AU - Trupl, J AU - Krcmery, V AD - Department of Medicine, Microbiology and Pharmacology, National Cancer Institute and St. Elizabeth Cancer Institute, Heydukova 10, 812 50 Bratislava, Slovak Republic Y1 - 1998/02// PY - 1998 DA - Feb 1998 SP - 183 VL - 47 IS - 2 SN - 0022-2615, 0022-2615 KW - Microbiology Abstracts B: Bacteriology KW - J 02855:Human Bacteriology: Others UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16481093?accountid=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=Health+Communication&rft.atitle=Social+support+functions+during+a+slowly-evolving+environmental+disaster%3A+The+case+of+amphibole+asbestos+exposure+in+Libby%2C+Montana&rft.au=Cline%2C+Rebecca+J.+W.%3BOrom%2C+Heather%3BChild%2C+Jeffrey+T.%3BHernandez%2C+Tanis%3BBlack%2C+Brad&rft.aulast=Cline&rft.aufirst=Rebecca+J.&rft.date=2015-11-01&rft.volume=30&rft.issue=11&rft.spage=1135&rft.isbn=&rft.btitle=&rft.title=Health+Communication&rft.issn=10410236&rft_id=info:doi/10.1080%2F10410236.2014.922456 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Serum caffeine and paraxanthine as markers for reported caffeine intake in pregnancy AN - 16457637; 4344162 AB - PURPOSE: Previous studies of maternal caffeine use and pregnancy outcome have relied on selfreported use. Even if these were perfectly accurate, inter-individual differences in caffeine metabolism result in a relatively weak correlation between caffeine intake and serum concentration. The purpose of this study was to determine whether the serum concentration of caffeine or its primary metabolite, paraxanthine, obtained at an unknown time during working hours, is useful to distinguish between pregnant women who report consuming small and large amounts of caffeine. METHODS: We selected from the Birmingham fetal growth study 60 women with normal pregnancy outcomes who reported consuming less than or equal to 0.8 mg/kg/day of caffeine in a 24-hour dietary recall, 60 who consumed 0.81-2.5 mg/kg/day, 60 who consumed 2.51-5.0 mg/kg/day and 59 who consumed greater than or equal to 5.01 mg/kg/day. These women had serum drawn for storage during regular clinic hours on the same day as the recall interview. Caffeine and paraxanthine were measured in the stored serum using high performance liquid chromatography. RESULTS: The weighted kappa coefficient between strata of caffeine intake and quartiles of serum paraxanthine was 0.58 among smokers and 0.53 among nonsmokers, versus 0.44 and 0.51, respectively, for quartiles of serum caffeine. The Pearson correlation coefficient between intake and paraxanthine was 0.50 for smokers and 0.53 for nonsmokers, and 0.37 and 0.51, respectively, for serum caffeine. These values are comparable to the correlation between reported smoking and serum cotinine in pregnancy. CONCLUSIONS: The serum concentrations of paraxanthine, and to a lesser degree, caffeine are useful to distinguish between women with varying levels of caffeine intake. JF - Annals of Epidemiology AU - Klebanoff, MA AU - Levine, R J AU - Dersimonian, R AU - Clemens, J D AU - Wilkins, D G AD - DESPR, NICHD, NIH, 6100 Bldg Room 7B03, Bethesda, MD 20892-7510, USA Y1 - 1998/02// PY - 1998 DA - Feb 1998 SP - 107 EP - 111 VL - 8 IS - 2 SN - 1047-2797, 1047-2797 KW - caffeine KW - dietary intake KW - man KW - paraxanthine KW - pregnancy KW - serum levels KW - Toxicology Abstracts KW - X 24120:Food, additives & contaminants UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16457637?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+Epidemiology&rft.atitle=Serum+caffeine+and+paraxanthine+as+markers+for+reported+caffeine+intake+in+pregnancy&rft.au=Klebanoff%2C+MA%3BLevine%2C+R+J%3BDersimonian%2C+R%3BClemens%2C+J+D%3BWilkins%2C+D+G&rft.aulast=Klebanoff&rft.aufirst=MA&rft.date=1998-02-01&rft.volume=8&rft.issue=2&rft.spage=107&rft.isbn=&rft.btitle=&rft.title=Annals+of+Epidemiology&rft.issn=10472797&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Case-control study of childhood acute lymphoblastic leukemia and residential radon exposure AN - 16456548; 4357725 AB - Several ecologic analyses have shown significant positive associations between mean indoor radon concentrations and risk of leukemia at all ages (acute myeloid leukemia and chronic lymphocytic leukemia) and for children (all leukemia, acute myeloid leukemia, and acute lymphoblastic leukemia). As part of an age-matched, case-control study of childhood ALL in the United States, we investigated the association between the incidence of ALL in children under age 15 years and indoor radon exposure. Radon detectors were placed in current and previous homes of subjects where they resided for 6 months or longer. Children were included in analyses if radon measurements covered 70% or more of the 5-year period prior to diagnosis for case subjects (or from birth for case subjects under age 5 years) and the corresponding reference dates for control subjects. In contrast to prior ecologic studies, the results from this analytic study provide no evidence for an association between indoor radon exposure and childhood ALL. JF - J. NATL. CANCER INST. AU - Lubin, J H AU - Linet AU - Boice, JD Jr AU - Buckley, J AU - Conrath, S M AU - Hatch, EE AU - Kleinerman, R A AU - Tarone, R E AU - Wacholder, Sh AU - Robison, L L AD - National Institutes of Health, Executive Plaza North, Rm. 403, Bethesda, MD 20892-7368, USA Y1 - 1998/02// PY - 1998 DA - Feb 1998 SP - 294 EP - 300 VL - 90 IS - 4 SN - 0027-8874, 0027-8874 KW - Risk Abstracts; Health & Safety Science Abstracts; Pollution Abstracts KW - R2 23030:Natural hazards KW - H 8000:Radiation Safety/Electrical Safety KW - P 8000:RADIATION UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16456548?accountid=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=J.+NATL.+CANCER+INST.&rft.atitle=Case-control+study+of+childhood+acute+lymphoblastic+leukemia+and+residential+radon+exposure&rft.au=Lubin%2C+J+H%3BLinet%3BBoice%2C+JD+Jr%3BBuckley%2C+J%3BConrath%2C+S+M%3BHatch%2C+EE%3BKleinerman%2C+R+A%3BTarone%2C+R+E%3BWacholder%2C+Sh%3BRobison%2C+L+L&rft.aulast=Lubin&rft.aufirst=J&rft.date=1998-02-01&rft.volume=90&rft.issue=4&rft.spage=294&rft.isbn=&rft.btitle=&rft.title=J.+NATL.+CANCER+INST.&rft.issn=00278874&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Dry deposition modeling of nitrate and sulfate by using particle size distribution data AN - 16401356; 4315413 AB - Dry deposition and air sampling were undertaken simultaneously in the ambient air of Ping Tung area by using several dry deposition plates, two MOUDIs (Micro-orifice Uniform Deposit Impactors) and one NRI (Noll Rotary Impactor) from December 1995 to May 1996 in Southern Taiwan. The NRI and MOUDI were used to collect ambient coarse and fine particulate, respectively. Dry deposition plate was applied to collect particle deposition flux. An ion chromatography (Dionex 2000i/sP) equipped with 4 mm AG4A-SC and AS4A-SC column was employed to analyze the anion species (NO sub(3) super(-) and SO sub(4) super(2-)). The eluent solution is 1.8 mM sodium carbonate/1.7mM sodium bicarbonate. The calculated dry deposition flux for each particle size range was obtained by using measured mass-size distribution data between 0.18 and 100 mu m diameter and a dry deposition model. The mean modeled/measured (Md/Ma) ratio of dry deposition flux varied between 1.11 and 1.28, between 1.28 and 1.42 and between 0.88 and 0.97 for nitrate, sulfate and total particle mass, respectively. The results indicated that nitrate and sulfate were slightly overestimated by a dry deposition model, while total particle mass was slightly underestimated by this model. In general, by using the particle size distribution data, this dry deposition model can provide a good predication for the dry deposition flux of nitrate, sulfate and total particle mass. More than 87.5% of nitrate and more than 92.9% of sulfate dry deposition flux are contributed by particle diameters larger than 10 mu m. This is due to the fact that particle size larger than 10 mu m have higher dry deposition velocities (>4.65 cm/sec) and control the majority of the dry deposition flux. JF - Journal of Environmental Science and Health, Part A: Toxic/Hazardous Substances & Environmental Engineering AU - Chen, S J AU - Lin, C C AU - Chiu, S C AD - Department of Environmental Protection Technology, National Ping-Tung University of Science and Technology, Nei Pu 91207, Ping Tung, Taiwan Y1 - 1998/02// PY - 1998 DA - Feb 1998 SP - 307 EP - 334 VL - A33 IS - 2 SN - 1093-4529, 1093-4529 KW - Taiwan, Ping Tung KW - Pollution Abstracts KW - P 0000:AIR POLLUTION UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16401356?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Apollution&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Environmental+Science+and+Health%2C+Part+A%3A+Toxic%2FHazardous+Substances+%26+Environmental+Engineering&rft.atitle=Dry+deposition+modeling+of+nitrate+and+sulfate+by+using+particle+size+distribution+data&rft.au=Chen%2C+S+J%3BLin%2C+C+C%3BChiu%2C+S+C&rft.aulast=Chen&rft.aufirst=S&rft.date=1998-02-01&rft.volume=A33&rft.issue=2&rft.spage=307&rft.isbn=&rft.btitle=&rft.title=Journal+of+Environmental+Science+and+Health%2C+Part+A%3A+Toxic%2FHazardous+Substances+%26+Environmental+Engineering&rft.issn=10934529&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Helicobacter pylori adheres selectively to Fusobacterium spp. AN - 16364791; 4270222 AB - Helicobacter pylori strains ATCC 43504 and ATCC 43629 were tested for their ability to coaggregate with 79 strains of bacteria representing 16 genera. All except two of the strains were of human origin, and most of the strains were isolated from the oral cavity. The helicobacters failed to coaggregate with all strains except the fusobacteria. Several coaggregations were partially or completely inhibited by lactose. Strong coaggregation was seen with each of four subspecies of Fusobacterium nucleatum and with Fusobacterium periodonticum ATCC 33693, all of human dental plaque origin. In contrast, the helicobacters failed to coaggregate with non-plaque isolates, Fusobacterium mortiferum ATCC 25557 and Fusobacterium ulcerans ATCC 49185. Heat treatment of the fusobacteria inactivated their ability to coaggregate, whereas heating of the helicobacter partners had no effect, suggesting the presence of an adhesin on the fusobacteria and a corresponding receptor on the helicobacters. The potential ability of H. pylori to colonize the oral cavity by adhering selectively to the ubiquitous fusobacteria gives credence to the possibility that dental plaque may serve as a reservoir for this pathogen outside of the stomach. JF - Oral Microbiology and Immunology AU - Andersen, R N AU - Ganeshkumar, N AU - Kolenbrander, P E AD - National Institutes of Health, Building 30, Room 310, 30 Convent Drive MSC 4350, Bethesda, MD 20892-4350, USA Y1 - 1998/02// PY - 1998 DA - Feb 1998 SP - 51 EP - 54 VL - 13 IS - 1 SN - 0902-0055, 0902-0055 KW - bacteria KW - coaggregates KW - lactose KW - man KW - Microbiology Abstracts B: Bacteriology KW - J 02844:Dental and oral UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16364791?accountid=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=Oral+Microbiology+and+Immunology&rft.atitle=Helicobacter+pylori+adheres+selectively+to+Fusobacterium+spp.&rft.au=Andersen%2C+R+N%3BGaneshkumar%2C+N%3BKolenbrander%2C+P+E&rft.aulast=Andersen&rft.aufirst=R&rft.date=1998-02-01&rft.volume=13&rft.issue=1&rft.spage=51&rft.isbn=&rft.btitle=&rft.title=Oral+Microbiology+and+Immunology&rft.issn=09020055&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Population structure of the relapsing fever spirochete Borrelia hermsii as indicated by polymorphism of two multigene families that encode imunogenic outer surface lipoproteins AN - 16337136; 4270323 AB - The tick-borne relapsing fever spirochete Borrelia hermsii evades the mammalian immune system by periodically switching expression among members of two multigene families that encode immunogenic, antigenically distinct outer surface proteins. The type strain, B. hermsii HS1, has at least 40 complete genes and pseudogenes that participate in this multiphasic antigenic variation. Originally termed vmp (for variable major protein) genes, they have been reclassified as vsp (for variable small protein) and vlp (for variable large protein) genes, based on size and amino acid sequence similarities. To date, antigenic variation in B. hermsii has been studied only in the type strain, HS1. Nucleotide sequence comparisons of 23 B. hermsii HS1 genes revealed five distinct groups, the vsp gene family and four subfamilies of vlp genes. We used PCR with family- and subfamily-specific primers, followed by restriction fragment length polymorphism analysis, to compare the vsp and vlp repertoires of HS1 and seven other B. hermsii isolates from Washington, Idaho, and California. This analysis, together with pulsed-field gel electrophoresis genome profiles, revealed that the eight isolates formed three distinct groups, which likely represent clonal lineages. Members of the three groups coexisted in the same geographic area, but they could also be isolated across large geographical distances. This population structure may result from immune selection by the host, as has been proposed for other pathogens with polymorphic antigens. JF - Infection and Immunity AU - Hinnebusch, B J AU - Barbour, A G AU - Restrepo, B I AU - Schwan, T G AD - Laboratory of Microbial Structure and Function, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 S. 4th St., Hamilton, MT 59840, USA, joe_hinnebusch@nih.gov Y1 - 1998/02// PY - 1998 DA - Feb 1998 SP - 432 EP - 440 VL - 66 IS - 2 SN - 0019-9567, 0019-9567 KW - nucleotide sequence KW - polymerase chain reaction KW - vlp gene KW - vmp gene KW - vsp gene KW - Genetics Abstracts; Microbiology Abstracts B: Bacteriology KW - J 02725:DNA KW - G 07290:Population genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16337136?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Infection+and+Immunity&rft.atitle=Population+structure+of+the+relapsing+fever+spirochete+Borrelia+hermsii+as+indicated+by+polymorphism+of+two+multigene+families+that+encode+imunogenic+outer+surface+lipoproteins&rft.au=Hinnebusch%2C+B+J%3BBarbour%2C+A+G%3BRestrepo%2C+B+I%3BSchwan%2C+T+G&rft.aulast=Hinnebusch&rft.aufirst=B&rft.date=1998-02-01&rft.volume=66&rft.issue=2&rft.spage=432&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Development of a preliminary ground water flow model for water resources management in the Pingtung Plain, Taiwan AN - 16316607; 4249295 AB - Pingtung Plain is formed by Quaternary alluvial fan material from the three main rivers: Kaoping, Tungkang and Linpien. Ground water is the major water supply source on the plain. This is principally extracted from two aquifers. The natural ground water source is derived mainly from direct rainfall percolation and infiltration from the three rivers, with their catchments lying partly outside the plain. Rainfall characteristics are therefore the main factors controlling water resources availability. Pingtung Plain is an important primary production area for southern Taiwan, the comparatively warm climate allowing a long growing season, diversified cropping and the rearing of aquacultural produces. Approximately 75 percent of irrigation and domestic water supplies are derived from ground water. A water balance for the entire plain indicates that ground water resources, under optimized management, are sufficient to meet the existing multi-purpose uses. Development of a hydrogeological conceptual model is the first phase of a numerical ground water flow simulation. Preliminary results are encouraging, with the final simulations affording better insight to the hydraulic behavior of the aquifer system. Data input requirements for model operation fall into three categories: hydrological stresses, hydrogeological parameters and boundary conditions. After the model is built, the normal numerical modeling process requires significant calibration and sensitivity analyses for the hydrogeological parameters and stresses which are the most sensitive, but the least well defined. A well-calibrated simulation model can lead to a reliable and realistic management model. With this in mind, the calibration processes detailed are presented, and these data are introduced as initial values in the calibration process. JF - Ground Water AU - Ting, Cheh-Shyh AU - Zhou, Yangxiao AU - De Vries, JJ AU - Simmers, I AD - Dep. Civ. Eng., Natl. Pingtung Univ. Sci. and Technol., No. 1, Hseuh Fu Rd., Nei Pu Hsiang, Pingtung, Taiwan, ROC Y1 - 1998/02// PY - 1998 DA - Feb 1998 SP - 20 EP - 36 VL - 36 IS - 1 SN - 0017-467X, 0017-467X KW - Water Resources Abstracts KW - SW 0840:Groundwater UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16316607?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Awaterresources&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Ground+Water&rft.atitle=Development+of+a+preliminary+ground+water+flow+model+for+water+resources+management+in+the+Pingtung+Plain%2C+Taiwan&rft.au=Ting%2C+Cheh-Shyh%3BZhou%2C+Yangxiao%3BDe+Vries%2C+JJ%3BSimmers%2C+I&rft.aulast=Ting&rft.aufirst=Cheh-Shyh&rft.date=1998-02-01&rft.volume=36&rft.issue=1&rft.spage=20&rft.isbn=&rft.btitle=&rft.title=Ground+Water&rft.issn=0017467X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - SuppNotes - Contact: Ground Water Publishing Co., 6375 Riverside Dr, Dublin, OH, 43017 (USA). PH: (800) 332-2104. FAX: (614) 761-3446. N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - BIAcore for macromolecular interaction AN - 16293438; 4294717 AB - Examination of the literature for the period of this review revealed nearly two hundred citations that employed surface plasmon resonance (SPR) spectroscopy using BIAcore technology to evaluate biospecific interactions, demonstrating the increasing popularity of this powerful technique. Among these we noted the development of several new applications/modifications of standard techniques. In general, we find the qualitative aspects of the reported experiments to be excellent but the quantitative descriptions (k sub(T), k sub(on), k sub(off), and K sub(eq)) as well as the binding models still lagging behind. JF - Current Opinion in Biotechnology AU - Fivash, M AU - Towler, E M AU - Fisher, R J AD - Data Management Services, Inc., Protein Chemistry Laboratory, SAIC, Frederick NCI-Frederick Cancer Research and Development Center, PO Box B, Frederick, MD 21702, USA Y1 - 1998/02// PY - 1998 DA - Feb 1998 SP - 97 EP - 101 VL - 9 IS - 1 SN - 0958-1669, 0958-1669 KW - BIAcore KW - reviews KW - surface plasmon resonance spectroscopy KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - W 30965:Miscellaneous, Reviews KW - W3 33250:Methods: Others UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16293438?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+Opinion+in+Biotechnology&rft.atitle=BIAcore+for+macromolecular+interaction&rft.au=Fivash%2C+M%3BTowler%2C+E+M%3BFisher%2C+R+J&rft.aulast=Fivash&rft.aufirst=M&rft.date=1998-02-01&rft.volume=9&rft.issue=1&rft.spage=97&rft.isbn=&rft.btitle=&rft.title=Current+Opinion+in+Biotechnology&rft.issn=09581669&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Cell cycle arrest in Era GTPase mutants: A potential growth rate-regulated checkpoint in Escherichia coli AN - 16282712; 4282155 AB - Era is a low-molecular-weight GTPase essential for Escherichia coli viability. The gene encoding Era is found in the rnc operon, and the synthesis of both RNase III and Era increases with growth rate. Mutants that are partially defective in Era GTPase activity or that are reduced in the synthesis of wild-type Era become arrested in the cell cycle at the predivisional two-cell stage. The partially defective Era GTPase mutation (era1) suppresses several temperature-sensitive lethal alleles that affect chromosome replication and chromosome partitioning but not cell division. Our results suggest that Era plays an important role in cell cycle progression at a specific point in the cycle, after chromosome partitioning but before cytokinesis. Possible functions for Era in cell cycle progression and the initiation of cell division are discussed. JF - Molecular Microbiology AU - Britton, R A AU - Powell, B S AU - Dasgupta, S AU - Sun, Qin AU - Margolin, W AU - Lupski, J R AU - Court, D L AD - Lab. Gene Regulation and Chromosome Biol., ABL-Basic Res. Prog., NCI/FCRDC, Frederick, MD 21702, USA Y1 - 1998/02// PY - 1998 DA - Feb 1998 SP - 739 EP - 750 VL - 27 IS - 4 SN - 0950-382X, 0950-382X KW - Era protein KW - cell cycle KW - era gene KW - guanosinetriphosphatase KW - mutation KW - Genetics Abstracts; Microbiology Abstracts B: Bacteriology KW - G 07210:Cell cycle KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16282712?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+Microbiology&rft.atitle=Cell+cycle+arrest+in+Era+GTPase+mutants%3A+A+potential+growth+rate-regulated+checkpoint+in+Escherichia+coli&rft.au=Britton%2C+R+A%3BPowell%2C+B+S%3BDasgupta%2C+S%3BSun%2C+Qin%3BMargolin%2C+W%3BLupski%2C+J+R%3BCourt%2C+D+L&rft.aulast=Britton&rft.aufirst=R&rft.date=1998-02-01&rft.volume=27&rft.issue=4&rft.spage=739&rft.isbn=&rft.btitle=&rft.title=Molecular+Microbiology&rft.issn=0950382X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Carbon disulfide neurotoxicity in rats. II. Toxicokinetics AN - 16276733; 4273294 AB - Carbon disulfide (CS sub(2)) is an important industrial chemical widely used in the production of rayon, cellophane, fungicides and biocides. The uptake and elimination kinetics of CS sub(2) was characterized for a single iv dose and for a single inhalation exposure. The uptake of CS sub(2) into the blood was rapid with half times of 6 to 9 minutes. Elimination was relatively quick with terminal elimination half times of 41 to 77 minutes. The plateau CS sub(2) blood concentration was lower in females than in males and lower in the male 50 ppm treatment group than would be predicted by linear dose proportionality compared to the 500 ppm and 800 ppm treatments. The CS sub(2) blood concentration for the female 50 ppm group was below the limit of detection. The total and central compartment apparent volumes of distribution, 4.2 l/kg and .9 l/kg, were estimated from a single 50 mg/kg iv dose. The concentration of CS sub(2) in blood resulting from repeated exposure, was investigated in a 13 week inhalation study. Blood samples were taken in rats previously exposed to 0, 50, 500, and 800 ppm CS sub(2) for 2, 4, 8, or 13 weeks. The concentration of CS sub(2) in the blood of male rats remained relatively constant throughout study. However the female 500 and 800 ppm groups showed a marked decrease over the course of the 13 week study. The concentration of CS sub(2) in the blood from the 500 and 800 ppm groups of both sexes at all time points was higher compared to the 50 ppm group, than would be predicted by linear dose proportionality. The concentration of 2-thiothiazolidine-4-carboxylic acid in urine collected from the same animals lacked dose proportionality between the treatment groups at all time points. CS sub(2) exposure caused dose-related decreases in body weight gain in both male and female rats. JF - Neurotoxicology AU - Moorman, M P AU - Sills, R C AU - Collins, B J AU - Morgan, D L AD - Respiratory Toxicology Group, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA Y1 - 1998/02// PY - 1998 DA - Feb 1998 SP - 89 EP - 98 VL - 19 IS - 1 SN - 0161-813X, 0161-813X KW - carbon disulfide KW - neurotoxicity KW - rats KW - toxicokinetics KW - Toxicology Abstracts; CSA Neurosciences Abstracts KW - N3 11104:Mammals (except primates) KW - X 24153:Metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16276733?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Knowledge-Based+Systems&rft.atitle=A+prioritization+model+for+locating+relief+logistic+centers+using+analytic+hierarchy+process+with+interval+comparison+matrix&rft.au=Bozorgi-Amiri%2C+Ali%3BAsvadi%2C+Saman&rft.aulast=Bozorgi-Amiri&rft.aufirst=Ali&rft.date=2015-09-01&rft.volume=86&rft.issue=&rft.spage=173&rft.isbn=&rft.btitle=&rft.title=Knowledge-Based+Systems&rft.issn=09507051&rft_id=info:doi/10.1016%2Fj.knosys.2015.06.005 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Carbon disulfide neurotoxicity in rats. VIII. Summary AN - 16272746; 4273296 AB - The carbon disulfide (CS sub(2)) studies reported here underscore the importance of addressing neurotoxicity issues by including a battery of biologic and mechanistic endpoints over both a dose and temporal range. In general, the continuum of effects was initiated in sensitive endpoints at the cellular level which progressed to behavioral alterations in the hindlimb and forelimb functioning followed by electrophysiological and morphological changes. JF - Neurotoxicology AU - Harry, G J AU - Graham, D G AU - Valentine, WM AU - Morgan, D L AU - Sills, R C AD - Environmental Toxicology Program (MD C1-04), National Institute of Environmental Health Sciences, Research Triangle Park, N.C. 27709, USA Y1 - 1998/02// PY - 1998 DA - Feb 1998 SP - 159 EP - 162 VL - 19 IS - 1 SN - 0161-813X, 0161-813X KW - carbon disulfide KW - neurotoxicity KW - rats KW - Toxicology Abstracts; CSA Neurosciences Abstracts KW - N3 11104:Mammals (except primates) KW - X 24154:Pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16272746?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurotoxicology&rft.atitle=Carbon+disulfide+neurotoxicity+in+rats.+VIII.+Summary&rft.au=Harry%2C+G+J%3BGraham%2C+D+G%3BValentine%2C+WM%3BMorgan%2C+D+L%3BSills%2C+R+C&rft.aulast=Harry&rft.aufirst=G&rft.date=1998-02-01&rft.volume=19&rft.issue=1&rft.spage=159&rft.isbn=&rft.btitle=&rft.title=Neurotoxicology&rft.issn=0161813X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Carbon disulfide neurotoxicity in rats. V. Morphology of axonal swelling in the muscular branch of the posterior tibial nerve and spinal cord AN - 16267479; 4273298 AB - The study objectives were to examine the morphological progression and dose response of carbon disulfide (CS sub(2)) distal axonopathy in the muscular branch of the posterior tibial nerve (MBPTN) and spinal cord. Male and female F344 rats were exposed to 0, 50, 500 or 800 ppm CS sub(2) by inhalation, 6 hours/day, 5 days per week, for 2, 4, 8 or 13 weeks. At 8 weeks, in the MBPTN, single fascicles contained individual swollen axons. By 13 weeks, multiple fascicles had giant swollen axons with thin myelin sheaths and occasional degenerated and regenerated axons. At 8 weeks, in the spinal cord, white matter changes in cervical segments 1 and 2 consisted of prominent multifocal axonal swelling in the fasciculus gracilis nerve tracts. In lumbar segments 1 and 2, multifocal axonal swelling was first present at 8 weeks in the lateral and ventro-medial funiculus. By 13 weeks, axonal swelling was diffuse in the fasciculus gracilis nerve tracts of the cervical spinal cord and the lateral and ventral funiculus nerve tracts in the lumbar spinal cord. Compared to the spinal cord, where axonal swelling was present in rats exposed to 800 and 500 ppm, in the muscular branch of the posterior tibial nerve, axonal swelling was only present at 800 ppm at both 8 and 13 weeks. Electron microscopic examination demonstrated marked accumulations of neurofilaments in swollen axons in the spinal cord and MBPTN. Axonal swelling was not present in the spinal cord at 50 ppm, or in the MBPT at 50 and 500 ppm. Axonal swelling was not present at earlier time points of 2 and 4 weeks in either the spinal cord or MBPTN. JF - Neurotoxicology AU - Sills, R C AU - Harry, G J AU - Morgan, D L AU - Valentine, WM AU - Graham, D G AD - Environmental Toxicology Program (MD B3-08), National Institute of Environmental Health Sciences, Research Triangle Park, N.C. 27709, USA Y1 - 1998/02// PY - 1998 DA - Feb 1998 SP - 117 EP - 128 VL - 19 IS - 1 SN - 0161-813X, 0161-813X KW - axons KW - carbon disulfide KW - neurotoxicity KW - peripheral nerves KW - posterior tibial nerve KW - rats KW - spinal cord KW - Toxicology Abstracts; CSA Neurosciences Abstracts KW - N3 11104:Mammals (except primates) KW - X 24154:Pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16267479?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurotoxicology&rft.atitle=Carbon+disulfide+neurotoxicity+in+rats.+V.+Morphology+of+axonal+swelling+in+the+muscular+branch+of+the+posterior+tibial+nerve+and+spinal+cord&rft.au=Sills%2C+R+C%3BHarry%2C+G+J%3BMorgan%2C+D+L%3BValentine%2C+WM%3BGraham%2C+D+G&rft.aulast=Sills&rft.aufirst=R&rft.date=1998-02-01&rft.volume=19&rft.issue=1&rft.spage=117&rft.isbn=&rft.btitle=&rft.title=Neurotoxicology&rft.issn=0161813X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Isolation of a high-affinity stable single-chain Fv specific for mesothelin from DNA-immunized mice by phage display and construction of a recombinant immunotoxin with anti-tumor activity. AN - 79673305; 9435250 AB - Mesothelin is a differentiation antigen present on the surface of ovarian cancers, mesotheliomas, and several other types of human cancers. Because among normal tissues, mesothelin is present only on mesothelial cells, it represents a good target for antibody-mediated delivery of cytotoxic agents. In the present study mice were immunized with an eukaryotic expression vector coding for mesothelin. When high serum antibody titers were obtained, a phage display library was made from the splenic mRNA of these mice. After three rounds of panning on recombinant mesothelin, a single-chain Fv (scFv)-displaying phage was selected that bound specifically to recombinant mesothelin and mesothelin-positive cells. The scFv was used to construct an immunotoxin by genetically fusing it with a truncated mutant of Pseudomonas exotoxin A. The purified immunotoxin binds mesothelin with high affinity (Kd 11 nm), is stable for over 40 hr at 37 degrees C and is very cytotoxic to cells expressing mesothelin. It also produces regressions of tumors expressing mesothelin. This combination of selective cytotoxicity, high activity, and stability makes the immunotoxin a good candidate for development as a therapeutic agent. This work also shows that DNA immunization can be used to isolate and clone antibodies against epitopes present on human proteins in their native conformation. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Chowdhury, P S AU - Viner, J L AU - Beers, R AU - Pastan, I AD - Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA. Y1 - 1998/01/20/ PY - 1998 DA - 1998 Jan 20 SP - 669 EP - 674 VL - 95 IS - 2 SN - 0027-8424, 0027-8424 KW - Antibodies, Neoplasm KW - 0 KW - Antigens, Neoplasm KW - Exotoxins KW - GPI-Linked Proteins KW - Immunoglobulin Variable Region KW - Immunotoxins KW - Membrane Glycoproteins KW - Recombinant Proteins KW - mesothelin KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Animals KW - Humans KW - Recombinant Proteins -- immunology KW - Molecular Sequence Data KW - Mice KW - Recombinant Proteins -- genetics KW - Mice, Inbred BALB C KW - Immunization KW - Female KW - Gene Library KW - Immunoglobulin Variable Region -- genetics KW - Immunotoxins -- immunology KW - Immunoglobulin Variable Region -- immunology KW - DNA -- immunology KW - Antibodies, Neoplasm -- immunology KW - Antigens, Neoplasm -- genetics KW - Antigens, Neoplasm -- immunology KW - Membrane Glycoproteins -- immunology KW - Membrane Glycoproteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79673305?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=unknown&rft.jtitle=The+China+Quarterly&rft.atitle=Book+Reviews%3A+Out+to+Work%3A+Migration%2C+Gender+and+the+Changing+Lives+of+Rural+Women+in+Contemporary+China&rft.au=Goodburn%2C+Charlotte&rft.aulast=Goodburn&rft.aufirst=Charlotte&rft.date=2016-03-01&rft.volume=225&rft.issue=&rft.spage=271&rft.isbn=&rft.btitle=&rft.title=The+China+Quarterly&rft.issn=03057410&rft_id=info:doi/10.1017%2FS0305741016000138 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-02-24 N1 - Date created - 1998-02-24 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF035617; GENBANK N1 - SuppNotes - Cited By: J Biol Chem. 1980 Nov 10;255(21):10331-7 [7000776] Nat Biotechnol. 1996 Oct;14(10):1239-45 [9631086] Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8616-20 [1924323] Cancer Res. 1992 Jan 1;52(1):181-6 [1727378] Nature. 1992 Mar 12;356(6365):152-4 [1545867] Am J Surg Pathol. 1992 Mar;16(3):259-68 [1599018] J Biol Chem. 1992 Aug 15;267(23):16007-10 [1644788] Behring Inst Mitt. 1992 Apr;(91):6-12 [1524572] Anal Biochem. 1992 Sep;205(2):263-70 [1332541] N Engl J Med. 1993 Oct 21;329(17):1219-24 [7692295] J Biol Chem. 1994 Jan 14;269(2):805-8 [8288629] Cancer Res. 1994 May 15;54(10):2714-8 [8168102] Biochemistry. 1994 May 10;33(18):5451-9 [7910034] Biochim Biophys Acta. 1994 May 27;1198(1):27-45 [8199194] Int J Cancer. 1994 Jul 1;58(1):142-9 [8014011] J Biol Chem. 1994 Jul 15;269(28):18327-31 [7913461] J Immunol Methods. 1994 Dec 2;176(2):145-52 [7983375] J Immunol Methods. 1995 May 11;182(1):41-50 [7769243] Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):136-40 [8552591] Nat Med. 1996 Mar;2(3):350-3 [8612238] Proc Natl Acad Sci U S A. 1996 May 14;93(10):5141-5 [8643542] Science. 1996 Jul 19;273(5273):352-4 [8662521] J Med Primatol. 1996 Jun;25(3):242-50 [8892046] Int J Cancer. 1997 May 16;71(4):638-44 [9178820] Mol Immunol. 1997 Jan;34(1):9-20 [9182872] J Clin Oncol. 1997 Apr;15(4):1567-74 [9193354] Nature. 1989 Jun 1;339(6223):394-7 [2498664] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Deoxyhypusine synthase activity is essential for cell viability in the yeast Saccharomyces cerevisiae. AN - 79669597; 9430712 AB - Deoxyhypusine synthase catalyzes the first step in the posttranslational synthesis of an unusual amino acid, hypusine (N epsilon-(4-amino-2-hydroxybutyl)lysine), in the eukaryotic translation initiation factor 5A (eIF-5A) precursor protein. The null mutation in the single copy gene, yDHS, encoding deoxyhypusine synthase results in the loss of viability in the yeast Saccharomyces cerevisiae. Upon depletion of deoxyhypusine synthase, and consequently of eIF-5A, cessation of growth was accompanied by a marked enlargement of cells, suggesting a defect in cell cycle progression or in cell division. Two residues of the yeast enzyme, Lys308 and Lys350, corresponding to Lys287 and Lys329, respectively, known to be critical for the activity of the human enzyme, were targeted for site-directed mutagenesis. The chromosomal ydhs null mutation was complemented by the plasmid-borne yDHS wild-type gene, but not by mutated genes encoding inactive proteins, including that with Lys350-->Arg substitution or with substitutions at both Lys308 and Lys350. The mutated gene ydhs (K308R) encoding a protein with diminished activities (< 1% of wild type) could support growth but only to a very limited extent. These findings provide strong evidence that the hypusine modification is indeed essential for the survival of S. cerevisiae and imply a vital function for eIF-5A in all eukaryotes. JF - The Journal of biological chemistry AU - Park, M H AU - Joe, Y A AU - Kang, K R AD - Oral and Pharyngeal Cancer Branch, NIDR, National Institutes of Health, Bethesda, Maryland 20892-4340, USA. mpark@yoda.nidr.nih.gov Y1 - 1998/01/16/ PY - 1998 DA - 1998 Jan 16 SP - 1677 EP - 1683 VL - 273 IS - 3 SN - 0021-9258, 0021-9258 KW - Peptide Initiation Factors KW - 0 KW - RNA-Binding Proteins KW - eukaryotic translation initiation factor 5A KW - Oxidoreductases Acting on CH-NH Group Donors KW - EC 1.5.- KW - deoxyhypusine synthase KW - EC 1.5.1.- KW - Lysine KW - K3Z4F929H6 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Polymerase Chain Reaction KW - Peptide Initiation Factors -- metabolism KW - Alleles KW - Humans KW - Cell Cycle KW - Lysine -- metabolism KW - Amino Acid Substitution KW - Cell Survival KW - Catalysis KW - Oxidoreductases Acting on CH-NH Group Donors -- metabolism KW - Oxidoreductases Acting on CH-NH Group Donors -- genetics KW - Saccharomyces cerevisiae -- enzymology KW - Saccharomyces cerevisiae -- cytology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79669597?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Deoxyhypusine+synthase+activity+is+essential+for+cell+viability+in+the+yeast+Saccharomyces+cerevisiae.&rft.au=Park%2C+M+H%3BJoe%2C+Y+A%3BKang%2C+K+R&rft.aulast=Park&rft.aufirst=M&rft.date=1998-01-16&rft.volume=273&rft.issue=3&rft.spage=1677&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 - 1998-02-12 N1 - Date created - 1998-02-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Recognition of an antigenic peptide derived from tyrosinase-related protein-2 by CTL in the context of HLA-A31 and -A33. AN - 79803133; 9551926 AB - Tumor-infiltrating lymphocytes (TILs) derived from tumor-bearing patients recognize tumor-associated Ags presented by MHC class I molecules. The infusion of TIL586 along with IL-2 into the autologous patient with metastatic melanoma resulted in the objective regression of tumor. Two T cell epitopes derived from tumor Ags, tyrosinase-related protein (TRP)-1 and TRP-2, were shown to be recognized by HLA-A31 restricted TIL586 and its T cell clones. In this study we tested the hypothesis that these two peptides can be recognized by CTL from non-HLA-A31 patients with melanoma. It was found that both peptides were capable of binding to HLA-A3, -A11, -A31, -A33, and -A68 of the HLA-A3 supertype. Importantly, we found that HLA-A33-positive TIL1244 and its T cell clones can recognize TRP197-205 presented by both HLA-A31 and -A33 molecules, suggesting that a single TCR can recognize peptide/A31 and peptide/A33 complexes. However, peptide titration experiments showed that the affinity of TCR receptor to peptide/A33 could be higher than that to the peptide/A31. These studies have important implications for the development of peptide-based cancer vaccines. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Wang, R F AU - Johnston, S L AU - Southwood, S AU - Sette, A AU - Rosenberg, S A AD - Surgery Branch, National Cancer Institute, Bethesda, MD 20892, USA. rongfu@pop.nci.nih.gov Y1 - 1998/01/15/ PY - 1998 DA - 1998 Jan 15 SP - 890 EP - 897 VL - 160 IS - 2 SN - 0022-1767, 0022-1767 KW - Antigens, Neoplasm KW - 0 KW - Epitopes, T-Lymphocyte KW - HLA-A Antigens KW - HLA-A*33 antigen KW - HLA-A31 antigen KW - Peptide Fragments KW - Intramolecular Oxidoreductases KW - EC 5.3.- KW - dopachrome isomerase KW - EC 5.3.3.12 KW - Abridged Index Medicus KW - Index Medicus KW - Clone Cells KW - Tumor Cells, Cultured KW - Humans KW - Cytotoxicity Tests, Immunologic KW - Antigens, Neoplasm -- metabolism KW - Protein Binding -- immunology KW - Lymphocytes, Tumor-Infiltrating -- enzymology KW - Peptide Fragments -- metabolism KW - Epitopes, T-Lymphocyte -- metabolism KW - Intramolecular Oxidoreductases -- metabolism KW - T-Lymphocytes, Cytotoxic -- immunology KW - HLA-A Antigens -- metabolism KW - Intramolecular Oxidoreductases -- immunology KW - T-Lymphocytes, Cytotoxic -- metabolism KW - Peptide Fragments -- immunology KW - T-Lymphocytes, Cytotoxic -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79803133?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=unknown&rft.jtitle=French+Politics%2C+Culture+%26+Society&rft.atitle=IS+INTEGRATION+A+ZERO-SUM+GAME%3F%3A+Negotiating+Space+for+Ethnic+Minorities+in+Europe&rft.au=Garrett%2C+Amanda&rft.aulast=Garrett&rft.aufirst=Amanda&rft.date=2015-12-01&rft.volume=33&rft.issue=3&rft.spage=116&rft.isbn=&rft.btitle=&rft.title=French+Politics%2C+Culture+%26+Society&rft.issn=15376370&rft_id=info:doi/10.3167%2Ffpcs.2015.330306 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-04-30 N1 - Date created - 1998-04-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetic analysis of diagnostic systems of alcoholism in males. AN - 79694163; 9474446 AB - Research into genes involved in alcoholism could benefit from use of diagnostic systems most sensitive to detecting genetic influences. In this study, heritable influences were estimated in a single twin sample with commonly used criteria for alcoholism. Male twin probands ascertained through alcohol and drug abuse treatment programs and their same-sex cotwins (54 monozygotic and 65 dizygotic pairs) were diagnosed independently by DSM-III (alcohol dependence and alcohol abuse and/or dependence), Feighner (probable and definite alcoholism), and Cloninger (type 1 and type 2 alcoholism) systems. Using univariate structural equation modeling, heritability was estimated for each diagnostic system. The highest heritability estimates were obtained for Feighner probable alcoholism (h2 = .63), Cloninger type 2 alcoholism (h2 = .54), and DSM-III alcohol dependence (h2 = .52). Certain diagnostic systems appear to have greater sensitivity for detecting genetic influence and may therefore be more appropriate for use in molecular genetic studies attempting to find genes for alcoholism. JF - Biological psychiatry AU - van den Bree, M B AU - Johnson, E O AU - Neale, M C AU - Svikis, D S AU - McGue, M AU - Pickens, R W AD - Intramural Research Program, National Institute on Drug Abuse, Baltimore, Maryland 21224, USA. Y1 - 1998/01/15/ PY - 1998 DA - 1998 Jan 15 SP - 139 EP - 145 VL - 43 IS - 2 SN - 0006-3223, 0006-3223 KW - Index Medicus KW - Analysis of Variance KW - Psychiatric Status Rating Scales KW - Twins, Monozygotic KW - Models, Genetic KW - Humans KW - Adult KW - Twin Studies as Topic KW - Aged KW - Middle Aged KW - Twins, Dizygotic KW - Adolescent KW - Male KW - Alcoholism -- diagnosis KW - Alcoholism -- genetics KW - Alcoholism -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79694163?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Genetic+analysis+of+diagnostic+systems+of+alcoholism+in+males.&rft.au=van+den+Bree%2C+M+B%3BJohnson%2C+E+O%3BNeale%2C+M+C%3BSvikis%2C+D+S%3BMcGue%2C+M%3BPickens%2C+R+W&rft.aulast=van+den+Bree&rft.aufirst=M&rft.date=1998-01-15&rft.volume=43&rft.issue=3&rft.spage=153&rft.isbn=&rft.btitle=&rft.title=Far+Eastern+Affairs&rft.issn=0206149X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-04-03 N1 - Date created - 1998-04-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Early induction of apoptosis in hematopoietic cell lines after exposure to flavopiridol. AN - 79665138; 9427698 AB - Flavopiridol (NSC 649890; Behringwerke L86-8275, Marburg, Germany), is a potent inhibitor of cyclin dependent kinases (CDKs) 1, 2, and 4. It has potent antiproliferative effects in vitro and is active in tumor models in vivo. While surveying the effect of flavopiridol on cell cycle progression in different cell types, we discovered that hematopoietic cell lines, including SUDHL4, SUDHL6 (B-cell lines), Jurkat, and MOLT4 (T-cell lines), and HL60 (myeloid), displayed notable sensitivity to flavopiridol-induced apoptosis. For example, after 100 nmol/L for 12 hours, SUDHL4 cells displayed a similar degree of DNA fragmentation to that shown by the apoptosis-resistant PC3 prostate carcinoma cells only after 3,000 nmol/L for 48 hours. After exposure to 1,000 nmol/L flavopiridol for 12 hours, typical apoptotic morphology was observed in SUDHL4 cells, but not in PC3 prostate carcinoma cells despite comparable potency (SUDHL4: 120 nmol/L; PC3: 203 nmol/L) in causing growth inhibition by 50% (IC50). Flavopiridol did not induce topoisomerase I or II cleavable complex activity. A relation of p53, bcl2, or bax protein levels to apoptosis in SUDHL4 was not appreciated. While flavopiridol caused cell cycle arrest with decline in CDK1 activity in PC3 cells, apoptosis of SUDHL4 cells occurred without evidence of cell cycle arrest. These results suggest that antiproliferative activity of flavopiridol (manifest by cell cycle arrest) may be separated in different cell types from a capacity to induce apoptosis. Cells from hematopoietic neoplasms appear in this limited sample to be very susceptible to flavopiridol-induced apoptosis and therefore clinical trials in hematopoietic neoplasms should be of high priority. JF - Blood AU - Parker, B W AU - Kaur, G AU - Nieves-Neira, W AU - Taimi, M AU - Kohlhagen, G AU - Shimizu, T AU - Losiewicz, M D AU - Pommier, Y AU - Sausville, E A AU - Senderowicz, A M AD - Laboratory of Biological Chemistry, National Cancer Institute, NIH, Bethesda, MD 20892, USA. Y1 - 1998/01/15/ PY - 1998 DA - 1998 Jan 15 SP - 458 EP - 465 VL - 91 IS - 2 SN - 0006-4971, 0006-4971 KW - Flavonoids KW - 0 KW - Growth Inhibitors KW - Piperidines KW - alvocidib KW - 45AD6X575G KW - Abridged Index Medicus KW - Index Medicus KW - Cells, Cultured KW - Humans KW - Male KW - Hematopoietic Stem Cells -- pathology KW - Hematopoiesis -- drug effects KW - Piperidines -- toxicity KW - Apoptosis -- drug effects KW - Prostate -- pathology KW - Hematopoietic Stem Cells -- drug effects KW - Growth Inhibitors -- toxicity KW - Flavonoids -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79665138?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Early+induction+of+apoptosis+in+hematopoietic+cell+lines+after+exposure+to+flavopiridol.&rft.au=Parker%2C+B+W%3BKaur%2C+G%3BNieves-Neira%2C+W%3BTaimi%2C+M%3BKohlhagen%2C+G%3BShimizu%2C+T%3BLosiewicz%2C+M+D%3BPommier%2C+Y%3BSausville%2C+E+A%3BSenderowicz%2C+A+M&rft.aulast=Parker&rft.aufirst=B&rft.date=1998-01-15&rft.volume=91&rft.issue=2&rft.spage=458&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-02-11 N1 - Date created - 1998-02-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Frequent nitric oxide synthase-2 expression in human colon adenomas: implication for tumor angiogenesis and colon cancer progression. AN - 79663161; 9443414 AB - An increased expression of nitric oxide synthase (NOS) has been observed in human colon carcinoma cell lines as well as in human gynecological, breast, and central nervous system tumors. This observation suggests a pathobiological role of tumor-associated NO production. Hence, we investigated NOS expression in human colon cancer in respect to tumor staging, NOS-expressing cell type(s), nitrotyrosine formation, inflammation, and vascular endothelial growth factor expression. Ca2+-dependent NOS activity was found in normal colon and in tumors but was significantly decreased in adenomas (P < 0.001) and carcinomas (Dukes' stages A-D: P < 0.002). Ca2+-independent NOS activity, indicating inducible NOS (NOS2), is markedly expressed in approximately 60% of human colon adenomas (P < 0.001 versus normal tissues) and in 20-25% of colon carcinomas (P < 0.01 versus normal tissues). Only low levels were found in the surrounding normal tissue. NOS2 activity decreased with increasing tumor stage (Dukes' A-D) and was lowest in colon metastases to liver and lung. NOS2 was detected in tissue mononuclear cells (TMCs), endothelium, and tumor epithelium. There was a statistically significant correlation between NOS2 enzymatic activity and the level of NOS2 protein detected by immunohistochemistry (P < 0.01). Western blot analysis of tumor extracts with Ca2+-independent NOS activity showed up to three distinct NOS2 protein bands at Mr 125,000-Mr 138,000. The same protein bands were heavily tyrosine-phosphorylated in some tumor tissues. TMCs, but not the tumor epithelium, were immunopositive using a polyclonal anti-nitrotyrosine antibody. However, only a subset of the NOS2-expressing TMCs stained positively for 3-nitrotyrosine, which is a marker for peroxynitrite formation. Furthermore, vascular endothelial growth factor expression was detected in adenomas expressing NOS2. These data are consistent with the hypothesis that excessive NO production by NOS2 may contribute to the pathogenesis of colon cancer progression at the transition of colon adenoma to carcinoma in situ. JF - Cancer research AU - Ambs, S AU - Merriam, W G AU - Bennett, W P AU - Felley-Bosco, E AU - Ogunfusika, M O AU - Oser, S M AU - Klein, S AU - Shields, P G AU - Billiar, T R AU - Harris, C C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, NIH, Bethesda, Maryland 20892-4255, USA. Y1 - 1998/01/15/ PY - 1998 DA - 1998 Jan 15 SP - 334 EP - 341 VL - 58 IS - 2 SN - 0008-5472, 0008-5472 KW - DNA Primers KW - 0 KW - DNA, Neoplasm KW - Endothelial Growth Factors KW - Lymphokines KW - Neoplasm Proteins KW - Vascular Endothelial Growth Factor A KW - Vascular Endothelial Growth Factors KW - 3-nitrotyrosine KW - 3604-79-3 KW - Tyrosine KW - 42HK56048U KW - NOS2 protein, human KW - EC 1.14.13.39 KW - Nitric Oxide Synthase KW - Nitric Oxide Synthase Type II KW - Index Medicus KW - Lymphokines -- metabolism KW - Endothelium, Vascular -- enzymology KW - Humans KW - Disease Progression KW - DNA, Neoplasm -- analysis KW - Polymerase Chain Reaction KW - Blotting, Western KW - Phosphorylation KW - Carcinoma -- blood supply KW - Carcinoma -- pathology KW - Colon -- enzymology KW - Endothelial Growth Factors -- metabolism KW - Carcinoma -- enzymology KW - Tyrosine -- metabolism KW - Tyrosine -- analogs & derivatives KW - Neoplasm Proteins -- analysis KW - Immunohistochemistry KW - DNA Primers -- chemistry KW - Adenoma -- enzymology KW - Colonic Neoplasms -- blood supply KW - Neovascularization, Pathologic -- enzymology KW - Nitric Oxide Synthase -- metabolism KW - Colonic Neoplasms -- pathology KW - Adenoma -- pathology KW - Adenoma -- blood supply KW - Colonic Neoplasms -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79663161?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Frequent+nitric+oxide+synthase-2+expression+in+human+colon+adenomas%3A+implication+for+tumor+angiogenesis+and+colon+cancer+progression.&rft.au=Ambs%2C+S%3BMerriam%2C+W+G%3BBennett%2C+W+P%3BFelley-Bosco%2C+E%3BOgunfusika%2C+M+O%3BOser%2C+S+M%3BKlein%2C+S%3BShields%2C+P+G%3BBilliar%2C+T+R%3BHarris%2C+C+C&rft.aulast=Ambs&rft.aufirst=S&rft.date=1998-01-15&rft.volume=58&rft.issue=2&rft.spage=334&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 - 1998-02-04 N1 - Date created - 1998-02-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cross-resistance to methotrexate and metals in human cisplatin-resistant cell lines results from a pleiotropic defect in accumulation of these compounds associated with reduced plasma membrane binding proteins. AN - 79661325; 9443404 AB - Cross-resistance to a wide array of toxic chemicals is a common phenomenon in cisplatin-resistant cell lines. In this study, two independently isolated cisplatin-resistant cell lines derived from a human hepatoma and a cervical adenocarcinoma were shown to be cross-resistant to methotrexate (MTX) and several metal salts, such as sodium arsenite, sodium arsenate, antimony potassium tartrate, and cadmium chloride. A pleiotropic defect resulting in reduced accumulation of cisplatin, 3[H]MTX, 73As3+, and 73As5+ was found in both cisplatin-resistant cell lines. Analysis by immunoblot, indirect immunofluorescence, and Northern hybridization showed dramatically reduced expression of the folate binding protein that mediates MTX uptake in both human cisplatin-resistant cell lines. By photoaffinity labeling with UV irradiation, specific binding proteins of Mr 230,000 and Mr 48,000 for 73As3+ and Mr 190,000 for 73As5+ were found in enriched plasma membrane of both human cisplatin-sensitive parental cell lines. Expression of these specific binding proteins was decreased in cells selected for cisplatin resistance. A protein band at Mr 36,000 that binds to 73As3+ was overexpressed in both human cisplatin-resistant cell lines. The finding of loss of distinct binding proteins for MTX, arsenate, and arsenite in association with decreased accumulation of these agents in cisplatin-resistant cells suggests a pleiotropic, possibly regulatory, alteration in these cells. JF - Cancer research AU - Shen, D AU - Pastan, I AU - Gottesman, M M AD - Laboratory of Cell Biology, National Cancer Institute, NIH, Bethesda, Maryland 20892-4255, USA. Y1 - 1998/01/15/ PY - 1998 DA - 1998 Jan 15 SP - 268 EP - 275 VL - 58 IS - 2 SN - 0008-5472, 0008-5472 KW - Antineoplastic Agents KW - 0 KW - Arsenicals KW - Carrier Proteins KW - Folate Receptors, GPI-Anchored KW - Membrane Proteins KW - Metals KW - Neoplasm Proteins KW - Receptors, Cell Surface KW - Cisplatin KW - Q20Q21Q62J KW - Methotrexate KW - YL5FZ2Y5U1 KW - Index Medicus KW - Liver Neoplasms -- metabolism KW - Blotting, Northern KW - Fluorescent Antibody Technique, Indirect KW - Membrane Proteins -- metabolism KW - Humans KW - Arsenicals -- pharmacology KW - Carcinoma, Squamous Cell -- metabolism KW - Drug Resistance, Neoplasm KW - Drug Resistance, Multiple KW - Tumor Cells, Cultured KW - Arsenicals -- pharmacokinetics KW - Carcinoma, Squamous Cell -- genetics KW - Membrane Proteins -- drug effects KW - Cell Membrane -- metabolism KW - Liver Neoplasms -- genetics KW - Receptors, Cell Surface -- metabolism KW - Carrier Proteins -- metabolism KW - Cisplatin -- toxicity KW - Carrier Proteins -- genetics KW - Neoplasm Proteins -- genetics KW - Antineoplastic Agents -- toxicity KW - Receptors, Cell Surface -- genetics KW - Methotrexate -- metabolism KW - Metals -- metabolism KW - Neoplasm Proteins -- metabolism KW - Methotrexate -- toxicity KW - Metals -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79661325?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+International+Migration+Review&rft.atitle=Migration%2C+Modernity%2C+and+Social+Transformation+in+South+Asia&rft.au=Mills%2C+Mary+Beth&rft.aulast=Mills&rft.aufirst=Mary&rft.date=2005-01-01&rft.volume=39&rft.issue=3&rft.spage=769&rft.isbn=&rft.btitle=&rft.title=The+International+Migration+Review&rft.issn=01979183&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-02-04 N1 - Date created - 1998-02-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Overlapping Sp1 and AP2 binding sites in a promoter element of the lens-specific MIP gene. AN - 79629065; 9421492 AB - The MIP gene, the founder of the MIP family of channel proteins, is specifically expressed in fiber cells of the ocular lens and expression is regulated temporally and spatially during development. We previously found that a DNA fragment containing 253 bp of 5'-flanking sequence and 42 bp of exon 1 of the human MIP gene contains regulatory elements responsible for lens-specific expression of the MIP gene. In this report we have analyzed the function of overlapping Sp1 and AP2 binding sites present in the MIP promoter. Using DNase I footprinting analysis we found that purified Sp1 and AP2 transcription factors interact with several domains of the human MIP promoter sequence -253/+42. Furthermore, addition of purified Sp1 to Drosophila nuclear extracts activates in vitro transcription from the MIP promoter -253/+42. This promoter activity is competed by oligonucleotides containing domains footprinted with Sp1. Using promoter-reporter gene ( CAT ) constructs we found that the sequence -39/-70 contains a cis regulatory element essential for promoter activity in transient assays in lens cells. EMSA analysis showed that lens nuclear extracts contain factors that bind to the MIP 5'-flanking sequence containing overlapping Sp1 and AP2 binding domains at positions -37/-65. Supershift experiments with lens nuclear extracts indicated that Sp3 is also able to interact with this regulatory element, suggesting that Sp1 and Sp3 may be involved in regulation of transcription of the MIP gene in the lens. JF - Nucleic acids research AU - Ohtaka-Maruyama, C AU - Wang, X AU - Ge, H AU - Chepelinsky, A B AD - Laboratory of Molecular and Developmental Biology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1998/01/15/ PY - 1998 DA - 1998 Jan 15 SP - 407 EP - 414 VL - 26 IS - 2 SN - 0305-1048, 0305-1048 KW - Bacterial Proteins KW - 0 KW - DNA-Binding Proteins KW - Membrane Proteins KW - Sp1 Transcription Factor KW - Transcription Factor AP-2 KW - Transcription Factors KW - DNA KW - 9007-49-2 KW - Immunophilins KW - EC 5.2.1.8 KW - Peptidylprolyl Isomerase KW - Index Medicus KW - Animals KW - Exons KW - Humans KW - Amino Acid Sequence KW - Binding Sites KW - Gene Deletion KW - Mutagenesis KW - Regulatory Sequences, Nucleic Acid KW - Base Sequence KW - Chickens KW - Transfection KW - DNA Footprinting KW - Molecular Sequence Data KW - Promoter Regions, Genetic KW - Bacterial Proteins -- genetics KW - Bacterial Proteins -- chemistry KW - Transcription Factors -- metabolism KW - Membrane Proteins -- chemistry KW - DNA -- metabolism KW - Sp1 Transcription Factor -- metabolism KW - DNA -- chemistry KW - Membrane Proteins -- genetics KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79629065?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Overlapping+Sp1+and+AP2+binding+sites+in+a+promoter+element+of+the+lens-specific+MIP+gene.&rft.au=Ohtaka-Maruyama%2C+C%3BWang%2C+X%3BGe%2C+H%3BChepelinsky%2C+A+B&rft.aulast=Ohtaka-Maruyama&rft.aufirst=C&rft.date=1998-01-15&rft.volume=30&rft.issue=6&rft.spage=479&rft.isbn=&rft.btitle=&rft.title=Gender+in+Management&rft.issn=17542413&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-02-26 N1 - Date created - 1998-02-26 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - U36308; GENBANK N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1995 May 9;92(10):4676-80 [7753863] Oncogene. 1995 May 4;10(9):1841-8 [7753559] J Biol Chem. 1995 May 26;270(21):12737-44 [7759528] EMBO J. 1995 Jul 17;14(14):3510-9 [7628452] J Biol Chem. 1995 Oct 6;270(40):23511-9 [7559515] J Biol Chem. 1995 Oct 27;270(43):25402-10 [7592707] J Biol Chem. 1995 Oct 27;270(43):25879-84 [7592774] Cell. 1997 May 16;89(4):619-28 [9160753] J Biol Chem. 1997 Aug 22;272(34):21260-7 [9261136] J Biol Chem. 1997 Sep 19;272(38):24038-45 [9295357] Nucleic Acids Res. 1983 Mar 11;11(5):1475-89 [6828386] Nucleic Acids Res. 1985 Apr 25;13(8):2709-30 [2987864] Biochem Biophys Res Commun. 1986 Mar 28;135(3):965-71 [2421726] J Cell Biol. 1988 Mar;106(3):705-14 [3279052] Dev Biol. 1988 May;127(1):209-19 [2834246] Nucleic Acids Res. 1989 Apr 11;17(7):2639-53 [2717405] Nucleic Acids Res. 1989 Aug 11;17(15):6419 [2771659] Genes Dev. 1990 Oct;4(10):1811-22 [2123467] Genes Dev. 1991 Jan;5(1):105-19 [1989904] Mol Cell Biol. 1991 Apr;11(4):2189-99 [2005904] J Biol Chem. 1991 May 15;266(14):8907-15 [2026603] Development. 1991 Sep;113(1):283-93 [1722450] Genomics. 1991 Dec;11(4):981-90 [1840563] Nucleic Acids Res. 1992 Jul 11;20(13):3287-95 [1385862] Nucleic Acids Res. 1992 Jul 25;20(14):3701-12 [1641336] Exp Eye Res. 1995 Sep;61(3):351-62 [7556498] Exp Eye Res. 1995 Sep;61(3):293-301 [7556493] Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7452-6 [1502157] Gene. 1995 Dec 29;167(1-2):321-5 [8566800] Nat Genet. 1996 Feb;12(2):212-5 [8563764] Nature. 1996 May 16;381(6579):235-8 [8622765] Nature. 1996 May 16;381(6579):238-41 [8622766] EMBO J. 1996 Oct 15;15(20):5659-67 [8896459] J Biol Chem. 1996 Nov 15;271(46):28853-60 [8910531] J Biol Chem. 1997 Jan 10;272(2):1308-14 [8995437] Mol Cell Biol. 1997 Jun;17(6):3056-64 [9154804] Mol Cell Biol. 1992 Oct;12(10):4251-61 [1341900] Development. 1992 Aug;115(4):1149-64 [1451662] Nucleic Acids Res. 1992 Nov 11;20(21):5519-25 [1454515] J Biol Chem. 1993 Apr 15;268(11):8230-9 [8096519] Mol Cell Biol. 1993 Jul;13(7):4174-85 [8321221] Development. 1993 Oct;119(2):433-46 [7904558] J Biol Chem. 1994 Jan 14;269(2):1046-50 [8288559] Mol Cell Biol. 1994 Feb;14(2):1383-94 [8289814] J Biol Chem. 1994 Apr 15;269(15):11425-34 [7512565] Mol Cell Biol. 1994 Sep;14(9):5692-700 [8065305] Nature. 1994 Sep 1;371(6492):72-4 [8072529] Dev Biol. 1994 Sep;165(1):165-77 [8088434] Development. 1994 Sep;120(9):2369-83 [7525178] Mol Cell Biol. 1995 Feb;15(2):653-60 [7823934] J Biol Chem. 1995 Jan 20;270(3):1221-9 [7836383] J Biol Chem. 1995 Apr 14;270(15):8514-20 [7721749] J Biol Chem. 1995 Apr 14;270(15):9010-16 [7536742] J Biol Chem. 1995 Apr 21;270(16):9494-9 [7721877] EMBO J. 1995 Apr 3;14(7):1508-19 [7729426] Proc Natl Acad Sci U S A. 1995 Apr 25;92(9):3953-7 [7732011] Dev Biol. 1995 May;169(1):1-14 [7750631] Proc Natl Acad Sci U S A. 1995 May 9;92(10):4681-5 [7753864] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Stereoselective actions of halothane at GABA(A) receptors. AN - 79785866; 9543259 AB - Isoflurane anesthesia exhibits stereoselectivity, and a corresponding stereoselectivity ((+)->(-)-isomer) has been reported at GABA(A) receptors in vitro. The objective of the present study was to determine if the positive modulatory actions of halothane at GABA(A) receptors exhibited a similar stereoselectivity. Both (R)- and (S)-halothane ((+)- and (-)- isomers, respectively) enhanced [3H]flunitrazepam binding to brain membranes in a concentration dependent manner without a significant difference in either potency (EC50) or efficacy (Emax). While both (R)- and (S)-halothane enhanced [3H]muscimol binding, the potency of the (+)-isomer was slightly greater than the corresponding (-)-isomer (0.91 +/- 0.17 versus 1.45 +/- 0.04% atmospheres, respectively (P < 0.02)). Thus, subtle structural differences between inhalational anesthetics can have a significant impact on the degree of stereoselectivity at the receptor level and may provide insights for the development of more specific drugs. JF - European journal of pharmacology AU - Harris, B D AU - Moody, E J AU - Skolnick, P AD - Laboratory of Neuroscience, NIDDK, National Institutes of Health, Bethesda, MD 20892-0008, USA. Y1 - 1998/01/12/ PY - 1998 DA - 1998 Jan 12 SP - 349 EP - 352 VL - 341 IS - 2-3 SN - 0014-2999, 0014-2999 KW - Anesthetics, Inhalation KW - 0 KW - GABA Agonists KW - GABA Modulators KW - Receptors, GABA-A KW - Muscimol KW - 2763-96-4 KW - Flunitrazepam KW - 620X0222FQ KW - Halothane KW - UQT9G45D1P KW - Index Medicus KW - Animals KW - Stereoisomerism KW - Drug Interactions KW - GABA Agonists -- pharmacology KW - GABA Modulators -- pharmacology KW - Binding, Competitive KW - Mice KW - Flunitrazepam -- pharmacology KW - Muscimol -- pharmacology KW - Male KW - Halothane -- pharmacology KW - Halothane -- chemistry KW - Anesthetics, Inhalation -- pharmacology KW - Anesthetics, Inhalation -- chemistry KW - Receptors, GABA-A -- metabolism KW - Receptors, GABA-A -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79785866?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+International+Migration+Review&rft.atitle=Cultures+in+Contact%3A+World+Migrations+in+the+Second+Millennium&rft.au=Triadafilopoulos%2C+Triadafilos&rft.aulast=Triadafilopoulos&rft.aufirst=Triadafilos&rft.date=2005-01-01&rft.volume=39&rft.issue=2&rft.spage=526&rft.isbn=&rft.btitle=&rft.title=The+International+Migration+Review&rft.issn=01979183&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-05-21 N1 - Date created - 1998-05-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Retrograde transport of Golgi-localized proteins to the ER. AN - 79654066; 9425149 AB - The ER is uniquely enriched in chaperones and folding enzymes that facilitate folding and unfolding reactions and ensure that only correctly folded and assembled proteins leave this compartment. Here we address the extent to which proteins that leave the ER and localize to distal sites in the secretory pathway are able to return to the ER folding environment during their lifetime. Retrieval of proteins back to the ER was studied using an assay based on the capacity of the ER to retain misfolded proteins. The lumenal domain of the temperature-sensitive viral glycoprotein VSVGtsO45 was fused to Golgi or plasma membrane targeting domains. At the nonpermissive temperature, newly synthesized fusion proteins misfolded and were retained in the ER, indicating the VSVGtsO45 ectodomain was sufficient for their retention within the ER. At the permissive temperature, the fusion proteins were correctly delivered to the Golgi complex or plasma membrane, indicating the lumenal epitope of VSVGtsO45 also did not interfere with proper targeting of these molecules. Strikingly, Golgi-localized fusion proteins, but not VSVGtsO45 itself, were found to redistribute back to the ER upon a shift to the nonpermissive temperature, where they misfolded and were retained. This occurred over a time period of 15 min-2 h depending on the chimera, and did not require new protein synthesis. Significantly, recycling did not appear to be induced by misfolding of the chimeras within the Golgi complex. This suggested these proteins normally cycle between the Golgi and ER, and while passing through the ER at 40 degrees C become misfolded and retained. The attachment of the thermosensitive VSVGtsO45 lumenal domain to proteins promises to be a useful tool for studying the molecular mechanisms and specificity of retrograde traffic to the ER. JF - The Journal of cell biology AU - Cole, N B AU - Ellenberg, J AU - Song, J AU - DiEuliis, D AU - Lippincott-Schwartz, J AD - Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/01/12/ PY - 1998 DA - 1998 Jan 12 SP - 1 EP - 15 VL - 140 IS - 1 SN - 0021-9525, 0021-9525 KW - G protein, vesicular stomatitis virus KW - 0 KW - KDEL receptor KW - Membrane Glycoproteins KW - Receptors, Peptide KW - Recombinant Fusion Proteins KW - Viral Envelope Proteins KW - Cycloheximide KW - 98600C0908 KW - Index Medicus KW - Recombinant Fusion Proteins -- biosynthesis KW - Animals KW - Receptors, Peptide -- chemistry KW - COS Cells KW - Models, Molecular KW - Simian virus 40 -- genetics KW - Temperature KW - Cell Membrane -- physiology KW - Recombinant Fusion Proteins -- chemistry KW - Mutagenesis, Site-Directed KW - Receptors, Peptide -- biosynthesis KW - Transfection KW - Cycloheximide -- pharmacology KW - Protein Folding KW - CHO Cells KW - Cricetinae KW - Protein Conformation KW - Viral Envelope Proteins -- chemistry KW - Viral Envelope Proteins -- biosynthesis KW - Endoplasmic Reticulum -- physiology KW - Golgi Apparatus -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79654066?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+cell+biology&rft.atitle=Retrograde+transport+of+Golgi-localized+proteins+to+the+ER.&rft.au=Cole%2C+N+B%3BEllenberg%2C+J%3BSong%2C+J%3BDiEuliis%2C+D%3BLippincott-Schwartz%2C+J&rft.aulast=Cole&rft.aufirst=N&rft.date=1998-01-12&rft.volume=140&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+cell+biology&rft.issn=00219525&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-02-10 N1 - Date created - 1998-02-10 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Cell Biol. 1995 Aug;130(4):781-96 [7642697] Curr Opin Cell Biol. 1995 Aug;7(4):530-5 [7495573] J Biol Chem. 1995 Oct 20;270(42):25057-63 [7559636] EMBO J. 1995 Oct 2;14(19):4695-704 [7588599] J Cell Biol. 1995 Nov;131(4):895-912 [7490292] Biochem Soc Trans. 1995 Aug;23(3):541-4 [8566411] Mol Biol Cell. 1995 Jul;6(7):871-87 [7579700] J Cell Biol. 1995 Dec;131(6 Pt 2):1715-26 [8557739] J Cell Biol. 1996 Mar;132(6):985-98 [8601597] Science. 1996 Apr 12;272(5259):227-34 [8602507] Cell. 1996 Apr 19;85(2):205-15 [8612273] J Biol Chem. 1996 Feb 23;271(8):4031-7 [8626736] J Biol Chem. 1997 Aug 1;272(31):19554-61 [9235960] Nature. 1997 Sep 4;389(6646):81-5 [9288971] J Histochem Cytochem. 1977 Jul;25(7):935-41 [894009] Proc Natl Acad Sci U S A. 1981 Jan;78(1):293-7 [7017713] Cell. 1983 Apr;32(4):1026-8 [6340834] Nature. 1984 Oct 18-24;311(5987):626-31 [6090948] J Virol. 1985 May;54(2):374-82 [2985803] J Biol Chem. 1985 Jun 10;260(11):6654-62 [3922977] J Cell Biol. 1987 Nov;105(5):1957-69 [2824524] J Cell Biol. 1988 Jul;107(1):89-99 [2839523] Cell. 1989 Mar 10;56(5):801-13 [2647301] J Cell Biol. 1989 Jul;109(1):61-72 [2745557] Cell. 1989 Nov 17;59(4):591-601 [2573430] J Histochem Cytochem. 1989 Dec;37(12):1817-23 [2685110] J Histochem Cytochem. 1989 Dec;37(12):1835-44 [2584692] Annu Rev Cell Biol. 1989;5:247-75 [2688705] Annu Rev Cell Biol. 1989;5:277-307 [2688707] J Biol Chem. 1990 Apr 25;265(12):6879-83 [2157712] Cell. 1990 Jun 29;61(7):1349-57 [2194670] J Cell Biol. 1990 Sep;111(3):857-66 [1697299] Biochem J. 1990 Aug 15;270(1):97-102 [2204342] J Cell Biol. 1991 Feb;112(4):567-77 [1847146] J Cell Biol. 1991 Feb;112(4):579-88 [1993732] Nature. 1991 Aug 1;352(6334):441-4 [1861723] Nature. 1992 Jan 2;355(6355):33-45 [1731198] Cell. 1992 Jan 24;68(2):353-64 [1310258] J Cell Sci. 1991 Nov;100 ( Pt 3):415-30 [1808196] Cell. 1992 May 15;69(4):625-35 [1316805] J Cell Biol. 1993 Jan;120(1):5-13 [8416995] J Cell Biol. 1993 Jan;120(2):325-38 [8380600] J Cell Sci. 1992 Dec;103 ( Pt 4):875-80 [1336779] J Cell Biol. 1993 Mar;120(5):1123-35 [8436587] Virology. 1993 Apr;193(2):545-62 [8460475] J Cell Biol. 1993 Apr;121(2):317-33 [8468349] Cell. 1993 Jun 18;73(6):1079-90 [8513494] Eur J Cell Biol. 1993 Apr;60(2):371-5 [8330634] EMBO J. 1993 Jul;12(7):2821-9 [8392934] J Biol Chem. 1993 Sep 5;268(25):19092-100 [8395529] Science. 1993 Sep 3;261(5126):1280-1 [8362242] Science. 1994 Jan 21;263(5145):387-90 [8278814] Mol Biol Cell. 1996 Apr;7(4):631-50 [8730104] J Biol Chem. 1996 Jul 19;271(29):17183-9 [8663407] Mol Biol Cell. 1996 Mar;7(3):483-93 [8868475] J Cell Biol. 1996 Oct;135(2):341-54 [8896593] J Biol Chem. 1997 Jan 17;272(3):1970-5 [8999888] Proc Natl Acad Sci U S A. 1997 Mar 4;94(5):1828-33 [9050864] J Cell Biol. 1997 Jun 16;137(6):1211-28 [9182657] J Cell Biol. 1986 May;102(5):1558-66 [3084497] J Biol Chem. 1986 Nov 5;261(31):14681-9 [3021750] J Cell Biol. 1994 Apr;125(2):253-68 [8163544] J Cell Biol. 1994 May;125(3):557-71 [8175881] J Cell Sci. 1994 Mar;107 ( Pt 3):529-37 [8006071] J Cell Biol. 1994 Jul;126(1):41-52 [8027184] J Cell Biol. 1994 Sep;126(5):1157-72 [7914893] J Cell Biol. 1994 Nov;127(3):653-65 [7962050] Nature. 1994 Nov 3;372(6501):55-63 [7969419] Cell. 1994 Dec 30;79(7):1199-207 [8001155] J Cell Biol. 1994 Dec;127(6 Pt 1):1557-74 [7798312] J Biol Chem. 1995 Feb 24;270(8):3551-3 [7876089] EMBO J. 1995 Apr 3;14(7):1329-39 [7729411] J Cell Sci. 1995 Apr;108 ( Pt 4):1617-27 [7615680] J Biol Chem. 1986 Nov 5;261(31):14690-6 [3021751] Cell. 1987 Jul 17;50(2):289-300 [3594573] EMBO J. 1994 Apr 1;13(7):1696-705 [8157008] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The catalytic domain of PKC-epsilon, in reciprocal PKC-delta and -epsilon chimeras, is responsible for conferring tumorgenicity to NIH3T3 cells, whereas both regulatory and catalytic domains of PKC-epsilon contribute to in vitro transformation. AN - 79680514; 9467942 AB - Protein kinase C-epsilon (PKC-epsilon) has been shown to increase growth and cause malignant transformation when overexpressed in NIH3T3 cells, whereas PKC-delta reduced fibroblast growth. Two reciprocal chimeric proteins (PKC-epsilondelta and PKC-deltaepsilon were constructed by exchanging the regulatory and catalytic domains of PKC-delta and -epsilon and were stably overexpressed in NIH3T3 cells. Fibroblasts that overexpressed either chimera showed maximum cell density and morphology that were intermediate between cells overexpressing PKC-delta and those that overexpressed PKC-epsilon. Moreover, all lines that expressed chimeras were capable of anchorage-independent growth in the presence of TPA, which indicated that both the regulatory and catalytic domains of PKC-epsilon could independently induce NIH3T3 transformation, although the combination of both domains, as found in PKC-epsilon, was the most active form. In contrast, the translocation pattern and ability to induce tumors in nude mice was attributable to the catalytic domains exclusively. In particular, cells that expressed PKC-deltaepsilon retained PKC-epsilon's full potency of tumorgenicity when injected into nude mice. In sum, our findings not only reinforce the concept that only certain PKC isozymes contribute to carcinogenesis but also show that different domains of PKCs mediate the physiologically distinguishable events of transformation and tumorgenesis. JF - Oncogene AU - Wang, Q J AU - Acs, P AU - Goodnight, J AU - Blumberg, P M AU - Mischak, H AU - Mushinski, J F AD - Laboratory of Genetics, National Cancer Institute, Bethesda, Maryland 20892-4255, USA. Y1 - 1998/01/08/ PY - 1998 DA - 1998 Jan 08 SP - 53 EP - 60 VL - 16 IS - 1 SN - 0950-9232, 0950-9232 KW - Isoenzymes KW - 0 KW - Recombinant Fusion Proteins KW - Prkcd protein, mouse KW - EC 2.7.1.- KW - Prkce protein, mouse KW - Protein Kinase C KW - EC 2.7.11.13 KW - Protein Kinase C-delta KW - Protein Kinase C-epsilon KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - 3T3 Cells KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Mice, Nude KW - Mice KW - Cell Transformation, Neoplastic KW - Cell Division KW - Catalysis KW - Recombinant Fusion Proteins -- metabolism KW - Protein Kinase C -- metabolism KW - Protein Kinase C -- genetics KW - Recombinant Fusion Proteins -- genetics KW - Isoenzymes -- genetics KW - Isoenzymes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79680514?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncogene&rft.atitle=The+catalytic+domain+of+PKC-epsilon%2C+in+reciprocal+PKC-delta+and+-epsilon+chimeras%2C+is+responsible+for+conferring+tumorgenicity+to+NIH3T3+cells%2C+whereas+both+regulatory+and+catalytic+domains+of+PKC-epsilon+contribute+to+in+vitro+transformation.&rft.au=Wang%2C+Q+J%3BAcs%2C+P%3BGoodnight%2C+J%3BBlumberg%2C+P+M%3BMischak%2C+H%3BMushinski%2C+J+F&rft.aulast=Wang&rft.aufirst=Q&rft.date=1998-01-08&rft.volume=16&rft.issue=1&rft.spage=53&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-02 N1 - Date created - 1998-03-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Long-term feeding of sodium saccharin to nonhuman primates: implications for urinary tract cancer. AN - 79657187; 9428778 AB - It was observed in the early 1970s that saccharin produced bladder cancer in rats. However, it has been unclear whether sodium saccharin when consumed by humans poses a substantial carcinogenic hazard. Numerous epidemiologic studies have not shown any evidence of increased urothelial proliferation associated with ingestion of sodium saccharin. Our purpose was to determine the effects of long-term feeding of sodium saccharin to three species of nonhuman primates. Twenty monkeys of three species (six African green, seven rhesus, six cynomolgus, and one hybrid [of rhesus male and cynomolgus female parentage]) were treated with sodium saccharin (25 mg in the diet/kg body weight daily for 5 days a week) beginning within 24 hours after birth and continuing for up to 24 years. Sixteen monkeys (seven rhesus and nine cynomolgus) served as controls. During their last 2 years of life, urine was collected from selected treated and control animals and evaluated for various urinary chemistries and for the presence of calculi, microcrystalluria, and precipitate. Urinary bladders were examined by light microscopy and by scanning electron microscopy. Sodium saccharin treatment had no effect on the urine or urothelium in any of these monkeys. There was no evidence of increased urothelial cell proliferation, and there was no evidence of formation of solid material in the urine. Although the dose of sodium saccharin administered to these monkeys was only five to 10 times the allowable daily intake for humans, the results provide additional evidence that sodium saccharin is without a carcinogenic effect on the primate urinary tract. JF - Journal of the National Cancer Institute AU - Takayama, S AU - Sieber, S M AU - Adamson, R H AU - Thorgeirsson, U P AU - Dalgard, D W AU - Arnold, L L AU - Cano, M AU - Eklund, S AU - Cohen, S M AD - Division of Basic Sciences, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1998/01/07/ PY - 1998 DA - 1998 Jan 07 SP - 19 EP - 25 VL - 90 IS - 1 SN - 0027-8874, 0027-8874 KW - Carcinogens KW - 0 KW - Saccharin KW - FST467XS7D KW - Index Medicus KW - Animals KW - Cell Division -- drug effects KW - Ultrasonography KW - Male KW - Haplorhini KW - Female KW - Microscopy, Electron, Scanning KW - Saccharin -- administration & dosage KW - Urothelium -- drug effects KW - Carcinogens -- administration & dosage KW - Saccharin -- toxicity KW - Carcinogens -- toxicity KW - Urine -- chemistry KW - Urinary Bladder -- drug effects KW - Urinary Bladder -- diagnostic imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79657187?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Long-term+feeding+of+sodium+saccharin+to+nonhuman+primates%3A+implications+for+urinary+tract+cancer.&rft.au=Takayama%2C+S%3BSieber%2C+S+M%3BAdamson%2C+R+H%3BThorgeirsson%2C+U+P%3BDalgard%2C+D+W%3BArnold%2C+L+L%3BCano%2C+M%3BEklund%2C+S%3BCohen%2C+S+M&rft.aulast=Takayama&rft.aufirst=S&rft.date=1998-01-07&rft.volume=90&rft.issue=1&rft.spage=19&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 - 1998-01-22 N1 - Date created - 1998-01-22 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Natl Cancer Inst. 1998 Jan 7;90(1):2-3 [9428771] J Natl Cancer Inst. 1998 Jun 17;90(12):934-6 [9637144] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mammary carcinoma cells over-expressing tissue inhibitor of metalloproteinases-1 show enhanced vascular endothelial growth factor expression. AN - 79654506; 9426694 AB - The tissue inhibitor of metalloproteinases-1 (TIMP-1) has at least 2 independent functions, i.e., regulation of matrix metalloproteinases and erythroid-potentiating activity. We investigated the effects of TIMP-1 over-expression on tumor growth, using cloned lines derived from a TIMP-1-transfected rat breast carcinoma cell line. The in vitro growth rate of the TIMP-1-transfected clones was indistinguishable from that of the control. In contrast, the highest TIMP-1-producing clone (159.0 ng/ml), designated as T-H, formed 4.6-fold larger s.c. tumors than did the control after 14 days. Tumors derived from an intermediate TIMP-1-producing clone (45.4 ng/ml), designated as T-M, were 1.9-fold larger than the control. TIMP-1 over-expression was associated with increased vascular endothelial growth factor (VEGF) expression, vascularization and proliferative activity of the s.c. tumors. Similar to the rat breast carcinoma cells, transfection of TIMP-1 cDNA into the human breast carcinoma cell line MCF-7 resulted in up-regulation of VEGF, with a linear relationship between TIMP-1 and VEGF production in 9 cell clones examined. There was, however, no change in VEGF expression when the rat and human breast carcinoma cell lines were exposed to exogenous recombinant TIMP-1. Our findings suggest that over-expression of TIMP-1 confers growth advantage on breast carcinoma cells in vivo and that up-regulation of VEGF expression may play an important role in this TIMP-1-mediated, growth-stimulating effect. JF - International journal of cancer AU - Yoshiji, H AU - Harris, S R AU - Raso, E AU - Gomez, D E AU - Lindsay, C K AU - Shibuya, M AU - Sinha, C C AU - Thorgeirsson, U P AD - Tumor Biology and Carcinogenesis Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1998/01/05/ PY - 1998 DA - 1998 Jan 05 SP - 81 EP - 87 VL - 75 IS - 1 SN - 0020-7136, 0020-7136 KW - Endothelial Growth Factors KW - 0 KW - Lymphokines KW - Neoplasm Proteins KW - Tissue Inhibitor of Metalloproteinase-1 KW - Vascular Endothelial Growth Factor A KW - Vascular Endothelial Growth Factors KW - Index Medicus KW - Rats KW - Animals KW - Tumor Cells, Cultured KW - Transfection KW - Humans KW - Genetic Vectors -- genetics KW - Neovascularization, Pathologic -- pathology KW - Female KW - Cell Division KW - Lymphokines -- metabolism KW - Tissue Inhibitor of Metalloproteinase-1 -- metabolism KW - Endothelial Growth Factors -- metabolism KW - Neoplasm Proteins -- genetics KW - Mammary Neoplasms, Experimental -- blood supply KW - Mammary Neoplasms, Experimental -- genetics KW - Mammary Neoplasms, Experimental -- metabolism KW - Neoplasm Proteins -- metabolism KW - Tissue Inhibitor of Metalloproteinase-1 -- genetics KW - Mammary Neoplasms, Experimental -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79654506?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+journal+of+cancer&rft.atitle=Mammary+carcinoma+cells+over-expressing+tissue+inhibitor+of+metalloproteinases-1+show+enhanced+vascular+endothelial+growth+factor+expression.&rft.au=Yoshiji%2C+H%3BHarris%2C+S+R%3BRaso%2C+E%3BGomez%2C+D+E%3BLindsay%2C+C+K%3BShibuya%2C+M%3BSinha%2C+C+C%3BThorgeirsson%2C+U+P&rft.aulast=Yoshiji&rft.aufirst=H&rft.date=1998-01-05&rft.volume=75&rft.issue=1&rft.spage=81&rft.isbn=&rft.btitle=&rft.title=International+journal+of+cancer&rft.issn=00207136&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-01-22 N1 - Date created - 1998-01-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Combinations of paclitaxel and vinblastine and their effects on tubulin polymerization and cellular cytotoxicity: characterization of a synergistic schedule. AN - 79653900; 9426691 AB - Paclitaxel (PTX) and vinblastine (VBL) represent 2 classes of drugs that target tubulin but have separate binding properties and opposing mechanisms of action. To evaluate the potential use of these agents together in a chemotherapeutic regimen, we investigated their effects on the dynamics of tubulin polymerization and cellular cytotoxicity, when administered singly or in combination. In human epidermoid carcinoma KB cells and MCF-7 breast carcinoma cells, we observed a time- and dose-dependent effect on cytoskeletal dynamics for both PTX and VBL. Tubulin polymerization induced by PTX was stable for more than 24 hr. When PTX treatment was followed by VBL, a time- and dose-dependent reversal of tubulin polymerization was observed. In contrast, rapid tubulin polymerization occurred when VBL was followed by PTX. When both agents were added simultaneously, a diminution of PTX-induced tubulin polymerization was observed with increasing doses of VBL; a maximum reduction was achieved when equal concentrations were used. Examination of the tubulin pattern by immunofluorescence in MCF-7 breast cancer cells confirmed and extended our findings. Bundle formation followed treatment with PTX. Addition of increasing concentrations of VBL prevented bundling; however, the normal cytoskeletal architecture was not restored. Cytotoxicity studies carried out using the median dose effect principles and the combination index analysis showed synergism when VBL and PTX were administered sequentially and antagonism for simultaneous administration. Our results demonstrate changes in tubulin dynamics following drug treatment and provide a rationale for combined PTX/VBL therapy after careful evaluation of the schedule of administration. JF - International journal of cancer AU - Giannakakou, P AU - Villalba, L AU - Li, H AU - Poruchynsky, M AU - Fojo, T AD - Medicine Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA. Y1 - 1998/01/05/ PY - 1998 DA - 1998 Jan 05 SP - 57 EP - 63 VL - 75 IS - 1 SN - 0020-7136, 0020-7136 KW - Antineoplastic Agents, Phytogenic KW - 0 KW - Tubulin KW - Vinblastine KW - 5V9KLZ54CY KW - Paclitaxel KW - P88XT4IS4D KW - Index Medicus KW - Drug Screening Assays, Antitumor KW - Drug Interactions KW - Drug Administration Schedule KW - HeLa Cells -- drug effects KW - Tumor Cells, Cultured -- drug effects KW - Dose-Response Relationship, Drug KW - Humans KW - Antineoplastic Combined Chemotherapy Protocols -- pharmacology KW - Vinblastine -- pharmacology KW - Paclitaxel -- administration & dosage KW - Tubulin -- drug effects KW - Vinblastine -- administration & dosage KW - Antineoplastic Agents, Phytogenic -- pharmacology KW - Paclitaxel -- pharmacology KW - Antineoplastic Agents, Phytogenic -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79653900?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+journal+of+cancer&rft.atitle=Combinations+of+paclitaxel+and+vinblastine+and+their+effects+on+tubulin+polymerization+and+cellular+cytotoxicity%3A+characterization+of+a+synergistic+schedule.&rft.au=Giannakakou%2C+P%3BVillalba%2C+L%3BLi%2C+H%3BPoruchynsky%2C+M%3BFojo%2C+T&rft.aulast=Giannakakou&rft.aufirst=P&rft.date=1998-01-05&rft.volume=75&rft.issue=1&rft.spage=57&rft.isbn=&rft.btitle=&rft.title=International+journal+of+cancer&rft.issn=00207136&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-01-22 N1 - Date created - 1998-01-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Impaired learning in rats in a 14-unit T-maze by 7-nitroindazole, a neuronal nitric oxide synthase inhibitor, is attenuated by the nitric oxide donor, molsidomine. AN - 79707653; 9489851 AB - In previous experiments, it was demonstrated that systemic or central administration of the nitric oxide synthase (NO synthase) inhibitor, NG-nitro-L-arginine (N-Arg), produced dose-dependent learning impairments in rats in a 14-unit T-maze; and that sodium nitroprusside, a NO donor, could attenuate the impairment. Since N-Arg is not specific for neuronal NO synthase and produces hypertension, it is possible that effects on the cardiovasculature may have contributed to the impaired maze performance. In the present experiment, we have investigated the maze performance of 3-4 months old male Fischer-344 rats following treatment with 7-nitroindazole, a NO synthase inhibitor that is selective for neuronal NO synthase and does not produce hypertension. In addition, we examined the effects of the NO donor, molsidomine, which is much longer acting than sodium nitroprusside. Rats were pretrained to avoid footshock in a straight runway and received training in a 14-unit T-maze 24 h later. In an initial dose-response study, rats received intraperitoneal (i.p.) injections of either 7-nitroindazole (25, 50, or 65 mg/kg) or peanut oil 30 min prior to maze training. 7-nitroindazole produced significant, dose-dependent maze acquisition deficits, with 65 mg/kg producing the greatest learning impairment. This dose of 7-nitroindazole had no significant effect on systolic blood pressure. Following the dose-response study, rats were given i.p. injections of either 7-nitroindazole (70 mg/kg) plus saline, 7-nitroindazole (70 mg/kg) plus the NO donor, molsidomine (2 or 4 mg/kg), or peanut oil plus saline as controls. Both doses of molsidomine significantly attenuated the learning deficit induced by 7-nitroindazole relative to controls. These findings represent the first evidence that impaired learning produced by inhibition of neuronal NO synthase can be overcome by systemic administration of a NO donor. JF - European journal of pharmacology AU - Meyer, R C AU - Spangler, E L AU - Patel, N AU - London, E D AU - Ingram, D K AD - Molecular Physiology and Genetics Section, Nathan W. Shock Laboratories, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA. Y1 - 1998/01/02/ PY - 1998 DA - 1998 Jan 02 SP - 17 EP - 22 VL - 341 IS - 1 SN - 0014-2999, 0014-2999 KW - Enzyme Inhibitors KW - 0 KW - Indazoles KW - Vasodilator Agents KW - Nitric Oxide KW - 31C4KY9ESH KW - Molsidomine KW - D46583G77X KW - Nitric Oxide Synthase KW - EC 1.14.13.39 KW - 7-nitroindazole KW - UX0N37CMVH KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Dose-Response Relationship, Drug KW - Nitric Oxide Synthase -- antagonists & inhibitors KW - Neurons -- enzymology KW - Nitric Oxide -- biosynthesis KW - Blood Pressure -- drug effects KW - Drug Synergism KW - Male KW - Maze Learning -- drug effects KW - Indazoles -- administration & dosage KW - Enzyme Inhibitors -- administration & dosage KW - Indazoles -- pharmacology KW - Enzyme Inhibitors -- pharmacology KW - Indazoles -- antagonists & inhibitors KW - Vasodilator Agents -- pharmacology KW - Molsidomine -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79707653?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Impaired+learning+in+rats+in+a+14-unit+T-maze+by+7-nitroindazole%2C+a+neuronal+nitric+oxide+synthase+inhibitor%2C+is+attenuated+by+the+nitric+oxide+donor%2C+molsidomine.&rft.au=Meyer%2C+R+C%3BSpangler%2C+E+L%3BPatel%2C+N%3BLondon%2C+E+D%3BIngram%2C+D+K&rft.aulast=Meyer&rft.aufirst=R&rft.date=1998-01-02&rft.volume=341&rft.issue=1&rft.spage=17&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 - 1998-04-29 N1 - Date created - 1998-04-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Coordinate transactivation of the interleukin-2 CD28 response element by c-Rel and ATF-1/CREB2. AN - 79633811; 9417115 AB - The interleukin-2 CD28 response element (CD28RE) acts as a composite enhancer, in conjunction with a 3'-12-O-tetradecanoylphorbol-13-acetate response element (TRE)-like element, to confer CD28 receptor-dependent inducibility to the interleukin-2 promoter in T-cells. When inserted as a single copy upstream of a basal promoter, this composite enhancer, termed the CD28RE-TRE, is both highly active and CD28-inducible in transactivation assays. A multicomponent nuclear protein complex that binds the CD28RE-TRE was isolated by DNA affinity chromatography from nuclear extracts of mitogen- and CD28 receptor-costimulated human T-cells. Immunological and biochemical analyses of this complex reveal the presence of c-Rel, ATF-1, and CREB2 as major DNA-binding components. Coexpression of c-Rel in combination with ATF-1, CREB2, or ATF-1/CREB2 leads to synergistic transactivation of a CD28RE-TRE reporter plasmid in quiescent Jurkat T-cells. Furthermore, CD28-dependent transactivation of the CD28RE-TRE is specifically inhibited by cAMP response element-binding protein (CREB) dominant-negative expression vectors. Moreover, mutant promoter constructs in which the internal 5'-CD28RE and 3'-TRE-like sequences have been topologically positioned 180 degrees out of phase with one another show loss of mitogen- and CD28-dependent inducibility. Finally, the addition of the CREB-binding transcriptional coactivator p300 leads to a dramatic CREB-dependent increase in both mitogen- and CD28-mediated transactivation of the CD28RE-TRE. These findings demonstrate that full physiological responsiveness to CD28 receptor stimulation in T-cells is dependent on topologically linked sequences within the CD28RE-TRE composite enhancer and provide strong support of a direct role for the CREB family of transcription factors and p300/CREB-binding protein coactivator proteins in cytokine gene induction during T-cell activation. JF - The Journal of biological chemistry AU - Butscher, W G AU - Powers, C AU - Olive, M AU - Vinson, C AU - Gardner, K AD - Laboratory of Pathology, NCI, National Institutes of Health, Bethesda, Maryland 20892-1500, USA. Y1 - 1998/01/02/ PY - 1998 DA - 1998 Jan 02 SP - 552 EP - 560 VL - 273 IS - 1 SN - 0021-9258, 0021-9258 KW - Activating Transcription Factor 1 KW - 0 KW - Antibodies, Monoclonal KW - Antigens, CD28 KW - DNA-Binding Proteins KW - Interleukin-2 KW - Proto-Oncogene Proteins KW - Proto-Oncogene Proteins c-rel KW - Transcription Factors KW - Ionomycin KW - 56092-81-0 KW - DNA KW - 9007-49-2 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Humans KW - Jurkat Cells KW - Ionomycin -- pharmacology KW - Antibodies, Monoclonal -- immunology KW - Mutagenesis KW - Chromatography, Affinity KW - Antibody Specificity KW - T-Lymphocytes -- metabolism KW - Promoter Regions, Genetic KW - Genetic Vectors KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Up-Regulation KW - T-Lymphocytes -- drug effects KW - T-Lymphocytes -- immunology KW - Antigens, CD28 -- genetics KW - Transcription Factors -- metabolism KW - Antigens, CD28 -- isolation & purification KW - Proto-Oncogene Proteins -- metabolism KW - Interleukin-2 -- genetics KW - Transcriptional Activation KW - Antigens, CD28 -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79633811?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Coordinate+transactivation+of+the+interleukin-2+CD28+response+element+by+c-Rel+and+ATF-1%2FCREB2.&rft.au=Butscher%2C+W+G%3BPowers%2C+C%3BOlive%2C+M%3BVinson%2C+C%3BGardner%2C+K&rft.aulast=Butscher&rft.aufirst=W&rft.date=1998-01-02&rft.volume=273&rft.issue=1&rft.spage=552&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 - 1998-02-03 N1 - Date created - 1998-02-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Activation and processing of non-anchored yapsin 1 (Yap3p). AN - 79631568; 9417119 AB - A C-terminally truncated form of yapsin 1 (yeast aspartic protease 3), the first member of the novel sub-class of aspartic proteases with specificity for basic residues (designated the Yapsins), was overexpressed and purified to apparent homogeneity, yielding approximately 1 microg of yapsin 1/g of wet yeast. N-terminal amino acid analysis of the purified protein confirmed that the propeptide was absent and that the mature enzyme began at Ala68. The mature enzyme was shown to be composed of approximately equimolar amounts of two subunits, designated alpha and beta, that were associated to each other by a disulfide bond. C-terminally truncated proyapsin 1 was also expressed in the baculovirus/Sf9 insect cell expression system and secreted as a zymogen that could be activated upon incubation at an acidic pH with an optimum at approximately 4.0. When expressed without its pro-region, it was localized intracellularly and lacked activity, indicating that the pro-region was required for the correct folding of the enzyme. The activation of proyapsin 1 in vitro exhibited linear kinetics and generated an intermediate form of yapsin 1 or pseudo-yapsin 1. JF - The Journal of biological chemistry AU - Cawley, N X AU - Olsen, V AU - Zhang, C F AU - Chen, H C AU - Tan, M AU - Loh, Y P AD - Section on Cellular Neurobiology, Laboratory of Developmental Neurobiology, NICHD, National Institutes of Health, Bethesda, Maryland 20892, USA.cawley@codon.nih.gov Y1 - 1998/01/02/ PY - 1998 DA - 1998 Jan 02 SP - 584 EP - 591 VL - 273 IS - 1 SN - 0021-9258, 0021-9258 KW - Enzyme Precursors KW - 0 KW - Fungal Proteins KW - Recombinant Proteins KW - Saccharomyces cerevisiae Proteins KW - aspartic proteinase A KW - EC 3.4.23 KW - Aspartic Acid Endopeptidases KW - EC 3.4.23.- KW - YPS1 protein, S cerevisiae KW - EC 3.4.23.25 KW - Index Medicus KW - Enzyme Precursors -- metabolism KW - Electrophoresis, Polyacrylamide Gel KW - Enzyme Activation KW - Amino Acid Sequence KW - Recombinant Proteins -- genetics KW - Mutagenesis, Site-Directed KW - Recombinant Proteins -- isolation & purification KW - Baculoviridae -- genetics KW - Blotting, Western KW - Recombinant Proteins -- metabolism KW - Kinetics KW - Molecular Sequence Data KW - Enzyme Precursors -- isolation & purification KW - Substrate Specificity KW - Enzyme Precursors -- genetics KW - Fungal Proteins -- metabolism KW - Aspartic Acid Endopeptidases -- genetics KW - Protein Processing, Post-Translational KW - Aspartic Acid Endopeptidases -- isolation & purification KW - Aspartic Acid Endopeptidases -- metabolism KW - Fungal Proteins -- isolation & purification KW - Fungal Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79631568?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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+and+processing+of+non-anchored+yapsin+1+%28Yap3p%29.&rft.au=Cawley%2C+N+X%3BOlsen%2C+V%3BZhang%2C+C+F%3BChen%2C+H+C%3BTan%2C+M%3BLoh%2C+Y+P&rft.aulast=Cawley&rft.aufirst=N&rft.date=1998-01-02&rft.volume=273&rft.issue=1&rft.spage=584&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 - 1998-02-03 N1 - Date created - 1998-02-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A novel ets-related transcription factor, ERT/ESX/ESE-1, regulates expression of the transforming growth factor-beta type II receptor. AN - 79631256; 9417054 AB - A 2.5-kilobase cDNA clone that encodes a 371-amino acid novel transcription factor was isolated from a human placenta cDNA library using a yeast one-hybrid system. The novel ets-related transcription factor (ERT) showed a homology with the ETS DNA-binding domain. Using constructs of the transforming growth factor-beta (TGF-beta) type II receptor (RII) promoter linked to the luciferase gene, we have demonstrated that ERT activates transcription of the TGF-beta RII gene through the 5'-TTTCCTGTTTCC-3' response element spanning nucleotides +13 to +24 and multiple additional ETS binding sites between -1816 and -82 of the TGF-beta RII promoter. A specific interaction between ERT and the ETS binding sites was also demonstrated using an electrophoretic mobility shift assay. Deletion mapping of ERT protein suggests that the transactivation domain resides in the amino terminus while the DNA-binding domain is localized to the carboxyl-terminal region. Our results suggest that ERT might be a major transcription factor involved in the transcriptional regulation of the TGF-beta RII gene. JF - The Journal of biological chemistry AU - Choi, S G AU - Yi, Y AU - Kim, Y S AU - Kato, M AU - Chang, J AU - Chung, H W AU - Hahm, K B AU - Yang, H K AU - Rhee, H H AU - Bang, Y J AU - Kim, S J AD - Laboratory of Cell Regulation and Carcinogenesis, NCI, National Institutes of Health, Bethesda, Maryland 20892-5055, USA. Y1 - 1998/01/02/ PY - 1998 DA - 1998 Jan 02 SP - 110 EP - 117 VL - 273 IS - 1 SN - 0021-9258, 0021-9258 KW - DNA, Complementary KW - 0 KW - Proto-Oncogene Proteins KW - Proto-Oncogene Proteins c-ets KW - Receptors, Transforming Growth Factor beta KW - Transcription Factors KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - transforming growth factor-beta type II receptor KW - EC 2.7.11.30 KW - Index Medicus KW - Promoter Regions, Genetic KW - Humans KW - Molecular Sequence Data KW - Transcription, Genetic KW - Protein Binding KW - Cloning, Molecular KW - Receptors, Transforming Growth Factor beta -- genetics KW - Transcription Factors -- metabolism KW - Proto-Oncogene Proteins -- metabolism KW - Gene Expression Regulation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79631256?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=A+novel+ets-related+transcription+factor%2C+ERT%2FESX%2FESE-1%2C+regulates+expression+of+the+transforming+growth+factor-beta+type+II+receptor.&rft.au=Choi%2C+S+G%3BYi%2C+Y%3BKim%2C+Y+S%3BKato%2C+M%3BChang%2C+J%3BChung%2C+H+W%3BHahm%2C+K+B%3BYang%2C+H+K%3BRhee%2C+H+H%3BBang%2C+Y+J%3BKim%2C+S+J&rft.aulast=Choi&rft.aufirst=S&rft.date=1998-01-02&rft.volume=273&rft.issue=1&rft.spage=110&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 - 1998-02-03 N1 - Date created - 1998-02-03 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF017307; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Language, Play, Emotional Availability, and Acceptance in Cocaine-Exposed and Non-Cocaine-Exposed Young Children and Their Mothers AN - 85513211; 200101017 AB - This study assessed language, play, emotional availability, & acceptance in cocaine-exposed & non-cocaine-exposed children & their mothers at 18 months. Although prenatal cocaine exposure is thought to put the developing nervous system at risk, & likewise drug-abusing mothers are thought to disadvantage their developing children, cocaine-exposed youngsters showed no systematic differences in measures of language, play, emotional availability, & acceptance from their demographically similar non-cocaine-exposed peers. More gender (& social class) effects than cocaine-exposure effects emerged in these measures. The implications of this pattern of findings for cognitive & socioemotional functioning in childhood & for social policy are discussed. 5 Tables, 72 References. Adapted from the source document JF - Revue PArole AU - Bornstein, Marc H AU - Mayes, Linda C AU - Park, Jaihyun AD - National Instit Child Health & Human Development, Bethesda, MD Marc_H_Bornstein@nih.gov Y1 - 1998///0, PY - 1998 DA - 0, 1998 SP - 235 EP - 260 VL - 7-8 SN - 0770-545X, 0770-545X KW - Parent Child Interaction (62760) KW - Emotions (21600) KW - Drug Effects (19900) KW - Language Acquisition (41600) KW - Cognitive Development (12850) KW - Interpersonal Behavior (37550) KW - article KW - 4015: psycholinguistics; child language acquisition UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85513211?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Allba&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Revue+PArole&rft.atitle=Language%2C+Play%2C+Emotional+Availability%2C+and+Acceptance+in+Cocaine-Exposed+and+Non-Cocaine-Exposed+Young+Children+and+Their+Mothers&rft.au=Bornstein%2C+Marc+H%3BMayes%2C+Linda+C%3BPark%2C+Jaihyun&rft.aulast=Bornstein&rft.aufirst=Marc&rft.date=1998-01-01&rft.volume=7-8&rft.issue=&rft.spage=235&rft.isbn=&rft.btitle=&rft.title=Revue+PArole&rft.issn=0770545X&rft_id=info:doi/ LA - English DB - Linguistics and Language Behavior Abstracts (LLBA) N1 - Date revised - 2003-10-01 N1 - Last updated - 2016-09-27 N1 - SubjectsTermNotLitGenreText - Language Acquisition (41600); Parent Child Interaction (62760); Drug Effects (19900); Interpersonal Behavior (37550); Emotions (21600); Cognitive Development (12850) ER - TY - JOUR T1 - Overview of human tremor physiology. AN - 85411604; pmid-9827594 AB - The physiology differs in the many forms of human tremor. Tremors may derive from mechanical oscillations, mechanical reflex oscillations, normal central oscillators, and pathologic central oscillators. Methods of studying tremor include accelerometry and electromyography (EMG). An excellent method consists of accelerometry and EMG combined with spectral analysis and weighting of the body part, which allows separation of tremors coming from mechanical reflex and central oscillators. Physiologic tremor is a mechanical tremor with a possible contribution of the normal 8-12 Hz central oscillator; exaggerated physiologic tremor is a mechanical reflex tremor. Essential tremor (ET) comes from a central oscillator that can be easily influenced with sensory input. The classic rest tremor of Parkinson's disease (PD) comes from a central oscillator that seems less easily influenced with sensory input but can be affected by transcranial magnetic stimulation. Other tremors with central oscillators are palatal tremor and orthostatic tremor. Other tremors whose physiology involves central loops includes cerebellar tremor and cortical tremor. Neuropathic tremors may be a result of delays in peripheral loops, but central oscillators play a role in some. JF - Movement disorders : official journal of the Movement Disorder Society AU - Hallett, M AD - National Institute of Neurological Disorders and Stroke, Bethesda, Maryland 20892-1428, USA. Y1 - 1998 PY - 1998 DA - 1998 SP - 43 EP - 48 VL - 13 Suppl 3 SN - 0885-3185, 0885-3185 KW - Index Medicus KW - National Library of Medicine KW - Electromyography -- methods KW - Muscle Spindles -- physiology KW - Humans KW - Reflex, Stretch -- physiology KW - Biological Clocks -- physiology KW - Tremor -- diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85411604?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Movement+disorders+%3A+official+journal+of+the+Movement+Disorder+Society&rft.atitle=Overview+of+human+tremor+physiology.&rft.au=Hallett%2C+M&rft.aulast=Hallett&rft.aufirst=M&rft.date=1998-01-01&rft.volume=13+Suppl+3&rft.issue=&rft.spage=43&rft.isbn=&rft.btitle=&rft.title=Movement+disorders+%3A+official+journal+of+the+Movement+Disorder+Society&rft.issn=08853185&rft_id=info:doi/ LA - English DB - ComDisDome N1 - Date revised - 2008-01-14 N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Assessing functional outcomes: an overview. AN - 85408545; pmid-9720127 AB - Assessment of functional outcomes requires, first, a good working definition and, second, sufficiently reliable and valid measures from which to choose. With the advent of new or refined conceptualizations of patient outcomes, the functional domain has expanded to address not only routine activities of daily life but also the richly diverse aspects believed to constitute quality of life. This article defines and places the concept of functional outcomes within a context of various published and proposed classification schemes, and supports an expanded definition on the basis of these schemes, emerging models of health care that combine biomedical with social science approaches, and the visionary contributions of respected colleagues in the field. JF - Seminars in speech and language AU - Frattali, C M AD - National Institutes of Health, W.G. Magnuson Clinical Center, Rehabilitation Medicine Department, Bethesda, Maryland 20892-1604, USA. Y1 - 1998 PY - 1998 DA - 1998 SP - 209 EP - 220 VL - 19 IS - 3 SN - 0734-0478, 0734-0478 KW - Index Medicus KW - National Library of Medicine KW - Humans KW - Communication Disorders -- diagnosis KW - Treatment Outcome KW - Activities of Daily Living KW - Quality of Life KW - Communication Disorders -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85408545?accountid=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=Seminars+in+speech+and+language&rft.atitle=Assessing+functional+outcomes%3A+an+overview.&rft.au=Frattali%2C+C+M&rft.aulast=Frattali&rft.aufirst=C&rft.date=1998-01-01&rft.volume=19&rft.issue=3&rft.spage=209&rft.isbn=&rft.btitle=&rft.title=Seminars+in+speech+and+language&rft.issn=07340478&rft_id=info:doi/ LA - English DB - ComDisDome N1 - Date revised - 2008-01-14 N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Sources of Child Vocabulary Competence: A Multivariate Model AN - 85293671; llba-9902062 AB - Sources of individual variation in child vocabulary competence are examined in the context of a multivariate developmental ecological model. Maternal sociodemographic characteristics, personological characteristcs, & vocabulary, as well as child gender, social competence, & vocabulary competence were evaluated simultaneously in 126 children age 1:8 & their mothers. Measures of child vocabulary competence included two measures each of spontaneous speech, experimenter assessments, & maternal reports. Maternal measures, from proximal to distal, included vocabulary, verbal intelligence, personality, attitudes toward parenting, knowledge of parenting, & SES. Structural equation modelling supported several direct unique predictive relations: child gender (girls higher) & social competence as well as maternal attitudes toward parenting predicted child vocabulary competence, & mothers' vocabulary predicted child vocabulary comprehension & two measures of mother-reported child vocabulary expression. In addition, children's vocabulary competence was influenced indirectly by mothers' vocabulary, social personality, & knowledge of child development. Maternal vocabulary itself was positively influenced by SES, maternal verbal intelligence, & mothers' knowledge about parenting. Individual variation in child vocabulary competence might best be understood as arising within a nexus of contextual factors both proximal & distal to the child. 5 Tables, 2 Figures, 55 References. Adapted from the source document JF - Journal of Child Language AU - Bornstein, Marc H AU - Haynes, Maurice O AU - Painter, Kathleen M AD - Laboratory Comparative Ethnology National Instit Child Health & Human Development National Instits Health, Bethesda MD 20892-2030 Marc_H_Bornstein@nih.gov PY - 1998 SP - 367 EP - 393 VL - 25 IS - 2 SN - 0305-0009, 0305-0009 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85293671?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Child+Language&rft.atitle=Sources+of+Child+Vocabulary+Competence%3A+A+Multivariate+Model&rft.au=Bornstein%2C+Marc+H%3BHaynes%2C+Maurice+O%3BPainter%2C+Kathleen+M&rft.aulast=Bornstein&rft.aufirst=Marc&rft.date=1998-01-01&rft.volume=25&rft.issue=2&rft.spage=367&rft.isbn=&rft.btitle=&rft.title=Journal+of+Child+Language&rft.issn=03050009&rft_id=info:doi/ LA - English DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Axial specification for sensory organs versus non-sensory structures of the chicken inner ear. AN - 85274777; pmid-9389659 AB - A mature inner ear is a complex labyrinth containing multiple sensory organs and nonsensory structures in a fixed configuration. Any perturbation in the structure of the labyrinth will undoubtedly lead to functional deficits. Therefore, it is important to understand molecularly how and when the position of each inner ear component is determined during development. To address this issue, each axis of the otocyst (embryonic day 2.5, E2.5, stage 16-17) was changed systematically at an age when axial information of the inner ear is predicted to be fixed based on gene expression patterns. Transplanted inner ears were analyzed at E4.5 for gene expression of BMP4 (bone morphogenetic protein), SOHo-1 (sensory organ homeobox-1), Otx1 (cognate of Drosophila orthodenticle gene), p75NGFR (nerve growth factor receptor) and Msx1 (muscle segment homeobox), or at E9 for their gross anatomy and sensory organ formation. Our results showed that axial specification in the chick inner ear occurs later than expected and patterning of sensory organs in the inner ear was first specified along the anterior/posterior (A/P) axis, followed by the dorsal/ventral (D/V) axis. Whereas the A/P axis of the sensory organs was fixed at the time of transplantation, the A/P axis for most non-sensory structures was not and was able to be re-specified according to the new axial information from the host. The D/V axis for the inner ear was not fixed at the time of transplantation. The asynchronous specification of the A/P and D/V axes of the chick inner ear suggests that sensory organ formation is a multi-step phenomenon, rather than a single inductive event. JF - Development (Cambridge, England) AU - Wu, Doris Kar-Wah AU - Nunes, F D AU - Choo, D AD - National Institute on Deafness and Other Communication Disorders PY - 1998 SP - 11 EP - 20 VL - 125 IS - 1 SN - 0950-1991, 0950-1991 KW - Saccule and Utricle KW - Labyrinth KW - Transplantation KW - Hair Cells KW - Homeodomain Proteins KW - Chick Embryo KW - Animal KW - Cell Differentiation KW - Nerve Tissue Proteins KW - Phenotype KW - In Situ Hybridization KW - Cochlear Duct KW - Semicircular Canals KW - Bone Morphogenetic Proteins KW - Immunohistochemistry KW - Receptor, Nerve Growth Factor KW - Receptors, Nerve Growth Factor KW - Body Patterning KW - Gene Expression Regulation, Developmental UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85274777?accountid=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=Development+%28Cambridge%2C+England%29&rft.atitle=Axial+specification+for+sensory+organs+versus+non-sensory+structures+of+the+chicken+inner+ear.&rft.au=Wu%2C+Doris+Kar-Wah%3BNunes%2C+F+D%3BChoo%2C+D&rft.aulast=Wu&rft.aufirst=Doris&rft.date=1998-01-01&rft.volume=125&rft.issue=1&rft.spage=11&rft.isbn=&rft.btitle=&rft.title=Development+%28Cambridge%2C+England%29&rft.issn=09501991&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Age-related vasodilatory response to acetazolamide challenge in healthy adults: a dynamic contrast-enhanced MR study. AN - 85265934; pmid-9432155 AB - PURPOSE: We examined age-related changes in baseline regional cerebral blood volume (rCBV) and response to acetazolamide stimulation by using dynamic contrast-enhanced MR imaging. METHODS: Thirty healthy volunteers ranging widely in age (23 to 82 years) were examined before and after intravenous injection of acetazolamide with dynamic susceptibility contrast-enhanced MR imaging. rCBV values were normalized for intersubject and intrasubject comparison by estimating an arterial input function directly from the imaging data. Preacetazolamide baseline rCBV and the percentage volume change index (PVCI) of the postacetazolamide to preacetazolamide state were calculated and examined as a function of age. RESULTS: Older adults (>50 years) had lower baseline rCBV per unit tissue than did younger adults (<50 years), but higher rCBV after acetazolamide stimulation. Baseline rCBV tended to decrease with age in the medial frontal and frontoparietal gray matter regions. Response to acetazolamide stimulation, measured by PVCI, showed a significant age-related increase in gray matter, approximately 0.5% per year. CONCLUSION: rCBV can be significantly increased after acetazolamide stimulation in the healthy aged. These results support the notion that age-related decreases in rCBV measured at rest reflect reduced regional metabolic requirements rather than reduced capacity for regional substrate delivery. These data serve as a normative baseline for comparison studies of rCBV vascular reserve in aging persons with various cerebrovascular disorders. JF - AJNR. American Journal of Neuroradiology AU - Petrella, J R AU - DeCarli, C AU - Dagli, M AU - Grandin, C B AU - Duyn, J H AU - Frank, J A AU - Hoffman, E A AU - Theodore, W H AD - Laboratory of Diagnostic Radiology Research, National Institutes of Health, Bethesda, Md, USA. PY - 1998 SP - 39 EP - 44 VL - 19 IS - 1 SN - 0195-6108, 0195-6108 KW - Vasodilator Agents KW - Age Factors KW - Blood Volume KW - Injections, Intravenous KW - Aged, 80 and over KW - Human KW - Adult KW - Acetazolamide KW - Support, Non-U.S. Gov't KW - Middle Age KW - Aged KW - Cerebrovascular Circulation KW - Magnetic Resonance Imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85265934?accountid=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=AJNR.+American+Journal+of+Neuroradiology&rft.atitle=Age-related+vasodilatory+response+to+acetazolamide+challenge+in+healthy+adults%3A+a+dynamic+contrast-enhanced+MR+study.&rft.au=Petrella%2C+J+R%3BDeCarli%2C+C%3BDagli%2C+M%3BGrandin%2C+C+B%3BDuyn%2C+J+H%3BFrank%2C+J+A%3BHoffman%2C+E+A%3BTheodore%2C+W+H&rft.aulast=Petrella&rft.aufirst=J&rft.date=1998-01-01&rft.volume=19&rft.issue=1&rft.spage=39&rft.isbn=&rft.btitle=&rft.title=AJNR.+American+Journal+of+Neuroradiology&rft.issn=01956108&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Transmission of spongiform encephalopathy through biological products. AN - 85258531; pmid-9737380 AB - The transmissible spongiform encephalopathies (TSE) are rare but fatal neurological diseases that exist in sporadic, familial, and environmentally acquired forms. Environmentally acquired disease has until now been mostly iatrogenic in origin, recognized as responsible for nearly 200 deaths during the past 20 years. The two most important causes have been contamination of cadaver-derived human growth hormone and dura mater grafts, but a few instances related to contaminated neurosurgical instruments and corneal grafts have also occurred. Currently, a great deal of concern is being voiced about the potential risk of acquiring disease through blood or blood products, and although there is no supporting epidemiological evidence for such a danger, experiments are underway to define which blood components or plasma derivatives might pose the greatest problem. JF - Developments in Biological Standardization AU - Brown, P AD - Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. PY - 1998 SP - 73 EP - 78 VL - 93 SN - 0301-5149, 0301-5149 KW - Iatrogenic Disease KW - Human KW - Animal KW - Prion Diseases KW - Organ Transplantation KW - Biological Products UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85258531?accountid=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=Developments+in+Biological+Standardization&rft.atitle=Transmission+of+spongiform+encephalopathy+through+biological+products.&rft.au=Brown%2C+P&rft.aulast=Brown&rft.aufirst=P&rft.date=1998-01-01&rft.volume=93&rft.issue=&rft.spage=73&rft.isbn=&rft.btitle=&rft.title=Developments+in+Biological+Standardization&rft.issn=03015149&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Linguistic processing during repetitive transcranial magnetic stimulation. AN - 85227304; pmid-9443476 AB - To determine if linguistic processing could be selectively disrupted with repetitive transcranial magnetic stimulation (rTMS), rTMS was performed during a picture-word verification task. Seven right-handed subjects were trained in two conditions: picture-word verification, which required the subject to verify whether the picture of an object matched the subtitle name on the same page, and frame verification, which required subjects to verify whether there was a rectangular frame around the combined object picture and subtitle. Half of the trials were performed during rTMS. The effects of rTMS on performance were evaluated at the following four scalp positions: left anterior (the area where rTMS produced speech arrest), a mirror site on the right, and two positions in the left and right parietal region. Stimulation over the left deltoid muscle served as a control. Subjects had less difficulty in making picture-word matching decisions during unstimulated compared with stimulated trials at the left anterior and posterior positions. No significant difference in accuracy was detected in the frame verification condition, but response times in the frame verification condition were longer with stimulation at the left anterior position. Because rTMS of the dominant hemisphere affected linguistic processing independent of speech motor output, we confirm that rTMS may be used to investigate language and other cognitive functions. JF - Neurology AU - Flitman, S S AU - Grafman, J AU - Wassermann, E M AU - Cooper, V AU - O'Grady, J AU - Pascual-Leone, A AU - Hallett, M AD - Cognitive Neuroscience Section, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892-1440, USA. PY - 1998 SP - 175 EP - 181 VL - 50 IS - 1 SN - 0028-3878, 0028-3878 KW - Cerebral Cortex KW - Photic Stimulation KW - Form Perception KW - Human KW - Adult KW - Psychomotor Performance KW - Neuropsychological Tests KW - Electric Stimulation KW - Male KW - Female KW - Cognition KW - Reading KW - Magnetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85227304?accountid=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=Linguistic+processing+during+repetitive+transcranial+magnetic+stimulation.&rft.au=Flitman%2C+S+S%3BGrafman%2C+J%3BWassermann%2C+E+M%3BCooper%2C+V%3BO%27Grady%2C+J%3BPascual-Leone%2C+A%3BHallett%2C+M&rft.aulast=Flitman&rft.aufirst=S&rft.date=1998-01-01&rft.volume=50&rft.issue=1&rft.spage=175&rft.isbn=&rft.btitle=&rft.title=Neurology&rft.issn=00283878&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Asymmetry of chimpanzee planum temporale: humanlike pattern of Wernicke's brain language area homolog. AN - 85223865; pmid-9422693 AB - The anatomic pattern and left hemisphere size predominance of the planum temporale, a language area of the human brain, are also present in chimpanzees (Pan troglodytes). The left planum temporale was significantly larger in 94 percent (17 of 18) of chimpanzee brains examined. It is widely accepted that the planum temporale is a key component of Wernicke's receptive language area, which is also implicated in human communication-related disorders such as schizophrenia and in normal variations such as musical talent. However, anatomic hemispheric asymmetry of this cerebrocortical site is clearly not unique to humans, as is currently thought. The evolutionary origin of human language may have been founded on this basal anatomic substrate, which was already lateralized to the left hemisphere in the common ancestor of chimpanzees and humans 8 million years ago. JF - Science AU - Gannon, P J AU - Holloway, R L AU - Broadfield, D C AU - Braun, Allen R AD - Department of Otolaryngology and Arthur M. Fishberg Research Center for Neurobiology, Mount Sinai School of Medicine, New York, NY 10029, USA.; National Institute on Deafness and Other Communication Disorders PY - 1998 SP - 220 EP - 222 VL - 279 IS - 5348 SN - 0036-8075, 0036-8075 KW - Magnetic Resonance Imaging KW - Human KW - Temporal Lobe KW - Communication KW - Animal KW - Support, U.S. Gov't, Non-P.H.S. KW - Support, Non-U.S. Gov't KW - Laterality KW - Evolution KW - Hominidae KW - Pan troglodytes KW - Language KW - Dominance, Cerebral UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85223865?accountid=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=Science&rft.atitle=Asymmetry+of+chimpanzee+planum+temporale%3A+humanlike+pattern+of+Wernicke%27s+brain+language+area+homolog.&rft.au=Gannon%2C+P+J%3BHolloway%2C+R+L%3BBroadfield%2C+D+C%3BBraun%2C+Allen+R&rft.aulast=Gannon&rft.aufirst=P&rft.date=1998-01-01&rft.volume=279&rft.issue=5348&rft.spage=220&rft.isbn=&rft.btitle=&rft.title=Science&rft.issn=00368075&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Structural insights into the regulation of SOS mutagenesis. AN - 80067398; 9701508 AB - The Escherichia coli Umu proteins are best characterized by their role in damage inducible mutagenesis. Recently, we discovered that the intracellular levels of the UmuD and UmuC proteins are kept to a minimum by the Lon serine protease. Studies with the Salmonella typhimurium UmuD protein (which is 73% homologous with its E. coli counterpart) revealed that it too is degraded by Lon, suggesting that both UmuD proteins share conserved structural motifs. In contrast, E. coli UmuD' is removed from the cell by the ClpXP serine protease, but only when it is in a heterodimer complex with UmuD. We have generated deletion mutants of UmuD' and have coexpressed the mutant proteins with UmuD1 (a non-cleavable UmuD protein). By assaying the sensitivity of the mutant UmuD'-UmuD1 complex to ClpXP, we have been able to map regions of UmuD' that appear essential for efficient UmuD'-UmuD heterodimer formation. Previous experiments have suggested that the in vivo posttranslational processing of UmuD to UmuD' is inefficient. We have, however, discovered that limited cleavage occurs in an undamaged cell, but that these small amounts of UmuD' are rapidly degraded by ClpXP, thus giving rise to the appearance of inefficient cleavage. The ClpXP protease therefore plays dual roles in regulating SOS mutagenesis: it keeps the basal levels of UmuD' to a minimum in undamaged cells but it also acts in damaged cells to reduce the elevated levels of mutagenically active UmuD' protein, thereby returning the cell to a resting non-mutable state. JF - Acta biochimica Polonica AU - Gonzalez, M AU - Frank, E G AU - McDonald, J P AU - Levine, A S AU - Woodgate, R AD - Section on DNA Replication, Repair and Mutagenesis, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-2725, USA. Y1 - 1998 PY - 1998 DA - 1998 SP - 163 EP - 172 VL - 45 IS - 1 SN - 0001-527X, 0001-527X KW - Bacterial Proteins KW - 0 KW - Escherichia coli Proteins KW - Heat-Shock Proteins KW - DNA-Directed DNA Polymerase KW - EC 2.7.7.7 KW - UmuD protein, E coli KW - ATP-Dependent Proteases KW - EC 3.4.21.- KW - Serine Endopeptidases KW - Lon protein, E coli KW - EC 3.4.21.53 KW - Protease La KW - Index Medicus KW - Salmonella typhimurium -- metabolism KW - Escherichia coli -- metabolism KW - Bacterial Proteins -- metabolism KW - Substrate Specificity KW - Heat-Shock Proteins -- metabolism KW - Serine Endopeptidases -- metabolism KW - SOS Response (Genetics) KW - Mutagenesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80067398?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Acta+biochimica+Polonica&rft.atitle=Structural+insights+into+the+regulation+of+SOS+mutagenesis.&rft.au=Gonzalez%2C+M%3BFrank%2C+E+G%3BMcDonald%2C+J+P%3BLevine%2C+A+S%3BWoodgate%2C+R&rft.aulast=Gonzalez&rft.aufirst=M&rft.date=1998-01-01&rft.volume=45&rft.issue=1&rft.spage=163&rft.isbn=&rft.btitle=&rft.title=Acta+biochimica+Polonica&rft.issn=0001527X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-10-30 N1 - Date created - 1998-10-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Iron absorption in patients with Zollinger-Ellison syndrome treated with long-term gastric acid antisecretory therapy. AN - 80044681; 9692706 AB - Gastric acid secretion is important for absorption of dietary non-haem iron, and iron deficiency is common in gastric hyposecretory states such as after gastric resection. It is not known if prolonged, continuous treatment with potent acid suppressants such as omeprazole will lead to iron deficiency or lower body iron stores. To assess iron stores and the occurrence of iron deficiency anaemia in patients with Zollinger-Ellison syndrome (ZES) treated long-term with gastric antisecretory drugs. One hundred and nine patients with ZES but without previous gastric resections were studied. All patients underwent assessment of acid control on antisecretory agents, determination of tumour extent, evaluation of haematological parameters (Hct, haemoglobin, WBC, MCV, MCHC), and determination of serum iron parameters (iron, ferritin, transferrin, iron/ transferrin ratio). Acid control values for the last 4 years were reviewed, the presence or absence of acid hyposecretion determined using three different criteria and this result correlated with haematological and iron parameters. Eighty-nine patients were taking omeprazole, nine patients were taking histamine H2-antagonists and 11 patients were taking no drugs following curative resection. The mean duration of omeprazole treatment was 5.7 years (range 0.7-12.5 years) and total duration of any treatment was 10.1 years (range 0.7-21 years). Acid hyposecretion was present by at least one criterion in 45% of patients. There were no significant differences between patients with or without acid hyposecretion, taking or not taking omeprazole, having different durations of omeprazole treatment or different durations of total time receiving any antisecretory treatment, for any serum iron parameter, haematological parameter, or for the frequency of iron deficiency. Males and females did not differ in percentage with low ferritin levels or percentage with iron deficiency. Continuous treatment with omeprazole for 6 years or continuous treatment with any gastric antisecretory drug for 10 years does not cause decreased body iron stores or iron deficiency. These results suggest that, in contrast to recent results which show yearly monitoring of vitamin B12 in such patients is needed, such monitoring for iron parameters is not necessary. JF - Alimentary pharmacology & therapeutics AU - Stewart, C A AU - Termanini, B AU - Sutliff, V E AU - Serrano, J AU - Yu, F AU - Gibril, F AU - Jensen, R T AD - Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-1804, USA. Y1 - 1998/01// PY - 1998 DA - January 1998 SP - 83 EP - 98 VL - 12 IS - 1 SN - 0269-2813, 0269-2813 KW - Antacids KW - 0 KW - Anti-Ulcer Agents KW - Histamine H2 Antagonists KW - Iron KW - E1UOL152H7 KW - Omeprazole KW - KG60484QX9 KW - Index Medicus KW - United States KW - Humans KW - Anemia -- chemically induced KW - Aged KW - Histamine H2 Antagonists -- administration & dosage KW - Histamine H2 Antagonists -- adverse effects KW - National Institutes of Health (U.S.) KW - Adult KW - Middle Aged KW - Adolescent KW - Clinical Protocols KW - Female KW - Male KW - Histamine H2 Antagonists -- therapeutic use KW - Antacids -- administration & dosage KW - Anti-Ulcer Agents -- adverse effects KW - Omeprazole -- adverse effects KW - Anti-Ulcer Agents -- therapeutic use KW - Omeprazole -- administration & dosage KW - Iron -- blood KW - Intestinal Absorption -- physiology KW - Intestinal Absorption -- drug effects KW - Gastric Acid -- secretion KW - Zollinger-Ellison Syndrome -- drug therapy KW - Omeprazole -- therapeutic use KW - Antacids -- therapeutic use KW - Anti-Ulcer Agents -- administration & dosage KW - Iron -- deficiency KW - Zollinger-Ellison Syndrome -- blood KW - Antacids -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80044681?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Alimentary+pharmacology+%26+therapeutics&rft.atitle=Iron+absorption+in+patients+with+Zollinger-Ellison+syndrome+treated+with+long-term+gastric+acid+antisecretory+therapy.&rft.au=Stewart%2C+C+A%3BTermanini%2C+B%3BSutliff%2C+V+E%3BSerrano%2C+J%3BYu%2C+F%3BGibril%2C+F%3BJensen%2C+R+T&rft.aulast=Stewart&rft.aufirst=C&rft.date=1998-01-01&rft.volume=12&rft.issue=1&rft.spage=83&rft.isbn=&rft.btitle=&rft.title=Alimentary+pharmacology+%26+therapeutics&rft.issn=02692813&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-11-05 N1 - Date created - 1998-11-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A phase II study of carboplatin, cisplatin, interferon-alpha, and tamoxifen for patients with metastatic melanoma. AN - 80034924; 9679527 AB - The purpose of this trial was to determine the toxicity and antineoplastic activity of cisplatin, carboplatin, tamoxifen, and interferon-alpha (IFN-alpha) in patients with advanced melanoma. Eleven patients with metastatic melanoma were enrolled. The patients received carboplatin 400 mg/m2 i.v. on day 0; cisplatin 25 mg/m2 i.v. on days 7, 14, and 21; tamoxifen 20 mg p.o. b.i.d. on days 0-27; and interferon-alpha 5 million units/m2 subcutaneously 3 times per week. Cycles were repeated every 28 days. Patients were assessed for tumor response at the end of 2 cycles. Toxicity was severe, with 14 of 24 cycles given requiring some form of dose reduction. Carboplatin dose reductions were related to bone-marrow toxicity, whereas IFN-alpha caused fatigue, arthralgias, myalgias, and fever. The overall response rate was 18% (2 partial responses [PRs]). The combination of cisplatin, carboplatin, tamoxifen, and IFN-alpha is active in advanced melanoma; however, the toxicity is unacceptable. JF - Cancer investigation AU - Gause, B L AU - Sharfman, W H AU - Janik, J E AU - Curti, B D AU - Steis, R G AU - Urba, W J AU - Smith, J W AU - Alvord, W G AU - Longo, D L AD - National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, Maryland, USA. Y1 - 1998 PY - 1998 DA - 1998 SP - 374 EP - 380 VL - 16 IS - 6 SN - 0735-7907, 0735-7907 KW - Antineoplastic Agents KW - 0 KW - Interferon-alpha KW - Tamoxifen KW - 094ZI81Y45 KW - Carboplatin KW - BG3F62OND5 KW - Cisplatin KW - Q20Q21Q62J KW - Index Medicus KW - Interferon-alpha -- administration & dosage KW - Humans KW - Carboplatin -- administration & dosage KW - Carboplatin -- adverse effects KW - Tamoxifen -- administration & dosage KW - Cisplatin -- administration & dosage KW - Interferon-alpha -- adverse effects KW - Adult KW - Treatment Outcome KW - Tamoxifen -- adverse effects KW - Middle Aged KW - Cisplatin -- adverse effects KW - Female KW - Male KW - Melanoma -- secondary KW - Melanoma -- drug therapy KW - Antineoplastic Agents -- therapeutic use KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80034924?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+investigation&rft.atitle=A+phase+II+study+of+carboplatin%2C+cisplatin%2C+interferon-alpha%2C+and+tamoxifen+for+patients+with+metastatic+melanoma.&rft.au=Gause%2C+B+L%3BSharfman%2C+W+H%3BJanik%2C+J+E%3BCurti%2C+B+D%3BSteis%2C+R+G%3BUrba%2C+W+J%3BSmith%2C+J+W%3BAlvord%2C+W+G%3BLongo%2C+D+L&rft.aulast=Gause&rft.aufirst=B&rft.date=1998-01-01&rft.volume=16&rft.issue=6&rft.spage=374&rft.isbn=&rft.btitle=&rft.title=Cancer+investigation&rft.issn=07357907&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-08-06 N1 - Date created - 1998-08-06 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Cancer Invest. 1998;16(6):421-3 [9679534] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Clinical trials with Pseudomonas exotoxin immunotoxins. AN - 80016337; 9670614 JF - Current topics in microbiology and immunology AU - Pai, L H AU - Pastan, I AD - Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1998 PY - 1998 DA - 1998 SP - 83 EP - 96 VL - 234 SN - 0070-217X, 0070-217X KW - Antibodies, Monoclonal KW - 0 KW - Exotoxins KW - Immunotoxins KW - Recombinant Fusion Proteins KW - Index Medicus KW - Antibodies, Monoclonal -- biosynthesis KW - Immunotherapy KW - Humans KW - Clinical Trials, Phase I as Topic KW - Adult KW - Aged KW - Middle Aged KW - Recombinant Fusion Proteins -- therapeutic use KW - Male KW - Female KW - Antibodies, Monoclonal -- therapeutic use KW - Immunotoxins -- therapeutic use KW - Immunotoxins -- administration & dosage KW - Pseudomonas aeruginosa KW - Neoplasms -- therapy KW - Exotoxins -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80016337?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+topics+in+microbiology+and+immunology&rft.atitle=Clinical+trials+with+Pseudomonas+exotoxin+immunotoxins.&rft.au=Pai%2C+L+H%3BPastan%2C+I&rft.aulast=Pai&rft.aufirst=L&rft.date=1998-01-01&rft.volume=234&rft.issue=&rft.spage=83&rft.isbn=&rft.btitle=&rft.title=Current+topics+in+microbiology+and+immunology&rft.issn=0070217X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-08-06 N1 - Date created - 1998-08-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Clinical applications of immunotoxins. Introduction. AN - 80016295; 9670609 JF - Current topics in microbiology and immunology AU - FitzGerald, D AU - Pastan, I AU - Robertus, J AD - Laboratory of Molecular Biology, National Cancer Institute, NIH, Bethesda, MD 20892, USA. Y1 - 1998 PY - 1998 DA - 1998 SP - 1 EP - 11 VL - 234 SN - 0070-217X, 0070-217X KW - Bacterial Toxins KW - 0 KW - Immunotoxins KW - Plant Proteins KW - Recombinant Proteins KW - Index Medicus KW - Animals KW - Plant Proteins -- therapeutic use KW - Plant Proteins -- chemistry KW - Bacterial Toxins -- metabolism KW - Recombinant Proteins -- biosynthesis KW - Recombinant Proteins -- metabolism KW - Bacterial Toxins -- therapeutic use KW - Bacterial Toxins -- chemistry KW - Mice KW - Plant Proteins -- metabolism KW - Recombinant Proteins -- therapeutic use KW - Immunotoxins -- chemistry KW - Immunotoxins -- therapeutic use KW - Immunotoxins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80016295?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+topics+in+microbiology+and+immunology&rft.atitle=Clinical+applications+of+immunotoxins.+Introduction.&rft.au=FitzGerald%2C+D%3BPastan%2C+I%3BRobertus%2C+J&rft.aulast=FitzGerald&rft.aufirst=D&rft.date=1998-01-01&rft.volume=234&rft.issue=&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Current+topics+in+microbiology+and+immunology&rft.issn=0070217X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-08-06 N1 - Date created - 1998-08-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Immunotoxins for brain tumor therapy. AN - 80011527; 9670615 JF - Current topics in microbiology and immunology AU - Oldfield, E H AU - Youle, R J AD - Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892, USA. Y1 - 1998 PY - 1998 DA - 1998 SP - 97 EP - 114 VL - 234 SN - 0070-217X, 0070-217X KW - Immunotoxins KW - 0 KW - Index Medicus KW - Rats KW - Animals KW - Prospective Studies KW - Humans KW - Adult KW - Clinical Trials as Topic KW - Middle Aged KW - Male KW - Haplorhini KW - Female KW - Blood-Brain Barrier KW - Immunotoxins -- pharmacokinetics KW - Brain Neoplasms -- therapy KW - Brain Neoplasms -- metabolism KW - Immunotoxins -- therapeutic use KW - Immunotoxins -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80011527?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+topics+in+microbiology+and+immunology&rft.atitle=Immunotoxins+for+brain+tumor+therapy.&rft.au=Oldfield%2C+E+H%3BYoule%2C+R+J&rft.aulast=Oldfield&rft.aufirst=E&rft.date=1998-01-01&rft.volume=234&rft.issue=&rft.spage=97&rft.isbn=&rft.btitle=&rft.title=Current+topics+in+microbiology+and+immunology&rft.issn=0070217X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-08-06 N1 - Date created - 1998-08-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Potentiation of retinoic acid-induced differentiation of human acute promyelocytic leukemia NB4 cells by butyric acid, tributyrin, and hexamethylene bisacetamide. AN - 80008463; 9666515 AB - Cytodifferentiation therapy by all-trans-retinoic acid (RA) for acute promyelocytic leukemia patients is encouraging in spite of several limitations preventing better clinical outcomes. Most patients in complete remission induced by RA experience relapse and resist further treatment with RA. This resistance primarily is due to a systemic self-induced catabolism of RA, which interferes with the maintenance of effective plasma levels of RA. In this report we explored the possibility that treatment with combinations of RA and other differentiation agents may induce differentiation at lower RA concentrations, which in turn may produce diminished levels of resistance. We found that although n-butyric acid (BA), tributyrin (TB) (a prodrug of BA), or hexamethylene bisacetamide (HMBA) were inactive as sole agents they potentiated RA-induced differentiation of human acute promyelocytic NB4 cells. A measure of the effectiveness of these combinations was that the concentrations of RA in combination with BA and HMBA inducing half-maximal differentiation were 20- to 40-fold lower than those needed with RA alone. Furthermore, the concentrations of BA and HMBA in these combinations were at achievable plasma levels. Therefore, these combinations may have clinical utility for treatment of a variety of malignancies that are sensitive to RA alone. JF - Oncology research AU - Taimi, M AU - Chen, Z X AU - Breitman, T R AD - Laboratory of Biological Chemistry, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4255, USA. Y1 - 1998 PY - 1998 DA - 1998 SP - 75 EP - 84 VL - 10 IS - 2 SN - 0965-0407, 0965-0407 KW - Acetamides KW - 0 KW - Antineoplastic Agents KW - Butyrates KW - Triglycerides KW - Butyric Acid KW - 107-92-6 KW - Tretinoin KW - 5688UTC01R KW - hexamethylene bisacetamide KW - LA133J59VU KW - tributyrin KW - S05LZ624MF KW - Index Medicus KW - Tumor Cells, Cultured -- drug effects KW - Humans KW - Drug Synergism KW - Tretinoin -- pharmacology KW - Acetamides -- pharmacology KW - Triglycerides -- pharmacology KW - Butyrates -- metabolism KW - Butyrates -- pharmacology KW - Antineoplastic Agents -- metabolism KW - Leukemia, Promyelocytic, Acute -- metabolism KW - Leukemia, Promyelocytic, Acute -- pathology KW - Cell Differentiation -- drug effects KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80008463?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+research&rft.atitle=Potentiation+of+retinoic+acid-induced+differentiation+of+human+acute+promyelocytic+leukemia+NB4+cells+by+butyric+acid%2C+tributyrin%2C+and+hexamethylene+bisacetamide.&rft.au=Taimi%2C+M%3BChen%2C+Z+X%3BBreitman%2C+T+R&rft.aulast=Taimi&rft.aufirst=M&rft.date=1998-01-01&rft.volume=10&rft.issue=2&rft.spage=75&rft.isbn=&rft.btitle=&rft.title=Oncology+research&rft.issn=09650407&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-09-15 N1 - Date created - 1998-09-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Women's drug use and HIV risk: findings from NIDA's Cooperative Agreement for Community-Based Outreach/Intervention Research Program. AN - 79959917; 9640631 JF - Women & health AU - Coyle, S L AD - Community Research Branch of National Institute on Drug Abuse, USA. Y1 - 1998 PY - 1998 DA - 1998 SP - 1 EP - 18 VL - 27 IS - 1-2 SN - 0363-0242, 0363-0242 KW - Index Medicus KW - AIDS/HIV KW - Multicenter Studies as Topic KW - Risk Factors KW - Humans KW - National Institutes of Health (U.S.) KW - Adult KW - Community-Institutional Relations KW - United States -- epidemiology KW - Research Design KW - Puerto Rico -- epidemiology KW - Female KW - Women's Health KW - HIV Infections -- prevention & control KW - Community Health Services -- methods KW - Substance-Related Disorders -- complications KW - HIV Infections -- epidemiology KW - Community Health Services -- organization & administration KW - Substance-Related Disorders -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79959917?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Women+%26+health&rft.atitle=Women%27s+drug+use+and+HIV+risk%3A+findings+from+NIDA%27s+Cooperative+Agreement+for+Community-Based+Outreach%2FIntervention+Research+Program.&rft.au=Coyle%2C+S+L&rft.aulast=Coyle&rft.aufirst=S&rft.date=1998-01-01&rft.volume=27&rft.issue=1-2&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Women+%26+health&rft.issn=03630242&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-09-10 N1 - Date created - 1998-09-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A phase II study of 5-aza-2'deoxycytidine (decitabine) in hormone independent metastatic (D2) prostate cancer. AN - 79917815; 9619724 AB - Decitabine (5-aza-2'-deoxycytidine) is an S-phase-specific pyrimidine analog with hypomethylation properties. In laboratory models of prostate cancer (PC-3 and DU-145), decitabine induces cellular differentiation and enhanced expression of genes involved in tumor suppression, immunogenicity, and programmed cell death. We conducted a phase II study of decitabine in 14 men with progressive, metastatic prostate cancer recurrent after total androgen blockade and flutamide withdrawal. Decitabine was administered at a dose of 75 mg/m2/dose i.v. as a 1 hour infusion every 8 hours for three doses. Cycles of therapy were repeated every 5 to 8 weeks to allow for resolution of toxicity. Two of 12 patients evaluable for response had stable disease with a time to progression of more than 10 weeks. This activity was seen in 2 of 3 African-American patients. Toxicity was similar to previously reported experience. No significant changes in urinary concentrations of the angiogenic factor bFGF, a potential biomarker of tumor activity, were identified over time in 7 unselected patients with progressive disease. We conclude that decitabine is a well tolerated regimen with modest clinical activity against hormone-independent prostate cancer. Further investigations in patients of African-American origin may be warranted. JF - Tumori AU - Thibault, A AU - Figg, W D AU - Bergan, R C AU - Lush, R M AU - Myers, C E AU - Tompkins, A AU - Reed, E AU - Samid, D AD - Medicine Branch, Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. PY - 1998 SP - 87 EP - 89 VL - 84 IS - 1 SN - 0300-8916, 0300-8916 KW - Antimetabolites, Antineoplastic KW - 0 KW - Biomarkers, Tumor KW - Enzyme Inhibitors KW - Fibroblast Growth Factor 2 KW - 103107-01-3 KW - decitabine KW - 776B62CQ27 KW - DNA Modification Methylases KW - EC 2.1.1.- KW - Azacitidine KW - M801H13NRU KW - Index Medicus KW - Humans KW - Treatment Outcome KW - Aged KW - Predictive Value of Tests KW - Middle Aged KW - Male KW - Azacitidine -- therapeutic use KW - Enzyme Inhibitors -- therapeutic use KW - DNA Modification Methylases -- antagonists & inhibitors KW - Azacitidine -- analogs & derivatives KW - Prostatic Neoplasms -- blood KW - Fibroblast Growth Factor 2 -- blood KW - Prostatic Neoplasms -- drug therapy KW - Biomarkers, Tumor -- blood KW - Antimetabolites, Antineoplastic -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79917815?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Tumori&rft.atitle=A+phase+II+study+of+5-aza-2%27deoxycytidine+%28decitabine%29+in+hormone+independent+metastatic+%28D2%29+prostate+cancer.&rft.au=Thibault%2C+A%3BFigg%2C+W+D%3BBergan%2C+R+C%3BLush%2C+R+M%3BMyers%2C+C+E%3BTompkins%2C+A%3BReed%2C+E%3BSamid%2C+D&rft.aulast=Thibault&rft.aufirst=A&rft.date=1998-01-01&rft.volume=84&rft.issue=1&rft.spage=87&rft.isbn=&rft.btitle=&rft.title=Tumori&rft.issn=03008916&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-06-30 N1 - Date created - 1998-06-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Public health in central and eastern Europe and the role of environmental pollution. AN - 79906033; 9611616 AB - The central and eastern European countries that composed the former Eastern Bloc have experienced an alarming decline in public health since the dissolution of the Soviet Union. Death rates have increased in most age groups. Life expectancy, especially among males, has decreased in many countries; in Russia, male life expectancy dropped by six years between 1989 and 1994. By 2020, these countries are projected to have smaller increases in life expectancy than any other geographic region. The conditions responsible for the excess mortality are cardiovascular disease, cancer, and injuries among adults. The major factors in the sharp increase are poverty, social disintegration, and crime, overlaid on historically high rates of smoking, alcohol use, and psychosocial stress. Environmental pollution, although common and sometimes severe in the former Eastern Bloc, is another, albeit not the chief, cause of the sharp decline in public health since 1989. JF - Annual review of public health AU - Little, R E AD - Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27514, USA. Little1@NIEHS.NIH.gov Y1 - 1998 PY - 1998 DA - 1998 SP - 153 EP - 172 VL - 19 SN - 0163-7525, 0163-7525 KW - Index Medicus KW - Socioeconomic Factors KW - Europe, Eastern -- epidemiology KW - Humans KW - Life Expectancy -- trends KW - Public Health -- trends KW - Environmental Pollution -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79906033?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annual+review+of+public+health&rft.atitle=Public+health+in+central+and+eastern+Europe+and+the+role+of+environmental+pollution.&rft.au=Little%2C+R+E&rft.aulast=Little&rft.aufirst=R&rft.date=1998-01-01&rft.volume=19&rft.issue=&rft.spage=153&rft.isbn=&rft.btitle=&rft.title=Annual+review+of+public+health&rft.issn=01637525&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-07-29 N1 - Date created - 1998-07-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dysregulation of apoptosis in hepatocellular carcinoma. AN - 79902356; 9606809 AB - The tightly controlled homeostatic mechanisms between cell growth and apoptosis that exist in normal liver tissue are disrupted during hepatocarcinogenesis. The TGF (transforming growth factor)-beta signaling system is a central component of the mechanisms by which cell growth and apoptosis are controlled in the liver. The recent delineation of the TGF-beta signaling pathway has provided a unique framework for analysis of the impact that disruption of individual components of this signaling pathway can have on apoptosis during hepatocarcinogenesis. Here we review recent data on involvement of the TGF-beta signaling pathway in the dysregulation of apoptosis frequently observed in hepatocellular carcinomas. The data indicate that disruption of the TGF-beta pathway at the pre-receptor, receptor, and post-receptor levels occurs in hepatocellular carcinomas and can cause dysregulation of apoptosis. Also, substantial evidence now exists that phosphatidylinositol-3-kinase (PI3K) may function as an important negative regulator of the TGF-beta 1-induced apoptosis in hepatocellular carcinomas. Taken together, the available evidence indicates that disruption of the TGF-beta 1-induced apoptosis as well as growth inhibition is an important and integral part of the multistage process of liver carcinogenesis. JF - Seminars in liver disease AU - Thorgeirsson, S S AU - Teramoto, T AU - Factor, V M AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA. Y1 - 1998 PY - 1998 DA - 1998 SP - 115 EP - 122 VL - 18 IS - 2 SN - 0272-8087, 0272-8087 KW - Transforming Growth Factor beta KW - 0 KW - Index Medicus KW - Transforming Growth Factor beta -- physiology KW - Humans KW - Signal Transduction KW - Liver Neoplasms -- pathology KW - Apoptosis -- physiology KW - Carcinoma, Hepatocellular -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79902356?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Dysregulation+of+apoptosis+in+hepatocellular+carcinoma.&rft.au=Thorgeirsson%2C+S+S%3BTeramoto%2C+T%3BFactor%2C+V+M&rft.aulast=Thorgeirsson&rft.aufirst=S&rft.date=1998-01-01&rft.volume=18&rft.issue=2&rft.spage=115&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 - 1998-08-03 N1 - Date created - 1998-08-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Alzheimer's disease. Cholinergic therapy and beyond. AN - 79864879; 9581222 AB - While much of the Alzheimer's disease (AD) research community turns its spotlight on genetics, molecular biology, and the neurotoxicity of beta-amyloid, there is a more subtle but equally significant shift in focus emerging within AD therapeutic circles. Once devoid of specific treatment options, the field now enjoys a choice of two Food and Drug Administration (FDA)-approved cholinesterase inhibitors and the prospect of several more in the near future. In addition, therapy for AD is rapidly expanding beyond the central cholinergic hypothesis to include neuroprotective agents and the possibility of interfering with basic mechanisms involved in the pathogenesis of this disorder. Clinically, we have entered the era of viable cholinergic therapies, and we are already moving beyond that starting point to an era of effective combination approaches. This article provides a clinical framework for these current and potential new therapies. JF - The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry AU - Sunderland, T AD - Geriatric Psychiatry Branch, National Institute of Mental Health, Bethesda, MD 20892-1275, USA. Y1 - 1998 PY - 1998 DA - 1998 SP - S56 EP - S63 VL - 6 IS - 2 Suppl 1 SN - 1064-7481, 1064-7481 KW - Cholinergic Agonists KW - 0 KW - Cholinesterase Inhibitors KW - Index Medicus KW - Aged, 80 and over KW - Humans KW - Aged KW - Middle Aged KW - Age Distribution KW - Alzheimer Disease -- genetics KW - Cholinesterase Inhibitors -- therapeutic use KW - Cholinergic Agonists -- therapeutic use KW - Alzheimer Disease -- therapy KW - Cognitive Therapy -- methods KW - Alzheimer Disease -- diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79864879?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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+geriatric+psychiatry+%3A+official+journal+of+the+American+Association+for+Geriatric+Psychiatry&rft.atitle=Alzheimer%27s+disease.+Cholinergic+therapy+and+beyond.&rft.au=Sunderland%2C+T&rft.aulast=Sunderland&rft.aufirst=T&rft.date=1998-01-01&rft.volume=6&rft.issue=2+Suppl+1&rft.spage=S56&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+geriatric+psychiatry+%3A+official+journal+of+the+American+Association+for+Geriatric+Psychiatry&rft.issn=10647481&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-08-18 N1 - Date created - 1998-08-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tumor vaccination strategies combined with autologous peripheral stem cell transplantation. AN - 79864062; 9581240 AB - Despite advances in high-dose therapy with autologous stem cell transplantation for lymphomas, relapse of the underlying disease remains a significant obstacle. Recent advances in cancer vaccine development, specifically, the molecular identification of novel tumor antigens and understanding of cellular signals delivered by cytokines and costimulatory molecules required for efficient T-cell activation, now make it possible to consider combining active specific immunotherapy with PSCT as a strategy for elimination of minimal residual disease. As a model lymphoma-specific antigen, vaccination with patient-specific, immunoglobulin idiotype has been shown to be therapeutically effective when combined with marrow transplantation in small animal models. These preclinical studies predict the feasibility of immunization of human patients with B-cell malignancies vaccinated with this antigen in the post-transplant setting in ongoing clinical trials, especially for T-cell responses. In the future, other vaccine formulations, based on gene therapy approaches to enhance the immunogenicity of whole lymphoma cells or the identification of novel, defined antigens selectively expressed on lymphoma cells, as well as combined strategies of pre- and post-transplant tumor vaccination are envisioned. JF - Annals of oncology : official journal of the European Society for Medical Oncology AU - Kwak, L W AD - Department of Experimental Transplantation & Immunology, NCI, Bethesda, MD, USA. kwak@ncifcrf.gov Y1 - 1998 PY - 1998 DA - 1998 SP - S41 EP - S46 VL - 9 Suppl 1 SN - 0923-7534, 0923-7534 KW - Antigens, Neoplasm KW - 0 KW - Cancer Vaccines KW - Immunoglobulin Idiotypes KW - Neoplasm Proteins KW - Index Medicus KW - Animals KW - B-Lymphocytes -- pathology KW - Humans KW - Immunization Schedule KW - Immunoglobulin Idiotypes -- immunology KW - Feasibility Studies KW - Multiple Myeloma -- drug therapy KW - Adult KW - Treatment Outcome KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Antigens, Neoplasm -- immunology KW - Male KW - T-Lymphocytes -- immunology KW - Transplantation Conditioning KW - Combined Modality Therapy KW - Neoplasm Proteins -- immunology KW - B-Lymphocytes -- immunology KW - Mice KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Transplantation, Autologous KW - T-Lymphocytes -- pathology KW - Clinical Trials, Phase I as Topic KW - Multiple Myeloma -- therapy KW - Middle Aged KW - Female KW - Immunosuppression KW - Lymphoma -- mortality KW - Lymphoma -- therapy KW - Cancer Vaccines -- therapeutic use KW - Lymphoma -- drug therapy KW - Lymphoma -- immunology KW - Lymphoma -- pathology KW - Hematopoietic Stem Cell Transplantation -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79864062?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+oncology+%3A+official+journal+of+the+European+Society+for+Medical+Oncology&rft.atitle=Tumor+vaccination+strategies+combined+with+autologous+peripheral+stem+cell+transplantation.&rft.au=Kwak%2C+L+W&rft.aulast=Kwak&rft.aufirst=L&rft.date=1998-01-01&rft.volume=9+Suppl+1&rft.issue=&rft.spage=S41&rft.isbn=&rft.btitle=&rft.title=Annals+of+oncology+%3A+official+journal+of+the+European+Society+for+Medical+Oncology&rft.issn=09237534&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-07-02 N1 - Date created - 1998-07-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular epidemiology of breast cancer. AN - 79841447; 9575425 AB - Molecular epidemiology evaluates cancer risk based upon environmental exposures and genetically determined susceptibilities. Biomarkers, molecular indicators of exposure or disease state, are used to stake out the progression of a disease along plausible mechanistic pathways. Connecting biomarkers of exposure, (e.g., carcinogen DNA adducts), effect (e.g., mutations in tumor suppressor genes), or disease (e.g., histological abnormalities) can clarify the etiology of cancer, improve risk estimates, and lead to better preventive strategies. In this review, the following evidence is used to evaluate the possible contribution of environmental carcinogens to breast cancer: a) genetic predispositions in familial breast cancer, b) mutational spectra of the p53 tumor suppressor gene, c) chemical carcinogenesis in breast cancer models, and d) genetic polymorphisms in sporadic breast cancer. JF - In vivo (Athens, Greece) AU - Goldman, R AU - Shields, P G AD - Division of Basic Research, National Cancer Institute, National Institute of Health, Bethesda, MD 20892-4255, USA. PY - 1998 SP - 43 EP - 48 VL - 12 IS - 1 SN - 0258-851X, 0258-851X KW - Carcinogens KW - 0 KW - Index Medicus KW - Smoking KW - Animals KW - Genes, p53 KW - Polymorphism, Genetic KW - Molecular Epidemiology KW - Risk Factors KW - Humans KW - Genetic Diseases, Inborn -- genetics KW - Mutation KW - Female KW - Breast Neoplasms -- genetics KW - Breast Neoplasms -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79841447?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=In+vivo+%28Athens%2C+Greece%29&rft.atitle=Molecular+epidemiology+of+breast+cancer.&rft.au=Goldman%2C+R%3BShields%2C+P+G&rft.aulast=Goldman&rft.aufirst=R&rft.date=1998-01-01&rft.volume=12&rft.issue=1&rft.spage=43&rft.isbn=&rft.btitle=&rft.title=In+vivo+%28Athens%2C+Greece%29&rft.issn=0258851X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-06-11 N1 - Date created - 1998-06-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pharmacologic treatment of alcoholics with collateral depression: issues and future directions. AN - 79823878; 9564206 AB - Patients in treatment for alcoholism often suffer collateral depressive disorders. Fortunately, recent advances in medications development may significantly improve outcome for this population, but there remain several concerns about the clinical use of pharmacologic agents in these cases. These concerns are discussed, as are research findings that bear on them. Directions for future research are also identified. JF - Psychopharmacology bulletin AU - Litten, R Z AU - Allen, J P AD - Treatment Research Branch, National Institute on Alcohol Abuse and Alcoholism, Rockville, MD 20892-7003, USA. Y1 - 1998 PY - 1998 DA - 1998 SP - 107 EP - 110 VL - 34 IS - 1 SN - 0048-5764, 0048-5764 KW - Index Medicus KW - Humans KW - Depressive Disorder -- drug therapy KW - Alcoholism -- complications KW - Depressive Disorder -- complications KW - Alcoholism -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79823878?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psychopharmacology+bulletin&rft.atitle=Pharmacologic+treatment+of+alcoholics+with+collateral+depression%3A+issues+and+future+directions.&rft.au=Litten%2C+R+Z%3BAllen%2C+J+P&rft.aulast=Litten&rft.aufirst=R&rft.date=1998-01-01&rft.volume=34&rft.issue=1&rft.spage=107&rft.isbn=&rft.btitle=&rft.title=Psychopharmacology+bulletin&rft.issn=00485764&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-05-21 N1 - Date created - 1998-05-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - What you need to know: detecting alcohol problems in general medical practice. AN - 79809038; 9557105 AB - In the US, about 11% to 20% of patients presenting to general medical clinics are diagnosed as suffering from alcohol abuse or dependence. Alcohol screening in primary care settings, whether in the US or Singapore, can utilise various strategies for the early detection of alcohol problems. This paper briefly reviews several self-reports and screening procedures to assist general practitioners in identifying problem drinkers. The use of CAGE questionnaire, MAST, and its variation, SAAST and the AUDIT, are discussed and evaluated. Likewise, useful biochemical markers of excessive alcohol consumption like the liver enzymes (AST, ALT, GGT), MCV, CDT are described. They can be combined with each other to improve validity or used in conjunction with self-report screening tests for more accurate detection of problem drinkers. In particular, use of the AUDIT for routine screening of alcohol problems in primary care settings is recommended. Selective administration to those with at least two drinks per setting can overcome time constraints. Alternatively, sequential screening utilising the TRAUMA questionnaire with frequency and quantity questions administered to higher frequency drinkers can circumvent concerns about direct questioning. Use of self-reports and when possible, biochemical screening for alcohol problems should be a standard part of primary care practice. JF - Singapore medical journal AU - Allen, J AU - Litten, R Z AU - Lee, A AD - Treatment Research Branch, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland 20892-7003, USA. Y1 - 1998/01// PY - 1998 DA - January 1998 SP - 38 EP - 41 VL - 39 IS - 1 SN - 0037-5675, 0037-5675 KW - Biomarkers KW - 0 KW - Transferrin KW - Index Medicus KW - Family Practice -- standards KW - Humans KW - Biomarkers -- analysis KW - Transferrin -- analysis KW - Erythrocytes -- pathology KW - Liver -- enzymology KW - Alcoholism -- diagnosis KW - Surveys and Questionnaires KW - Alcoholism -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79809038?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Singapore+medical+journal&rft.atitle=What+you+need+to+know%3A+detecting+alcohol+problems+in+general+medical+practice.&rft.au=Allen%2C+J%3BLitten%2C+R+Z%3BLee%2C+A&rft.aulast=Allen&rft.aufirst=J&rft.date=1998-01-01&rft.volume=39&rft.issue=1&rft.spage=38&rft.isbn=&rft.btitle=&rft.title=Singapore+medical+journal&rft.issn=00375675&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-06-04 N1 - Date created - 1998-06-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Equianalgesic dose/ratio between methadone and other opioid agonists in cancer pain: comparison of two clinical experiences. AN - 79788450; 9541687 AB - Oral methadone is considered to be a valid opioid analgesic alternative to morphine and hydromorphone in treating cancer pain. However, the use of methadone could be complicated by the limited knowledge of the equianalgesic dose/ratio with the other analgesic opioids when switching in tolerant patients. In two Palliative Care Units, data collected regarding 88 advanced cancer patients with pain switched from different opioids to oral methadone were reviewed and compared with the aim of determining the equianalgesic dose ratio in relation to the dose of opioid previously administered. The results of this retrospective study suggest that: (1) methadone is much more potent than previously described in literature, (2) the dose ratio between hydromorphone and methadone is higher than as suggested by equianalgesic tables, and (3) the ratio correlates with total opioid dose administered before switching. The fact that methadone ratio is different according to the opioid dose used previously should be taken into careful consideration by the clinician in order to avoid severe toxicity or death during switchover. Prospective studies should be carried out in order to better define our findings. JF - Annals of oncology : official journal of the European Society for Medical Oncology AU - Ripamonti, C AU - De Conno, F AU - Groff, L AU - Belzile, M AU - Pereira, J AU - Hanson, J AU - Bruera, E AD - Pain Therapy and Palliative Care Division, National Cancer Institute, Milan, Italy. tdpint@mbox.vol.it Y1 - 1998/01// PY - 1998 DA - January 1998 SP - 79 EP - 83 VL - 9 IS - 1 SN - 0923-7534, 0923-7534 KW - Analgesics, Opioid KW - 0 KW - Receptors, Opioid KW - Hydromorphone KW - Q812464R06 KW - Methadone KW - UC6VBE7V1Z KW - Index Medicus KW - Administration, Oral KW - Hydromorphone -- therapeutic use KW - Dose-Response Relationship, Drug KW - Humans KW - Linear Models KW - Adult KW - Retrospective Studies KW - Aged KW - Middle Aged KW - Adolescent KW - Male KW - Female KW - Receptors, Opioid -- agonists KW - Pain -- etiology KW - Pain -- drug therapy KW - Neoplasms -- complications KW - Methadone -- therapeutic use KW - Analgesics, Opioid -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79788450?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+oncology+%3A+official+journal+of+the+European+Society+for+Medical+Oncology&rft.atitle=Equianalgesic+dose%2Fratio+between+methadone+and+other+opioid+agonists+in+cancer+pain%3A+comparison+of+two+clinical+experiences.&rft.au=Ripamonti%2C+C%3BDe+Conno%2C+F%3BGroff%2C+L%3BBelzile%2C+M%3BPereira%2C+J%3BHanson%2C+J%3BBruera%2C+E&rft.aulast=Ripamonti&rft.aufirst=C&rft.date=1998-01-01&rft.volume=9&rft.issue=1&rft.spage=79&rft.isbn=&rft.btitle=&rft.title=Annals+of+oncology+%3A+official+journal+of+the+European+Society+for+Medical+Oncology&rft.issn=09237534&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-05-27 N1 - Date created - 1998-05-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular and cell biology of TGF-beta. AN - 79758415; 9525693 AB - The TGF-betas are a remarkable set of peptides consisting of three highly homologous isoforms, TGF-beta 1, 2, and 3. Distinguished initially for their ability to inhibit the growth of most epithelial and hematopoietic cells and to regulate the production of extracellular matrix by mesenchymal cells, these peptides are now known to act via autocrine, paracrine, and endocrine modes to control a wide variety of developmental processes and to play key roles in the pathogenesis of many diseases including especially fibrotic diseases, parasitic diseases, autoimmune diseases, and carcinogenesis. The activity of these peptides is under tight control by processes including regulation of the expression of the isoforms and their receptors and of the trafficking and activation of their latent forms. JF - Mineral and electrolyte metabolism AU - Roberts, A B AD - Laboratory of Chemoprevention, National Cancer Institute, Bethesda, MD 20892-5055, USA. robertsa@dce41.nci.nih.gov Y1 - 1998 PY - 1998 DA - 1998 SP - 111 EP - 119 VL - 24 IS - 2-3 SN - 0378-0392, 0378-0392 KW - Extracellular Matrix Proteins KW - 0 KW - Growth Inhibitors KW - Transforming Growth Factor beta KW - Index Medicus KW - Regulatory Sequences, Nucleic Acid KW - Animals KW - Epithelial Cells -- cytology KW - Humans KW - Hematopoietic Stem Cells -- cytology KW - Gene Expression KW - Extracellular Matrix Proteins -- biosynthesis KW - Cell Division KW - Transforming Growth Factor beta -- pharmacology KW - Transforming Growth Factor beta -- physiology KW - Transforming Growth Factor beta -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79758415?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mineral+and+electrolyte+metabolism&rft.atitle=Molecular+and+cell+biology+of+TGF-beta.&rft.au=Roberts%2C+A+B&rft.aulast=Roberts&rft.aufirst=A&rft.date=1998-01-01&rft.volume=24&rft.issue=2-3&rft.spage=111&rft.isbn=&rft.btitle=&rft.title=Mineral+and+electrolyte+metabolism&rft.issn=03780392&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-05-01 N1 - Date created - 1998-05-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phase II study of suramin plus aminoglutethimide in two cohorts of patients with androgen-independent prostate cancer: simultaneous antiandrogen withdrawal and prior antiandrogen withdrawal. AN - 79744158; 9516950 AB - Management of prostate cancer progression after failure of initial hormonal therapy is controversial. Recently, the activity of the simple discontinuation of antiandrogen therapy has been established by several groups, as well as the enhanced activity when combined with adrenal suppression (i.e., aminoglutethimide and hydrocortisone). Furthermore, suramin has generated considerable interest following reports of response rates ranging from 17 to 70%. More recently, suramin response rates of 18 and 22% have been reported when the potential confounding variables of flutamide withdrawal and hydrocortisone were prospectively controlled. On the basis of the activity of combining aminoglutethimide with flutamide withdrawal, we designed a protocol in which suramin was combined with aminoglutethimide in two cohorts of patients (those with simultaneous antiandrogen withdrawal compared to those who had previously discontinued antiandrogen therapy). Eighty-one evaluable patients were enrolled in this study between June 1992 and November 1994. Patients were a priori divided into two cohorts, those receiving prior antiandrogen withdrawal (n = 56) and those receiving simultaneous antiandrogen withdrawal (n = 25) at the time the patients were enrolled into the trial. For the group that discontinued antiandrogen prior to enrolling in therapy, the partial response rate (> 50% decline in PSA for > 4 weeks) was 14.2%, whereas the partial response was 44% for those patients who discontinued their antiandrogen at the time of starting suramin and aminoglutethimide. The median time to progression was 3.9 months in patients failing prior antiandrogen withdrawal and 5.5 months in those patients having concomitant antiandrogen withdrawal (P = 0.36 for the overall difference). The progression-free survival estimate at 1 year for patients having prior antiandrogen withdrawal was 19.8% [95% confidence interval (CI), 11-32.9%]. For those patients who experienced antiandrogen withdrawal simultaneous with the treatment, the progression-free survival estimates at 1 and 2 years were 27.1 (95% CI, 13.2-47.6%) and 4.5% (95% CI, 0.8-21.6%). The median survival time for those patients having prior antiandrogen withdrawal was 14.2 months, whereas the median survival was 21.9 months for those having concomitant antiandrogen withdrawal (P = 0.029 for the overall difference). In conclusion, the partial response rate of 44% for those who had concomitant flutamide withdrawal with adrenal suppression was consistent with that of other reports using a similar maneuver. Although this study was not randomized and thus we should not over-interpret the results, flutamide withdrawal plus adrenal suppression appears to have greater activity than flutamide withdrawal alone. Furthermore, these data suggest that suramin adds little to the response rate observed for other adrenal suppressive agents in the presence of antiandrogen withdrawal. This interpretation is in agreement with those studies controlling for adrenal suppression and flutamide withdrawal prior to suramin administration, which noted modest activity of short duration. Given that antiandrogen withdrawal is now accepted as an active maneuver for a subset of patients progressing after maximum androgen blockade, we propose that future trials attempting to maximize response rates incorporate this maneuver whenever possible into prospectively designed regimens. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Dawson, N AU - Figg, W D AU - Brawley, O W AU - Bergan, R AU - Cooper, M R AU - Senderowicz, A AU - Headlee, D AU - Steinberg, S M AU - Sutherland, M AU - Patronas, N AU - Sausville, E AU - Linehan, W M AU - Reed, E AU - Sartor, O AD - Clinical Pharmacology Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. Y1 - 1998/01// PY - 1998 DA - January 1998 SP - 37 EP - 44 VL - 4 IS - 1 SN - 1078-0432, 1078-0432 KW - Androgen Antagonists KW - 0 KW - Aminoglutethimide KW - 0O54ZQ14I9 KW - Suramin KW - 6032D45BEM KW - Index Medicus KW - Survival Rate KW - Aged, 80 and over KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Male KW - Androgen Antagonists -- administration & dosage KW - Suramin -- adverse effects KW - Prostatic Neoplasms -- mortality KW - Aminoglutethimide -- administration & dosage KW - Suramin -- administration & dosage KW - Aminoglutethimide -- adverse effects KW - Prostatic Neoplasms -- drug therapy KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79744158?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=Phase+II+study+of+suramin+plus+aminoglutethimide+in+two+cohorts+of+patients+with+androgen-independent+prostate+cancer%3A+simultaneous+antiandrogen+withdrawal+and+prior+antiandrogen+withdrawal.&rft.au=Dawson%2C+N%3BFigg%2C+W+D%3BBrawley%2C+O+W%3BBergan%2C+R%3BCooper%2C+M+R%3BSenderowicz%2C+A%3BHeadlee%2C+D%3BSteinberg%2C+S+M%3BSutherland%2C+M%3BPatronas%2C+N%3BSausville%2C+E%3BLinehan%2C+W+M%3BReed%2C+E%3BSartor%2C+O&rft.aulast=Dawson&rft.aufirst=N&rft.date=1998-01-01&rft.volume=4&rft.issue=1&rft.spage=37&rft.isbn=&rft.btitle=&rft.title=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10780432&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-04-09 N1 - Date created - 1998-04-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nm23 and tumour metastasis: basic and translational advances. AN - 79737650; 9513729 AB - The nm23 genes were discovered on the basis of their reduced expression by highly metastatic cell lines. This trend was confirmed in cohorts of several types of human carcinomas and melanomas. Several transfection studies have demonstrated the suppressive effect of nm23 overexpression on the metastatic aggressiveness of melanoma and breast carcinoma cells in vivo. These transfection experiments have also demonstrated an effect of nm23 overexpression on cellular functions involved in the metastatic phenotype, such as cell motility, and point to a regulatory role for Nm23 proteins in cellular signalling pathways. Nm23 homologues from various species are also involved in normal tissue development and differentiation. Transfection of nm23-H1 into breast cancer cells provided a functional demonstration of the involvement of this gene in the differentiation of mammary epithelial cells. However, the molecular mechanism of these biological effects remains unknown. Several biochemical activities have been reported for Nm23, including NDP kinase activity, serine autophosphorylation and protein-histidine kinase activity. To define the possible significance of these biochemical activities, we carried out site-directed mutagenesis of the relevant codons of nm23-H1 cDNA and studied the effects upon transfection into MDA-MB-435 human breast carcinoma cells. We have also used Nm23 expression as a molecular marker to identify novel compounds that are active against the most aggressive tumour cells. This approach revealed that none of the standard agents currently in clinical use is preferentially active against the most aggressive tumour cells, and allowed us to identify new compounds that are preferentially inhibitory towards low-Nm23-expressing breast carcinoma and melanoma cell lines. This analysis also revealed a significant correlation between Nm23 levels and sensitivity of the tumour cells to alkylating agents. A functional implication of Nm23 proteins in this phenomenon was demonstrated after transfection of nm23 cDNAs into melanoma and breast and ovarian carcinoma cells. JF - Biochemical Society symposium AU - Freije, J M AU - MacDonald, N J AU - Steeg, P S AD - Women's Cancers Section, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1998 PY - 1998 DA - 1998 SP - 261 EP - 271 VL - 63 SN - 0067-8694, 0067-8694 KW - NM23 Nucleoside Diphosphate Kinases KW - 0 KW - Transcription Factors KW - NME1 protein, human KW - EC 2.7.4.6 KW - Nucleoside-Diphosphate Kinase KW - Monomeric GTP-Binding Proteins KW - EC 3.6.5.2 KW - Index Medicus KW - Breast Neoplasms -- genetics KW - Animals KW - Growth KW - Melanoma -- genetics KW - Transfection KW - Humans KW - Molecular Sequence Data KW - Cell Differentiation KW - Amino Acid Sequence KW - Transcription Factors -- physiology KW - Neoplasm Metastasis -- genetics KW - Transcription Factors -- chemistry KW - Transcription Factors -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79737650?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+Society+symposium&rft.atitle=Nm23+and+tumour+metastasis%3A+basic+and+translational+advances.&rft.au=Freije%2C+J+M%3BMacDonald%2C+N+J%3BSteeg%2C+P+S&rft.aulast=Freije&rft.aufirst=J&rft.date=1998-01-01&rft.volume=63&rft.issue=&rft.spage=261&rft.isbn=&rft.btitle=&rft.title=Biochemical+Society+symposium&rft.issn=00678694&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-04-23 N1 - Date created - 1998-04-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Review of epidemiologic studies of alcohol and prostate cancer: 1971-1996. AN - 79732675; 9507506 AB - Prostate cancer is the most common cancer among American men, with few established risk factors. The association between prostate cancer and alcohol, a potentially modifiable risk factor, has been examined in numerous studies. We systematically reviewed the literature on alcohol and the incidence of prostate cancer by searching for published cohort and case-control studies using computerized databases, references, and experts, by evaluating studies for validity, and by summarizing the results and providing research recommendations. We found compelling evidence for no association between low-to-moderate alcohol consumption and prostate cancer. Most studies, however, did not assess the risk of heavy drinking, where there has been some suggestion of increased risk, or of lifetime patterns of drinking. None of the studies have used genetic markers, nor have they been conducted in populations with known familial risk. Further studies in some populations may be warranted. JF - Nutrition and cancer AU - Breslow, R A AU - Weed, D L AD - Division of Cancer Prevention and Control, National Cancer Institute, Bethesda, MD 20892, USA. BreslowR@dcpcepn.nci.nih.gov Y1 - 1998 PY - 1998 DA - 1998 SP - 1 EP - 13 VL - 30 IS - 1 SN - 0163-5581, 0163-5581 KW - Ethanol KW - 3K9958V90M KW - Index Medicus KW - Risk Factors KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Male KW - Ethanol -- adverse effects KW - Prostatic Neoplasms -- epidemiology KW - Prostatic Neoplasms -- chemically induced KW - Ethanol -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79732675?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nutrition+and+cancer&rft.atitle=Review+of+epidemiologic+studies+of+alcohol+and+prostate+cancer%3A+1971-1996.&rft.au=Breslow%2C+R+A%3BWeed%2C+D+L&rft.aulast=Breslow&rft.aufirst=R&rft.date=1998-01-01&rft.volume=30&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Nutrition+and+cancer&rft.issn=01635581&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-04-24 N1 - Date created - 1998-04-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The C3(1)/SV40 T antigen transgenic mouse model of prostate and mammary cancer. AN - 79722643; 9502400 JF - Toxicologic pathology AU - Shibata, M A AU - Jorcyk, C L AU - Liu, M L AU - Yoshidome, K AU - Gold, L G AU - Green, J E AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. PY - 1998 SP - 177 EP - 182 VL - 26 IS - 1 SN - 0192-6233, 0192-6233 KW - Antigens, Polyomavirus Transforming KW - 0 KW - Index Medicus KW - Animals KW - Submandibular Gland Neoplasms -- pathology KW - Mice, Inbred C3H KW - Gene Expression KW - Bulbourethral Glands -- pathology KW - Prostate -- pathology KW - Mice KW - Prostatic Intraepithelial Neoplasia -- pathology KW - Urethral Neoplasms -- pathology KW - Male KW - Female KW - Prostatic Neoplasms -- pathology KW - Prostatic Neoplasms -- genetics KW - Mammary Neoplasms, Experimental -- genetics KW - Disease Models, Animal KW - Adenocarcinoma -- genetics KW - Antigens, Polyomavirus Transforming -- genetics KW - Mice, Transgenic -- genetics KW - Mammary Neoplasms, Experimental -- pathology KW - Adenocarcinoma -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79722643?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicologic+pathology&rft.atitle=The+C3%281%29%2FSV40+T+antigen+transgenic+mouse+model+of+prostate+and+mammary+cancer.&rft.au=Shibata%2C+M+A%3BJorcyk%2C+C+L%3BLiu%2C+M+L%3BYoshidome%2C+K%3BGold%2C+L+G%3BGreen%2C+J+E&rft.aulast=Shibata&rft.aufirst=M&rft.date=1998-01-01&rft.volume=26&rft.issue=1&rft.spage=177&rft.isbn=&rft.btitle=&rft.title=Toxicologic+pathology&rft.issn=01926233&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-04-09 N1 - Date created - 1998-04-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Preclinical evaluation of 9-chloro-2-methylellipticinium acetate alone and in combination with conventional anticancer drugs for the treatment of human brain tumor xenografts. AN - 79721491; 9498830 AB - Some ellipticine derivative salts, including 9-chloro-2-methylellipticinium (CME), have been found to have a marked selectivity against all eight brain tumor cell lines of the U.S. National Cancer Institute's disease-oriented in vitro screen. We initiated in vivo antitumor studies to explore the feasibility for further development of this class of compounds. We found that CME was extremely toxic to nude mice when given i.p. at a dose of 25 mg/kg for 3 consecutive days. Animals treated by this route experienced an increase in hepatic transaminases and histopathological changes in the liver, compatible with mitochondrial damage. In contrast, when the portal circulation was bypassed and the same dose of CME was given i.v., animals tolerated daily bolus injections for 5 consecutive days. This 5-day i.v. bolus schedule had consistent antitumor activity, with 28.1% growth delay on s.c. implanted human U251 gliomas. When the potentially high peaks of CME in the portal circulation were avoided by using a 3-day continuous infusion with osmotic minipumps implanted i.p. to release 3.4 mg kg(-1) h(-1) or 6.6 mg kg(-1) h(-1) CME, there were only modest increases in liver enzymes and leukopenia, but no meaningful antitumor activity was observed. In contrast, continuous infusion in the s.c. space was well tolerated and was accompanied by a demonstrable growth delay in s.c. U251 human gliomas of 37.8%. When CME was used in conjunction with carmustine, etoposide or cisplatin, no synergistic activities were observed, but additive effects were demonstrated. Our pharmacokinetic and disposition studies with CME argue against the notion that large and invasive tumors in the brain lack blood-brain barrier features. When CME was used in animals bearing orthotopically implanted U251 gliomas in the brain of nude mice, the survival of the treated animals was not better than vehicle controls, and the addition of CME to carmustine therapy did not improve the survival of those animals treated with carmustine alone. We conclude that, in spite of its marked cytotoxicity in vitro on a variety of human brain tumor cell lines, including U251 glioma cells, CME has a modest antitumor effect on extracranially implanted U251 glioma tumors, and no beneficial effect in animals bearing the same U251 tumor in the brain, owing to a poor penetration into the brain parenchyma. JF - Journal of cancer research and clinical oncology AU - Arguello, F AU - Alexander, M A AU - Greene, J F AU - Stinson, S F AU - Jorden, J L AU - Smith, E M AU - Kalavar, N T AU - Alvord, W G AU - Klabansky, R L AU - Sausville, E A AD - Division of Cancer Treatment, Diagnosis and Centers, Laboratory of Drug Discovery, Research and Development, National Institutes of Health, National Cancer Institute-FCRDC, Frederick, Maryland 21702, USA. Y1 - 1998/01// PY - 1998 DA - January 1998 SP - 19 EP - 26 VL - 124 IS - 1 SN - 0171-5216, 0171-5216 KW - 9-chloro-2-methylellipticinium acetate KW - 0 KW - Antineoplastic Agents KW - Ellipticines KW - Etoposide KW - 6PLQ3CP4P3 KW - Cisplatin KW - Q20Q21Q62J KW - Carmustine KW - U68WG3173Y KW - Index Medicus KW - Injections, Intraperitoneal KW - Animals KW - Drug Screening Assays, Antitumor KW - Injections, Intravenous KW - Chemical and Drug Induced Liver Injury KW - Humans KW - Blood-Brain Barrier -- physiology KW - Mice, Nude KW - Mice KW - Cisplatin -- administration & dosage KW - Neoplasm Transplantation KW - Feasibility Studies KW - Survival Rate KW - Etoposide -- administration & dosage KW - Transplantation, Heterologous KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Carmustine -- administration & dosage KW - Female KW - Glioma -- drug therapy KW - Brain Neoplasms -- drug therapy KW - Brain Neoplasms -- mortality KW - Antineoplastic Agents -- administration & dosage KW - Ellipticines -- therapeutic use KW - Glioma -- mortality KW - Ellipticines -- toxicity KW - Antineoplastic Agents -- toxicity KW - Antineoplastic Agents -- therapeutic use KW - Ellipticines -- administration & dosage KW - Ellipticines -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79721491?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+cancer+research+and+clinical+oncology&rft.atitle=Preclinical+evaluation+of+9-chloro-2-methylellipticinium+acetate+alone+and+in+combination+with+conventional+anticancer+drugs+for+the+treatment+of+human+brain+tumor+xenografts.&rft.au=Arguello%2C+F%3BAlexander%2C+M+A%3BGreene%2C+J+F%3BStinson%2C+S+F%3BJorden%2C+J+L%3BSmith%2C+E+M%3BKalavar%2C+N+T%3BAlvord%2C+W+G%3BKlabansky%2C+R+L%3BSausville%2C+E+A&rft.aulast=Arguello&rft.aufirst=F&rft.date=1998-01-01&rft.volume=124&rft.issue=1&rft.spage=19&rft.isbn=&rft.btitle=&rft.title=Journal+of+cancer+research+and+clinical+oncology&rft.issn=01715216&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-23 N1 - Date created - 1998-03-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Family history of alcoholism and gender: their combined effects on DSM-IV alcohol dependence and major depression. AN - 79720848; 9498321 AB - Data from a representative sample of U.S. adults were used to assess the extent of familial alcoholism, to examine its association with the odds of DSM-IV lifetime alcohol dependence, major depression, and their comorbid occurrence, and to determine whether the magnitude of this association was different for men and women. Self-report data from a sample of 42,862 U.S. adults (25,043 women) 18 years of age and over were analyzed by means of multiple logistic regression models that predicted the odds of various combinations of DSM-IV alcohol dependence and major depression. After adjusting for potential confounders through multiple logistic regression, family history saturation was associated with increased odds of dependence only, depression only, and all primary-secondary-concurrent combinations of these two disorders. The estimated effects were greatest for comorbid dependence and depression, next highest for dependence only and lowest for depression only. Differences in odds ratios among these groups increased with degree of family history saturation but were statistically significant at all levels of saturation. The effects of family history were greater for men than women for the outcome of primary depression followed by secondary dependence, but only at the higher levels of saturation. Among persons with lifetime major depression, family history of alcoholism had a positive independent association with the conditional odds of having experienced comorbid alcohol dependence. It had a weaker but still significant association with the odds of comorbid depression, conditional upon having experienced dependence, and this association was stronger among men than among women. For most outcomes, family history effects were stronger for paternal male and maternal female relatives than for paternal female and maternal male relatives. These findings supported prior research showing more familial alcoholism among persons with comorbid dependence and depression than among those with dependence alone. Gender differences were supportive of the proposed distinction between pure depression and depressive-spectrum disease. JF - Journal of studies on alcohol AU - Dawson, D A AU - Grant, B F AD - Biometry Branch, Division of Biometry and Epidemiology, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland 20892-7003, USA. Y1 - 1998/01// PY - 1998 DA - January 1998 SP - 97 EP - 106 VL - 59 IS - 1 SN - 0096-882X, 0096-882X KW - Index Medicus KW - Odds Ratio KW - Risk Factors KW - Models, Genetic KW - Humans KW - Adult KW - Longitudinal Studies KW - Male KW - Female KW - Comorbidity KW - Psychiatric Status Rating Scales KW - Depressive Disorder -- psychology KW - Alcoholism -- diagnosis KW - Child of Impaired Parents -- psychology KW - Depressive Disorder -- diagnosis KW - Depressive Disorder -- genetics KW - Gender Identity KW - Alcoholism -- genetics KW - Alcoholism -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79720848?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+studies+on+alcohol&rft.atitle=Family+history+of+alcoholism+and+gender%3A+their+combined+effects+on+DSM-IV+alcohol+dependence+and+major+depression.&rft.au=Dawson%2C+D+A%3BGrant%2C+B+F&rft.aulast=Dawson&rft.aufirst=D&rft.date=1998-01-01&rft.volume=59&rft.issue=1&rft.spage=97&rft.isbn=&rft.btitle=&rft.title=Journal+of+studies+on+alcohol&rft.issn=0096882X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-04-28 N1 - Date created - 1998-04-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Drug testing with alternative matrices I. Pharmacological effects and disposition of cocaine and codeine in plasma, sebum, and stratum corneum. AN - 79714492; 9491963 AB - This study examined the disposition of cocaine, codeine, and metabolites in stratum corneum, sebum, and plasma collected from five African-American males after administrations of cocaine and codeine during a 10-week inpatient clinical study. The subjects were experienced, healthy drug users with a recent history of cocaine and heroin abuse. The first drug administration was delayed by three weeks to allow for the elimination of previously administered drugs from the body. Subjects received three 75 mg cocaine hydrochloride/70 kg doses by the subcutaneous route and three 60 mg codeine sulfate/70 kg doses by the oral route on alternating days beginning in week 4. The same dosing sequence was repeated in week 8 with doubled (x 2) doses. Pharmacological measures (heart rate, pupil diameter, subject "High" and "Liking") were obtained simultaneously with blood. Stratum corneum was collected by scraping regions of the back once each week. Sebum was collected periodically from the forehead by applying Sebutape patches for 1-2-h intervals. Plasma, stratum corneum, and sebum were analyzed for cocaine, codeine, and metabolites by gas chromatography-mass spectrometry. Peak plasma cocaine concentrations occurred within the 30 min following dosing and followed peak pharmacological effects. Peak plasma codeine concentrations occurred within 1-2 h of dosing and before peak pharmacological effects. Cocaine and codeine were the primary analytes in sebum and stratum corneum. After dosing, these drugs appeared in sebum within 1-2 h and were detected for 1-2 days. Peak-drug concentrations in stratum corneum occurred one day after completion of dosing; elimination of the drugs continued over the next 1-2 weeks after dosing. Overall, no definitive relationship was observed between drug concentrations in sebum and stratum corneum compared with dose. Interpretation of drug distribution and elimination in sebum and stratum corneum was complicated by possible contamination of specimens with drugs from sweat. The mechanism(s) for deposition of cocaine and codeine in sebum and stratum corneum appeared to be complex and could involve the transfer of drugs between different body fluids (i.e., sebum and sweat) and other matrices (i.e., skin and hair). JF - Journal of analytical toxicology AU - Joseph, R E AU - Oyler, J M AU - Wstadik, A T AU - Ohuoha, C AU - Cone, E J AD - Addiction Research Center, Division of Intramural Research, National Institute on Drug Abuse, Baltimore, Maryland 21224, USA. PY - 1998 SP - 6 EP - 17 VL - 22 IS - 1 SN - 0146-4760, 0146-4760 KW - Narcotics KW - 0 KW - Cocaine KW - I5Y540LHVR KW - Codeine KW - Q830PW7520 KW - Index Medicus KW - Administration, Oral KW - Drug Administration Schedule KW - Area Under Curve KW - Dose-Response Relationship, Drug KW - Humans KW - Pain Measurement KW - Tissue Distribution KW - Heart Rate -- drug effects KW - Pupil -- drug effects KW - Psychomotor Performance -- drug effects KW - Adult KW - Gas Chromatography-Mass Spectrometry KW - Injections, Subcutaneous KW - Substance-Related Disorders -- metabolism KW - Inpatients KW - African Continental Ancestry Group KW - Male KW - Codeine -- analysis KW - Cocaine -- analysis KW - Sebum -- chemistry KW - Cocaine -- pharmacology KW - Narcotics -- pharmacology KW - Epidermis -- chemistry KW - Narcotics -- analysis KW - Codeine -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79714492?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+analytical+toxicology&rft.atitle=Drug+testing+with+alternative+matrices+I.+Pharmacological+effects+and+disposition+of+cocaine+and+codeine+in+plasma%2C+sebum%2C+and+stratum+corneum.&rft.au=Joseph%2C+R+E%3BOyler%2C+J+M%3BWstadik%2C+A+T%3BOhuoha%2C+C%3BCone%2C+E+J&rft.aulast=Joseph&rft.aufirst=R&rft.date=1998-01-01&rft.volume=22&rft.issue=1&rft.spage=6&rft.isbn=&rft.btitle=&rft.title=Journal+of+analytical+toxicology&rft.issn=01464760&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-06-25 N1 - Date created - 1998-06-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Present imperfect: a critical review of animal models of the mnemonic impairments in Alzheimer's disease. AN - 79710837; 9491942 AB - This paper reviews the current literature on animal models of the memory impairments of Alzheimer's disease (AD). The authors suggest that modeling of the mnemonic deficits in AD be limited to the amnesia observed early in the course of the disease, to eliminate the influence of impairments in non-mnemonic processes. Tasks should be chosen for their specificity and selectivity to the behavioral phenomena observed in early-stage AD and not for their relevance to hypothetical mnemonic processes. Tasks that manipulate the delay between learning and remembering are better able to differentiate Alzheimer patients from persons with other disorders, and better able to differentiate effects of manipulations in animals. The most commonly used manipulations that attempt to model the amnesia of AD are reviewed within these constraints. The authors conclude that of the models examined, lesions of the medial septal nucleus produce behavioral deficits that are most similar to the mnemonic impairments in the earliest stage of AD. However, the parallel is not definitive and more work is needed to clarify the relationship between neurobiology and behavior in AD. JF - Neuroscience and biobehavioral reviews AU - McDonald, M P AU - Overmier, J B AD - Department of Psychology, University of Minnesota, Minneapolis 55455, USA. mikemc@codon.nih.gov Y1 - 1998 PY - 1998 DA - 1998 SP - 99 EP - 120 VL - 22 IS - 1 SN - 0149-7634, 0149-7634 KW - Index Medicus KW - Animals KW - Humans KW - Disease Models, Animal KW - Memory Disorders -- chemically induced KW - Alzheimer Disease -- psychology KW - Memory Disorders -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79710837?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+and+biobehavioral+reviews&rft.atitle=Present+imperfect%3A+a+critical+review+of+animal+models+of+the+mnemonic+impairments+in+Alzheimer%27s+disease.&rft.au=McDonald%2C+M+P%3BOvermier%2C+J+B&rft.aulast=McDonald&rft.aufirst=M&rft.date=1998-01-01&rft.volume=22&rft.issue=1&rft.spage=99&rft.isbn=&rft.btitle=&rft.title=Neuroscience+and+biobehavioral+reviews&rft.issn=01497634&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-04-09 N1 - Date created - 1998-04-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A 0.5 G, 60 Hz magnetic field suppresses melatonin production in pinealocytes. AN - 79708606; 9492170 AB - The objective of this study was to develop a model for testing various hypotheses concerning possible mechanisms whereby electromagnetic fields might induce suppression of nighttime melatonin production in rodents. A published method for digesting freshly obtained pineal glands to the single cell level was modified, yielding better than 95% viability. An in vitro exposure facility developed for the Food and Drug Administration was used for 12-h overnight exposures of primary pinealocyte cultures to 0.05 mT, 60 Hz, vertical AC and 0.06 microT, DC fields. After exposure, cells were separated from the supernatant by centrifugation. Supernatant melatonin was measured by ELISA assays. Data from 10 experiments demonstrated an average 46% reduction in norepinephrine-induced production of melatonin in the pinealocytes. The results support the hypothesis that EM exposure can produce pineal gland melatonin suppression by affecting individual cells. JF - Bioelectromagnetics AU - Rosen, L A AU - Barber, I AU - Lyle, D B AD - Division of Research Grants, National Institutes of Health, Bethesda, Maryland 20892-7854, USA. LU2@CU.NIH.GOV Y1 - 1998 PY - 1998 DA - 1998 SP - 123 EP - 127 VL - 19 IS - 2 SN - 0197-8462, 0197-8462 KW - Melatonin KW - JL5DK93RCL KW - Norepinephrine KW - X4W3ENH1CV KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Environment, Controlled KW - Norepinephrine -- pharmacology KW - Cells, Cultured KW - Dose-Response Relationship, Radiation KW - Time Factors KW - Male KW - Female KW - Pineal Gland -- metabolism KW - Melatonin -- biosynthesis KW - Pineal Gland -- cytology KW - Electromagnetic Fields -- adverse effects KW - Melatonin -- radiation effects KW - Pineal Gland -- radiation effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79708606?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Bioelectromagnetics&rft.atitle=A+0.5+G%2C+60+Hz+magnetic+field+suppresses+melatonin+production+in+pinealocytes.&rft.au=Rosen%2C+L+A%3BBarber%2C+I%3BLyle%2C+D+B&rft.aulast=Rosen&rft.aufirst=L&rft.date=1998-01-01&rft.volume=19&rft.issue=2&rft.spage=123&rft.isbn=&rft.btitle=&rft.title=Bioelectromagnetics&rft.issn=01978462&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-31 N1 - Date created - 1998-03-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mortality among United States radiologic technologists, 1926-90. AN - 79704641; 9486465 AB - The possible mortality risk from low level chronic exposures to ionizing radiation was evaluated among 143,517 United States radiologic technologists certified by the American Registry of Radiologic Technologists between 1926-80. This is one of the few occupational studies of primarily women (73 percent) exposed to radiation during their employment. More than 2.8 million person-years of follow-up were accrued through 1990, and 7,345 deaths were identified. A strong healthy-worker effect was observed (standardized mortality ratios [SMR] for all causes and all cancers were 0.69 and 0.79, respectively). Lung cancer (429 deaths) was not increased with available measures of radiation exposure and no significant associations were observed for acute, myelogenous, and monocytic leukemia (74 deaths). Relative to the general population, the standardized mortality ratio (SMR) for female breast cancer was 0.99 (based on 425 deaths); however, breast cancer was significantly elevated relative to all other cancers in a test of homogeneity of SMRs (ratio of SMRs = 1.3, P < 0.0001). Significant risks were correlated with employment before 1940 (SMR = 1.5; 95 percent confidence interval [CI] = 1.2-1.9), when radiation doses were likely highest, and among women certified for more than 30 years (SMR = 1.4, CI = 1.2-1.7) for whom the cumulative exposure was likely greatest. Using an internal referent group, risk increased with duration of certification among the 1,890 women certified before 1940 (P-trend < 0.001). While the findings for breast cancer are consistent with a radiation effect, possible misclassification in exposure (based on number of years certified) and potential confounding associated with reproductive histories preclude a causal conclusion. JF - Cancer causes & control : CCC AU - Doody, M M AU - Mandel, J S AU - Lubin, J H AU - Boice, J D AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1998/01// PY - 1998 DA - January 1998 SP - 67 EP - 75 VL - 9 IS - 1 SN - 0957-5243, 0957-5243 KW - Index Medicus KW - Breast Neoplasms -- mortality KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Lung Neoplasms -- mortality KW - United States -- epidemiology KW - Time Factors KW - Male KW - Female KW - Cause of Death KW - Occupational Exposure KW - Mortality KW - Allied Health Personnel KW - Radiology -- manpower KW - Neoplasms, Radiation-Induced -- mortality KW - Radiation, Ionizing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79704641?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+causes+%26+control+%3A+CCC&rft.atitle=Mortality+among+United+States+radiologic+technologists%2C+1926-90.&rft.au=Doody%2C+M+M%3BMandel%2C+J+S%3BLubin%2C+J+H%3BBoice%2C+J+D&rft.aulast=Doody&rft.aufirst=M&rft.date=1998-01-01&rft.volume=9&rft.issue=1&rft.spage=67&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 - 1998-04-07 N1 - Date created - 1998-04-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cooperation of p53 loss of function and v-Ha-ras in transformation of mouse keratinocyte cell lines. AN - 79691206; 9473771 AB - We previously demonstrated that after transduction with the v-Ha-ras oncogene and grafting onto nude mouse hosts, primary epidermal keratinocytes with a null mutation in the p53 gene form tumors with increased growth rates and predisposition to malignant conversion relative to p53 wild-type keratinocytes (Weinberg WC, et al., Cancer Res 54:5584-5592, 1994). To further explore the cooperation between p53 loss of function and activation of the ras oncogene, cell lines were established from the normal epidermises of newborn and adult p53-null mice, and parallel subclones were reconstituted with the p53val135 temperature-sensitive mutant. Reconstituted lines C, G, N, and V demonstrated functional p53 transcriptional activator activity at the wild-type-permissive temperature of 32 degrees C, compared with the hygromycin-selected control line X and parental p53-null lines NHK4 and AK1b. Hygromycin-selected subclones, but not the parental lines, made normal skin in vivo; all cell lines made carcinomas after introduction of v-Ha-ras, independent of p53 status. These cell lines were compared in vitro at 32 degrees C to maximize the amount of p53val135 in the wild-type conformation. Expression of v-Ha-ras did not consistently alter p53-mediated transcriptional activity, suggesting tat ras acts downstream or independently of p53. No correlation was observed between p53-mediated transcriptional activity and in vitro growth rates, colony formation after exposure to ultraviolet light, or suppression by normal neighboring keratinocytes. However, keratinocyte cell lines devoid of p53 and expressing v-Ha-ras formed colonies in soft agar; this was blocked at 32 degrees C in all cell lines reconstituted with p53val135. These keratinocyte lines provide a model for exploring the role of p53 and the interaction of p53 and ras in keratinocyte transformation. JF - Molecular carcinogenesis AU - Azzoli, C G AU - Sagar, M AU - Wu, A AU - Lowry, D AU - Hennings, H AU - Morgan, D L AU - Weinberg, W C AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, MD 20892-4255, USA. Y1 - 1998/01// PY - 1998 DA - January 1998 SP - 50 EP - 61 VL - 21 IS - 1 SN - 0899-1987, 0899-1987 KW - Index Medicus KW - Animals KW - Ultraviolet Rays KW - Mice, Nude KW - Mice KW - Gene Expression Regulation KW - Cell Survival -- radiation effects KW - Cell Transplantation KW - Fluorescent Antibody Technique KW - Cell Division -- genetics KW - Gene Deletion KW - Keratinocytes -- radiation effects KW - Keratinocytes -- physiology KW - Cell Transformation, Neoplastic -- pathology KW - Genes, p53 -- physiology KW - Genes, ras -- physiology KW - Epidermis -- cytology KW - Genes, p53 -- genetics KW - Keratinocytes -- pathology KW - Keratinocytes -- metabolism KW - Cell Transformation, Neoplastic -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79691206?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+carcinogenesis&rft.atitle=Cooperation+of+p53+loss+of+function+and+v-Ha-ras+in+transformation+of+mouse+keratinocyte+cell+lines.&rft.au=Azzoli%2C+C+G%3BSagar%2C+M%3BWu%2C+A%3BLowry%2C+D%3BHennings%2C+H%3BMorgan%2C+D+L%3BWeinberg%2C+W+C&rft.aulast=Azzoli&rft.aufirst=C&rft.date=1998-01-01&rft.volume=21&rft.issue=1&rft.spage=50&rft.isbn=&rft.btitle=&rft.title=Molecular+carcinogenesis&rft.issn=08991987&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-02 N1 - Date created - 1998-03-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Altered expression of transforming growth factor betas during urethral and bulbourethral gland tumor progression in transgenic mice carrying the androgen-responsive C3(1) 5' flanking region fused to SV40 large T antigen. AN - 79691015; 9472712 AB - We demonstrate that targeted expression of SV40 large T antigen (TAg) to the urethral (periurethral) and bulbourethral gland epithelium leads to adenocarcinoma formation in these tissues after 7 months of age, which are extremely rare sites for spontaneous tumor formation in humans. The development of proliferative lesions in the urethral gland predictably follows a temporal course of progression with approximately one third of male animals developing urethral tumors by 1 year of age. Tumor progression in these organs correlates to the level of TAg and p53 expression. Immunoprecipitation confirmed that SV40 TAg protein was bound to p53 and Rb p110 in vivo. Expression of transforming growth factor beta (TGFbetas) was evaluated during tumor progression of urethral gland carcinomas. Elevations of intracellular and extracellular TGFbeta1 and extracellular TGFbeta3 were found in preneoplastic and neoplastic lesions, suggesting that increased TGFbetas may augment tumor growth. c-Met expression showed a tendency for increased expression in the urethral gland carcinomas. We speculate that the directed expression of SV40 TAg by the hormone responsive C3(1) gene and subsequent tumor formation in these organs is influenced by androgens, since these tissues and carcinomas express androgen receptor (AR) and arise only in male transgenic mice. Several cell lines established from the urethral carcinomas were also shown to express AR, but are not androgen dependent in culture. To our knowledge, this is the first transgenic animal model for urethral and bulbourethral carcinomas. This transgenic mouse model and the cell lines derived from it may provide a unique opportunity for dissecting molecular mechanisms involved in the tumorigenesis of these organs which otherwise rarely develop cancer. JF - Carcinogenesis AU - Shibata, M A AU - Jorcyk, C L AU - Devor, D E AU - Yoshidome, K AU - Rulong, S AU - Resau, J AU - Roche, N AU - Roberts, A B AU - Ward, J M AU - Green, J E AD - Laboratory of Cellular Regulation and Carcinogenesis, Division of Basic Sciences, National Cancer Institute, NIH, Bethesda, MD 20892, USA. Y1 - 1998/01// PY - 1998 DA - January 1998 SP - 195 EP - 205 VL - 19 IS - 1 SN - 0143-3334, 0143-3334 KW - Androgen-Binding Protein KW - 0 KW - Antigens, Polyomavirus Transforming KW - Recombinant Fusion Proteins KW - Retinoblastoma Protein KW - Transforming Growth Factor beta KW - Tumor Suppressor Protein p53 KW - Index Medicus KW - Tumor Suppressor Protein p53 -- biosynthesis KW - Animals KW - Neoplasm Invasiveness KW - Recombinant Fusion Proteins -- biosynthesis KW - Aging KW - Mice KW - Liver Neoplasms -- secondary KW - Mice, Transgenic KW - Tumor Suppressor Protein p53 -- metabolism KW - Protein Binding KW - Liver Neoplasms -- pathology KW - Antigens, Polyomavirus Transforming -- biosynthesis KW - Simian virus 40 KW - Retinoblastoma Protein -- metabolism KW - Neoplasm Metastasis KW - Male KW - Transforming Growth Factor beta -- biosynthesis KW - Genital Neoplasms, Male -- pathology KW - Bulbourethral Glands KW - Genital Neoplasms, Male -- metabolism KW - Androgen-Binding Protein -- genetics KW - Urethral Neoplasms -- pathology KW - Urethral Neoplasms -- metabolism KW - Androgen-Binding Protein -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79691015?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Altered+expression+of+transforming+growth+factor+betas+during+urethral+and+bulbourethral+gland+tumor+progression+in+transgenic+mice+carrying+the+androgen-responsive+C3%281%29+5%27+flanking+region+fused+to+SV40+large+T+antigen.&rft.au=Shibata%2C+M+A%3BJorcyk%2C+C+L%3BDevor%2C+D+E%3BYoshidome%2C+K%3BRulong%2C+S%3BResau%2C+J%3BRoche%2C+N%3BRoberts%2C+A+B%3BWard%2C+J+M%3BGreen%2C+J+E&rft.aulast=Shibata&rft.aufirst=M&rft.date=1998-01-01&rft.volume=19&rft.issue=1&rft.spage=195&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-02-27 N1 - Date created - 1998-02-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Overexpression of phosphoinositide-specific phospholipase Cgamma in NIH 3T3 cells promotes transformation and tumorigenicity. AN - 79687993; 9472710 AB - Phosphoinositide-specific phospholipase Cgamma (PLCgamma) is a key regulatory enzyme that binds to the phosphoryl-tyrosine residues in the cytoplasmic domain of certain activated receptors and catalyses the hydrolysis of phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] forming IP3 and diacylglycerol (DAG) in response to several mitogenic factors. Previously, we determined that microinjected PLCgamma induces DNA synthesis in G0-arrested NIH 3T3 cells, suggesting the possibility that PLCgamma may have an oncogenic potential. In this report, we demonstrate that overexpression of PLCgamma in NIH 3T3 cells results in altered growth properties and cellular transformation. The PLCgamma/3T3 transfectants do not require serum growth factors to proliferate, display anchorage-independent growth in soft agar and induce tumors when transplanted into nude mice. These findings suggest that overexpression of PLCgamma facilitates the transformation of NIH 3T3 cells. Furthermore, PLCgamma expression and activity have been shown to be elevated in many human tumors. Thus, PLCgamma signaling may contribute to the promotion and/or progression of human cancers. JF - Carcinogenesis AU - Smith, M R AU - Court, D W AU - Kim, H K AU - Park, J B AU - Rhee, S G AU - Rhim, J S AU - Kung, H F AD - Intramural Research Support Program, SAIC Frederick, Laboratory of Biochemical Physiology, National Cancer Institute, Frederick Cancer Research and Development Center, MD 21702, USA. smithmr@mail.nclcrf.gov Y1 - 1998/01// PY - 1998 DA - January 1998 SP - 177 EP - 185 VL - 19 IS - 1 SN - 0143-3334, 0143-3334 KW - Culture Media, Serum-Free KW - 0 KW - Isoenzymes KW - Recombinant Proteins KW - Type C Phospholipases KW - EC 3.1.4.- KW - Phospholipase C gamma KW - EC 3.1.4.3 KW - Index Medicus KW - 3T3 Cells KW - Animals KW - Recombinant Proteins -- biosynthesis KW - Humans KW - Mice KW - Mice, Nude KW - Neoplasms, Experimental -- pathology KW - Transfection KW - Flow Cytometry KW - Cell Cycle KW - Signal Transduction KW - Female KW - Cell Adhesion KW - Cell Division KW - Isoenzymes -- biosynthesis KW - Type C Phospholipases -- biosynthesis KW - Cell Transformation, Neoplastic UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79687993?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Overexpression+of+phosphoinositide-specific+phospholipase+Cgamma+in+NIH+3T3+cells+promotes+transformation+and+tumorigenicity.&rft.au=Smith%2C+M+R%3BCourt%2C+D+W%3BKim%2C+H+K%3BPark%2C+J+B%3BRhee%2C+S+G%3BRhim%2C+J+S%3BKung%2C+H+F&rft.aulast=Smith&rft.aufirst=M&rft.date=1998-01-01&rft.volume=19&rft.issue=1&rft.spage=177&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-02-27 N1 - Date created - 1998-02-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Screening for alcohol problems in the military: recommended tests. AN - 79687529; 9465564 AB - This article suggests two new techniques for identifying alcohol problems in a military setting. The Alcohol Use Disorders Identification Test is a well validated self-report procedure and requires approximately 2 minutes for administration. Measurement of carbohydrate-deficient transferrin provides a useful biochemical index of recent heavy alcohol consumption. Employment of these tests could improve selection of individuals seeking entry to the military, aid recognition of current personnel in need of treatment, and assist in evaluating progress of patients in treatment. JF - Military medicine AU - Allen, J P AU - Cross, G M AU - Fertig, J B AU - Litten, R Z AD - National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892-7003, USA. Y1 - 1998/01// PY - 1998 DA - January 1998 SP - 9 EP - 12 VL - 163 IS - 1 SN - 0026-4075, 0026-4075 KW - Biomarkers KW - 0 KW - Transferrin KW - carbohydrate-deficient transferrin KW - Index Medicus KW - Humans KW - Surveys and Questionnaires KW - Mass Screening -- methods KW - Biomarkers -- blood KW - Male KW - Female KW - Transferrin -- analogs & derivatives KW - Alcoholism -- diagnosis KW - Military Personnel KW - Transferrin -- analysis KW - Alcoholism -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79687529?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Military+medicine&rft.atitle=Screening+for+alcohol+problems+in+the+military%3A+recommended+tests.&rft.au=Allen%2C+J+P%3BCross%2C+G+M%3BFertig%2C+J+B%3BLitten%2C+R+Z&rft.aulast=Allen&rft.aufirst=J&rft.date=1998-01-01&rft.volume=163&rft.issue=1&rft.spage=9&rft.isbn=&rft.btitle=&rft.title=Military+medicine&rft.issn=00264075&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-04 N1 - Date created - 1998-03-04 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Mil Med. 1998 Apr;163(4):ix [9575778] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regenerative hyperplasia is not required for liver tumor induction in female B6C3F1 mice exposed to trihalomethanes. AN - 79687353; 9465273 AB - Chloroform (TCM), a water disinfection by-product, induced liver tumors in female mice when administered by gavage in corn oil but not when given in drinking water at comparable daily doses. Because short-term studies showed that the gavage doses also induced liver toxicity, it has been suggested that the liver tumor response occurs secondary to cytotoxicity and consequent regenerative hyperplasia induced by oxidative metabolism of TCM to the toxic dihalocarbonyl intermediate. This study compares dose-response relationships of gavage-administered chlorinated/brominated trihalomethanes for hepatotoxicity, replicative DNA synthesis, and hepatocarcinogenicity in female B6C3F1 mice. The liver tumor data were obtained from previously published studies. Because bromine is a better leaving group than chlorine, metabolism of bromodichloromethane (BDCM) should produce the same intermediates as would be formed from TCM. Hence, the toxicity and carcinogenicity of BDCM was expected to be qualitatively similar to that of TCM. Dose responses for liver weight, serum sorbitol dehydrogenase and alanine aminotransferase (ALT) activities, hepatocyte degeneration, and hepatocyte labeling index (LI, a measure of replicative DNA synthesis) in female mice were similar following 3 weeks of gavage administration (once per day, 5 days per week) with TCM, BDCM, or chlorodibromomethane (CDBM). Fits of composite data for these trihalomethanes to a Hill equation model revealed sigmoidal dose responses for ALT activity and hepatocyte LI and a nearly linear low-dose response for liver tumor incidence. For this family of chemicals, the mouse liver tumor response was not associated with an elevated hepatocyte LI at doses of approximately 1 mmol/kg or less. High incidences of liver tumors were observed with BDCM and CDBM at doses that had a marginal effect or no effect on the hepatocyte LI. Thus, the carcinogenic effects of trihalomethanes are not simply a consequence of cytotoxicity and regenerative hyperplasia. The possible contributions from other activation pathways, including GSH conjugation and reductive metabolism, need to be considered in assessments of the carcinogenicity of the trihalomethanes. JF - Toxicology and applied pharmacology AU - Melnick, R L AU - Kohn, M C AU - Dunnick, J K AU - Leininger, J R AD - Environmental Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. melnickr@niehs.nih.gov Y1 - 1998/01// PY - 1998 DA - January 1998 SP - 137 EP - 147 VL - 148 IS - 1 SN - 0041-008X, 0041-008X KW - Carcinogens KW - 0 KW - Hydrocarbons, Brominated KW - Hydrocarbons, Halogenated KW - Trihalomethanes KW - chlorodibromomethane KW - 3T4AJR1H24 KW - bromodichloromethane KW - 7LN464CH2O KW - Chloroform KW - 7V31YC746X KW - L-Iditol 2-Dehydrogenase KW - EC 1.1.1.14 KW - Alanine Transaminase KW - EC 2.6.1.2 KW - bromoform KW - TUT9J99IMU KW - Index Medicus KW - Administration, Oral KW - Animals KW - Hyperplasia -- chemically induced KW - Alanine Transaminase -- blood KW - L-Iditol 2-Dehydrogenase -- blood KW - Dose-Response Relationship, Drug KW - Chloroform -- toxicity KW - Mice KW - Hydrocarbons, Brominated -- toxicity KW - Female KW - DNA Replication -- drug effects KW - Organ Size -- drug effects KW - Liver Neoplasms -- pathology KW - Liver -- pathology KW - Hydrocarbons, Halogenated -- toxicity KW - Liver -- drug effects KW - Liver Neoplasms -- enzymology KW - Liver Neoplasms -- chemically induced KW - Carcinogens -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79687353?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Regenerative+hyperplasia+is+not+required+for+liver+tumor+induction+in+female+B6C3F1+mice+exposed+to+trihalomethanes.&rft.au=Melnick%2C+R+L%3BKohn%2C+M+C%3BDunnick%2C+J+K%3BLeininger%2C+J+R&rft.aulast=Melnick&rft.aufirst=R&rft.date=1998-01-01&rft.volume=148&rft.issue=1&rft.spage=137&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 - 1998-02-24 N1 - Date created - 1998-02-24 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Toxicol Appl Pharmacol. 1998 Nov;153(1):133-6 [9875307] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - An alternative test for trend in exposure-response analysis. AN - 79686535; 9470101 AB - The Mantel-extension chi-square test for overall trend is commonly used in evaluating dose-response relationships in epidemiologic studies. As illustrated by others, it is not an optimal test for a monotonic dose-response. In addition, the result of this test depends heavily upon the scores assigned to the exposure categories. The selection of the score may have a substantial impact on the test statistic and consequently, on the interpretation of the study results. A monotonic dose-response relationship exists when risk increases (or decreases) with increasing exposure. Although the Mantel-extension test is one of the most cited test for trend, it is not a sensitive test to reflect the incremental risk change of a dose-response relationship which may potentially generate misleading results. We propose an alternative test for the evaluation of monotonic dose-response, which reconfigurates the Mantel-Haenszel chi square test for dichotomous exposure series into a polychotomous exposure series. The proposed test generates chi values that are sensitive to incremental increase (or decrease) in risk at each exposure category and does not require exposure scores. The test is a simple summation of Mantel-Haenszel chi statistics obtained in for 2 x 2 tables over adjacent exposure categories (i.e., the sum of Mantel-Haenszel chi values between categories 1 and 2, 2 and 3, 3 and 4 and 1-1 and 1). Several examples are presented to illustrate that the proposed test generates more realistic chi values than those obtained by the Mantel-extension test for trend. JF - Journal of exposure analysis and environmental epidemiology AU - Dosemeci, M AU - Benichou, J AD - Epidemiology and Biostatistics Program, National Cancer Institute, Rockville, MD 20892, USA. DosemecM@epndce.nci.nih.gov PY - 1998 SP - 9 EP - 15 VL - 8 IS - 1 SN - 1053-4245, 1053-4245 KW - Environmental Pollutants KW - 0 KW - Index Medicus KW - Dose-Response Relationship, Drug KW - Humans KW - Chi-Square Distribution KW - Environmental Exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79686535?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+exposure+analysis+and+environmental+epidemiology&rft.atitle=An+alternative+test+for+trend+in+exposure-response+analysis.&rft.au=Dosemeci%2C+M%3BBenichou%2C+J&rft.aulast=Dosemeci&rft.aufirst=M&rft.date=1998-01-01&rft.volume=8&rft.issue=1&rft.spage=9&rft.isbn=&rft.btitle=&rft.title=Journal+of+exposure+analysis+and+environmental+epidemiology&rft.issn=10534245&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-04 N1 - Date created - 1998-03-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Safety of salivary gland-administered replication-deficient recombinant adenovirus in rats. AN - 79682696; 9466733 AB - We have examined the safety of a replication-deficient recombinant adenovirus administered at a single, high dose intraductally to rat submandibular glands or systemically via the femoral vein. The virus used directed the synthesis of human aquaporin-1, a water channel protein, and is termed AdhAQP1. Comparisons were made 1 and 9 days post-infection with animals administered either a similar virus encoding no transgene or the viral suspension buffer. Animals were specifically not given anti-inflammatory drugs to impede the well-known immunopathologic response to recombinant adenoviral administration. Serum chemistries and hematological parameters were monitored. Rats were subjected to complete gross necropsy and selected tissues were evaluated by histopathology. Most clinical chemistry and hematology values were within normal ranges; however, evidence of inflammation (e.g., elevated lactic dehydrogenase, total leukocyte count) was seen. Gross pathology was normal, as was histopathology, excepting rare focal areas of necrosis. The results show that intrasalivary gland or intravenous AdhAQP1 administration leads to low levels of toxicity in rats. JF - Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology AU - Delporte, C AU - Miller, G AU - Kagami, H AU - Lillibridge, C D AU - O'Connell, B C AU - Atkinson, J C AU - Baum, B J AD - Gene Therapy and Therapeutics Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1998/01// PY - 1998 DA - January 1998 SP - 34 EP - 38 VL - 27 IS - 1 SN - 0904-2512, 0904-2512 KW - AQP1 protein, human KW - 0 KW - Aqp1 protein, rat KW - Aquaporins KW - Blood Group Antigens KW - Ion Channels KW - Aquaporin 1 KW - 146410-94-8 KW - Dentistry KW - Index Medicus KW - Animals KW - Humans KW - Safety KW - Submandibular Gland KW - Femoral Vein KW - Rats KW - Toxicity Tests KW - Inflammation -- etiology KW - Rats, Wistar KW - Immunohistochemistry KW - Male KW - Inflammation -- pathology KW - Genetic Vectors KW - Gene Transfer Techniques -- adverse effects KW - Ion Channels -- biosynthesis KW - Ion Channels -- genetics KW - Adenoviridae -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79682696?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+oral+pathology+%26+medicine+%3A+official+publication+of+the+International+Association+of+Oral+Pathologists+and+the+American+Academy+of+Oral+Pathology&rft.atitle=Safety+of+salivary+gland-administered+replication-deficient+recombinant+adenovirus+in+rats.&rft.au=Delporte%2C+C%3BMiller%2C+G%3BKagami%2C+H%3BLillibridge%2C+C+D%3BO%27Connell%2C+B+C%3BAtkinson%2C+J+C%3BBaum%2C+B+J&rft.aulast=Delporte&rft.aufirst=C&rft.date=1998-01-01&rft.volume=27&rft.issue=1&rft.spage=34&rft.isbn=&rft.btitle=&rft.title=Journal+of+oral+pathology+%26+medicine+%3A+official+publication+of+the+International+Association+of+Oral+Pathologists+and+the+American+Academy+of+Oral+Pathology&rft.issn=09042512&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-05 N1 - Date created - 1998-03-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Reactive astrogliosis in neonatal rat spinal cord after exposure to cerebrospinal fluid from patients with amyotrophic lateral sclerosis. AN - 79681938; 9454639 AB - Previous studies have proposed the presence of circulating toxic factor(s) in the cerebrospinal fluid (CSF) of patients with amyotrophic lateral sclerosis (ALS). In the present study we show that there is an increased number of astrocytes intensely immunoreactive for glial fibrillary acidic protein (GFAP) in the gray matter of the spinal cords of neonatal rats exposed to ALS CSF. There is also increased expression of GFAP in the astrocytes of the white matter of neonatal rat spinal cords exposed to ALS CSF. Western blot analysis also confirmed the increased expression of GFAP. Accordingly, our study provides for the first time a clear evidence for the pathological response of glia to the circulating toxic factor(s) in the CSF of ALS patients. JF - Experimental neurology AU - Shahani, N AU - Nalini, A AU - Gourie-Devi, M AU - Raju, T R AD - Department of Neurophysiology, National Institute of Mental Health and Neurosciences, Bangalore, India. Y1 - 1998/01// PY - 1998 DA - January 1998 SP - 295 EP - 298 VL - 149 IS - 1 SN - 0014-4886, 0014-4886 KW - Glial Fibrillary Acidic Protein KW - 0 KW - Index Medicus KW - Rats KW - Animals KW - Humans KW - Rats, Wistar KW - Glial Fibrillary Acidic Protein -- metabolism KW - Immunologic Techniques KW - Cerebrospinal Fluid -- physiology KW - Gliosis -- pathology KW - Amyotrophic Lateral Sclerosis -- cerebrospinal fluid KW - Spinal Cord -- pathology KW - Astrocytes -- pathology KW - Animals, Newborn -- physiology KW - Astrocytes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79681938?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Experimental+neurology&rft.atitle=Reactive+astrogliosis+in+neonatal+rat+spinal+cord+after+exposure+to+cerebrospinal+fluid+from+patients+with+amyotrophic+lateral+sclerosis.&rft.au=Shahani%2C+N%3BNalini%2C+A%3BGourie-Devi%2C+M%3BRaju%2C+T+R&rft.aulast=Shahani&rft.aufirst=N&rft.date=1998-01-01&rft.volume=149&rft.issue=1&rft.spage=295&rft.isbn=&rft.btitle=&rft.title=Experimental+neurology&rft.issn=00144886&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-06 N1 - Date created - 1998-03-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transforming growth factor-betas in neurodegenerative disease. AN - 79677199; 9460794 AB - Transforming growth factors-betas (TGF-betas), a family of multifunctional peptide growth factors, affect cells of the central nervous system (CNS). The three mammalian TGF-beta isoforms, TGF-betas 1, 2 and 3, are expressed in adult human brain. Since neuronal degeneration is a defining feature of CNS degenerative diseases, TGF-beta may be important because it can influence neuronal survival. In vitro TGF-beta promotes survival of rat spinal cord motoneurons and dopaminergic neurons. In addition to direct effects on neuronal survival, TGF-beta treatment of cultured astrocytes induces a reactive phenotype. Thus, TGF-beta may also normalize the extracellular matrix environment in degenerative diseases. The expression of TGF-betas change in response to neuronal injury. TGF-beta 1 expression increases in astrocytes and microglia in animal models of cerebral ischemia, while TGF-beta 2 expression increases in activated astroglial cells in human neurodegenerative diseases. TGF-betas protect neurons from a variety of insults. TGF-beta maintains survival of chick telencephalic neurons made hypoxic by treatment with cyanide and decreases the area of infarction when administered in animal models of cerebral ischemia. In vitro TGF-beta protects neurons from damage induced by treatment with beta-amyloid peptide, FeSO4 (induces production of reactive oxygen species), Ca2+ ionophores, glutamate, glutamate receptor agonists and MPTP (toxic for dopaminergic neurons). TGF-beta maintains mitochondrial potential and Ca2+ homeostasis and inhibits apoptosis in neurons. TGF-beta does not prevent neuronal degeneration in a rat model of Parkinson's disease and has yet to be tested in newly developed transgenic mouse models of Alzheimer's disease. TGF-beta is a potent neuroprotective agent which may affect the pathogenesis of neurodegenerative diseases of the CNS. JF - Progress in neurobiology AU - Flanders, K C AU - Ren, R F AU - Lippa, C F AD - Laboratory of Chemoprevention, National Cancer Institute, Bethesda, MD 20892-5055, USA. FLANDERK@DCE41.NCI.NIH.GOV Y1 - 1998/01// PY - 1998 DA - January 1998 SP - 71 EP - 85 VL - 54 IS - 1 SN - 0301-0082, 0301-0082 KW - Transforming Growth Factor beta KW - 0 KW - Index Medicus KW - Animals KW - Humans KW - Disease Models, Animal KW - Transforming Growth Factor beta -- physiology KW - Neurodegenerative Diseases -- metabolism KW - Neurodegenerative Diseases -- pathology KW - Transforming Growth Factor beta -- chemistry KW - Transforming Growth Factor beta -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79677199?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Progress+in+neurobiology&rft.atitle=Transforming+growth+factor-betas+in+neurodegenerative+disease.&rft.au=Flanders%2C+K+C%3BRen%2C+R+F%3BLippa%2C+C+F&rft.aulast=Flanders&rft.aufirst=K&rft.date=1998-01-01&rft.volume=54&rft.issue=1&rft.spage=71&rft.isbn=&rft.btitle=&rft.title=Progress+in+neurobiology&rft.issn=03010082&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-17 N1 - Date created - 1998-03-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Protein kinase C regulation of organic anion transport in renal proximal tubule. AN - 79675871; 9458835 AB - Fluorescence microscopy and digital image analysis were used to examine the role of protein kinase C (PKC) in the control of organic anion (fluorescein, FL) transport in killifish renal proximal tubules. Phorbol ester (1-100 nM) reduced cellular and luminal accumulation of FL, and protein kinase inhibitors [staurosporine and 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine, 10-1,000 nM] increased cellular and luminal accumulation. Phorbol ester effects were blocked by staurosporine. The increases in tissue fluorescence caused by staurosporine were blocked by p-aminohippurate, indicating that they represent increased FL transport on the organic anion system. Neither phorbol ester nor staurosporine had any effects on the cell-to-lumen transport of a fluorescent organic anion that was generated intracellularly from a nonfluorescent, uncharged precursor. Finally, studies with a fluorescent PKC inhibitor showed that phorbol ester caused PKC translocation from cytoplasm to the plasma membrane. Together, these findings indicate that renal organic anion transport is negatively correlated with PKC activity and that PKC directly or indirectly controls the basolateral step in transport. JF - The American journal of physiology AU - Miller, D S AD - Intracellular Regulation Section, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 1998/01// PY - 1998 DA - January 1998 SP - F156 EP - F164 VL - 274 IS - 1 Pt 2 SN - 0002-9513, 0002-9513 KW - Enzyme Inhibitors KW - 0 KW - 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine KW - 84477-87-2 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Staurosporine KW - H88EPA0A3N KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Fluorescein KW - TPY09G7XIR KW - Index Medicus KW - Animals KW - 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine -- pharmacology KW - Staurosporine -- pharmacology KW - Epithelial Cells -- physiology KW - Epithelial Cells -- drug effects KW - Killifishes KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Enzyme Inhibitors -- pharmacology KW - Homeostasis KW - Models, Biological KW - Biological Transport -- drug effects KW - Protein Kinase C -- metabolism KW - Kidney Tubules, Proximal -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79675871?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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+physiology&rft.atitle=Protein+kinase+C+regulation+of+organic+anion+transport+in+renal+proximal+tubule.&rft.au=Miller%2C+D+S&rft.aulast=Miller&rft.aufirst=D&rft.date=1998-01-01&rft.volume=274&rft.issue=1+Pt+2&rft.spage=F156&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+physiology&rft.issn=00029513&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-02-23 N1 - Date created - 1998-02-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Fibrin sheath formation and chemotherapy extravasation: a case report. AN - 79674730; 9458537 AB - Fibrin sheath formation around venous access devices (VADs) frequently leads to persistent withdrawal occlusion (PWO). PWO is a common problem encountered with VADs. Although PWO is often easily managed with small doses of thrombolytic therapy (e.g., urokinase), it could result in a more serious complication, such as chemotherapy extravasation. Careful assessment of all VADs is important to identify complications such as fibrin sheath formation, which can potentially lead to extravasation. To rule out fibrin sheath formation, catheter dye studies need to be obtained when fibrinolytic therapy has failed to restore catheter function. The purpose of this paper is to illustrate a retrospective case report demonstrating drug extravasation caused by the development of fibrin sheath formation. JF - Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer AU - Mayo, D J AD - National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1998/01// PY - 1998 DA - January 1998 SP - 51 EP - 56 VL - 6 IS - 1 SN - 0941-4355, 0941-4355 KW - Cyclophosphamide KW - 8N3DW7272P KW - Fibrin KW - 9001-31-4 KW - Plasminogen Activators KW - EC 3.4.21.- KW - Urokinase-Type Plasminogen Activator KW - EC 3.4.21.73 KW - Paclitaxel KW - P88XT4IS4D KW - Index Medicus KW - Breast Neoplasms -- drug therapy KW - Cyclophosphamide -- administration & dosage KW - Paclitaxel -- administration & dosage KW - Urokinase-Type Plasminogen Activator -- therapeutic use KW - Humans KW - Constriction, Pathologic -- etiology KW - Antineoplastic Combined Chemotherapy Protocols -- administration & dosage KW - Equipment Failure KW - Plasminogen Activators -- therapeutic use KW - Constriction, Pathologic -- drug therapy KW - Middle Aged KW - Infusions, Intravenous -- instrumentation KW - Female KW - Catheterization, Central Venous -- adverse effects KW - Fibrin -- metabolism KW - Catheters, Indwelling -- adverse effects KW - Extravasation of Diagnostic and Therapeutic Materials -- etiology KW - Extravasation of Diagnostic and Therapeutic Materials -- drug therapy KW - Catheterization, Central Venous -- instrumentation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79674730?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Supportive+care+in+cancer+%3A+official+journal+of+the+Multinational+Association+of+Supportive+Care+in+Cancer&rft.atitle=Fibrin+sheath+formation+and+chemotherapy+extravasation%3A+a+case+report.&rft.au=Mayo%2C+D+J&rft.aulast=Mayo&rft.aufirst=D&rft.date=1998-01-01&rft.volume=6&rft.issue=1&rft.spage=51&rft.isbn=&rft.btitle=&rft.title=Supportive+care+in+cancer+%3A+official+journal+of+the+Multinational+Association+of+Supportive+Care+in+Cancer&rft.issn=09414355&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-19 N1 - Date created - 1998-03-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A high-risk lesion for invasive breast cancer, ductal carcinoma in situ, exhibits frequent overexpression of retinoid X receptor. AN - 79674122; 9456240 AB - The development of prevention strategies for breast cancer will require a molecular map of carcinogenesis. We have investigated gene expression patterns in premalignant and early carcinomatous human breast lesions that confer to the patient varying risks for developing invasive breast cancer. The relative expression levels of one of the retinoid receptors, retinoid X receptor (RXR), was determined by in situ hybridization to 58 biopsy specimens; RXR mRNA grain density over each lesion was compared to that over the normal ductal/lobular units in each section. Overexpression of RXR mRNA was observed in 66% of noncomedo ductal carcinoma in situ (DCIS), which confer a >8-fold increase in breast cancer risk, and 88% of comedo DCIS lesions, which are associated with a yet higher risk. In contrast, only 8% of lesions that confer little or no increase in breast cancer risk overexpressed RXR mRNA (P = 0.0008). Limited in situ hybridization data using retinoic acid receptor (RAR) riboprobes showed overexpression of RAR alpha, but not RAR beta or -gamma, in only a modest percentage (36%) of cases, suggesting that all members of the retinoid receptor superfamily are not similarly regulated. Immunohistochemistry performed on 52 DCIS specimens for alpha, beta, and gamma isoforms of RXR confirmed its overexpression at the protein level and implicate RXR alpha as the predominant overexpressed form. The data indicate that RXR overexpression is associated with an increased risk for the development of invasive breast cancer in human breast lesions and suggest the hypothesis that it is causally involved in breast oncogenesis. The implications for retinoid chemoprevention are discussed. JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology AU - Lawrence, J A AU - Merino, M J AU - Simpson, J F AU - Manrow, R E AU - Page, D L AU - Steeg, P S AD - Chemprevention Branch, Division of Cancer Prevention, National Cancer Institute, Bethesda, Maryland 20892, USA. julial@helix.nih.gov Y1 - 1998/01// PY - 1998 DA - January 1998 SP - 29 EP - 35 VL - 7 IS - 1 SN - 1055-9965, 1055-9965 KW - Biomarkers, Tumor KW - 0 KW - Receptors, Retinoic Acid KW - Retinoid X Receptors KW - Retinoids KW - Transcription Factors KW - Index Medicus KW - Gene Expression Regulation, Neoplastic KW - Risk KW - Neoplasm Invasiveness KW - In Situ Hybridization KW - Retinoids -- therapeutic use KW - Humans KW - In Vitro Techniques KW - Cohort Studies KW - Up-Regulation KW - Female KW - Receptors, Retinoic Acid -- metabolism KW - Breast Neoplasms -- genetics KW - Biomarkers, Tumor -- metabolism KW - Carcinoma in Situ -- pathology KW - Carcinoma, Ductal, Breast -- pathology KW - Breast Neoplasms -- pathology KW - Transcription Factors -- metabolism KW - Carcinoma in Situ -- genetics KW - Carcinoma, Ductal, Breast -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79674122?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+high-risk+lesion+for+invasive+breast+cancer%2C+ductal+carcinoma+in+situ%2C+exhibits+frequent+overexpression+of+retinoid+X+receptor.&rft.au=Lawrence%2C+J+A%3BMerino%2C+M+J%3BSimpson%2C+J+F%3BManrow%2C+R+E%3BPage%2C+D+L%3BSteeg%2C+P+S&rft.aulast=Lawrence&rft.aufirst=J&rft.date=1998-01-01&rft.volume=7&rft.issue=1&rft.spage=29&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 - 1998-03-11 N1 - Date created - 1998-03-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nuclear factor-kappa B contributes to excitotoxin-induced apoptosis in rat striatum. AN - 79671036; 9443930 AB - Excitotoxin-induced destruction of striatal neurons, proposed as a model of Huntington's disease, involves a process having the biochemical stigmata of apoptosis. Recent studies suggested that transcription factor nuclear factor (NF)-kappa B may be involved in excitotoxicity. To further analyze the contribution of NF kappa B to excitotoxic neuronal death in vivo, changes in binding activities of NF kappa B and other transcription factors as well as the consequences of inhibiting NF kappa B nuclear translocation were measured after the infusion of quinolinic acid (120 nmol) into rat striatum. Internucleosomal DNA fragmentation and terminal transferase-mediated dUTP digoxigenin nick end labeling-positive nuclei appeared 12 hr later and intensified over the next 12 hr. NF kappa B binding activity increased several-fold from 2 to 12 hr, then gradually declined during the next 12 hr. Other transcription factor changes included AP-1, whose binding peaked about 6 hr after quinolinic acid administration, and E2F-1, which was only modestly and transiently elevated. In contrast, quinolinic acid lead to a reduction in OCT-1, beginning after 12 hr, and briefly in SP-1 binding. The NF kappa B, AP-1, and OCT-1 changes were attenuated both by the N-methyl-D-aspartate receptor antagonist MK-801 and the protein synthesis inhibitor cycloheximide. Moreover, quinolinic acid-induced internucleosomal DNA fragmentation and striatal cell death were significantly reduced by the intrastriatal administration of NF kappa B SN50, a cell-permeable recombinant peptide that blocks NF kappa B nuclear translocation. These results illustrate the complex temporal pattern of transcription factor change attending the apoptotic destruction produced in rat striatum by quinolinic acid. They further suggest that NF kappa B activation contributes to the excitotoxin-induced death of striatal neurons. JF - Molecular pharmacology AU - Qin, Z H AU - Wang, Y AU - Nakai, M AU - Chase, T N AD - Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/01// PY - 1998 DA - January 1998 SP - 33 EP - 42 VL - 53 IS - 1 SN - 0026-895X, 0026-895X KW - NF-kappa B KW - 0 KW - Neurotoxins KW - Nucleosomes KW - Receptors, N-Methyl-D-Aspartate KW - Transcription Factors KW - DNA KW - 9007-49-2 KW - Quinolinic Acid KW - F6F0HK1URN KW - Index Medicus KW - Rats KW - Receptors, N-Methyl-D-Aspartate -- biosynthesis KW - Animals KW - Rats, Sprague-Dawley KW - Transcription Factors -- metabolism KW - DNA Damage KW - Neurons -- drug effects KW - DNA -- metabolism KW - Nucleosomes -- metabolism KW - Neurons -- cytology KW - Receptors, N-Methyl-D-Aspartate -- antagonists & inhibitors KW - Quinolinic Acid -- toxicity KW - Corpus Striatum -- cytology KW - Apoptosis -- physiology KW - Apoptosis -- drug effects KW - Corpus Striatum -- drug effects KW - NF-kappa B -- physiology KW - Neurotoxins -- toxicity KW - NF-kappa B -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79671036?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Nuclear+factor-kappa+B+contributes+to+excitotoxin-induced+apoptosis+in+rat+striatum.&rft.au=Qin%2C+Z+H%3BWang%2C+Y%3BNakai%2C+M%3BChase%2C+T+N&rft.aulast=Qin&rft.aufirst=Z&rft.date=1998-01-01&rft.volume=53&rft.issue=1&rft.spage=33&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 - 1998-02-20 N1 - Date created - 1998-02-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Structure-activity analysis of the interaction of curacin A, the potent colchicine site antimitotic agent, with tubulin and effects of analogs on the growth of MCF-7 breast cancer cells. AN - 79670304; 9443933 AB - Originally purified as a major lipid component of a strain of the cyanobacterium Lyngbya majuscula isolated in Curaçao, curacin A is a potent inhibitor of cell growth and mitosis, binding rapidly and tightly at the colchicine site of tubulin. Because its molecular structure differs so greatly from that of colchicine and other colchicine site inhibitors, we prepared a series of curacin A analogs to determine the important structural features of the molecule. These modifications include reduction and E-to-Z transitions of the olefinic bonds in the 14-carbon side chain of the molecule; disruption of and configurational changes in the cyclopropyl moiety; disruption, oxidation, and configurational reversal in the thiazoline moiety; configurational reversal and substituent modifications at C13; and demethylation at C10. Inhibitory effects on tubulin assembly, the binding of colchicine to tubulin, and the growth of MCF-7 human breast carcinoma cells were examined. The most important portions of curacin A required for its interaction with tubulin seem to be the thiazoline ring and the side chain at least through C4, the portion of the side chain including the C9-C10 olefinic bond, and the C10 methyl group. Only two modifications totally eliminated the tubulin-drug interaction. The inactive compounds were a segment containing most of the side chain, including its two substituents, and analogs in which the methyl group at the C13 oxygen atom was replaced by a benzoate residue. Antiproliferative activity comparable with that observed with curacin A was only reproduced in compounds that were potent inhibitors of the binding of colchicine to tubulin. Molecular modeling and quantitative structure-activity relationship studies demonstrated that most active analogs overlapped extensively with curacin A but failed to provide an explanation for the apparent structural analogy between curacin A and colchicine. JF - Molecular pharmacology AU - Verdier-Pinard, P AU - Lai, J Y AU - Yoo, H D AU - Yu, J AU - Marquez, B AU - Nagle, D G AU - Nambu, M AU - White, J D AU - Falck, J R AU - Gerwick, W H AU - Day, B W AU - Hamel, E AD - Laboratory of Drug Discovery Research and Development, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland 21702, USA. Y1 - 1998/01// PY - 1998 DA - January 1998 SP - 62 EP - 76 VL - 53 IS - 1 SN - 0026-895X, 0026-895X KW - Antineoplastic Agents KW - 0 KW - Cyclopropanes KW - DNA, Neoplasm KW - Thiazoles KW - Tubulin KW - curacin A KW - 155233-30-0 KW - Colchicine KW - SML2Y3J35T KW - Index Medicus KW - Animals KW - Drug Interactions KW - Models, Molecular KW - Humans KW - Cell Division -- drug effects KW - Structure-Activity Relationship KW - Binding Sites KW - G2 Phase -- physiology KW - Cattle KW - G2 Phase -- drug effects KW - Tumor Cells, Cultured KW - Mitosis KW - Models, Chemical KW - Molecular Conformation KW - DNA, Neoplasm -- metabolism KW - Thiazoles -- pharmacology KW - Breast Neoplasms -- drug therapy KW - Cyclopropanes -- metabolism KW - Breast Neoplasms -- pathology KW - Thiazoles -- metabolism KW - Antineoplastic Agents -- metabolism KW - Tubulin -- metabolism KW - Cyclopropanes -- pharmacology KW - Breast Neoplasms -- embryology KW - Antineoplastic Agents -- pharmacology KW - Colchicine -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79670304?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Structure-activity+analysis+of+the+interaction+of+curacin+A%2C+the+potent+colchicine+site+antimitotic+agent%2C+with+tubulin+and+effects+of+analogs+on+the+growth+of+MCF-7+breast+cancer+cells.&rft.au=Verdier-Pinard%2C+P%3BLai%2C+J+Y%3BYoo%2C+H+D%3BYu%2C+J%3BMarquez%2C+B%3BNagle%2C+D+G%3BNambu%2C+M%3BWhite%2C+J+D%3BFalck%2C+J+R%3BGerwick%2C+W+H%3BDay%2C+B+W%3BHamel%2C+E&rft.aulast=Verdier-Pinard&rft.aufirst=P&rft.date=1998-01-01&rft.volume=53&rft.issue=1&rft.spage=62&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 - 1998-02-20 N1 - Date created - 1998-02-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Bcl-2 immunohistochemistry in a surgical series of non-small cell lung cancer patients. AN - 79663434; 9445135 AB - The bcl-2 gene is implicated in oncogenesis by its ability to prolong cell survival through the inhibition of apoptosis, without increasing cell proliferation. An association between immunohistochemical staining for bcl-2 protein and the histological type and prognosis of non-small cell carcinoma was hypothesized by Pezzella et al. (N Engl J Med 329:690-694, 1993). In a case series, we stained formalin-fixed, paraffin-embedded tumor tissue from 106 surgical non-small cell lung cancer patients with an antibody to bcl-2 protein (DAKO clone 124, Carpinteria, CA). The resulting bcl-2 staining data were evaluated for associations with demographic, histological, immunohistochemical, and genetic features, including p53 mutations. Bcl-2 staining was observed in tumors from 29 of 106 (27%) of subjects, but was significantly less frequent in subjects' adenocarcinoma histology (8 of 55, 14.6%) (P = .007). This finding persisted after adjustment for age, gender, stage, grade, smoking history, and disease-free survival. In univariate analyses, no association was seen with age, weight, body mass index, gender, or pack-years smoking; tumor grade, stage, or patient performance status; p53 or c-erbB2 immunohistochemical staining, or p53 mutations. These data agree with earlier reports that bcl-2 staining is less common in adenocarcinomas; however, our data do not support the hypothesis that bcl-2 staining confers a better prognosis overall, in squamous cell carcinoma, or in an older patient population. JF - Human pathology AU - Fleming, M V AU - Guinee, D G AU - Chu, W S AU - Freedman, A N AU - Caporaso, N E AU - Bennett, W P AU - Colby, T V AU - Tazelaar, H AU - Abbondanzo, S L AU - Jett, J AU - Pairolero, P AU - Trastek, V AU - Liotta, L A AU - Harris, C C AU - Travis, W D AD - Laboratory of Human Carcinogenesis, NCI, NIH, Bethesda, MD, USA. Y1 - 1998/01// PY - 1998 DA - January 1998 SP - 60 EP - 64 VL - 29 IS - 1 SN - 0046-8177, 0046-8177 KW - Proto-Oncogene Proteins c-bcl-2 KW - 0 KW - Tumor Suppressor Protein p53 KW - Receptor, ErbB-2 KW - EC 2.7.10.1 KW - Index Medicus KW - Adenocarcinoma -- metabolism KW - Tumor Suppressor Protein p53 -- analysis KW - Receptor, ErbB-2 -- metabolism KW - Humans KW - Genes, p53 -- genetics KW - Carcinoma, Squamous Cell -- metabolism KW - Middle Aged KW - Immunohistochemistry KW - Male KW - Female KW - Carcinoma, Large Cell -- metabolism KW - Carcinoma, Non-Small-Cell Lung -- metabolism KW - Proto-Oncogene Proteins c-bcl-2 -- analysis KW - Lung Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79663434?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+pathology&rft.atitle=Bcl-2+immunohistochemistry+in+a+surgical+series+of+non-small+cell+lung+cancer+patients.&rft.au=Fleming%2C+M+V%3BGuinee%2C+D+G%3BChu%2C+W+S%3BFreedman%2C+A+N%3BCaporaso%2C+N+E%3BBennett%2C+W+P%3BColby%2C+T+V%3BTazelaar%2C+H%3BAbbondanzo%2C+S+L%3BJett%2C+J%3BPairolero%2C+P%3BTrastek%2C+V%3BLiotta%2C+L+A%3BHarris%2C+C+C%3BTravis%2C+W+D&rft.aulast=Fleming&rft.aufirst=M&rft.date=1998-01-01&rft.volume=29&rft.issue=1&rft.spage=60&rft.isbn=&rft.btitle=&rft.title=Human+pathology&rft.issn=00468177&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-02-05 N1 - Date created - 1998-02-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The immunophilin FKBP65 forms an association with the serine/threonine kinase c-Raf-1. AN - 79660771; 9438387 AB - FKBP65 is a member of the FK506-binding protein class of immunophilins and is the only member reported to contain four peptidylprolyl cis-trans isomerase domains and an unrelated COOH-terminal domain. In this report, we show that the heat shock protein hsp90 and the serine/threonine protein kinase c-Raf-1 are components of FKBP65 immune complexes. The NH2-terminal regulatory domain of c-Raf-1 appears to be required for its interaction with FKBP65. Using GST-FKBP65 fusion protein and purified Raf proteins, we show that full-length FKBP65 can interact with c-Raf-1 but not B-Raf. The activation kinetics of c-Raf-1 after v-H-RasV12 injection of Xenopus oocytes appear to correlate with FKBP65/c-Raf-1 interaction, suggesting that FKBP65 may preferentially associate with forms of c-Raf-1 that are more posttranslationally modified. The interaction of FKBP65 with the c-Raf-heat shock protein 90 heterocomplex implicates this immunophilin in signal-transduction processes. JF - Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research AU - Coss, M C AU - Stephens, R M AU - Morrison, D K AU - Winterstein, D AU - Smith, L M AU - Simek, S L AD - Division of Basic Science, National Cancer Institute-Frederick Cancer Research and Development Center, NIH, Frederick, Maryland 21702-1201, USA. Y1 - 1998/01// PY - 1998 DA - January 1998 SP - 41 EP - 48 VL - 9 IS - 1 SN - 1044-9523, 1044-9523 KW - Carrier Proteins KW - 0 KW - DNA-Binding Proteins KW - FK506-binding protein, Xenopus KW - HSP90 Heat-Shock Proteins KW - Recombinant Fusion Proteins KW - Xenopus Proteins KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Proto-Oncogene Proteins c-raf KW - EC 2.7.11.1 KW - Tacrolimus Binding Proteins KW - EC 5.2.1.- KW - Index Medicus KW - Recombinant Fusion Proteins -- metabolism KW - Xenopus laevis KW - Animals KW - Spodoptera KW - Glutathione Transferase -- metabolism KW - HSP90 Heat-Shock Proteins -- metabolism KW - Protein Binding KW - Mutagenesis KW - Carrier Proteins -- metabolism KW - Proto-Oncogene Proteins c-raf -- genetics KW - Proto-Oncogene Proteins c-raf -- metabolism KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79660771?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+immunophilin+FKBP65+forms+an+association+with+the+serine%2Fthreonine+kinase+c-Raf-1.&rft.au=Coss%2C+M+C%3BStephens%2C+R+M%3BMorrison%2C+D+K%3BWinterstein%2C+D%3BSmith%2C+L+M%3BSimek%2C+S+L&rft.aulast=Coss&rft.aufirst=M&rft.date=1998-01-01&rft.volume=9&rft.issue=1&rft.spage=41&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 - 1998-02-06 N1 - Date created - 1998-02-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Questionnaires for collecting detailed occupational information for community-based case control studies. AN - 79660607; 9438334 AB - In case control studies, collection of information on the workplace environment has generally been limited to self-reports of exposures or to job title, type of employer, and the dates the jobs were held, supplemented sometimes by work activities. This information, however, may be insufficient to assess the potential and level of exposure accurately due to recall difficulties and the variability of exposures within a job. A solution to this problem is to use job-specific questionnaires. The organization of a series of such questionnaires developed for a case control study of brain tumors is described. Three types of questionnaires, or modules, were developed, task-based, industry-based, and modules based on jobs with nonspecific types of tasks (e.g., laborer). The format of these modules starts with questions on the general work environment (type of employer) and proceeds to questions on tasks. More detailed information is then gathered on materials and equipment used, sensory descriptions, dermal exposure, work practices, engineering controls, and personal protective equipment use. The questionnaires cover a wide variety of exposures including solvents, heavy metals, polycyclic aromatic hydrocarbons, machining fluids, electromagnetic frequency fields, and many other exposures and, therefore, can be used in other case control studies. JF - American Industrial Hygiene Association journal AU - Stewart, P A AU - Stewart, W F AU - Siemiatycki, J AU - Heineman, E F AU - Dosemeci, M AD - Occupational Studies Section, National Cancer Institute, Bethesda, MD 20892-7364, USA. Y1 - 1998/01// PY - 1998 DA - January 1998 SP - 39 EP - 44 VL - 59 IS - 1 SN - 0002-8894, 0002-8894 KW - Index Medicus KW - Reproducibility of Results KW - Humans KW - Occupational Diseases -- etiology KW - Brain Neoplasms -- etiology KW - Occupational Exposure KW - Surveys and Questionnaires -- standards KW - Occupational Health KW - Interviews as Topic -- standards KW - Job Description KW - Case-Control Studies KW - Workplace KW - Medical History Taking -- standards UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79660607?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Industrial+Hygiene+Association+journal&rft.atitle=Questionnaires+for+collecting+detailed+occupational+information+for+community-based+case+control+studies.&rft.au=Stewart%2C+P+A%3BStewart%2C+W+F%3BSiemiatycki%2C+J%3BHeineman%2C+E+F%3BDosemeci%2C+M&rft.aulast=Stewart&rft.aufirst=P&rft.date=1998-01-01&rft.volume=59&rft.issue=1&rft.spage=39&rft.isbn=&rft.btitle=&rft.title=American+Industrial+Hygiene+Association+journal&rft.issn=00028894&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-02-05 N1 - Date created - 1998-02-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ethics of randomized clinical trials. AN - 79659755; 9440766 JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Emanuel, E J AU - Patterson, W B AD - Dana-Farber Cancer Institute, Boston, MA 02115-6084, USA. eemanuel@nih.gov Y1 - 1998/01// PY - 1998 DA - January 1998 SP - 365 EP - 6; discussion 366-71 VL - 16 IS - 1 SN - 0732-183X, 0732-183X KW - Doxorubicin KW - 80168379AG KW - Cyclophosphamide KW - 8N3DW7272P KW - Paclitaxel KW - P88XT4IS4D KW - Cisplatin KW - Q20Q21Q62J KW - Fluorouracil KW - U3P01618RT KW - Methotrexate KW - YL5FZ2Y5U1 KW - Bioethics KW - Index Medicus KW - Biomedical and Behavioral Research KW - Professional Patient Relationship KW - Cyclophosphamide -- administration & dosage KW - Paclitaxel -- administration & dosage KW - Researcher-Subject Relations KW - Humans KW - Professional-Family Relations KW - Prognosis KW - Comprehension KW - Doxorubicin -- administration & dosage KW - Disclosure KW - Risk Assessment KW - Cisplatin -- administration & dosage KW - Fluorouracil -- administration & dosage KW - Uncertainty KW - Adult KW - Ethical Theory KW - Personal Autonomy KW - Methotrexate -- administration & dosage KW - Female KW - Breast Neoplasms -- drug therapy KW - Carcinoma, Ductal, Breast -- drug therapy KW - Carcinoma, Ductal, Breast -- psychology KW - Breast Neoplasms -- psychology KW - Patient Advocacy KW - Ethics, Medical KW - Randomized Controlled Trials as Topic -- psychology KW - Randomized Controlled Trials as Topic -- standards KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Therapeutic Human Experimentation KW - Physician-Patient Relations UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79659755?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Ethics+of+randomized+clinical+trials.&rft.au=Emanuel%2C+E+J%3BPatterson%2C+W+B&rft.aulast=Emanuel&rft.aufirst=E&rft.date=1998-01-01&rft.volume=16&rft.issue=1&rft.spage=365&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 - 1998-01-27 N1 - Date created - 1998-01-27 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Clin Oncol. 1998 Jul;16(7):2570 [9667280] J Clin Oncol. 1998 Apr;16(4):1637 [9552081] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Drinking water source and chlorination byproducts. II. Risk of colon and rectal cancers. AN - 79655388; 9430265 AB - We evaluated the association between chlorination byproducts and colon and rectal cancer risk in a population-based case-control study conducted in Iowa in 1986-1989. Data were gathered from 685 colon cancer cases, 655 rectal cancer cases, and 2,434 controls. We calculated odds ratios for the 560 colon cancer cases, 537 rectal cancer cases, and 1,983 controls for whom water exposure information was available for at least 70% of their lifetime. We estimated exposure to chlorination byproducts with two types of measures: duration of lifetime at residences served by chlorinated water and estimated lifetime trihalomethane exposure. For rectal cancer, we observed an association with duration of chlorinated surface water use, with adjusted odds ratios of 1.1, 1.6, 1.6, and 2.6 for 1-19, 20-39, 40-59, and > or =60 years of exposure, compared with no exposure. Rectal cancer risk was also associated with several different measures of estimated lifetime trihalomethane exposure. For colon cancer and subsites, we detected no important increase in risk associated with duration of chlorinated surface water, nor with trihalomethane estimates. When we evaluated chlorination byproducts jointly with other factors, we found larger relative risk estimates for rectal cancer among subjects with low dietary fiber intake. The risk related to > or =40 years of exposure to a chlorinated surface water source was 2.4 (95% confidence interval = 1.5-4.0) for persons with low fiber intake and 0.9 (95% confidence interval = 0.4-1.8) for persons with high fiber intake, relative to the risk of persons with high-fiber diets and no exposure to chlorinated surface water. We observed a similar risk differential for low and high levels of physical activity. JF - Epidemiology (Cambridge, Mass.) AU - Hildesheim, M E AU - Cantor, K P AU - Lynch, C F AU - Dosemeci, M AU - Lubin, J AU - Alavanja, M AU - Craun, G AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1998/01// PY - 1998 DA - January 1998 SP - 29 EP - 35 VL - 9 IS - 1 SN - 1044-3983, 1044-3983 KW - Chlorofluorocarbons, Methane KW - 0 KW - Chlorine KW - 4R7X1O2820 KW - Index Medicus KW - Odds Ratio KW - Chlorofluorocarbons, Methane -- analysis KW - Dietary Fiber -- administration & dosage KW - Aged, 80 and over KW - Risk Factors KW - Humans KW - Adult KW - Case-Control Studies KW - Confidence Intervals KW - Aged KW - Middle Aged KW - Iowa -- epidemiology KW - Colonic Neoplasms -- epidemiology KW - Chlorine -- analysis KW - Colonic Neoplasms -- etiology KW - Water Supply KW - Rectal Neoplasms -- etiology KW - Chlorine -- adverse effects KW - Rectal Neoplasms -- epidemiology KW - Water Purification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79655388?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Epidemiology+%28Cambridge%2C+Mass.%29&rft.atitle=Drinking+water+source+and+chlorination+byproducts.+II.+Risk+of+colon+and+rectal+cancers.&rft.au=Hildesheim%2C+M+E%3BCantor%2C+K+P%3BLynch%2C+C+F%3BDosemeci%2C+M%3BLubin%2C+J%3BAlavanja%2C+M%3BCraun%2C+G&rft.aulast=Hildesheim&rft.aufirst=M&rft.date=1998-01-01&rft.volume=9&rft.issue=1&rft.spage=29&rft.isbn=&rft.btitle=&rft.title=Epidemiology+%28Cambridge%2C+Mass.%29&rft.issn=10443983&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-02-05 N1 - Date created - 1998-02-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Drinking water source and chlorination byproducts. I. Risk of bladder cancer. AN - 79653318; 9430264 AB - We conducted a population-based case-control study of bladder cancer in Iowa in 1986-1989 to evaluate the risk posed by tapwater containing chlorination byproducts. We combined information about residential history, drinking water source, beverage intake, and other factors with historical data from water utilities and measured contaminant levels to create indices of past exposure to chlorination byproducts. The study comprised 1,123 cases and 1,983 controls who had data relating to at least 70% of their lifetime drinking water source. After we adjusted for potential confounders, we calculated odds ratios for duration of chlorinated surface water of 1.0 (referent), 1.0, 1.1, 1.2, and 1.5 for 0, 1-19, 20-39, 40-59, and > or =60 years of use. We also found associations with total and average lifetime byproduct intake, as represented by trihalomethane estimates. Positive findings were restricted to men and to ever-smokers. Among men, odds ratios were 1.0 (referent), 1.1, 1.3, 1.5, and 1.9, and among ever-smokers, 1.0, 1.1, 1.3, 1.8, and 2.2, after adjustment for intensity and timing of smoking. Among nonsmoking men and women, regardless of smoking habit, there was no association. Among men, smoking and exposure to chlorinated surface water mutually enhanced the risk of bladder cancer. The overall association of bladder cancer risk with duration of chlorinated surface water use that we found is consistent with the findings of other investigations, but the differences in risk between men and women, and between smokers and nonsmokers, have not been widely observed. JF - Epidemiology (Cambridge, Mass.) AU - Cantor, K P AU - Lynch, C F AU - Hildesheim, M E AU - Dosemeci, M AU - Lubin, J AU - Alavanja, M AU - Craun, G AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1998/01// PY - 1998 DA - January 1998 SP - 21 EP - 28 VL - 9 IS - 1 SN - 1044-3983, 1044-3983 KW - Chlorofluorocarbons, Methane KW - 0 KW - Chlorine KW - 4R7X1O2820 KW - Index Medicus KW - Odds Ratio KW - Humans KW - Aged KW - Chlorofluorocarbons, Methane -- analysis KW - Aged, 80 and over KW - Risk Factors KW - Adult KW - Confounding Factors (Epidemiology) KW - Case-Control Studies KW - Middle Aged KW - Female KW - Iowa -- epidemiology KW - Male KW - Urinary Bladder Neoplasms -- etiology KW - Chlorine -- analysis KW - Urinary Bladder Neoplasms -- epidemiology KW - Water Supply KW - Chlorine -- adverse effects KW - Water Purification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79653318?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Epidemiology+%28Cambridge%2C+Mass.%29&rft.atitle=Drinking+water+source+and+chlorination+byproducts.+I.+Risk+of+bladder+cancer.&rft.au=Cantor%2C+K+P%3BLynch%2C+C+F%3BHildesheim%2C+M+E%3BDosemeci%2C+M%3BLubin%2C+J%3BAlavanja%2C+M%3BCraun%2C+G&rft.aulast=Cantor&rft.aufirst=K&rft.date=1998-01-01&rft.volume=9&rft.issue=1&rft.spage=21&rft.isbn=&rft.btitle=&rft.title=Epidemiology+%28Cambridge%2C+Mass.%29&rft.issn=10443983&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-02-05 N1 - Date created - 1998-02-05 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Epidemiology. 1998 Jan;9(1):7-8 [9430261] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Disruption of the pRb/E2F pathway and inhibition of apoptosis are major oncogenic events in liver constitutively expressing c-myc and transforming growth factor alpha. AN - 79641115; 9426068 AB - The oncogene c-myc and transforming growth factor (TGF) alpha are frequently coexpressed in human cancers, suggesting that their interaction may be a critical step in malignant growth. Consistent with this idea, we recently demonstrated in a transgenic mouse model that TGF-alpha dramatically enhances c-myc-induced hepatocarcinogenesis. To elucidate this synergistic effect, we have now investigated regulation of cell cycle and apoptosis during neoplastic development in the liver of c-myc and c-myc/TGFalpha transgenic mice. Both lines displayed dramatic increases of mitotic and apoptotic rates before the onset of hepatocellular carcinoma (HCC), but only c-myc/TGF-alpha livers showed significant levels of net proliferation (mitosis minus apoptosis). Subsequently, mitosis declined in peritumorous tissues, concomitant with the previously reported induction of TGF-beta1, whereas c-myc and c-myc/TGFalpha HCCs maintained mitotic hyperactivity. The c-myc/TGF-alpha HCCs were also characterized by a particularly strong expression of TGF-alpha and very low apoptotic index in contrast to high levels of apoptosis in peritumorous tissues and c-myc HCCs. The differential levels of cell proliferation in noncancerous and cancerous tissues correlated with a stronger induction of cyclin D1 mRNA and protein in c-myc/TGF-alpha and c-myc HCCs associated with intense pRb hyperphosphorylation. Severe deregulation of G1-S transition was also indicated by the dramatic up-regulation, particularly in the HCCs, of pRb-free E2F1-DP1 and E2F2-DP1 transcription factor heterodimers, as assessed by immunoprecipitation and immunohistochemistry. The existence of increased E2F activity during hepatocarcinogenesis was further indicated by the transcriptional induction of putative E2F target genes involved in cell cycle progression, such as endogenous c-myc, cyclin A, Cdc2, and E2F itself. Cdc2 overexpression and the elevated mitotic indices in the HCCs correlated also with induction of cyclin B steady-state levels. The data suggest that coexpression of c-myc and TGF-alpha leads to a selective growth advantage for hepatic (pre)neoplastic cells by disrupting the pRb/E2F pathway and by TGF-alpha-mediated reduction of apoptosis. JF - Cancer research AU - Santoni-Rugiu, E AU - Jensen, M R AU - Thorgeirsson, S S AD - Laboratory of Experimental Carcinogenesis, Division of Basic Sciences, National Cancer Institute, Bethesda, Maryland 20892-4255, USA. Y1 - 1998/01/01/ PY - 1998 DA - 1998 Jan 01 SP - 123 EP - 134 VL - 58 IS - 1 SN - 0008-5472, 0008-5472 KW - Arid4a protein, mouse KW - 0 KW - Carrier Proteins KW - Cell Cycle Proteins KW - DNA-Binding Proteins KW - E2F Transcription Factors KW - E2F1 Transcription Factor KW - E2F2 Transcription Factor KW - E2f1 protein, mouse KW - Neoplasm Proteins KW - Proto-Oncogene Proteins c-myc KW - Retinoblastoma Protein KW - Retinoblastoma-Binding Protein 1 KW - Tfdp1 protein, mouse KW - Transcription Factor DP1 KW - Transcription Factors KW - Transforming Growth Factor alpha KW - CDC2 Protein Kinase KW - EC 2.7.11.22 KW - Index Medicus KW - Animals KW - CDC2 Protein Kinase -- metabolism KW - Transgenes KW - S Phase KW - Mice KW - Mice, Transgenic KW - Cell Cycle Proteins -- metabolism KW - Phosphorylation KW - G1 Phase KW - Mitotic Index KW - Cell Division KW - Apoptosis KW - Transcription Factors -- metabolism KW - Liver Neoplasms, Experimental -- metabolism KW - Proto-Oncogene Proteins c-myc -- genetics KW - Proto-Oncogene Proteins c-myc -- metabolism KW - Transforming Growth Factor alpha -- metabolism KW - Transcription Factors -- genetics KW - Transforming Growth Factor alpha -- genetics KW - Liver Neoplasms, Experimental -- etiology KW - Liver Neoplasms, Experimental -- pathology KW - Neoplasm Proteins -- genetics KW - Retinoblastoma Protein -- metabolism KW - Neoplasm Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79641115?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Disruption+of+the+pRb%2FE2F+pathway+and+inhibition+of+apoptosis+are+major+oncogenic+events+in+liver+constitutively+expressing+c-myc+and+transforming+growth+factor+alpha.&rft.au=Santoni-Rugiu%2C+E%3BJensen%2C+M+R%3BThorgeirsson%2C+S+S&rft.aulast=Santoni-Rugiu&rft.aufirst=E&rft.date=1998-01-01&rft.volume=58&rft.issue=1&rft.spage=123&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 - 1998-01-20 N1 - Date created - 1998-01-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interleukin-15 augments superoxide production and microbicidal activity of human monocytes against Candida albicans. AN - 79634997; 9423851 AB - Interleukin-15 (IL-15) is a newly described cytokine that shares biological activities with IL-2. We report here results demonstrating the ability of IL-15 to enhance superoxide production and antifungal activity of human monocytes. After 18 and 48 h of treatment with IL-15, human elutriated monocytes manifested enhanced superoxide production in response to either phorbol myristate acetate or opsonized Candida albicans blastoconidia. Similar results were obtained when monocytes were treated with IL-2, but to a lesser extent. Combination studies with IL-15 and IL-2 showed no additive or synergistic effects. Following incubation of monocytes with IL-15 for 18 h, there was no significant increase in mRNA transcripts for components of the NADPH oxidase complex, p40-phox, p47-phox, and gp91-phox, suggesting a posttranscriptional modulation of enhanced superoxide production. Antibodies against the gamma chain of the IL-2 receptor and, to a lesser extent, against the beta chain partially abrogated the IL-15-mediated enhanced superoxide production. Additionally, human monocytes showed enhanced killing activity against C. albicans after 18 h of incubation with IL-15 or IL-2, but this treatment did not enhance the ability of these cells to phagocytose the organism. In addition, the enhanced fungicidal activity seen after 18 h of treatment was no longer detectable after 48 h of cytokine treatment. Culture supernatants from the IL-15-treated monocytes were assayed for the presence of other proinflammatory cytokines. IL-15 treatment did not induce the release of detectable levels of tumor necrosis factor alpha, IL-1beta, or IL-12. Our results indicate that IL-15 upregulates the microbicidal activity of human monocytes against C. albicans. JF - Infection and immunity AU - Vázquez, N AU - Walsh, T J AU - Friedman, D AU - Chanock, S J AU - Lyman, C A AD - Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/01// PY - 1998 DA - January 1998 SP - 145 EP - 150 VL - 66 IS - 1 SN - 0019-9567, 0019-9567 KW - CYBB protein, human KW - 0 KW - Culture Media, Conditioned KW - Interleukin-1 KW - Interleukin-15 KW - Interleukin-2 KW - Membrane Glycoproteins KW - Phosphoproteins KW - Receptors, Interleukin-2 KW - Tumor Necrosis Factor-alpha KW - neutrophil cytosol factor 40K KW - Superoxides KW - 11062-77-4 KW - Interleukin-12 KW - 187348-17-0 KW - NADPH Oxidase KW - EC 1.6.3.1 KW - neutrophil cytosolic factor 1 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - NADPH Oxidase -- metabolism KW - Interleukin-2 -- pharmacology KW - Humans KW - Phagocytosis -- immunology KW - Culture Media, Conditioned -- analysis KW - Receptors, Interleukin-2 -- immunology KW - Interleukin-12 -- metabolism KW - Interleukin-1 -- metabolism KW - Respiratory Burst -- immunology KW - Neutralization Tests KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Cytotoxicity Tests, Immunologic KW - Interleukin-2 -- immunology KW - Tumor Necrosis Factor-alpha -- metabolism KW - Membrane Glycoproteins -- metabolism KW - Phosphoproteins -- metabolism KW - Superoxides -- metabolism KW - Monocytes -- immunology KW - Monocytes -- metabolism KW - Interleukin-15 -- pharmacology KW - Candida albicans -- immunology KW - Interleukin-15 -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79634997?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Infection+and+immunity&rft.atitle=Interleukin-15+augments+superoxide+production+and+microbicidal+activity+of+human+monocytes+against+Candida+albicans.&rft.au=V%C3%A1zquez%2C+N%3BWalsh%2C+T+J%3BFriedman%2C+D%3BChanock%2C+S+J%3BLyman%2C+C+A&rft.aulast=V%C3%A1zquez&rft.aufirst=N&rft.date=1998-01-01&rft.volume=66&rft.issue=1&rft.spage=145&rft.isbn=&rft.btitle=&rft.title=Infection+and+immunity&rft.issn=00199567&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-01-27 N1 - Date created - 1998-01-27 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cytokine. 1996 Jan;8(1):42-8 [8742065] Immunodeficiency. 1993;4(1-4):187-90 [8167697] EMBO J. 1996 Sep 16;15(18):4928-39 [8890166] Nat Med. 1997 Feb;3(2):189-95 [9018238] J Immunol. 1997 Jun 15;158(12):5978-87 [9190952] Blood. 1997 Oct 1;90(7):2804-9 [9326248] Biochim Biophys Acta. 1959 Jul;34:255-6 [14422133] J Clin Invest. 1975 Jun;55(6):1357-72 [166094] J Exp Med. 1983 Sep 1;158(3):670-89 [6411853] Cell Immunol. 1984 May;85(2):373-83 [6232002] Nature. 1987 Jan 15-21;325(6101):262-5 [3100957] J Immunol. 1987 Aug 15;139(4):1342-7 [3039002] Science. 1994 May 13;264(5161):965-8 [8178155] Proc Natl Acad Sci U S A. 1994 May 24;91(11):4935-9 [8197160] EMBO J. 1994 Jun 15;13(12):2822-30 [8026467] J Exp Med. 1994 Oct 1;180(4):1395-403 [7523571] Blood. 1995 Jan 1;85(1):38-42 [7803808] J Immunol. 1995 Jan 15;154(2):483-90 [7814861] J Leukoc Biol. 1995 Jan;57(1):13-9 [7829965] J Exp Med. 1995 Mar 1;181(3):1255-9 [7869044] J Immunol. 1995 Jul 15;155(2):785-95 [7608555] EMBO J. 1995 Aug 1;14(15):3654-63 [7641685] J Exp Med. 1995 Oct 1;182(4):1067-77 [7561680] Int J Immunopharmacol. 1995 May;17(5):385-92 [7591362] J Immunol. 1996 Jan 15;156(2):663-9 [8543818] J Immunol. 1996 Jan 15;156(2):735-41 [8543827] Exp Hematol. 1996 Mar;24(4):559-67 [8608807] Exp Hematol. 1996 Feb;24(2):151-7 [8641336] J Immunol. 1996 Sep 1;157(5):2103-8 [8757333] Immunobiology. 1988 Apr;177(1):32-9 [2838419] Proc Natl Acad Sci U S A. 1988 Jul;85(14):5215-9 [2839835] J Immunol. 1989 Jul 15;143(2):671-7 [2661688] J Infect Dis. 1990 May;161(5):999-1005 [2157774] J Biol Chem. 1990 Nov 25;265(33):20241-6 [2173701] Infect Immun. 1991 Oct;59(10):3393-7 [1894353] J Pediatr. 1991 Dec;119(6):845-57 [1660069] J Clin Invest. 1996 Mar 15;97(6):1373-81 [8617868] J Clin Invest. 1995 Dec;96(6):2578-82 [8675621] Cancer Res. 1992 May 1;52(9):2530-7 [1568222] Leuk Res. 1992 Jun-Jul;16(6-7):703-9 [1321933] Clin Infect Dis. 1992 Sep;15(3):508-24 [1520801] Am J Hematol. 1993 Aug;43(4):279-85 [8396850] Immunodeficiency. 1993;4(1-4):181-5 [8167696] Exp Hematol. 1996 Feb;24(2):169-75 [8641338] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phosphorylation of dopamine transporters and rapid adaptation to cocaine. AN - 79632707; 9328076 JF - Advances in pharmacology (San Diego, Calif.) AU - Vaughan, R A AU - Huff, R A AU - Uhl, G R AU - Kuhar, M J AD - National Institute on Drug Abuse Intramural Research Program, Baltimore, Maryland 21224, USA. Y1 - 1998 PY - 1998 DA - 1998 SP - 1042 EP - 1045 VL - 42 SN - 1054-3589, 1054-3589 KW - Carrier Proteins KW - 0 KW - Dopamine Plasma Membrane Transport Proteins KW - Membrane Glycoproteins KW - Membrane Transport Proteins KW - Nerve Tissue Proteins KW - Phorbol Esters KW - Phosphoproteins KW - phorbol-12,13-didecanoate KW - 24928-17-4 KW - Protein Kinases KW - EC 2.7.- KW - Cocaine KW - I5Y540LHVR KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Rats KW - Protein Kinases -- metabolism KW - Phorbol Esters -- pharmacology KW - Animals KW - Synaptosomes -- drug effects KW - Phosphorylation KW - Corpus Striatum -- metabolism KW - Substance-Related Disorders KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Nerve Tissue Proteins -- metabolism KW - Synaptosomes -- metabolism KW - Carrier Proteins -- metabolism KW - Phosphoproteins -- isolation & purification KW - Cocaine -- pharmacology KW - Phosphoproteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79632707?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Advances+in+pharmacology+%28San+Diego%2C+Calif.%29&rft.atitle=Phosphorylation+of+dopamine+transporters+and+rapid+adaptation+to+cocaine.&rft.au=Vaughan%2C+R+A%3BHuff%2C+R+A%3BUhl%2C+G+R%3BKuhar%2C+M+J&rft.aulast=Vaughan&rft.aufirst=R&rft.date=1998-01-01&rft.volume=42&rft.issue=&rft.spage=1042&rft.isbn=&rft.btitle=&rft.title=Advances+in+pharmacology+%28San+Diego%2C+Calif.%29&rft.issn=10543589&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-11-25 N1 - Date created - 1997-11-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Quinolinic acid in vivo synthesis rates, extracellular concentrations, and intercompartmental distributions in normal and immune-activated brain as determined by multiple-isotope microdialysis. AN - 79632584; 9422373 AB - Quinolinic acid (QUIN) kills neurons by activation of NMDA receptors that are accessed via the extracellular fluid (ECF). In vivo microdialysis was employed to quantify the dynamics of ECF QUIN levels. [(13)C7]QUIN was perfused through the probe for in vivo calibration to accurately quantify ECF QUIN concentrations. Osmotic pumps infused [(2H)3]QUIN subcutaneously to quantify blood contributions to ECF and tissue levels. Local QUIN production rates and influx and efflux rates across the blood-brain barrier were calculated from the extraction fraction of [(13)C7]QUIN, probe geometry, tissue diffusion coefficients, the extracellular volume fraction, and [(2)H3]QUIN/QUIN ratios in blood and dialysates. In normal brain, 85% of ECF QUIN levels (110 nM) originated from blood, whereas 59% of tissue homogenate QUIN (130 pmol/g) originated from local de novo synthesis. During systemic immune activation (intraperitoneal injection of endotoxin), blood QUIN levels increased (10.2-fold) and caused a rise in homogenate (10.8-fold) and ECF (18.5-fold) QUIN levels with an increase in the proportions of QUIN derived from blood. During CNS inflammation (local infusion of endotoxin), increases in brain homogenate (246-fold) and ECF (66-fold) QUIN levels occurred because of an increase in local synthesis rate (146-fold) and a reduction in efflux/influx ratio (by 53%). These results demonstrate that brain homogenate measures are a reflection of ECF concentrations, although there are quantitative differences in the values obtained. The mechanisms that maintain ECF QUIN levels at low values cannot do so when there are large increases in local brain synthesis or when there are large elevations in blood QUIN concentrations. JF - Journal of neurochemistry AU - Beagles, K E AU - Morrison, P F AU - Heyes, M P AD - Laboratory of Neurotoxicology, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892-1262, USA. Y1 - 1998/01// PY - 1998 DA - January 1998 SP - 281 EP - 291 VL - 70 IS - 1 SN - 0022-3042, 0022-3042 KW - Endotoxins KW - 0 KW - Isotopes KW - Quinolinic Acid KW - F6F0HK1URN KW - Index Medicus KW - Osmolar Concentration KW - Injections, Intraperitoneal KW - Animals KW - Gerbillinae KW - Reference Values KW - Corpus Striatum -- metabolism KW - Blood-Brain Barrier -- physiology KW - Encephalomyelitis -- chemically induced KW - Tissue Distribution KW - Endotoxins -- pharmacology KW - Microdialysis -- methods KW - Administration, Topical KW - Female KW - Encephalomyelitis -- metabolism KW - Quinolinic Acid -- metabolism KW - Extracellular Space -- metabolism KW - Brain -- metabolism KW - Brain -- immunology KW - Immune System -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79632584?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Quinolinic+acid+in+vivo+synthesis+rates%2C+extracellular+concentrations%2C+and+intercompartmental+distributions+in+normal+and+immune-activated+brain+as+determined+by+multiple-isotope+microdialysis.&rft.au=Beagles%2C+K+E%3BMorrison%2C+P+F%3BHeyes%2C+M+P&rft.aulast=Beagles&rft.aufirst=K&rft.date=1998-01-01&rft.volume=70&rft.issue=1&rft.spage=281&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 - 1998-02-02 N1 - Date created - 1998-02-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Free radicals and MPTP-induced selective destruction of substantia nigra compacta neurons. AN - 79632384; 9328018 JF - Advances in pharmacology (San Diego, Calif.) AU - Chiueh, C C AU - Rauhala, P AD - Unit on Neurotoxicology and Neuroprotection, National Institute of Mental Health, Bethesda, Maryland 20892, USA. Y1 - 1998 PY - 1998 DA - 1998 SP - 796 EP - 800 VL - 42 SN - 1054-3589, 1054-3589 KW - Antioxidants KW - 0 KW - Free Radicals KW - Melanins KW - Reactive Oxygen Species KW - Hydroxyl Radical KW - 3352-57-6 KW - 1-Methyl-4-phenylpyridinium KW - R865A5OY8J KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Rats KW - Animals KW - 1-Methyl-4-phenylpyridinium -- toxicity KW - Hydroxyl Radical -- metabolism KW - Free Radicals -- metabolism KW - PC12 Cells KW - Substantia Nigra -- metabolism KW - Reactive Oxygen Species -- metabolism KW - Neurons -- metabolism KW - Antioxidants -- pharmacology KW - Substantia Nigra -- pathology KW - Neurons -- drug effects KW - MPTP Poisoning KW - Melanins -- metabolism KW - Oxidative Stress -- drug effects KW - Substantia Nigra -- drug effects KW - Dopamine -- metabolism KW - Neurons -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79632384?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Advances+in+pharmacology+%28San+Diego%2C+Calif.%29&rft.atitle=Free+radicals+and+MPTP-induced+selective+destruction+of+substantia+nigra+compacta+neurons.&rft.au=Chiueh%2C+C+C%3BRauhala%2C+P&rft.aulast=Chiueh&rft.aufirst=C&rft.date=1998-01-01&rft.volume=42&rft.issue=&rft.spage=796&rft.isbn=&rft.btitle=&rft.title=Advances+in+pharmacology+%28San+Diego%2C+Calif.%29&rft.issn=10543589&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-11-25 N1 - Date created - 1997-11-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The rate hypothesis and agonist substitution approaches to cocaine abuse treatment. AN - 79631545; 9328065 JF - Advances in pharmacology (San Diego, Calif.) AU - Gorelick, D A AD - Treatment Branch, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 21224, USA. Y1 - 1998 PY - 1998 DA - 1998 SP - 995 EP - 997 VL - 42 SN - 1054-3589, 1054-3589 KW - Dopamine Uptake Inhibitors KW - 0 KW - Piperazines KW - Bupropion KW - 01ZG3TPX31 KW - vanoxerine KW - 90X28IKH43 KW - Mazindol KW - C56709M5NH KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Animals KW - Bupropion -- therapeutic use KW - Piperazines -- therapeutic use KW - Humans KW - Dopamine Uptake Inhibitors -- therapeutic use KW - Mazindol -- therapeutic use KW - Substance-Related Disorders -- physiopathology KW - Substance-Related Disorders -- drug therapy KW - Cocaine -- pharmacokinetics KW - Substance-Related Disorders -- psychology KW - Cocaine -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79631545?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Advances+in+pharmacology+%28San+Diego%2C+Calif.%29&rft.atitle=The+rate+hypothesis+and+agonist+substitution+approaches+to+cocaine+abuse+treatment.&rft.au=Gorelick%2C+D+A&rft.aulast=Gorelick&rft.aufirst=D&rft.date=1998-01-01&rft.volume=42&rft.issue=&rft.spage=995&rft.isbn=&rft.btitle=&rft.title=Advances+in+pharmacology+%28San+Diego%2C+Calif.%29&rft.issn=10543589&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-11-25 N1 - Date created - 1997-11-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Blockade and recovery of spontaneous rhythmic activity after application of neurotransmitter antagonists to spinal networks of the chick embryo. AN - 79629190; 9412508 AB - We studied the regulation of spontaneous activity in the embryonic (day 10-11) chick spinal cord. After bath application of either an excitatory amino acid (AP-5 or CNQX) and a nicotinic cholinergic (DHbetaE or mecamylamine) antagonist, or glycine and GABA receptor (bicuculline, 2-hydroxysaclofen, and strychnine) antagonists, spontaneous activity was blocked for a period (30-90 min) but then reappeared in the presence of the drugs. The efficacy of the antagonists was assessed by their continued ability to block spinal reflex pathways during the reappearance of spontaneous activity. Spontaneous activity ceased over the 4-5 hour monitoring period when both sets of antagonists were applied together. After application of glycine and GABA receptor antagonists, the frequency of occurrence of spontaneous episodes slowed and became highly variable. By contrast, during glutamatergic and nicotinic cholinergic blockade, the frequency of occurrence of spontaneous episodes initially slowed and then recovered to stabilize near the predrug level of activity. Whole-cell recordings made from ventral spinal neurons revealed that this recovery was accompanied by an increase in the amplitude of spontaneously occurring synaptic events. We also measured changes in the apparent equilibrium potential of the rhythmic, synaptic drive of ventral spinal neurons using voltage or discontinuous current clamp. After excitatory blockade, the apparent equilibrium potential of the rhythmic synaptic drive shifted approximately 10 mV more negative to approximately -30 mV. In the presence of bicuculline, the apparent equilibrium potential of the synaptic drive shifted toward the glutamate equilibrium potential. Considered with other evidence, these findings suggest that spontaneous rhythmic output is a general property of developing spinal networks, and that GABA and glycinergic networks alter their function to compensate for the blockade of excitatory transmission. JF - The Journal of neuroscience : the official journal of the Society for Neuroscience AU - Chub, N AU - O'Donovan, M J AD - Section on Developmental Neurobiology, Laboratory of Neural Control, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/01/01/ PY - 1998 DA - 1998 Jan 01 SP - 294 EP - 306 VL - 18 IS - 1 SN - 0270-6474, 0270-6474 KW - Cholinergic Antagonists KW - 0 KW - Excitatory Amino Acid Antagonists KW - GABA Antagonists KW - GABA-A Receptor Antagonists KW - Glycine Agents KW - Neurotransmitter Agents KW - Nicotinic Antagonists KW - phaclofen KW - 108351-35-5 KW - 2-hydroxysaclofen KW - 117354-64-0 KW - Dihydro-beta-Erythroidine KW - 23255-54-1 KW - Mecamylamine KW - 6EE945D3OK KW - 6-Cyano-7-nitroquinoxaline-2,3-dione KW - 6OTE87SCCW KW - 2-Amino-5-phosphonovalerate KW - 76726-92-6 KW - Baclofen KW - H789N3FKE8 KW - Strychnine KW - H9Y79VD43J KW - Glycine KW - TE7660XO1C KW - Bicuculline KW - Y37615DVKC KW - Index Medicus KW - Bicuculline -- pharmacology KW - Animals KW - Dihydro-beta-Erythroidine -- pharmacology KW - Chick Embryo KW - 6-Cyano-7-nitroquinoxaline-2,3-dione -- pharmacology KW - Evoked Potentials -- physiology KW - Mecamylamine -- pharmacology KW - Baclofen -- analogs & derivatives KW - Action Potentials -- drug effects KW - Cholinergic Antagonists -- pharmacology KW - GABA Antagonists -- pharmacology KW - Excitatory Amino Acid Antagonists -- pharmacology KW - 2-Amino-5-phosphonovalerate -- pharmacology KW - Glycine -- pharmacology KW - Nicotinic Antagonists -- pharmacology KW - Strychnine -- pharmacology KW - Neuronal Plasticity -- drug effects KW - Periodicity KW - Glycine Agents -- pharmacology KW - Baclofen -- pharmacology KW - Motor Neurons -- physiology KW - Neurotransmitter Agents -- physiology KW - Neurotransmitter Agents -- antagonists & inhibitors KW - Motor Neurons -- drug effects KW - Spinal Cord -- cytology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79629190?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Blockade+and+recovery+of+spontaneous+rhythmic+activity+after+application+of+neurotransmitter+antagonists+to+spinal+networks+of+the+chick+embryo.&rft.au=Chub%2C+N%3BO%27Donovan%2C+M+J&rft.aulast=Chub&rft.aufirst=N&rft.date=1998-01-01&rft.volume=18&rft.issue=1&rft.spage=294&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 - 1998-01-16 N1 - Date created - 1998-01-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dopaminergic genes and substance abuse. AN - 79628893; 9328073 JF - Advances in pharmacology (San Diego, Calif.) AU - Uhl, G R AU - Vandenbergh, D J AU - Rodriguez, L A AU - Miner, L AU - Takahashi, N AD - Molecular Neurobiology Branch, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 21224, USA. Y1 - 1998 PY - 1998 DA - 1998 SP - 1024 EP - 1032 VL - 42 SN - 1054-3589, 1054-3589 KW - Carrier Proteins KW - 0 KW - DRD4 protein, human KW - Dopamine Plasma Membrane Transport Proteins KW - Drd4 protein, mouse KW - Membrane Glycoproteins KW - Membrane Transport Proteins KW - Nerve Tissue Proteins KW - Neuropeptides KW - Receptors, Dopamine KW - Receptors, Dopamine D2 KW - Vesicular Biogenic Amine Transport Proteins KW - Receptors, Dopamine D4 KW - 137750-34-6 KW - Catechol O-Methyltransferase KW - EC 2.1.1.6 KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Animals KW - Alleles KW - Disease Susceptibility KW - Polymorphism, Genetic KW - Humans KW - Mice KW - Receptors, Dopamine D2 -- genetics KW - Mice, Transgenic KW - Catechol O-Methyltransferase -- genetics KW - Membrane Glycoproteins -- biosynthesis KW - Carrier Proteins -- genetics KW - Receptors, Dopamine -- genetics KW - Dopamine -- metabolism KW - Substance-Related Disorders -- metabolism KW - Substance-Related Disorders -- genetics KW - Carrier Proteins -- biosynthesis KW - Membrane Glycoproteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79628893?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Advances+in+pharmacology+%28San+Diego%2C+Calif.%29&rft.atitle=Dopaminergic+genes+and+substance+abuse.&rft.au=Uhl%2C+G+R%3BVandenbergh%2C+D+J%3BRodriguez%2C+L+A%3BMiner%2C+L%3BTakahashi%2C+N&rft.aulast=Uhl&rft.aufirst=G&rft.date=1998-01-01&rft.volume=42&rft.issue=&rft.spage=1024&rft.isbn=&rft.btitle=&rft.title=Advances+in+pharmacology+%28San+Diego%2C+Calif.%29&rft.issn=10543589&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-11-25 N1 - Date created - 1997-11-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Neurobiological substrates underlying conditioned effects of cocaine. AN - 79628844; 9328064 JF - Advances in pharmacology (San Diego, Calif.) AU - Pert, A AD - Biological Psychiatry Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998 PY - 1998 DA - 1998 SP - 991 EP - 995 VL - 42 SN - 1054-3589, 1054-3589 KW - Dopamine Antagonists KW - 0 KW - Excitatory Amino Acid Antagonists KW - Receptors, Dopamine D1 KW - Receptors, Dopamine D2 KW - Dizocilpine Maleate KW - 6LR8C1B66Q KW - Cocaine KW - I5Y540LHVR KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Rats KW - Brain -- physiopathology KW - Animals KW - Receptors, Dopamine D1 -- physiology KW - Humans KW - Brain -- drug effects KW - Motor Activity -- drug effects KW - Receptors, Dopamine D2 -- physiology KW - Brain -- physiology KW - Excitatory Amino Acid Antagonists -- pharmacology KW - Dizocilpine Maleate -- pharmacology KW - Substance-Related Disorders -- physiopathology KW - Dopamine Antagonists -- pharmacology KW - Conditioning (Psychology) -- physiology KW - Dopamine -- physiology KW - Cocaine -- pharmacology KW - Conditioning (Psychology) -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79628844?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Advances+in+pharmacology+%28San+Diego%2C+Calif.%29&rft.atitle=Neurobiological+substrates+underlying+conditioned+effects+of+cocaine.&rft.au=Pert%2C+A&rft.aulast=Pert&rft.aufirst=A&rft.date=1998-01-01&rft.volume=42&rft.issue=&rft.spage=991&rft.isbn=&rft.btitle=&rft.title=Advances+in+pharmacology+%28San+Diego%2C+Calif.%29&rft.issn=10543589&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-11-25 N1 - Date created - 1997-11-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Accounting for errors in dose estimates used in studies of workers exposed to external radiation. AN - 79628139; 9415578 AB - This paper discusses approaches for accounting for errors in dose estimates used in dose-response analyses of data from epidemiologic studies of workers exposed to external radiation and illustrates these approaches with analyses of data on workers at the Hanford site. In these analyses, estimates of the excess relative risk are corrected for bias in recorded doses as estimates of organ dose, and confidence intervals reflect uncertainty in the correction factors. For the Hanford data, these procedures did not greatly modify results for all cancer excluding leukemia, but the upper confidence limit for leukemia was increased by about 40%, a difference that is of some importance in comparing worker-based estimates and confidence intervals with estimates that serve as the basis of radiation protection standards. It is argued that aside from taking account of uncertainty in correction factors, no additional corrections are needed to address random errors resulting from variation in exposure energies and geometries. In addition, it is shown that because the larger cumulative doses, which are most influential in dose-response analyses, are the sums of large numbers of independent dosimeter readings, random errors resulting from variation in laboratory measurements are unlikely to be important for epidemiologic purposes. It is hoped that the approaches illustrated in this paper will be applied to future analyses of data from worker studies, especially combined analyses of data from several countries. Taking account of uncertainty in factors that correct for systematic bias will be especially important as uncertainty resulting from sampling variation decreases. JF - Health physics AU - Gilbert, E S AD - Radiation Epidemiology Branch, National Cancer Institute, Rockville, MD 20852, USA. Y1 - 1998/01// PY - 1998 DA - January 1998 SP - 22 EP - 29 VL - 74 IS - 1 SN - 0017-9078, 0017-9078 KW - Index Medicus KW - Humans KW - Dose-Response Relationship, Radiation KW - Bias (Epidemiology) KW - Occupational Exposure -- statistics & numerical data KW - Power Plants KW - Occupational Exposure -- adverse effects KW - Radiation Injuries -- epidemiology KW - Nuclear Reactors KW - Radiation Injuries -- mortality KW - Film Dosimetry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79628139?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Health+physics&rft.atitle=Accounting+for+errors+in+dose+estimates+used+in+studies+of+workers+exposed+to+external+radiation.&rft.au=Gilbert%2C+E+S&rft.aulast=Gilbert&rft.aufirst=E&rft.date=1998-01-01&rft.volume=74&rft.issue=1&rft.spage=22&rft.isbn=&rft.btitle=&rft.title=Health+physics&rft.issn=00179078&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-01-12 N1 - Date created - 1998-01-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Monoclonal antibodies to cytochromes P450. AN - 79619513; 14577233 JF - Methods in molecular biology (Clifton, N.J.) AU - Gelboin, H V AU - Shou, M AU - Goldfarb, I AU - Yang, T J AU - Krausz, K AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, Bethesda, MD, USA. Y1 - 1998 PY - 1998 DA - 1998 SP - 227 EP - 237 VL - 107 SN - 1064-3745, 1064-3745 KW - Antibodies, Monoclonal KW - 0 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Durapatite KW - 91D9GV0Z28 KW - Index Medicus KW - Animals KW - Chromatography KW - Ascitic Fluid -- immunology KW - Hybridomas -- immunology KW - Mice KW - Cytochrome P-450 Enzyme System -- immunology KW - Antibodies, Monoclonal -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79619513?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Methods+in+molecular+biology+%28Clifton%2C+N.J.%29&rft.atitle=Monoclonal+antibodies+to+cytochromes+P450.&rft.au=Gelboin%2C+H+V%3BShou%2C+M%3BGoldfarb%2C+I%3BYang%2C+T+J%3BKrausz%2C+K&rft.aulast=Gelboin&rft.aufirst=H&rft.date=1998-01-01&rft.volume=107&rft.issue=&rft.spage=227&rft.isbn=&rft.btitle=&rft.title=Methods+in+molecular+biology+%28Clifton%2C+N.J.%29&rft.issn=10643745&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-12-11 N1 - Date created - 2003-10-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The relationship between cannabis use and DSM-IV cannabis abuse and dependence: results from the National Longitudinal Alcohol Epidemiologic Survey. AN - 79617214; 10689658 AB - The purpose of-this study was to determine the risk of Diagnostic and Statistical Manual of Mental Disorders--Fourth Edition (DSM-IV) cannabis abuse and dependence at different levels of cannabis use in a nationally representative sample of the U.S. general population. Two separate logistic regression analyses were conducted to determine the association between cannabis use, and abuse and dependence. The risk of cannabis abuse and dependence was found to increase with the frequency of smoking occasions and slightly decreased with age. More severe comorbidity was associated with dependence compared to abuse, suggesting that cannabis might be used to self-medicate major depression. The strength of the association between cannabis use and abuse was also increased as a function of the number of joints smoked among females, but not males. These results were discussed in terms of differential societal reactions, the self-medication hypothesis, and gender biases in diagnosing cannabis abuse. JF - Journal of substance abuse AU - Grant, B F AU - Pickering, R AD - Division of Biometry and Epidemiology, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892-7003, USA. Y1 - 1998 PY - 1998 DA - 1998 SP - 255 EP - 264 VL - 10 IS - 3 SN - 0899-3289, 0899-3289 KW - Index Medicus KW - United States KW - Depressive Disorder, Major -- diagnosis KW - Sex Factors KW - Humans KW - Depressive Disorder, Major -- epidemiology KW - Longitudinal Studies KW - Psychometrics KW - Comorbidity KW - Self Medication -- psychology KW - Cross-Sectional Studies KW - Risk Factors KW - Depressive Disorder, Major -- psychology KW - Adult KW - Health Surveys KW - Middle Aged KW - Adolescent KW - Female KW - Male KW - Marijuana Smoking -- psychology KW - Alcoholism -- epidemiology KW - Alcoholism -- diagnosis KW - Marijuana Smoking -- epidemiology KW - Marijuana Abuse -- diagnosis KW - Marijuana Abuse -- psychology KW - Marijuana Abuse -- epidemiology KW - Psychiatric Status Rating Scales -- statistics & numerical data KW - Alcoholism -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79617214?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+substance+abuse&rft.atitle=The+relationship+between+cannabis+use+and+DSM-IV+cannabis+abuse+and+dependence%3A+results+from+the+National+Longitudinal+Alcohol+Epidemiologic+Survey.&rft.au=Grant%2C+B+F%3BPickering%2C+R&rft.aulast=Grant&rft.aufirst=B&rft.date=1998-01-01&rft.volume=10&rft.issue=3&rft.spage=255&rft.isbn=&rft.btitle=&rft.title=Journal+of+substance+abuse&rft.issn=08993289&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-03-21 N1 - Date created - 2000-03-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The benzoquinone ansamycin 17-allylamino-17-demethoxygeldanamycin binds to HSP90 and shares important biologic activities with geldanamycin. AN - 73930159; 9744771 AB - Benzoquinone ansamycins are antibiotics with anticancer potential. First described as tyrosine kinase inhibitors, they are now frequently used to target HSP90 chaperone function. While herbimycin A and geldanamycin (GA) have been widely used in preclinical studies, both drugs are poor candidates for clinical trials owing to their in vivo toxicity and lack of stability. We therefore examined the biologic effects of 17-allylamino-17-demethoxygeldanamycin (17-AG), an ansamycin derivative with lower in vivo toxicity than GA. Binding of 17-AG to HSP90 was studied in vitro using a GA-affinity beads competition assay. We analyzed the drug-induced destabilization of p185erbB2, Raf-1 and mutant p53 in SKBR3 breast cancer cells by Western blotting. The antiproliferative activities of 17-AG and GA were compared using the MTT assay. We found that, in a similar manner to GA itself, 17-AG bound specifically to HSP90. It also led to degradation of the receptor tyrosine kinase p185erbB2, the serine/threonine kinase Raf-1 and mutant p53. Both GA and 17-AG displayed comparable antiproliferative effects in SKBR3 and MCF7 cells. Even though HSP90 binding by 17-AG was weaker than by GA, 17-AG and GA caused biologic effects in tumor cells at similar doses. 17-AG shares the important biologic features of its parent compound GA. Since 17-AG has a better toxicity profile than GA, it is an interesting candidate benzoquinone ansamycin for clinical development. JF - Cancer chemotherapy and pharmacology AU - Schulte, T W AU - Neckers, L M AD - Medicine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1928, USA. tschulte@helix.nih.gov Y1 - 1998 PY - 1998 DA - 1998 SP - 273 EP - 279 VL - 42 IS - 4 SN - 0344-5704, 0344-5704 KW - Antibiotics, Antineoplastic KW - 0 KW - Benzoquinones KW - Enzyme Inhibitors KW - HSP90 Heat-Shock Proteins KW - Lactams, Macrocyclic KW - Quinones KW - Tumor Suppressor Protein p53 KW - Rifabutin KW - 1W306TDA6S KW - Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - Receptor, ErbB-2 KW - Proto-Oncogene Proteins c-raf KW - EC 2.7.11.1 KW - geldanamycin KW - Z3K3VJ16KU KW - Index Medicus KW - Mutation -- drug effects KW - 3T3 Cells KW - Animals KW - Proto-Oncogene Proteins c-raf -- chemistry KW - Receptor, ErbB-2 -- metabolism KW - Humans KW - Cell Division -- drug effects KW - Proto-Oncogene Proteins c-raf -- metabolism KW - Mice KW - Tumor Suppressor Protein p53 -- metabolism KW - Protein-Tyrosine Kinases -- antagonists & inhibitors KW - Protein-Tyrosine Kinases -- genetics KW - Tumor Cells, Cultured KW - Tumor Suppressor Protein p53 -- chemistry KW - Receptor, ErbB-2 -- chemistry KW - Female KW - Antibiotics, Antineoplastic -- metabolism KW - Rifabutin -- analogs & derivatives KW - Antibiotics, Antineoplastic -- pharmacology KW - HSP90 Heat-Shock Proteins -- metabolism KW - Enzyme Inhibitors -- pharmacology KW - Enzyme Inhibitors -- metabolism KW - Quinones -- pharmacology KW - Quinones -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73930159?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+chemotherapy+and+pharmacology&rft.atitle=The+benzoquinone+ansamycin+17-allylamino-17-demethoxygeldanamycin+binds+to+HSP90+and+shares+important+biologic+activities+with+geldanamycin.&rft.au=Schulte%2C+T+W%3BNeckers%2C+L+M&rft.aulast=Schulte&rft.aufirst=T&rft.date=1998-01-01&rft.volume=42&rft.issue=4&rft.spage=273&rft.isbn=&rft.btitle=&rft.title=Cancer+chemotherapy+and+pharmacology&rft.issn=03445704&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-10-08 N1 - Date created - 1998-10-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Clinical pharmacology of UCN-01: initial observations and comparison to preclinical models. AN - 73924600; 9750030 AB - UCN-01 (7-hydroxystaurosporine; NSC 638850) is a protein kinase antagonist selected for clinical trial based in part on evidence of efficacy in a preclinical renal carcinoma xenograft model. Schedule studies and in vitro studies suggested that a 72-h continuous infusion would be appropriate. In rats and dogs, maximum tolerated doses produced peak plasma concentrations of approximately 0.2-0.3 microM. However, concentrations 10-fold greater are well tolerated in humans, and the compound has a markedly prolonged T1/2. Specific binding to human alpha1-acidic glycoprotein has been demonstrated. These findings reinforce the need to consider actual clinical pharmacology data in "real time" with phase I studies. JF - Cancer chemotherapy and pharmacology AU - Sausville, E A AU - Lush, R D AU - Headlee, D AU - Smith, A C AU - Figg, W D AU - Arbuck, S G AU - Senderowicz, A M AU - Fuse, E AU - Tanii, H AU - Kuwabara, T AU - Kobayashi, S AD - DTP Clinical Trials Unit, Medicine Branch, Division of Clinical Sciences, National Cancer Institute, Bethesda, MD, USA. sausville@dtpax2.ncifcrf.gov Y1 - 1998 PY - 1998 DA - 1998 SP - S54 EP - S59 VL - 42 Suppl SN - 0344-5704, 0344-5704 KW - Alkaloids KW - 0 KW - Antineoplastic Agents KW - Blood Proteins KW - Enzyme Inhibitors KW - 7-hydroxystaurosporine KW - 7BU5H4V94A KW - Protein Kinase C KW - EC 2.7.11.13 KW - Staurosporine KW - H88EPA0A3N KW - Index Medicus KW - Transplantation, Heterologous -- immunology KW - Animals KW - Infusions, Intravenous KW - Humans KW - Mice KW - Mice, Nude KW - Protein Binding KW - Staurosporine -- analogs & derivatives KW - Chromatography, High Pressure Liquid KW - Rats KW - Adult KW - Dogs KW - Blood Proteins -- metabolism KW - Protein Kinase C -- antagonists & inhibitors KW - Antineoplastic Agents -- pharmacokinetics KW - Enzyme Inhibitors -- toxicity KW - Alkaloids -- toxicity KW - Antineoplastic Agents -- toxicity KW - Enzyme Inhibitors -- pharmacology KW - Enzyme Inhibitors -- pharmacokinetics KW - Alkaloids -- pharmacology KW - Alkaloids -- pharmacokinetics KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73924600?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+chemotherapy+and+pharmacology&rft.atitle=Clinical+pharmacology+of+UCN-01%3A+initial+observations+and+comparison+to+preclinical+models.&rft.au=Sausville%2C+E+A%3BLush%2C+R+D%3BHeadlee%2C+D%3BSmith%2C+A+C%3BFigg%2C+W+D%3BArbuck%2C+S+G%3BSenderowicz%2C+A+M%3BFuse%2C+E%3BTanii%2C+H%3BKuwabara%2C+T%3BKobayashi%2C+S&rft.aulast=Sausville&rft.aufirst=E&rft.date=1998-01-01&rft.volume=42+Suppl&rft.issue=&rft.spage=S54&rft.isbn=&rft.btitle=&rft.title=Cancer+chemotherapy+and+pharmacology&rft.issn=03445704&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-10-07 N1 - Date created - 1998-10-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - National Cancer Institute Clinical Trials Program in Colorectal Cancer. AN - 73909158; 9750034 AB - Colorectal cancer will be diagnosed in approximately 150,000 patients in the USA this year. Chemotherapy has recently been shown to improve survival when given as adjuvant therapy to surgery in patients with stage III colorectal cancer. Demonstration of this benefit required large, randomized controlled trials. Either 5-fluorouracil (5-FU) and leucovorin for 6 months or 5-FU and levamisole for 12 months are currently considered standard adjuvant treatment for stage III colorectal cancer. However, current adjuvant trials are comparing continuous infusion and intravenous bolus 5-FU regimens and oral uracil/Ftorafur with intravenous 5-FU and leucovorin, as well as studying the timing of chemotherapy in the adjuvant setting. Subsequent adjuvant trials will examine newer regimens with activity in advanced colorectal cancer, as well as the efficacy of monoclonal antibodies. Other trials will study which type of surgery is optimal and whether adjuvant therapy is helpful in stage II colon cancer. Trials in metastatic disease will focus on combinations of newer agents which may improve survival in this patient group. Studies in rectal cancer will focus on determining which agents are optimal in combination with radiation therapy in the adjuvant setting. Molecular characteristics of tumor cells are being defined, which may guide therapy in the future. Careful, logically designed clinical trials will hopefully provide more efficacious therapy for this common cancer. JF - Cancer chemotherapy and pharmacology AU - Conley, B A AU - Kaplan, R S AU - Arbuck, S G AD - Clinical Investigations Branch, Cancer Therapy Evaluation Program, National Cancer Institute, National Institutes of Health, Rockville, MD 20852, USA. Y1 - 1998 PY - 1998 DA - 1998 SP - S75 EP - S79 VL - 42 Suppl SN - 0344-5704, 0344-5704 KW - Antimetabolites, Antineoplastic KW - 0 KW - Antineoplastic Agents KW - Fluorouracil KW - U3P01618RT KW - Index Medicus KW - United States KW - Humans KW - Fluorouracil -- therapeutic use KW - National Institutes of Health (U.S.) KW - Clinical Trials as Topic -- trends KW - Antineoplastic Agents -- therapeutic use KW - Colorectal Neoplasms -- drug therapy KW - Antimetabolites, Antineoplastic -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73909158?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+chemotherapy+and+pharmacology&rft.atitle=National+Cancer+Institute+Clinical+Trials+Program+in+Colorectal+Cancer.&rft.au=Conley%2C+B+A%3BKaplan%2C+R+S%3BArbuck%2C+S+G&rft.aulast=Conley&rft.aufirst=B&rft.date=1998-01-01&rft.volume=42+Suppl&rft.issue=&rft.spage=S75&rft.isbn=&rft.btitle=&rft.title=Cancer+chemotherapy+and+pharmacology&rft.issn=03445704&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-10-07 N1 - Date created - 1998-10-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The role of protein glycosylation inhibitors in the prevention of metastasis and therapy of cancer. AN - 73897784; 9727627 AB - Oligosaccharide moieties of cell-surface glycoproteins are thought to be involved in recognition events during cancer metastasis and invasion. Swainsonine, an inhibitor of the Golgi alpha-mannosidase II, has been shown to block pulmonary colonization by tumor cells and stimulate components of the immune system. Swainsonine also abrogates much of the toxicity of chemotherapeutic agents and stimulates bone marrow hematopoietic progenitor cells, suggesting additional therapeutic applications. We are currently characterizing the ability of swainsonine to modify cell growth in human and murine bone marrow progenitor cells. Furthermore, we are examining crucial steps in metastasis that depend upon cell surface molecules that play a role in cell-matrix interactions. Our work shows that tumor cell adhesion to collagen IV in vitro is rapidly stimulated by cis-polyunsaturated fatty acids and is dependent on protein kinase C activity. We are investigating the hypothesis that integrins are critical components of this adhesion and are examining potential signal transduction pathways that lead to the modulation of cell adhesion. JF - Cancer detection and prevention AU - Roberts, J D AU - Klein, J L AU - Palmantier, R AU - Dhume, S T AU - George, M D AU - Olden, K AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1998 PY - 1998 DA - 1998 SP - 455 EP - 462 VL - 22 IS - 5 SN - 0361-090X, 0361-090X KW - Antineoplastic Agents, Phytogenic KW - 0 KW - Enzyme Inhibitors KW - Glycoproteins KW - Arachidonic Acid KW - 27YG812J1I KW - Protein Kinase C KW - EC 2.7.11.13 KW - Swainsonine KW - RSY4RK37KQ KW - Index Medicus KW - Protein Kinase C -- metabolism KW - Arachidonic Acid -- physiology KW - Animals KW - Protein Kinase C -- antagonists & inhibitors KW - Arachidonic Acid -- antagonists & inhibitors KW - Tumor Cells, Cultured KW - Glycosylation -- drug effects KW - Glycoproteins -- metabolism KW - Humans KW - Mice, Nude KW - Mice KW - Hematopoietic Stem Cells -- metabolism KW - Signal Transduction KW - Cell Adhesion KW - Neoplasms -- drug therapy KW - Neoplasms -- pathology KW - Enzyme Inhibitors -- therapeutic use KW - Antineoplastic Agents, Phytogenic -- therapeutic use KW - Swainsonine -- therapeutic use KW - Neoplasms -- physiopathology KW - Neoplasm Metastasis -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73897784?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+detection+and+prevention&rft.atitle=The+role+of+protein+glycosylation+inhibitors+in+the+prevention+of+metastasis+and+therapy+of+cancer.&rft.au=Roberts%2C+J+D%3BKlein%2C+J+L%3BPalmantier%2C+R%3BDhume%2C+S+T%3BGeorge%2C+M+D%3BOlden%2C+K&rft.aulast=Roberts&rft.aufirst=J&rft.date=1998-01-01&rft.volume=22&rft.issue=5&rft.spage=455&rft.isbn=&rft.btitle=&rft.title=Cancer+detection+and+prevention&rft.issn=0361090X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-11-10 N1 - Date created - 1998-11-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Age at smoking onset and its association with alcohol consumption and DSM-IV alcohol abuse and dependence: results from the National Longitudinal Alcohol Epidemiologic Survey. AN - 73871902; 9720007 AB - The major purpose of this study was to examine the relationship of early onset smoking with lifetime drinking and the subsequent development of DSM-IV alcohol abuse and dependence using a large representative sample of the U.S. general population. Prevalences of lifetime drinking, alcohol abuse and dependence, and their associated severity were compared among smoking groups defined by age at onset of smoking and among nonsmokers. Linear logistic regression analyses were conducted to assess the relationship between age at smoking onset and lifetime drinking, alcohol abuse and dependence, controlling for important covariates. Early onset smoking was a significant predictor of lifetime drinking and the subsequent development of lifetime alcohol abuse and dependence, a relationship that generally remained consistent for males, females, whites and blacks. Early onset smoking was significantly associated with more excessive alcohol consumption and more severe alcohol use disorders relative to late onset smokers and nonsmokers. Early onset smoking was also significantly associated with heavier and longer smoking careers compared to late onset smokers. Implications of these findings are discussed in terms of prevention of adolescent smoking and the need for further research on understanding the mechanisms underlying the associations between early onset smoking and lifetime drinking, alcohol abuse and dependence. JF - Journal of substance abuse AU - Grant, B F AD - Division of Biometry and Epidemiology, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20852-7003, USA. Y1 - 1998 PY - 1998 DA - 1998 SP - 59 EP - 73 VL - 10 IS - 1 SN - 0899-3289, 0899-3289 KW - Index Medicus KW - Severity of Illness Index KW - Regression Analysis KW - Age of Onset KW - Chi-Square Distribution KW - Humans KW - Social Behavior KW - Aged KW - Longitudinal Studies KW - Adult KW - Interviews as Topic KW - Middle Aged KW - United States -- epidemiology KW - Female KW - Male KW - Prevalence KW - Alcoholism -- epidemiology KW - Smoking -- psychology KW - Alcohol Drinking -- epidemiology KW - Alcoholism -- psychology KW - Smoking -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73871902?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+substance+abuse&rft.atitle=Age+at+smoking+onset+and+its+association+with+alcohol+consumption+and+DSM-IV+alcohol+abuse+and+dependence%3A+results+from+the+National+Longitudinal+Alcohol+Epidemiologic+Survey.&rft.au=Grant%2C+B+F&rft.aulast=Grant&rft.aufirst=B&rft.date=1998-01-01&rft.volume=10&rft.issue=1&rft.spage=59&rft.isbn=&rft.btitle=&rft.title=Journal+of+substance+abuse&rft.issn=08993289&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-11-30 N1 - Date created - 1998-11-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mortality of industrial workers exposed to acrylonitrile. AN - 73859585; 9714511 AB - This study was designed to evaluate the relationship between occupational exposure to acrylonitrile and cancer mortality. Workers (18079 white men, 4293 white women, 2191 nonwhite men, and 897 nonwhite women) employed in acrylonitrile production or use in the 1950s through 1983 were followed through 1989 for vital status and cause of death. Exposure-response relationships were evaluated from quantitative estimates of historical exposures. Tobacco use was determined for a sample of workers to assess potential confounding. Mortality rates between the exposed and unexposed workers in the cohort were compared using the Poisson regression. Analyses by cumulative, average, peak, intensity, duration, and lagged exposure revealed no elevated risk of cancers of the stomach, brain, breast, prostate or lymphatic and hematopoietic systems. Mortality from lung cancer was elevated for the highest quintile of cumulative exposure. When the decile categories were used, the relative risk did not continue to increase at higher levels. Adjustment for cigarette use reduced the risk for lung cancer only slightly. Separate analyses for wage and salaried workers, long-term and short-term workers, fiber and nonfiber plants, and individual plants revealed no clear exposure-response patterns. The results indicate that exposure to acrylonitrile at the levels studied is not associated with an increased relative risk for most cancers of a priori interest. The excess of lung cancer in the highest quintile of cumulative exposure may indicate carcinogenic activity at the highest levels of exposure, but analyses of exposure-response do not provide strong or consistent evidence for a causal association. JF - Scandinavian journal of work, environment & health AU - Blair, A AU - Stewart, P A AU - Zaebst, D D AU - Pottern, L AU - Zey, J N AU - Bloom, T F AU - Miller, B AU - Ward, E AU - Lubin, J AD - Occupational Epidemiology Branch, National Cancer Institute, Bethesda, Maryland 20892, United States. BLAIRA@epndce.nci.nih.gov Y1 - 1998 PY - 1998 DA - 1998 SP - 25 EP - 41 VL - 24 Suppl 2 SN - 0355-3140, 0355-3140 KW - Acrylonitrile KW - MP1U0D42PE KW - Index Medicus KW - Regression Analysis KW - Humans KW - Aged KW - Poisson Distribution KW - Smoking -- epidemiology KW - Age Distribution KW - Lung Neoplasms -- diagnosis KW - Survival Rate KW - Risk Factors KW - Adult KW - Cohort Studies KW - Case-Control Studies KW - Incidence KW - Middle Aged KW - Data Collection KW - Lung Neoplasms -- mortality KW - Lung Neoplasms -- chemically induced KW - United States -- epidemiology KW - Sex Distribution KW - Male KW - Female KW - Occupational Exposure -- statistics & numerical data KW - Neoplasms -- diagnosis KW - Acrylonitrile -- adverse effects KW - Neoplasms -- mortality KW - Neoplasms -- chemically induced KW - Occupational Exposure -- adverse effects KW - Chemical Industry -- statistics & numerical data KW - Cause of Death UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73859585?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Scandinavian+journal+of+work%2C+environment+%26+health&rft.atitle=Mortality+of+industrial+workers+exposed+to+acrylonitrile.&rft.au=Blair%2C+A%3BStewart%2C+P+A%3BZaebst%2C+D+D%3BPottern%2C+L%3BZey%2C+J+N%3BBloom%2C+T+F%3BMiller%2C+B%3BWard%2C+E%3BLubin%2C+J&rft.aulast=Blair&rft.aufirst=A&rft.date=1998-01-01&rft.volume=24+Suppl+2&rft.issue=&rft.spage=25&rft.isbn=&rft.btitle=&rft.title=Scandinavian+journal+of+work%2C+environment+%26+health&rft.issn=03553140&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-10-22 N1 - Date created - 1998-10-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Construction and analysis of multidrug resistance transgenic mice. AN - 73851278; 9711584 JF - Methods in enzymology AU - Evans, G L AD - Clinical Gene Therapy Branch, National Center for Human Genome Research, Bethesda, Maryland 20892, USA. Y1 - 1998 PY - 1998 DA - 1998 SP - 572 EP - 594 VL - 292 SN - 0076-6879, 0076-6879 KW - DNA Primers KW - 0 KW - DNA Probes KW - DNA, Complementary KW - P-Glycoprotein KW - RNA KW - 63231-63-0 KW - Verapamil KW - CJ0O37KU29 KW - Index Medicus KW - Animals KW - Homozygote KW - Humans KW - Leukocytes -- physiology KW - Transcription, Genetic KW - Organ Specificity KW - Mice KW - Mice, Transgenic KW - Leukopenia -- prevention & control KW - RNA -- biosynthesis KW - Leukopenia -- chemically induced KW - Polymerase Chain Reaction -- methods KW - In Situ Hybridization, Fluorescence -- methods KW - Time Factors KW - Verapamil -- toxicity KW - P-Glycoprotein -- genetics KW - P-Glycoprotein -- biosynthesis KW - Drug Resistance, Multiple -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73851278?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Methods+in+enzymology&rft.atitle=Construction+and+analysis+of+multidrug+resistance+transgenic+mice.&rft.au=Evans%2C+G+L&rft.aulast=Evans&rft.aufirst=G&rft.date=1998-01-01&rft.volume=292&rft.issue=&rft.spage=572&rft.isbn=&rft.btitle=&rft.title=Methods+in+enzymology&rft.issn=00766879&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-09-16 N1 - Date created - 1998-09-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Purification and reconstitution of human P-glycoprotein. AN - 73851197; 9711577 AB - Human Pgp from the vinblastine-resistant cell line, KB-V1, can be purified by sequential conventional chromatography on DEAE-sepharose CL-6B resin followed by a wheat germ agglutinin column. By including glycerol (osmolyte protectant) and lipid during the solubilization and chromatography procedures most of the biological activity of Pgp can be retained. The activity of Pgp in the detergent extract or in the concentrated column fractions is stable for at least 8-10 months when stored at -80 degrees. However, repeated cycles of freezing and thawing of fractions result in considerable loss of activity. We have purified Pgp from KB-C1 (a subclone of KB 3-1 that is resistant to 1 microgram/ml colchicine) by following the same protocol. When this method was used for purification of Pgp from MDR1-transfected NIH 3T3 transfectants (N3-V2400, grown in the presence of 2.4 micrograms/ml vinblastine), the protein was eluted with 0.1 M NaCl from the DEAE-Sepharose CL-6B column as usual. However, during WGA lectin chromatography, the protein was eluted with a lower concentration of sugar (0.1 M instead of 0.25 M NAG). This altered elution pattern appears to be due to a difference in the glycosylation of human Pgp in mouse NIH 3T3 cells. This is consistent with the observation that human Pgp expressed in NIH 3T3 cells migrates faster compared to the protein from KB-V1 cells on 8-10% acrylamide gel. Similarly, other workers have purified Chinese hamster Pgp either by a single-step chromatography on Reactive Red 120 agarose or by a combination of anion exchange and immunoaffinity chromatography (see the article by Senior et al. for the purification and properties of ATPase activity of Chinese hamster Pgp). The high level of drug-stimulated ATP hydrolysis by Pgp (Table I), like other ion-transporting ATPases, indicates that this is a high-capacity pump that can function as an effective multidrug transporter. This is further supported by the qualitative demonstration of ATP-dependent vinblastine transport in proteoliposomes reconstituted with pure Pgp (see Fig. 2). Thus, these experiments provide strong evidence that purified Pgp retains its activity and that it functions as an ATP-dependent drug transporter. JF - Methods in enzymology AU - Ambudkar, S V AU - Lelong, I H AU - Zhang, J AU - Cardarelli, C AD - Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998 PY - 1998 DA - 1998 SP - 492 EP - 504 VL - 292 SN - 0076-6879, 0076-6879 KW - Indicators and Reagents KW - 0 KW - Liposomes KW - P-Glycoprotein KW - Proteolipids KW - Recombinant Proteins KW - proteoliposomes KW - Vinblastine KW - 5V9KLZ54CY KW - Verapamil KW - CJ0O37KU29 KW - Adenosine Triphosphatases KW - EC 3.6.1.- KW - Colchicine KW - SML2Y3J35T KW - Daunorubicin KW - ZS7284E0ZP KW - Index Medicus KW - Clone Cells KW - KB Cells KW - 3T3 Cells KW - Animals KW - Solubility KW - Chromatography, Ion Exchange -- methods KW - Electrophoresis, Polyacrylamide Gel KW - Humans KW - Mice KW - Vinblastine -- toxicity KW - Verapamil -- pharmacology KW - Drug Resistance, Multiple KW - Daunorubicin -- pharmacology KW - Transfection -- methods KW - Recombinant Proteins -- isolation & purification KW - Colchicine -- pharmacology KW - Recombinant Proteins -- metabolism KW - Kinetics KW - Chromatography, Affinity -- methods KW - Cricetinae KW - Adenosine Triphosphatases -- drug effects KW - P-Glycoprotein -- metabolism KW - Adenosine Triphosphatases -- metabolism KW - P-Glycoprotein -- isolation & purification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73851197?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Methods+in+enzymology&rft.atitle=Purification+and+reconstitution+of+human+P-glycoprotein.&rft.au=Ambudkar%2C+S+V%3BLelong%2C+I+H%3BZhang%2C+J%3BCardarelli%2C+C&rft.aulast=Ambudkar&rft.aufirst=S&rft.date=1998-01-01&rft.volume=292&rft.issue=&rft.spage=492&rft.isbn=&rft.btitle=&rft.title=Methods+in+enzymology&rft.issn=00766879&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-09-16 N1 - Date created - 1998-09-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - HIV/AIDS and drug abuse: epidemiology and prevention. AN - 70117950; 9848034 AB - In the United States, the AIDS epidemic is a dynamic process with increasing rates of AIDS reported among women, minority populations, heterosexual men, and users of drugs by routes other than injection. The 1993 CDC AIDS definition change has created some difficulties in interpreting trends in the United States. Drug use continues to represent a significant problem among HIV-infected persons. Several strategies have been advanced to decrease transmission of HIV among drug users, their sexual partners and children. However, more effective and comprehensive prevention and treatment strategies are needed. JF - Journal of addictive diseases AU - Haverkos, H W AD - Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Rockville, MD, USA. Y1 - 1998 PY - 1998 DA - 1998 SP - 91 EP - 103 VL - 17 IS - 4 SN - 1055-0887, 1055-0887 KW - Index Medicus KW - AIDS/HIV KW - Needle-Exchange Programs KW - Humans KW - Infant, Newborn KW - Aged KW - Child KW - Community-Institutional Relations KW - Child, Preschool KW - Infant KW - Sexual Behavior KW - Public Health KW - Adult KW - Incidence KW - Middle Aged KW - Adolescent KW - United States -- epidemiology KW - Female KW - Male KW - Acquired Immunodeficiency Syndrome -- epidemiology KW - Risk-Taking KW - Acquired Immunodeficiency Syndrome -- transmission KW - Acquired Immunodeficiency Syndrome -- psychology KW - Substance-Related Disorders -- complications KW - Substance-Related Disorders -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70117950?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+addictive+diseases&rft.atitle=HIV%2FAIDS+and+drug+abuse%3A+epidemiology+and+prevention.&rft.au=Haverkos%2C+H+W&rft.aulast=Haverkos&rft.aufirst=H&rft.date=1998-01-01&rft.volume=17&rft.issue=4&rft.spage=91&rft.isbn=&rft.btitle=&rft.title=Journal+of+addictive+diseases&rft.issn=10550887&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-02-19 N1 - Date created - 1999-02-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The germ cell--the mother of all stem cells. AN - 70113388; 9853836 AB - The germline, uniquely amongst the lineages of the embryo, carries the genome from generation to generation and is therefore the only lineage which retains true developmental totipotency. Paradoxically, when mouse primordial germ cells (PGCs) are introduced into a host blastocyst, they do not contribute to either the germline or the soma, suggesting that they are restricted in developmental potency. Conversely, in vivo PGCs give rise to embryonal carcinoma (EC) cells, the pluripotent stem cells of teratomas, benign tumors containing derivatives of the three primary germ layers. Similarly, PGCs can be converted in vitro into embryonic germ (EG) cells, pluripotent stem cells capable of giving rise to somatic and germline chimeras. The ability of PGCs to form EC cells in vivo and EG cells in vitro suggests that developmental potency of PGCs is regulateable. The molecular mechanisms controlling PGC growth and differentiation are gradually being elucidated through the characterization of sterile mutants and through the use of in vitro culture systems. Understanding how a PGC can give rise to a pluripotent stem cell could give significant insights into the regulation of developmental totipotency as well as having important implications for male fertility and the etiology of testicular cancer. JF - The International journal of developmental biology AU - Donovan, P J AD - Cell Biology of Development and Differentiation Group, ABL-Basic Research Program, NCI-FCRDC, Frederick MD, USA. pdonovan@lac.jci.tju.edu Y1 - 1998 PY - 1998 DA - 1998 SP - 1043 EP - 1050 VL - 42 IS - 7 SN - 0214-6282, 0214-6282 KW - Index Medicus KW - Animals KW - Culture Techniques KW - Neoplastic Stem Cells KW - Teratoma -- pathology KW - Cell Differentiation KW - Mice KW - Embryo, Mammalian KW - Male KW - Female KW - Embryonal Carcinoma Stem Cells KW - Cell Division KW - Germ Cells KW - Stem Cells UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70113388?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+International+journal+of+developmental+biology&rft.atitle=The+germ+cell--the+mother+of+all+stem+cells.&rft.au=Donovan%2C+P+J&rft.aulast=Donovan&rft.aufirst=P&rft.date=1998-01-01&rft.volume=42&rft.issue=7&rft.spage=1043&rft.isbn=&rft.btitle=&rft.title=The+International+journal+of+developmental+biology&rft.issn=02146282&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-02-23 N1 - Date created - 1999-02-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Prevalence of anxiety disorders and their comorbidity with mood and addictive disorders. AN - 70070346; 9829013 AB - The co-occurrence of anxiety disorders with other mental, addictive, and physical disorders has important implications for treatment and for prediction of clinical course and associated morbidity. Cross-sectional and prospective data on 20,291 individuals from the Epidemiologic Catchment Area (ECA) study were analysed to determine one-month, current disorders, one-year incidence, and one-year and lifetime prevalence of anxiety, mood, and addictive disorders, and to identify the onset and offset of disorders within the one-year prospective period. Nearly half (47.2%) of those meeting lifetime criteria for major depression also have met criteria for a comorbid anxiety disorder. The average age of onset of any lifetime anxiety disorder (16.4 years) and social phobia (11.6 years) among those with major depression was much younger than the onset age for major depression (23.2 years) and panic disorder. Anxiety disorders, especially social and simple phobias, appear to have an early onset in adolescence with potentially severe consequences, predisposing those affected to greater vulnerability to major depression and addictive disorders. JF - The British journal of psychiatry. Supplement AU - Regier, D A AU - Rae, D S AU - Narrow, W E AU - Kaelber, C T AU - Schatzberg, A F AD - Division of Epidemiology and Services Research, National Institute of Mental Health, National Institutes of Health, Rockville, Maryland 20857, USA. Y1 - 1998 PY - 1998 DA - 1998 SP - 24 EP - 28 IS - 34 SN - 0960-5371, 0960-5371 KW - Index Medicus KW - Cross-Sectional Studies KW - Prospective Studies KW - Age of Onset KW - Humans KW - Adult KW - Retrospective Studies KW - Diagnosis, Dual (Psychiatry) KW - Aged KW - Middle Aged KW - Massachusetts -- epidemiology KW - Adolescent KW - Prevalence KW - Substance-Related Disorders -- etiology KW - Mood Disorders -- epidemiology KW - Anxiety Disorders -- epidemiology KW - Anxiety Disorders -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70070346?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+British+journal+of+psychiatry.+Supplement&rft.atitle=Prevalence+of+anxiety+disorders+and+their+comorbidity+with+mood+and+addictive+disorders.&rft.au=Regier%2C+D+A%3BRae%2C+D+S%3BNarrow%2C+W+E%3BKaelber%2C+C+T%3BSchatzberg%2C+A+F&rft.aulast=Regier&rft.aufirst=D&rft.date=1998-01-01&rft.volume=&rft.issue=34&rft.spage=24&rft.isbn=&rft.btitle=&rft.title=The+British+journal+of+psychiatry.+Supplement&rft.issn=09605371&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-12-03 N1 - Date created - 1998-12-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pharmacokinetics of methyl palmoxirate, an inhibitor of beta-oxidation, in rats and humans. AN - 70063782; 9820128 AB - Recent studies from our laboratory have shown that methyl palmoxirate (MEP), an inhibitor of mitochondrial beta-oxidation of long chain fatty acids, can be used to increase incorporation of radiolabeled palmitic acid into brain lipids and reduce beta-oxidation of the fatty acid. Thus, MEP allows the use of carbon labeled palmitate for studying brain lipid metabolism in animals and humans by quantitative autoradiography or positron emission tomography (PET). As it is essential to pretreat human subjects with an acute dose of MEP prior to intravenous injection of [1-11C]palmitate for PET scanning, this study was undertaken to determine the plasma elimination half-life of MEP in rats and human subjects and to provide insight about the drug's absorption and metabolism. A gas chromatographic method was developed to measure MEP in body fluids. Following oral administration of MEP to rats (2.5 and 10 mg/kg) and to humans, the unmetabolized drug could not be detected in plasma or urine (sensitivity of detection was 1 ng). However, when MEP was injected intravenously (10 mg/kg) in rats, a peak initial concentration could be measured in plasma (7.7 microg/mL), the clearance of the drug from plasma was rapid (t1/2 = 0.6 min), which indicates that MEP readily enters tissue lipid pools or is metabolized like long-chain fatty acids. As no adverse experience occured in the 11 human subjects studied, oral administration of a single dose of MEP was safe under the conditions of this study and may be used to increase the incorporation of positron labeled palmitic acid for studying brain lipid metabolism in vivo by PET. JF - Life sciences AU - Chang, M C AU - Connolly, C AU - Hill, D AU - Purdon, A D AU - Hayakawa, T AU - Grimes, G AU - Shetty, H U AD - Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA. mcjchang@box-m.nih.gov Y1 - 1998 PY - 1998 DA - 1998 SP - PL297 EP - PL302 VL - 63 IS - 20 SN - 0024-3205, 0024-3205 KW - Epoxy Compounds KW - 0 KW - Hypoglycemic Agents KW - Propionates KW - methyl 2-tetradecylglycidate KW - NPL6006Y4B KW - Index Medicus KW - Rats KW - Administration, Oral KW - Animals KW - Rats, Inbred F344 KW - Oxidation-Reduction -- drug effects KW - Injections, Intravenous KW - Humans KW - Brain -- drug effects KW - Mitochondria -- drug effects KW - Mitochondria -- metabolism KW - Brain -- metabolism KW - Male KW - Epoxy Compounds -- adverse effects KW - Epoxy Compounds -- pharmacokinetics KW - Propionates -- pharmacokinetics KW - Hypoglycemic Agents -- administration & dosage KW - Hypoglycemic Agents -- adverse effects KW - Epoxy Compounds -- administration & dosage KW - Propionates -- adverse effects KW - Propionates -- administration & dosage KW - Hypoglycemic Agents -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70063782?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Life+sciences&rft.atitle=Pharmacokinetics+of+methyl+palmoxirate%2C+an+inhibitor+of+beta-oxidation%2C+in+rats+and+humans.&rft.au=Chang%2C+M+C%3BConnolly%2C+C%3BHill%2C+D%3BPurdon%2C+A+D%3BHayakawa%2C+T%3BGrimes%2C+G%3BShetty%2C+H+U&rft.aulast=Chang&rft.aufirst=M&rft.date=1998-01-01&rft.volume=63&rft.issue=20&rft.spage=PL297&rft.isbn=&rft.btitle=&rft.title=Life+sciences&rft.issn=00243205&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-12-01 N1 - Date created - 1998-12-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cigarette smoking during early cocaine abstinence. AN - 70046590; 9809135 AB - Use of cocaine has been reported to increase cigarette smoking, but there are no published studies of cigarette smoking during early cocaine abstinence. The authors assessed ad libitum cigarette smoking of 12 cocaine-dependent smokers housed on a closed research ward. Last cocaine use averaged 0.6 grams 1.8 days before admission. Smoking was measured indirectly with computerized cigarette dispensers. There was no significant difference between self-reported daily number of cigarettes smoked before admission and the number of cigarettes dispensed daily for the first 7 full days after admission. These findings suggest that early cocaine abstinence does not significantly alter cigarette smoking. JF - The American journal on addictions AU - Radzius, A AU - Gorelick, D A AU - Henningfield, J E AD - National Institute on Drug Abuse, Baltimore, MD 21224, USA. Y1 - 1998 PY - 1998 DA - 1998 SP - 305 EP - 308 VL - 7 IS - 4 SN - 1055-0496, 1055-0496 KW - Narcotics KW - 0 KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Substance Withdrawal Syndrome KW - Humans KW - Adult KW - Cocaine -- pharmacology KW - Narcotics -- pharmacology KW - Male KW - Female KW - Smoking KW - Cocaine-Related Disorders -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70046590?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+on+addictions&rft.atitle=Cigarette+smoking+during+early+cocaine+abstinence.&rft.au=Radzius%2C+A%3BGorelick%2C+D+A%3BHenningfield%2C+J+E&rft.aulast=Radzius&rft.aufirst=A&rft.date=1998-01-01&rft.volume=7&rft.issue=4&rft.spage=305&rft.isbn=&rft.btitle=&rft.title=The+American+journal+on+addictions&rft.issn=10550496&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-01-29 N1 - Date created - 1999-01-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - p53 mutations and DNA ploidy in colorectal adenocarcinomas. AN - 70041806; 9807634 AB - The p53 tumour suppressor gene has an important role in the the maintenance of genome stability and its mutational inactivation may be at the origin of aneuploidy in cancer cells. The aim of this study was to determine whether p53 mutations were associated to DNA aneuploidy, as assessed by flow cytometry, in colorectal adenocarcinomas. Analysis of p53 mutations spectrum of the sorted nuclei was done by Denaturing Gradient Gel Electrophoresis (DGGE) and DNA sequencing. Overall, we studied 20 adenocarcinomas, the corresponding control mucosa, and 7 lymph node metastases. Five tumours (25%) were DNA diploid, while 15 tumours (75%) were composed of DNA aneuploid and diploid subpopulations. DNA diploid control mucosa and adenocarcinomas showed no p53 mutations, while 60% of the tumours with DNA aneuploidy had p53 mutations. Therefore, p53 mutations occurred significantly more often in DNA aneuploid than in DNA diploid tumours (p < 0.04, Fisher's exact test). Incidences of DNA aneuploidy and p53 mutations in lymph node metastases were 60 and 86%, respectively. In all tumours showing a p53 mutation, the wild-type allele was not or only bearly visible in DNA aneuploid cells suggesting that, in such cells, aneuploidy is accompanied by complete p53 functional inactivation. The present observations suggest that p53 mutations may have a role in the origin of aneuploidy at late stages of colorectal carcinogenesis. JF - Analytical cellular pathology : the journal of the European Society for Analytical Cellular Pathology AU - Campomenosi, P AU - Assereto, P AU - Bogliolo, M AU - Fronza, G AU - Abbondandolo, A AU - Capasso, A AU - Bellomo, P F AU - Monaco, R AU - Rapallo, A AU - Sciutto, A AU - Orecchia, R AU - Geido, E AU - Giaretti, W AD - CSTA-Mutagenesis Laboratory, National Cancer Institute-Genova, Italy. Y1 - 1998 PY - 1998 DA - 1998 SP - 1 EP - 12 VL - 17 IS - 1 SN - 0921-8912, 0921-8912 KW - Index Medicus KW - Lymphatic Metastasis -- genetics KW - Base Sequence KW - Aged, 80 and over KW - Humans KW - Adult KW - Molecular Sequence Data KW - Aged KW - Middle Aged KW - Metaplasia -- genetics KW - Flow Cytometry KW - Ploidies KW - Male KW - Female KW - Aneuploidy KW - Genes, p53 -- genetics KW - Mutation -- genetics KW - Adenocarcinoma -- genetics KW - Colorectal Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70041806?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Analytical+cellular+pathology+%3A+the+journal+of+the+European+Society+for+Analytical+Cellular+Pathology&rft.atitle=p53+mutations+and+DNA+ploidy+in+colorectal+adenocarcinomas.&rft.au=Campomenosi%2C+P%3BAssereto%2C+P%3BBogliolo%2C+M%3BFronza%2C+G%3BAbbondandolo%2C+A%3BCapasso%2C+A%3BBellomo%2C+P+F%3BMonaco%2C+R%3BRapallo%2C+A%3BSciutto%2C+A%3BOrecchia%2C+R%3BGeido%2C+E%3BGiaretti%2C+W&rft.aulast=Campomenosi&rft.aufirst=P&rft.date=1998-01-01&rft.volume=17&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Analytical+cellular+pathology+%3A+the+journal+of+the+European+Society+for+Analytical+Cellular+Pathology&rft.issn=09218912&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-01-14 N1 - Date created - 1999-01-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mammary gland carcinogenicity of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine in Sprague-Dawley rats on high- and low-fat diets. AN - 70014377; 9795967 AB - 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a carcinogenic heterocyclic amine derived from cooked meat. Mammary gland tumors were induced in female Sprague-Dawley rats given 10 doses of PhIP (75 mg/kg po) once per day from 43 days of age and then placed on a defined high-fat (23.5% corn oil) or low-fat (5% corn oil) diet for 25 weeks. Mammary tumor incidence was 49% (44 of 90 rats) and 31% (27 of 88 rats) in the high- and low-fat groups, respectively. No tumors were found in vehicle control rats on the high-or the low-fat diet (n = 44 and 43, respectively). The higher tumor incidence in the high-fat group was due to an increase specifically in carcinomas (classified as tubulopapillary carcinomas) rather than benign tumors (tubular adenomas and fibroadenomas). The incidence of carcinomas was 45% and 24% in PhIP-treated rats on the high- and low-fat diets, respectively. In addition, the percentage of carcinomas showing stromal invasion was highest in the high-fat diet group (22% vs. 8%, high- vs. low-fat diet). Proliferating cell nuclear antigen immunostaining (PCNA) index revealed six times more proliferation in carcinomas from rats on the high-fat diet than in rats on the low-fat diet. Adenomas from rats on different diets had similar PCNA indexes. The tumor apoptotic index, quantitated by immunohistochemical detection (terminal deoxynucleotidyl transferase nick end labeling), was twice as high in carcinomas from rats on the high-fat diet as in carcinomas from rats on the low-fat diet but was similar between the two groups of adenomas. The PCNA-to-apoptosis ratio was 43 and 17 in carcinomas from rats on the high- and low-fat diets, respectively, indicating that the growth rate of carcinomas was greater in rats on the high-fat diet. The results from this study show that the high-fat diet increases the incidence, invasiveness, and growth of PhIP-induced mammary gland carcinomas. JF - Nutrition and cancer AU - Snyderwine, E G AU - Thorgeirsson, U P AU - Venugopal, M AU - Roberts-Thomson, S J AD - Division of Basic Sciences, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1998 PY - 1998 DA - 1998 SP - 160 EP - 167 VL - 31 IS - 3 SN - 0163-5581, 0163-5581 KW - Carcinogens KW - 0 KW - Dietary Fats KW - Imidazoles KW - Proliferating Cell Nuclear Antigen KW - 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine KW - 909C6UN66T KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Meat -- adverse effects KW - Immunohistochemistry KW - Female KW - Mammary Neoplasms, Experimental -- chemically induced KW - Diet, Fat-Restricted KW - Dietary Fats -- adverse effects KW - Mammary Neoplasms, Experimental -- metabolism KW - Imidazoles -- adverse effects KW - Mammary Neoplasms, Experimental -- pathology KW - Carcinogens -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70014377?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nutrition+and+cancer&rft.atitle=Mammary+gland+carcinogenicity+of+2-amino-1-methyl-6-phenylimidazo%5B4%2C5-b%5Dpyridine+in+Sprague-Dawley+rats+on+high-+and+low-fat+diets.&rft.au=Snyderwine%2C+E+G%3BThorgeirsson%2C+U+P%3BVenugopal%2C+M%3BRoberts-Thomson%2C+S+J&rft.aulast=Snyderwine&rft.aufirst=E&rft.date=1998-01-01&rft.volume=31&rft.issue=3&rft.spage=160&rft.isbn=&rft.btitle=&rft.title=Nutrition+and+cancer&rft.issn=01635581&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-12-29 N1 - Date created - 1998-12-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cocaine and GBR photoaffinity labels as probes of dopamine transporter structure. AN - 69976897; 9779451 AB - Several aspects of DAT structure and function have been elucidated using a combination of photoaffinity labeling, proteolysis, enzymatic deglycosylation, and epitope-specific immunoprecipitation. The two photolabels are incorporated in different regions of the protein, suggesting that the binding sites for the ligands are distinct or partially nonoverlapping, consistent with results produced by site-directed mutagenesis and analysis of chimeras. These studies have also verified several aspects of DAT structure previously hypothesized based only on theoretical considerations, including the presence of at least one transmembrane helix or other membrane-anchoring structure in two different regions of the protein, identification of the glycosylated domain, and some topological properties. It should be possible to extend and adapt these techniques to further delineate DAT structural properties and to identify other functional domains such as phosphorylation sites or active sulfhydryl moieties. JF - Methods in enzymology AU - Vaughan, R A AD - Molecular Neurobiology Branch, National Institute on Drug Abuse, Intramural Research Program, Baltimore, Maryland 21224, USA. Y1 - 1998 PY - 1998 DA - 1998 SP - 219 EP - 230 VL - 296 SN - 0076-6879, 0076-6879 KW - Affinity Labels KW - 0 KW - Azides KW - Carbohydrates KW - Carrier Proteins KW - Dopamine Plasma Membrane Transport Proteins KW - Iodine Radioisotopes KW - Membrane Glycoproteins KW - Membrane Transport Proteins KW - Nerve Tissue Proteins KW - Piperazines KW - Recombinant Proteins KW - SLC6A3 protein, human KW - 1-(2-(diphenylmethoxy)ethyl)-4-(2-(4-azido-3-iodophenyl)ethyl)piperazine KW - 123632-48-4 KW - RTI 82 KW - 141782-67-4 KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Animals KW - Humans KW - Glycosylation KW - Binding Sites KW - Mutagenesis, Site-Directed KW - Chromatography, Gel -- methods KW - Transfection KW - Recombinant Proteins -- metabolism KW - Recombinant Proteins -- chemistry KW - Radioligand Assay -- methods KW - Carbohydrates -- analysis KW - Chromatography, Affinity -- methods KW - Piperazines -- chemistry KW - Carrier Proteins -- metabolism KW - Carrier Proteins -- chemistry KW - Cocaine -- chemistry KW - Brain -- metabolism KW - Azides -- chemistry KW - Carrier Proteins -- isolation & purification KW - Piperazines -- pharmacokinetics KW - Cocaine -- analogs & derivatives KW - Azides -- pharmacokinetics KW - Cocaine -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69976897?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Methods+in+enzymology&rft.atitle=Cocaine+and+GBR+photoaffinity+labels+as+probes+of+dopamine+transporter+structure.&rft.au=Vaughan%2C+R+A&rft.aulast=Vaughan&rft.aufirst=R&rft.date=1998-01-01&rft.volume=296&rft.issue=&rft.spage=219&rft.isbn=&rft.btitle=&rft.title=Methods+in+enzymology&rft.issn=00766879&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-12-16 N1 - Date created - 1998-12-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Breast cancer risk among women under 55 years of age by joint effects of usage of oral contraceptives and hormone replacement therapy. AN - 69970184; 9774759 AB - To assess effects on breast cancer risk of exposure to both oral contraceptives and menopausal hormones, an increasingly common exposure. A case-control study of breast cancer among women under the age of 55 years in Atlanta, GA involving 1,031 cases and 919 population controls was conducted. Ever use of oral contraceptives was associated with a relative risk of 1.1 (95% 0.9-1.4), whereas the relative risk for hormone replacement therapy was 0.9 (95% CI 0.7-1.2). Seventeen percent of the cases versus 19% of the population controls reported exposure to both agents, resulting in a relative risk of 1.0 (95% CI 0.7-1.4) relative to those unexposed to either preparation. Although there was little variation in risk associated with joint effects by either age or race, there were statistically nonsignificant elevations in risk for this exposure among women who had experienced a natural menopause (relative risk = 2.0, 95% CI 0.7-5.6), were relatively thin (relative risk = 1.5, 0.8-3.0), or who had a first degree relative with breast cancer (relative risk = 2.0, 0.6-7.0). When joint effects of longer term use of both agents were considered, subjects who reported use of oral contraceptives for 10 or more years and hormone replacement for 3 or more years had a relative risk of 3.2 (95% CI 1.4-7.4) compared with nonusers of either preparation. Although our results must be cautiously interpreted given small numbers within subgroups, they raise concern and emphasize the need for further evaluation on breast cancer risk of the increasingly common exposure to both oral contraceptives and hormone replacement therapy. JF - Menopause (New York, N.Y.) AU - Brinton, L A AU - Brogan, D R AU - Coates, R J AU - Swanson, C A AU - Potischman, N AU - Stanford, J L AD - Environmental Epidemiology Branch, National Cancer Institute, Bethesda, Maryland 20892-7374, USA. Y1 - 1998 PY - 1998 DA - 1998 SP - 145 EP - 151 VL - 5 IS - 3 SN - 1072-3714, 1072-3714 KW - Contraceptives, Oral KW - 0 KW - Index Medicus KW - Body Weight KW - Age Factors KW - Georgia -- epidemiology KW - Risk Factors KW - Humans KW - Continental Population Groups KW - Adult KW - Case-Control Studies KW - Middle Aged KW - Body Constitution KW - Menopause KW - Female KW - Contraceptives, Oral -- adverse effects KW - Breast Neoplasms -- genetics KW - Estrogen Replacement Therapy -- adverse effects KW - Breast Neoplasms -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69970184?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Menopause+%28New+York%2C+N.Y.%29&rft.atitle=Breast+cancer+risk+among+women+under+55+years+of+age+by+joint+effects+of+usage+of+oral+contraceptives+and+hormone+replacement+therapy.&rft.au=Brinton%2C+L+A%3BBrogan%2C+D+R%3BCoates%2C+R+J%3BSwanson%2C+C+A%3BPotischman%2C+N%3BStanford%2C+J+L&rft.aulast=Brinton&rft.aufirst=L&rft.date=1998-01-01&rft.volume=5&rft.issue=3&rft.spage=145&rft.isbn=&rft.btitle=&rft.title=Menopause+%28New+York%2C+N.Y.%29&rft.issn=10723714&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-12-03 N1 - Date created - 1998-12-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The effect of an antisense expression plasmid to the IGF-1 receptor on hamster mesothelioma proliferation. AN - 69963553; 9776253 AB - We have evaluated the effect of antisense IGF receptor transcripts on the proliferation and tumorigenicity in an SV40-induced, immunocompetent hamster mesothelioma model (H9A). Expression of IGF-1 and IGF-1 receptor (IGF-1 R) genes was identified from H9A RNA using RT-PCR and Northern blot analysis. H9A cells were electroporated with inducible expression vectors (under the transcriptional control of heat shock promotor HSP70) containing a cDNA fragment corresponding to bp 1-309 of IGF-1 R in the sense or antisense orientation to generate the respective clones A3 sense or B9 antisense. At 39 degrees C, the B9 antisense transfectants demonstrated significantly less proliferation than A3 sense transfectants (p2 < 0.02). At 34 degrees C, cell growth of A3 sense and B9 antisense transfected cells was not significantly different. The A3 sense clones resulted in greater numbers of tumours in vivo compared to the B9 antisense clone (p2 = 0.0001). The inhibitory effect of IGF-1R antisense transcripts on hamster mesothelioma demonstrated in this study by decreased growth and tumorigenicity in vitro and in vivo may have implications for the therapy of human mesothelioma. JF - Developments in biological standardization AU - Pass, H I AU - Mew, D J AU - Carbone, M AU - Donington, J S AU - Baserga, R AU - Steinberg, S M AD - Thoracic Oncology Section, NCI/NIH, Bethesda, MD, USA. Y1 - 1998 PY - 1998 DA - 1998 SP - 321 EP - 328 VL - 94 SN - 0301-5149, 0301-5149 KW - HSP70 Heat-Shock Proteins KW - 0 KW - Oligonucleotides, Antisense KW - Insulin-Like Growth Factor I KW - 67763-96-6 KW - Receptor, IGF Type 1 KW - EC 2.7.10.1 KW - Index Medicus KW - Insulin-Like Growth Factor I -- biosynthesis KW - HSP70 Heat-Shock Proteins -- metabolism KW - Animals KW - Tumor Cells, Cultured KW - Simian virus 40 -- isolation & purification KW - Humans KW - Asbestosis -- complications KW - Cell Transformation, Neoplastic -- drug effects KW - Plasmids KW - Cricetinae KW - Receptor, IGF Type 1 -- physiology KW - Pleural Neoplasms -- virology KW - Mesothelioma -- etiology KW - Pleural Neoplasms -- pathology KW - Mesothelioma -- pathology KW - Receptor, IGF Type 1 -- genetics KW - Oligonucleotides, Antisense -- pharmacology KW - Mesothelioma -- virology KW - Pleural Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69963553?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Developments+in+biological+standardization&rft.atitle=The+effect+of+an+antisense+expression+plasmid+to+the+IGF-1+receptor+on+hamster+mesothelioma+proliferation.&rft.au=Pass%2C+H+I%3BMew%2C+D+J%3BCarbone%2C+M%3BDonington%2C+J+S%3BBaserga%2C+R%3BSteinberg%2C+S+M&rft.aulast=Pass&rft.aufirst=H&rft.date=1998-01-01&rft.volume=94&rft.issue=&rft.spage=321&rft.isbn=&rft.btitle=&rft.title=Developments+in+biological+standardization&rft.issn=03015149&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-12-22 N1 - Date created - 1998-12-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mechanisms of isoniazid resistance in Mycobacterium tuberculosis. AN - 69266388; 16904399 AB - Isoniazid (INH) is a widely used front-line antituberculous agent with bacteriocidal activity at concentrations as low as 150 nM against Mycobacterium tuberculosis. INH is a prodrug and requires activation by an endogenous mycobacterial enzyme, the catalase-peroxidase KatG, before exerting toxic effects on cellular targets. Resistance to INH develops primarily through failure to activate the prodrug due to point mutations in the katG gene. In addition to mutations in katG, mutations in several other loci, such as the alkylhydroperoxidase AhpC and the enoylreductase InhA, may contribute to INH resistance. Although these markers can be used to accurately predict clinical INH resistance in a large number of cases, the molecular mechanisms involved remain largely speculative and incomplete. JF - Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy AU - Barry, C E AU - Slayden, R A AU - Mdluli, K AD - Tuberculosis Research Unit, Rocky Mountain Laboratories, National Institutes for Allergy and Infectious Disease, National Institutes of Health, Hamilton, Montana 59840, USA. clifton_barry@nih.gov Y1 - 1998 PY - 1998 DA - 1998 SP - 128 EP - 134 VL - 1 IS - 2 SN - 1368-7646, 1368-7646 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69266388?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+resistance+updates+%3A+reviews+and+commentaries+in+antimicrobial+and+anticancer+chemotherapy&rft.atitle=Mechanisms+of+isoniazid+resistance+in+Mycobacterium+tuberculosis.&rft.au=Barry%2C+C+E%3BSlayden%2C+R+A%3BMdluli%2C+K&rft.aulast=Barry&rft.aufirst=C&rft.date=1998-01-01&rft.volume=1&rft.issue=2&rft.spage=128&rft.isbn=&rft.btitle=&rft.title=Drug+resistance+updates+%3A+reviews+and+commentaries+in+antimicrobial+and+anticancer+chemotherapy&rft.issn=13687646&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2007-06-28 N1 - Date created - 2006-08-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The impact of a family history of alcoholism on the relationship between age at onset of alcohol use and DSM-IV alcohol dependence: results from the National Longitudinal Alcohol Epidemiologic Survey. AN - 69263806; 15706789 AB - Both the age at onset of alcohol use and a family history of alcoholism can influence a person's risk of becoming alcohol dependent. The relationship between lifetime alcohol dependence, age at first alcohol use, and a family history of alcoholism was investigated using data obtained in the 1992 National Longitudinal Alcohol Epidemiologic Survey. This analysis demonstrated that regardless of the family history of alcoholism, respondents with an earlier age of drinking onset were more likely to become alcohol dependent compared with respondents with a later age of drinking onset. Among all age, race, and gender subgroups studied, however, people with a family history of alcoholism had a higher prevalence of lifetime alcohol dependence than did people without such a history. JF - Alcohol health and research world AU - Grant, B F AD - Biometry Branch, Division of Biometry and Epidemiology, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland, USA. Y1 - 1998 PY - 1998 DA - 1998 SP - 144 EP - 147 VL - 22 IS - 2 SN - 0090-838X, 0090-838X KW - Index Medicus KW - Age of Onset KW - Humans KW - Longitudinal Studies KW - Alcoholism -- epidemiology KW - Alcoholism -- genetics KW - Diagnostic and Statistical Manual of Mental Disorders UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69263806?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Alcohol+health+and+research+world&rft.atitle=The+impact+of+a+family+history+of+alcoholism+on+the+relationship+between+age+at+onset+of+alcohol+use+and+DSM-IV+alcohol+dependence%3A+results+from+the+National+Longitudinal+Alcohol+Epidemiologic+Survey.&rft.au=Grant%2C+B+F&rft.aulast=Grant&rft.aufirst=B&rft.date=1998-01-01&rft.volume=22&rft.issue=2&rft.spage=144&rft.isbn=&rft.btitle=&rft.title=Alcohol+health+and+research+world&rft.issn=0090838X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-03-17 N1 - Date created - 2005-02-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Endothelin signalling in the development of neural crest-derived melanocytes. AN - 69250083; 10392719 AB - In both mice and humans, mutations in the genes encoding the endothelin B receptor and its ligand endothelin 3 lead to deficiencies in neural crest-derived melanocytes and enteric neurons. The discrete steps at which endothelins exert their functions in melanocyte development were examined in mouse neural crest cell cultures. Such cultures, kept in the presence of fetal calf serum, gave rise to cells expressing the early melanoblast marker Dct even in the absence of the phorbol ester tetradecanoyl phorbol acetate (TPA) or endothelins. However, these early Dct+ cells did not proliferate and pigmented cells never formed unless TPA or endothelins were added. In fact, endothelin 2 was as potent as TPA in promoting the generation of both Dct+ melanoblasts and pigmented cells, and endothelin 1 or endothelin 3 stimulated the generation of melanoblasts and of pigmented cells to an even greater extent. The inhibition of this stimulation by the selective endothelin B receptor antagonist BQ-788 (N-cis-2,6-dimethylpiperidinocarbonyl-L-alpha-methylleucyl-D -1-methoxycarbonyltryptophanyl-D-norleucine) suggested that the three endothelins all signal through the endothelin B receptor. This receptor was indeed expressed in Dct+ melanoblasts, in addition to cells lacking Dct expression. The results demonstrate that endothelins are potent stimulators of melanoblast proliferation and differentiation. JF - Biochemistry and cell biology = Biochimie et biologie cellulaire AU - Opdecamp, K AU - Kos, L AU - Arnheiter, H AU - Pavan, W J AD - Laboratory of Developmental Neurogenetics, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1998 PY - 1998 DA - 1998 SP - 1093 EP - 1099 VL - 76 IS - 6 SN - 0829-8211, 0829-8211 KW - Endothelin-1 KW - 0 KW - Endothelin-2 KW - Endothelin-3 KW - Endothelins KW - Receptor, Endothelin B KW - Receptors, Endothelin KW - Bromodeoxyuridine KW - G34N38R2N1 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - Endothelin-3 -- metabolism KW - Dose-Response Relationship, Drug KW - Mice KW - Receptors, Endothelin -- metabolism KW - Cell Survival KW - Endothelin-1 -- metabolism KW - Tetradecanoylphorbol Acetate -- metabolism KW - In Situ Hybridization KW - Endothelin-2 -- metabolism KW - Cells, Cultured KW - Mice, Inbred C57BL KW - Time Factors KW - Bromodeoxyuridine -- metabolism KW - Cell Division KW - Melanocytes -- physiology KW - Endothelins -- physiology KW - Neural Crest -- embryology KW - Signal Transduction UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69250083?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+and+cell+biology+%3D+Biochimie+et+biologie+cellulaire&rft.atitle=Endothelin+signalling+in+the+development+of+neural+crest-derived+melanocytes.&rft.au=Opdecamp%2C+K%3BKos%2C+L%3BArnheiter%2C+H%3BPavan%2C+W+J&rft.aulast=Opdecamp&rft.aufirst=K&rft.date=1998-01-01&rft.volume=76&rft.issue=6&rft.spage=1093&rft.isbn=&rft.btitle=&rft.title=Biochemistry+and+cell+biology+%3D+Biochimie+et+biologie+cellulaire&rft.issn=08298211&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-09-22 N1 - Date created - 1999-09-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Recent insights into the molecular basis of intrinsic resistance of colorectal cancer: new challenges for systemic therapeutic approaches. AN - 69203495; 10326673 JF - Cancer treatment and research AU - Grem, J L AD - Developmental Therapeutics Department, National Cancer Institute, National Naval Medical Center, Bethesda, MD 20889, USA. Y1 - 1998 PY - 1998 DA - 1998 SP - 293 EP - 338 VL - 98 SN - 0927-3042, 0927-3042 KW - Antimetabolites, Antineoplastic KW - 0 KW - Pyrimidines KW - Thymidylate Synthase KW - EC 2.1.1.45 KW - Fluorouracil KW - U3P01618RT KW - Index Medicus KW - Fluorouracil -- therapeutic use KW - Pyrimidines -- adverse effects KW - Thymidylate Synthase -- drug effects KW - Combined Modality Therapy KW - Humans KW - Cell Death -- drug effects KW - Antimetabolites, Antineoplastic -- therapeutic use KW - Drug Resistance, Neoplasm -- genetics KW - Colorectal Neoplasms -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69203495?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+treatment+and+research&rft.atitle=Recent+insights+into+the+molecular+basis+of+intrinsic+resistance+of+colorectal+cancer%3A+new+challenges+for+systemic+therapeutic+approaches.&rft.au=Grem%2C+J+L&rft.aulast=Grem&rft.aufirst=J&rft.date=1998-01-01&rft.volume=98&rft.issue=&rft.spage=293&rft.isbn=&rft.btitle=&rft.title=Cancer+treatment+and+research&rft.issn=09273042&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-07-14 N1 - Date created - 1999-07-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Assignment of the cyclin I gene (Ccni) to mouse chromosome 5E3.3-F1. 3 by in situ hybridization. AN - 69186624; 10072591 JF - Cytogenetics and cell genetics AU - Jensen, M R AU - Audolfsson, T AU - Keck, C L AU - Zimonjic, D B AU - Thorgeirsson, S S AD - Laboratory of Experimental Carcinogenesis, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD,USA. Y1 - 1998 PY - 1998 DA - 1998 SP - 242 EP - 243 VL - 83 IS - 3-4 SN - 0301-0171, 0301-0171 KW - CCNI protein, human KW - 0 KW - Ccni protein, mouse KW - Cyclin I KW - Cyclins KW - DNA, Complementary KW - Index Medicus KW - Animals KW - Humans KW - In Situ Hybridization, Fluorescence KW - Mice KW - Chromosome Mapping KW - Chromosomes -- genetics KW - Cyclins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69186624?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cytogenetics+and+cell+genetics&rft.atitle=Assignment+of+the+cyclin+I+gene+%28Ccni%29+to+mouse+chromosome+5E3.3-F1.+3+by+in+situ+hybridization.&rft.au=Jensen%2C+M+R%3BAudolfsson%2C+T%3BKeck%2C+C+L%3BZimonjic%2C+D+B%3BThorgeirsson%2C+S+S&rft.aulast=Jensen&rft.aufirst=M&rft.date=1998-01-01&rft.volume=83&rft.issue=3-4&rft.spage=242&rft.isbn=&rft.btitle=&rft.title=Cytogenetics+and+cell+genetics&rft.issn=03010171&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-03-30 N1 - Date created - 1999-03-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The effects of dietary boric acid on bone strength in rats. AN - 69179820; 10050932 AB - The effects of dietary boron (B) (from boric acid [BA]) on bone strength were evaluated using male F344 rats. B was administered by dietary admixture of BA to NIH-07 feed at concentrations of 200, 1000, 3000, and 9000 ppm. The latter two levels were found in previous studies to be reproductively toxic to both males and the developing fetus. The first two levels are below and just at, respectively, the levels for producing fetal malformations, and are below the dose required to produce male reproductive toxicity. Resistance to destructive testing was measured on femora, tibiae, and lumbar vertebrae. Although femur and tibia resistance to bending force were not affected by any amount of dietary B, vertebral resistance to a crushing force was increased by approximately 10%, at all dose levels (200-9000 ppm). These data show that even levels of BA that are not reproductively toxic can affect the strength of the axial skeleton in rats. JF - Biological trace element research AU - Chapin, R E AU - Ku, W W AU - Kenney, M A AU - McCoy, H AD - NIEHS, RTP, NC 27709, USA. Y1 - 1998 PY - 1998 DA - 1998 SP - 395 EP - 399 VL - 66 IS - 1-3 SN - 0163-4984, 0163-4984 KW - Boric Acids KW - 0 KW - boric acid KW - R57ZHV85D4 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Tibia -- physiology KW - Animals KW - Tibia -- drug effects KW - Femur -- physiology KW - Calcium -- blood KW - Dose-Response Relationship, Drug KW - Body Weight -- physiology KW - Humerus -- drug effects KW - Humerus -- physiology KW - Rats KW - Rats, Inbred F344 KW - Body Weight -- drug effects KW - Female KW - Femur -- drug effects KW - Male KW - Bone Density -- drug effects KW - Boric Acids -- metabolism KW - Diet KW - Boric Acids -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69179820?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+trace+element+research&rft.atitle=The+effects+of+dietary+boric+acid+on+bone+strength+in+rats.&rft.au=Chapin%2C+R+E%3BKu%2C+W+W%3BKenney%2C+M+A%3BMcCoy%2C+H&rft.aulast=Chapin&rft.aufirst=R&rft.date=1998-01-01&rft.volume=66&rft.issue=1-3&rft.spage=395&rft.isbn=&rft.btitle=&rft.title=Biological+trace+element+research&rft.issn=01634984&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-05-04 N1 - Date created - 1999-05-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular epidemiology of human cancer. AN - 69178290; 10026991 AB - A challenging goal of molecular epidemiology is to identify an individual's risk of cancer. Molecular epidemiology integrates molecular biology, in vitro and in vivo laboratory models, biochemistry and epidemiology to infer individual cancer risk. Molecular dosimetry of carcinogen exposure is an important facet of molecular epidemiology and cancer risk assessment. Carcinogen macromolecular adduct levels, cytogenetic alterations and somatic cell mutations can be measured to determine the biologically effective doses of carcinogens. Molecular epidemiology also explores host cancer susceptibilities, such as carcinogen metabolism, DNA repair, and epigenetic and genetic alterations in tumor suppressor genes. p53 is a prototype tumor suppressor gene and is well suited for analysis of mutational spectrum in human cancer. The analyses of germ line and somatic mutation spectra of the p53 tumor suppressor gene provide important clues for cancer risk assessment in molecular epidemiology. For example, characteristic p53 mutation spectra have been associated with: dietary aflatoxin B1 exposure and hepatocellular carcinoma; sunlight exposure and skin carcinoma; and cigarette smoking and lung cancer. The mutation spectrum also reveals those p53 mutants that provide cells with a selective clonal expansion advantage during the multistep process of carcinogenesis. The p53 gene encodes a multifunctional protein involved in the cellular response to stress including DNA damage and hypoxia. Certain p53 mutants lose tumor suppressor activity and gain oncogenic activity, which is one explanation for the commonality of p53 mutations in human cancer. Molecular epidemiological results can be evaluated for causation by inference of the Bradford-Hill criteria, i.e., strength of association (consistency, specificity and temporality) and biological plausibility, which utilizes the "weight of the evidence principle." JF - Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer AU - Hussain, S P AU - Harris, C C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, NIH, Bethesda, MD 20892-4255, USA. Y1 - 1998 PY - 1998 DA - 1998 SP - 22 EP - 36 VL - 154 SN - 0080-0015, 0080-0015 KW - Carcinogens KW - 0 KW - Tumor Suppressor Protein p53 KW - Index Medicus KW - Tumor Suppressor Protein p53 -- physiology KW - Apoptosis KW - Molecular Epidemiology KW - Genes, Tumor Suppressor KW - Humans KW - Carcinogens -- toxicity KW - Tumor Suppressor Protein p53 -- chemistry KW - Genetic Predisposition to Disease KW - Neoplasms -- genetics KW - Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69178290?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Recent+results+in+cancer+research.+Fortschritte+der+Krebsforschung.+Progres+dans+les+recherches+sur+le+cancer&rft.atitle=Molecular+epidemiology+of+human+cancer.&rft.au=Hussain%2C+S+P%3BHarris%2C+C+C&rft.aulast=Hussain&rft.aufirst=S&rft.date=1998-01-01&rft.volume=154&rft.issue=&rft.spage=22&rft.isbn=&rft.btitle=&rft.title=Recent+results+in+cancer+research.+Fortschritte+der+Krebsforschung.+Progres+dans+les+recherches+sur+le+cancer&rft.issn=00800015&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-03-05 N1 - Date created - 1999-03-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular aspects of vasopressin receptor function. AN - 69175506; 10026824 AB - The molecular mechanisms governing the G protein coupling selectivity of different members of the vasopressin receptor family were studied by using a combined molecular genetic/biochemical approach. While the V1a and V1b vasopressin receptors are selectively linked to G proteins of the Gq/11 class, the V2 vasopressin receptor is preferentially coupled to Gs. Systematic functional analysis of V1a/V2 hybrid receptors showed that the second intracellular loop of the V1a receptor is required and sufficient for efficient coupling to Gq/11, whereas the third intracellular loop of the V2 receptor is required and sufficient for coupling to Gs. By using a strategy involving the coexpression of the wild type V1a receptor with chimeric G protein alpha s/alpha q subunits, two C-terminal alpha q/11 residues were identified that are critical for proper receptor recognition. We previously demonstrated -in transiently transfected COS-7 cells- that selected mutant V2 vasopressin receptors (all of which have been identified in X-linked nephrogenic diabetes insipidus patients) containing inactivating mutations in the C-terminal third of the receptor protein (including missense, frameshift, or nonsense mutations) can be functionally rescued by coexpression with a C-terminal V2 receptor fragment (V2-tail) spanning the region where the various mutations occur. Co-immunoprecipitation experiments and a newly developed sandwich ELISA revealed that the V2-tail polypeptide directly interacts with the mutant V2 receptors thus creating a functional receptor protein. To study the potential therapeutic usefulness of these findings, CHO cell lines stably expressing low levels of functionally inactive mutant V2 vasopressin receptors (E242stop, Y280C, and W284stop) were created and infected with a recombinant adenovirus coding for the V2-tail polypeptide. Following adenovirus infection, arginine vasopressin (AVP) gained the ability to stimulate cAMP formation in all CHO cell clones studied. Adenovirus-mediated gene transfer also proved to be a highly efficient method to achieve expression of the V2-tail fragment (as well as of the wild type V2 vasopressin receptor) in MDCK renal tubular cells. We therefore speculate that the targeted expression of receptor fragments in vivo may represent a novel strategy in the treatment of human diseases caused by inactivating mutations in distinct G protein-coupled receptors. JF - Advances in experimental medicine and biology AU - Schöneberg, T AU - Kostenis, E AU - Liu, J AU - Gudermann, T AU - Wess, J AD - Laboratory of Bioorganic Chemistry, NIH-NIDDK, Bethesda, Maryland 20892, USA. Y1 - 1998 PY - 1998 DA - 1998 SP - 347 EP - 358 VL - 449 SN - 0065-2598, 0065-2598 KW - Receptors, Vasopressin KW - 0 KW - Recombinant Fusion Proteins KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - Index Medicus KW - Animals KW - Protein Structure, Secondary KW - COS Cells KW - Models, Molecular KW - Humans KW - Amino Acid Sequence KW - Diabetes Insipidus -- genetics KW - Recombinant Fusion Proteins -- chemistry KW - Mutagenesis, Site-Directed KW - Recombinant Fusion Proteins -- metabolism KW - X Chromosome KW - Transfection KW - GTP-Binding Proteins -- metabolism KW - Molecular Sequence Data KW - Receptors, Vasopressin -- physiology KW - Receptors, Vasopressin -- chemistry KW - Receptors, Vasopressin -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69175506?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Advances+in+experimental+medicine+and+biology&rft.atitle=Molecular+aspects+of+vasopressin+receptor+function.&rft.au=Sch%C3%B6neberg%2C+T%3BKostenis%2C+E%3BLiu%2C+J%3BGudermann%2C+T%3BWess%2C+J&rft.aulast=Sch%C3%B6neberg&rft.aufirst=T&rft.date=1998-01-01&rft.volume=449&rft.issue=&rft.spage=347&rft.isbn=&rft.btitle=&rft.title=Advances+in+experimental+medicine+and+biology&rft.issn=00652598&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-03-10 N1 - Date created - 1999-03-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Translational control elements in the major human transforming growth factor-beta 1 mRNA. AN - 69164683; 9932227 AB - Polysome analysis indicates that the major 2.4 kb transforming growth factor-beta 1 (TGF-beta 1) transcript is poorly translated, both in cultured cells, and in vivo in mouse liver. In contrast, the TGF-beta 2 transcripts are efficiently translated. The contribution of the 5'- and 3'-untranslated regions (UTRs) to the translational inhibition of the full-length TGF-beta 1 transcript was studied by deletion analysis. Despite their high G + C content, both UTRs stimulated translation in vitro. However, polysome analysis of synthetic TGF-beta 1 mRNAs transfected into MCF-7 cells suggests that the cell contains a limited pool of trans-acting factors that interact with the 5'UTR to make it inhibitory in vivo. Further deletion analysis in vitro revealed multiple stimulatory and inhibitory regions in the 5'UTR. This has important implications for the translatability of the naturally occurring shorter TGF-beta 1 transcripts and provides a framework for higher resolution mapping studies. Overall, the poor translational efficiency of the major TGF-beta 1 mRNA in vivo appears to be due to a combination of poor initiation sequence context, and inhibitory interactions of limiting transacting factors with cis-inhibitory elements embedded in an otherwise stimulatory 5'UTR. JF - Growth factors (Chur, Switzerland) AU - Allison, R S AU - Mumy, M L AU - Wakefield, L M AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1998 PY - 1998 DA - 1998 SP - 89 EP - 100 VL - 16 IS - 2 SN - 0897-7194, 0897-7194 KW - 3' Untranslated Regions KW - 0 KW - 5' Untranslated Regions KW - RNA, Messenger KW - Transforming Growth Factor beta KW - Index Medicus KW - Regulatory Sequences, Nucleic Acid KW - Tumor Cells, Cultured KW - Open Reading Frames KW - Humans KW - Protein Biosynthesis KW - Transforming Growth Factor beta -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69164683?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Growth+factors+%28Chur%2C+Switzerland%29&rft.atitle=Translational+control+elements+in+the+major+human+transforming+growth+factor-beta+1+mRNA.&rft.au=Allison%2C+R+S%3BMumy%2C+M+L%3BWakefield%2C+L+M&rft.aulast=Allison&rft.aufirst=R&rft.date=1998-01-01&rft.volume=16&rft.issue=2&rft.spage=89&rft.isbn=&rft.btitle=&rft.title=Growth+factors+%28Chur%2C+Switzerland%29&rft.issn=08977194&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-04-13 N1 - Date created - 1999-04-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Diet and mammary gland carcinogenesis. AN - 69161305; 9928542 AB - The variation in human breast cancer incidence rates worldwide suggests that lifestyle factors, especially diet, influence breast cancer risk. There is convincing evidence that diets associated with rapid growth and greater adult height increase breast cancer risk. In addition, diet and other lifestyle factors which lead to high body mass, especially during postmenopausal years, also appear to increase risk. Several dietary components have been evaluated in epidemiological and animal studies for their role in breast cancer. Dietary fat was once implicated in the high incidence of breast cancer in the Western world, but its role in breast cancer is now controversial. In contrast, alcohol consumption is currently recognized as the best-established dietary risk factor in this disease. Carcinogens that cause mammary gland cancer in rats such as heterocyclic amines and polycyclic aromatic hydrocarbons are found in cooked meat, but it is not yet known if these carcinogens are etiological factors in human breast cancer. Fruits and vegetables are rich in potential chemopreventive factors that may lower breast cancer risk. Practical approaches to dietary modification that include increasing fruit and vegetable consumption, eating a low fat diet, reducing cooked meat consumption, and avoiding alcohol are likely to be of potential overall benefit in lowering the risk of human breast cancer. JF - Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer AU - Snyderwine, E G AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, Bethesda, MD 20892-4255, USA. Y1 - 1998 PY - 1998 DA - 1998 SP - 3 EP - 10 VL - 152 SN - 0080-0015, 0080-0015 KW - Carcinogens KW - 0 KW - Dietary Fats KW - Index Medicus KW - Animals KW - Dietary Fats -- adverse effects KW - Risk Factors KW - Humans KW - Energy Metabolism -- physiology KW - Incidence KW - Mammary Neoplasms, Experimental -- etiology KW - Female KW - Breast Neoplasms -- etiology KW - Breast Neoplasms -- epidemiology KW - Diet -- adverse effects KW - Carcinogens -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69161305?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Recent+results+in+cancer+research.+Fortschritte+der+Krebsforschung.+Progres+dans+les+recherches+sur+le+cancer&rft.atitle=Diet+and+mammary+gland+carcinogenesis.&rft.au=Snyderwine%2C+E+G&rft.aulast=Snyderwine&rft.aufirst=E&rft.date=1998-01-01&rft.volume=152&rft.issue=&rft.spage=3&rft.isbn=&rft.btitle=&rft.title=Recent+results+in+cancer+research.+Fortschritte+der+Krebsforschung.+Progres+dans+les+recherches+sur+le+cancer&rft.issn=00800015&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-03-12 N1 - Date created - 1999-03-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Immunity to pertussis. Not all virulence factors are protective antigens. AN - 69136098; 9889975 AB - As with diphtheria, immunity to pertussis is complex because it involves both individual and community protection against infection with B. pertussis. Although B. pertussis has at least five proteins required for virulence and an additional two "toxic" components, only serum neutralizing antibodies to PT (antitoxin) have been shown to confer immunity to pertussis. JF - Advances in experimental medicine and biology AU - Robbins, J B AU - Schneerson, R AU - Bryla, D A AU - Trollfors, B AU - Taranger, J AU - Lagergård, T AD - National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998 PY - 1998 DA - 1998 SP - 207 EP - 218 VL - 452 SN - 0065-2598, 0065-2598 KW - Pertussis Vaccine KW - 0 KW - Index Medicus KW - Humans KW - Child KW - Child, Preschool KW - Whooping Cough -- prevention & control KW - Whooping Cough -- immunology KW - Pertussis Vaccine -- immunology KW - Pertussis Vaccine -- therapeutic use KW - Whooping Cough -- physiopathology KW - Bordetella pertussis -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69136098?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Advances+in+experimental+medicine+and+biology&rft.atitle=Immunity+to+pertussis.+Not+all+virulence+factors+are+protective+antigens.&rft.au=Robbins%2C+J+B%3BSchneerson%2C+R%3BBryla%2C+D+A%3BTrollfors%2C+B%3BTaranger%2C+J%3BLagerg%C3%A5rd%2C+T&rft.aulast=Robbins&rft.aufirst=J&rft.date=1998-01-01&rft.volume=452&rft.issue=&rft.spage=207&rft.isbn=&rft.btitle=&rft.title=Advances+in+experimental+medicine+and+biology&rft.issn=00652598&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-02-02 N1 - Date created - 1999-02-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In vivo imaging of brain nicotinic acetylcholine receptors with 5-[123I]iodo-A-85380 using single photon emission computed tomography. AN - 69104257; 9870715 AB - The distribution and kinetics of 5-[123I]iodo-A-85380, a novel ligand for brain nicotinic acetylcholine receptors (nAChRs), were evaluated in the Rhesus monkey using single photon emission computed tomography (SPECT). Peak levels of radioactivity were measured in brain at 90 min after injection of the tracer. Accumulation of radioactivity was highest in the thalamus, intermediate in the frontal cortex and basal ganglia, and lowest in the cerebellum. The ratio of specific to nonspecific binding (V3") in the thalamus, estimated from the (thalamic-cerebellar)/cerebellar radioactivity ratio, reached a value of 6 at 4 h post-injection. Specific binding was reduced by subcutaneous injection of 1 mg/kg cytisine at 2.25 h after injection of radiotracer. At 2.5 h after cytisine administration, radioactivity in the thalamus was reduced by 84%, in the frontal cortex, by 76%, and in the basal ganglia, by 57% of the level measured at the time of cytisine administration, demonstrating that the binding was reversible. On the basis of these findings, together with other data indicating high affinity, receptor subtype selectivity, low nonspecific binding and lack of toxicity in animals, 5-[123I]iodo-A-85380 appears to be a promising ligand for SPECT imaging of nAChRs in the human brain. JF - Life sciences AU - Chefer, S I AU - Horti, A G AU - Lee, K S AU - Koren, A O AU - Jones, D W AU - Gorey, J G AU - Links, J M AU - Mukhin, A G AU - Weinberger, D R AU - London, E D AD - Brain Imaging Center, Intramural Research Program, National Institute on Drug Abuse, National Institute of Health, Baltimore, MD 21224, USA. Y1 - 1998 PY - 1998 DA - 1998 SP - PL355 EP - PL360 VL - 63 IS - 25 SN - 0024-3205, 0024-3205 KW - A 85380 KW - 0 KW - Azetidines KW - Iodine Radioisotopes KW - Radiopharmaceuticals KW - Receptors, Nicotinic KW - Index Medicus KW - Animals KW - Tomography, Emission-Computed, Single-Photon KW - Macaca mulatta KW - Tissue Distribution KW - Male KW - Radiopharmaceuticals -- pharmacokinetics KW - Azetidines -- pharmacokinetics KW - Receptors, Nicotinic -- metabolism KW - Radiopharmaceuticals -- metabolism KW - Azetidines -- metabolism KW - Brain -- metabolism KW - Brain -- ultrastructure KW - Brain -- diagnostic imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69104257?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Life+sciences&rft.atitle=In+vivo+imaging+of+brain+nicotinic+acetylcholine+receptors+with+5-%5B123I%5Diodo-A-85380+using+single+photon+emission+computed+tomography.&rft.au=Chefer%2C+S+I%3BHorti%2C+A+G%3BLee%2C+K+S%3BKoren%2C+A+O%3BJones%2C+D+W%3BGorey%2C+J+G%3BLinks%2C+J+M%3BMukhin%2C+A+G%3BWeinberger%2C+D+R%3BLondon%2C+E+D&rft.aulast=Chefer&rft.aufirst=S&rft.date=1998-01-01&rft.volume=63&rft.issue=25&rft.spage=PL355&rft.isbn=&rft.btitle=&rft.title=Life+sciences&rft.issn=00243205&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-01-08 N1 - Date created - 1999-01-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Age of onset of drug use and its association with DSM-IV drug abuse and dependence: results from the National Longitudinal Alcohol Epidemiologic Survey. AN - 69080038; 9854701 AB - The purpose of this study was to examine the relationship between early onset drug use and the development of lifetime DSM-IV drug abuse and dependence using a representative sample of the U.S. population. Prevalences of lifetime drug abuse and dependence were estimated for each year of age of onset of drug use from ages 13 and younger to 21 and older for the overall sample of drug users by race and gender. Linear logistic analyses were conducted to assess the relationship between age of drug use onset and lifetime drug use disorders controlling for important covariates. The major finding of this study was that early onset drug use is a significant predictor of the subsequent development of drug abuse over the life course. Early onset drug use was also a significant predictor of the subsequent development of lifetime alcohol dependence among males, females, and nonblacks, but not among blacks. After adjusting for important model covariates, the likelihood of lifetime drug abuse and dependence among the total sample of lifetime drug users was reduced by 4% and 5% with each year drug use onset was delayed. Implications of these findings are discussed in terms of the importance of collecting national data on drug use, abuse and dependence and the need for further research and its integration with prevention efforts. JF - Journal of substance abuse AU - Grant, B F AU - Dawson, D A AD - Division of Biometry and Epidemiology, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland 20852-7003, USA. Y1 - 1998 PY - 1998 DA - 1998 SP - 163 EP - 173 VL - 10 IS - 2 SN - 0899-3289, 0899-3289 KW - Index Medicus KW - Regression Analysis KW - Age Factors KW - Sex Factors KW - Humans KW - African Americans -- statistics & numerical data KW - European Continental Ancestry Group -- psychology KW - Aged KW - European Continental Ancestry Group -- statistics & numerical data KW - Longitudinal Studies KW - Cross-Sectional Studies KW - African Americans -- psychology KW - Adult KW - Incidence KW - Middle Aged KW - Adolescent KW - United States -- epidemiology KW - Male KW - Female KW - Substance-Related Disorders -- diagnosis KW - Psychiatric Status Rating Scales KW - Alcoholism -- epidemiology KW - Alcoholism -- diagnosis KW - Substance-Related Disorders -- psychology KW - Alcoholism -- psychology KW - Substance-Related Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69080038?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+substance+abuse&rft.atitle=Age+of+onset+of+drug+use+and+its+association+with+DSM-IV+drug+abuse+and+dependence%3A+results+from+the+National+Longitudinal+Alcohol+Epidemiologic+Survey.&rft.au=Grant%2C+B+F%3BDawson%2C+D+A&rft.aulast=Grant&rft.aufirst=B&rft.date=1998-01-01&rft.volume=10&rft.issue=2&rft.spage=163&rft.isbn=&rft.btitle=&rft.title=Journal+of+substance+abuse&rft.issn=08993289&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-03-16 N1 - Date created - 1999-03-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Symptoms and characteristics of individuals with different types of recovery from DSM-IV alcohol dependence. AN - 69079749; 9854699 AB - Symptoms and criteria for DSM-IV alcohol dependence and demographic and drinking characteristics are compared for three groups. Group I (N = 1,044) consists of persons who formerly met the criteria for dependence but were abstinent in the past year, Group II (N = 2,325) consists of persons who were formerly dependent but did not meet the criteria for abuse or dependence in the past year despite drinking, and Group III (N = 22,204) consists of persons who never met the criteria for dependence. Members of Group II lay between members of Groups I and III in terms of the numbers of prior dependence symptoms and criteria, past level of intake, degree of familial alcoholism and history of alcohol treatment. Both groups of former alcoholics were equally likely to have experienced withdrawal, drinking more/longer than intended and tolerance. The criteria that most strongly distinguished the groups were continued use despite physical or psychological consequences, time spent drinking and activities given up, all of which were far more common in Group I than in Group II. Members of Group II had earlier onsets of heavy drinking and dependence than members of Group I, supporting the existence of a developmentally limited subtype of alcoholism that is subject to spontaneous remission in early adulthood without treatment. The paper compares three options for tightening the criteria for dependence, all of which remove more members from Group II (28% to 41% depending on option) than from Group I (12% to 19%). JF - Journal of substance abuse AU - Dawson, D A AD - Division of Biometry and Epidemiology, National Institutes on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892-7003, USA. Y1 - 1998 PY - 1998 DA - 1998 SP - 127 EP - 142 VL - 10 IS - 2 SN - 0899-3289, 0899-3289 KW - Index Medicus KW - Humans KW - Adult KW - Treatment Outcome KW - Alcohol Withdrawal Delirium -- diagnosis KW - Middle Aged KW - Follow-Up Studies KW - Male KW - Individuality KW - Female KW - Alcoholism -- rehabilitation KW - Psychiatric Status Rating Scales KW - Alcoholism -- diagnosis KW - Alcoholism -- classification KW - Alcoholism -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69079749?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+substance+abuse&rft.atitle=Symptoms+and+characteristics+of+individuals+with+different+types+of+recovery+from+DSM-IV+alcohol+dependence.&rft.au=Dawson%2C+D+A&rft.aulast=Dawson&rft.aufirst=D&rft.date=1998-01-01&rft.volume=10&rft.issue=2&rft.spage=127&rft.isbn=&rft.btitle=&rft.title=Journal+of+substance+abuse&rft.issn=08993289&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-03-16 N1 - Date created - 1999-03-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Working Sisters from Outside: Rural Chinese Household Workers in Beijing AN - 61433354; 9904131 AB - Draws on in-depth interviews & field observations of rural women migrating to Beijing, People's Republic of China, in search of work as housemaids in official & informal labor markets. This evidence is set in the larger context of economic reform & rural-urban migration patterns in China. The situation of the "working sisters from outside," as seen in an extended case study of one household worker, casts light on the rich-poor gap under improving economic conditions for the country as a whole. 28 References. Adapted from the source document. JF - Current Research on Occupations and Professions AU - Kejing, Dai AU - Dempsey, Paula R AD - Instit Sociology Chinese Academy Social Sciences, 5 Jianguomen Nei Da Jie 5 Hao Beijing Y1 - 1998///0, PY - 1998 DA - 0, 1998 SP - 11 EP - 29 VL - 10 KW - Economic Change KW - Domestics KW - Income Inequality KW - Rural Women KW - Peking, Peoples Republic of China KW - Rural to Urban Migration KW - article KW - 0621: complex organization; jobs, work organization, workplaces, & unions UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/61433354?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Asocabs&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+Research+on+Occupations+and+Professions&rft.atitle=Working+Sisters+from+Outside%3A+Rural+Chinese+Household+Workers+in+Beijing&rft.au=Kejing%2C+Dai%3BDempsey%2C+Paula+R&rft.aulast=Kejing&rft.aufirst=Dai&rft.date=1998-01-01&rft.volume=10&rft.issue=&rft.spage=11&rft.isbn=&rft.btitle=&rft.title=Current+Research+on+Occupations+and+Professions&rft.issn=&rft_id=info:doi/ LA - English DB - Sociological Abstracts N1 - Date revised - 2007-04-01 N1 - Last updated - 2016-09-28 N1 - CODEN - CROPEO N1 - SubjectsTermNotLitGenreText - Rural Women; Rural to Urban Migration; Peking, Peoples Republic of China; Domestics; Economic Change; Income Inequality ER - TY - JOUR T1 - Homology Model Building of Hho1p Supports its Role as a Yeast Histone H1 Protein AN - 20241661; 8720606 AB - Biochemical studies to date have not been able to identify the linker histone H1 protein in the budding yeast Saccharomyces cerevisiae. Database homology searching against the complete yeast genome has identified a gene, HHO1, (or YPL127C, formerly LPI17) which encodes a protein that has two regions that show similarity to the pea histone H1 globular domain. To determine whether Hho1p can assume the shape of an H1 protein, homology model building experiments were performed using the structure of chicken histone H5 globular domain as the basis for comparison. A statistically significant match between each of the two globular domains of Hho1p and the chicken histone H5 structure was obtained, and probability values indicate that there is a less than 1 in 100 chance that such a match would be the result of a random event. These findings support the proposal that Hho1p acts as an "H1 dimer" and could be responsible for the decreased linker DNA length observed between nucleosomal core particles. JF - In Silico Biology AU - Baxevanis, Andreas D AU - Landsman, David AD - Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA, e-mail: andy[at]nhgri.nih.gov Y1 - 1998 PY - 1998 DA - 1998 SP - 5 EP - 11 PB - IOS Press, Nieuwe Hemweg 6B VL - 1 IS - 1 SN - 1386-6338, 1386-6338 KW - Microbiology Abstracts C: Algology, Mycology & Protozoology; Biochemistry Abstracts 2: Nucleic Acids; Biotechnology and Bioengineering Abstracts KW - histone H1 KW - HHO1 KW - homology model building KW - protein structure prediction KW - Y chromosome KW - Genomes KW - Databases KW - Histone H5 KW - Homology KW - Core particles KW - Statistical analysis KW - DNA KW - Histone H1 KW - Saccharomyces cerevisiae KW - Models KW - N 14820:DNA Metabolism & Structure KW - W 30960:Bioinformatics & Computer Applications KW - K 03310:Genetics & Taxonomy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20241661?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=In+Silico+Biology&rft.atitle=Homology+Model+Building+of+Hho1p+Supports+its+Role+as+a+Yeast+Histone+H1+Protein&rft.au=Baxevanis%2C+Andreas+D%3BLandsman%2C+David&rft.aulast=Baxevanis&rft.aufirst=Andreas&rft.date=1998-01-01&rft.volume=1&rft.issue=1&rft.spage=5&rft.isbn=&rft.btitle=&rft.title=In+Silico+Biology&rft.issn=13866338&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 - Genomes; Y chromosome; Databases; Histone H5; Homology; Core particles; DNA; Statistical analysis; Histone H1; Models; Saccharomyces cerevisiae ER - TY - JOUR T1 - Sources of Systematic Error in Functional Annotation of Genomes: Domain Rearrangement, Non-Orthologous Gene Displacement and Operon Disruption AN - 20128679; 8720604 AB - Functional annotation of proteins encoded in newly sequenced genomes can be expected to meet two conflicting objectives: (i) provide as much information as possible, and (ii) avoid erroneous functional assignments and over-predictions. The continuing exponential growth of the number of sequenced genomes makes the quality of sequence annotation a critical factor in the efforts to utilize this new information. When dubious functional assignments are used as a basis for subsequent predictions, they tend to proliferate, leading to "database explosion". It is therefore important to identify the common factors that hamper functional annotation. As a first step towards that goal, we have compared the annotations of the Mycoplasma genitalium and Methanococcus jannaschii genomes produced in several independent studies. The most common causes of questionable predictions appear to be: i) non-critical use of annotations from existing database entries; ii) taking into account only the annotation of the best database hit; iii) insufficient masking of low complexity regions (e.g. non-globular domains) in protein sequences, resulting in spurious database hits obscuring relevant ones; iv) ignoring multi-domain organization of the query proteins and/or the database hits; v) non-critical functional inferences on the basis of the functions of neighboring genes in an operon; vi) non-orthologous gene displacement, i.e. involvement of structurally unrelated proteins in the same function. These observations suggest that case by case validation of functional annotation by expert biologists remains crucial for productive genome analysis. JF - In Silico Biology AU - Galperin, Michael Y AU - Koonin, Eugene V AD - National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland 20894, USA, E-mail: galperin[at]ncbi.nlm.nih.gov Y1 - 1998 PY - 1998 DA - 1998 SP - 55 EP - 67 PB - IOS Press, Nieuwe Hemweg 6B VL - 1 IS - 1 SN - 1386-6338, 1386-6338 KW - Microbiology Abstracts B: Bacteriology; Genetics Abstracts; Biotechnology and Bioengineering Abstracts KW - genome comparison KW - prediction of gene functions KW - systematic error KW - database annotation KW - automatic genome annotation, KW - manual genome annotation KW - low complexity KW - non-globular domains KW - multi-domain proteins KW - non-orthologous gene displacement KW - Genomes KW - Databases KW - Methanococcus KW - Mycoplasma genitalium KW - Information processing KW - gene rearrangement KW - Operons KW - J 02310:Genetics & Taxonomy KW - W 30960:Bioinformatics & Computer Applications KW - G 07770:Bacteria UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20128679?accountid=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=In+Silico+Biology&rft.atitle=Sources+of+Systematic+Error+in+Functional+Annotation+of+Genomes%3A+Domain+Rearrangement%2C+Non-Orthologous+Gene+Displacement+and+Operon+Disruption&rft.au=Galperin%2C+Michael+Y%3BKoonin%2C+Eugene+V&rft.aulast=Galperin&rft.aufirst=Michael&rft.date=1998-01-01&rft.volume=1&rft.issue=1&rft.spage=55&rft.isbn=&rft.btitle=&rft.title=In+Silico+Biology&rft.issn=13866338&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 - Genomes; Databases; gene rearrangement; Information processing; Operons; Methanococcus; Mycoplasma genitalium ER - TY - JOUR T1 - Theophylline-induced mesenteric periarteritis in F344/N rats AN - 18387267; 5376867 AB - The toxicity and carcinogenic potential of theophylline (an alkaloid bronchodilator drug) was investigated in male and female F344/N rats in 16-day, 14-week, and 2-year gavage and feeding studies. In 16-day studies, rats were fed diets containing 0, 500, 1000, 2000, 4000, and 8000 ppm of theophylline or given 0, 12.5 (twice daily), 25 (once daily), 50 (once daily), 50 (twice daily), 100 (once daily), 200 (once daily), 200 (twice daily), and 400 (once daily) mg theophylline/kg body weight in corn oil by gavage. In 14-week studies, rats were fed diets containing 0, 1000, 2000, and 4000 ppm theophylline or given 0, 37.5, 75, and 150 mg/kg body weight theophylline in corn oil by gavage. In 2-year gavage studies, rats were given 0, 7.5, 25, and 75 mg/kg body weight in corn oil. In 16-day gavage studies, treatment-related periarteritis occurred in arteries of the pancreas and adjacent to the mesenteric lymph nodes of early death male and female rats given 400 mg/kg once daily. In the 14-week studies, treatment-related periarteritis occurred at similar sites and in male rats exposed to 75 and 150 mg/kg, and in all exposed female rats (gavage studies), in females exposed to 1000 ppm, and in both sexes exposed to 2000 and 4000 ppm (feeding studies). In the 2-year study, chronic periarteritis was significantly increased only in the males receiving 75 mg/kg of theophylline. The adventitia, media and intima of medium- and large-sized mesenteric arteries were involved. Similar to other vasodilator chemicals, the pathogenesis of theophylline-induced vascular lesions may be a consequence of hemodynamic changes induced in the vascular wall. JF - Archives of Toxicology AU - Nyska, A AU - Herbert, R A AU - Chan, P C AU - Haseman, J K AU - Hailey, J R AD - Environmental Toxicology Program, National Institute of Environmental Health Sciences, P.O. Box 12233, Research Triangle Park, NC 27709, USA Y1 - 1998 PY - 1998 DA - 1998 SP - 731 EP - 737 PB - Springer-Verlag (Berlin), Heidelberger Platz 3 Berlin 14197 Germany, [mailto:subscriptions@springer.de] VL - 72 IS - 11 SN - 0340-5761, 0340-5761 KW - mesenteric periarteritis KW - rats KW - Toxicology Abstracts KW - X 24112:Chronic exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18387267?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+Toxicology&rft.atitle=Theophylline-induced+mesenteric+periarteritis+in+F344%2FN+rats&rft.au=Nyska%2C+A%3BHerbert%2C+R+A%3BChan%2C+P+C%3BHaseman%2C+J+K%3BHailey%2C+J+R&rft.aulast=Nyska&rft.aufirst=A&rft.date=1998-01-01&rft.volume=72&rft.issue=11&rft.spage=731&rft.isbn=&rft.btitle=&rft.title=Archives+of+Toxicology&rft.issn=03405761&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - HIV Risk Behaviors Associated with the Injection Process: Multiperson Use of Drug Injection Equipment and Paraphernalia in Injection Drug User Networks AN - 17576875; 4499022 AB - This study examines drug acquisition and multiperson use of paraphernalia, drugs, and needles/syringes. Ethnographers observed 54 injection episodes in which IDUs were linked by HIV risk behaviors, and developed a typology of higher-risk, lower-risk, and nonsharing-risk networks. Multiperson use of injection paraphernalia or drug solution occurred in most injection events (94%). Serial use of syringes/needles occurred infrequently (14%) relative to "backloading" (37%) and reuse of paraphernalia (cookers 84%, cotton 77%, water 77%). Higher-risk injection networks were characterized by larger size and pooling of resources for drugs. Prevention messages must include avoiding reuse of injection paraphernalia and transfer of drug solution. JF - Substance Use and Misuse AU - Needle, R H AU - Coyle, S AU - Cesari, H AU - Trotter, R AU - Clatts, M AU - Koester, S AU - Price, L AU - McLellan, E AU - Finlinson, A AU - Bluthenthal, R N AU - Pierce, T AU - Johnson, J AU - Jones, T S AU - Williams, M AD - National Institute on Drug Abuse, Rockville, Maryland, USA, rh28e@nih.gov Y1 - 1998 PY - 1998 DA - 1998 SP - 2403 EP - 2423 VL - 33 IS - 12 SN - 1082-6084, 1082-6084 KW - HIV-1 KW - drug abuse KW - needles KW - Health & Safety Science Abstracts; Virology & AIDS Abstracts KW - Risk assessment KW - Acquired immune deficiency syndrome KW - Drug abuse KW - Disease transmission KW - Education KW - Human immunodeficiency virus KW - Human immunodeficiency virus 1 KW - Syringes KW - H 11000:Diseases/Injuries/Trauma KW - V 22005:AIDS: Epidemiological aspects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17576875?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthsafetyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Substance+Use+and+Misuse&rft.atitle=HIV+Risk+Behaviors+Associated+with+the+Injection+Process%3A+Multiperson+Use+of+Drug+Injection+Equipment+and+Paraphernalia+in+Injection+Drug+User+Networks&rft.au=Needle%2C+R+H%3BCoyle%2C+S%3BCesari%2C+H%3BTrotter%2C+R%3BClatts%2C+M%3BKoester%2C+S%3BPrice%2C+L%3BMcLellan%2C+E%3BFinlinson%2C+A%3BBluthenthal%2C+R+N%3BPierce%2C+T%3BJohnson%2C+J%3BJones%2C+T+S%3BWilliams%2C+M&rft.aulast=Needle&rft.aufirst=R&rft.date=1998-01-01&rft.volume=33&rft.issue=12&rft.spage=2403&rft.isbn=&rft.btitle=&rft.title=Substance+Use+and+Misuse&rft.issn=10826084&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Human immunodeficiency virus 1; Human immunodeficiency virus; Risk assessment; Education; Acquired immune deficiency syndrome; Drug abuse; Disease transmission; Syringes ER - TY - JOUR T1 - Evaluation of the patient with recurrent bacterial infections AN - 17332863; 4613031 AB - Recurrent bacterial infection is a complaint encountered regularly in the course of both adult and pediatric care. Defects of neutrophils and monocytes are most commonly associated with recurrent infection, but abnormalities of immunoglobulins and complement must be considered. Defensins, small antibacterial peptides, have been implicated recently in some of the infectious diathesis of cystic fibrosis. A thorough history and physical examination focused on severity, sequelae, and microbiology of infections can usually determine whether a patient needs further evaluation. The diseases and syndromes most frequently associated with recurrent infection are presented, along with discriminating clinical, pathologic, and microbiologic features. JF - Annual Review of Medicine AU - Holland, S M AU - Gallin, JI AD - Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA, smh@nih.gov Y1 - 1998 PY - 1998 DA - 1998 SP - 185 EP - 199 VL - 49 SN - 0066-4219, 0066-4219 KW - man KW - Microbiology Abstracts B: Bacteriology KW - Bacteria KW - Pediatrics KW - Reviews KW - Leukocytes (neutrophilic) KW - Recurrent infection KW - Monocytes KW - Children KW - J 02833:Immune response and immune mechanisms UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17332863?accountid=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=Annual+Review+of+Medicine&rft.atitle=Evaluation+of+the+patient+with+recurrent+bacterial+infections&rft.au=Holland%2C+S+M%3BGallin%2C+JI&rft.aulast=Holland&rft.aufirst=S&rft.date=1998-01-01&rft.volume=49&rft.issue=&rft.spage=185&rft.isbn=&rft.btitle=&rft.title=Annual+Review+of+Medicine&rft.issn=00664219&rft_id=info:doi/10.1146%2Fannurev.med.49.1.185 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Children; Leukocytes (neutrophilic); Reviews; Recurrent infection; Pediatrics; Bacteria; Monocytes DO - http://dx.doi.org/10.1146/annurev.med.49.1.185 ER - TY - JOUR T1 - Cardiopulmonary effects of inhaled nitric oxide in normal dogs and during E. coli pneumonia and sepsis AN - 17286620; 4514926 AB - We investigated the effect of inhaled nitric oxide (NO) at increasing fractional inspired O sub(2) concentrations (FI sub(O2)) on hemodynamic and pulmonary function during Escherichia coli pneumonia. Thirty-eight conscious, spontaneously breathing, tracheotomized 2-yr-old beagles had intrabronchial inoculation with either 0.75 or 1.5 x 10 super(10) colony-forming units/kg of E. coli 0111:B4 (infected) or 0.9% saline (noninfected) in one or four pulmonary lobes. We found that neither the severity nor distribution (lobar vs. diffuse) of bacterial pneumonia altered the effects of NO. However, in infected animals, with increasing FI sub(O2) (0.08, 0.21, 0.50, and 0.85), NO (80 parts/million) progressively increased arterial PO sub(2) [-0.3 plus or minus 0.6, 3 plus or minus 1, 13 plus or minus 4, 10 plus or minus 9 (mean plus or minus SE) Torr, respectively] and decreased the mean arterial-alveolar O sub(2) gradient (0.5 plus or minus 0.3, 4 plus or minus 2, -8 plus or minus 7, -10 plus or minus 9 Torr, respectively). In contrast, in noninfected animals, the effect of NO was significantly different and opposite; NO progressively decreased mean PO sub(2) with increasing FI sub(O2) (2 plus or minus 1, -5 plus or minus 3, -2 plus or minus 3, and -12 plus or minus 5 Torr, respectively; P < 0.05 compared with infected animals) and increased mean arterial-alveolar O sub(2) gradient (0.3 plus or minus 0.04, 2 plus or minus 2, 1 plus or minus 3, 11 plus or minus 5 Torr; P < 0.05 compared with infected animals). In normal and infected animals alike, only at FI sub(O2) less than or equal to 0.21 did NO significantly lower mean pulmonary artery pressure, pulmonary artery occlusion pressure, and pulmonary vascular resistance index (all P < 0.01). However, inhaled NO had no significant effect on increases in mean pulmonay artery pressure associated with bacterial pneumonia. Thus, during bacterial pneumonia, inhaled NO had only modest effects on oxygenation dependent on high FI sub(O2) and did not affect sepsis-induced pulmonary hypertension. These data do not support a role for inhaled NO in bacterial pneumonia. Further studies are necessary to determine whether, in combination with ventilatory support, NO may have more pronounced effects. JF - Journal of Applied Physiology AU - Quezado, ZMN AU - Natanson, C AU - Karzai, W AU - Danner, R L AU - Koev, CA AU - Fitz, Y AU - Dolan, D P AU - Richmond, S AU - Banks, S M AU - Wilson, L AU - Eichacker, P Q AD - Critical Care Medicine Dept., National Institutes of Health, Bldg. 10, Rm. 7D43, 9000 Rockville Pike, Bethesda, MD 20892, USA Y1 - 1998/01// PY - 1998 DA - Jan 1998 SP - 107 EP - 115 VL - 84 IS - 1 SN - 8750-7587, 8750-7587 KW - dogs KW - Microbiology Abstracts B: Bacteriology KW - Ventilation KW - Hemodynamics KW - Sepsis KW - Lung KW - Escherichia coli KW - Nitric oxide KW - Pneumonia KW - J 02855:Human Bacteriology: Others KW - J 02845:Ear, nose and respiratory tract UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17286620?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Applied+Physiology&rft.atitle=Cardiopulmonary+effects+of+inhaled+nitric+oxide+in+normal+dogs+and+during+E.+coli+pneumonia+and+sepsis&rft.au=Quezado%2C+ZMN%3BNatanson%2C+C%3BKarzai%2C+W%3BDanner%2C+R+L%3BKoev%2C+CA%3BFitz%2C+Y%3BDolan%2C+D+P%3BRichmond%2C+S%3BBanks%2C+S+M%3BWilson%2C+L%3BEichacker%2C+P+Q&rft.aulast=Quezado&rft.aufirst=ZMN&rft.date=1998-01-01&rft.volume=84&rft.issue=1&rft.spage=107&rft.isbn=&rft.btitle=&rft.title=Journal+of+Applied+Physiology&rft.issn=87507587&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Sepsis; Ventilation; Nitric oxide; Hemodynamics; Pneumonia; Lung ER - TY - CONF T1 - Mechanisms of axonal transport: Target sites for neurotoxicants AN - 17182274; 4480543 AB - The process of axonal transport is critical for maintenance of the axonal membrane and nerve endings. Various toxicants produce morphological alterations in the axon of the peripheral nervous system. Thus, alterations in axonal transport have been a major research focus in toxicant-induced peripheral axonopathies. Axonal transport can be altered at a specific step in the mechanism by the movement of a specific component, or by more general biochemical alterations. This manuscript presents basic principles of axonal transport in the nervous system and the complicated interdependent nature of the biological process. This information is presented to give a mechanistic framework in which one can evaluate data from in vitro studies. While information obtained about the process in either type of system is important in the understanding of the pathogenesis and progression of toxicant-induced neuropathies, an emphasis is placed on the need for in vivo studies to determine biological relevance and the causative nature of axonal transport deficits in peripheral neuropathies. JF - In Vitro & Molecular Toxicology AU - Harry, G J Y1 - 1998 PY - 1998 DA - 1998 SP - 83 EP - 93 PB - Mary Ann Liebert, Inc., 2 Madison Ave Larchmont NY 10538 USA VL - 11 IS - 1 KW - CSA Neurosciences Abstracts; Toxicology Abstracts KW - Axonal transport KW - Conferences KW - Reviews KW - Neurotoxicity KW - Peripheral nervous system KW - Neuropathy KW - N3 11101:General KW - N3 11430:Conference proceedings KW - X 24270:Proceedings UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17182274?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=In+Vitro+%26+Molecular+Toxicology&rft.atitle=Mechanisms+of+axonal+transport%3A+Target+sites+for+neurotoxicants&rft.au=Harry%2C+G+J&rft.aulast=Harry&rft.aufirst=G&rft.date=1998-01-01&rft.volume=11&rft.issue=1&rft.spage=83&rft.isbn=&rft.btitle=&rft.title=In+Vitro+%26+Molecular+Toxicology&rft.issn=10979336&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Improved stability and yield of a Fv-toxin fusion protein by computer design and protein engineering of the Fv AN - 17155560; 4451954 AB - The conversion of the anti-mesothelin monoclonal antibody K1 to a single-chain Fv (scFv) that is fused to a truncated form of Pseudomonas exotoxin A (PE) results in a fusion protein (immunotoxin) that is unstable and refolds very inefficiently. We have devised a method that identities candidate residues in the framework region of K1 Fv that, when mutated, improved the yield and stability of the protein. The method works by initially aligning the framework sequences of K1 V sub(H) and V sub(L) with those of other scFvs that are stable and give a good yield as immunotoxins. Then we assigned a character to each residue that indicates its state of exposure based on the known crystal structures of Fabs. This identifies residues that are not compatible with their environment in the folded state of the protein. Next we calculated the frequencies of different amino acids for each position of the Fvs based on the available sequence database. This identifies residues that are not commonly present in the conserved positions. If these residues are compatible with their exposure profile they are left unaltered. Otherwise, they are identified as candidate residues for mutation. We identified two such residues in the V sub(H) (T82 and A85) and two in the V sub(L) (H36 and V60) of K1 that did not seem appropriate for their respective positions. By mutating these residues in K1 into those that occur most commonly in the sequence database or in stable scFvs, we significantly improved the stability and yield of the K1 scFv immunotoxins. By making single and combined mutations we assessed the relative contribution of mutations at these four sites towards the stability and yield of K1 scFv immunotoxins. The method we devised is probably general and can be used to improve other scFvs. JF - Journal of Molecular Biology AU - Chowdhury, P S AU - Vasmatzis, G AU - Beers, R AU - Lee, Byungkook AU - Pastan, I AD - Laboratory of Molecular Biology, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Building 37 Room 4E16, 37 Convent Drive MSC 4255, Bethesda MD 20892-4255, USA, pasta@helix.nih.qov Y1 - 1998 PY - 1998 DA - 1998 SP - 917 EP - 928 VL - 281 IS - 5 SN - 0022-2836, 0022-2836 KW - Fv-toxin KW - amino acid sequence KW - exotoxin A KW - mesothelin KW - scFv antibodies KW - Microbiology Abstracts B: Bacteriology KW - Mathematical models KW - Monoclonal antibodies KW - Pseudomonas KW - Immunotoxins KW - J 02822:Biosynthesis and physicochemical properties UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17155560?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Molecular+Biology&rft.atitle=Improved+stability+and+yield+of+a+Fv-toxin+fusion+protein+by+computer+design+and+protein+engineering+of+the+Fv&rft.au=Chowdhury%2C+P+S%3BVasmatzis%2C+G%3BBeers%2C+R%3BLee%2C+Byungkook%3BPastan%2C+I&rft.aulast=Chowdhury&rft.aufirst=P&rft.date=1998-01-01&rft.volume=281&rft.issue=5&rft.spage=917&rft.isbn=&rft.btitle=&rft.title=Journal+of+Molecular+Biology&rft.issn=00222836&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Pseudomonas; Immunotoxins; Mathematical models; Monoclonal antibodies ER - TY - JOUR T1 - Nucleotide excision repair and anti-cancer chemotherapy AN - 17153241; 4449034 AB - DNA repair is an important effector of anti-cancer drug resistance. In recent years, it has become apparent that DNA repair is an extremely complex process. Processes within DNA repair that may contribute to one or more drug resistance phenotypes include; O-6-alkyltransferase activity, base excision repair, mismatch repair, nucleotide excision repair, and gene specific repair. Clearly, several of these processes may show increased activity within any single cell, or tumor, at any one time. This review attempts to touch briefly upon the question of the distinctions between each of these specific pathways; and then seeks to expand on nucleotide excision repair as a possible effector of cellular and clinical resistance to platinum-based anticancer therapy. JF - Cytotechnology AU - Reed, E AD - Medical Ovarian Cancer Section, Medicine Branch, Division of Clinical Sciences, National Cancer Institute, Building 10, Room 12N226, Bethesda, MD 20892, USA, reed92@helix.nih.gov Y1 - 1998 PY - 1998 DA - 1998 SP - 187 EP - 201 VL - 27 IS - 1-3 SN - 0920-9069, 0920-9069 KW - nucleotide excision repair KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Chemotherapy KW - Reviews KW - DNA repair KW - Cancer KW - W 30965:Miscellaneous, Reviews KW - W3 33000:General topics and reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17153241?accountid=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=Cytotechnology&rft.atitle=Nucleotide+excision+repair+and+anti-cancer+chemotherapy&rft.au=Reed%2C+E&rft.aulast=Reed&rft.aufirst=E&rft.date=1998-01-01&rft.volume=27&rft.issue=1-3&rft.spage=187&rft.isbn=&rft.btitle=&rft.title=Cytotechnology&rft.issn=09209069&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - SuppNotes - Special Issue: Multiple Drug Resistance in Cancer 2. Molecular, Cellular and Clinical Aspects. N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - DNA repair; Reviews; Chemotherapy; Cancer ER - TY - JOUR T1 - Patterns of drug use among nonmetropolitan and rural adults AN - 17134244; 4434147 AB - This article examines illegal drug use among adults living in nonmetropolitan and rural areas of the United States using data from the National Household Survey on Drug Abuse. Subjects were classified into three categories by residence: nonmetropolitan-urban, metropolitan-rural, and nonmetropolitan-rural. Respondents indicate about 10% of adults were current users of marijuana or other illegal drugs. Discriminant analysis was used to examine differences among groups of individuals classified as current users, past users, and nonusers. For both marijuana and other illegal drugs, the variables that accounted most for group differences were age, marital, status, employment status, occupation, and income. Only minor differences in drug use were exhibited across the three residential categories. It is recommended that future research on the rural and nonmetropolitan adult population incorporate both structural level measures of socioeconomic and demographic characteristics of localities, and individual level measures of peer influence, work stress, family factors, and psychosocial characteristics. JF - Substance Use and Misuse AU - Robertson, E AU - Donnermeyer, J F AD - Division of Epidemiology and Prevention Research, National Institute on Drug Abuse, Rockville, MD, USA Y1 - 1998 PY - 1998 DA - 1998 SP - 2109 EP - 2129 VL - 33 IS - 10 SN - 1082-6084, 1082-6084 KW - cannabis KW - drug abuse KW - substance abuse KW - Health & Safety Science Abstracts KW - Research programs KW - Rural areas KW - H 4000:Food and Drugs UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17134244?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthsafetyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Substance+Use+and+Misuse&rft.atitle=Patterns+of+drug+use+among+nonmetropolitan+and+rural+adults&rft.au=Robertson%2C+E%3BDonnermeyer%2C+J+F&rft.aulast=Robertson&rft.aufirst=E&rft.date=1998-01-01&rft.volume=33&rft.issue=10&rft.spage=2109&rft.isbn=&rft.btitle=&rft.title=Substance+Use+and+Misuse&rft.issn=10826084&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Rural areas; Research programs ER - TY - JOUR T1 - Exposure assessment for a study of workers exposed to acrylonitrile AN - 17131497; 4435920 AB - Procedures used to develop estimates of exposure to acrylonitrile for a cohort study (>25 000 workers in 8 monomer, fiber, and resin companies from 1952 to 1983) are presented. Visits to the companies were made, interviews of workers were conducted, historical records were made, and measurements were taken. On the basis of similar tasks, locations, other exposures, and a similar distribution of exposures to acrylonitrile, 3600 exposure groups were formed. Special procedures were used to reduce the misclassification of workers performing tasks that varied in time but that were inadequately reflected in the job title. A software program organized and retained all exposure information on each exposure group. Quantitative estimates of acrylonitrile exposure were developed using a hierarchical approach in a software program that documented the derivation of each estimate and facilitated data review. Two of the estimation methods were evaluated in a comparison with measurement data. JF - Scandinavian Journal of Work, Environment & Health AU - Stewart, P A AU - Zaebst, D AU - Zey, J N AU - Herrick, R AU - Dosemeci, M AU - Hornung, R AU - Bloom, T AU - Pottern, L AU - Miller, BA AU - Blair, A AD - National Cancer Institute, EPN 418, 6130 Executive Boulevard MSC 7364, Bethesda, MD 20892-7364, USA Y1 - 1998 PY - 1998 DA - 1998 SP - 42 EP - 53 PB - Finnish Inst. of Occupational Health VL - 24 SN - 0355-3140, 0355-3140 KW - acrylonitrile KW - man KW - Toxicology Abstracts; Health & Safety Science Abstracts KW - Risk assessment KW - Mortality KW - Occupational exposure KW - H 1000:Occupational Safety and Health KW - X 24152:Chronic exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17131497?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Scandinavian+Journal+of+Work%2C+Environment+%26+Health&rft.atitle=Exposure+assessment+for+a+study+of+workers+exposed+to+acrylonitrile&rft.au=Stewart%2C+P+A%3BZaebst%2C+D%3BZey%2C+J+N%3BHerrick%2C+R%3BDosemeci%2C+M%3BHornung%2C+R%3BBloom%2C+T%3BPottern%2C+L%3BMiller%2C+BA%3BBlair%2C+A&rft.aulast=Stewart&rft.aufirst=P&rft.date=1998-01-01&rft.volume=24&rft.issue=&rft.spage=42&rft.isbn=&rft.btitle=&rft.title=Scandinavian+Journal+of+Work%2C+Environment+%26+Health&rft.issn=03553140&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Mortality; Occupational exposure; Risk assessment ER - TY - JOUR T1 - Relationships of serum carotenoids, retinol, alpha -tocopherol, and selenium with breast cancer risk: Results from a prospective study in Columbia, Missouri (United States) AN - 17129967; 4430961 AB - To evaluate relationships of serum carotenoids, alpha -tocopherol, selenium, and retinol with breast cancer prospectively, we conducted a case-control study nested in a cohort from the Breast Cancer Serum Bank in Columbia, Missouri (United States). Women free of cancer donated blood to this bank in 1977-87. During up to 9.5 years of follow-up (median = 2.7 years), 105 cases of histologically confirmed breast cancer were diagnosed. For each case, two women alive and free of cancer at the age of the case's diagnosis and matched on age and date of blood collection were selected as controls. A nonsignificant gradient of decreasing risk of breast cancer with increasing serum beta -cryptoxanthin was apparent for all women. Serum lycopene also was associated inversely with risk, and among women who donated blood at least two years before diagnosis, a significant gradient of decreasing breast cancer risk with increasing lycopene concentration was evident. A marginally significant gradient of decreasing risk with increasing serum lutein/zeaxanthin also was apparent among these women. We did not observe any evidence for protective effects of alpha - and beta -carotene, alpha -tocopherol, retinol, or selenium for breast cancer. Results of this study suggest that the carotenoids beta -cryptoxanthin, lycopene, and lutein/zeaxanthin may protect against breast cancer. JF - Cancer Causes & Control AU - Dorgan, J F AU - Sowell, A AU - Swanson, CA AU - Potischman, N AU - Miller, R AU - Schussler, N AU - Stephenson, HE Jr AD - Division of Epidemiology and Genetics, National Cancer Institute, Executive Plaza North, Room 443, 6130 Executive Boulevard, Bethesda, MD 20892-7374, USA Y1 - 1998/01// PY - 1998 DA - Jan 1998 SP - 89 EP - 97 VL - 9 IS - 1 SN - 0957-5243, 0957-5243 KW - USA, Missouri, Columbia KW - breast cancer KW - carotenoids KW - diets KW - nutrients KW - Toxicology Abstracts; Risk Abstracts KW - Diets KW - Breast cancer KW - Nutrients KW - Carotenoids KW - X 24240:Miscellaneous KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17129967?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Causes+%26+Control&rft.atitle=Relationships+of+serum+carotenoids%2C+retinol%2C+alpha+-tocopherol%2C+and+selenium+with+breast+cancer+risk%3A+Results+from+a+prospective+study+in+Columbia%2C+Missouri+%28United+States%29&rft.au=Dorgan%2C+J+F%3BSowell%2C+A%3BSwanson%2C+CA%3BPotischman%2C+N%3BMiller%2C+R%3BSchussler%2C+N%3BStephenson%2C+HE+Jr&rft.aulast=Dorgan&rft.aufirst=J&rft.date=1998-01-01&rft.volume=9&rft.issue=1&rft.spage=89&rft.isbn=&rft.btitle=&rft.title=Cancer+Causes+%26+Control&rft.issn=09575243&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Breast cancer; Diets; Nutrients; Carotenoids ER - TY - JOUR T1 - Tea and Coffee Consumption and Risk of Colon and Rectal Cancer in Middle-Aged Finnish Men AN - 16556803; 4376644 AB - The association between coffee and black tea consumption and the subsequent risk of colon and rectal cancer was investigated within a Finnish clinical trial cohort. One hundred eleven cases of colon cancer and 83 cases of rectal cancer were diagnosed over a median of 8.0 years of follow-up. Proportional hazards regression models were used to derive adjusted relative risks (RR) and 95% confidence intervals (CI) for the association between coffee and tea consumption and cancer incidence. After controlling for confounders, coffee was not significantly associated with colon or rectal cancer. A positive association was seen for increased consumption of tea drinking and colon cancer. Compared with persons who did not drink tea, those who consumed <1 cup/day had an RR of 1.40 (95% CI = 0.84-2.33) and those who consumed greater than or equal to 1 cup/day had an RR of 2.09 (95% CI = 1.34-3.26, p for trend = 0.001). In contrast, tea consumption had little effect on rectal cancer incidence. This study does not support the hypothesis that coffee and tea protect against colorectal cancer risk. However, given the strength of the tea-colon cancer association and the significant gradient of risk we observed across level of intake, further epidemiologic research of this relationship in other populations seems warranted. JF - Nutrition and Cancer AU - Hartman, T J AU - Tangrea, JA AU - Pietinen, P AU - Malila, N AU - Virtanen, M AU - Taylor, PR AU - Albanes, D AD - Division of Clinical Sciences, National Cancer Institute, Bethesda, MD 20892, USA Y1 - 1998 PY - 1998 DA - 1998 SP - 41 EP - 48 VL - 31 IS - 1 SN - 0163-5581, 0163-5581 KW - Finland KW - beverages KW - coffee KW - colon KW - colorectal carcinoma KW - males KW - tea KW - Risk Abstracts KW - Food KW - Cancer KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16556803?accountid=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=Nutrition+and+Cancer&rft.atitle=Tea+and+Coffee+Consumption+and+Risk+of+Colon+and+Rectal+Cancer+in+Middle-Aged+Finnish+Men&rft.au=Hartman%2C+T+J%3BTangrea%2C+JA%3BPietinen%2C+P%3BMalila%2C+N%3BVirtanen%2C+M%3BTaylor%2C+PR%3BAlbanes%2C+D&rft.aulast=Hartman&rft.aufirst=T&rft.date=1998-01-01&rft.volume=31&rft.issue=1&rft.spage=41&rft.isbn=&rft.btitle=&rft.title=Nutrition+and+Cancer&rft.issn=01635581&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Food; Cancer ER - TY - JOUR T1 - Breast cancer risk and lifetime occupational history: employment in professional and managerial occupations AN - 16499124; 4397091 AB - In this case-control study, occupational histories were used to assess the relation between risk of breast cancer and employment in professional and managerial occupations while adjusting for reproductive and other risk factors. Incident, primary, female cases of breast cancer diagnosed between 1986 and 1991, and randomly selected controls were interviewed to obtain detailed medical, reproductive, and occupational histories. Mantel-Haenszel crude odds ratios (OR) and 95% confidence intervals (95% CIs) were used to estimate risk of breast cancer related to the job of longest duration. Unconditional logistic regression was used to estimate crude and adjusted ORs and 95% CIs associated with having ever been employed and duration of employment in a professional or managerial occupation. In this population, employment in professional and managerial occupations is not associated with post-menopausal risk of breast cancer, but seems to be related to a reduction in risk of premenopausal breast cancer. Methodological limitations of this study including response rates are discussed. JF - Occupational and Environmental Medicine AU - Petralia, SA AU - Vena, JE AU - Freudenheim, J L AU - Marshall, J R AU - Michalek, A AU - Brasure, J AU - Swanson, M AU - Graham, S AD - Occupational Epidemiology Branch, National Cancer Institute, Executive Plaza North, Rm 418, 6130 Executive Boulevard, Bethesda, MD 20892, USA Y1 - 1998/01// PY - 1998 DA - Jan 1998 SP - 43 EP - 48 VL - 55 IS - 1 SN - 1351-0711, 1351-0711 KW - Health & Safety Science Abstracts; Risk Abstracts KW - R2 23080:Industrial and labor KW - H 1000:Occupational Safety and Health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16499124?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Occupational+and+Environmental+Medicine&rft.atitle=Breast+cancer+risk+and+lifetime+occupational+history%3A+employment+in+professional+and+managerial+occupations&rft.au=Petralia%2C+SA%3BVena%2C+JE%3BFreudenheim%2C+J+L%3BMarshall%2C+J+R%3BMichalek%2C+A%3BBrasure%2C+J%3BSwanson%2C+M%3BGraham%2C+S&rft.aulast=Petralia&rft.aufirst=SA&rft.date=1998-01-01&rft.volume=55&rft.issue=1&rft.spage=43&rft.isbn=&rft.btitle=&rft.title=Occupational+and+Environmental+Medicine&rft.issn=13510711&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Reproductive endpoints in general toxicity studies: Are they predictive? AN - 16499123; 4395222 AB - The ability to use necropsy and in-life vaginal cytology data from 90-d general toxicity studies to predict the outcome of more definitive reproductive toxicity tests was evaluated using data from 18 compounds tested by the National Toxicology Program. Sperm motility and vaginal cytology evaluations (SMVCE) were performed at the end of 90-d toxicity studies. When these same compounds were tested in the definitive Reproductive Assessment by Continuous Breeding (RACB) design, 13 of the 18 compounds were classified the same way by both tests. The different conclusions for five compounds can be explained by differences in dose used or in endpoints evaluated. We conclude that reproductive-system necropsy data from general toxicity studies can provide a valuable preliminary indication of the likely reproductive toxicity of the compound under study. JF - Reproductive Toxicology AU - Chapin, R E AU - Sloane, R A AU - Haseman, J K AD - B3-05, NIEHS, PO Box 12233, RTP, NC 27709, USA, chapin@niehs.nih.gov Y1 - 1998 PY - 1998 DA - 1998 SP - 489 EP - 494 VL - 12 IS - 4 SN - 0890-6238, 0890-6238 KW - sperm motility test KW - vaginal cytology KW - Toxicology Abstracts KW - X 24221:Toxicity testing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16499123?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Reproductive+Toxicology&rft.atitle=Reproductive+endpoints+in+general+toxicity+studies%3A+Are+they+predictive%3F&rft.au=Chapin%2C+R+E%3BSloane%2C+R+A%3BHaseman%2C+J+K&rft.aulast=Chapin&rft.aufirst=R&rft.date=1998-01-01&rft.volume=12&rft.issue=4&rft.spage=489&rft.isbn=&rft.btitle=&rft.title=Reproductive+Toxicology&rft.issn=08906238&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Risk and safety of repetitive transcranial magnetic stimulation: report and suggested guidelines from the International Workshop on the Safety of Repetitive Transcranial Magnetic Stimulation, June 5-7, 1996 AN - 16488457; 4366604 AB - Single-pulse transcranial magnetic stimulation (TMS) is a safe and useful tool for investigating various aspects of human neurophysiology, particularly corticospinal function, in health and disease. Repetitive TMS (rTMS), however, is a more powerful and potentially dangerous modality, capable of regionally blocking or facilitating cortical processes. Although there is evidence that rTMS is useful for treating clinical depression, and possibly other brain disorders, it had caused 7 known seizures by 1996 and could have other undesirable effects. In June 1996 a workshop was organized to review the available data on the safety of rTMS and to develop guidelines for its safe use. This article summarizes the workshop's deliberations. In addition to issues of risk and safety, it also addresses the principles and applications of rTMS, nomenclature, and potential therapeutic effects of rTMS. The guidelines for the use of rTMS, which are summarized in an appendix, cover the ethical issues, recommended limits on stimulation parameters, monitoring of subjects (both physiologically and neuropsychologically), expertise and function of the rTMS team, medical and psychosocial management of induced seizures, and contraindications to rTMS. JF - Evoked Potentials AU - Wassermann, E M AD - Medical Neurology Branch, National Institute of Neurological Disorders and Stroke, Building 10, Room 5N226, National Institutes of Health, 10 Center Drive, MSC-1428, Bethesda, MD 20892-1428, USA, wassermann@nih.gov Y1 - 1998/01// PY - 1998 DA - Jan 1998 SP - 1 EP - 16 VL - 108 IS - 1 SN - 0168-5597, 0168-5597 KW - man KW - transcranial magnetic stimulation KW - Toxicology Abstracts; CSA Neurosciences Abstracts KW - X 24210:Radiation & radioactive materials KW - N3 11020:Neuroprotocols and apparatus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16488457?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Evoked+Potentials&rft.atitle=Risk+and+safety+of+repetitive+transcranial+magnetic+stimulation%3A+report+and+suggested+guidelines+from+the+International+Workshop+on+the+Safety+of+Repetitive+Transcranial+Magnetic+Stimulation%2C+June+5-7%2C+1996&rft.au=Wassermann%2C+E+M&rft.aulast=Wassermann&rft.aufirst=E&rft.date=1998-01-01&rft.volume=108&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Evoked+Potentials&rft.issn=01685597&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - A nested case-control study of dietary factors and the risk of incident cytological abnormalities of the cervix AN - 16451170; 4351699 AB - Several earlier case-control studies reported inverse associations of cervical squamous intraepithelial lesions (SIL) with high dietary or biomarker levels of carotenoids, folate, and vitamins C and E. However, most studies did not measure the primary causal factor, cancer-associated genital human papillomaviruses (HPV), now detected by sensitive viral DNA tests. This nested case-control study assessed whether high dietary intakes of these nutrients, plus zinc and vitamin A, reduced SIL risk in cancer-associated HPV DNA-positive women. Using a 60-item food-frequency questionnaire, nutrient estimates were obtained for 33 incident cases with high-grade lesions, 121 with low-grade lesions, 97 with equivocal SIL, and 806 cytologically normal controls sampled from a large prospective cohort study. Baseline cervicovaginal lavages were tested for HPV DNA by the polymerase chain reaction. Among DNA-positive cases (n = 68) and controls (n = 69), age-adjusted odds ratios (ORs) of SIL in the highest vs. the lowest nutrient quartiles were 1.4 [95% confidence interval (CI) = 0.5-4.2] for vitamin A, 0.6 (CI = 0.2-2.0) for beta -carotene, 1.3 (CI = 0.4-3.6) for vitamin C, 1.0 (CI = 0.4-3.6) for vitamin E, 0.7 (CI = 0.3-2.1) for folate, and 0.8 (CI = 0.3-2.2) for zinc. ORs in HPV DNA-negative women approximated 1.0, with the exception of vitamin E (OR = 0.5, CI = 0.3-0.9). These results do not support a protective role for the above nutrients against low-grade or equivocal SIL, which constituted the majority of diagnoses in this study. JF - Nutrition and Cancer AU - Wideroff, L AU - Potischman, N AU - Glass, A G AU - Greer, CE AU - Manos, M M AU - Scott AU - Burk, R D AU - Sherman, ME AU - Wacholder, S AU - Schiffman, M AD - Epidemiology and Biostatistics Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA Y1 - 1998 PY - 1998 DA - 1998 SP - 130 EP - 136 VL - 30 IS - 2 SN - 0163-5581, 0163-5581 KW - cancer KW - cervix KW - cytology KW - diets KW - nutrition KW - papilloma KW - Health & Safety Science Abstracts KW - H 11000:Diseases/Injuries/Trauma UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16451170?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthsafetyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nutrition+and+Cancer&rft.atitle=A+nested+case-control+study+of+dietary+factors+and+the+risk+of+incident+cytological+abnormalities+of+the+cervix&rft.au=Wideroff%2C+L%3BPotischman%2C+N%3BGlass%2C+A+G%3BGreer%2C+CE%3BManos%2C+M+M%3BScott%3BBurk%2C+R+D%3BSherman%2C+ME%3BWacholder%2C+S%3BSchiffman%2C+M&rft.aulast=Wideroff&rft.aufirst=L&rft.date=1998-01-01&rft.volume=30&rft.issue=2&rft.spage=130&rft.isbn=&rft.btitle=&rft.title=Nutrition+and+Cancer&rft.issn=01635581&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Determining the structures of large proteins and protein complexes by NMR AN - 16442353; 4344280 AB - Recent advances in multidimensional NMR methodology to obtain super(1)H, super(15)N and super(13)C resonance assignments, interproton-distance and torsion-angle restraints, and restraints that characterize long-range order have, coupled with new methods of structure refinement, permitted solution structures of proteins in excess of 250 residues to be solved. These developments may permit the determination by NMR of the structures of macromolecules up to 50-60 kDa, thereby bringing into reach numerous systems of considerable biological interest, including a large variety of protein-protein and protein-nucleic-acid complexes. JF - Trends in Biotechnology AU - Clore, G M AU - Gronenborn, A M AD - The Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0520, USA Y1 - 1998/01// PY - 1998 DA - Jan 1998 SP - 22 EP - 34 VL - 16 IS - 1 SN - 0167-7799, 0167-7799 KW - N.M.R. KW - protein structure KW - reviews KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Agricultural and Environmental Biotechnology Abstracts KW - W3 33340:Other proteins, peptides, amino acids KW - W2 32340:Other peptides, proteins, amino acids KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16442353?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Trends+in+Biotechnology&rft.atitle=Determining+the+structures+of+large+proteins+and+protein+complexes+by+NMR&rft.au=Clore%2C+G+M%3BGronenborn%2C+A+M&rft.aulast=Clore&rft.aufirst=G&rft.date=1998-01-01&rft.volume=16&rft.issue=1&rft.spage=22&rft.isbn=&rft.btitle=&rft.title=Trends+in+Biotechnology&rft.issn=01677799&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Reactive oxygen-mediated protein oxidation in aging and disease AN - 16415030; 4324479 AB - Highly reactive oxygen species that are formed during normal metabolism and under conditions of oxidative stress are able to oxidize proteins or convert lipid and carbohydrate derivatives to compounds that react with functional groups on proteins. Among other changes, these ROS-mediated reactions lead to the formation of protein carbonyl derivatives, which serves as a marker of ROS-mediated protein damage. On the basis of this marker, it is established that oxidatively damaged protein is associated with aging and some diseases. The accumulation of oxidatively damaged protein reflects the balance among a myriad of factors that govern the rates of ROS generation and the rate at which damaged protein is degraded. Peroxynitrite, which is formed under normal physiological conditions, is able to oxidize methionine residues in proteins and to nitrate tyrosine residues; however, its ability to do so is dependent on the availability of CO sub(2), which stimulates the nitration of tyrosine residues but inhibits the oxidation of methionine residues. Nitration of tyrosine residues may contribute to peroxynitrite toxicity, as nitration precludes the phosphorylation or nucleotidylation of tyrosine residues and thereby seriously compromises one of the most important mechanisms of cellular regulation and signal transduction. JF - Drug Metabolism Reviews AU - Stadtman, E R AU - Berlett, B S AD - Laboratory of Biochemistry, National Heart, Lung, and Blood Institute, National Institutes of Health, Building 3, Room 222, Bethesda, MD 20892-0342, USA Y1 - 1998 PY - 1998 DA - 1998 SP - 225 EP - 243 VL - 30 IS - 2 SN - 0360-2532, 0360-2532 KW - reactive oxigen species KW - Toxicology Abstracts KW - X 24240:Miscellaneous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16415030?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Drug+Metabolism+Reviews&rft.atitle=Reactive+oxygen-mediated+protein+oxidation+in+aging+and+disease&rft.au=Stadtman%2C+E+R%3BBerlett%2C+B+S&rft.aulast=Stadtman&rft.aufirst=E&rft.date=1998-01-01&rft.volume=30&rft.issue=2&rft.spage=225&rft.isbn=&rft.btitle=&rft.title=Drug+Metabolism+Reviews&rft.issn=03602532&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Homologous DNA pairing domain peptides of RecA protein: intrinsic propensity to form beta -structures and filaments AN - 16407819; 4322092 AB - The 20 amino acid residue peptides derived from RecA loop L2 have been shown to be the pairing domain of RecA. The peptides bind to ss- and dsDNA, unstack ssDNA, and pair the ssDNA to its homologous target in a duplex DNA. As shown by circular dichroism, upon binding to DNA the disordered peptides adopt a beta -structure conformation. Here we show that the conformational change of the peptide from random coil to beta -structure is important in binding ss- and dsDNA. The beta -structure in the DNA pairing peptides can be induced by many environmental conditions such as high pH, high concentration, and non-micellar sodium dodecyl sulfate (6 mM). This behavior indicates an intrinsic property of these peptides to form a beta -structure. A beta -structure model for the loop L2 of RecA protein when bound to DNA is thus proposed. The fact that aromatic residues at the central position 203 strongly modulate the peptide binding to DNA and subsequent biochemical activities can be accounted for by the direct effect of the aromatic amino acids on the peptide conformational change. The DNA-pairing domain of RecA visualized by electron microscopy self-assembles into a filamentous structure like RecA. The relevance of such a peptide filamentous structure to the structure of RecA when bound to DNA is discussed. JF - Journal of Molecular Biology AU - Wang, Lijiang AU - Voloshin, ON AU - Stasiak, A AU - Camerini-Otero, R D AD - Bldg 10, Rm 9D20, Genetics and Biochemistry Branch National Institutes of Health Bethesda, MD 20892, USA Y1 - 1998 PY - 1998 DA - 1998 SP - 1 EP - 11 VL - 277 IS - 1 SN - 0022-2836, 0022-2836 KW - DNA-binding protein KW - RecA protein KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - J 02725:DNA KW - N 14940:Nucleic acid-binding proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16407819?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Molecular+Biology&rft.atitle=Homologous+DNA+pairing+domain+peptides+of+RecA+protein%3A+intrinsic+propensity+to+form+beta+-structures+and+filaments&rft.au=Wang%2C+Lijiang%3BVoloshin%2C+ON%3BStasiak%2C+A%3BCamerini-Otero%2C+R+D&rft.aulast=Wang&rft.aufirst=Lijiang&rft.date=1998-01-01&rft.volume=277&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Journal+of+Molecular+Biology&rft.issn=00222836&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Paradoxical effect of GM-CSF gene transfer on the tumorigenicity and immunogenicity of murine tumors AN - 16400451; 4315982 AB - The effect of granulocyte/macrophage colony-stimulating factor (GM-CSF) gene transfer on the tumorigenicity and immunogenicity of 2 different murine tumor lines was determined. Transduction of B16 melanoma cells with the GM-CSF gene rendered the cells more immunogenic. In contrast, transduction of NG4TL4 fibrosarcoma in FVB/N mice (NG) with the GM-CSF gene showed increased tumorigenicity in a high producer line (NG-MGh). The parent NG or NG-MG cells induced the same level of cytotoxic T-lymphocyte (CTL) response and the same magnitude of tumor transplantation immunity. However, the proliferation of the NG-MGh cells was increased 2- to 10-fold. There was no increase in apoptosis in the NG cells and there was no increase of NG-MGh cells in S-phase, hence the increase of the proliferative activity appeared to be indeed inherent to the cells. Mixing the splenocytes from the NG-MGh tumor bearers with the NG tumor cells did not increase tumorigenicity but totally inhibited the growth of the NG tumor, indicating that suppressor cells were not present. Mixing 10,000 rad X-irradiated NG-MGh cells with viable NG tumor cells resulted in 3- to 10-fold increased NG tumor growth rate. The in vitro proliferation of NG cells was increased by adding both GM-CSFs and macrophages and not by either one alone, suggesting that interaction between macrophages and GM-CSFs resulted in the production of tumor growth enhancing factor(s). Our findings suggest that transduction of NG tumor cells with the GM-CSF gene increases tumorigenicity, which is attributed both to an increased inherent proliferative ability of the tumor cells and to the in vivo production of a tumor growth enhancing factor(s) at the tumor site. JF - International Journal of Cancer AU - Wang, Jie AU - Yang, Wen K AU - Yang, Yili AU - Wei, Sung-Jan AU - Yang, Den-Mei AU - Whang-Peng, J AU - Chen, Yuh-Min AU - Ting, Kai-Li AD - Bldg. 10, Room 4B17, National Institutes of Health, Bethesda, MD 20892-1360, USA, ct53j@nih.gov Y1 - 1998/01// PY - 1998 DA - Jan 1998 SP - 459 EP - 466 VL - 75 IS - 3 SN - 0020-7136, 0020-7136 KW - FVB/N mice KW - NG-MGh cells KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - W 30965:Miscellaneous, Reviews KW - W3 33180:Gene based (protocols, clinical trials, and animal models) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16400451?accountid=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=International+Journal+of+Cancer&rft.atitle=Paradoxical+effect+of+GM-CSF+gene+transfer+on+the+tumorigenicity+and+immunogenicity+of+murine+tumors&rft.au=Wang%2C+Jie%3BYang%2C+Wen+K%3BYang%2C+Yili%3BWei%2C+Sung-Jan%3BYang%2C+Den-Mei%3BWhang-Peng%2C+J%3BChen%2C+Yuh-Min%3BTing%2C+Kai-Li&rft.aulast=Wang&rft.aufirst=Jie&rft.date=1998-01-01&rft.volume=75&rft.issue=3&rft.spage=459&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Cancer&rft.issn=00207136&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - The adhesion-associated sca operon in Streptococcus gordonii encodes an inducible high-affinity ABC transporter for Mn super(2+) uptake AN - 16363251; 4269449 AB - ScaA lipoprotein in Streptococcus gordonii is a member of the LraI family of homologous polypeptides found among streptococci, pneumococci, and enterococci. It is the product of the third gene within the scaCBA operon encoding the components of an ATP-binding cassette (ABC) transporter system. Inactivation of scaC (ATP-binding protein) or scaA (substrate-binding protein) genes resulted in both impaired growth of cells and >70% inhibition of super(54)Mn super(2+) uptake in media containing 20-fold in sca mutants. The addition of 0.1 mM Mn super(2+) to the transformation medium restored only partly the transformability of mutant cells, implying an alternate role for Sca proteins in the transformation process. Cells of sca mutants were unaffected in other binding properties tested and were unaffected in sensitivity to oxidants. The results show that Sca permease is a high-affinity mechanism for the acquisition of Mn super(2+) and is essential for growth of streptococci under Mn super(2+)-limiting conditions. JF - Journal of Bacteriology AU - Kolenbrander, P E AU - Andersen, R N AU - Baker, R A AU - Jenkinson, H F AD - Building 30, Room 310, 30 Convent Dr. MSC 4350, National Institutes of Health, Bethesda, MD 20892-4350, USA, kolenbrander@yoda.nidr.nih.gov Y1 - 1998/01// PY - 1998 DA - Jan 1998 SP - 290 EP - 295 VL - 180 IS - 2 SN - 0021-9193, 0021-9193 KW - ATP-binding casette KW - ATP-binding protein KW - ScaA protein KW - enterococci KW - manganese KW - pneumococci KW - scaA gene KW - Microbiology Abstracts B: Bacteriology KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16363251?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Bacteriology&rft.atitle=The+adhesion-associated+sca+operon+in+Streptococcus+gordonii+encodes+an+inducible+high-affinity+ABC+transporter+for+Mn+super%282%2B%29+uptake&rft.au=Kolenbrander%2C+P+E%3BAndersen%2C+R+N%3BBaker%2C+R+A%3BJenkinson%2C+H+F&rft.aulast=Kolenbrander&rft.aufirst=P&rft.date=1998-01-01&rft.volume=180&rft.issue=2&rft.spage=290&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=00219193&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Non-Hodgkin's lymphoma and agricultural use of the insecticide lindane AN - 16328737; 4270251 AB - Data from population-based case-control studies of non-Hodgkin's lymphoma among white men from Kansas, Nebraska, Iowa, and Minnesota were pooled to evaluate potential risks from environmental exposures in more detail, while controlling for potential confounding factors. These data provided the opportunity to evaluate the risk of non-Hodgkin's lymphoma from potential exposures to lindane, a pesticide that causes cancer in laboratory animals and has been associated with human cancer in a few epidemiologic investigations. This pooled data set includes 987 individuals with non-Hodgkin's lymphoma and 2,895 population-based controls. Information was obtained by telephone or in person interviews, which included detailed questions on farm practices and agricultural use of chemicals. Logistic regression was used to calculate odds ratios (ORs) adjusted for age, state of residence, and subject or proxy interviews. Reported use of lindane significantly increased the risk of non-Hodgkin's's lymphoma by 50%. Some use characteristics were suggestive of an association. ORs were greater among persons who first used the pesticide 20 years before diagnosis (OR = 1.7) than more recently (OR = 1.3), among those who reported more frequent use (OR = 2.0 for use 5 or more days per year versus 1.6 for fewer than five days per year), and from use on crops (OR = 1.9), rather than from use on animals (OR = 1.3), although these differences were not statistically significant. On the other hand, ORs were lower when based on direct interviews (OR = 1.3) than on data from proxy respondents (OR = 2.1) and adjustment for potential confounding by use of 2,4-D and diazinon reduced the ORs associated with lindane use from 1.5 to 1.2 and 1.3, respectively. Lindane does not appear to be a major etiologic factor in the development of non-Hodgkin's's lymphoma, although a small role cannot be ruled out. JF - American Journal of Industrial Medicine AU - Blair, A AU - Cantor, K P AU - Zahm, SH AD - Occupational Epidemiology Branch, National Cancer Institute, EPN Room 418, Bethesda, MD 20892-7364, USA, blair@epndce.nci.nih.gov Y1 - 1998/01// PY - 1998 DA - Jan 1998 SP - 82 EP - 87 VL - 33 IS - 1 SN - 0271-3586, 0271-3586 KW - lymphoma KW - Health & Safety Science Abstracts; Risk Abstracts; Toxicology Abstracts KW - R2 23080:Industrial and labor KW - X 24132:Chronic exposure KW - H 1000:Occupational Safety and Health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16328737?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Journal+of+Industrial+Medicine&rft.atitle=Non-Hodgkin%27s+lymphoma+and+agricultural+use+of+the+insecticide+lindane&rft.au=Blair%2C+A%3BCantor%2C+K+P%3BZahm%2C+SH&rft.aulast=Blair&rft.aufirst=A&rft.date=1998-01-01&rft.volume=33&rft.issue=1&rft.spage=82&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Industrial+Medicine&rft.issn=02713586&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Subtracted differential display: Genes with amphetamine-altered expression patterns include calcineurin AN - 16295287; 4278904 AB - Genes whose expression changes with administration of abused substances provide candidate biochemical mechanisms for drug-induced long-term brain changes. To identify such genes, and to avoid the false-positive results frequently obtained from differential display PCR, we applied a subtracted differential display (SDD) approach. We subtracted single-stranded cDNA prepared from drug-treated animals with excess mRNA from saline-treated animals, and visa versa, prior to differential display amplifications. Two of initial amphetamine-regulated cDNAs identified in this fashion encoded calcineurin A, a neuron-specific protein phosphatase catalytic subunit whose striatal expression was upregulated ca. 1.5-fold. SDD may enhance the utility of differential display approaches to identifying regulated genes in tissues in which mRNA complexities are high. JF - Molecular Brain Research AU - Wang, X B AU - Uhl, G R AD - Molecular Neurobiology Branch, Intramural Research Program, National Institute on Drug Abuse, Box 5180, Baltimore, MD 21224, USA Y1 - 1998/01/01/ PY - 1998 DA - 1998 Jan 01 SP - 345 EP - 347 PB - Elsevier Science B.V. VL - 53 IS - 1-2 SN - 0169-328X, 0169-328X KW - subtracted differential display KW - Calcium & Calcified Tissue Abstracts; CSA Neurosciences Abstracts; Toxicology Abstracts KW - T 20058:Phosphatases KW - N3 11106:Neurobiology of drug abuse KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16295287?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+Brain+Research&rft.atitle=Subtracted+differential+display%3A+Genes+with+amphetamine-altered+expression+patterns+include+calcineurin&rft.au=Wang%2C+X+B%3BUhl%2C+G+R&rft.aulast=Wang&rft.aufirst=X&rft.date=1998-01-01&rft.volume=53&rft.issue=1-2&rft.spage=345&rft.isbn=&rft.btitle=&rft.title=Molecular+Brain+Research&rft.issn=0169328X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - H2M3 super(wt)-restricted, Listeria monocytogenes-immune CD8 T cells respond to multiple formylated peptides and to a variety of gram-positive and gram-negative bacteria AN - 16285500; 4284532 AB - A subset of H2M3 super(wt)-restricted, Listeria monocytogenes (LM)-immune CD8 effectors recognize antigen-presenting cells (APC) preincubated with heat-killed LM. The responsible product, which we have previously designated heat-killed Listeria-associated antigen (HAA), is extremely hydrophobic and resistant to proteolytic degradation. Despite the protease resistance of HAA, we now report that HAA-immune clones are uniformly responsive to fMIGWII, a formylated oligopeptide derived from the recently described LM product, lemA. While fMIGWII was by far the most potent peptide tested, over half our clones also responded to the LM-derived peptide fMIVIL and cross-reactive responses to two other unrelated formylated peptides at concentrations of <1 mu M were frequently observed. One of these peptides (fBlaZ) did not share any amino acid in common with fMIGWII except N-formyl methionine at position 1. Unformylated variants of the same peptides were inactive. HAA-immune CD8 cells also responded in an H2M3 super(wt)-restricted manner to APC pretreated with heat-killed or live preparations of other Gram-positive and Gram-negative bacteria such as Streptococcus pyogenes (SP) and Proteus vulgaris (PV). Unlike fMIGWII which is water soluble and protease sensitive, the native antigens extracted from SP and PV, like HAA, were very hydrophobic and proteinase K resistant, presumably reflecting in each case the association of cross-reactive polypeptides with bacterial lipid or phospholipid. Thus, HAA/lemA-immune, H2M3 super(wt)-restricted effectors can respond to a variety of formylated peptides and bacterial antigens in vitro. Similar cross-reactions in vivo might have physiologically significant implications. JF - International Immunology AU - Nataraj, C AU - Huffman, G R AU - Kurlander, R J AD - Building 10/Rm 2C390, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892-1508, USA Y1 - 1998 PY - 1998 DA - 1998 SP - 7 EP - 15 VL - 10 IS - 1 SN - 0953-8178, 0953-8178 KW - CD8 antigen KW - Listeria monocytogenes KW - gram-negative bacteria KW - gram-positive bacteria KW - lymphocytes T KW - peptides KW - Microbiology Abstracts B: Bacteriology; Immunology Abstracts KW - F 06801:Bacteria KW - J 02833:Immune response and immune mechanisms UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16285500?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+Immunology&rft.atitle=H2M3+super%28wt%29-restricted%2C+Listeria+monocytogenes-immune+CD8+T+cells+respond+to+multiple+formylated+peptides+and+to+a+variety+of+gram-positive+and+gram-negative+bacteria&rft.au=Nataraj%2C+C%3BHuffman%2C+G+R%3BKurlander%2C+R+J&rft.aulast=Nataraj&rft.aufirst=C&rft.date=1998-01-01&rft.volume=10&rft.issue=1&rft.spage=7&rft.isbn=&rft.btitle=&rft.title=International+Immunology&rft.issn=09538178&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - DNA adduct formation by polycyclic aromatic hydrocarbon dihydrodiol epoxides AN - 16283959; 4295675 AB - Classically, active metabolites of chemical carcinogens were identified by isolating various metabolites produced in experimental animals and determining which of these exhibited carcinogenic activity comparable to, or greater than, that of the parent compound. This approach was not successful for the polycyclic aromatic hydrocarbon carcinogens, however, because most metabolites examined with this approach were found to be much weaker carcinogens than the parent hydrocarbon from which they were derived. Metabolic activation of polycyclic aromatic hydrocarbons was clarified, however, by initially identifying metabolites that were responsible for covalent binding to DNA in cells or tissues [these were found to be vicinal dihydrodiol epoxides in which the epoxide is in a bay or fjord region] and, only thereafter, demonstrating that these metabolites exhibited high tumorigenic activities. It has been shown that this dihydrodiol epoxide route of activation applies to a fairly wide range of hydrocarbon structures, but other mechanisms of metabolic activation have also been investigated. For example, it has been suggested that the active metabolites of some polycyclic aromatic hydrocarbons may be radical cations that induce mutation through the intermediacy of apurinic sites in DNA, rather than through the DNA adducts themselves. The proposed radical cations are not stable enough to be isolated, and therefore, there is no direct evidence that these intermediates are carcinogenic. JF - Chemical Research in Toxicology AU - Szeliga, J AU - Dipple, A AD - Chem. Carcinogenesis Lab., ABL-Basic Res. Prog., NCI-Frederick Cancer Res. and Dev. Cent., Frederick, MD 21702, USA Y1 - 1998/01// PY - 1998 DA - Jan 1998 SP - 1 EP - 11 VL - 11 IS - 1 SN - 0893-228X, 0893-228X KW - DNA adducts KW - dihydrodiol epoxide KW - free radicals KW - metabolic activation KW - polycyclic aromatic hydrocarbons KW - Toxicology Abstracts KW - X 24190:Polycyclic hydrocarbons UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16283959?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemical+Research+in+Toxicology&rft.atitle=DNA+adduct+formation+by+polycyclic+aromatic+hydrocarbon+dihydrodiol+epoxides&rft.au=Szeliga%2C+J%3BDipple%2C+A&rft.aulast=Szeliga&rft.aufirst=J&rft.date=1998-01-01&rft.volume=11&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Chemical+Research+in+Toxicology&rft.issn=0893228X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Aralkylation of guanosine with para-substituted styrene oxides AN - 16282254; 4295673 AB - To probe mechanisms of nucleoside aralkylation, product distributions and product stereochemistries were determined in reactions of optically active p-methyl- and p-bromostyrene oxide with guanosine. The proportion of 7-, N super(2)-, and O super(6)-substituted guanosine products was similar to 0.32:0.62:0.06 in neutral, aqueous reactions with the (R)-p-methylstyrene oxide and similar to 0.85: 0.09:0.04 in reactions with the (R)-p-bromostyrene oxide. The exocyclic positions opened the epoxide at the alpha -carbon. Epoxide ring opening by the nitrogen at the 7-position showed little preference for the alpha - or beta -carbons in reactions with p-methylstyrene oxide. However, the p-bromostyrene oxide favored reaction at the beta -carbon almost 4-fold over reaction at the alpha -carbon. Almost total inversion of stereochemistry was found to occur in reactions at the 7-position. In contrast, the ratio of inversion to retention of configuration in N super(2)- and O super(6)-substituted products was similar to 2:1 and similar to 1:1 for reactions with the p-methylstyrene oxide and similar to 6:1 and similar to 3:1 for reactions with p-bromostyrene oxide, respectively. These experiments suggest that an S sub(N)2 mechanism is in effect with reactions at the 7-position, whereas substrates of an increasingly ionic nature are involved in reactions at the N super(2)- and O super(6)-positions, respectively. JF - Chemical Research in Toxicology AU - Barlow, T AU - Dipple, A AD - Chem. Carcinogenesis Lab., ABL-Basic Res. Prog., NCI-Frederick Cancer Res. and Dev. Cent., P.O. Box B, Frederick, MD 21702, USA Y1 - 1998/01// PY - 1998 DA - Jan 1998 SP - 44 EP - 53 VL - 11 IS - 1 SN - 0893-228X, 0893-228X KW - aralkylation KW - carcinogens KW - guanosine KW - oxidation KW - p-Bromostyrene oxide KW - p-Methyl-bromostyrene oxide KW - styrene oxide KW - Toxicology Abstracts KW - X 24155:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16282254?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemical+Research+in+Toxicology&rft.atitle=Aralkylation+of+guanosine+with+para-substituted+styrene+oxides&rft.au=Barlow%2C+T%3BDipple%2C+A&rft.aulast=Barlow&rft.aufirst=T&rft.date=1998-01-01&rft.volume=11&rft.issue=1&rft.spage=44&rft.isbn=&rft.btitle=&rft.title=Chemical+Research+in+Toxicology&rft.issn=0893228X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Proposed mechanism of acetate accumulation in two recombinant Escherichia coli strains during high density fermentation AN - 16282105; 4290145 AB - The productivity of Escherichia coli as a producer of recombinant proteins is affected by its metabolic properties, especially by acetate production. Two commercially used E. coli strains, BL21 ( lambda DE3) and JM109, differ significantly in their acetate production during batch fermentation at high initial glucose concentrations. E. coli BL21 grows to an optical density (OD, 600 nm) of 100 and produces no more than 2 g/L acetate, while E. coli JM109 grows to an OD (600 nm) of 80 and produces up to 14 g/L acetate. Even in fed-batch fermentation, when glucose concentration is maintained between 0.5 and 1.0 g/L, JM109 accumulates 4 times more acetate than BL21. To investigate the difference between the two strains, metabolites and enzymes involved in carbon utilization and acetate production were analyzed (isocitrate, ATP, phosphoenolpyruvate, pyruvate, isocitrate lyase, and isocitrate dehydrogenase). The results showed that during batch fermentation isocitrate lyase activity and isocitrate concentration were higher in BL21 than in JM109, while pyruvate concentration was higher in JM109. The activation of the glyoxylate shunt pathway at high glucose concentrations is suggested as a possible explanation for the lower acetate accumulation in E. coli BL21. Metabolic flux analysis of the batch cultures supports the activity of the glyoxylate shunt in E. coli BL21. JF - Biotechnology and Bioengineering AU - van de Walle, M AU - Shiloach, J AD - Biotechnology Unit-LCDB, NIDDK, National Institutes of Health, BLDG 6, RM B1-33, Bethesda, MD 20892-2715, USA Y1 - 1998/01// PY - 1998 DA - Jan 1998 SP - 71 EP - 78 PB - JOHN WILEY & SONS, INC. VL - 57 IS - 1 SN - 0006-3592, 0006-3592 KW - acetic acid KW - fermentation KW - Biotechnology and Bioengineering Abstracts; Microbiology Abstracts A: Industrial & Applied Microbiology; Agricultural and Environmental Biotechnology Abstracts KW - A 01002:Acids, amino acids, peptides & proteins KW - W 30965:Miscellaneous, Reviews KW - W2 32360:Organic acids UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16282105?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biotechnology+and+Bioengineering&rft.atitle=Proposed+mechanism+of+acetate+accumulation+in+two+recombinant+Escherichia+coli+strains+during+high+density+fermentation&rft.au=van+de+Walle%2C+M%3BShiloach%2C+J&rft.aulast=van+de+Walle&rft.aufirst=M&rft.date=1998-01-01&rft.volume=57&rft.issue=1&rft.spage=71&rft.isbn=&rft.btitle=&rft.title=Biotechnology+and+Bioengineering&rft.issn=00063592&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Inhibition of HIV-1 replication by combined expression of gag dominant negative mutant and a human ribonuclease in a tightly controlled HIV-1 inducible vector AN - 16276048; 4283188 AB - An HIV-1-based expression vector has been constructed that produces protective genes tightly regulated by HIV-1 Tat and Rev proteins. The vector contains either a single protective gene (HIV-1 gag dominant negative mutant (delta-gag)) or a combination of two different protective genes (delta-gag and eosinophil-derived neurotoxin (EDN), a human ribonuclease) which are expressed from a dicistronic mRNA. After stable transfection of CEM T cells and following challenge with HIV-1, viral production was completely inhibited in cells transduced with the vector producing both delta-gag and EDN and delayed in cells producing delta-gag alone. In addition, cotransfection of HeLa-Tat cells with an infectious HIV-1 molecular clone and either protective vector demonstrated that the HIV-1 packaging signals present in the constructs were functional and allowed the efficient assembly of the protective RNAs into HIV-1 virions, thus potentially transmitting protection to the HIV-1 target cells. JF - Gene Therapy AU - Cara, A AU - Rybak, S M AU - Newton, D L AU - Crowley, R AU - Rottschafer, SE AU - Reitz, Jr AU - Gusella, G L AD - Lab. Biochem. Physiol., Bldg. 567, Rm. 152, Frederick, NCI-Frederick Cancer Res. and Dev. Cent., Frederick, MD 21702, USA Y1 - 1998/01// PY - 1998 DA - Jan 1998 SP - 65 EP - 75 VL - 5 IS - 1 SN - 0969-7128, 0969-7128 KW - HIV-1 KW - Rev protein KW - Tat protein KW - eosinophil-derived neurotoxin KW - expression vectors KW - gag gene KW - human immunodeficiency virus 1 KW - ribonuclease KW - virions KW - Biotechnology and Bioengineering Abstracts; Virology & AIDS Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - W3 33181:Gene therapy vectors KW - V 22002:AIDS: Molecular and in vitro aspects KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16276048?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Gene+Therapy&rft.atitle=Inhibition+of+HIV-1+replication+by+combined+expression+of+gag+dominant+negative+mutant+and+a+human+ribonuclease+in+a+tightly+controlled+HIV-1+inducible+vector&rft.au=Cara%2C+A%3BRybak%2C+S+M%3BNewton%2C+D+L%3BCrowley%2C+R%3BRottschafer%2C+SE%3BReitz%2C+Jr%3BGusella%2C+G+L&rft.aulast=Cara&rft.aufirst=A&rft.date=1998-01-01&rft.volume=5&rft.issue=1&rft.spage=65&rft.isbn=&rft.btitle=&rft.title=Gene+Therapy&rft.issn=09697128&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Interleukin-2-mediated modulation of plasma cell tumor growth in a model of multiple myeloma AN - 16273548; 4262463 AB - A number of studies have demonstrated that inoculation of certain types of cancer cells engineered for expression of the interleukin-2 (IL-2) gene results in reduced tumorigenicity and/or protection from subsequent challenge with a tumorigenic dose of wild-type cells. In the current studies, we have employed murine plasma cell tumors to examine IL-2-mediated tumor rejection as a possible model for therapeutic approaches to human myeloma or plasma cell leukemia. Two murine plasma cell tumor lines, S107 and X24, were infected with a retroviral vector expressing the human IL-2 gene, and the antitumor potential of IL-2-expressing infectants was characterized in syngeneic BALB/c and BALB/c nu/nu mice. Results demonstrate that tumorigenicity of both lines correlates inversely with the amount of IL-2 produced by the tumor cells. However, there are clear differences between the two lines in terms of reduced tumorigenicity and the ability to protect against co-injected parental tumor cells that appear unrelated to IL-2 levels. More importantly, intravenous immunization of animals with irradiated, IL-2 secreting cells from either line leads to significant protection from challenge with highly metastatic parental cells. These results suggest that such an approach may warrant consideration in the treatment of human plasma cell dyscrasias. JF - Human Gene Therapy AU - Kopantzev, E AU - Roschke, V AU - Rudikoff, S AD - National Cancer Institute, NIH, Bldg. 37, Rm. 2B15, 37 Convent Drive, MSC 4255, Bethesda, MD 20892-4255, USA Y1 - 1998/01/01/ PY - 1998 DA - 1998 Jan 01 SP - 13 EP - 19 VL - 9 IS - 1 SN - 1043-0342, 1043-0342 KW - mice KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - W3 33170:Cellular based KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16273548?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+Gene+Therapy&rft.atitle=Interleukin-2-mediated+modulation+of+plasma+cell+tumor+growth+in+a+model+of+multiple+myeloma&rft.au=Kopantzev%2C+E%3BRoschke%2C+V%3BRudikoff%2C+S&rft.aulast=Kopantzev&rft.aufirst=E&rft.date=1998-01-01&rft.volume=9&rft.issue=1&rft.spage=13&rft.isbn=&rft.btitle=&rft.title=Human+Gene+Therapy&rft.issn=10430342&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - On the antigenic determinants of the lipopolysaccharides of Vibrio cholerae O:1, serotypes Ogawa and Inaba AN - 16259753; 4272188 AB - Monoclonal, murine IgG sub(1)s S-20-4, A-20-6, and IgA 2D6, directed against Vibrio cholerae O:1 Ogawa-lipopolysaccharide exhibited the same fine specificities and similar affinities for the synthetic methyl alpha -glycosides of the (oligo)saccharide fragments mimicking the Ogawa O-polysaccharide (O-PS). They did not react with the corresponding synthetic fragments of Inaba O-PS. IgG sub(1)s S-20-4 and A-20-6 have absolute affinity constants for synthetic Ogawa mono- to hexasaccharides of from similar to 10 super(5) to similar to 10 super(6) M super(-1). For IgG sub(1)s S-20-4, A-20-6, and IgA 2D6, the nonreducing terminal residue of Ogawa O-PS is the dominant determinant, accounting for similar to 90% of the maximal binding energy shown by these antibodies. Binding studies of derivatives of the Ogawa monosaccharide and IgGs S-20-4 and A-20-6 revealed that the C-2 O-methyl group fits into a somewhat flexible antibody cavity and that hydrogen bonds involving the oxygen and, respectively, the OH at the 2- and 3-position of the sugar moiety as well as the 2'-position in the amide side chain are required. Monoclonal IgA ZAC-3 and IgG sub(3) I-24-2 are specific for V. cholerae O:1 serotypes Ogawa/Inaba-LPS. The former did not show binding with members of either series of the synthetic ligands related to the O-antigens of the Ogawa or Inaba serotypes, in agreement with its reported specificity for the lipid/core region (1). Inhibition studies revealed that the binding of purified IgG sub(3) I-24-2 to Ogawa-LPS might be mediated by a region in the junction of the OPS to the lipid-core region of the LPS. cDNA cloning and analysis of the anti-Ogawa antibodies S-20-4, A-20-6, and 2D6 revealed a very high degree of homology among the heavy chains. Among the light chains, no such homology between S-20-4 and A-20-6 on the one hand, and 2D6 on the other hand, exists. For the anti-Inaba/Ogawa antibodies I-24-2 and ZAC-3, their heavy chains are completely different, with some homology among the light chains. JF - Journal of Biological Chemistry AU - Wang, Jin AU - Villeneuve, S AU - Zhang, Jian AU - Lei, Ping-Sheng AU - Miller, CE AU - Lafaye, P AU - Nato, F AU - Szu, S C AU - Karpas, A AU - Bystricky, S AU - Robbins, J B AU - Kovac, P AU - Fournier, J-M AU - Glaudemans, CPJ AD - Laboratory of Medicinal Chemistry, NIDDK, NICHD, National Institutes of Health, Bethesda, MD 20892, USA Y1 - 1998/01// PY - 1998 DA - Jan 1998 SP - 2777 EP - 2783 VL - 273 IS - 5 SN - 0021-9258, 0021-9258 KW - antigenic determinants KW - cholera KW - lipopolysaccharides KW - monoclonal antibodies KW - Microbiology Abstracts B: Bacteriology KW - J 02832:Antigenic properties and virulence KW - J 02730:Carbohydrates UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16259753?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Biological+Chemistry&rft.atitle=On+the+antigenic+determinants+of+the+lipopolysaccharides+of+Vibrio+cholerae+O%3A1%2C+serotypes+Ogawa+and+Inaba&rft.au=Wang%2C+Jin%3BVilleneuve%2C+S%3BZhang%2C+Jian%3BLei%2C+Ping-Sheng%3BMiller%2C+CE%3BLafaye%2C+P%3BNato%2C+F%3BSzu%2C+S+C%3BKarpas%2C+A%3BBystricky%2C+S%3BRobbins%2C+J+B%3BKovac%2C+P%3BFournier%2C+J-M%3BGlaudemans%2C+CPJ&rft.aulast=Wang&rft.aufirst=Jin&rft.date=1998-01-01&rft.volume=273&rft.issue=5&rft.spage=2777&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - D3 dopamine receptor-deficient mouse: evidence for reduced anxiety. AN - 79466660; 9402626 AB - Mice without functional D3 dopamine receptors were examined in two animal models for anxiety: the open-field test and the elevated plus-maze test. In the open field, D3 receptor-deficient mice (D3-/-) entered the center significantly more often than normal (D3+/+) littermates, suggesting an anxiolytic-like effect of the D3 receptor mutation. Consistent with this finding, D3-/- mice entered open arms of the plus maze significantly more often and longer than D3+/+ littermates, but did not differ in closed-arm entries, an index of general activity. Heterozygous (D3 +/-) animals showed intermediate behavioral changes. We interpret these results as indicative of reduced anxiety in mice without D3 receptors. Our findings thus suggest that D3 dopamine receptors are involved in the regulation of anxiety. JF - Physiology & behavior AU - Steiner, H AU - Fuchs, S AU - Accili, D AD - Laboratory of Neurophysiology, National Institute of Mental Health, Bethesda, MD 20892, USA. hsteiner@nb.utmem.edu Y1 - 1997/12/31/ PY - 1997 DA - 1997 Dec 31 SP - 137 EP - 141 VL - 63 IS - 1 SN - 0031-9384, 0031-9384 KW - Drd3 protein, mouse KW - 0 KW - Receptors, Dopamine D2 KW - Receptors, Dopamine D3 KW - Index Medicus KW - Animals KW - Chimera KW - Mice, Inbred C57BL KW - Exploratory Behavior -- physiology KW - Motor Activity -- physiology KW - Mice KW - Male KW - Mutagenesis KW - Mice, Knockout KW - Anxiety -- psychology KW - Receptors, Dopamine D2 -- deficiency KW - Anxiety -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79466660?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Physiology+%26+behavior&rft.atitle=D3+dopamine+receptor-deficient+mouse%3A+evidence+for+reduced+anxiety.&rft.au=Steiner%2C+H%3BFuchs%2C+S%3BAccili%2C+D&rft.aulast=Steiner&rft.aufirst=H&rft.date=1997-12-31&rft.volume=63&rft.issue=1&rft.spage=137&rft.isbn=&rft.btitle=&rft.title=Physiology+%26+behavior&rft.issn=00319384&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-02-04 N1 - Date created - 1998-02-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Validation of benzene exposure assessment. AN - 79548803; 9472334 AB - We conducted a methodologic study to validate a quantitative retrospective exposure assessment method used in a follow-up study of workers exposed to benzene. Assessment of exposure to benzene was carried out in 672 factories in 12 cities in China. Historical exposure data were collected for 3179 unique job titles. The basic unit for exposure assessment was a factory/work-unit/job-title combination over seven periods between 1949 and 1987. A total of 18,435 exposure estimates was developed, using all available historical information, including 8477 monitoring data. Overall, 38% of the estimates were based on benzene monitoring data. The highest time-weighted average exposures occurred in the rubber industry (30.7 ppm), particularly for rubber glue applicators (52.6 ppm). Because of its recognized link with benzene exposure, the association between a clinical diagnosis of benzene poisoning (hematotoxicity) and benzene exposure was evaluated (412 cases and 614,509 person-years) to validate the exposure-assessment method. Relative risks of benzene hematotoxicity increased very sharply with increasing estimated intensity of benzene exposure. Odds ratios were 2.2 (95% CI: 1.7-2.9), 4.7 (95% CI: 3.4-6.5), and 7.2 (95% CI: 5.3-9.8) for the intensity levels of less than 5 ppm, 5-19 ppm, 20-39 ppm, and 40 and more ppm, respectively. This sharp trend between benzene hematotoxicity and estimated exposure to benzene indicated that the exposure-estimation method used in this cancer epidemiology study is reliable. JF - Annals of the New York Academy of Sciences AU - Dosemeci, M AU - Rothman, N AU - Yin, S N AU - Li, G L AU - Linet, M AU - Wacholder, S AU - Chow, W H AU - Hayes, R B AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA. DosemecM@EPNDCE.NCI.NIH.GOV Y1 - 1997/12/26/ PY - 1997 DA - 1997 Dec 26 SP - 114 EP - 121 VL - 837 SN - 0077-8923, 0077-8923 KW - Benzene KW - J64922108F KW - Index Medicus KW - Occupational Exposure KW - Humans KW - Retrospective Studies KW - Follow-Up Studies KW - Time Factors KW - Male KW - Female KW - China KW - Risk Assessment KW - Occupational Diseases KW - Benzene -- poisoning UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79548803?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Validation+of+benzene+exposure+assessment.&rft.au=Dosemeci%2C+M%3BRothman%2C+N%3BYin%2C+S+N%3BLi%2C+G+L%3BLinet%2C+M%3BWacholder%2C+S%3BChow%2C+W+H%3BHayes%2C+R+B&rft.aulast=Dosemeci&rft.aufirst=M&rft.date=1997-12-26&rft.volume=837&rft.issue=&rft.spage=114&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 - 1998-03-04 N1 - Date created - 1998-03-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The catalytic domain of protein kinase Cdelta confers protection from down-regulation induced by bryostatin 1. AN - 79483237; 9407126 AB - Bryostatin 1 (Bryo) has been shown to induce biphasic dose-response curves for down-regulating protein kinase Cdelta (PKCdelta) as well as for protecting PKCdelta from down-regulation induced by phorbol 12-myristate 13-acetate (PMA). To identify regions within PKCdelta that confer these responses to Bryo, we utilized reciprocal PKCalpha and PKCdelta chimeras (PKCalpha/delta and PKCdelta/alpha) constructed by exchanging the regulatory and catalytic domains of these PKCs. These chimeras and wild-type PKCalpha/alpha and PKCdelta/delta constructed in the same way were stably expressed in NIH 3T3 fibroblasts. Twenty-four h of treatment with Bryo induced a biphasic dose-response curve for down-regulating both wild-type PKCdelta/delta and the PKCalpha/delta chimera. In contrast, Bryo led to a nearly complete down-regulation of both PKCalpha/alpha and PKCdelta/alpha and also produced a faster mobility form of these species on SDS-polyacrylamide gel electrophoresis. The nature of both the regulatory and, to a lesser extent, the catalytic domains affected the potency of Bryo to down-regulate the chimeric PKC proteins as well as to protect PKCalpha/delta and PKCdelta/delta from down-regulation. Bryo at high concentrations also inhibited the down-regulation of PKCdelta/delta and PKCalpha/delta induced by 1 microM PMA when co-applied. The portion of PKC protected by Bryo from down-regulation by either Bryo or PMA was localized in the particulate fraction of the cells. We conclude that the catalytic domain of PKCdelta confers protection from down-regulation induced by Bryo or Bryo plus PMA, suggesting that this domain contains the isotype-specific determinants involved in the unique effect of Bryo on PKCdelta. JF - The Journal of biological chemistry AU - Lorenzo, P S AU - Bögi, K AU - Acs, P AU - Pettit, G R AU - Blumberg, P M AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1997/12/26/ PY - 1997 DA - 1997 Dec 26 SP - 33338 EP - 33343 VL - 272 IS - 52 SN - 0021-9258, 0021-9258 KW - Antineoplastic Agents KW - 0 KW - Bryostatins KW - Isoenzymes KW - Lactones KW - Macrolides KW - Recombinant Fusion Proteins KW - bryostatin 1 KW - 37O2X55Y9E KW - Prkcd protein, mouse KW - EC 2.7.1.- KW - Prkca protein, mouse KW - EC 2.7.11.13 KW - Protein Kinase C KW - Protein Kinase C-alpha KW - Protein Kinase C-delta KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - 3T3 Cells KW - Animals KW - Enzyme Activation KW - Mice KW - Binding Sites KW - Recombinant Fusion Proteins -- metabolism KW - Transfection KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Catalysis KW - Protein Kinase C -- metabolism KW - Protein Kinase C -- genetics KW - Down-Regulation -- drug effects KW - Isoenzymes -- genetics KW - Antineoplastic Agents -- pharmacology KW - Isoenzymes -- metabolism KW - Lactones -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79483237?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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+catalytic+domain+of+protein+kinase+Cdelta+confers+protection+from+down-regulation+induced+by+bryostatin+1.&rft.au=Lorenzo%2C+P+S%3BB%C3%B6gi%2C+K%3BAcs%2C+P%3BPettit%2C+G+R%3BBlumberg%2C+P+M&rft.aulast=Lorenzo&rft.aufirst=P&rft.date=1997-12-26&rft.volume=272&rft.issue=52&rft.spage=33338&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 - 1998-01-23 N1 - Date created - 1998-01-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Asian genotypes of JC virus in Native Americans and in a Pacific Island population: markers of viral evolution and human migration. AN - 79482252; 9405649 AB - The human polyomavirus JC (JCV) causes the central nervous system demyelinating disease progressive multifocal leukoencephalopathy. Previously, we showed that 40% of Caucasians in the United States excrete JCV in the urine as detected by PCR. We have now studied 68 Navaho from New Mexico, 25 Flathead from Montana, and 29 Chamorro from Guam. By using PCR amplification of a fragment of the VP1 gene, JCV DNA was detected in the urine of 45 (66%) Navaho, 14 (56%) Flathead, and 20 (69%) Chamorro. Genotyping of viral DNAs in these cohorts by cycle sequencing showed predominantly type 2 (Asian), rather than type 1 (European). Type 1 is the major type in the United States and Hungary. Type 2 can be further subdivided into 2A, 2B, and 2C. Type 2A is found in China and Japan. Type 2B is a subtype related to the East Asian type, and is now found in Europe and the United States. The large majority (56-89%) of strains excreted by Native Americans and Pacific Islanders were the type 2A subtype, consistent with the origin of these strains in Asia. These findings indicate that JCV infection of Native Americans predates contact with Europeans, and likely predates migration of Amerind ancestors across the Bering land bridge around 12,000-30,000 years ago. If JCV had already differentiated into stable modern genotypes and subtypes prior to first settlement, the origin of JCV in humans may date from 50,000 to 100,000 years ago or more. We conclude that JCV may have coevolved with the human species, and that it provides a convenient marker for human migrations in both prehistoric and modern times. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Agostini, H T AU - Yanagihara, R AU - Davis, V AU - Ryschkewitsch, C F AU - Stoner, G L AD - Neurotoxicology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1997/12/23/ PY - 1997 DA - 1997 Dec 23 SP - 14542 EP - 14546 VL - 94 IS - 26 SN - 0027-8424, 0027-8424 KW - Biomarkers KW - 0 KW - Index Medicus KW - Indians, North American KW - Humans KW - Geography KW - JC Virus -- genetics KW - Genetics, Population KW - Genome, Viral KW - Evolution, Molecular UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79482252?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Asian+genotypes+of+JC+virus+in+Native+Americans+and+in+a+Pacific+Island+population%3A+markers+of+viral+evolution+and+human+migration.&rft.au=Agostini%2C+H+T%3BYanagihara%2C+R%3BDavis%2C+V%3BRyschkewitsch%2C+C+F%3BStoner%2C+G+L&rft.aulast=Agostini&rft.aufirst=H&rft.date=1997-12-23&rft.volume=94&rft.issue=26&rft.spage=14542&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 - 1998-02-02 N1 - Date created - 1998-02-02 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Clin Microbiol. 1991 Oct;29(10):2130-8 [1682343] Brain. 1958 Mar;81(1):93-111 [13523006] J Gen Virol. 1992 Oct;73 ( Pt 10):2669-78 [1328479] Ann Neurol. 1983 Jan;13(1):79-86 [6830169] J Virol. 1988 May;62(5):1730-5 [2833622] Proc Natl Acad Sci U S A. 1988 Aug;85(16):6002-6 [3166138] Adv Virus Res. 1994;43:147-86 [8191953] Arch Virol. 1995;140(11):1919-34 [7503691] Cell Mol Biol (Noisy-le-grand). 1995;41 Suppl 1:S145-61 [8574142] J Gen Virol. 1996 May;77 ( Pt 5):919-27 [8609488] J Clin Microbiol. 1996 Jan;34(1):159-64 [8748293] J Neurovirol. 1996 Aug;2(4):259-67 [8799217] Arch Virol. 1997;142(4):637-55 [9170494] Arch Virol. 1997;142(5):875-82 [9191854] J Infect Dis. 1997 Jul;176(1):1-8 [9207343] J Neurovirol. 1995 Sep;1(3-4):316-20 [9222370] Mult Scler. 1996 Feb;1(4):193-9 [9345433] J Virol. 1992 Apr;66(4):2057-66 [1312620] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hepatitis B virus X protein and p53 tumor suppressor interactions in the modulation of apoptosis. AN - 79478182; 9405677 AB - We have reported previously that the hepatitis B virus oncoprotein, HBx, can bind to the C terminus of p53 and inhibit several critical p53-mediated cellular processes, including DNA sequence-specific binding, transcriptional transactivation, and apoptosis. Recognizing the importance of p53-mediated apoptosis for maintaining homeostasis and preventing neoplastic transformation, here we further examine the physical interaction between HBx and p53 as well as the functional consequences of this association. In vitro binding studies indicate that the ayw and adr viral subtypes of HBx bind similar amounts of glutathione S-transferase-p53 with the distal C terminus of HBx (from residues 111 to 154) being critical for this interaction. Using a microinjection technique, we show that this same C-terminal region of HBx is necessary for sequestering p53 in the cytoplasm and abrogating p53-mediated apoptosis. The transcriptional transactivation domain of HBx also maps to its C terminus; however, a comparison of the ability of full-length and truncated HBx protein to abrogate p53-induced apoptosis versus transactivate simian virus 40- or human nitric oxide synthase-2 promoter-driven reporter constructs indicates that these two functional properties are distinct and thus may contribute to hepatocarcinogenesis differently. Collectively, our data indicate that the distal C-terminal domain of HBx, independent of its transactivation activity, complexes with p53 in the cytoplasm, partially preventing its nuclear entry and ability to induce apoptosis. These pathobiological effects of HBx may contribute to the early stages of hepatocellular carcinogenesis. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Elmore, L W AU - Hancock, A R AU - Chang, S F AU - Wang, X W AU - Chang, S AU - Callahan, C P AU - Geller, D A AU - Will, H AU - Harris, C C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1997/12/23/ PY - 1997 DA - 1997 Dec 23 SP - 14707 EP - 14712 VL - 94 IS - 26 SN - 0027-8424, 0027-8424 KW - Trans-Activators KW - 0 KW - Tumor Suppressor Protein p53 KW - hepatitis B virus X protein KW - Index Medicus KW - Fibroblasts -- pathology KW - Genes, Tumor Suppressor KW - Cells, Cultured KW - Humans KW - Adult KW - Gene Expression Regulation KW - Protein Binding KW - Fibroblasts -- metabolism KW - Male KW - Child, Preschool KW - Trans-Activators -- metabolism KW - Liver -- pathology KW - Apoptosis KW - Trans-Activators -- genetics KW - Liver -- metabolism 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/79478182?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Hepatitis+B+virus+X+protein+and+p53+tumor+suppressor+interactions+in+the+modulation+of+apoptosis.&rft.au=Elmore%2C+L+W%3BHancock%2C+A+R%3BChang%2C+S+F%3BWang%2C+X+W%3BChang%2C+S%3BCallahan%2C+C+P%3BGeller%2C+D+A%3BWill%2C+H%3BHarris%2C+C+C&rft.aulast=Elmore&rft.aufirst=L&rft.date=1997-12-23&rft.volume=94&rft.issue=26&rft.spage=14707&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 - 1998-02-02 N1 - Date created - 1998-02-02 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cell. 1993 Nov 19;75(4):653-60 [8242741] Cancer Res. 1994 Jan 1;54(1):231-5 [8261444] Mol Cell Biol. 1994 Feb;14(2):989-98 [7507209] Proc Natl Acad Sci U S A. 1994 Jan 18;91(2):822-6 [8290606] Proc Natl Acad Sci U S A. 1994 Mar 15;91(6):2230-4 [8134379] Annu Rev Med. 1994;45:297-323 [8198385] N Engl J Med. 1994 Jul 7;331(1):49-50 [8202105] Nature. 1994 Jul 21;370(6486):220-3 [8028670] Cancer Res. 1994 Sep 15;54(18):4855-78 [8069852] Cell. 1994 Sep 23;78(6):915-8 [7522969] Lab Invest. 1994 Sep;71(3):324-49 [7933984] Carcinogenesis. 1994 Dec;15(12):2875-7 [8001249] Crit Rev Oncol Hematol. 1994 Oct;17(2):71-91 [7818788] Hepatology. 1995 Feb;21(2):313-21 [7843699] Nat Genet. 1995 Jan;9(1):41-7 [7704023] J Med Virol. 1995 Jan;45(1):82-90 [7714496] J Hepatol. 1995;22(1 Suppl):34-7 [7602073] Genes Dev. 1995 Sep 1;9(17):2170-83 [7657168] Chem Res Toxicol. 1995 Apr-May;8(3):473-7 [7578935] Cancer Res. 1995 Dec 15;55(24):6012-6 [8521383] Eur J Cancer. 1995 Oct;31A(11):1847-50 [8541111] EMBO J. 1996 Feb 15;15(4):827-38 [8631304] Proc Natl Acad Sci U S A. 1990 Aug;87(15):5628-32 [2165598] Mol Biol Med. 1990 Jun;7(3):243-60 [2170810] Nature. 1991 Apr 4;350(6317):427-8 [1849234] Oncogene. 1992 Mar;7(3):397-403 [1549357] Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):3030-4 [1557408] J Exp Med. 1992 Jul 1;176(1):261-4 [1377225] Oncogene. 1993 Feb;8(2):491-6 [8093978] Oncogene. 1993 May;8(5):1109-17 [8386823] Cancer Res. 1993 Jun 15;53(12):2884-7 [8389246] Cell. 1993 Aug 27;74(4):609-19 [8358790] Nature. 1991 Apr 4;350(6317):429-31 [1672732] Science. 1991 May 10;252(5007):842-4 [1827531] Nature. 1991 May 23;351(6324):317-20 [2034275] Nature. 1991 Jun 6;351(6326):453-6 [2046748] Cancer Res. 1991 Jul 1;51(13):3356-61 [2054775] Science. 1991 Nov 15;254(5034):1001-3 [1948068] J Virol. 1992 Feb;66(2):983-91 [1309924] Proc Natl Acad Sci U S A. 1996 Mar 19;93(6):2442-7 [8637893] Mol Carcinog. 1996 Apr;15(4):261-9 [8634084] Carcinogenesis. 1996 May;17(5):1007-12 [8640905] Genes Dev. 1996 May 15;10(10):1219-32 [8675009] Proc Natl Acad Sci U S A. 1996 May 28;93(11):5647-52 [8643631] Nat Med. 1996 Jul;2(7):804-10 [8673928] J Biol Chem. 1996 Jun 28;271(26):15443-50 [8663128] World J Surg. 1996 Feb;20(2):215-20 [8661820] J Natl Cancer Inst. 1996 Oct 16;88(20):1442-55 [8841019] Genes Dev. 1996 Oct 1;10(19):2438-51 [8843196] Proc Natl Acad Sci U S A. 1996 Oct 1;93(20):10578-83 [8855220] Cancer Res. 1997 Feb 1;57(3):426-32 [9012469] Proc Natl Acad Sci U S A. 1997 Jul 22;94(15):8162-7 [9223332] Cancer Res. 1997 Nov 15;57(22):5137-42 [9371515] J Surg Res. 1993 Oct;55(4):427-32 [7692140] J Natl Cancer Inst. 1983 Dec;71(6):1143-50 [6418939] Jpn J Cancer Res. 1989 Jul;80(7):617-21 [2507484] EMBO J. 1990 Apr;9(4):1137-45 [2323335] Oncogene. 1988 Nov;3(5):545-52 [2856254] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Neuromedin B receptor activation causes tyrosine phosphorylation of p125FAK by a phospholipase C independent mechanism which requires p21rho and integrity of the actin cytoskeleton. AN - 79473761; 9405068 AB - Recent studies show that tyrosine phosphorylation by a number of neuropeptides may be an important intracellular pathway in mediating changes in cell function, particularly related to growth. Neuromedin B (NMB), a mammalian bombesin related peptide, functions through a distinct receptor, the neuromedin B receptor (NMB-R), of which little is known about its cellular basis of action. In the present study we explored the ability of NMB-R activation to cause tyrosine phosphorylation of focal adhesion kinase (p125(FAK)), an important substrate for tyrosine phosphorylation by other neuropeptides. NMB caused rapid increases in p125(FAK) phosphorylation which reached maximum at 2 min in both rat C6 glioblastoma cells which possess native NMB-Rs and rat neuromedin B receptor (rNMR-R) transfected BALB 3T3 cells. NMB had a half-maximal effect was at 0.4 nM and was 30-fold more potent than gastrin-releasing peptide (GRP). The stoichiometric relationships between increased p125(FAK) tyrosine phosphorylation and other cellular processes was similar in both C6 cells and rNMB-R transfected cells. TPA (1 microM) caused 45% and the calcium ionophore, A23187, 11% of maximal tyrosine phosphorylation of p125(FAK) seen with NMB. A23187 potentiated the effect of TPA. Pretreatment with the selective PKC inhibitor, GF109203X, inhibited TPA-induced p125(FAK) tyrosine phosphorylation, but it had no effect on the NMB stimulation. Pretreatment with thapsigargin completely inhibited NMB-stimulated increases in [Ca2+]i, but had no effect on NMB-stimulation of p125(FAK) phosphorylation either alone or with GF109203X. The tyrosine kinase inhibitor, tyrphostin A25, inhibited NMB-induced phosphorylation of p125(FAK) by 52%. However, tyrphostin A25 did not inhibit NMB-stimulated increases in [3H]inositol phosphates. Cytochalasin D, an agent which disrupts actin microfilaments, inhibited BN- and TPA-induced tyrosine phosphorylation of p125(FAK) completely. In contrast, colchicine, an agent which disrupts microtubules, had no effect. Pretreatment with Clostridium botulinum C3 exoenzyme which inactivates the small GTP-binding protein rho p21, also inhibited tyrosine phosphorylation of p125(FAK) by 55%. These results demonstrate that activation of NMB-R can cause rapid tyrosine phosphorylation of p125(FAK). NMB-induced tyrosine phosphorylation of p125(FAK) is independent of NMB-induced changes in [Ca2+]i or PKC. The integrity of the actin cytoskeleton but not of microtubules is necessary for NMB-stimulated phosphorylation of p125(FAK). The ras-related small GTP-binding protein rho p21 is at least partially involved in mediating NMB-induced tyrosine phosphorylation of p125(FAK). These results suggest that similar to some other neuropeptides, activation of this pathway may be an important mechanism in mediating cellular changes by this receptor such as growth. JF - Biochemistry AU - Tsuda, T AU - Kusui, T AU - Jensen, R T AD - Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-1804, USA. Y1 - 1997/12/23/ PY - 1997 DA - 1997 Dec 23 SP - 16328 EP - 16337 VL - 36 IS - 51 SN - 0006-2960, 0006-2960 KW - Actins KW - 0 KW - Cell Adhesion Molecules KW - Enzyme Inhibitors KW - Indoles KW - Maleimides KW - Nitriles KW - Receptors, Bombesin KW - Tyrphostins KW - tyrphostin 25 KW - 118409-58-8 KW - Phosphotyrosine KW - 21820-51-9 KW - Cytochalasin D KW - 22144-77-0 KW - Calcimycin KW - 37H9VM9WZL KW - Thapsigargin KW - 67526-95-8 KW - Gastrin-Releasing Peptide KW - 80043-53-4 KW - Neurokinin B KW - 86933-75-7 KW - neuromedin B KW - 87096-84-2 KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - exoenzyme C3, Clostridium botulinum KW - Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - Focal Adhesion Kinase 1 KW - EC 2.7.10.2 KW - Focal Adhesion Protein-Tyrosine Kinases KW - Ptk2 protein, mouse KW - Ptk2 protein, rat KW - Type C Phospholipases KW - EC 3.1.4.- KW - Botulinum Toxins KW - EC 3.4.24.69 KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - rho GTP-Binding Proteins KW - EC 3.6.5.2 KW - bisindolylmaleimide I KW - L79H6N0V6C KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Colchicine KW - SML2Y3J35T KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Animals KW - Calcimycin -- pharmacology KW - Actin Cytoskeleton -- drug effects KW - Calcium -- metabolism KW - Rats KW - Colchicine -- pharmacology KW - Tumor Cells, Cultured KW - Phosphorylation KW - Maleimides -- pharmacology KW - Gastrin-Releasing Peptide -- metabolism KW - Neurokinin B -- pharmacology KW - Nitriles -- pharmacology KW - Actin Cytoskeleton -- chemistry KW - Mice KW - Neurokinin B -- metabolism KW - Thapsigargin -- pharmacology KW - Neurokinin B -- genetics KW - Transfection -- genetics KW - ADP Ribose Transferases -- metabolism KW - Enzyme Inhibitors -- pharmacology KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Cytochalasin D -- pharmacology KW - Indoles -- pharmacology KW - Neurokinin B -- analogs & derivatives KW - GTP-Binding Proteins -- metabolism KW - Phosphotyrosine -- metabolism KW - Cell Adhesion Molecules -- metabolism KW - Actins -- metabolism KW - Receptors, Bombesin -- metabolism KW - Protein-Tyrosine Kinases -- metabolism KW - Type C Phospholipases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79473761?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Neuromedin+B+receptor+activation+causes+tyrosine+phosphorylation+of+p125FAK+by+a+phospholipase+C+independent+mechanism+which+requires+p21rho+and+integrity+of+the+actin+cytoskeleton.&rft.au=Tsuda%2C+T%3BKusui%2C+T%3BJensen%2C+R+T&rft.aulast=Tsuda&rft.aufirst=T&rft.date=1997-12-23&rft.volume=36&rft.issue=51&rft.spage=16328&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-01-22 N1 - Date created - 1998-01-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Isothiocyanate derivatives of 9-[3-(cis-3,5-dimethyl-1-piperazinyl)propyl]carbazole (rimcazole): irreversible ligands for the dopamine transporter. AN - 79524403; 9435903 AB - Cocaine has been reported to bind to the dopamine transporter in a biphasic fashion, and it has been hypothesized that the low-affinity component may play a modulatory role in cocaine's psychomotor stimulant effects. In an effort to gain further insight into the roles of the two sites, we have prepared a series of irreversible ligands based on rimcazole (9-[3-(cis-3,5-dimethyl-1-piperazinyl)propyl]carbazole, 2), a compound that has been postulated to bind only to the low-affinity site. The alkylating moiety (isothiocyanate) is attached to the distal nitrogen of the piperazine ring via alkyl chains of varying lengths or directly attached to one of the aromatic groups. It was found that substitution on the piperazine nitrogen caused an initial decrease in affinity that was recovered as the alkyl chain length increased. Importantly, the analogue 16, with the highest affinity for the dopamine transporter (DAT), binds in a monophasic and irreversible manner, as evidenced by the greatly diminished binding of [3H]WIN 35,428 in tissue that had been preincubated with the ligand and then thoroughly washed using centrifugation. The dose-dependent reduction in Bmax was accompanied by a concentration-related decrease in KD values. This shift in KD to a lower value suggests that the preincubation with 16 produced a preferential irreversible binding to the low-affinity [3H]WIN 35,428 site on the dopamine transporter. These ligands may prove to be important tools with which to study the significance of the low-affinity site on the DAT. Since rimcazole does not share the behavioral profile of cocaine, and in fact appears to play a modulatory role, these compounds may provide leads for a novel cocaine-abuse treatment. JF - Journal of medicinal chemistry AU - Husbands, S M AU - Izenwasser, S AU - Loeloff, R J AU - Katz, J L AU - Bowen, W D AU - Vilner, B J AU - Newman, A H AD - Psychobiology Section, National Institute on Drug Abuse-Intramural Research Program, Baltimore, Maryland 21224, USA. Y1 - 1997/12/19/ PY - 1997 DA - 1997 Dec 19 SP - 4340 EP - 4346 VL - 40 IS - 26 SN - 0022-2623, 0022-2623 KW - Carbazoles KW - 0 KW - Carrier Proteins KW - Dopamine Plasma Membrane Transport Proteins KW - Isothiocyanates KW - Ligands KW - Membrane Glycoproteins KW - Membrane Transport Proteins KW - Nerve Tissue Proteins KW - Receptors, sigma KW - Slc6a3 protein, rat KW - (1R-(exo,exo))-3-(4-fluorophenyl)-8-methyl-8- azabicyclo(3.2.1)octane-2-carboxylic acid, methyl ester KW - 50370-56-4 KW - rimcazole KW - C3N1PS8CX1 KW - Cocaine KW - I5Y540LHVR KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Animals KW - Guinea Pigs KW - Receptors, sigma -- metabolism KW - Cocaine-Related Disorders -- drug therapy KW - Dopamine -- metabolism KW - Liver -- metabolism KW - Brain -- metabolism KW - Protein Binding KW - Binding Sites KW - Rats KW - Cocaine -- analogs & derivatives KW - Binding, Competitive KW - Cocaine -- metabolism KW - Isothiocyanates -- pharmacology KW - Carbazoles -- metabolism KW - Isothiocyanates -- metabolism KW - Carrier Proteins -- metabolism KW - Carbazoles -- chemistry KW - Carbazoles -- pharmacology KW - Isothiocyanates -- chemistry KW - Carbazoles -- chemical synthesis KW - Isothiocyanates -- chemical synthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79524403?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+medicinal+chemistry&rft.atitle=Isothiocyanate+derivatives+of+9-%5B3-%28cis-3%2C5-dimethyl-1-piperazinyl%29propyl%5Dcarbazole+%28rimcazole%29%3A+irreversible+ligands+for+the+dopamine+transporter.&rft.au=Husbands%2C+S+M%3BIzenwasser%2C+S%3BLoeloff%2C+R+J%3BKatz%2C+J+L%3BBowen%2C+W+D%3BVilner%2C+B+J%3BNewman%2C+A+H&rft.aulast=Husbands&rft.aufirst=S&rft.date=1997-12-19&rft.volume=40&rft.issue=26&rft.spage=4340&rft.isbn=&rft.btitle=&rft.title=Journal+of+medicinal+chemistry&rft.issn=00222623&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-02-13 N1 - Date created - 1998-02-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Enzyme-substrate intermediate at a specific lysine residue is required for deoxyhypusine synthesis. The role of Lys329 in human deoxyhypusine synthase. AN - 79478296; 9405486 AB - Deoxyhypusine synthase catalyzes the first step in the post-translational synthesis of hypusine [Nepsilon-(4-amino-2-hydroxybutyl)lysine] in eukaryotic translation initiation factor 5A. We recently reported biochemical evidence for a covalent enzyme-substrate intermediate involving a specific lysine residue (Lys329) in human deoxyhypusine synthase (Wolff, E. C., Folk, J. E., and Park, M. H. (1997) J. Biol. Chem. 272, 15865-15871). In an effort to evaluate the role of this enzyme-substrate intermediate in catalysis, we carried out site-directed mutagenesis (Lys to Arg and/or Ala) of the conserved lysine residues in human deoxyhypusine synthase. A drastic reduction in enzyme intermediate formation and enzymatic activities was observed with mutant proteins with substitution at Lys287 but not with those with mutations at residues 141, 156, 205, 212, 226, 251, or 338. Lys to Ala or Lys to Arg substitution at Lys329 totally abolished covalent enzyme-substrate intermediate formation and deoxyhypusine synthesis activity, indicating that Lys329 is the unique site for the enzyme intermediate and that it is absolutely required for deoxyhypusine synthesis in the eukaryotic translation initiation factor 5A precursor. The K329A mutant showed spermidine cleavage activity ( approximately 6% of the wild type enzyme) suggesting that in contrast to deoxyhypusine synthesis, spermidine cleavage can occur without enzyme intermediate formation. JF - The Journal of biological chemistry AU - Joe, Y A AU - Wolff, E C AU - Lee, Y B AU - Park, M H AD - Oral and Pharyngeal Cancer Branch, NIDR, National Institutes of Health, Bethesda, Maryland 20892-4340, USA. Y1 - 1997/12/19/ PY - 1997 DA - 1997 Dec 19 SP - 32679 EP - 32685 VL - 272 IS - 51 SN - 0021-9258, 0021-9258 KW - Biopolymers KW - 0 KW - deoxyhypusine KW - 82543-85-9 KW - Oxidoreductases Acting on CH-NH Group Donors KW - EC 1.5.- KW - deoxyhypusine synthase KW - EC 1.5.1.- KW - Lysine KW - K3Z4F929H6 KW - Spermidine KW - U87FK77H25 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Spermidine -- metabolism KW - Humans KW - Substrate Specificity KW - Oxidoreductases Acting on CH-NH Group Donors -- metabolism KW - Oxidoreductases Acting on CH-NH Group Donors -- genetics KW - Lysine -- analogs & derivatives KW - Lysine -- biosynthesis KW - Oxidoreductases Acting on CH-NH Group Donors -- chemistry KW - Lysine -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79478296?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Enzyme-substrate+intermediate+at+a+specific+lysine+residue+is+required+for+deoxyhypusine+synthesis.+The+role+of+Lys329+in+human+deoxyhypusine+synthase.&rft.au=Joe%2C+Y+A%3BWolff%2C+E+C%3BLee%2C+Y+B%3BPark%2C+M+H&rft.aulast=Joe&rft.aufirst=Y&rft.date=1997-12-19&rft.volume=272&rft.issue=51&rft.spage=32679&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 - 1998-01-22 N1 - Date created - 1998-01-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Replacement of conserved cysteines in human tissue inhibitor of metalloproteinases-1. AN - 79476829; 9405413 AB - Tissue inhibitor of metalloproteinases-1 (TIMP-1) is resistant to extremes of temperature and pH. This is thought to be due in part to the presence of six sulfhydryl bridges presumed to maintain the structural integrity of the molecule. As part of a study looking at structure-function relationships, a number of the conserved cysteine residues in TIMP-1 were targeted for replacement with serine. Single and double replacements of these conserved cysteines, as well as replacements around these cysteines, were expressed using a vaccinia virus system and analyzed for functional and structural competence. Analysis by circular dichroism indicated that these mutants maintained secondary structures similar to those of wild-type TIMP-1. Trypsin susceptibility experiments indicated that the tertiary structure of the mutants had not been drastically changed. Analysis of functional competence demonstrated that there were significant changes in some of these mutants. Assays using collagen fibrils or gelatin as substrates indicated that the double mutant C1S/C70S, but not C3S/C99S, had lost inhibitory activity against human fibroblast-type collagenase (FIB-CL) and at high concentrations only had slight activity against Mr 72,000 gelatinase (Mr 72,000 gelatinase). Kinetic analysis of TIMP-1 inhibition of FIB-CL cleavage of a peptide substrate indicated that mutants C1S/C70S, C3S/C99S, and CEEC --> CQQC retained their ability to inhibit FIB-CL in a manner similar to wild-type TIMP-1, while mutants C1S and C70S showed little inhibitory activity. The mutants C99S and C137S could also inhibit FIB-CL cleavage of the peptide substrate. The results indicated that the degree of inhibition by the TIMP-1 mutants varied somewhat depending on the choice of substrates. Interestingly, replacing both cysteines from a disulfide bond in the wild-type molecule resulted in a more competent inhibitor than either of the single site "parent" mutations. Taken together, these experiments indicate that TIMP-1 can be rendered inactive by the loss of a single cysteine. JF - The Journal of biological chemistry AU - Caterina, N C AU - Windsor, L J AU - Yermovsky, A E AU - Bodden, M K AU - Taylor, K B AU - Birkedal-Hansen, H AU - Engler, J A AD - National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1997/12/19/ PY - 1997 DA - 1997 Dec 19 SP - 32141 EP - 32149 VL - 272 IS - 51 SN - 0021-9258, 0021-9258 KW - Matrix Metalloproteinase Inhibitors KW - 0 KW - Tissue Inhibitor of Metalloproteinase-1 KW - Gelatinases KW - EC 3.4.24.- KW - Cysteine KW - K848JZ4886 KW - Index Medicus KW - Fibroblasts -- enzymology KW - Humans KW - Circular Dichroism KW - Amino Acid Sequence KW - Molecular Weight KW - Structure-Activity Relationship KW - Mutagenesis, Site-Directed KW - Conserved Sequence KW - Kinetics KW - Gelatinases -- antagonists & inhibitors KW - Molecular Sequence Data KW - Substrate Specificity KW - Protein Conformation KW - Cysteine -- metabolism KW - Tissue Inhibitor of Metalloproteinase-1 -- chemistry KW - Tissue Inhibitor of Metalloproteinase-1 -- metabolism KW - Cysteine -- genetics KW - Tissue Inhibitor of Metalloproteinase-1 -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79476829?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Replacement+of+conserved+cysteines+in+human+tissue+inhibitor+of+metalloproteinases-1.&rft.au=Caterina%2C+N+C%3BWindsor%2C+L+J%3BYermovsky%2C+A+E%3BBodden%2C+M+K%3BTaylor%2C+K+B%3BBirkedal-Hansen%2C+H%3BEngler%2C+J+A&rft.aulast=Caterina&rft.aufirst=N&rft.date=1997-12-19&rft.volume=272&rft.issue=51&rft.spage=32141&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 - 1998-01-22 N1 - Date created - 1998-01-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - alpha B-crystallin TATA sequence mutations: lens-preference for the proximal TATA box and the distal TATA-like sequence in transgenic mice. AN - 79504705; 9425284 AB - The mouse alpha B-crystallin promoter is active in lens (preferentially), heart and skeletal muscle, and contains a proximal (-28/-22) and distal (-76/-69) TATA sequence. The present investigation explores by site-specific mutagenesis of alpha B-crystallin promoter-chloramphenicol acetyltransferase (cat) reporter gene constructs the function of these two potential TATA boxes in transfected lens cells and transgenic mice. Unexpectedly, mutagenesis of either or both TATA sequences had no effect on promoter activity in transfected lens cells. By contrast, in transgenic mice mutagenesis of the proximal, distal or both TATA sequences preferentially reduced promoter activity in the lens, with minimal effect in the heart or muscle. 5' RACE analysis of lens and muscle RNA of transgenic mice showed that elimination of the proximal TATA box led to transcription initiation at position -48. This upstream initiation site was apparently not due to the utilization of the distal TATA sequence, since the transgene carrying mutations in both TATA sequences also initiated at position -48. The preferential function of the distal TATA sequence in the lens is probably due to the binding of a transcription factor unrelated to transcription initiation, while the preferential lens function of the proximal TATA box appears to involve transcription initiation. JF - Biochemical and biophysical research communications AU - Haynes, J I AU - Gopal-Srivastava, R AU - Piatigorsky, J AD - Laboratory of Molecular and Developmental biology, NEI, NIH, Bethesda, Maryland 20892, USA. Y1 - 1997/12/18/ PY - 1997 DA - 1997 Dec 18 SP - 407 EP - 413 VL - 241 IS - 2 SN - 0006-291X, 0006-291X KW - Crystallins KW - 0 KW - Heat-Shock Proteins KW - Index Medicus KW - Animals KW - Base Sequence KW - Cells, Cultured KW - DNA Mutational Analysis KW - Molecular Sequence Data KW - Transcription, Genetic KW - Mice KW - Gene Expression Regulation KW - Mice, Transgenic KW - Muscle, Skeletal -- metabolism KW - Myocardium -- metabolism KW - Promoter Regions, Genetic KW - Lens, Crystalline -- metabolism KW - Lens, Crystalline -- cytology KW - Heat-Shock Proteins -- biosynthesis KW - Crystallins -- genetics KW - TATA Box KW - Heat-Shock Proteins -- genetics KW - Crystallins -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79504705?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=alpha+B-crystallin+TATA+sequence+mutations%3A+lens-preference+for+the+proximal+TATA+box+and+the+distal+TATA-like+sequence+in+transgenic+mice.&rft.au=Haynes%2C+J+I%3BGopal-Srivastava%2C+R%3BPiatigorsky%2C+J&rft.aulast=Haynes&rft.aufirst=J&rft.date=1997-12-18&rft.volume=241&rft.issue=2&rft.spage=407&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 - 1998-01-26 N1 - Date created - 1998-01-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Amyloid precursor protein requires the insulin signaling pathway for neurotrophic activity. AN - 79570288; 9495542 AB - Picomolar concentrations of purified amyloid precursor protein (APP) potentiate the neurotrophic activity of suboptimal concentrations of NGF on PC12 cells. To understand the molecular basis for this potentiation, we have characterized the signal transduction pathway used by APP for its neurotrophic activity. APP stimulated the tyrosine phosphorylation of a number of proteins including insulin receptor substrate-1 (IRS-1). Incubation of naive cells with antisense oligonucleotides to IRS-1 mRNA resulted in a dramatic reduction of IRS-1 levels and inhibition of APP stimulated neurite outgrowth. Phosphotidylinositol 3-kinase became associated with IRS-1 and activated upon APP stimulation. Extracellular signal-regulated kinase (ERK 1 and ERK 2) phosphorylation was detected by both immunoblot analysis and immunocytochemistry using antibodies directed to their phosphorylated (and hence, activated) form. There was also an elevation of ERK kinase activity. The potentiation of NGF activity was reflected in a correspondingly synergistic elevation of tyrosine phosphorylated ERK. The pattern of signal transduction targets indicates that APP potentiated the neurotrophic effects of NGF via the activation of the IRS-1 signaling pathway. JF - Brain research. Molecular brain research AU - Wallace, W C AU - Akar, C A AU - Lyons, W E AU - Kole, H K AU - Egan, J M AU - Wolozin, B AD - Laboratory of Cellular and Molecular Biology, National Institute on Aging, Gerontology Research Center, Johns Hopkins Bayview Campus, Baltimore, MD 21224, USA. waldo@helix.nih.gov Y1 - 1997/12/15/ PY - 1997 DA - 1997 Dec 15 SP - 213 EP - 227 VL - 52 IS - 2 SN - 0169-328X, 0169-328X KW - Amyloid beta-Protein Precursor KW - 0 KW - Insulin Receptor Substrate Proteins KW - Irs1 protein, rat KW - Nerve Growth Factors KW - Oligonucleotides, Antisense KW - Phosphoproteins KW - RNA, Messenger KW - Phosphotyrosine KW - 21820-51-9 KW - Phosphatidylinositol 3-Kinases KW - EC 2.7.1.- KW - Receptor, Insulin KW - EC 2.7.10.1 KW - Calcium-Calmodulin-Dependent Protein Kinases KW - EC 2.7.11.17 KW - Mitogen-Activated Protein Kinase 1 KW - EC 2.7.11.24 KW - Mitogen-Activated Protein Kinase 3 KW - Mitogen-Activated Protein Kinases KW - Index Medicus KW - Animals KW - Calcium-Calmodulin-Dependent Protein Kinases -- metabolism KW - Transcription, Genetic -- drug effects KW - Phosphatidylinositol 3-Kinases -- metabolism KW - Enzyme Activation KW - Phosphotyrosine -- metabolism KW - RNA, Messenger -- genetics KW - Rats KW - Phosphorylation KW - Molecular Sequence Data KW - Drug Synergism KW - Receptor, Insulin -- physiology KW - PC12 Cells KW - Signal Transduction -- physiology KW - Phosphoproteins -- biosynthesis KW - Neurites -- drug effects KW - Nerve Growth Factors -- pharmacology KW - Signal Transduction -- drug effects KW - Oligonucleotides, Antisense -- pharmacology KW - Amyloid beta-Protein Precursor -- pharmacology KW - Amyloid beta-Protein Precursor -- isolation & purification KW - Neurites -- physiology KW - Phosphoproteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79570288?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain+research.+Molecular+brain+research&rft.atitle=Amyloid+precursor+protein+requires+the+insulin+signaling+pathway+for+neurotrophic+activity.&rft.au=Wallace%2C+W+C%3BAkar%2C+C+A%3BLyons%2C+W+E%3BKole%2C+H+K%3BEgan%2C+J+M%3BWolozin%2C+B&rft.aulast=Wallace&rft.aufirst=W&rft.date=1997-12-15&rft.volume=52&rft.issue=2&rft.spage=213&rft.isbn=&rft.btitle=&rft.title=Brain+research.+Molecular+brain+research&rft.issn=0169328X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-05-04 N1 - Date created - 1998-05-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Amyloid precursor protein potentiates the neurotrophic activity of NGF. AN - 79570187; 9495541 AB - Cortical amyloid precursor protein (APP) is induced and secreted in response to subcortical lesions of cholinergic innervation. To understand the physiological role of the induced APP, we have characterized its neurotrophic activity on PC12 cells. Highly purified human APP751 (50-1000 pM) induced outgrowth of neurites. The neurotrophic activity was inhibited by an antibody that was directed to the C-terminal portion of the secreted APP but not by an antibody directed to the KPI domain. The neurotrophic activity of APP was independent of the TrkA NGF receptor because neither phospholipase C-gamma1 nor TrkA exhibited tyrosine phosphorylations with APP treatment. Furthermore, APP stimulated neurite outgrowth from PC12 cells lacking TrkA receptors. At lower concentrations (10-50 pM), APP synergistically potentiated the neurotrophic effects of NGF when added with NGF or before NGF as a priming pretreatment. These results implicate APP, a rapidly induced protein in the injured cortex, as a potentiating agent that may render compromised neurons more responsive to low levels of NGF or other neurotrophins. JF - Brain research. Molecular brain research AU - Wallace, W C AU - Akar, C A AU - Lyons, W E AD - Laboratory of Cellular and Molecular Biology, National Institute on Aging, Gerontology Research Center, Baltimore, MD 21224, USA. waldo@helix.nih.gov Y1 - 1997/12/15/ PY - 1997 DA - 1997 Dec 15 SP - 201 EP - 212 VL - 52 IS - 2 SN - 0169-328X, 0169-328X KW - Amyloid beta-Protein Precursor KW - 0 KW - Antibodies KW - Nerve Growth Factors KW - Proto-Oncogene Proteins KW - Receptors, Nerve Growth Factor KW - Recombinant Proteins KW - Phosphotyrosine KW - 21820-51-9 KW - Receptor Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - Receptor, trkA KW - Phospholipases KW - EC 3.1.- KW - Index Medicus KW - Animals KW - Recombinant Proteins -- pharmacology KW - Recombinant Proteins -- biosynthesis KW - Cerebral Cortex -- metabolism KW - Humans KW - Rats KW - Recombinant Proteins -- isolation & purification KW - Transfection KW - Phosphotyrosine -- analysis KW - Antibodies -- pharmacology KW - Kinetics KW - Phospholipases -- metabolism KW - Kidney KW - Drug Synergism KW - Cell Line KW - PC12 Cells KW - Receptors, Nerve Growth Factor -- physiology KW - Receptors, Nerve Growth Factor -- drug effects KW - Proto-Oncogene Proteins -- drug effects KW - Neurites -- drug effects KW - Nerve Growth Factors -- pharmacology KW - Receptor Protein-Tyrosine Kinases -- drug effects KW - Amyloid beta-Protein Precursor -- biosynthesis KW - Amyloid beta-Protein Precursor -- pharmacology KW - Amyloid beta-Protein Precursor -- isolation & purification KW - Receptor Protein-Tyrosine Kinases -- physiology KW - Neurites -- physiology KW - Proto-Oncogene Proteins -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79570187?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain+research.+Molecular+brain+research&rft.atitle=Amyloid+precursor+protein+potentiates+the+neurotrophic+activity+of+NGF.&rft.au=Wallace%2C+W+C%3BAkar%2C+C+A%3BLyons%2C+W+E&rft.aulast=Wallace&rft.aufirst=W&rft.date=1997-12-15&rft.volume=52&rft.issue=2&rft.spage=201&rft.isbn=&rft.btitle=&rft.title=Brain+research.+Molecular+brain+research&rft.issn=0169328X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-05-04 N1 - Date created - 1998-05-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CONF T1 - Peripheral cocaine-blocking agents: new medications for cocaine dependence. An introduction to immunological and enzymatic approaches to treating cocaine dependence reported by Fox, Gorelick and Cohen in the immediately succeeding articles (see pages 153-174). AN - 79548449; 9449012 JF - Drug and alcohol dependence AU - Sparenborg, S AU - Vocci, F AU - Zukin, S Y1 - 1997/12/15/ PY - 1997 DA - 1997 Dec 15 SP - 149 EP - 151 VL - 48 IS - 3 KW - Antibodies, Catalytic KW - 0 KW - Vaccines KW - Butyrylcholinesterase KW - EC 3.1.1.- KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Humans KW - Behavior, Addictive -- drug therapy KW - Butyrylcholinesterase -- therapeutic use KW - Antibodies, Catalytic -- therapeutic use KW - Blood-Brain Barrier KW - Cocaine-Related Disorders -- enzymology KW - Cocaine-Related Disorders -- drug therapy KW - Cocaine -- pharmacokinetics KW - Cocaine -- immunology KW - Vaccines -- therapeutic use KW - Cocaine-Related Disorders -- immunology KW - Cocaine -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79548449?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&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=Drug+and+alcohol+dependence&rft.atitle=Peripheral+cocaine-blocking+agents%3A+new+medications+for+cocaine+dependence.+An+introduction+to+immunological+and+enzymatic+approaches+to+treating+cocaine+dependence+reported+by+Fox%2C+Gorelick+and+Cohen+in+the+immediately+succeeding+articles+%28see+pages+153-174%29.&rft.au=Sparenborg%2C+S%3BVocci%2C+F%3BZukin%2C+S&rft.aulast=Sparenborg&rft.aufirst=S&rft.date=1997-12-15&rft.volume=48&rft.issue=3&rft.spage=149&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 - 1998-05-04 N1 - Date created - 1998-05-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A large nucleoprotein assembly at the ends of the viral DNA mediates retroviral DNA integration. AN - 79480042; 9405379 AB - We have probed the nucleoprotein organization of Moloney murine leukemia virus (MLV) pre-integration complexes using a novel footprinting technique that utilizes a simplified in vitro phage Mu transposition system. We find that several hundred base pairs at each end of the viral DNA are organized in a large nucleoprotein complex, which we call the intasome. This structure is not formed when pre-integration complexes are made by infecting cells with integrase-minus virus, demonstrating a requirement for integrase. In contrast, footprinting of internal regions of the viral DNA did not reveal significant differences between pre-integration complexes with and without integrase. Treatment with high salt disrupts the intasome in parallel with loss of intermolecular integration activity. We show that a cellular factor is required for reconstitution of the intasome. Finally, we demonstrate that DNA-protein interactions involving extensive regions at the ends of the viral DNA are functionally important for retroviral DNA integration activity. Current in vitro integration systems utilizing purified integrase lack the full fidelity of the in vivo reaction. Our results indicate that both host factors and long viral DNA substrates may be required to reconstitute an in vitro system with all the hallmarks of DNA integration in vivo. JF - The EMBO journal AU - Wei, S Q AU - Mizuuchi, K AU - Craigie, R AD - Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1997/12/15/ PY - 1997 DA - 1997 Dec 15 SP - 7511 EP - 7520 VL - 16 IS - 24 SN - 0261-4189, 0261-4189 KW - DNA Transposable Elements KW - 0 KW - DNA, Viral KW - DNA-Binding Proteins KW - Nucleoproteins KW - Oligodeoxyribonucleotides KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Bacteriophage mu KW - Polymerase Chain Reaction KW - Animals KW - Base Sequence KW - Base Composition KW - DNA Footprinting KW - Molecular Sequence Data KW - Mice KW - Mutagenesis, Insertional KW - DNA -- metabolism KW - Nucleoproteins -- metabolism KW - Moloney murine leukemia virus -- genetics KW - Virus Integration KW - DNA, Viral -- genetics KW - Moloney murine leukemia virus -- metabolism KW - DNA-Binding Proteins -- metabolism KW - DNA, Viral -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79480042?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=A+large+nucleoprotein+assembly+at+the+ends+of+the+viral+DNA+mediates+retroviral+DNA+integration.&rft.au=Wei%2C+S+Q%3BMizuuchi%2C+K%3BCraigie%2C+R&rft.aulast=Wei&rft.aufirst=S&rft.date=1997-12-15&rft.volume=16&rft.issue=24&rft.spage=7511&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 - 1998-02-19 N1 - Date created - 1998-02-19 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Virol. 1990 Dec;64(12):5958-65 [2173775] Nat Struct Biol. 1997 Jul;4(7):567-77 [9228950] EMBO J. 1992 Jan;11(1):291-303 [1310932] J Biol Chem. 1992 May 15;267(14):9639-44 [1577801] Annu Rev Biochem. 1992;61:1011-51 [1323232] J Biol Chem. 1992 Oct 25;267(30):21273-6 [1383220] Proc Natl Acad Sci U S A. 1992 Oct 1;89(19):9237-41 [1329090] Nucleic Acids Res. 1993 Mar 25;21(6):1419-25 [8464733] Nucleic Acids Res. 1993 Jul 25;21(15):3507-11 [8346030] Cell. 1993 Aug 27;74(4):723-33 [8395353] J Virol. 1982 Oct;44(1):330-43 [6292495] Cell. 1984 Jul;37(3):1043-52 [6204767] J Virol. 1986 Aug;59(2):328-40 [2426463] Cell. 1987 May 8;49(3):347-56 [3032450] Cell. 1988 Aug 12;54(4):497-504 [3401925] Proc Natl Acad Sci U S A. 1989 Apr;86(8):2525-9 [2539592] Genes Dev. 1989 Apr;3(4):469-78 [2721960] Science. 1989 Nov 10;246(4931):780-6 [2814500] J Virol. 1989 Dec;63(12):5319-27 [2555556] J Virol. 1990 Jun;64(6):2711-5 [2335814] Proc Natl Acad Sci U S A. 1990 Jun;87(11):4164-8 [2349226] Proc Natl Acad Sci U S A. 1990 Jul;87(13):5119-23 [2164223] Cell. 1990 Aug 24;62(4):829-37 [2167180] Cell. 1990 Oct 5;63(1):87-95 [2170022] Science. 1990 Sep 28;249(4976):1555-8 [2171144] J Virol. 1994 Sep;68(9):5911-7 [8057470] J Biol Chem. 1994 Oct 7;269(40):25031-41 [7929189] Mol Microbiol. 1994 May;12(4):665-77 [7934890] Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):9823-7 [7937898] Nucleic Acids Res. 1994 Oct 25;22(21):4454-61 [7971276] Annu Rev Biochem. 1994;63:133-73 [7526778] Science. 1994 Dec 23;266(5193):1981-6 [7801124] Biochemistry. 1995 Aug 8;34(31):9826-33 [7632683] Nat Struct Biol. 1995 Sep;2(9):807-10 [7552753] EMBO J. 1995 Oct 2;14(19):4893-903 [7588618] J Mol Biol. 1995 Oct 20;253(2):333-46 [7563093] J Virol. 1995 Dec;69(12):7483-8 [7494254] J Virol. 1996 Jun;70(6):3571-80 [8648691] Curr Opin Struct Biol. 1996 Feb;6(1):76-83 [8696976] J Biol Chem. 1996 Aug 16;271(33):19633-6 [8702660] Proc Natl Acad Sci U S A. 1996 Nov 26;93(24):13659-64 [8942990] Biochemistry. 1997 Jan 7;36(1):173-80 [8993331] J Virol. 1997 Feb;71(2):1334-40 [8995657] Cell. 1997 Feb 21;88(4):483-92 [9038339] Genes Cells. 1997 Jan;2(1):1-12 [9112436] Cell. 1991 Dec 20;67(6):1211-21 [1760846] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The carboxyl terminus of the human calcium receptor. Requirements for cell-surface expression and signal transduction. AN - 79465055; 9395465 AB - The G-protein-coupled calcium receptor plays a key role in extracellular calcium homeostasis. To examine the role of the membrane-spanning domains and the approximately 200-residue cytoplasmic carboxyl terminus of the calcium receptor in cell-surface expression and signal transduction, we transfected HEK-293 cells with a series of truncation and carboxyl-terminal missense mutants and analyzed expression by immunoblotting, glycosidase digestion, intact cell immunoassay, and extracellular calcium-stimulated phosphoinositide hydrolysis assay. Two truncation mutants terminating at residues 706 and 802 within the second and third intracellular loops, respectively, were not properly glycosylated, failed to reach the cell-surface, and showed no calcium response, indicating that mutant receptors with the full extracellular domain but only three or five transmembrane domains are improperly folded and/or processed. Truncation mutants terminating at residues 888 and 903 within the carboxyl terminus were equivalent to the wild type in all assays, whereas mutants truncated at residues 865 and 874 showed no response to calcium, despite only approximately 25% reduction in cell-surface expression. Mutants with a full-length carboxyl terminus but with residues between positions 874 and 888 replaced with alanines showed either no (Ala875, Ala876, and Ala879) or significantly reduced (Ala881-Ala883) calcium response at levels of cell-surface expression equivalent to those of the wild-type receptor. These results indicate that deletion of the majority of the carboxyl terminus is compatible with normal processing, cell-surface expression, and signal transduction of the receptor. The truncation and alanine substitution mutants identify a small region between residues 874 and 888 critical for normal signal transduction by the receptor. JF - The Journal of biological chemistry AU - Ray, K AU - Fan, G F AU - Goldsmith, P K AU - Spiegel, A M AD - Metabolic Diseases Branch, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1997/12/12/ PY - 1997 DA - 1997 Dec 12 SP - 31355 EP - 31361 VL - 272 IS - 50 SN - 0021-9258, 0021-9258 KW - Calcium-Binding Proteins KW - 0 KW - Phosphatidylinositols KW - Hexosaminidases KW - EC 3.2.1.- KW - Amidohydrolases KW - EC 3.5.- KW - Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase KW - EC 3.5.1.52 KW - Index Medicus KW - Amidohydrolases -- metabolism KW - Phosphatidylinositols -- metabolism KW - Protein Structure, Secondary KW - Hexosaminidases -- metabolism KW - Transfection KW - Humans KW - Pituitary Gland -- chemistry KW - Glycosylation KW - Hydrolysis KW - Surface Properties KW - Mutagenesis KW - Calcium-Binding Proteins -- genetics KW - Calcium-Binding Proteins -- chemistry KW - Signal Transduction UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79465055?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=The+carboxyl+terminus+of+the+human+calcium+receptor.+Requirements+for+cell-surface+expression+and+signal+transduction.&rft.au=Ray%2C+K%3BFan%2C+G+F%3BGoldsmith%2C+P+K%3BSpiegel%2C+A+M&rft.aulast=Ray&rft.aufirst=K&rft.date=1997-12-12&rft.volume=272&rft.issue=50&rft.spage=31355&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 - 1998-01-15 N1 - Date created - 1998-01-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Furin-mediated cleavage of Pseudomonas exotoxin-derived chimeric toxins. AN - 79461054; 9395513 AB - Pseudomonas exotoxin (PE) requires proteolytic cleavage to generate a 37-kDa C-terminal fragment that translocates to the cytosol and ADP-ribosylates elongation factor 2. Cleavage within cells is mediated by furin, occurs between arginine 279 and glycine 280, and requires an arginine at both P1 and P4 residues. To study the proteolytic processing of PE-derived chimeric toxins, TGFalpha-PE38 (transforming growth factor fused to the domains II and III of PE) and a mutant form, TGFalpha-PE38gly279, were each produced in Escherichia coli. When assessed on various epidermal growth factor (EGF) receptor-positive cell lines, TGFalpha-PE38 was 100-500-fold more toxic than TGFalpha-PE38gly279. In contrast to PE, where cleavage by furin is only evident at pH 5.5, furin cleaved TGFalpha-PE38 over a broad pH range, while TGFalpha-PE38gly279 was resistant to cleavage. TGFalpha-PE38 was poorly toxic for furin-deficient LoVo cells, unless it was first pretreated in vitro with furin. Furin treatment produced a nicked protein that was 30-fold more toxic than its unnicked counterpart. Using the single chain immunotoxin HB21scFv-PE40 as a substrate, furin-mediated processing of an antibody-based immunotoxin was also evaluated. HB21scFv-PE40, which targets cells expressing the transferrin receptor, was cleaved in a similar fashion to that of TGFalpha-PE38 and nicked HB21scFv-PE40 exhibited increased toxicity for LoVo cells. In short-term experiments, the rate of reduction in protein synthesis by furin-nicked immunotoxins was increased compared with unnicked protein, indicating that cleavage by furin can be a rate-limiting step. We conclude that furin-mediated cleavage of PE-derived immunotoxins is important for their cytotoxic activity. JF - The Journal of biological chemistry AU - Chiron, M F AU - Fryling, C M AU - FitzGerald, D AD - Biotherapy Section, Laboratory of Molecular Biology, DBS, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1997/12/12/ PY - 1997 DA - 1997 Dec 12 SP - 31707 EP - 31711 VL - 272 IS - 50 SN - 0021-9258, 0021-9258 KW - Exotoxins KW - 0 KW - Recombinant Fusion Proteins KW - Transforming Growth Factor alpha KW - transforming growth factor type alpha-Pseudomonas exotoxin A KW - Subtilisins KW - EC 3.4.21.- KW - Furin KW - EC 3.4.21.75 KW - Index Medicus KW - Animals KW - Humans KW - Hydrogen-Ion Concentration KW - Mice KW - Recombinant Fusion Proteins -- toxicity KW - Recombinant Fusion Proteins -- chemistry KW - Recombinant Fusion Proteins -- metabolism KW - Tumor Cells, Cultured KW - Cell Survival -- drug effects KW - Kinetics KW - CHO Cells KW - Cricetinae KW - Transforming Growth Factor alpha -- toxicity KW - Exotoxins -- metabolism KW - Exotoxins -- toxicity KW - Exotoxins -- chemistry KW - Transforming Growth Factor alpha -- chemistry KW - Transforming Growth Factor alpha -- metabolism KW - Subtilisins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79461054?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Furin-mediated+cleavage+of+Pseudomonas+exotoxin-derived+chimeric+toxins.&rft.au=Chiron%2C+M+F%3BFryling%2C+C+M%3BFitzGerald%2C+D&rft.aulast=Chiron&rft.aufirst=M&rft.date=1997-12-12&rft.volume=272&rft.issue=50&rft.spage=31707&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 - 1998-01-15 N1 - Date created - 1998-01-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Differential regulation of the transcriptional activity of the orphan nuclear receptor NGFI-B by membrane depolarization and nerve growth factor. AN - 79459724; 9395454 AB - The immediate-early gene NGFI-B (also called nur77) encodes an orphan nuclear receptor that activates transcription through a unique response element (NBRE). NGFI-B is rapidly induced and modified via phosphorylation by a variety of stimuli that induce cells to differentiate or to proliferate. We have shown that the in vitro phosphorylation of Ser350 located within the "A-box," a motif necessary for DNA binding by NGFI-B, results in a decrease in the binding of NGFI-B to its response element (Hirata, Y., Kiuchi, K., Chen, H.-C., Milbrandt, J., and Guroff, G. (1993) J. Biol. Chem. 268, 24808-24812). We show here that nerve growth factor (NGF)-induced changes in the in vivo phosphorylation of Ser350 accompany transcriptional deactivation of NGFI-B in PC12 cells, that membrane depolarization and NGF treatment cause differential phosphorylation of NGFI-B, and that the transcriptional activation caused by exogenous expression of NGFI-B or membrane depolarization can be inhibited by NGF treatment. In addition, the mutation of Ser350 to Ala abolished the inhibitory effect of NGF on the transcriptional activation of NGFI-B in PC12 cells. These data could provide new insights into the regulation of transcriptional activity required for some neurons to switch from activity-dependent survival to neurotrophin-dependent survival during development. JF - The Journal of biological chemistry AU - Katagiri, Y AU - Hirata, Y AU - Milbrandt, J AU - Guroff, G AD - Section on Growth Factors, NICHD, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1997/12/12/ PY - 1997 DA - 1997 Dec 12 SP - 31278 EP - 31284 VL - 272 IS - 50 SN - 0021-9258, 0021-9258 KW - DNA-Binding Proteins KW - 0 KW - Nerve Growth Factors KW - Nr4a1 protein, rat KW - Nuclear Receptor Subfamily 4, Group A, Member 1 KW - Receptors, Cytoplasmic and Nuclear KW - Receptors, Steroid KW - Recombinant Proteins KW - Transcription Factors KW - Serine KW - 452VLY9402 KW - Epidermal Growth Factor KW - 62229-50-9 KW - Potassium Chloride KW - 660YQ98I10 KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Rats KW - Mutagenesis, Site-Directed KW - Animals KW - Phosphorylation KW - Recombinant Proteins -- metabolism KW - Potassium Chloride -- metabolism KW - DNA -- metabolism KW - Epidermal Growth Factor -- pharmacology KW - Serine -- metabolism KW - PC12 Cells KW - Binding Sites KW - Nerve Growth Factors -- metabolism KW - Transcription Factors -- metabolism KW - Receptors, Cytoplasmic and Nuclear -- metabolism KW - Receptors, Steroid -- metabolism KW - DNA-Binding Proteins -- genetics KW - Receptors, Cytoplasmic and Nuclear -- genetics KW - Receptors, Steroid -- genetics KW - Transcription Factors -- genetics KW - Transcriptional Activation KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79459724?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Differential+regulation+of+the+transcriptional+activity+of+the+orphan+nuclear+receptor+NGFI-B+by+membrane+depolarization+and+nerve+growth+factor.&rft.au=Katagiri%2C+Y%3BHirata%2C+Y%3BMilbrandt%2C+J%3BGuroff%2C+G&rft.aulast=Katagiri&rft.aufirst=Y&rft.date=1997-12-12&rft.volume=272&rft.issue=50&rft.spage=31278&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 - 1998-01-15 N1 - Date created - 1998-01-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetic toxicities of human teratogens AN - 16247638; 4231028 AB - Birth defects cause a myriad of societal problems and place tremendous anguish on the affected individual and his or her family. Current estimates categorize about 3% of all newborn infants as having some form of birth defect or congenital anomaly. As more precise means of detecting subtle anomalies become available this estimate, no doubt, will increase. Even though birth defects have been observed in newborns throughout history, our knowledge about the causes and mechanisms through which these defects are manifested is limited. For example, it has been estimated that around 20% of all birth defects are due to gene mutations, 5-10% to chromosomal abnormalities, and another 5-l0% to exposure to a known teratogenic agent or maternal factor [D.A. Beckman, R.L. Brent, Mechanisms of teratogenesis, Ann. Rev. Pharmacol. Toxicol. 24 (1984) 483-500; K. Nelson, L.B. Holmes, Malformations due to presumed spontaneous mutations in newborn infants, N. Engl. J. Med. 320 (1989) 19-23.]. Together, these percentages account for only 30-40%, leaving the etiology of more than half of all human birth defects unexplained. It has been speculated that environmental factors account for no more than one-tenth of all congenital anomalies [D.A. Beckman, R.L. Brent, Mechanisms of teratogenesis, Ann. Rev. Pharmacol. Toxicol. 24 (1984) 483-500]. Furthermore, since ``there is no evidence in humans that the exposure of an individual to any mutagen measurably increases the risk of congenital anomalies in his or her offspring'' [J.F. Crow, C. Denniston, Mutation in human populations, Adv. Human Genet. 14 (1985) 59-121; J.M. Friedman, J.E. Polifka, Teratogenic Effects of Drugs: A Resource for Clinicians (TERIS), The John Hopkins University Press, Baltimore, 1994], the mutagenic activity of environmental agents and drugs as a factor in teratogenesis has been given very little attention. Epigenetic activity has also been given only limited consideration as a mechanism for teratogenesis. As new molecular methods are developed for assessing processes associated with teratogenesis, especially those with a genetic or an epigenetic basis, additional environmental factors may be identified. These are especially important because they are potentially preventable. This paper examines the relationships between chemicals identified as human teratogens (agents that cause birth defects) and their mutagenic activity as evaluated in one or more of the established short-term bioassays currently used to measure such damage. Those agents lacking mutagenic activity but with published evidence that they may otherwise alter the expressions or regulate interactions of the genetic material, i.e. exhibit epigenetic activity, have likewise been identified. The information used in making these comparisons comes from the published literature as well as from unpublished data of the U.S. National Toxicology Program (NTP). JF - Mutation Research AU - Bishop, J B AU - Witt, K L AU - Sloane, R A AD - Reproductive Toxicology Group, Laboratory of Toxicology, National Institute of Environmental Health Sciences, PO Box 12233 A2-10, Research Triangle Park, NC 27709, USA Y1 - 1997/12/12/ PY - 1997 DA - 1997 Dec 12 SP - 9 EP - 43 PB - Elsevier Science B.V. VL - 396 IS - 1-2 SN - 0027-5107, 0027-5107 KW - epigenetic activity KW - man KW - teratogens KW - Genetics Abstracts; Toxicology Abstracts KW - G 07220:General theory/testing systems KW - X 24250:Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16247638?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+Research&rft.atitle=Genetic+toxicities+of+human+teratogens&rft.au=Bishop%2C+J+B%3BWitt%2C+K+L%3BSloane%2C+R+A&rft.aulast=Bishop&rft.aufirst=J&rft.date=1997-12-12&rft.volume=396&rft.issue=1-2&rft.spage=9&rft.isbn=&rft.btitle=&rft.title=Mutation+Research&rft.issn=00275107&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Distinct tyrosine phosphorylation sites in JAK3 kinase domain positively and negatively regulate its enzymatic activity. AN - 79454880; 9391116 AB - Cytokines are critically important for the growth and development of a variety of cells. Janus kinases (JAKs) associate with cytokine receptors and are essential for transmitting downstream cytokine signals. However, the regulation of the enzymatic activity of the JAKs is not well understood. Here, we investigated the role of tyrosine phosphorylation of JAK3 in regulating its kinase activity by analyzing mutations of tyrosine residues within the putative activation loop of the kinase domain. Specifically, tyrosine residues 980 and 981 of JAK3 were mutated to phenylalanine individually or doubly. We found that JAK3 is autophosphorylated on multiple sites including Y980 and Y981. Compared with the activity of wild-type (WT) JAK3, mutant Y980F demonstrated markedly decreased kinase activity, and optimal phosphorylation of JAK3 on other sites was dependent on Y980 phosphorylation. The mutant Y980F also exhibited reduced phosphorylation of its substrates, gammac and STAT5A. In contrast, mutant Y981F had greatly increased kinase activity, whereas the double mutant, YY980/981FF, had intermediate activity. These results indicate that Y980 positively regulates JAK3 kinase activity whereas Y981 negatively regulates JAK3 kinase activity. These observations in JAK3 are similar to the findings in the kinase that is closely related to the JAK family, ZAP-70; mutations of tyrosine residues within the putative activation loop of ZAP-70 also have opposing actions. Thus, it will be important to determine whether this feature of regulation is unique to JAK3 or if it is also a feature of other JAKs. Given the importance of JAKs and particularly JAK3, it will be critical to fully dissect the positive and negative regulatory function of these and other tyrosine residues in the control of kinase activity and hence cytokine signaling. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Zhou, Y J AU - Hanson, E P AU - Chen, Y Q AU - Magnuson, K AU - Chen, M AU - Swann, P G AU - Wange, R L AU - Changelian, P S AU - O'Shea, J J AD - Lymphocyte Cell Biology Section, National Institutes of Health, Bethesda, MD 20892, USA. ZHOUY@arb.niams.nih.gov Y1 - 1997/12/09/ PY - 1997 DA - 1997 Dec 09 SP - 13850 EP - 13855 VL - 94 IS - 25 SN - 0027-8424, 0027-8424 KW - DNA, Complementary KW - 0 KW - DNA-Binding Proteins KW - Milk Proteins KW - STAT5 Transcription Factor KW - Trans-Activators KW - Tyrosine KW - 42HK56048U KW - Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - Janus Kinase 3 KW - EC 2.7.10.2 KW - Index Medicus KW - Trans-Activators -- metabolism KW - Animals KW - DNA, Complementary -- genetics KW - COS Cells KW - Enzyme Activation KW - Tyrosine -- chemistry KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Phosphorylation KW - Point Mutation KW - Tyrosine -- genetics KW - Binding Sites -- genetics KW - DNA-Binding Proteins -- metabolism KW - Protein-Tyrosine Kinases -- genetics KW - Protein-Tyrosine Kinases -- metabolism KW - Protein-Tyrosine Kinases -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79454880?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Distinct+tyrosine+phosphorylation+sites+in+JAK3+kinase+domain+positively+and+negatively+regulate+its+enzymatic+activity.&rft.au=Zhou%2C+Y+J%3BHanson%2C+E+P%3BChen%2C+Y+Q%3BMagnuson%2C+K%3BChen%2C+M%3BSwann%2C+P+G%3BWange%2C+R+L%3BChangelian%2C+P+S%3BO%27Shea%2C+J+J&rft.aulast=Zhou&rft.aufirst=Y&rft.date=1997-12-09&rft.volume=94&rft.issue=25&rft.spage=13850&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 - 1998-01-15 N1 - Date created - 1998-01-15 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Methods Enzymol. 1991;200:3-37 [1835513] Immunol Today. 1990 Oct;11(10):350-4 [2171545] Cytokine. 1993 Mar;5(2):95-106 [8392875] Nature. 1993 Nov 11;366(6451):129-35 [8232552] Nature. 1993 Nov 11;366(6451):166-70 [7901766] Cell. 1994 Jan 28;76(2):253-62 [8293462] Nature. 1994 May 26;369(6478):330-3 [8183373] Nature. 1994 Jul 14;370(6485):151-3 [8022485] Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6374-8 [8022790] Curr Opin Cell Biol. 1994 Apr;6(2):239-46 [7517688] Oncogene. 1994 Aug;9(8):2415-23 [7518579] J Biol Chem. 1994 Nov 25;269(47):29520-9 [7961936] Science. 1994 Nov 11;266(5187):1039-42 [7973657] Science. 1994 Nov 11;266(5187):1042-5 [7973658] Science. 1994 Nov 11;266(5187):1045-7 [7973659] Nature. 1994 Dec 22-29;372(6508):746-54 [7997262] Semin Cancer Biol. 1994 Aug;5(4):239-46 [7528561] J Exp Med. 1995 Apr 1;181(4):1425-31 [7535338] Immunity. 1995 Apr;2(4):321-9 [7719937] Bioessays. 1995 Apr;17(4):321-30 [7537961] Blood. 1995 Jun 15;85(12):3444-51 [7780132] EMBO J. 1995 Jun 1;14(11):2499-508 [7781602] J Biol Chem. 1995 Aug 11;270(32):18730-3 [7642520] Nature. 1995 Sep 7;377(6544):65-8 [7659163] Proc Natl Acad Sci U S A. 1995 Sep 12;92(19):8705-9 [7568001] Proc Natl Acad Sci U S A. 1995 Sep 12;92(19):8831-5 [7568026] Nature. 1995 Oct 19;377(6550):591-4 [7566171] Annu Rev Biochem. 1995;64:621-51 [7574495] Science. 1995 Nov 3;270(5237):794-7 [7481767] Science. 1995 Nov 3;270(5237):797-800 [7481768] Science. 1995 Nov 3;270(5237):800-2 [7481769] Immunity. 1995 Dec;3(6):771-82 [8777722] EMBO J. 1996 Feb 15;15(4):799-809 [8631301] Blood. 1996 Apr 15;87(8):3151-60 [8605329] Immunity. 1996 Feb;4(2):123-32 [8624803] J Biol Chem. 1996 May 3;271(18):10738-44 [8631883] Eur J Immunol. 1996 Jun;26(6):1322-7 [8647212] Proc Natl Acad Sci U S A. 1996 Mar 5;93(5):2077-82 [8700888] Mol Cell Biol. 1996 Sep;16(9):5026-35 [8756661] J Biol Chem. 1996 Aug 23;271(34):20494-500 [8702790] J Biol Chem. 1996 Aug 30;271(35):21381-90 [8702919] J Leukoc Biol. 1996 Oct;60(4):441-52 [8864127] EMBO J. 1996 Nov 15;15(22):6251-61 [8947048] Immunity. 1996 Dec;5(6):605-15 [8986719] Nature. 1997 Feb 13;385(6617):595-602 [9024657] Mol Cell Biol. 1997 May;17(5):2497-501 [9111318] J Biol Chem. 1992 Aug 15;267(23):16660-8 [1322912] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Studies on the enzymatic and transcriptional activity of the dimerization cofactor for hepatocyte nuclear factor 1. AN - 79449967; 9391049 AB - The relationship between the enzymatic and the transcriptional activity of the bifunctional protein pterin-4a-carbinolamine dehydratase/dimerization cofactor for hepatocyte nuclear factor 1 (DCoH) has been elucidated by site-directed mutagenesis. DCoH dimers harbor a binding site for hepatocyte nuclear factor 1 (HNF1), two active centers that bind pterins, and a saddle-shaped surface that resembles nucleic acid binding domains. Two domains of the protein have been selectively targeted to determine if a change in one activity affects the other. No strong correlation has been found, supporting the idea that carbinolamine dehydratase activity is not required for HNF1 binding in vitro or transcriptional coactivation in vivo. Double mutations in the active center, however, influence the in vivo transcriptional activity but not HNF1 binding. This finding suggests that some active center residues also are used during transcription, possibly for binding of another (macro)molecule. Several mutations in the saddle led to a surprising increase in transcription, therefore linking this domain to transcriptional regulation as well. The transcriptional function of DCoH therefore is composed of two parts, HNF1 binding and another contributing effect that involves the active site and, indirectly, the saddle. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Johnen, G AU - Kaufman, S AD - Laboratory of Neurochemistry, National Institute of Mental Health, Bethesda, MD 20892, USA. johnen@codon.nih.gov Y1 - 1997/12/09/ PY - 1997 DA - 1997 Dec 09 SP - 13469 EP - 13474 VL - 94 IS - 25 SN - 0027-8424, 0027-8424 KW - DNA-Binding Proteins KW - 0 KW - Nuclear Proteins KW - Recombinant Proteins KW - Transcription Factors KW - Hepatocyte Nuclear Factor 1 KW - 126548-29-6 KW - Hepatocyte Nuclear Factor 1-beta KW - 138674-15-4 KW - Hydro-Lyases KW - EC 4.2.1.- KW - pterin-4a-carbinolamine dehydratase KW - EC 4.2.1.96 KW - Index Medicus KW - Animals KW - Models, Molecular KW - Dimerization KW - Recombinant Proteins -- genetics KW - Mutagenesis, Site-Directed KW - Recombinant Proteins -- metabolism KW - Kinetics KW - CHO Cells KW - Binding Sites -- genetics KW - Recombinant Proteins -- chemistry KW - Cricetinae KW - Protein Conformation KW - Transcription Factors -- metabolism KW - Hydro-Lyases -- genetics KW - Transcription Factors -- chemistry KW - Hydro-Lyases -- chemistry KW - Transcription Factors -- genetics KW - Hydro-Lyases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79449967?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Studies+on+the+enzymatic+and+transcriptional+activity+of+the+dimerization+cofactor+for+hepatocyte+nuclear+factor+1.&rft.au=Johnen%2C+G%3BKaufman%2C+S&rft.aulast=Johnen&rft.aufirst=G&rft.date=1997-12-09&rft.volume=94&rft.issue=25&rft.spage=13469&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 - 1998-01-15 N1 - Date created - 1998-01-15 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1991 Jan 15;88(2):385-9 [1988938] J Biol Chem. 1970 Sep 25;245(18):4751-9 [5456148] FEBS Lett. 1992 May 4;302(1):73-6 [1350256] Eur J Biochem. 1992 Aug 15;208(1):139-44 [1355046] Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10109-13 [1359535] Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):11891-4 [1465414] Mol Cell Biol. 1993 Jan;13(1):421-31 [8417340] PCR Methods Appl. 1992 Nov;2(2):124-30 [1477668] J Biol Chem. 1993 Mar 5;268(7):4828-31 [8444860] Curr Opin Genet Dev. 1993 Apr;3(2):246-53 [8504250] Am J Hum Genet. 1993 Sep;53(3):768-74 [8352282] Proc Natl Acad Sci U S A. 1994 Feb 15;91(4):1366-70 [8108417] Science. 1994 Mar 11;263(5152):1444-6 [8128228] Science. 1994 Jul 29;265(5172):615-21 [8036511] Nature. 1994 Dec 1;372(6505):432-8 [7984237] Science. 1995 Apr 28;268(5210):556-9 [7725101] Biochemistry. 1995 May 2;34(17):5801-10 [7727440] Development. 1995 Apr;121(4):1217-26 [7743933] EMBO J. 1995 May 1;14(9):2034-42 [7744010] Proc Natl Acad Sci U S A. 1995 May 23;92(11):4743-7 [7761394] Eur J Biochem. 1995 Jul 15;231(2):414-23 [7635153] Proc Natl Acad Sci U S A. 1995 Dec 19;92(26):12384-8 [8618906] Structure. 1995 Jun 15;3(6):531-4 [8590013] J Biol Chem. 1973 Jun 25;248(12):4235-41 [4711606] Nature. 1987 Apr 23-29;326(6115):811-2 [2952886] Anal Biochem. 1988 Nov 15;175(1):91-5 [3245580] Nature. 1990 Dec 6;348(6301):515-20 [2147232] Proc Natl Acad Sci U S A. 1990 Dec;87(24):9838-42 [2263635] Cell. 1996 Feb 23;84(4):575-85 [8598044] FASEB J. 1996 Feb;10(2):267-82 [8641560] Mol Cell Biol. 1996 Jun;16(6):3125-37 [8649424] Science. 1996 May 31;272(5266):1331-3 [8650542] FEBS Lett. 1996 Jun 24;389(1):35-9 [8682201] Protein Sci. 1996 Oct;5(10):1963-72 [8897596] Eur J Biochem. 1996 Nov 1;241(3):858-64 [8944775] Nature. 1996 Dec 5;384(6608):455-8 [8945470] J Mol Biol. 1997 Jan 10;265(1):20-9 [8995521] Nucleic Acids Res. 1997 Apr 15;25(8):1476-84 [9092652] Science. 1991 Dec 20;254(5039):1762-7 [1763325] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Topology of allosteric regulation of lactose permease. AN - 79449926; 9391057 AB - Sugar transport by some permeases in Escherichia coli is allosterically regulated by the phosphorylation state of the intracellular regulatory protein, enzyme IIAglc of the phosphoenolpyruvate:sugar phosphotransferase system. A sensitive radiochemical assay for the interaction of enzyme IIAglc with membrane-associated lactose permease was used to characterize the binding reaction. The binding is stimulated by transportable substrates such as lactose, melibiose, and raffinose, but not by sugars that are not transported (maltose and sucrose). Treatment of lactose permease with N-ethylmaleimide, which blocks ligand binding and transport by alkylating Cys-148, also blocks enzyme IIAglc binding. Preincubation with the substrate analog beta-D-galactopyranosyl 1-thio-beta-D-galactopyranoside protects both lactose transport and enzyme IIAglc binding against inhibition by N-ethylmaleimide. A collection of lactose permease replacement mutants at Cys-148 showed, with the exception of C148V, a good correlation of relative transport activity and enzyme IIAglc binding. The nature of the interaction of enzyme IIAglc with the cytoplasmic face of lactose permease was explored. The N- and C-termini, as well as five hydrophilic loops in the permease, are exposed on the cytoplasmic surface of the membrane and it has been proposed that the central cytoplasmic loop of lactose permease is the major determinant for interaction with enzyme IIAglc. Lactose permease mutants with polyhistidine insertions in cytoplasmic loops IV/V and VI/VII and periplasmic loop VII/VIII retain transport activity and therefore substrate binding, but do not bind enzyme IIAglc, indicating that these regions of lactose permease may be involved in recognition of enzyme IIAglc. Taken together, these results suggest that interaction of lactose permease with substrate promotes a conformational change that brings several cytoplasmic loops into an arrangement optimal for interaction with the regulatory protein, enzyme IIAglc. A topological map of the proposed interaction is presented. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Seok, Y J AU - Sun, J AU - Kaback, H R AU - Peterkofsky, A AD - Laboratory of Biochemical Genetics, National Heart, Lung and Blood Institute, Bethesda, MD 20892-4036, USA. Y1 - 1997/12/09/ PY - 1997 DA - 1997 Dec 09 SP - 13515 EP - 13519 VL - 94 IS - 25 SN - 0027-8424, 0027-8424 KW - Carbohydrates KW - 0 KW - Escherichia coli Proteins KW - LacY protein, E coli KW - Membrane Transport Proteins KW - Monosaccharide Transport Proteins KW - Symporters KW - crr protein, E coli KW - lactose permease KW - 9068-45-5 KW - Phosphoenolpyruvate Sugar Phosphotransferase System KW - EC 2.7.1.- KW - Ethylmaleimide KW - O3C74ACM9V KW - Index Medicus KW - Models, Molecular KW - Phosphoenolpyruvate Sugar Phosphotransferase System -- metabolism KW - Escherichia coli -- genetics KW - Amino Acid Sequence KW - Escherichia coli -- enzymology KW - Mutagenesis, Site-Directed KW - Molecular Sequence Data KW - Allosteric Regulation KW - Substrate Specificity KW - Allosteric Site KW - Ethylmaleimide -- pharmacology KW - Mutagenesis, Insertional KW - Protein Conformation KW - Membrane Transport Proteins -- chemistry KW - Membrane Transport Proteins -- metabolism KW - Membrane Transport Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79449926?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Topology+of+allosteric+regulation+of+lactose+permease.&rft.au=Seok%2C+Y+J%3BSun%2C+J%3BKaback%2C+H+R%3BPeterkofsky%2C+A&rft.aulast=Seok&rft.aufirst=Y&rft.date=1997-12-09&rft.volume=94&rft.issue=25&rft.spage=13515&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 - 1998-01-15 N1 - Date created - 1998-01-15 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1965 Sep;54(3):891-9 [5324399] Curr Opin Struct Biol. 1997 Aug;7(4):537-42 [9266176] Eur J Biochem. 1980;108(1):223-31 [6250828] Proc Natl Acad Sci U S A. 1982 Mar;79(5):1457-61 [7041121] J Biol Chem. 1983 Jan 10;258(1):31-4 [6336750] J Membr Biol. 1983;76(2):95-112 [6358502] EMBO J. 1985 Dec 16;4(13A):3633-8 [3912175] Proc Natl Acad Sci U S A. 1987 Aug;84(16):5535-9 [3303027] Biochim Biophys Acta. 1990 Nov 2;1029(1):113-6 [2171650] Protein Expr Purif. 1991 Apr-Jun;2(2-3):179-87 [1821787] Int Rev Cytol. 1992;137:97-125 [1330966] J Biol Chem. 1992 Dec 5;267(34):24819-23 [1447219] Res Microbiol. 1992 Mar-Apr;143(3):251-61 [1333089] Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):11954-8 [1465425] Biochemistry. 1993 Jan 12;32(1):32-7 [8418852] Science. 1993 Jan 29;259(5095):673-7 [8430315] Prog Nucleic Acid Res Mol Biol. 1993;44:31-65 [8434125] Microbiol Rev. 1993 Sep;57(3):543-94 [8246840] J Bacteriol. 1994 Jan;176(2):543-6 [8288553] Biochemistry. 1994 Oct 11;33(40):12160-5 [7918437] Biochemistry. 1994 Oct 11;33(40):12166-71 [7918438] J Exp Biol. 1994 Nov;196:183-95 [7823021] Biochemistry. 1995 Jul 18;34(28):8950-9 [7619794] Biochemistry. 1996 Jan 23;35(3):990-8 [8547282] J Bacteriol. 1996 Oct;178(20):6082-6 [8830713] Biochemistry. 1997 May 27;36(21):6408-14 [9174357] J Biol Chem. 1968 Jul 10;243(13):3711-24 [4872728] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - How Escherichia coli can bias the results of molecular cloning: Preferential selection of defective genomes of hepatitis C virus during the cloning procedure AN - 16262969; 4250315 AB - Cloned PCR products containing hepatitis C virus (HCV) genomic fragments have been used for analyses of HCV genomic heterogeneity and protein expression. These studies assume that the clones derived are representative of the entire virus population and that subsets are not inadvertently selected. The aim of the present study was to express HCV structural proteins. However, we found that there was a strong cloning selection for defective genomes and that most clones generated initially were incapable of expressing the HCV proteins. The HCV structural region (C-E1-E2-p7) was directly amplified by long reverse transcription-PCR from the plasma of an HCV-infected patient or from a control plasmid containing a viable full-length cDNA of HCV derived from the same patient but cloned in a different vector. The PCR products were cloned into a mammalian expression vector, amplified in Escherichia coli, and tested for their ability to produce HCV structural proteins. Twenty randomly picked clones derived from the HCV-infected patient all contained nucleotide mutations leading to absence or truncation of the expected HCV products. Of 25 clones derived from the control plasmid, only 8% were fully functional for polyprotein synthesis. The insertion of extra nucleotides in the region just upstream of the start codon of the HCV insert led to a statistically significant increase in the number of fully functional clones derived from the patient (42%) and from the control plasmid (72-92%). Nonrandom selection of clones during the cloning procedure has enormous implications for the study of viral heterogeneity, because it can produce a false spectrum of genomic diversity. It can also be an impediment to the construction of infectious viral clones. JF - Proceedings of the National Academy of Sciences, USA AU - Forns, X AU - Bukh, J AU - Purcell, R H AU - Emerson, SU AD - Hepatitis Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-0740, USA, semerson@atlas.niaid.nih.gov Y1 - 1997/12/09/ PY - 1997 DA - 1997 Dec 09 SP - 13909 EP - 13914 VL - 94 IS - 25 SN - 0027-8424, 0027-8424 KW - cloning KW - gene expression KW - Virology & AIDS Abstracts; Genetics Abstracts; Microbiology Abstracts B: Bacteriology KW - V 22050:Viral genetics including virus reactivation KW - G 07313:Viruses KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16262969?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.atitle=How+Escherichia+coli+can+bias+the+results+of+molecular+cloning%3A+Preferential+selection+of+defective+genomes+of+hepatitis+C+virus+during+the+cloning+procedure&rft.au=Forns%2C+X%3BBukh%2C+J%3BPurcell%2C+R+H%3BEmerson%2C+SU&rft.aulast=Forns&rft.aufirst=X&rft.date=1997-12-09&rft.volume=94&rft.issue=25&rft.spage=13909&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Ascorbate recycling in human neutrophils: Induction by bacteria AN - 16260641; 4250300 AB - Ascorbate (vitamin C) recycling occurs when extracellular ascorbate is oxidized, transported as dehydroascorbic acid, and reduced intracellularly to ascorbate. We investigated microorganism induction of ascorbate recycling in human neutrophils and in microorganisms themselves. Ascorbate recycling was determined by measuring intracellular ascorbate accumulation. Ascorbate recycling in neutrophils was induced by both Gram-positive and Gram-negative pathogenic bacteria, and the fungal pathogen Candida albicans. Induction of recycling resulted in as high as a 30-fold increase in intracellular ascorbate compared with neutrophils not exposed to microorganisms. Recycling occurred at physiologic concentrations of extracellular ascorbate within 20 min, occurred over a 100-fold range of effector/target ratios, and depended on oxidation of extracellular ascorbate to dehydroascorbic acid. Ascorbate recycling did not occur in bacteria nor in C. albicans. Ascorbate did not enter microorganisms, and dehydroascorbic acid entry was less than could be accounted for by diffusion. Because microorganism lysates reduced dehydroascorbic acid to ascorbate, ascorbate recycling was absent because of negligible entry of the substrate dehydroascorbic acid. Because ascorbate recycling occurs in human neutrophils but not in microorganisms, it may represent a eukaryotic defense mechanism against oxidants with possible clinical implications. JF - Proceedings of the National Academy of Sciences, USA AU - Wang, Yaohui AU - Russo, T A AU - Kwon, Oran AU - Chanock, S AU - Rumsey, S C AU - Levine, M AD - Molecular and Clinical Nutrition Section, Building 10, Room 4D52 MSC 1372, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-1372, USA Y1 - 1997/12/09/ PY - 1997 DA - 1997 Dec 09 SP - 13816 EP - 13819 VL - 94 IS - 25 SN - 0027-8424, 0027-8424 KW - ascorbic acid KW - bacteria KW - dehydroascorbic acid KW - man KW - Microbiology Abstracts B: Bacteriology; Immunology Abstracts KW - F 06772:Other cells (leukocytes, eosinophils, basophils, neutrophils, platelets) KW - F 06801:Bacteria KW - J 02833:Immune response and immune mechanisms UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16260641?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.atitle=Ascorbate+recycling+in+human+neutrophils%3A+Induction+by+bacteria&rft.au=Wang%2C+Yaohui%3BRusso%2C+T+A%3BKwon%2C+Oran%3BChanock%2C+S%3BRumsey%2C+S+C%3BLevine%2C+M&rft.aulast=Wang&rft.aufirst=Yaohui&rft.date=1997-12-09&rft.volume=94&rft.issue=25&rft.spage=13816&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - 17-beta-estradiol fails to induce micronuclei in the bone marrow cells of rodents. AN - 79549044; 9465917 JF - Mutation research AU - Shelby, M D AU - Tice, R R AU - Witt, K L AD - National Institutes of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. shelby@niehs.nih.gov Y1 - 1997/12/05/ PY - 1997 DA - 1997 Dec 05 SP - 89 EP - 90 VL - 395 IS - 1 SN - 0027-5107, 0027-5107 KW - Estradiol KW - 4TI98Z838E KW - Index Medicus KW - Rats KW - Injections, Intraperitoneal KW - Mice, Inbred Strains KW - Animals KW - Rats, Inbred F344 KW - Reproducibility of Results KW - Dose-Response Relationship, Drug KW - Mice KW - Male KW - Female KW - Micronucleus Tests KW - Estradiol -- administration & dosage KW - Estradiol -- toxicity KW - Bone Marrow -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79549044?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=17-beta-estradiol+fails+to+induce+micronuclei+in+the+bone+marrow+cells+of+rodents.&rft.au=Shelby%2C+M+D%3BTice%2C+R+R%3BWitt%2C+K+L&rft.aulast=Shelby&rft.aufirst=M&rft.date=1997-12-05&rft.volume=395&rft.issue=1&rft.spage=89&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 - 1998-03-06 N1 - Date created - 1998-03-06 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment On: Mutat Res. 1995 Nov;345(1-2):87-95 [8524359] Mutat Res. 1997 Dec 5;395(1):83-8 [9465916] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transcriptional regulation of the human monocyte chemoattractant protein-1 gene. Cooperation of two NF-kappaB sites and NF-kappaB/Rel subunit specificity. AN - 79442905; 9388261 AB - Human monocyte chemoattractant protein-1 (human MCP-1) mRNA accumulated in THP-1 cells 2 h after lipopolysaccharide (LPS) stimulation. DNase I footprinting revealed that LPS stimulation induced protein binding to the two closely located NF-kappaB sites, A1 and A2. By electrophoretic gel mobility shift assay and supershift assay, the binding of (p65)2, c-Rel/p65, p50/p65, and p50/c-Rel to the A2 oligonucleotide probe was detected after LPS stimulation. In contrast, 12-o-tetradecanoylphorbol 13-acetate did not induce a significant amount of MCP-1 mRNA in THP-1 cells 2 h after stimulation, and only p50/p65 bound to the A2 probe. trans-Activity of each NF-kappaB/Rel dimer was investigated by transfecting P19 cells with p65, p50, and/or c-Rel expression vectors, and a luciferase construct containing the enhancer region of the human MCP-1 gene. Expression of recombinant p65 or p65 and c-Rel resulted in elevated luciferase activities, indicating that (p65)2 and c-Rel/p65 had trans-activity. The binding of (p65)2 and/or c-Rel/p65 to the A2 probe was also detected from 12-o-tetradecanoylphorbol 13-acetate-stimulated HeLa, HOS, and A172 cells in which expression of MCP-1 mRNA was elevated. Finally, the role of the A1 site was investigated. Both (p65)2 and c-Rel/p65 bound to the A1 probe by electrophoretic mobility shift assay and a mutation in the A1 or A2 site resulted in a loss of the enhancer activity. These results suggest that the binding of (p65)2 and c-Rel/p65 to the A1 and A2 sites of this gene is important for the tissue- and stimulus-specific transcription of the human MCP-1 gene. JF - The Journal of biological chemistry AU - Ueda, A AU - Ishigatsubo, Y AU - Okubo, T AU - Yoshimura, T AD - Immunopathology Section, Laboratory of Immunobiology, National Cancer Institute-Frederick, Cancer Research and Development Center, Frederick, Maryland 21702, USA. Y1 - 1997/12/05/ PY - 1997 DA - 1997 Dec 05 SP - 31092 EP - 31099 VL - 272 IS - 49 SN - 0021-9258, 0021-9258 KW - Chemokine CCL2 KW - 0 KW - Lipopolysaccharides KW - NF-kappa B KW - NF-kappa B p50 Subunit KW - RNA, Messenger KW - Transcription Factor RelA KW - DNA KW - 9007-49-2 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Sequence Homology, Nucleic Acid KW - HeLa Cells KW - DNA -- metabolism KW - Dimerization KW - Humans KW - Lipopolysaccharides -- pharmacology KW - Protein Binding KW - Binding Sites KW - Base Sequence KW - RNA, Messenger -- metabolism KW - DNA Footprinting KW - Molecular Sequence Data KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Cell Line KW - Protein Conformation KW - Chemokine CCL2 -- genetics KW - Transcription, Genetic KW - Gene Expression Regulation KW - NF-kappa B -- physiology KW - NF-kappa B -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79442905?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Transcriptional+regulation+of+the+human+monocyte+chemoattractant+protein-1+gene.+Cooperation+of+two+NF-kappaB+sites+and+NF-kappaB%2FRel+subunit+specificity.&rft.au=Ueda%2C+A%3BIshigatsubo%2C+Y%3BOkubo%2C+T%3BYoshimura%2C+T&rft.aulast=Ueda&rft.aufirst=A&rft.date=1997-12-05&rft.volume=272&rft.issue=49&rft.spage=31092&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 - 1998-01-08 N1 - Date created - 1998-01-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Second primary cancers related to smoking and treatment of small-cell lung cancer. Lung Cancer Working Cadre. AN - 79448393; 9392619 AB - An increased risk of second primary cancers has been reported in patients who survive small-cell carcinoma of the lung. The treatment's contribution to the development of second cancers is difficult to assess, in part because the number of long-term survivors seen at any one institution is small. We designed a multi-institution study to investigate the risk among survivors of developing second primary cancers other than small-cell lung carcinoma. Demographic, smoking, and treatment information were obtained from the medical records of 611 patients who had been cancer free for more than 2 years after therapy for histologically proven small-cell lung cancer, and person-years of follow-up were cumulated. Population-based rates of cancer incidence and mortality were used to estimate the expected number of cancers or deaths. The actuarial risk of second cancers was estimated by the Kaplan-Meier method. Relative to the general population, the risk of all second cancers among these patients (mostly non-small-cell cancers of the lung) was increased 3.5-fold. Second lung cancer risk was increased 13-fold among those who received chest irradiation in comparison to a sevenfold increase among nonirradiated patients. It was higher in those who continued smoking, with evidence of an interaction between chest irradiation and continued smoking (relative risk = 21). Patients treated with various forms of combination chemotherapy had comparable increases in risk (9.4- to 13-fold, overall), except for a 19-fold risk increase among those treated with alkylating agents who continued smoking. Because of their substantially increased risk, survivors should stop smoking and may consider entering trials of secondary chemoprevention. JF - Journal of the National Cancer Institute AU - Tucker, M A AU - Murray, N AU - Shaw, E G AU - Ettinger, D S AU - Mabry, M AU - Huber, M H AU - Feld, R AU - Shepherd, F A AU - Johnson, D H AU - Grant, S C AU - Aisner, J AU - Johnson, B E AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA. tuckerp@epndce.nci.nih.gov Y1 - 1997/12/03/ PY - 1997 DA - 1997 Dec 03 SP - 1782 EP - 1788 VL - 89 IS - 23 SN - 0027-8874, 0027-8874 KW - Antineoplastic Agents KW - 0 KW - Index Medicus KW - Risk KW - Humans KW - Actuarial Analysis KW - Male KW - Female KW - Radiotherapy -- adverse effects KW - Lung Neoplasms -- radiotherapy KW - Neoplasms, Second Primary -- etiology KW - Lung Neoplasms -- drug therapy KW - Carcinoma, Small Cell -- radiotherapy KW - Smoking -- adverse effects KW - Carcinoma, Small Cell -- drug therapy KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79448393?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Second+primary+cancers+related+to+smoking+and+treatment+of+small-cell+lung+cancer.+Lung+Cancer+Working+Cadre.&rft.au=Tucker%2C+M+A%3BMurray%2C+N%3BShaw%2C+E+G%3BEttinger%2C+D+S%3BMabry%2C+M%3BHuber%2C+M+H%3BFeld%2C+R%3BShepherd%2C+F+A%3BJohnson%2C+D+H%3BGrant%2C+S+C%3BAisner%2C+J%3BJohnson%2C+B+E&rft.aulast=Tucker&rft.aufirst=M&rft.date=1997-12-03&rft.volume=89&rft.issue=23&rft.spage=1782&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 - 1997-12-18 N1 - Date created - 1997-12-18 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Natl Cancer Inst. 1997 Dec 3;89(23):1745-7 [9392609] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Differential alterations in metabolic pattern of the six major UsnRNAs during development AN - 856761351; 13860809 AB - The uridylic acid rich nuclear RNAs (U1-U6 snRNAs) are involved mainly in the processing of pre-mRNA and pre-rRNA. So, any control of cell growth through pre-mRNA/pre-rRNA processing may have some regulation through altered UsnRNAs metabolism. With this idea, attempts have been made to see how the metabolism of the six major UsnRNAs' changed during the normal process of cellular proliferation associated with differentiation from pluripotent/totipotent stem cells of early embryonic stage to much more differentiated state of different cell/tissue lineages in different tissues/organs during the fetal and neonatal stages of growth. It has been seen that the levels of the six major UsnRNAs were high in day 8 embryo when the cells were mainly pluripotent/totipotent in nature, and during the progression of embryonic development the levels of these UsnRNAs gradually decreased (35-65%) up to the midgestational period (day 13) with some exception, when the organogenesis has already been started. However in the fetal life, the levels of these UsnRNAs were maximum or comparable around 18 c 2 days of gestation in comparison to that in day 8 embryo when the kinetics of the maturational status of the different organs were quite high. But, the levels of these UsnRNAs' became low during day 21 of fetal life or in day 0 of birth (perturation period) in all the tissues/organs except high UsnRNAs' level in spleen. In the neonatal life, around 3 c 1 days of birth these UsnRNAs' levels again became maximum in all the tissues/organs (except in thymus) followed by decrease up to 5/6 days, and to become steady with slight increase within one to two weeks, when the kinetics of the organ maturation reached to a steady state. In case of thymus, the levels of the U3-U6 snRNAs were high on day 0 of birth followed by decrease in their level on day 1/2 and then increased to become steady within 2-4 weeks; whereas the U1 and U2 snRNAs' levels were high on day 3 of birth and the subsequent changes were similar to that in other tissues/organs. Thus the different UsnRNAs' metabolism in the perturation period and in the early stages of neonatal life has indicated the differential cellular functions in these two stages of development. These alterations in the metabolism of these UsnRNAs might be due to the differential changes in the rate of synthesis of these UsnRNAs and/or with their differential turnover rate in the different stages of development. Also, the differential variations of these UsnRNAs' levels have been observed among the different tissues/organs at the respective stages of development indicating the differences in the UsnRNAs' metabolism among the different cell/tissue lineages. Thus, it can be concluded that the metabolism of these UsnRNAs were developmentally regulated with some cell/tissue lineage variations, which might have some role in the developmentally regulated cellular process of proliferation and differentiation, through altered RNA splicing and processing. JF - Molecular and Cellular Biochemistry AU - Ray, Rabindranath AU - Ray, Kaushik AU - Panda, Chinmay K AD - Department of Oncogene Regulation, Chittaranjan National Cancer Institute, Calcutta, India Y1 - 1997/12// PY - 1997 DA - Dec 1997 SP - 79 EP - 88 PB - Springer-Verlag, Tiergartenstrasse 17 Heidelberg 69121 Germany VL - 177 IS - 1-2 SN - 0300-8177, 0300-8177 KW - Toxicology Abstracts KW - snRNA KW - Organogenesis KW - Thymus KW - Spleen KW - Developmental stages KW - Fetuses KW - Birth KW - RNA processing KW - Differentiation KW - Embryogenesis KW - Splicing KW - Stem cells KW - RNA KW - Kinetics KW - Gestation KW - Embryos KW - Neonates KW - Cell proliferation KW - Metabolism KW - X 24500:Reviews, Legislation, Book & Conference Notices UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/856761351?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+and+Cellular+Biochemistry&rft.atitle=Differential+alterations+in+metabolic+pattern+of+the+six+major+UsnRNAs+during+development&rft.au=Ray%2C+Rabindranath%3BRay%2C+Kaushik%3BPanda%2C+Chinmay+K&rft.aulast=Ray&rft.aufirst=Rabindranath&rft.date=1997-12-01&rft.volume=177&rft.issue=1-2&rft.spage=79&rft.isbn=&rft.btitle=&rft.title=Molecular+and+Cellular+Biochemistry&rft.issn=03008177&rft_id=info:doi/10.1023%2FA%3A1006879718779 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2011-03-01 N1 - Last updated - 2012-03-29 N1 - SubjectsTermNotLitGenreText - snRNA; Organogenesis; Thymus; Developmental stages; Spleen; Fetuses; RNA processing; Birth; Differentiation; Stem cells; Splicing; Embryogenesis; RNA; Kinetics; Gestation; Embryos; Neonates; Cell proliferation; Metabolism DO - http://dx.doi.org/10.1023/A:1006879718779 ER - TY - JOUR T1 - Cardiopulmonary resuscitation in pediatric intensive care units. AN - 85267389; pmid-9403741 AB - OBJECTIVE: To determine the effectiveness of cardiopulmonary resuscitation (CPR) in the pediatric intensive care unit (ICU). DESIGN: A nonconcurrent cohort study of consecutive admissions. SETTING: Thirty-two pediatric ICUs. PATIENTS: Consecutive admissions to 32 pediatric ICUs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Pediatric ICU patients were followed for the occurrence of a cardiopulmonary arrest (external cardiac massage for at least 2 mins). Patients who were in a state of continuous cardiopulmonary arrest on admission, or who never achieved stable vital signs, were excluded from the study. A total of 205 patients, from a sample of 11,165 (1.8%) pediatric admissions, experienced a cardiopulmonary arrest. Overall, 28 (13.7%) patients survived to hospital discharge. Neither mean ages nor age distribution affected survival. Only two diagnostic categories, traumatic illness, and other etiologies, were associated with survival. None of the patients fitting this category survived (p = .0028). The durations of CPR for survivors and nonsurvivors were 22.5 +/- 10.1 and 24.8 +/- 1.9 mins, respectively (p = .015). For CPR durations of 30 mins, the survival rates were 18.6%, 12.2%, and 5.6%, respectively (linear trend p = .022). Thirty-five (17.1%) patients had a cardiopulmonary arrest before pediatric ICU admission and another arrest in the pediatric ICU. Only two (5.7%) of these 35 patients survived to discharge. Pediatric ICU survival decreased as the number of pediatric ICU arrests increased. Patients with one arrest (n = 155), two arrests (n = 29), and more than three arrests (n = 21) experienced survival rates of 14%, 14%, and 9.5%, respectively. Severity of illness, as measured by the Pediatric Risk of Mortality III score, was a significant predictor of survival (p < .001). CONCLUSIONS: Pediatric ICU cardiac arrest is an uncommon event. When it does occur, prehospital CPR, duration of resuscitation, traumatic etiology, and severity of illness are important factors associated with survival. JF - Critical Care Medicine AU - Slonim, A D AU - Patel, K M AU - Ruttimann, U E AU - Pollack, M M AD - Critical Care Medicine Department, Warren G. Magnuson Clinical Center, National Institutes of Health, USA. PY - 1997 SP - 1951 EP - 1955 VL - 25 IS - 12 SN - 0090-3493, 0090-3493 KW - Severity of Illness Index KW - Intensive Care Units, Pediatric KW - Support, U.S. Gov't, P.H.S. KW - Human KW - Infant, Newborn KW - Child KW - Heart Arrest KW - Outcome Assessment (Health Care) KW - Child, Preschool KW - Infant KW - Survival Rate KW - Risk Factors KW - Cohort Studies KW - Adolescent KW - Male KW - Female KW - Cardiopulmonary Resuscitation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85267389?accountid=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=Critical+Care+Medicine&rft.atitle=Cardiopulmonary+resuscitation+in+pediatric+intensive+care+units.&rft.au=Slonim%2C+A+D%3BPatel%2C+K+M%3BRuttimann%2C+U+E%3BPollack%2C+M+M&rft.aulast=Slonim&rft.aufirst=A&rft.date=1997-12-01&rft.volume=25&rft.issue=12&rft.spage=1951&rft.isbn=&rft.btitle=&rft.title=Critical+Care+Medicine&rft.issn=00903493&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Current noise spectrum and capacitance due to the membrane motor of the outer hair cell: theory. AN - 85254879; pmid-9414211 AB - The voltage-dependent motility of the outer hair cell is based on a membrane motor densely distributed in the lateral membrane. The gating charge of the membrane motor is manifested as a bell-shaped membrane potential dependence of the membrane capacitance. In this paper it is shown that movements of the gating charge should produce a high-pass current noise described by an inverse Lorentzian similar to the one shown by Kolb and Läuger for ion carriers. The frequency dependence of the voltage-dependent capacitance is also derived. These derivations are based on membrane motor models with two or three states. These two models lead to similar predictions on the capacitance and current noise. It is expected that the examination of the spectral properties of these quantities would be a useful means of determining the relaxation time for conformational transitions of the membrane motor. JF - Biophysical Journal AU - Iwasa, Kuni H AD - National Institute on Deafness and Other Communication Disorders PY - 1997 SP - 2965 EP - 2971 VL - 73 IS - 6 SN - 0006-3495, 0006-3495 KW - Ion Channel Gating KW - Comparative Study KW - Electric Conductivity KW - Hair Cells, Outer KW - Animal KW - Cell Membrane KW - Membrane Potentials KW - Electrophysiology KW - Biomechanics KW - Biophysics KW - Models, Biological UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85254879?accountid=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=Current+noise+spectrum+and+capacitance+due+to+the+membrane+motor+of+the+outer+hair+cell%3A+theory.&rft.au=Iwasa%2C+Kuni+H&rft.aulast=Iwasa&rft.aufirst=Kuni&rft.date=1997-12-01&rft.volume=73&rft.issue=6&rft.spage=2965&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 - Altered gene expression in drug-resistant human breast cancer cells. AN - 79638892; 9815641 AB - It is increasingly recognized that drug-resistant cells undergo transitions not directly linked to "classical" drug resistance. We examined the expression of growth factors, growth factor receptors, and the estrogen receptor in 17 drug-resistant and 2 revertant human breast cancer sublines to provide an understanding of the phenotypic changes that occur and how these changes could affect the biology of the cell. These sublines were derived from five parental human breast cancer cell lines (MCF-7, ZR75B, T47D, MDA-MB-231, and MDA-MB-453). The expression of estrogen receptor was absent or decreased in 6 of the 15 resistant MCF-7, ZR75B, and T47D sublines. Increases of as much as 49-fold compared to parental levels were observed in transforming growth factor alpha, epidermal growth factor receptor, c-erbB2, and/or c-erbB3 mRNA expression in 14 of the 17 resistant sublines. Altered amphiregulin and insulin-like growth factor-I receptor expression was observed in nine and four drug-resistant sublines, respectively. No major alterations were observed in epidermal growth factor and c-erbB4 expression. Few alterations were observed in two sublines derived from estrogen receptor-negative cells. Higher levels of phosphotyrosine residues were detected in a subset of the resistant sublines, indicating an increased tyrosine kinase activity in these cells. Interestingly, decreased growth rates were observed in all of the sublines, despite up-regulated growth factor-related gene expression. Taken together, these data suggest that loss of estrogen receptor, increased expression of growth factor pathway genes, and decreased growth rate regularly occur in drug-resistant breast cancer cells. Although we do not know whether the altered expression of growth factor pathway genes is linked as a cause or a consequence of the reduced growth rate, it is well established that decreased growth rate confers drug resistance. These phenotypic changes in drug-resistant human breast cancer cells could serve to initiate, support, or extend the drug resistance. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Wosikowski, K AU - Schuurhuis, D AU - Kops, G J AU - Saceda, M AU - Bates, S E AD - Medicine Branch, Division of Clinical Science, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. Y1 - 1997/12// PY - 1997 DA - December 1997 SP - 2405 EP - 2414 VL - 3 IS - 12 Pt 1 SN - 1078-0432, 1078-0432 KW - Antineoplastic Agents KW - 0 KW - Proto-Oncogene Proteins KW - RNA, Messenger KW - Receptors, Estrogen KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - Receptor, ErbB-2 KW - Receptor, ErbB-3 KW - DNA Topoisomerases, Type II KW - EC 5.99.1.3 KW - Index Medicus KW - DNA Topoisomerases, Type II -- biosynthesis KW - Receptor, ErbB-2 -- genetics KW - Receptors, Estrogen -- genetics KW - Tumor Cells, Cultured KW - DNA Topoisomerases, Type II -- genetics KW - Humans KW - Cell Division -- drug effects KW - Transcription, Genetic KW - Receptors, Estrogen -- analysis KW - RNA, Messenger -- genetics KW - Proto-Oncogenes KW - Female KW - Gene Expression Regulation, Neoplastic KW - Breast Neoplasms -- genetics KW - Receptor, Epidermal Growth Factor -- genetics KW - Genes, erbB-2 KW - Antineoplastic Agents -- toxicity KW - Proto-Oncogene Proteins -- genetics KW - Drug Resistance, Multiple -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79638892?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=Altered+gene+expression+in+drug-resistant+human+breast+cancer+cells.&rft.au=Wosikowski%2C+K%3BSchuurhuis%2C+D%3BKops%2C+G+J%3BSaceda%2C+M%3BBates%2C+S+E&rft.aulast=Wosikowski&rft.aufirst=K&rft.date=1997-12-01&rft.volume=3&rft.issue=12+Pt+1&rft.spage=2405&rft.isbn=&rft.btitle=&rft.title=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10780432&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-03-03 N1 - Date created - 1999-03-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Management of neutralizing antibody to Ceredase in a patient with type 3 Gaucher disease. AN - 79608546; 9382912 AB - The beneficial effects of macrophage-targeted glucocerebrosidase (Ceredase) in patients with Gaucher disease are well established. A minority of recipients develop transient nonneutralizing antibodies to the exogenous enzyme. A 7-year-old patient with type 3 Gaucher disease whose clinical course began to deteriorate while receiving Ceredase developed a progressively increasing titer of IgG antibody that blocked the catalytic activity of Ceredase. We sought to develop a strategy that would restore the benefit of enzyme replacement therapy in this patient. The patient was treated with two courses of a combination of plasma exchange, cyclophosphamide, intravenous IgG, and large doses of Ceredase. After the second course of this regimen, the titer of the neutralizing antibody in the blood gradually declined to negligible levels. Clinical parameters that had been deteriorating (reduction of hemoglobin level, increased serum acid phosphates activity, repeated skeletal infarctions, progressive enlargement and infarction of the spleen) all improved. There has been no recurrence of the neutralizing antibody in this patient. Very few patients with Gaucher disease who are treated with Ceredase develop a neutralizing antibody to the exogenous enzyme. In the rare instances where this phenomenon occurs, it is likely that the strategy we have used (plasma exchange, cyclophosphamide, intravenous IgG, and large doses of enzyme) may provide benefit to such individuals. It is also likely that this technique may be helpful when enzyme replacement therapy is attempted in patients with other disorders in which the genetic mutation abrogates the production of the protein (CRIM-negative individuals). JF - Pediatrics AU - Brady, R O AU - Murray, G J AU - Oliver, K L AU - Leitman, S F AU - Sneller, M C AU - Fleisher, T A AU - Barton, N W AD - Developmental and Metabolic Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20852-1260, USA. Y1 - 1997/12// PY - 1997 DA - December 1997 SP - 1 VL - 100 IS - 6 KW - Immunoglobulin G KW - 0 KW - Immunoglobulins, Intravenous KW - Immunosuppressive Agents KW - alglucerase KW - 27T56C7KK0 KW - Cyclophosphamide KW - 8N3DW7272P KW - Glucosylceramidase KW - EC 3.2.1.45 KW - Index Medicus KW - Infusions, Intravenous KW - Humans KW - Antibody Formation KW - Child KW - Immunoglobulins, Intravenous -- therapeutic use KW - Cyclophosphamide -- therapeutic use KW - Glucosylceramidase -- administration & dosage KW - Gaucher Disease -- drug therapy KW - Glucosylceramidase -- therapeutic use KW - Glucosylceramidase -- immunology KW - Gaucher Disease -- enzymology KW - Plasmapheresis KW - Immunoglobulin G -- immunology KW - Immunosuppressive Agents -- therapeutic use KW - Immunoglobulin G -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79608546?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pediatrics&rft.atitle=Management+of+neutralizing+antibody+to+Ceredase+in+a+patient+with+type+3+Gaucher+disease.&rft.au=Brady%2C+R+O%3BMurray%2C+G+J%3BOliver%2C+K+L%3BLeitman%2C+S+F%3BSneller%2C+M+C%3BFleisher%2C+T+A%3BBarton%2C+N+W&rft.aulast=Brady&rft.aufirst=R&rft.date=1997-12-01&rft.volume=100&rft.issue=6&rft.spage=E11&rft.isbn=&rft.btitle=&rft.title=Pediatrics&rft.issn=1098-4275&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-01-18 N1 - Date created - 2000-12-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Altered dopaminergic function and negative symptoms in drug-free patients with schizophrenia. [123I]-iodobenzamide SPECT study. AN - 79586467; 9519100 AB - Previous in vivo studies of schizophrenia with dopamine D2 receptor radioligands have yielded contradictory results. No prior study has used multiple scans to examine within-subject clinical change. Twenty-one patients were studied with [123I]-iodobenzamide single photon emission computed tomography about two weeks after neuroleptic withdrawal. Thirteen of the 21 completed a second scan about four weeks after neuroleptic withdrawal. Sixteen controls were scanned for comparison. There was no significant difference between groups in [123I]-iodobenzamide uptake at either scanning session. No significant correlations with demographic variables (age, illness duration, drug-free period), or clinical ratings (positive and negative symptoms, movement disorder) were observed at either scanning session. There was a significant correlation between change in [123I]-iodobenzamide uptake and change in negative symptom ratings for the subjects who underwent two scans (r = 0.72, P < 0.05). Worsening of negative symptoms may be associated with increased availability of striatal D2 receptors, perhaps because of decreased concentrations of endogenous dopamine. JF - The British journal of psychiatry : the journal of mental science AU - Knable, M B AU - Egan, M F AU - Heinz, A AU - Gorey, J AU - Lee, K S AU - Coppola, R AU - Weinberger, D R AD - Clinical Disorder Branch, National Institute of Mental Health, Washington, DC 20032, USA. Y1 - 1997/12// PY - 1997 DA - December 1997 SP - 574 EP - 577 VL - 171 SN - 0007-1250, 0007-1250 KW - Antipsychotic Agents KW - 0 KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Tomography, Emission-Computed, Single-Photon KW - Substance Withdrawal Syndrome -- metabolism KW - Humans KW - Adult KW - Antipsychotic Agents -- metabolism KW - Middle Aged KW - Male KW - Female KW - Schizophrenia -- metabolism KW - Dopamine -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79586467?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+British+journal+of+psychiatry+%3A+the+journal+of+mental+science&rft.atitle=Altered+dopaminergic+function+and+negative+symptoms+in+drug-free+patients+with+schizophrenia.+%5B123I%5D-iodobenzamide+SPECT+study.&rft.au=Knable%2C+M+B%3BEgan%2C+M+F%3BHeinz%2C+A%3BGorey%2C+J%3BLee%2C+K+S%3BCoppola%2C+R%3BWeinberger%2C+D+R&rft.aulast=Knable&rft.aufirst=M&rft.date=1997-12-01&rft.volume=171&rft.issue=&rft.spage=574&rft.isbn=&rft.btitle=&rft.title=The+British+journal+of+psychiatry+%3A+the+journal+of+mental+science&rft.issn=00071250&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-04-03 N1 - Date created - 1998-04-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Amphotropic or gibbon ape leukemia virus retrovirus binding and transduction correlates with the level of receptor mRNA in human hematopoietic cell lines. AN - 79575739; 9454686 AB - The low level of amphotropic retrovirus mediated gene transfer into human hematopoietic stem cells (HSC) has been an impediment to gene therapy for hematopoietic diseases (1). We have previously shown that mouse and human HSC have low levels of the mRNA encoding PiT-2, the amphotropic retrovirus receptor. We hypothesized that the low level of PiT-2 mRNA was responsible for the low frequency of transduction of HSC by amphotropic retroviral vectors (2). In this study we compared the level of PiT-2 and PiT-1, the Gibbon Ape Leukemia Virus receptor (GaLV), in 5 human tissue culture cell lines. PiT-2 and PiT-1 mRNA levels were highest in K562 cells and lowest in HL60 cells. In hematopoietic cell lines, the level of PiT-2 or PiT-1 mRNA correlated directly with retrovirus binding and transduction with the appropriate (amphotropic or GaLV) retrovirus vector. The level of expression of PiT-2 and PiT-1 mRNA could be increased by treatment of HL60 cells with either PMA or Interleukin-1alpha. The increase in the level of PiT-2 and PiT-1 mRNA correlated with increased transduction with both amphotropic and GaLV retroviral vectors. We conclude that the improved transduction was a direct effect of the increased levels of receptor mRNA and unrelated to changes in the cell cycle status. JF - Blood cells, molecules & diseases AU - Sabatino, D E AU - Do, B Q AU - Pyle, L C AU - Seidel, N E AU - Girard, L J AU - Spratt, S K AU - Orlic, D AU - Bodine, D M AD - National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892-4442, USA. Y1 - 1997/12// PY - 1997 DA - December 1997 SP - 422 EP - 433 VL - 23 IS - 3 SN - 1079-9796, 1079-9796 KW - Interleukin-1 KW - 0 KW - RNA, Messenger KW - Receptors, Virus KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - AIDS/HIV KW - Interleukin-1 -- pharmacology KW - Blotting, Northern KW - Tumor Cells, Cultured KW - HeLa Cells KW - HL-60 Cells KW - Humans KW - Jurkat Cells KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Genetic Vectors -- genetics KW - Cell Cycle -- genetics KW - Cell Cycle -- drug effects KW - RNA, Messenger -- metabolism KW - Transformation, Genetic KW - Leukemia Virus, Gibbon Ape -- metabolism KW - Receptors, Virus -- metabolism KW - Receptors, Virus -- genetics KW - Hematopoietic Stem Cells -- virology KW - Hematopoietic Stem Cells -- metabolism KW - Leukemia Virus, Gibbon Ape -- genetics KW - Receptors, Virus -- drug effects KW - Hematopoietic Stem Cells -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79575739?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+cells%2C+molecules+%26+diseases&rft.atitle=Amphotropic+or+gibbon+ape+leukemia+virus+retrovirus+binding+and+transduction+correlates+with+the+level+of+receptor+mRNA+in+human+hematopoietic+cell+lines.&rft.au=Sabatino%2C+D+E%3BDo%2C+B+Q%3BPyle%2C+L+C%3BSeidel%2C+N+E%3BGirard%2C+L+J%3BSpratt%2C+S+K%3BOrlic%2C+D%3BBodine%2C+D+M&rft.aulast=Sabatino&rft.aufirst=D&rft.date=1997-12-01&rft.volume=23&rft.issue=3&rft.spage=422&rft.isbn=&rft.btitle=&rft.title=Blood+cells%2C+molecules+%26+diseases&rft.issn=10799796&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-24 N1 - Date created - 1998-03-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - HIV-1 acquires resistance to two classes of antiviral drugs through homologous recombination. AN - 79556320; 9477118 AB - Genetic recombination contributes to the genomic heterogeneity of human immunodeficiency virus type 1 (HIV-1). In the present study, we demonstrate that HIV-1 readily develops resistance to two classes of anti-HIV-1 drugs through in vitro genetic recombination involving large segments of the viral genome. Co-transfection of COS-7 cells with an HIV-1 plasmid (pSUM13) carrying five mutations in the reverse transcriptase (RT)-encoding region (A62V, V75I, F77L, F116Y, Q151M), conferring resistance to multiple dideoxynucleoside analogs (ddNs), and another HIV-1 plasmid (pSUM431) carrying five mutations in the protease-encoding region (V321, L33F, K451, 184V, L89M), conferring resistance to protease inhibitors such as KNI-272, readily produced HIV-1 carrying both sets of mutations when propagated in MT-2 cells in the presence of azidothymidine (AZT) and KNI-272. The resultant HIV-1 variant was highly resistant to both ddNs and KNI-272. Co-infection of MT-2 cells with HIV-1SUM13 carrying the RT mutations and HIV-1SUM431 carrying the mutations in the protease also generated HIV-1 with both sets of mutations when cultured with AZT and KNI-272. We also report here that the problematic artifactual recombination occurring during genetic analyses of heterogeneous nucleic acid sequences using polymerase chain reaction can be successfully obviated. JF - Antiviral research AU - Yusa, K AU - Kavlick, M F AU - Kosalaraksa, P AU - Mitsuya, H AD - Medicine Branch, Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1997/12// PY - 1997 DA - December 1997 SP - 179 EP - 189 VL - 36 IS - 3 SN - 0166-3542, 0166-3542 KW - Anti-HIV Agents KW - 0 KW - HIV Protease Inhibitors KW - Oligopeptides KW - Reverse Transcriptase Inhibitors KW - kynostatin 272 KW - 147318-81-8 KW - Zidovudine KW - 4B9XT59T7S KW - Zalcitabine KW - 6L3XT8CB3I KW - HIV Reverse Transcriptase KW - EC 2.7.7.49 KW - HIV Protease KW - EC 3.4.23.- KW - Didanosine KW - K3GDH6OH08 KW - Index Medicus KW - AIDS/HIV KW - Virus Replication KW - Polymerase Chain Reaction KW - Animals KW - COS Cells KW - Transfection KW - Humans KW - Drug Resistance, Microbial -- genetics KW - Zalcitabine -- pharmacology KW - Cell Line, Transformed KW - Didanosine -- pharmacology KW - Mutagenesis KW - HIV Protease -- genetics KW - HIV-1 -- genetics KW - Reverse Transcriptase Inhibitors -- pharmacology KW - Zidovudine -- pharmacology KW - HIV-1 -- physiology KW - HIV Reverse Transcriptase -- genetics KW - Anti-HIV Agents -- pharmacology KW - Recombination, Genetic KW - HIV Protease Inhibitors -- pharmacology KW - HIV-1 -- growth & development KW - Oligopeptides -- pharmacology KW - HIV-1 -- drug effects KW - Drug Resistance, Multiple -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79556320?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antiviral+research&rft.atitle=HIV-1+acquires+resistance+to+two+classes+of+antiviral+drugs+through+homologous+recombination.&rft.au=Yusa%2C+K%3BKavlick%2C+M+F%3BKosalaraksa%2C+P%3BMitsuya%2C+H&rft.aulast=Yusa&rft.aufirst=K&rft.date=1997-12-01&rft.volume=36&rft.issue=3&rft.spage=179&rft.isbn=&rft.btitle=&rft.title=Antiviral+research&rft.issn=01663542&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-26 N1 - Date created - 1998-03-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Fluconazole versus nystatin in the prevention of candida infections in children and adolescents undergoing remission induction or consolidation chemotherapy for cancer. AN - 79547885; 9462438 AB - An open, prospective, randomized pilot study was performed to assess the efficacy and safety of oral fluconazole 3 mg/kg once daily compared with oral nystatin 50,000 units/kg/day in four divided doses in preventing candida infections in 50 children undergoing remission induction or consolidation therapy for cancer. In 21 of 25 fluconazole-treated and 20 of 25 nystatin-treated patients the overall outcome of prophylaxis was clearly successful. Mild and transient oropharyngeal candidosis was observed in two and three patients in the fluconazole and nystatin groups respectively. One patient randomized to fluconazole and two patients randomized to nystatin required empirical treatment with amphotericin B and one patient assigned to fluconazole developed tissue-proven candida colitis. Initially non-colonized patients remained yeast-free throughout treatment with no differences between the two study arms. Initially colonized patients stayed colonized throughout treatment although at the end of the study, more patients randomized to nystatin were still harbouring yeasts (P = 0.05). Almost exclusively, Candida albicans (95%) was isolated. A change in species was observed in one patient in each arm of the study. Candida krusei or Candida glabrata were not encountered. Transient elevations of hepatic transaminases were more common in the fluconazole group, although not statistically significant (28% vs 12%, P = 0.15). Reversible grade I gastrointestinal and skin symptoms were observed in four patients randomized to fluconazole (16 vs 0%, P < 0.05). Fluconazole was as safe and effective as nystatin in controlling yeast colonization and in preventing superficial and invasive candida infections and the empirical use of amphotericin B in children and adolescents undergoing intensive chemotherapy for cancer. JF - The Journal of antimicrobial chemotherapy AU - Groll, A H AU - Just-Nuebling, G AU - Kurz, M AU - Mueller, C AU - Nowak-Goettl, U AU - Schwabe, D AU - Shah, P M AU - Kornhuber, B AD - Department of Paediatrics, Johann Wolfgang Goethe University Hospital, Frankfurt am Main, Germany. agroll@pbmac.nci.nih.gov Y1 - 1997/12// PY - 1997 DA - December 1997 SP - 855 EP - 862 VL - 40 IS - 6 SN - 0305-7453, 0305-7453 KW - Antifungal Agents KW - 0 KW - Antineoplastic Agents KW - Nystatin KW - 1400-61-9 KW - Fluconazole KW - 8VZV102JFY KW - Index Medicus KW - Infant KW - Feces -- microbiology KW - Prospective Studies KW - Humans KW - Child KW - Candida albicans KW - Pruritus -- chemically induced KW - Adolescent KW - Oropharynx -- microbiology KW - Male KW - Female KW - Child, Preschool KW - Fluconazole -- adverse effects KW - Neoplasms -- drug therapy KW - Neoplasms -- complications KW - Fluconazole -- therapeutic use KW - Candidiasis -- prevention & control KW - Nystatin -- therapeutic use KW - Antineoplastic Agents -- therapeutic use KW - Candidiasis -- etiology KW - Antifungal Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79547885?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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+antimicrobial+chemotherapy&rft.atitle=Fluconazole+versus+nystatin+in+the+prevention+of+candida+infections+in+children+and+adolescents+undergoing+remission+induction+or+consolidation+chemotherapy+for+cancer.&rft.au=Groll%2C+A+H%3BJust-Nuebling%2C+G%3BKurz%2C+M%3BMueller%2C+C%3BNowak-Goettl%2C+U%3BSchwabe%2C+D%3BShah%2C+P+M%3BKornhuber%2C+B&rft.aulast=Groll&rft.aufirst=A&rft.date=1997-12-01&rft.volume=40&rft.issue=6&rft.spage=855&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+antimicrobial+chemotherapy&rft.issn=03057453&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-12 N1 - Date created - 1998-03-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Statistical research needs in mechanistic modelling for carcinogenic risk assessment. AN - 79542734; 9447651 AB - If the broad spectrum of mechanistic research conducted on an environmental carcinogen is to be used in quantifying cancer risks, statisticians must play a key role. Statistical methods are critically needed for a scientifically valid analysis of a complicated series of linked experimental findings. This will require a greater understanding of the underlying biology than is common in statistical consulting, aiding in the development of complicated mechanistically based mathematical descriptions of mean response and in the creation of statistical methods for the estimation of model parameters (e.g. likelihoods) able to use both the underlying model and much of the available data. JF - Statistical methods in medical research AU - Portier, C AU - el Masri, H AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, NC 27709, USA. Y1 - 1997/12// PY - 1997 DA - December 1997 SP - 305 EP - 315 VL - 6 IS - 4 SN - 0962-2802, 0962-2802 KW - Index Medicus KW - Animals KW - Neoplastic Processes KW - Humans KW - Research Design KW - Neoplasms -- physiopathology KW - Neoplasms -- epidemiology KW - Models, Biological KW - Risk Assessment UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79542734?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Statistical+methods+in+medical+research&rft.atitle=Statistical+research+needs+in+mechanistic+modelling+for+carcinogenic+risk+assessment.&rft.au=Portier%2C+C%3Bel+Masri%2C+H&rft.aulast=Portier&rft.aufirst=C&rft.date=1997-12-01&rft.volume=6&rft.issue=4&rft.spage=305&rft.isbn=&rft.btitle=&rft.title=Statistical+methods+in+medical+research&rft.issn=09622802&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-12 N1 - Date created - 1998-03-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cellular response to DNA damage from a potent carcinogen involves stabilization of p53 without induction of p21(waf1/cip1). AN - 79538464; 9450475 AB - The effect of a potent mammary carcinogen, anti benzo[g]chrysene 11,12-dihydrodiol 13,14-epoxide, on the progress of human mammary carcinoma MCF-7 cells through the cell cycle was investigated. While these cells, which express wild-type p53, were arrested in G1 after treatment with actinomycin D (a positive control), treatment with the mammary carcinogen did not cause G1 arrest but instead delayed the cells in the DNA synthesis phase. In concert with the absence of a G1 arrest, it was found that though both chemical treatments led to increased levels of p53, only the p53 induced by actinomycin D was transcriptionally active and increased the levels of the cyclin dependent kinase inhibitor, p21(waf1/cip1). Since treatment of the cells with the mammary carcinogen did not abrogate the G1 arrest induced by actinomycin D, the lack of p21(waf1/cip1) and of G1 arrest, resulting from treatment with the mammary carcinogen alone, was not due to some general inhibition of transcription or translation. An analogous difference between these two chemicals was demonstrated also in other human cell systems. The stealth-like property of the mammary carcinogen that allows it to damage DNA without turning on the cells' 'guardian of the genome' defense mechanism presumably increases the likelihood of malignant change because DNA replication continues on a damaged template. It is suggested that this stealth characteristic may be a major contributor to the high carcinogenic potency of this mammary carcinogen and possibly to that of other highly potent carcinogens. JF - Carcinogenesis AU - Khan, Q A AU - Vousden, K H AU - Dipple, A AD - Chemistry of Carcinogenesis, ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, MD 21702, USA. Y1 - 1997/12// PY - 1997 DA - December 1997 SP - 2313 EP - 2318 VL - 18 IS - 12 SN - 0143-3334, 0143-3334 KW - CDKN1A protein, human KW - 0 KW - Carcinogens KW - Chrysenes KW - Cyclin-Dependent Kinase Inhibitor p21 KW - Cyclins KW - Tumor Suppressor Protein p53 KW - benzo(g)chrysene-11,12-dihydrodiol-13,14-epoxide KW - 132832-27-0 KW - Dactinomycin KW - 1CC1JFE158 KW - Index Medicus KW - Dactinomycin -- pharmacology KW - Transcription, Genetic -- drug effects KW - Tumor Cells, Cultured KW - Humans KW - Female KW - Carcinogens -- pharmacology KW - DNA Damage KW - Cyclins -- metabolism KW - Chrysenes -- pharmacology KW - Tumor Suppressor Protein p53 -- metabolism KW - Cell Cycle -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79538464?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cellular+response+to+DNA+damage+from+a+potent+carcinogen+involves+stabilization+of+p53+without+induction+of+p21%28waf1%2Fcip1%29.&rft.au=Khan%2C+Q+A%3BVousden%2C+K+H%3BDipple%2C+A&rft.aulast=Khan&rft.aufirst=Q&rft.date=1997-12-01&rft.volume=18&rft.issue=12&rft.spage=2313&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-02-11 N1 - Date created - 1998-02-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - An ongoing prospective randomized comparison of interleukin-2 regimens for the treatment of metastatic renal cell cancer. AN - 79537743; 9457400 AB - This article compares the pharmacokinetics, toxicity, and clinical efficacy of high-dose intravenous, low-dose intravenous, and intermediate-dose subcutaneous recombinant interleukin-2 (rIL-2) regimens in patients with measurable metastatic renal cell carcinoma. This trial began as a two-arm randomized study comparing two bolus intravenous rIL-2 regimens. High-dose (720,000 IU/kg) and low-dose (72,000 IU/kg) rIL-2 were administered every 8 hours for up to 15 consecutive doses. Later, a third arm of outpatient subcutaneous rIL-2 (week 1: 250,000 IU/kg/day for 5 of 7 days; weeks 2-6: 125,000 IU/kg/day for 5 of 7 days) was added, and only concurrently randomized patients were compared. A sample of patients underwent pharmacokinetic studies of serum IL-2 levels following their first dose. Accrual to this study is ongoing and results are preliminary. In the two-arm comparison of high-dose versus low-dose intravenous rIL-2, 116 and 112 patients have been randomized, respectively, and the median follow-up is 52 months. Low-dose rIL-2 induced significantly less hypotension, thrombocytopenia, malaise, pulmonary toxicity, and neurotoxicity than high-dose rIL-2. The initial overall response rate (partial plus complete responses) was 19% with high-dose rIL-2 and 10% with low-dose rIL-2. Responses to high-dose rIL-2 tended to be more durable. With 54 to 56 patients randomized per arm in the three-arm comparison, the high-dose intravenous, low-dose intravenous, and subcutaneous outpatient rIL-2 regimens have produced response rates of 16%, 4%, and 11%, respectively. Subcutaneous rIL-2 therapy was infrequently associated with grade 3 or 4 toxicity (similar to low-dose intravenous rIL-2 therapy). Survival data remain incomplete with median follow-up in the three-arm trial at 27 months. The optimal IL-2 regimen for treating metastatic renal cell carcinoma is not known. Alternative regimens with much less acute toxicity than high-dose IL-2 can cause regression of renal cell carcinoma, but duration of therapy, chronicity of symptoms, and quality-of-life issues may be important in properly evaluating the tolerability of different regimens. Because the main benefit of IL-2 therapy is not its initial response rate but its induction of durable, complete responses, further accrual and follow-up will be necessary to compare properly the impact of these regimens on patient survival. JF - The cancer journal from Scientific American AU - Yang, J C AU - Rosenberg, S A AD - Surgery Branch, National Cancer Institute, Bethesda, Maryland, USA. Y1 - 1997/12// PY - 1997 DA - December 1997 SP - S79 EP - S84 VL - 3 Suppl 1 SN - 1081-4442, 1081-4442 KW - Interleukin-2 KW - 0 KW - Index Medicus KW - Prospective Studies KW - Humans KW - Dose-Response Relationship, Immunologic KW - Treatment Outcome KW - Injections, Subcutaneous KW - Kidney Neoplasms -- therapy KW - Interleukin-2 -- blood KW - Interleukin-2 -- adverse effects KW - Interleukin-2 -- administration & dosage KW - Carcinoma, Renal Cell -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79537743?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+cancer+journal+from+Scientific+American&rft.atitle=An+ongoing+prospective+randomized+comparison+of+interleukin-2+regimens+for+the+treatment+of+metastatic+renal+cell+cancer.&rft.au=Yang%2C+J+C%3BRosenberg%2C+S+A&rft.aulast=Yang&rft.aufirst=J&rft.date=1997-12-01&rft.volume=3+Suppl+1&rft.issue=&rft.spage=S79&rft.isbn=&rft.btitle=&rft.title=The+cancer+journal+from+Scientific+American&rft.issn=10814442&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-04-22 N1 - Date created - 1998-04-22 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Cancer J Sci Am. 1997 Dec;3 Suppl 1:S68-9 [9457397] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Uterine carcinoma in mice treated neonatally with tamoxifen. AN - 79536574; 9450472 AB - The induction of preneoplastic and neoplastic lesions by the widely used antiestrogen Tamoxifen was studied in female mice. Outbred CD-1 mice were treated with Tamoxifen (1, 2, 5, 10, 25 or 50 microg/pup/day) for the first 5 days after birth. At 14-17 months, reproductive tract tissues were examined for pathological changes. In the ovary, corpora lutea were lacking while cysts were quite common in Tamoxifen-exposed mice at all doses; cystadenomas were seen in two mice. Structural malformations and epithelial hyperplasia of the oviduct were seen in 100% of the treated mice. Malformations of the uterus, cervix, and vagina were also seen. Excessive vaginal keratinization was not a common feature although vaginal adenosis was observed more often after Tamoxifen treatment than previously reported after similar treatment with diethylstilbestrol (DES). The most striking histological features, however, were seen in the uterus. One hundred percent of the Tamoxifen-treated mice at all doses exhibited uterine hypoplasia with focal areas of basal cell hyperplasia in the lining endometrium. Progressive cellular atypias were seen in the lining endometrium ranging from atypical hyperplasia to uterine adenocarcinoma; the highest incidence of uterine adenocarcinoma was 7/14 (50%) observed in the Tamoxifen 10 microg/pup/day dose group. No similar tumors were observed in corresponding control mice. The induction of atypical uterine hyperplasia and adenocarcinoma combined with other abnormalities observed in genital tract structure following neonatal treatment with Tamoxifen suggests the developing reproductive tract is exquisitely sensitive to perturbation by compounds with hormonal activity. These studies provide the basis for future investigation into the mechanisms of Tamoxifen's carcinogenic effects in experimental animals, and to the risk benefit analysis for the prophylactic use of Tamoxifen in healthy women who are at risk of developing breast cancer. JF - Carcinogenesis AU - Newbold, R R AU - Jefferson, W N AU - Padilla-Burgos, E AU - Bullock, B C AD - Laboratory of Toxicology, Environmental Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1997/12// PY - 1997 DA - December 1997 SP - 2293 EP - 2298 VL - 18 IS - 12 SN - 0143-3334, 0143-3334 KW - Tamoxifen KW - 094ZI81Y45 KW - Index Medicus KW - Animals, Newborn KW - Animals KW - Fallopian Tubes -- pathology KW - Endometrial Neoplasms -- chemically induced KW - Ovarian Cysts -- chemically induced KW - Mice KW - Vaginal Diseases -- chemically induced KW - Female KW - Adenocarcinoma -- chemically induced KW - Uterine Neoplasms -- chemically induced KW - Tamoxifen -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79536574?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Uterine+carcinoma+in+mice+treated+neonatally+with+tamoxifen.&rft.au=Newbold%2C+R+R%3BJefferson%2C+W+N%3BPadilla-Burgos%2C+E%3BBullock%2C+B+C&rft.aulast=Newbold&rft.aufirst=R&rft.date=1997-12-01&rft.volume=18&rft.issue=12&rft.spage=2293&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-02-11 N1 - Date created - 1998-02-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Alterations in the reproductive patterns of female mice exposed to xenobiotics. AN - 79536401; 9441715 AB - Chemicals, by virtue of their varied interactions with biological molecules, are expected to differ in the way they may alter female reproduction. Reproductive toxicity may reflect effects either on the female germ cells or on various maternal processes such as ovulation, implantation, pregnancy, and parturition. In either case, the ultimate manifestation of chemical toxicity on female reproduction is a decrease in the number of normal young born. Very little information is available on the effects of chemicals that are nonhormonal in nature on the long-term ability of treated females to produce offspring. This report presents the results of long-term female total reproductive capacity (TRC) tests on 29 chemicals, including pharmaceuticals, pesticides, and alkylating and industrial agents. For each chemical, the minimum test involved an evaluation of the maximum tolerated dose administered as a single intraperitoneal injection. Females were single-pair mated with an untreated male for most of the female's reproductive life span (a minimum of 347 days posttreatment) and scored for the number of live births produced during this period. Confirmatory dominant lethal experiments or histological examinations for numbers of small follicles were carried out when mutagenic effects or cytotoxicity, respectively, were suspected as the basis for reduced fertility. Of the 29 chemicals studied, 17 had reproductive effects which may be grouped into one of three classes: (1) those that reduced the total number of young and litters per female, (2) those that reduced the total number of young but not of litters, and (3) those that had no significant effect on the total number of young produced but reduced the size of the first and/or second litters. The TRC provides a capacity for detecting a range of toxic insults upon female reproduction. Many of the chemicals were indeed shown to affect the reproductive performance of females through mutagenic and/or cytotoxic effects on follicles. In some cases, however, no causative mechanism could be identified for the observed reduction in reproductive performance. Nevertheless, with this report the number of chemicals tested by this TRC procedure has been quadrupled and the categories of chemicals tested have been substantially broadened. JF - Fundamental and applied toxicology : official journal of the Society of Toxicology AU - Bishop, J B AU - Morris, R W AU - Seely, J C AU - Hughes, L A AU - Cain, K T AU - Generoso, W M AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1997/12// PY - 1997 DA - December 1997 SP - 191 EP - 204 VL - 40 IS - 2 SN - 0272-0590, 0272-0590 KW - Alkylating Agents KW - 0 KW - Pesticides KW - Xenobiotics KW - Index Medicus KW - Injections, Intraperitoneal KW - Animals KW - Ovary -- drug effects KW - Mice KW - Structure-Activity Relationship KW - Pregnancy KW - Ovarian Follicle -- drug effects KW - Pesticides -- toxicity KW - Mutagenicity Tests KW - Ovary -- pathology KW - Ovarian Follicle -- pathology KW - Alkylating Agents -- toxicity KW - Staining and Labeling KW - Female KW - Male KW - Litter Size -- drug effects KW - Xenobiotics -- administration & dosage KW - Reproduction -- drug effects KW - Xenobiotics -- toxicity KW - Fertility -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79536401?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Alterations+in+the+reproductive+patterns+of+female+mice+exposed+to+xenobiotics.&rft.au=Bishop%2C+J+B%3BMorris%2C+R+W%3BSeely%2C+J+C%3BHughes%2C+L+A%3BCain%2C+K+T%3BGeneroso%2C+W+M&rft.aulast=Bishop&rft.aufirst=J&rft.date=1997-12-01&rft.volume=40&rft.issue=2&rft.spage=191&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 - 1998-03-09 N1 - Date created - 1998-03-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chemically reactive intermediates and pulmonary xenobiotic toxicity. AN - 79527895; 9443161 AB - After reading this lengthy review, the reader may consider it foolhardy to attempt to summarize the data contained herein. If so, the author and the reader are in complete accord. I set out to integrate, wherever possible, pathological changes in tissues and cells as determined by light, scanning, and TEM with chemical, biochemical, molecular, biological, and genetic techniques. I am not so naive as to equate correlation with causation, but in experimental biology, one is often compelled to rely on a number correlations to suggest causation. These data may also act as a stepping-off point helping the investigator design experiments to support/confirm or refute/disprove the hypothesis under investigation. Science is rarely black and white but rather gray, and the young investigator must be wary of scientists who argue their points too vociferously, too loudly, or too selectively. The truth in science is often a Gordian knot. JF - Pharmacological reviews AU - Gram, T E AD - Section on Drug Interactions, Developmental Therapeutics Program, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1997/12// PY - 1997 DA - December 1997 SP - 297 EP - 341 VL - 49 IS - 4 SN - 0031-6997, 0031-6997 KW - Anti-Infective Agents, Urinary KW - 0 KW - Antibiotics, Antineoplastic KW - Antineoplastic Agents KW - Antioxidants KW - Carcinogens KW - DNA Adducts KW - Dichloroethylenes KW - Herbicides KW - Naphthalenes KW - Nitrosamines KW - Terpenes KW - Xenobiotics KW - Bleomycin KW - 11056-06-7 KW - Butylated Hydroxytoluene KW - 1P9D0Z171K KW - vinylidene chloride KW - 21SK105J9D KW - 4-ipomeanol KW - 32954-58-8 KW - Benzo(a)pyrene KW - 3417WMA06D KW - 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone KW - 7S395EDO61 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Nitrofurantoin KW - 927AH8112L KW - Skatole KW - 9W945B5H7R KW - Paraquat KW - PLG39H7695 KW - Index Medicus KW - Terpenes -- toxicity KW - Anti-Infective Agents, Urinary -- toxicity KW - Nitrosamines -- toxicity KW - Animals KW - Antioxidants -- toxicity KW - Skatole -- toxicity KW - Butylated Hydroxytoluene -- toxicity KW - Carcinogens -- toxicity KW - Bleomycin -- toxicity KW - Paraquat -- toxicity KW - Antibiotics, Antineoplastic -- toxicity KW - Dichloroethylenes -- toxicity KW - Biotransformation KW - Benzo(a)pyrene -- toxicity KW - Antineoplastic Agents -- toxicity KW - Lung Neoplasms -- chemically induced KW - Herbicides -- toxicity KW - Hyperoxia -- chemically induced KW - Naphthalenes -- toxicity KW - Nitrofurantoin -- toxicity KW - Lung -- ultrastructure KW - Lung -- drug effects KW - Cytochrome P-450 Enzyme System -- metabolism KW - Xenobiotics -- toxicity KW - Lung -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79527895?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pharmacological+reviews&rft.atitle=Chemically+reactive+intermediates+and+pulmonary+xenobiotic+toxicity.&rft.au=Gram%2C+T+E&rft.aulast=Gram&rft.aufirst=T&rft.date=1997-12-01&rft.volume=49&rft.issue=4&rft.spage=297&rft.isbn=&rft.btitle=&rft.title=Pharmacological+reviews&rft.issn=00316997&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-02-26 N1 - Date created - 1998-02-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Comparative pulmonary absorption, distribution, and toxicity of copper gallium diselenide, copper indium diselenide, and cadmium telluride in Sprague-Dawley rats. AN - 79526503; 9439735 AB - Copper gallium diselenide (CGS), copper indium diselenide (CIS), and cadmium telluride (CdTe) are novel compounds used in the photovoltaic and semiconductor industries. This study was conducted to characterize the relative toxicities of these compounds and to evaluate the pulmonary absorption and distribution after intratracheal instillation. Female Sprague-Dawley rats were administered a single equimolar dose (70 mM) of CGS (21 mg/kg), CIS (24 mg/kg), CdTe (17 mg/kg), or saline by intratracheal instillation. Bronchoalveolar lavage fluid (BALF) protein, fibronectin, inflammatory cells, lung hydroxyproline, and tissue distribution were measured 1, 3, 7, 14, and 28 days after instillation. Relative lung weights were significantly increased in CIS- and CdTe-treated rats at most time points. Inflammatory lesions in the lungs consisting of an influx of macrophages, lymphocytes, and PMNs were most severe in CdTe-treated rats, intermediate in CIS-treated rats, and minimal in rats receiving CGS. Hyperplasia of alveolar type 2 cells was present in CIS- and CdTe-treated rats and was greatest in CdTe-treated rats. Pulmonary interstitial fibrosis was observed in CdTe-treated rats at all time points. All three compounds caused marked increases in total BALF cell numbers, with the greatest increase observed in CIS-treated rats. BALF protein, fibronectin, and lung hydroxyproline were significantly increased in all treated animals and were highest in CdTe-treated animals. There was no apparent pulmonary absorption or tissue distribution of CGS. Indium levels increased in extrapulmonary tissues of CIS-treated rats, although Cu and Se levels remained unchanged. CdTe was absorbed from the lung to a greater extent than CGS and CIS. Cd and Te levels decreased in the lung and increased in extrapulmonary tissues. Of these compounds CdTe presents the greatest potential health risk because it causes severe pulmonary inflammation and fibrosis and because it is readily absorbed from the lung may potentially cause extrapulmonary toxicity. JF - Toxicology and applied pharmacology AU - Morgan, D L AU - Shines, C J AU - Jeter, S P AU - Blazka, M E AU - Elwell, M R AU - Wilson, R E AU - Ward, S M AU - Price, H C AU - Moskowitz, P D AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1997/12// PY - 1997 DA - December 1997 SP - 399 EP - 410 VL - 147 IS - 2 SN - 0041-008X, 0041-008X KW - Cadmium Compounds KW - 0 KW - Fibronectins KW - copper gallium diselenide KW - copper indium diselenide KW - Indium KW - 045A6V3VFX KW - Copper KW - 789U1901C5 KW - Gallium KW - CH46OC8YV4 KW - Selenium KW - H6241UJ22B KW - Tellurium KW - NQA0O090ZJ KW - Hydroxyproline KW - RMB44WO89X KW - cadmium telluride KW - STG188WO13 KW - Index Medicus KW - Rats KW - Fibronectins -- chemistry KW - Animals KW - Rats, Sprague-Dawley KW - Kidney -- pathology KW - Bronchoalveolar Lavage Fluid -- chemistry KW - Body Weight -- drug effects KW - Kidney -- drug effects KW - Absorption KW - Spleen -- pathology KW - Spleen -- drug effects KW - Bronchoalveolar Lavage Fluid -- cytology KW - Hydroxyproline -- metabolism KW - Female KW - Organ Size -- drug effects KW - Gallium -- metabolism KW - Indium -- toxicity KW - Copper -- metabolism KW - Cadmium Compounds -- toxicity KW - Gallium -- toxicity KW - Indium -- metabolism KW - Lung -- metabolism KW - Lung -- pathology KW - Tellurium -- metabolism KW - Selenium -- metabolism KW - Selenium -- toxicity KW - Tellurium -- toxicity KW - Cadmium Compounds -- metabolism KW - Lung -- drug effects KW - Copper -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79526503?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Comparative+pulmonary+absorption%2C+distribution%2C+and+toxicity+of+copper+gallium+diselenide%2C+copper+indium+diselenide%2C+and+cadmium+telluride+in+Sprague-Dawley+rats.&rft.au=Morgan%2C+D+L%3BShines%2C+C+J%3BJeter%2C+S+P%3BBlazka%2C+M+E%3BElwell%2C+M+R%3BWilson%2C+R+E%3BWard%2C+S+M%3BPrice%2C+H+C%3BMoskowitz%2C+P+D&rft.aulast=Morgan&rft.aufirst=D&rft.date=1997-12-01&rft.volume=147&rft.issue=2&rft.spage=399&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 - 1998-02-19 N1 - Date created - 1998-02-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Single-strand conformation polymorphism analysis to detect p53 mutations: characterization and development of controls. AN - 79525967; 9439440 AB - Single-strand conformation polymorphism (SSCP) analysis is widely used to prescreen mutations in p53 gene. However, standardization of SSCP to detect p53 mutations has rarely been pursued so far. We have developed complete conditions for a temperature-controlled nonradioactive SSCP for mutation detection in amplified p53 exons 4-8, where mutations frequently occur in human tumors. Easily obtainable and clearly distinguishable positive controls were developed by replacing the regular 5' primers in amplification with primers that include one to three mutated sites. Careful purification of the amplified products by gel electrophoresis appeared to be essential. The efficiency of the method was studied by using previously sequenced samples with p53 mutations and the various positive controls. The use of two temperatures (exon 4: 4 degrees C and 15 degrees C; other exons: 4 degrees C and 20 degrees C) in combination with other optimized conditions resulted in 98% efficiency in mutation detection, which was considered sufficient for routine screening. JF - Clinical chemistry AU - Welsh, J A AU - Castrén, K AU - Vähäkangas, K H AD - Laboratory of Human Carcinogenesis, NCI, National Institutes of Health, Bethesda, MD 20892, USA. welshj@intra.nci.nih.gov Y1 - 1997/12// PY - 1997 DA - December 1997 SP - 2251 EP - 2255 VL - 43 IS - 12 SN - 0009-9147, 0009-9147 KW - Index Medicus KW - Reproducibility of Results KW - Exons KW - Humans KW - Reference Standards KW - Temperature KW - Polymorphism, Single-Stranded Conformational KW - Genes, p53 KW - Mutation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79525967?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+chemistry&rft.atitle=Single-strand+conformation+polymorphism+analysis+to+detect+p53+mutations%3A+characterization+and+development+of+controls.&rft.au=Welsh%2C+J+A%3BCastr%C3%A9n%2C+K%3BV%C3%A4h%C3%A4kangas%2C+K+H&rft.aulast=Welsh&rft.aufirst=J&rft.date=1997-12-01&rft.volume=43&rft.issue=12&rft.spage=2251&rft.isbn=&rft.btitle=&rft.title=Clinical+chemistry&rft.issn=00099147&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-02-05 N1 - Date created - 1998-02-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Lactoperoxidase-catalyzed oxidation of the anticancer agent mitoxantrone by nitrogen dioxide (NO2.) radicals. AN - 79521195; 9437521 AB - Mitoxantrone [1,4-dihydroxy-5,8-bis[[2-[(2-hydroxyethyl)amino]ethyl] amino]-9,10-anthracenedione, MXH2] is a novel anticancer agent frequently employed in the chemotherapy of leukemia and breast cancer. Earlier studies have shown that metabolic oxidation to reactive 1,4-quinone or/and 5,8-diiminequinone intermediates may be an important mechanism of activation of this agent, pertinent to its cytotoxic action in vivo. Here we report that in the presence of nitrite ions (NO2-), MXH2 undergoes oxidation by the mammalian enzyme lactoperoxidase (LPO) and hydrogen peroxide and that the process proceeds at a rate that is proportional to NO2- concentration. In contrast, when MXH2 was exposed to LPO/H2O2 in the absence of nitrite, oxidation of the drug was either completely absent or markedly inhibited. These experiments were carried out using concentrated solutions of MXH2 (approximately 100 microM) at near neutral pH where dimers of the drug predominate. We propose that oxidation of MXH2 is mediated by an LPO/ H2O2 metabolite of NO2-, most likely the .NO2 radical. Because in mitoxantrone therapy the drug is administered intravenously, it is directly exposed to nitrogen oxides and other free radicals produced by blood components. It is therefore possible that the ability of mitoxantrone to react with the nitrogen dioxide radical may be relevant to the biological action of the drug in vivo. JF - Chemical research in toxicology AU - Reszka, K J AU - Matuszak, Z AU - Chignell, C F AD - Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences/NIH, Research Triangle Park, North Carolina 27709, USA. reszka@niehs.nih.gov Y1 - 1997/12// PY - 1997 DA - December 1997 SP - 1325 EP - 1330 VL - 10 IS - 12 SN - 0893-228X, 0893-228X KW - Antineoplastic Agents KW - 0 KW - Free Radicals KW - Nitrates KW - sodium nitrate KW - 8M4L3H2ZVZ KW - Hydrogen Peroxide KW - BBX060AN9V KW - Mitoxantrone KW - BZ114NVM5P KW - Lactoperoxidase KW - EC 1.11.1.- KW - Nitrogen Dioxide KW - S7G510RUBH KW - Index Medicus KW - Oxidation-Reduction KW - Animals KW - Spectrometry, Fluorescence KW - Hydrogen-Ion Concentration KW - Hydrogen Peroxide -- pharmacology KW - Nitrates -- administration & dosage KW - Mitoxantrone -- chemistry KW - Mitoxantrone -- metabolism KW - Antineoplastic Agents -- metabolism KW - Lactoperoxidase -- metabolism KW - Nitrogen Dioxide -- pharmacology KW - Antineoplastic Agents -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79521195?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Lactoperoxidase-catalyzed+oxidation+of+the+anticancer+agent+mitoxantrone+by+nitrogen+dioxide+%28NO2.%29+radicals.&rft.au=Reszka%2C+K+J%3BMatuszak%2C+Z%3BChignell%2C+C+F&rft.aulast=Reszka&rft.aufirst=K&rft.date=1997-12-01&rft.volume=10&rft.issue=12&rft.spage=1325&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 - 1998-02-19 N1 - Date created - 1998-02-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A monoclonal antibody inhibitory to human P450 2D6: a paradigm for use in combinatorial determination of individual P450 role in specific drug tissue metabolism. AN - 79518560; 9429232 AB - Human cytochrome P450 2D6 metabolizes more than 50 common drugs and is polymorphically expressed, with 5-10% of the population lacking expression caused by mutant genes. This may result in a defective and toxic response in deficient individuals treated with 2D6 drug substrates. Baculovirus-expressed 2D6 was used to immunize mice for hybridoma production and two clones yielded monoclonal antibodies, that were positive against 2D6 by ELISA and inhibited 2D6 catalysed metabolism of bufuralol, dextromethorphan and phenanthrene by more than 90%. The inhibitory activity was highly specific to 2D6 and the monoclonal antibodies did not bind to 11 other P450s, nor inhibit seven human P450s tested. Analysis of eight human liver microsome samples showed that their basal bufuralol 1'-hydroxylase activity varied from 6.7-83.5 pmol min-1 nmol-1 P450. The monoclonal antibody 512-1-8 inhibited 2D6-dependent bufuralol 1'-hydroxylase in these samples by 10-70% indicating a widely variable role for 2D6 in human liver bufuralol 1'-hydroxylase activity and a role for other P450s in bufuralol metabolism. Independent analysis of several recombinant human P450s showed that 2D6, 2C8, 2C9, 2C19 and 1A2 exhibited bufuralol 1'-hydroxylase activity with 2D6 and 2C19 being the most active. Further analysis of three liver samples was made with individual inhibitory monoclonal antibodies. Inhibitory antibodies to 2D6, 2B6, 2E1, 2C8/9/19, 3A4 and 1A2 were added to the microsomes either singly or additively. Inhibitory activity of bufuralol 1'-hydroxylase was observed with antibodies to 2D6 (14-76%), 2C8/9/19 (24-69%) and 1A2 (2-25%) indicating a variable and different role for each of these P450s in the bufuralol 1'-hydroxylase of human liver. The monoclonal antibodies to 2B6, 2E1 and 3A4 were not inhibitory, indicating that these enzymes play no role in bufuralol 1'-hydroxylase metabolism. When the three antibodies to 2D6, 2C8/9/19 and 1A2, respectively, were all added, the total bufuralol 1'-hydroxylase of the liver samples was inhibited by more than 90%, indicating that the latter P450s catalyse all of liver bufuralol 1'-hydroxylase metabolism. These studies demonstrate that inhibitory monoclonal antibodies offer a simple and precise method for assessing the quantitative role of each P450 in the metabolism of a P450 substrate in a tissue, which include drugs, carcinogens, mutagens, toxic chemicals and endobiotics. JF - Pharmacogenetics AU - Gelboin, H V AU - Krausz, K W AU - Shou, M AU - Gonzalez, F J AU - Yang, T J AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, Bethesda, MD 20892, USA. gelboinh@intra.nci.nih.gov Y1 - 1997/12// PY - 1997 DA - December 1997 SP - 469 EP - 477 VL - 7 IS - 6 SN - 0960-314X, 0960-314X KW - Antibodies, Monoclonal KW - 0 KW - Cytochrome P-450 CYP2D6 Inhibitors KW - Ethanolamines KW - Phenanthrenes KW - phenanthrene KW - 448J8E5BST KW - Dextromethorphan KW - 7355X3ROTS KW - bufuralol KW - 891H89GFT4 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Mixed Function Oxygenases KW - EC 1.- KW - Cytochrome P-450 CYP2D6 KW - EC 1.14.14.1 KW - bufuralol 1'-hydroxylase KW - EC 1.14.99.- KW - Index Medicus KW - Phenanthrenes -- metabolism KW - Animals KW - Ethanolamines -- metabolism KW - Dextromethorphan -- metabolism KW - Mixed Function Oxygenases -- metabolism KW - Humans KW - Cytochrome P-450 Enzyme System -- metabolism KW - Mice KW - Tissue Distribution KW - Mice, Inbred BALB C KW - Antibodies, Monoclonal -- biosynthesis KW - Microsomes, Liver -- metabolism KW - Microsomes, Liver -- enzymology KW - Cytochrome P-450 CYP2D6 -- immunology KW - Antibodies, Monoclonal -- pharmacology KW - Cytochrome P-450 CYP2D6 -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79518560?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pharmacogenetics&rft.atitle=A+monoclonal+antibody+inhibitory+to+human+P450+2D6%3A+a+paradigm+for+use+in+combinatorial+determination+of+individual+P450+role+in+specific+drug+tissue+metabolism.&rft.au=Gelboin%2C+H+V%3BKrausz%2C+K+W%3BShou%2C+M%3BGonzalez%2C+F+J%3BYang%2C+T+J&rft.aulast=Gelboin&rft.aufirst=H&rft.date=1997-12-01&rft.volume=7&rft.issue=6&rft.spage=469&rft.isbn=&rft.btitle=&rft.title=Pharmacogenetics&rft.issn=0960314X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-02-10 N1 - Date created - 1998-02-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of dietary fat on codon 12 and 13 Ha-ras gene mutations in 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine-induced rat mammary gland tumors. AN - 79517779; 9433479 AB - Activating mutations in and expression of the Ha-ras gene were examined in benign and malignant female Sprague-Dawley rat mammary gland tumors induced by the heterocyclic amine 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and promoted by a diet high in polyunsaturated fat. Ha-ras mutations were detected in codons 12 and 13 by selective polymerase chain reaction amplification of mutated sequences and nucleotide sequencing. The percentage of Ha-ras mutations in carcinomas from PhIP-treated rats was significantly higher in rats on a low-fat diet than in rats on a high-fat diet (82% (nine of 11) vs 26% (seven of 27), respectively, P < 0.01). In addition, whereas 56% of the carcinomas with Ha-ras mutations from rats on a low-fat diet carried double Ha-ras mutations, none of the carcinomas from rats on a high-fat diet had double mutations. Ha-ras mutations were also detected in benign tumors (largely adenomas) induced by PhIP in rats on different diets; two of eight and three of four benign tumors examined from rats on low-fat and high-fat diets, respectively, had Ha-ras mutations, suggesting that activating Ha-ras mutations alone are not sufficient for PhIP-induced tumors to become malignant. No differences were observed in the level of Ha-ras mRNA expression in the different groups. In our animal model, a high-fat diet increased the incidence and percentage of malignant PhIP-induced mammary gland tumors yet decreased the percentage of carcinomas showing Ha-ras mutations. Thus, the complement of genetic alterations associated with PhIP-induced mammary gland carcinogenesis is probably altered by the level of dietary fat. JF - Molecular carcinogenesis AU - Roberts-Thomson, S J AU - Snyderwine, E G AD - Chemical Carcinogenesis Section, National Cancer Institute, Bethesda, Maryland 20892-4255, USA. Y1 - 1997/12// PY - 1997 DA - December 1997 SP - 348 EP - 354 VL - 20 IS - 4 SN - 0899-1987, 0899-1987 KW - Carcinogens KW - 0 KW - Codon KW - Dietary Fats, Unsaturated KW - Imidazoles KW - RNA, Messenger KW - 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine KW - 909C6UN66T KW - Index Medicus KW - Rats KW - Polymerase Chain Reaction KW - Animals KW - Rats, Sprague-Dawley KW - Base Sequence KW - Transcription, Genetic KW - RNA, Messenger -- biosynthesis KW - Female KW - Mutagenesis KW - Genes, ras KW - Mammary Neoplasms, Experimental -- chemically induced KW - Point Mutation KW - Mammary Neoplasms, Experimental -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79517779?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+carcinogenesis&rft.atitle=Effect+of+dietary+fat+on+codon+12+and+13+Ha-ras+gene+mutations+in+2-amino-1-methyl-6-phenylimidazo%5B4%2C5-b%5Dpyridine-induced+rat+mammary+gland+tumors.&rft.au=Roberts-Thomson%2C+S+J%3BSnyderwine%2C+E+G&rft.aulast=Roberts-Thomson&rft.aufirst=S&rft.date=1997-12-01&rft.volume=20&rft.issue=4&rft.spage=348&rft.isbn=&rft.btitle=&rft.title=Molecular+carcinogenesis&rft.issn=08991987&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-02-05 N1 - Date created - 1998-02-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Radioimmunotherapy targeting of HER2/neu oncoprotein on ovarian tumor using lead-212-DOTA-AE1. AN - 79513197; 9430475 AB - The specificity, toxicity and efficacy of lead (212Pb) radioimmunotherapy were evaluated in nude mice bearing the SK-OV-3 human ovarian tumor cell line expressing the HER2/neu proto-oncogene. The therapeutic agent used was the tumor-specific anti-HER2/neu monoclonal antibody AE1 conjugated to 212Pb, 212Bi being the daughter and thus the source of the alpha-particle and beta emissions. A bifunctional derivative of tetraazacyclododecanetetraacetic acid (p-SCN-Bz-DOTA) was used to couple 212Pb to the anti-HER2/neu monoclonal antibody AE1. The chelating agent did not alter the binding affinity to its antigenic target or the pharmacokinetics and tissue distribution of the AE1 antibody. Toxicity and therapeutic efficacy of 212Pb-AE1 were evaluated in nude mouse ascites or solid tumor models, wherein SK-OV-3 cells were administered i.p. or s.c., respectively. The dose-limiting acute toxicity after i.v. administration of 212Pb-AE1 was bone marrow suppression, which was observed at doses above 25 microCi. Therefore, doses of 10 and 20 microCi were used in efficacy trials. The i.p. administration of 212Pb-AE1 3 days after i.p. tumor inoculation led to a significant (P2 = 0.015) prolongation of tumor-free survival. In a second model, i.v. treatment with 212Pb-AE1 3 days after s.c. tumor inoculation prevented subsequent tumor development in all animals treated with 10 or 20 microCi of 212Pb-AE1 (P2 = 0.002 compared to control groups). This efficacy in the adjuvant setting was antibody specific because treatments with equivalently labeled control antibody or unlabeled AE1 antibody or no treatment were less effective. The rate of growth of small (mean tumor volume, 15 mm3) SK-OV-3 tumors was modestly inhibited. However, tumor growth was not inhibited in mice bearing larger (mean tumor volume, 146 mm3) SK-OV-3 tumors by the administration of a single dose of 10 or 20 microCi of 212Pb-AE1. Lead-212-AE1 as an intact radiolabeled monoclonal antibody may be of only modest value in the therapy of bulky solid tumors due to the short physical half-life of 212Pb and time required to achieve a useful tumor-to-normal tissue ratio of radionuclide after administration. However, the radiolabeled monoclonal antibody may be useful in therapy of tumors in the adjuvant setting. Furthermore, 212Pb may be of value in select situations, including treatment of leukemia, intercavitary therapy or strategies that target vascular endothelial cells of tumors. JF - Journal of nuclear medicine : official publication, Society of Nuclear Medicine AU - Horak, E AU - Hartmann, F AU - Garmestani, K AU - Wu, C AU - Brechbiel, M AU - Gansow, O A AU - Landolfi, N F AU - Waldmann, T A AD - Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1997/12// PY - 1997 DA - December 1997 SP - 1944 EP - 1950 VL - 38 IS - 12 SN - 0161-5505, 0161-5505 KW - Antibodies, Monoclonal KW - 0 KW - Lead Radioisotopes KW - Receptor, ErbB-2 KW - EC 2.7.10.1 KW - Index Medicus KW - Neoplasm Transplantation KW - Animals KW - Antibodies, Monoclonal -- pharmacokinetics KW - Humans KW - Mice, Nude KW - Mice KW - Tissue Distribution KW - Female KW - Antibodies, Monoclonal -- therapeutic use KW - Ovarian Neoplasms -- metabolism KW - Radioimmunotherapy KW - Ovarian Neoplasms -- radiotherapy KW - Receptor, ErbB-2 -- metabolism KW - Lead Radioisotopes -- therapeutic use KW - Lead Radioisotopes -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79513197?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+nuclear+medicine+%3A+official+publication%2C+Society+of+Nuclear+Medicine&rft.atitle=Radioimmunotherapy+targeting+of+HER2%2Fneu+oncoprotein+on+ovarian+tumor+using+lead-212-DOTA-AE1.&rft.au=Horak%2C+E%3BHartmann%2C+F%3BGarmestani%2C+K%3BWu%2C+C%3BBrechbiel%2C+M%3BGansow%2C+O+A%3BLandolfi%2C+N+F%3BWaldmann%2C+T+A&rft.aulast=Horak&rft.aufirst=E&rft.date=1997-12-01&rft.volume=38&rft.issue=12&rft.spage=1944&rft.isbn=&rft.btitle=&rft.title=Journal+of+nuclear+medicine+%3A+official+publication%2C+Society+of+Nuclear+Medicine&rft.issn=01615505&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-02-05 N1 - Date created - 1998-02-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Acidic urine pH is associated with elevated levels of free urinary benzidine and N-acetylbenzidine and urothelial cell DNA adducts in exposed workers. AN - 79507408; 9419400 AB - We evaluated the influence of urine pH on the proportion of urinary benzidine (BZ) and N-acetylbenzidine present in the free, unconjugated state and on exfoliated urothelial cell DNA adduct levels in 32 workers exposed to BZ in India. Postworkshift urine pH was inversely correlated with the proportions of BZ (r = -0.78; P or = 7. As reported previously, polymorphisms in NAT1, NAT2, and GSTM1 had no impact on DNA adduct levels. This is the first study to demonstrate that urine pH has a strong influence on the presence of free urinary aromatic amine compounds and on urothelial cell DNA adduct levels in exposed humans. Because there is evidence that acidic urine has a similar influence on aromatic amines derived from cigarette smoke, urine pH, which is influenced by diet, may be an important susceptibility factor for bladder cancer caused by tobacco in the general population. 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 - Talaska, G AU - Hayes, R B AU - Bhatnagar, V K AU - Bell, D A AU - Lakshmi, V M AU - Kashyap, S K AU - Dosemeci, M AU - Kashyap, R AU - Hsu, F F AU - Jaeger, M AU - Hirvonen, A AU - Parikh, D J AU - Davis, B B AU - Zenser, T V AD - Occupational Epidemiology Branch, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1997/12// PY - 1997 DA - December 1997 SP - 1039 EP - 1042 VL - 6 IS - 12 SN - 1055-9965, 1055-9965 KW - Benzidines KW - 0 KW - DNA Adducts KW - benzidine KW - 2X02101HVF KW - N-acetylbenzidine KW - Q1I4IM38KC KW - Index Medicus KW - Genotype KW - Analysis of Variance KW - Urothelium -- drug effects KW - Hydrogen-Ion Concentration KW - Humans KW - DNA Adducts -- analysis KW - Urine KW - Benzidines -- analysis KW - Occupational Exposure -- analysis KW - Benzidines -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79507408?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Acidic+urine+pH+is+associated+with+elevated+levels+of+free+urinary+benzidine+and+N-acetylbenzidine+and+urothelial+cell+DNA+adducts+in+exposed+workers.&rft.au=Rothman%2C+N%3BTalaska%2C+G%3BHayes%2C+R+B%3BBhatnagar%2C+V+K%3BBell%2C+D+A%3BLakshmi%2C+V+M%3BKashyap%2C+S+K%3BDosemeci%2C+M%3BKashyap%2C+R%3BHsu%2C+F+F%3BJaeger%2C+M%3BHirvonen%2C+A%3BParikh%2C+D+J%3BDavis%2C+B+B%3BZenser%2C+T+V&rft.aulast=Rothman&rft.aufirst=N&rft.date=1997-12-01&rft.volume=6&rft.issue=12&rft.spage=1039&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 - 1998-01-22 N1 - Date created - 1998-01-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Neurochemistry of cocaine withdrawal. AN - 79501964; 9425570 AB - Neural circuits comprised of dopamine-containing and dopamine-receptive neurons are altered functionally after the repeated intermittent administration of cocaine and its withdrawal. The characterization of these neuroadaptive changes at various times after repeated exposure to cocaine is important because they may relate to addictive or withdrawal states associated with cocaine abuse. They also may suggest targets leading to the development of medications to treat one or more aspects of cocaine dependence. JF - Current opinion in neurology AU - Pilotte, N S AD - National Institute on Drug Abuse, Division of Basic Research, Rockville, MD 20857, USA. np22f@nih.gov Y1 - 1997/12// PY - 1997 DA - December 1997 SP - 534 EP - 538 VL - 10 IS - 6 SN - 1350-7540, 1350-7540 KW - Narcotics KW - 0 KW - Cocaine KW - I5Y540LHVR KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Animals KW - Humans KW - Dopamine -- physiology KW - Substance Withdrawal Syndrome -- metabolism KW - Brain Chemistry -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79501964?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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&rft.atitle=Neurochemistry+of+cocaine+withdrawal.&rft.au=Pilotte%2C+N+S&rft.aulast=Pilotte&rft.aufirst=N&rft.date=1997-12-01&rft.volume=10&rft.issue=6&rft.spage=534&rft.isbn=&rft.btitle=&rft.title=Current+opinion+in+neurology&rft.issn=13507540&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-05 N1 - Date created - 1998-03-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characterization of a novel bisacridone and comparison with PSC 833 as a potent and poorly reversible modulator of P-glycoprotein. AN - 79497000; 9415704 AB - Novel compounds, composed of two acridone moieties connected by a propyl or butyl spacer, were synthesized and tested as potential modulators of P-glycoprotein (P-gp)-mediated multidrug resistance. The propyl derivative 1,3-bis(9-oxoacridin-10-yl)-propane (PBA) was extremely potent and, at a concentration of 1 microM, increased steady state accumulation of vinblastine (VLB) approximately 9-fold in the multidrug-resistant cell line KB8-5. In contrast to the readily reversible effects of VRP and cyclosporin A on VLB uptake and similar to the effects of the cyclosporin analog PSC 833, this modulation by PBA was not fully reversed 6-8 hr after transfer of cells to PBA-free medium. Continuous exposure to 3 microM PBA was nontoxic and could completely reverse VLB resistance in KB8-5 cells. Consistent with its effects on VLB transport, the drug resistance-modulating effect of PSC 833 was significantly more persistent than that of VRP. However, the effect of PBA was, like that of VRP, rapidly reversed once the modulator was removed from the extracellular environment. PBA was able to compete with radiolabeled azidopine for binding to P-gp and to stimulate P-gp ATPase activity. However, both the steady state accumulation of PBA and the rate of efflux of PBA were similar in drug-sensitive KB3-1 and drug-resistant KB8-5 cells, suggesting that this compound is not efficiently transported by P-gp. These results indicate that PBA represents a new class of potent and poorly reversible synthetic modulators of P-gp-mediated VLB transport. JF - Molecular pharmacology AU - Horton, J K AU - Thimmaiah, K N AU - Altenberg, G A AU - Castro, A F AU - Germain, G S AU - Gowda, G K AU - Houghton, P J AD - Sealy Center for Molecular Science, University of Texas Medical Branch, Galveston 77555, USA. horton1@niehs.nih.gov Y1 - 1997/12// PY - 1997 DA - December 1997 SP - 948 EP - 957 VL - 52 IS - 6 SN - 0026-895X, 0026-895X KW - Acridines KW - 0 KW - Antineoplastic Agents, Phytogenic KW - Cyclosporins KW - Fluorescent Dyes KW - P-Glycoprotein KW - Rhodamines KW - Rhodamine 123 KW - 1N3CZ14C5O KW - Vinblastine KW - 5V9KLZ54CY KW - acridone KW - 6BK306GUQA KW - Adenosine Triphosphatases KW - EC 3.6.1.- KW - valspodar KW - Q7ZP55KF3X KW - Index Medicus KW - KB Cells KW - Drug Interactions KW - Humans KW - Vinblastine -- pharmacokinetics KW - Adenosine Triphosphatases -- metabolism KW - Carcinoma, Squamous Cell -- metabolism KW - Vinblastine -- toxicity KW - Drug Resistance, Multiple KW - Antineoplastic Agents, Phytogenic -- pharmacokinetics KW - Antineoplastic Agents, Phytogenic -- toxicity KW - Tumor Cells, Cultured KW - Fluorescent Dyes -- pharmacokinetics KW - Carcinoma, Squamous Cell -- drug therapy KW - Rhodamines -- pharmacokinetics KW - Acridines -- pharmacology KW - P-Glycoprotein -- drug effects KW - P-Glycoprotein -- metabolism KW - Cyclosporins -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79497000?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+a+novel+bisacridone+and+comparison+with+PSC+833+as+a+potent+and+poorly+reversible+modulator+of+P-glycoprotein.&rft.au=Horton%2C+J+K%3BThimmaiah%2C+K+N%3BAltenberg%2C+G+A%3BCastro%2C+A+F%3BGermain%2C+G+S%3BGowda%2C+G+K%3BHoughton%2C+P+J&rft.aulast=Horton&rft.aufirst=J&rft.date=1997-12-01&rft.volume=52&rft.issue=6&rft.spage=948&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 - 1998-01-29 N1 - Date created - 1998-01-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The Saccharomyces cerevisiae RAD30 gene, a homologue of Escherichia coli dinB and umuC, is DNA damage inducible and functions in a novel error-free postreplication repair mechanism. AN - 79486197; 9409821 AB - Damage-inducible mutagenesis in prokaryotes is largely dependent upon the activity of the UmuD'C-like proteins. Since many DNA repair processes are structurally and/or functionally conserved between prokaryotes and eukaryotes, we investigated the role of RAD30, a previously uncharacterized Saccharomyces cerevisiae DNA repair gene related to the Escherichia coli dinB, umuC and S. cerevisiae REV1 genes, in UV resistance and UV-induced mutagenesis. Similar to its prokaryotic homologues, RAD30 was found to be damage inducible. Like many S. cerevisiae genes involved in error-prone DNA repair, epistasis analysis clearly places RAD30 in the RAD6 group and rad30 mutants display moderate UV sensitivity reminiscent of rev mutants. However, unlike rev mutants, no defect in UV-induced reversion was seen in rad30 strains. While rad6 and rad18 are both epistatic to rad30, no epistasis was observed with rev1, rev3, rev7 or rad5, all of which are members of the RAD6 epistasis group. These findings suggest that RD30 participates in a novel error-free repair pathway dependent on RAD6 and RAD18, but independent of REV1, REV3, REV7 and RAD5. JF - Genetics AU - McDonald, J P 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 20892-2725, USA. Y1 - 1997/12// PY - 1997 DA - December 1997 SP - 1557 EP - 1568 VL - 147 IS - 4 SN - 0016-6731, 0016-6731 KW - Bacterial Proteins KW - 0 KW - DinB protein, E coli KW - Escherichia coli Proteins KW - Fungal Proteins KW - RNA, Fungal KW - Saccharomyces cerevisiae Proteins KW - UmuC protein, E coli KW - 98059-80-4 KW - RAD6 protein, S cerevisiae KW - EC 2.3.2.23 KW - Ubiquitin-Conjugating Enzymes KW - DNA-Directed DNA Polymerase KW - EC 2.7.7.7 KW - Adenosine Triphosphatases KW - EC 3.6.1.- KW - RAD5 protein, S cerevisiae KW - DNA Helicases KW - EC 3.6.4.- KW - Ligases KW - EC 6.- KW - Index Medicus KW - Ligases -- genetics KW - Ultraviolet Rays KW - Bacterial Proteins -- chemistry KW - Molecular Sequence Data KW - Escherichia coli -- genetics KW - Amino Acid Sequence KW - Epistasis, Genetic KW - DNA Replication KW - Mutagenesis KW - Cloning, Molecular KW - Saccharomyces cerevisiae -- genetics KW - Fungal Proteins -- chemistry KW - Fungal Proteins -- physiology KW - DNA Repair -- physiology KW - Genes, Fungal KW - DNA Damage KW - Fungal Proteins -- genetics KW - Saccharomyces cerevisiae -- radiation effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79486197?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+Saccharomyces+cerevisiae+RAD30+gene%2C+a+homologue+of+Escherichia+coli+dinB+and+umuC%2C+is+DNA+damage+inducible+and+functions+in+a+novel+error-free+postreplication+repair+mechanism.&rft.au=McDonald%2C+J+P%3BLevine%2C+A+S%3BWoodgate%2C+R&rft.aulast=McDonald&rft.aufirst=J&rft.date=1997-12-01&rft.volume=147&rft.issue=4&rft.spage=1557&rft.isbn=&rft.btitle=&rft.title=Genetics&rft.issn=00166731&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-02-19 N1 - Date created - 1998-02-19 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Mol Biol. 1976 Mar 5;101(3):417-25 [1255724] J Mol Biol. 1975 Nov 5;98(3):503-17 [1195397] Proc Natl Acad Sci U S A. 1981 Sep;78(9):5749-53 [7029544] Mol Gen Genet. 1981;184(3):471-8 [7038396] Methods Enzymol. 1983;101:228-45 [6310326] Proc Natl Acad Sci U S A. 1985 Jan;82(1):168-72 [3881753] Proc Natl Acad Sci U S A. 1986 Jun;83(11):3904-8 [2940594] 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] Microbiol Rev. 1988 Mar;52(1):70-102 [3280967] Nucleic Acids Res. 1988 Jul 25;16(14B):7119-31 [2970061] J Bacteriol. 1989 Jan;171(1):230-7 [2492497] Cell. 1989 Feb 24;56(4):619-30 [2645056] J Bacteriol. 1989 Oct;171(10):5659-67 [2676986] Proc Natl Acad Sci U S A. 1989 Oct;86(19):7301-5 [2552436] Nucleic Acids Res. 1990 May 25;18(10):3091-2 [2190191] Mutat Res. 1990 Jun;230(2):241-54 [2165215] J Mol Biol. 1990 Oct 5;215(3):403-10 [2231712] Methods Enzymol. 1991;194:281-301 [2005793] Nucleic Acids Res. 1991 Feb 25;19(4):893-8 [2017370] Annu Rev Biochem. 1991;60:477-511 [1883202] Biochimie. 1991 Apr;73(4):479-84 [1911948] Nucleic Acids Res. 1992 Mar 25;20(6):1425 [1561104] Mol Cell Biol. 1992 Sep;12(9):3807-18 [1324406] Proc Natl Acad Sci U S A. 1993 Sep 1;90(17):8169-73 [8367479] Mol Cell Biol. 1993 Dec;13(12):7213-21 [8246943] Nature. 1994 Mar 3;368(6466):32-8 [7906398] Radiat Res. 1994 Jul;139(1):24-33 [8016304] J Bacteriol. 1996 May;178(9):2559-63 [8626322] J Biol Chem. 1996 May 3;271(18):10767-74 [8631887] Mol Gen Genet. 1996 May 23;251(2):167-75 [8668127] Proc Natl Acad Sci U S A. 1996 Jul 23;93(15):7805-10 [8755557] Proc Natl Acad Sci U S A. 1996 Sep 3;93(18):9676-81 [8790390] Mutat Res. 1996 Oct 25;357(1-2):245-53 [8876701] Cancer Surv. 1996;28:117-40 [8977032] J Mol Biol. 1971 Oct 14;61(1):25-44 [4947693] J Mol Biol. 1974 Jul 25;87(1):103-19 [4610149] J Bacteriol. 1981 Apr;146(1):285-90 [7012117] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Glomerulosclerosis, arteriosclerosis, and vascular graft stenosis: treatment with oral heparinoids. AN - 79484425; 9407438 AB - At present there is no known treatment for established glomerulosclerosis or atherosclerosis. Since the principal lesion in glomerulosclerosis involves mesangial cells, a vascular smooth muscle cell, we searched for new therapeutic approaches affecting vascular smooth muscle function, especially with respect to modifying the turnover of extracellular matrix. We used mice transgenic for bovine growth hormone (bGH), since these mice develop end-stage renal disease due to progressive glomerulosclerosis. We previously showed that the subcutaneous injection of a non-anticoagulant heparin reduced glomerulosclerosis in bGH mice. Since injectable drugs are not a practical means of controlling glomerulosclerosis in humans, we assessed oral heparin-like compounds and found that oral pentosan polysulfate (PPS) reduced glomerulosclerosis in bGH mice at non-toxic doses. Because the positive therapeutic response in the bGH model could have been principally hormone-mediated, we examined other models of non-immune mediated glomerulosclerosis, including ROP Os/+ non-diabetic and diabetic mice. We found that an oral PPS (Elmiron), which is approved for other indications in humans, reduced sclerosis in all of these forms of chronic, progressive glomerulosclerosis. Based on the similarity of the cellular events in glomerulosclerosis and arteriosclerosis, we assessed the effect(s) of PPS in congenital (Watanabe rabbits) and induced (New Zealand White lipid-fed rabbits) models of arteriosclerosis. The extent and severity of the lesions was significantly reduced in both models by PPS treatment. Finally, we asked whether the proliferative and sclerotic lesion, which is the cause of vascular graft stenosis, might also respond to PPS treatment. To do this we cultured cells from the materials removed from stenotic arteriovenous grafts in hemodialysis patients. We found that PPS inhibits the proliferation and matrix production in a dose-dependent manner. JF - Kidney international. Supplement AU - Striker, G E AU - Lupia, E AU - Elliot, S AU - Zheng, F AU - McQuinn, C AU - Blagg, C AU - Selim, S AU - Vilar, J AU - Striker, L J AD - Renal Cell Biology Section, MDB, NIDDK, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1997/12// PY - 1997 DA - December 1997 SP - S120 EP - S123 VL - 63 SN - 0098-6577, 0098-6577 KW - Anticoagulants KW - 0 KW - Heparin KW - 9005-49-6 KW - Index Medicus KW - Animals KW - Cattle KW - Humans KW - Rabbits KW - Mice KW - Mice, Transgenic KW - Glomerulosclerosis, Focal Segmental -- pathology KW - Glomerulosclerosis, Focal Segmental -- drug therapy KW - Anticoagulants -- therapeutic use KW - Graft Occlusion, Vascular -- drug therapy KW - Heparin -- therapeutic use KW - Glomerulosclerosis, Focal Segmental -- etiology KW - Arteriosclerosis -- drug therapy KW - Arteriosclerosis -- pathology KW - Arteriosclerosis -- etiology KW - Graft Occlusion, Vascular -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79484425?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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.+Supplement&rft.atitle=Glomerulosclerosis%2C+arteriosclerosis%2C+and+vascular+graft+stenosis%3A+treatment+with+oral+heparinoids.&rft.au=Striker%2C+G+E%3BLupia%2C+E%3BElliot%2C+S%3BZheng%2C+F%3BMcQuinn%2C+C%3BBlagg%2C+C%3BSelim%2C+S%3BVilar%2C+J%3BStriker%2C+L+J&rft.aulast=Striker&rft.aufirst=G&rft.date=1997-12-01&rft.volume=63&rft.issue=&rft.spage=S120&rft.isbn=&rft.btitle=&rft.title=Kidney+international.+Supplement&rft.issn=00986577&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-02-05 N1 - Date created - 1998-02-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Compartmental model of vertebrate motoneurons for Ca2+-dependent spiking and plateau potentials under pharmacological treatment. AN - 79481954; 9405551 AB - In contrast to the limited response properties observed under normal experimental conditions, spinal motoneurons generate complex firing patterns, such as Ca2+-dependent regenerative spiking and plateaus, in the presence of certain neurotransmitters and ion-channel blockers. We have developed a quantitative motoneuron model, based on turtle motoneuron data, toinvestigate the roles of specific ionic currents and the effects of their soma and dendritic distribution in generating these complex firing patterns. In addition, the model is used to explore the effects of multiple ion channel blockers and neurotransmitters that are known to modulate motoneuron firing patterns. To represent the distribution of ionic currents across the soma and dendrites, the model contains two compartments. The soma compartment, representing the soma and proximal dendrites, contains Hodgkin-Huxley-like sodium (INa) and delayed rectifier K+ (IK-dr) currents, an N-like Ca2+ current (ICa-N), and a calcium-dependent K+ current [IK(Ca)]. The dendritic compartment, representing the lumped distal dendrites, contains, in addition to ICa-N and IK(Ca) as in the soma, a persistent L-like calcium current (ICa-L). We determined kinetic parameters for INa, IK-dr, ICa-N, and IK(Ca) in order to reproduce normal action-potential firing observed in turtle spinal motoneurons, including fast and slow afterhyperpolarizations (AHPs) and a linear steady-state frequency-current relation. With this parameter set as default, a sequence of pharmacological manipulations were systematically simulated. A small reduction of IK-dr [mimicking the experimental effect of tetraethylammonium (TEA) in low concentration] enhanced the slow AHP and caused calcium spiking (mediated by ICa-N) when INa was blocked. Firing patterns observed experimentally in high TEA [and tetrodotoxin (TTX)], namely calcium spikes riding on a calcium plateau, were reproduced only when both IK-dr and IK(Ca) were reduced. Dendritic plateau potentials, mediated by ICa-L, were reliably unmasked when IK(Ca) was reduced, mimicking the experimental effect of the bee venom apamin. The effect of 5-HT, which experimentally induces the ability to generate calcium-dependent plateau potentials but not calcium spiking, was reproduced in the model by reducing IK(Ca) alone. The plateau threshold current level, however, was reduced substantially if a simultaneous increase in ICa-L was simulated, suggesting that serotonin (5-HT) induces plateau potentials by regulating more than one conductance. The onset of the plateau potential showed significant delays in response to near-threshold, depolarizing current steps. In addition, the delay times were sensitive to the current step amplitude. The delay and its sensitivity were explained by examining the model's behavior near the threshold for plateau onset. This modeling study thus accurately accounts for the basic firing behavior of vertebrate motoneurons as well as a range of complex firing patterns invoked by ion-channel blockers and 5-HT. In addition, our computational results support the hypothesis that the electroresponsiveness of motoneurons depends on a nonuniform distribution of ionic conductances, and they predict modulatory effects of 5-HT and properties of plateau activation that have yet to be tested experimentally. JF - Journal of neurophysiology AU - Booth, V AU - Rinzel, J AU - Kiehn, O AD - Mathematical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health 9190, Bethesda, Maryland 20814, USA. Y1 - 1997/12// PY - 1997 DA - December 1997 SP - 3371 EP - 3385 VL - 78 IS - 6 SN - 0022-3077, 0022-3077 KW - Potassium Channels KW - 0 KW - Apamin KW - 24345-16-2 KW - Tetrodotoxin KW - 4368-28-9 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Animals KW - Patch-Clamp Techniques KW - Electric Conductivity KW - Apamin -- pharmacology KW - Action Potentials -- drug effects KW - Tetrodotoxin -- pharmacology KW - Turtles -- physiology KW - Calcium -- pharmacology KW - Models, Neurological KW - Potassium Channels -- drug effects KW - Cats -- physiology KW - Motor Neurons -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79481954?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neurophysiology&rft.atitle=Compartmental+model+of+vertebrate+motoneurons+for+Ca2%2B-dependent+spiking+and+plateau+potentials+under+pharmacological+treatment.&rft.au=Booth%2C+V%3BRinzel%2C+J%3BKiehn%2C+O&rft.aulast=Booth&rft.aufirst=V&rft.date=1997-12-01&rft.volume=78&rft.issue=6&rft.spage=3371&rft.isbn=&rft.btitle=&rft.title=Journal+of+neurophysiology&rft.issn=00223077&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-02-05 N1 - Date created - 1998-02-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dietary restriction mitigates ozone-induced lung inflammation in rats: a role for endogenous antioxidants. AN - 79474805; 9409561 AB - Studies were undertaken to determine whether dietary restriction protects against acute pulmonary oxidant challenge. Male F344 rats were fed NIH-31 diet either ad libitum or at restricted levels equal to 75% that of ad libitum intake. After 3 wk of dietary adaptation, animals were exposed by inhalation to 2.0 ppm ozone (O3) for 2 h or chamber air and evaluated for cellular and biochemical indices of pulmonary toxicity. Compared to air controls, bronchoalveolar lavage fluid (BALF) from O3 exposed ad libitum fed rats contained increased protein (145 versus 380 microg/ml), PMN infiltration (0 versus 11%) and fibronectin (45 versus 607 U/ml). Diet restriction abrogated these indicators of pulmonary inflammation induced by ozone. Binding of 18O3 to BALF protein and cells was significantly decreased in diet restricted rats while BALF ascorbate and glutathione levels, but not alpha-tocopherol or urate, were elevated compared to ad libitum fed rats. Taken together, these results indicate that dietary restriction affords protection against O3-induced oxidant toxicity. Protection is mediated partially by increases in ascorbate in the fluid bathing the lung surface, thereby providing an antioxidant sink which minimizes the ability of O3 to reach biological targets. JF - American journal of respiratory cell and molecular biology AU - Kari, F AU - Hatch, G AU - Slade, R AU - Crissman, K AU - Simeonova, P P AU - Luster, M AD - Environmental Immunology and Neurobiology Section, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA. Y1 - 1997/12// PY - 1997 DA - December 1997 SP - 740 EP - 747 VL - 17 IS - 6 SN - 1044-1549, 1044-1549 KW - Antioxidants KW - 0 KW - Oxygen Isotopes KW - Ozone KW - 66H7ZZK23N KW - Glutathione KW - GAN16C9B8O KW - Ascorbic Acid KW - PQ6CK8PD0R KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Bronchoalveolar Lavage Fluid -- chemistry KW - Glutathione -- analysis KW - Diet KW - Ascorbic Acid -- analysis KW - Male KW - Pneumonia -- prevention & control KW - Pneumonia -- chemically induced KW - Energy Intake KW - Ozone -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79474805?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+respiratory+cell+and+molecular+biology&rft.atitle=Dietary+restriction+mitigates+ozone-induced+lung+inflammation+in+rats%3A+a+role+for+endogenous+antioxidants.&rft.au=Kari%2C+F%3BHatch%2C+G%3BSlade%2C+R%3BCrissman%2C+K%3BSimeonova%2C+P+P%3BLuster%2C+M&rft.aulast=Kari&rft.aufirst=F&rft.date=1997-12-01&rft.volume=17&rft.issue=6&rft.spage=740&rft.isbn=&rft.btitle=&rft.title=American+journal+of+respiratory+cell+and+molecular+biology&rft.issn=10441549&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-01-07 N1 - Date created - 1998-01-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In vivo footprinting using N-ethyl,N-nitrosourea: improved resolution of the DNA-protein interactions in the human gamma-globin gene promoter region. AN - 79460775; 9398338 AB - N-Ethyl, N-nitrosourea (ENU) was used as a probing agent in conjunction with a modified ligation-mediated polymerase chain reaction in a new in vivo footprinting procedure. In the present work, we examined the promoter region of the human gamma-globin gene under both uninduced and hemin-induced conditions in K562 cells. In the course of comparing this method with the standard dimethyl sulfate (DMS) in vivo method and previously reported results, we were able to verify our new method. However, discrepancies between these methods were observed at the stage selector element, -50 region, of gamma-globin promoter. Our in vivo footprinting result showed DNA-protein interaction at this region under the hemin-induced condition which was not revealed by the conventional DMS in vivo footprinting method. This approach, using ENU-modified in vivo footprinting, is now being applied to clarify the mechanism of cytotoxic drug-induced fetal hemoglobin augmentation. Copyright 1997 Academic Press. JF - Analytical biochemistry AU - Kim, I H AU - Rodgers, G P AD - Laboratory of Chemical Biology, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1997/12/01/ PY - 1997 DA - 1997 Dec 01 SP - 1 EP - 8 VL - 254 IS - 1 SN - 0003-2697, 0003-2697 KW - DNA Primers KW - 0 KW - DNA-Binding Proteins KW - Proteins KW - Sulfuric Acid Esters KW - Hemin KW - 743LRP9S7N KW - Globins KW - 9004-22-2 KW - DNA KW - 9007-49-2 KW - Fetal Hemoglobin KW - 9034-63-3 KW - dimethyl sulfate KW - JW5CW40Z50 KW - Ethylnitrosourea KW - P8M1T4190R KW - Index Medicus KW - Polymerase Chain Reaction KW - Hemin -- pharmacology KW - DNA-Binding Proteins -- analysis KW - Leukemia, Erythroblastic, Acute KW - Tumor Cells, Cultured KW - Sulfuric Acid Esters -- metabolism KW - Humans KW - Electrophoresis, Agar Gel KW - Fetal Hemoglobin -- metabolism KW - Gene Expression Regulation KW - Ethylnitrosourea -- metabolism KW - DNA -- metabolism KW - Globins -- genetics KW - DNA Footprinting -- methods KW - Promoter Regions, Genetic -- genetics KW - Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79460775?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Analytical+biochemistry&rft.atitle=In+vivo+footprinting+using+N-ethyl%2CN-nitrosourea%3A+improved+resolution+of+the+DNA-protein+interactions+in+the+human+gamma-globin+gene+promoter+region.&rft.au=Kim%2C+I+H%3BRodgers%2C+G+P&rft.aulast=Kim&rft.aufirst=I&rft.date=1997-12-01&rft.volume=254&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Analytical+biochemistry&rft.issn=00032697&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-01-27 N1 - Date created - 1998-01-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Blockade of cerebral blood flow response to insulin-induced hypoglycemia by caffeine and glibenclamide in conscious rats. AN - 79459744; 9397030 AB - The possibility that adenosine and ATP-sensitive potassium channels (KATP) might be involved in the mechanisms of the increases in cerebral blood flow (CBF) that occur in insulin-induced hypoglycemia was examined. Cerebral blood flow was measured by the [14C]iodoantipyrine method in conscious rats during insulin-induced, moderate hypoglycemia (2 to 3 mmol/L glucose in arterial plasma) after intravenous injections of 10 to 20 mg/kg of caffeine, an adenosine receptor antagonist, or intracisternal infusion of 1 to 2 mumol/L glibenclamide, a KATP channel inhibitor. Cerebral blood flow was also measured in corresponding normoglycemic and drug-free control groups. Cerebral blood flow was 51% higher in untreated hypoglycemic than in untreated normoglycemic rats (P < 0.01). Caffeine had a small, statistically insignificant effect on CBF in normoglycemic rats, but reduced the CBF response to hypoglycemia in a dose-dependent manner, i.e., 27% increase with 10 mg/kg and complete elimination with 20 mg/kg. Chemical determinations by HPLC in extracts of freeze-blown brains showed significant increases in the levels of adenosine and its degradation products, inosine and hypoxanthine, during hypoglycemia (P < 0.05). Intracisternal glibenclamide had little effect on CBF in normoglycemia, but, like caffeine, produced dose-dependent reductions in the magnitude of the increases in CBF during hypoglycemia, i.e., +66% with glibenclamide-free artificial CSF administration, +25% with 1 mumol/L glibenclamide, and almost complete blockade (+5%) with 2 mumol/L glibenclamide. These results suggest that adenosine and KATP channels may play a role in the increases in CBF during hypoglycemia. JF - Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism AU - Horinaka, N AU - Kuang, T Y AU - Pak, H AU - Wang, R AU - Jehle, J AU - Kennedy, C AU - Sokoloff, L AD - Laboratory of Cerebral Metabolism, National Institute of Mental Health, Bethesda, Maryland 20892, USA. Y1 - 1997/12// PY - 1997 DA - December 1997 SP - 1309 EP - 1318 VL - 17 IS - 12 SN - 0271-678X, 0271-678X KW - Central Nervous System Stimulants KW - 0 KW - Hypoglycemic Agents KW - Insulin KW - Potassium Channels KW - Caffeine KW - 3G6A5W338E KW - Glyburide KW - SX6K58TVWC KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Insulin -- administration & dosage KW - Male KW - Potassium Channels -- metabolism KW - Hypoglycemia -- metabolism KW - Central Nervous System Stimulants -- pharmacology KW - Hypoglycemia -- physiopathology KW - Cerebrovascular Circulation -- drug effects KW - Caffeine -- pharmacology KW - Hypoglycemic Agents -- pharmacology KW - Hypoglycemia -- chemically induced KW - Glyburide -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79459744?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+cerebral+blood+flow+and+metabolism+%3A+official+journal+of+the+International+Society+of+Cerebral+Blood+Flow+and+Metabolism&rft.atitle=Blockade+of+cerebral+blood+flow+response+to+insulin-induced+hypoglycemia+by+caffeine+and+glibenclamide+in+conscious+rats.&rft.au=Horinaka%2C+N%3BKuang%2C+T+Y%3BPak%2C+H%3BWang%2C+R%3BJehle%2C+J%3BKennedy%2C+C%3BSokoloff%2C+L&rft.aulast=Horinaka&rft.aufirst=N&rft.date=1997-12-01&rft.volume=17&rft.issue=12&rft.spage=1309&rft.isbn=&rft.btitle=&rft.title=Journal+of+cerebral+blood+flow+and+metabolism+%3A+official+journal+of+the+International+Society+of+Cerebral+Blood+Flow+and+Metabolism&rft.issn=0271678X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-12-30 N1 - Date created - 1997-12-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of the 5-HT3 antagonist, ondansetron, on the behavioral and physiological effects of pentagastrin in patients with panic disorder and social phobia. AN - 79457972; 9397424 AB - Pentagastrin, a cholecystokinin (CCK) agonist, produces anxiety and panic in patients with panic disorder and social phobia. Preclinical data suggests that pentagastrin-induced anxiogenesis may be mediated via 5-HT3 receptors. In the present study, 14 patients with panic disorder or social phobia underwent pharmacological challenge in three conditions: (1) pretreatment with saline followed by pentagastrin infusion; (2) pretreatment with ondansetron followed by pentagastrin infusion; and (3) pretreatment with saline followed by saline infusion. As expected, pentagastrin administration led to increased anxiety, physical symptoms of panic attacks, pulse, plasma adrenocorticotropic hormone (ACTH), and cortisol. Pentagastrin's behavioral effects were not blocked by ondansetron, and in fact, tended to be exaggerated. Ondansetron pretreatment did not alter the pentagastrin-induced cortisol increase but significantly prolonged the pentagastrin-induced increase in ACTH. These findings suggest that pentagastrin's behavioral effects are not mediated by 5HT3 receptors. Mechanisms by which peripherally administered CCK agonists lead to anxiety remain to be elucidated. JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology AU - McCann, U D AU - Morgan, C M AU - Geraci, M AU - Slate, S O AU - Murphy, D L AU - Post, R M AD - Biological Psychiatry Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892-1272, USA. Y1 - 1997/12// PY - 1997 DA - December 1997 SP - 360 EP - 369 VL - 17 IS - 6 SN - 0893-133X, 0893-133X KW - Hormones KW - 0 KW - Serotonin Antagonists KW - Ondansetron KW - 4AF302ESOS KW - Pentagastrin KW - EF0NX91490 KW - Index Medicus KW - Hemodynamics -- drug effects KW - Psychiatric Status Rating Scales KW - Humans KW - Interpersonal Relations KW - Adult KW - Hormones -- blood KW - Male KW - Female KW - Phobic Disorders -- chemically induced KW - Panic Disorder -- chemically induced KW - Panic Disorder -- physiopathology KW - Behavior -- drug effects KW - Panic Disorder -- psychology KW - Serotonin Antagonists -- pharmacology KW - Phobic Disorders -- psychology KW - Pentagastrin -- pharmacology KW - Ondansetron -- pharmacology KW - Phobic Disorders -- physiopathology KW - Pentagastrin -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79457972?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Effects+of+the+5-HT3+antagonist%2C+ondansetron%2C+on+the+behavioral+and+physiological+effects+of+pentagastrin+in+patients+with+panic+disorder+and+social+phobia.&rft.au=McCann%2C+U+D%3BMorgan%2C+C+M%3BGeraci%2C+M%3BSlate%2C+S+O%3BMurphy%2C+D+L%3BPost%2C+R+M&rft.aulast=McCann&rft.aufirst=U&rft.date=1997-12-01&rft.volume=17&rft.issue=6&rft.spage=360&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 - 1998-01-09 N1 - Date created - 1998-01-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Coexpression of C-myc and transforming growth factor alfa in the liver promotes early replicative senescence and diminishes regenerative capacity after partial hepatectomy in transgenic mice. AN - 79457326; 9397983 AB - We have recently shown that overexpression of c-myc and transforming growth factor alpha (TGF-alpha) in the liver of double-transgenic mice results in severe DNA damage, aberrant hepatic growth, and development of tumors at a much younger age than that observed in c-myc single-transgenic mice. We now report that double-transgenic TGF-alpha/c-myc hepatocytes rapidly lose their ability to proliferate upon mitogenic stimulation following partial hepatectomy (PH). At 4 weeks of age, the overall rate of bromodeoxyuridine (BrdU) incorporation following PH was comparable in c-myc and TGF-alpha/c-myc livers and exceeded that seen in wild-type (WT) mice. However, by 10 weeks of age, c-myc single-transgenic hepatocytes showed proliferative advantages over the WT cells, whereas TGF-alpha/c-myc double-transgenic hepatocytes had a decreased capacity to proliferate upon mitogenic stimulation. This decreased proliferative response was accompanied by a reduction in the total fraction of proliferating hepatocytes, as well as by a decline in the induction of cyclin A, cyclin B, and cdc2 gene expression. These data show that constitutive coexpression of c-myc and TGF-alpha accelerates age-related loss in the regenerative potential following PH, and suggest that early replicative senescence of differentiated hepatocytes may have a role in providing a selective growth advantage to initiated cell populations in this model. JF - Hepatology (Baltimore, Md.) AU - Factor, V M AU - Jensen, M R AU - Thorgeirsson, S S AD - Laboratory of Experimental Carcinogenesis, DBS, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA. Y1 - 1997/12// PY - 1997 DA - December 1997 SP - 1434 EP - 1443 VL - 26 IS - 6 SN - 0270-9139, 0270-9139 KW - Cell Cycle Proteins KW - 0 KW - Cyclin A KW - Cyclin B KW - Proto-Oncogene Proteins c-myc KW - Transforming Growth Factor alpha KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Cyclin A -- metabolism KW - Animals KW - Blotting, Northern KW - Aging KW - Cyclin B -- metabolism KW - DNA -- analysis KW - Mice KW - Mice, Transgenic KW - Organ Size KW - DNA -- biosynthesis KW - Cell Cycle Proteins -- metabolism KW - Cells, Cultured KW - Immunohistochemistry KW - Male KW - Cell Division KW - Liver -- anatomy & histology KW - Transforming Growth Factor alpha -- genetics KW - Hepatectomy KW - Proto-Oncogene Proteins c-myc -- genetics KW - Liver -- metabolism KW - Proto-Oncogene Proteins c-myc -- metabolism KW - Liver Regeneration -- physiology KW - Transforming Growth Factor alpha -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79457326?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Coexpression+of+C-myc+and+transforming+growth+factor+alfa+in+the+liver+promotes+early+replicative+senescence+and+diminishes+regenerative+capacity+after+partial+hepatectomy+in+transgenic+mice.&rft.au=Factor%2C+V+M%3BJensen%2C+M+R%3BThorgeirsson%2C+S+S&rft.aulast=Factor&rft.aufirst=V&rft.date=1997-12-01&rft.volume=26&rft.issue=6&rft.spage=1434&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 - 1998-01-08 N1 - Date created - 1998-01-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetic requirements and mutational specificity of the Escherichia coli SOS mutator activity. AN - 79448747; 9393709 AB - To better understand the mechanisms of SOS mutagenesis in the bacterium Escherichia coli, we have undertaken a genetic analysis of the SOS mutator activity. The SOS mutator activity results from constitutive expression of the SOS system in strains carrying a constitutively activated RecA protein (RecA730). We show that the SOS mutator activity is not enhanced in strains containing deficiencies in the uvrABC nucleotide excision-repair system or the xth and nfo base excision-repair systems. Further, recA730-induced errors are shown to be corrected by the MutHLS-dependent mismatch-repair system as efficiently as the corresponding errors in the rec+ background. These results suggest that the SOS mutator activity does not reflect mutagenesis at so-called cryptic lesions but instead represents an amplification of normally occurring DNA polymerase errors. Analysis of the base-pair-substitution mutations induced by recA730 in a mismatch repair-deficient background shows that both transition and transversion errors are amplified, although the effect is much larger for transversions than for transitions. Analysis of the mutator effect in various dnaE strains, including dnaE antimutators, as well as in proofreading-deficient dnaQ (mutD) strains suggests that in recA730 strains, two types of replication errors occur in parallel: (i) normal replication errors that are subject to both exonucleolytic proofreading and dnaE antimutator effects and (ii) recA730-specific errors that are not susceptible to either proofreading or dnaE antimutator effects. The combined data are consistent with a model suggesting that in recA730 cells error-prone replication complexes are assembled at sites where DNA polymerization is temporarily stalled, most likely when a normal polymerase insertion error has created a poorly extendable terminal mismatch. The modified complex forces extension of the mismatch largely at the exclusion of proofreading and polymerase dissociation pathways. SOS mutagenesis targeted at replication-blocking DNA lesions likely proceeds in the same manner. JF - Journal of bacteriology 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, USA. Y1 - 1997/12// PY - 1997 DA - December 1997 SP - 7435 EP - 7445 VL - 179 IS - 23 SN - 0021-9193, 0021-9193 KW - Escherichia coli Proteins KW - 0 KW - DNA Polymerase II KW - EC 2.7.7.- KW - DNA Polymerase III KW - DNA polymerase III, alpha subunit KW - Rec A Recombinases KW - Endodeoxyribonucleases KW - EC 3.1.- KW - endodeoxyribonuclease uvrABC KW - EC 3.1.25.- KW - Index Medicus KW - DNA Repair KW - DNA Polymerase II -- metabolism KW - DNA Polymerase III -- genetics KW - Rec A Recombinases -- metabolism KW - Endodeoxyribonucleases -- metabolism KW - DNA Polymerase III -- metabolism KW - DNA Replication KW - SOS Response (Genetics) KW - Models, Genetic KW - Escherichia coli -- genetics KW - Mutagenesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79448747?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Genetic+requirements+and+mutational+specificity+of+the+Escherichia+coli+SOS+mutator+activity.&rft.au=Fijalkowska%2C+I+J%3BDunn%2C+R+L%3BSchaaper%2C+R+M&rft.aulast=Fijalkowska&rft.aufirst=I&rft.date=1997-12-01&rft.volume=179&rft.issue=23&rft.spage=7435&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 - 1997-12-30 N1 - Date created - 1997-12-30 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Genetics. 1993 Aug;134(4):1023-30 [8375645] Genetics. 1993 Aug;134(4):1031-8 [8375646] Genetics. 1993 Aug;134(4):1039-44 [8375647] Mutat Res. 1993 Oct;292(2):175-85 [7692254] J Biol Chem. 1993 Nov 15;268(32):23762-5 [8226906] Nucleic Acids Res. 1993 Oct 11;21(20):4788-95 [7694234] Curr Opin Genet Dev. 1993 Oct;3(5):719-25 [8274853] J Mol Biol. 1994 Feb 11;236(1):151-64 [8107100] Genetics. 1994 Feb;136(2):439-48 [7908652] J Bacteriol. 1994 Oct;176(20):6221-8 [7928992] Proc Natl Acad Sci U S A. 1986 Jun;83(11):3904-8 [2940594] Mutat Res. 1987 Jan;183(1):31-7 [3025722] Proc Natl Acad Sci U S A. 1987 May;84(10):3189-93 [2437576] Proc Natl Acad Sci U S A. 1987 Jun;84(12):4195-9 [3295877] Proc Natl Acad Sci U S A. 1987 Sep;84(17):6220-4 [3306672] Mol Gen Genet. 1987 Jul;208(3):542-8 [3312950] Proc Natl Acad Sci U S A. 1988 Mar;85(6):1816-20 [3279418] Mol Gen Genet. 1988 Aug;213(2-3):491-8 [2972909] Proc Natl Acad Sci U S A. 1988 Nov;85(21):8126-30 [3054881] J Biol Chem. 1988 Dec 15;263(35):18946-52 [3058691] Mol Gen Genet. 1988 Nov;214(3):467-73 [2851096] J Biol Chem. 1989 Feb 15;264(5):2898-905 [2521632] J Bacteriol. 1989 May;171(5):2415-23 [2651400] J Bacteriol. 1989 May;171(5):2480-4 [2651403] Microbiol Rev. 1989 Mar;53(1):1-24 [2540407] Mutat Res. 1997 Jan 3;373(1):61-6 [9015154] Proc Natl Acad Sci U S A. 1997 Feb 4;94(3):946-51 [9023362] Genetics. 1966 Jun;53(6):1119-36 [5335128] Mol Gen Genet. 1972;119(2):139-52 [4565754] J Bacteriol. 1974 Feb;117(2):477-87 [4590472] J Mol Biol. 1975 Sep 5;97(1):77-92 [1100853] Genetics. 1994 Oct;138(2):263-70 [7828810] Genetics. 1994 Nov;138(3):553-64 [7851754] Proc Natl Acad Sci U S A. 1995 Aug 15;92(17):7951-5 [7644519] J Bacteriol. 1995 Oct;177(20):5979-86 [7592352] Proc Natl Acad Sci U S A. 1995 Dec 5;92(25):11736-40 [8524839] Proc Natl Acad Sci U S A. 1996 Apr 2;93(7):2856-61 [8610131] Mutat Res. 1996 Feb 19;350(1):17-23 [8657178] J Biol Chem. 1996 May 3;271(18):10767-74 [8631887] J Biol Chem. 1996 Aug 2;271(31):18947-53 [8702558] Mutat Res. 1996 Oct 25;357(1-2):1-15 [8876675] Mol Gen Genet. 1978 Jul 25;163(3):277-83 [355854] Proc Natl Acad Sci U S A. 1978 Jul;75(7):3037-41 [356043] Proc Natl Acad Sci U S A. 1981 Mar;78(3):1773-7 [6453349] Mol Gen Genet. 1982;185(1):43-50 [6211591] Mol Gen Genet. 1982;186(2):298-300 [7050634] J Bacteriol. 1982 Oct;152(1):351-6 [6288664] Biochimie. 1982 Aug-Sep;64(8-9):571-5 [6814503] Proc Natl Acad Sci U S A. 1983 Jan;80(2):487-91 [6300848] J Mol Biol. 1984 Mar 5;173(3):293-305 [6230459] Microbiol Rev. 1984 Mar;48(1):60-93 [6371470] Cell. 1984 Jun;37(2):675-82 [6373019] Mol Gen Genet. 1985;199(1):64-9 [3158798] J Bacteriol. 1985 Sep;163(3):870-6 [3897198] Gene. 1985;39(2-3):181-9 [4092929] Basic Life Sci. 1975;5A:355-67 [1103845] Mol Gen Genet. 1976 Feb 27;144(1):53-8 [772414] Bacteriol Rev. 1976 Dec;40(4):869-907 [795416] Mol Gen Genet. 1978 Jun 1;162(1):35-41 [353524] Proc Natl Acad Sci U S A. 1989 Jul;86(14):5345-9 [2501784] J Biol Chem. 1990 Feb 5;265(4):2338-46 [1688852] Mutagenesis. 1990 Jan;5(1):31-4 [2184308] Mutagenesis. 1990 Jan;5(1):35-8 [2184309] J Bacteriol. 1991 Jan;173(1):334-44 [1987124] Proc Natl Acad Sci U S A. 1991 Feb 15;88(4):1251-5 [1847514] Annu Rev Biochem. 1991;60:477-511 [1883202] Genetics. 1991 Oct;129(2):317-26 [1660424] Mol Gen Genet. 1991 Nov;230(1-2):75-80 [1745244] J Bacteriol. 1992 Mar;174(6):1974-82 [1548237] Annu Rev Genet. 1991;25:229-53 [1812808] J Biol Chem. 1992 Jun 5;267(16):11431-8 [1534562] Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10777-81 [1438275] J Biol Chem. 1992 Dec 5;267(34):24485-500 [1447195] Nature. 1993 Apr 22;362(6422):709-15 [8469282] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tumor regression with regional distribution of the targeted toxin TF-CRM107 in patients with malignant brain tumors. AN - 79448112; 9396606 AB - We investigated regional therapy of recurrent malignant brain tumors with transferrin-CRM107, a conjugate of human transferrin (Tf) and a genetic mutant of diphtheria toxin (CRM107) that lacks native toxin binding. Physiological barriers to delivering proteins to tumor and surrounding infiltrated brain were circumvented with high-flow interstitial microinfusion. At least a 50% reduction in tumor volume on magnetic resonance imaging (MRI) occurred in 9 of 15 patients who could be evaluated (60%), including two complete responses. Peritumoral toxicity developed 1-4 weeks after treatment in three of three patients at 1.0 microg/ml, but in zero of nine patients treated at lower concentrations. No symptomatic systemic toxicity occurred. Regional perfusion with Tf-CRM107 produces tumor responses without systemic toxicity in patients with malignant brain tumors refractory to conventional therapy. Direct interstitial infusion can be used successfully to distribute a large protein in the tumor and infiltrated brain surrounding the tumor. JF - Nature medicine AU - Laske, D W AU - Youle, R J AU - Oldfield, E H AD - Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-1414, USA. Y1 - 1997/12// PY - 1997 DA - December 1997 SP - 1362 EP - 1368 VL - 3 IS - 12 SN - 1078-8956, 1078-8956 KW - Antibodies KW - 0 KW - Diphtheria Toxin KW - Transferrin KW - Index Medicus KW - Magnetic Resonance Imaging KW - Antibodies -- blood KW - Humans KW - Brain -- pathology KW - Adult KW - Aged KW - Middle Aged KW - Brain -- metabolism KW - Drug Design KW - Male KW - Female KW - Brain Neoplasms -- pathology KW - Brain Neoplasms -- therapy KW - Transferrin -- genetics KW - Transferrin -- therapeutic use KW - Diphtheria Toxin -- therapeutic use KW - Transferrin -- adverse effects KW - Diphtheria Toxin -- genetics KW - Diphtheria Toxin -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79448112?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+medicine&rft.atitle=Tumor+regression+with+regional+distribution+of+the+targeted+toxin+TF-CRM107+in+patients+with+malignant+brain+tumors.&rft.au=Laske%2C+D+W%3BYoule%2C+R+J%3BOldfield%2C+E+H&rft.aulast=Laske&rft.aufirst=D&rft.date=1997-12-01&rft.volume=3&rft.issue=12&rft.spage=1362&rft.isbn=&rft.btitle=&rft.title=Nature+medicine&rft.issn=10788956&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-01-09 N1 - Date created - 1998-01-09 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Nat Med. 1997 Dec;3(12):1323 [9396599] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Isolated limb reperfusion with tumor necrosis factor and melphalan in patients with extremity melanoma after failure of isolated limb perfusion with chemotherapeutics. AN - 79446661; 9392330 AB - This retrospective study evaluated the benefit of using tumor necrosis factor (TNF) and melphalan administered via an isolated limb perfusion (ILP) in a series of patients with metastatic melanoma who failed initial ILP with chemotherapeutics. Seventeen patients with extremity melanoma who underwent prior ILP with conventional chemotherapeutics (10 with melphalan; 4 with platinum; 2 with platinum, dacarbazine, thiotepa, actinomycin D, and nitrogen mustard; and 1 with thiotepa, actinomycin D, and nitrogen mustard) and had local recurrences were treated with a 90-minute isolated hyperthermic limb reperfusion with melphalan (10 mg/L limb volume) plus TNF (2-6 mg). Five prior ILPs were adjuvant and 12 were therapeutic. Reperfusion was associated with an overall 94% response rate and a 65% complete response (CR) rate. Of the patients who failed an initial ILP with melphalan alone the overall response rate was 90% after the reperfusion with TNF and melphalan. In patients who failed an initial ILP with agents other than melphalan the CR rate was 100% after ILP with TNF and melphalan. TNF/melphalan isolated limb reperfusion was found to be more effective in terms of CR after initial ILP regimens that did not utilize melphalan (100% CR after nonmelphalan ILP vs. 50% CR after melphalan ILP [P = 0.04]). Regional toxicity was comprised of mild skin blistering and peeling in 47% of patients. One patient developed Grade 3 (based on National Cancer Institute Common Toxicity Criteria) skin necrosis, and one developed Grade 5 muscle and nerve toxicity, requiring an amputation. Isolated limb reperfusion with TNF and melphalan can be performed safely with response rates similar to those of other trials of single perfusions. Repeat ILP using TNF and melphalan in patients with melanoma who have failed prior ILP with chemotherapeutics is justified. The utility of TNF (vs. melphalan alone) will be defined in ongoing Phase III trials. JF - Cancer AU - Bartlett, D L AU - Ma, G AU - Alexander, H R AU - Libutti, S K AU - Fraker, D L AD - Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1997/12/01/ PY - 1997 DA - 1997 Dec 01 SP - 2084 EP - 2090 VL - 80 IS - 11 SN - 0008-543X, 0008-543X KW - Antineoplastic Agents, Alkylating KW - 0 KW - Tumor Necrosis Factor-alpha KW - Melphalan KW - Q41OR9510P KW - Abridged Index Medicus KW - Index Medicus KW - Tumor Necrosis Factor-alpha -- administration & dosage KW - Aged, 80 and over KW - Melphalan -- administration & dosage KW - Humans KW - Hyperthermia, Induced KW - Adult KW - Treatment Outcome KW - Retrospective Studies KW - Aged KW - Middle Aged KW - Antineoplastic Agents, Alkylating -- administration & dosage KW - Male KW - Female KW - Skin Neoplasms -- drug therapy KW - Leg KW - Melanoma -- drug therapy KW - Perfusion -- methods KW - Arm KW - Antineoplastic Combined Chemotherapy Protocols -- administration & dosage KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79446661?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Isolated+limb+reperfusion+with+tumor+necrosis+factor+and+melphalan+in+patients+with+extremity+melanoma+after+failure+of+isolated+limb+perfusion+with+chemotherapeutics.&rft.au=Bartlett%2C+D+L%3BMa%2C+G%3BAlexander%2C+H+R%3BLibutti%2C+S+K%3BFraker%2C+D+L&rft.aulast=Bartlett&rft.aufirst=D&rft.date=1997-12-01&rft.volume=80&rft.issue=11&rft.spage=2084&rft.isbn=&rft.btitle=&rft.title=Cancer&rft.issn=0008543X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-12-17 N1 - Date created - 1997-12-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Astrocyte-specific expression of human T-cell lymphotropic virus type 1 (HTLV-1) Tax: induction of tumor necrosis factor alpha and susceptibility to lysis by CD8+ HTLV-1-specific cytotoxic T cells. AN - 79415671; 9371571 AB - Human T-cell lymphotropic virus type 1 (HTLV-1) is associated with a chronic neurological disease termed HTLV-1-associated myelopathy/tropical spastic paraperesis (HAM/TSP). Although the pathogenesis of this disease remains to be elucidated, the evidence suggests that immunopathological mechanisms are involved. Since HTLV-1 tax mRNA was colocalized with glial acidic fibrillary protein, a marker for astrocytes, we developed an in vitro model to assess whether HTLV-1 infection activates astrocytes to secrete cytokines or present viral immunodominant epitopes to virus-specific T cells. Two human astrocytic glioma cell lines, U251 and U373, were transfected with the 3' portion of the HTLV-1 genome and with the HTLV-1 tax gene under astrocyte-specific promoter control. In this study, we report that Tax-expressing astrocytic glioma transfectants activate the expression of tumor necrosis factor alpha mRNA in vitro. Furthermore, these Tax-expressing glioma transfectants can serve as immunological targets for HTLV-1-specific cytotoxic T lymphocytes (CTL). We propose that these events could contribute to the neuropathology of HAM/TSP, since infected astrocytes can become a source for inflammatory cytokines upon HTLV-1 infection and serve as targets for HTLV-1-specific CTL, resulting in parenchymal damage by direct lysis and/or cytokine release. JF - Journal of virology AU - Méndez, E AU - Kawanishi, T AU - Clemens, K AU - Siomi, H AU - Soldan, S S AU - Calabresi, P AU - Brady, J AU - Jacobson, S AD - Neuroimmunology Branch, National Institute of Neurologic Diseases and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1997/12// PY - 1997 DA - December 1997 SP - 9143 EP - 9149 VL - 71 IS - 12 SN - 0022-538X, 0022-538X KW - Gene Products, tax KW - 0 KW - RNA, Messenger KW - Tumor Necrosis Factor-alpha KW - Index Medicus KW - AIDS/HIV KW - Polymerase Chain Reaction KW - Tumor Cells, Cultured KW - Transfection KW - Humans KW - Cytotoxicity Tests, Immunologic KW - Gene Expression Regulation KW - Precipitin Tests KW - Human T-lymphotropic virus 1 -- genetics KW - Gene Products, tax -- biosynthesis KW - Astrocytes -- virology KW - CD8-Positive T-Lymphocytes -- immunology KW - Tumor Necrosis Factor-alpha -- immunology KW - Tumor Necrosis Factor-alpha -- biosynthesis KW - Human T-lymphotropic virus 1 -- immunology KW - Gene Products, tax -- genetics KW - Gene Products, tax -- immunology KW - Astrocytes -- immunology KW - Tumor Necrosis Factor-alpha -- genetics KW - Astrocytes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79415671?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Astrocyte-specific+expression+of+human+T-cell+lymphotropic+virus+type+1+%28HTLV-1%29+Tax%3A+induction+of+tumor+necrosis+factor+alpha+and+susceptibility+to+lysis+by+CD8%2B+HTLV-1-specific+cytotoxic+T+cells.&rft.au=M%C3%A9ndez%2C+E%3BKawanishi%2C+T%3BClemens%2C+K%3BSiomi%2C+H%3BSoldan%2C+S+S%3BCalabresi%2C+P%3BBrady%2C+J%3BJacobson%2C+S&rft.aulast=M%C3%A9ndez&rft.aufirst=E&rft.date=1997-12-01&rft.volume=71&rft.issue=12&rft.spage=9143&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 - 1997-12-24 N1 - Date created - 1997-12-24 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Virology. 1992 Jun;188(2):628-36 [1374983] J Neurovirol. 1995 Mar;1(1):50-61 [9222342] Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):11784-8 [1465399] J Neuroimmunol. 1993 Feb;42(2):223-6 [8429106] N Engl J Med. 1993 Apr 22;328(16):1173-82 [8455685] J Exp Med. 1993 Jun 1;177(6):1567-73 [8496677] J Neuroimmunol. 1993 Jun;45(1-2):133-6 [8331158] J Immunol. 1993 Oct 1;151(7):3874-83 [7690819] Acta Neuropathol. 1993;86(3):224-35 [8213080] Neurology. 1993 Dec;43(12):2621-4 [7504797] J Virol. 1994 Mar;68(3):1854-63 [7906313] Nature. 1994 Jan 13;367(6459):188-93 [8114918] J Neuroimmunol. 1994 Aug;53(1):23-9 [7914211] Ann Neurol. 1995 Feb;37(2):167-75 [7847858] Acta Neurol Scand. 1995 Sep;92(3):213-7 [7484074] J Neurovirol. 1995 Jun;1(2):145-56 [9222353] Genes Dev. 1994 Nov 15;8(22):2665-79 [7958924] Blood. 1977 Sep;50(3):481-92 [301762] Proc Natl Acad Sci U S A. 1980 Dec;77(12):7415-9 [6261256] Proc Natl Acad Sci U S A. 1984 Apr;81(8):2534-7 [6326131] J Clin Invest. 1985 Mar;75(3):836-43 [2858496] Lancet. 1985 Aug 24;2(8452):407-10 [2863442] Lancet. 1986 May 3;1(8488):1031-2 [2871307] Lancet. 1987 Jul 4;2(8549):49 [2885542] J Neuroimmunol. 1988 Apr;18(1):87-94 [3257971] Ann Neurol. 1988;23 Suppl:S143-50 [2894806] Int J Cancer. 1988 Jun 15;41(6):880-5 [2897342] Ann Neurol. 1988 Apr;23(4):339-46 [3132891] Neurology. 1988 Aug;38(8):1302-7 [2899862] Am J Med. 1988 Sep;85(3):289-91 [3414726] Blood. 1989 Jan;73(1):194-201 [2783372] Int J Cancer. 1989 Feb 15;43(2):327-33 [2563721] Am J Dis Child. 1989 Jul;143(7):771-4 [2741845] J Exp Med. 1989 Dec 1;170(6):1859-67 [2584928] Neurology. 1989 Dec;39(12):1566-72 [2586770] JAMA. 1990 Jan 5;263(1):60-4 [2293689] J Virol. 1990 Mar;64(3):1278-82 [2304144] Ann Neurol. 1990 Feb;27(2):149-56 [2317010] J Neurol Sci. 1990 Jul;97(2-3):183-93 [2401896] J Virol. 1990 Nov;64(11):5682-7 [1976827] Nature. 1990 Nov 15;348(6298):245-8 [2146511] Neurology. 1991 Apr;41(4):594-5 [2011262] Ann Neurol. 1991 Feb;29(2):194-201 [2012389] Annu Rev Med. 1991;42:97-105 [2035998] Int Immunol. 1991 Aug;3(8):761-7 [1911545] Autoimmunity. 1988;1(2):125-31 [2979611] J Neurovirol. 1996 Oct;2(5):323-9 [8912208] N Engl J Med. 1997 Mar 20;336(12):839-45 [9062093] J Immunol. 1992 Sep 15;149(6):1896-904 [1517560] N1 - Last updated - 2017-01-18 ER - TY - CONF T1 - Mouse models for breast cancer susceptibility AN - 17260293; 4562425 AB - Breast cancer is the most common form of malignancy in American women. Apart from age, a strong family history of breast cancer confers the highest known risk for neoplastic development by the various etiologic factors identified to date. Four genes have been identified (p53, BRCA1, BRCA2, ATM) that appear to confer substantial predispositions to human breast cancer. Gene targeting techniques have been used to create mice with specific defects in these genes. This review describes the status of these mice as models for breast cancer susceptibility and suggests future research directions which may increase our understanding of breast carcinogenesis. JF - Environmental Toxicology and Pharmacology AU - Bennett, L M AU - Wiseman, R W Y1 - 1997/12// PY - 1997 DA - Dec 1997 SP - 283 EP - 288 PB - Elsevier Science Ltd., P.O. Box 800 Kidlington Oxford OX5 1DX UK VL - 4 IS - 3-4 KW - mice KW - susceptibility KW - Toxicology Abstracts KW - Breast KW - Animal models KW - Toxicity testing KW - Cancer KW - X 24221:Toxicity testing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17260293?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+Toxicology+and+Pharmacology&rft.atitle=Mouse+models+for+breast+cancer+susceptibility&rft.au=Bennett%2C+L+M%3BWiseman%2C+R+W&rft.aulast=Bennett&rft.aufirst=L&rft.date=1997-12-01&rft.volume=4&rft.issue=3-4&rft.spage=283&rft.isbn=&rft.btitle=&rft.title=Environmental+Toxicology+and+Pharmacology&rft.issn=13826689&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - CONF T1 - Acquired risk factors and susceptibility to environmental toxicants AN - 17259964; 4562414 AB - Susceptibility to illness after exposure to environmental toxicants is determined by the interaction of numerous factors involving both constitutive and acquired traits. Constitutive susceptibility (risk) factors are the intrinsic traits determined by developmental stage, gender, and genetic makeup. Within a population, changes in constitutive risk factors tend to occur slowly, through aging, alterations in the birth or death rate, or by migration in or out of the population. Often overlooked is the effect of acquired susceptibility factors on susceptibility to environmental toxicants. Acquired susceptibility factors, which are related to the effects of living conditions, psychosocial factors, diet, behavior and access to medical care, may modify the effect of constitutive factors. Three examples demonstrate the interaction of acquired susceptibility factors with exposure and constitutive factors. The increased prevalence of asthma in children is suspected of having a strong environmental component but the underlying acquired susceptibility factors, if any, are difficult to identify because of the multifactorial nature of asthma and the use of surrogate risk factors such as parent's education. beta -Carotene is a dietary component which may modify acquired susceptibility. While numerous observational studies find that dietary beta -carotene reduces the risk of lung cancer in cigarette smokers, intervention studies do not support this role. Hepatitis B is an example of an infectious agent functioning as an acquired susceptibility factor. Hepatitis B synergistically increases the risk of hepatocellular carcinoma when accompanied by exposure to aflatoxin, a relationship that may be modified by constitutive risk factors, such as epoxide hydrolase capabilities. Acquired risk factors have the potential to greatly influence risk and their impact should be included in future studies of the health effects of environmental toxicants. JF - Environmental Toxicology and Pharmacology AU - Grassman, J Y1 - 1997/12// PY - 1997 DA - Dec 1997 SP - 209 EP - 217 PB - Elsevier Science Ltd., P.O. Box 800 Kidlington Oxford OX5 1DX UK VL - 4 IS - 3-4 KW - susceptibility factors KW - Toxicology Abstracts KW - Risk assessment KW - Toxicants KW - Environmental quality KW - Public health KW - X 24230:Legislation & recommended standards UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17259964?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+Toxicology+and+Pharmacology&rft.atitle=Acquired+risk+factors+and+susceptibility+to+environmental+toxicants&rft.au=Grassman%2C+J&rft.aulast=Grassman&rft.aufirst=J&rft.date=1997-12-01&rft.volume=4&rft.issue=3-4&rft.spage=209&rft.isbn=&rft.btitle=&rft.title=Environmental+Toxicology+and+Pharmacology&rft.issn=13826689&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - The importance of anatomical realism for validation of physiological models of disposition of inhaled toxicants AN - 16489873; 4392340 AB - The goodness of fit of three PBPK models to data for inhalation uptake of 1,3-butadiene by mice from closed chambers were compared. These models included a classical flow-limited model with blood consolidated into arterial and venous compartments, a flow-limited model with implicit blood and alveolar compartments, and a model with an actual alveolar compartment and blood distributed among compartments for arterial, venous, and capillary spaces. Using physiological and biochemical parameters from the literature, all three models reproduced observed steady-state blood butadiene concentrations. However, the first two models predicted more rapid uptake of butadiene than was observed. Assumptions such as ignoring extrahepatic metabolism or reducing the ventilation rate by 75% were required to enable these models to fit the butadiene uptake data. The behavior of the third model resembled that of the other two models when the single-pass extraction ratio of butadiene for all tissues was close to 1, but the model did reproduce observed butadiene uptake when an extraction ratio of 0.5 was used. The difference in predictions of the three models was traced to smaller computed blood:tissue gradients and tissue butadiene concentrations, hence reduced rates of metabolic clearance, when the blood is distributed. These results suggest that the common assumption of flow limitation in the disposition of an inhaled gas may not always be appropriate. Because structurally different models can reproduce the same uptake data and all these models cannot be correct, the assumptions on which these models were based must be investigated experimentally to ensure that they are physiologically realistic. JF - Toxicology and Applied Pharmacology AU - Kohn, M C AD - Laboratory of Computational Biology and Risk Analysis, National Institute of Environmental Health Sciences, PO Box 12233, Mail Drop A3-06, Research Triangle Park, NC 27709, USA Y1 - 1997/12// PY - 1997 DA - Dec 1997 SP - 448 EP - 458 VL - 147 IS - 2 SN - 0041-008X, 0041-008X KW - disposition KW - metabolism KW - Toxicology Abstracts KW - X 24221:Toxicity testing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16489873?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+and+Applied+Pharmacology&rft.atitle=The+importance+of+anatomical+realism+for+validation+of+physiological+models+of+disposition+of+inhaled+toxicants&rft.au=Kohn%2C+M+C&rft.aulast=Kohn&rft.aufirst=M&rft.date=1997-12-01&rft.volume=147&rft.issue=2&rft.spage=448&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 revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - A form of anti-Tac(Fv) which is both single-chain and disulfide stabilized: Comparison with its single-chain and disulfide-stabilized homologs AN - 16388258; 4297312 AB - Disulfide-stabilized Fvs (dsFvs) are recombinant proteins composed of a heavy-chain variable domain (V sub(H)) of an antibody connected via a disulfide bond to the light-chain variable domain (V sub(L)). In single-chain Fvs (scFvs), a peptide connector links V sub(H) and V sub(L). The dsFv form of the anti-Tac monoclonal antibody which reacts with the alpha subunit of the IL2 receptor was recently reported to be more stable and to aggregate less during renaturation than anti-Tac(scFv). In addition, it could be produced in a better yield owing to less aggregation. However, the yields are still too low to permit the production of material for clinical trials in which the dsFv will be used to image or treat IL2 receptor (CD25)-containing tumors. To increase the efficiency by which V sub(H) and V sub(L) associate and form a disulfide bond during renaturation, we have prepared an Fv form of anti-Tac which is both single chain and disulfide stabilized (scdsFv). The recombinant protein is expressed in Escherichia coli, where it accumulates in inclusion bodies. Using inclusion body protein as the reference point, the yield of purified anti-Tac(scdsFv) was 13% compared with 2% for anti-Tac(dsFv). Anti-Tac(scdsFv) has equivalent binding affinity, immunoreactivity after radiolabeling and stability. The results show that a linker between V sub(H) and V sub(L) facilitates heterodimer formation and leads to disulfide bond formation in a higher percentage of the molecules renatured. Thus anti-Tac(scdsFv) is the preferred form of anti-Tac(Fv) to be used for clinical studies. We anticipate that scdsFvs will be the optimum recombinant form of Fv to produce from bacteria. JF - Protein Engineering AU - Rajagopal, V AU - Pastan, I AU - Kreitman, R J AD - Laboratory of Molecular Biology, Division of Cancer Biology, National Cancer Institute, National Institutes of Health, 37/4E16, 37 Convent Drive, MSC 4255, Bethesda, MD 20892, USA Y1 - 1997/12// PY - 1997 DA - Dec 1997 SP - 1453 EP - 1459 VL - 10 IS - 12 SN - 0269-2139, 0269-2139 KW - CD25 antigen KW - Disulfide bonds KW - Escherichia coli KW - Fv KW - interleukin 2 receptors KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - W3 33375:Antibodies KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16388258?accountid=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=Protein+Engineering&rft.atitle=A+form+of+anti-Tac%28Fv%29+which+is+both+single-chain+and+disulfide+stabilized%3A+Comparison+with+its+single-chain+and+disulfide-stabilized+homologs&rft.au=Rajagopal%2C+V%3BPastan%2C+I%3BKreitman%2C+R+J&rft.aulast=Rajagopal&rft.aufirst=V&rft.date=1997-12-01&rft.volume=10&rft.issue=12&rft.spage=1453&rft.isbn=&rft.btitle=&rft.title=Protein+Engineering&rft.issn=02692139&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Immunization for prevention and treatment of cocaine abuse: legal and ethical implications AN - 16375270; 4261749 AB - A cocaine vaccine, currently under investigation by several laboratories, would be an innovative and exciting means of treating and preventing cocaine addiction. However, an approved vaccine will raise at least two major areas of concern. (1) Loss of privacy: cocaine antibodies might be used as a marker to identify, penalize, and stigmatize vaccinated individuals. (2) Selection for vaccination: should immunization be voluntary or compelled; should immunization be restricted to addicts, to those at risk of addiction, or should it be universal; should immunization be used in children? I propose to analogize cocaine addiction to an infectious disease which poses a major public health problem. This approach can provide an ethical and legal foundation on which we may begin to formulate a societal approach to the use of the cocaine vaccine. JF - Drug and Alcohol Dependence AU - Cohen, P J AD - Medications Development Division, National Institute on Drug Abuse, National Institutes of Health, Rockville, MD, USA Y1 - 1997/12// PY - 1997 DA - Dec 1997 SP - 167 EP - 174 VL - 48 IS - 3 SN - 0376-8716, 0376-8716 KW - cocaine KW - drug abuse KW - immunization KW - man KW - CSA Neurosciences Abstracts; Risk Abstracts KW - R2 23090:Policy and planning KW - N3 11106:Neurobiology of drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16375270?accountid=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=Drug+and+Alcohol+Dependence&rft.atitle=Immunization+for+prevention+and+treatment+of+cocaine+abuse%3A+legal+and+ethical+implications&rft.au=Cohen%2C+P+J&rft.aulast=Cohen&rft.aufirst=P&rft.date=1997-12-01&rft.volume=48&rft.issue=3&rft.spage=167&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 revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Potential new antifungal agents AN - 16336567; 4264559 AB - The increasing incidence of both mucosal and invasive fungal infections has led to the development of several new systemic antifungal agents. Potent and broad spectrum, third generation triazoles, echinocandins and pneumocandins, fungicidal inhibitors of 1,3-beta glucan synthase, and a liposomal formulation of nystatin have recently entered early clinical trials. Other promising agents with novel targets currently under investigation include the pradimicin family of antibiotics, nikkomycin Z, and perhaps, antimicrobial peptides. Immunomodulation by recombinant cytokines has been extensively studied in the laboratory, and effective antifungal vaccines are on the horizon. In conjuction with currently available agents, including the lipid formulations of amphotericin B, this expanded antifungal armamentarium holds promise to meet the evolving challenges of both invasive and mucosal fungal infections. JF - Current Opinion in Infectious Diseases AU - Groll, AH AU - Walsh, T J AD - Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bldg. 10, Rm. 13N240, 10 Center Drive, Bethesda, MD 20892, USA Y1 - 1997/12// PY - 1997 DA - Dec 1997 SP - 449 EP - 458 VL - 10 IS - 6 SN - 0951-7375, 0951-7375 KW - antifungal agents KW - diseases KW - fungi KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Microbiology Abstracts C: Algology, Mycology & Protozoology KW - A 01067:Antifungal & fungicidal KW - K 03087:Fungi: human UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16336567?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologya&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+Opinion+in+Infectious+Diseases&rft.atitle=Potential+new+antifungal+agents&rft.au=Groll%2C+AH%3BWalsh%2C+T+J&rft.aulast=Groll&rft.aufirst=AH&rft.date=1997-12-01&rft.volume=10&rft.issue=6&rft.spage=449&rft.isbn=&rft.btitle=&rft.title=Current+Opinion+in+Infectious+Diseases&rft.issn=09517375&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Transgenic mice overexpressing a dominant-negative mutant type II transforming growth factor beta receptor show enhanced tumorigenesis in the mammary gland and lung in response to the carcinogen 7,12-dimethylbenz-[a]-anthracene AN - 16329908; 4269399 AB - To test the hypothesis that the transforming growth factor- beta (TGF- beta ) system has tumor suppressor activity in the mammary gland, we have generated transgenic mice overexpressing a dominant-negative mutant form of the type II TGF- beta receptor, under the control of the mouse mammary tumor virus-long terminal repeat. High-level expression of the transgene was observed in the mammary and salivary glands, with lower expression in the lung, spleen, and testis. Older nulliparous transgenic mice (9-17 months) showed a marked increase in the incidence and degree of lobulo-alveolar side-branching in the mammary glands when compared to wild-type littermates (24.8% of glands examined histologically versus 14.4%; P = 0.004), suggesting a role for endogenous TGF- beta s in regulating development or maintenance of mammary alveoli. Spontaneous tumorigenesis was unchanged in the transgenic mice. However, following initiation with the carcinogen 7,12-dimethylbenz[a]anthracene, the transgenic group showed a significant increase in the incidence and multiplicity of mammary tumors when compared with wild-type littermates (40% incidence in transgenic mice versus 22% for wild-type, with 4 of 25 transgenics developing multiple mammary tumors versus 0 of 27 wild-type; P = 0.03). An early increase in the incidence of lung tumors was also observed in transgenic mice, but no difference between genotype groups was seen in the incidence of tumors in tissues in which the transgene is not expressed. The data show that the endogenous TGF- beta system has tumor suppressor activity in the mammary gland and lung. JF - Cancer Research AU - Boettinger, E P AU - Jakubczak, J L AU - Haines, D C AU - Bagnall, K AU - Wakefield, L M AD - Laboratory of Chemoprevention, Building 41, Room C629, 41 Library Drive, MSC 5055, Bethesda, MD 20892-5055, USA, wakefiel@dce41.nci.nih.gov Y1 - 1997/12// PY - 1997 DA - Dec 1997 SP - 5564 EP - 5570 VL - 57 IS - 24 SN - 0008-5472, 0008-5472 KW - 7,12-dimethylbenz(a)anthracene KW - 9,10-Dimethyl-1,2-benzanthracene KW - Transgenic mice KW - polycyclic aromatic hydrocarbons KW - transforming growth factor- beta KW - Toxicology Abstracts; Oncogenes & Growth Factors Abstracts KW - X 24190:Polycyclic hydrocarbons KW - B 26165:TGF beta and TGF beta receptor/inhibins/activins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16329908?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Research&rft.atitle=Transgenic+mice+overexpressing+a+dominant-negative+mutant+type+II+transforming+growth+factor+beta+receptor+show+enhanced+tumorigenesis+in+the+mammary+gland+and+lung+in+response+to+the+carcinogen+7%2C12-dimethylbenz-%5Ba%5D-anthracene&rft.au=Boettinger%2C+E+P%3BJakubczak%2C+J+L%3BHaines%2C+D+C%3BBagnall%2C+K%3BWakefield%2C+L+M&rft.aulast=Boettinger&rft.aufirst=E&rft.date=1997-12-01&rft.volume=57&rft.issue=24&rft.spage=5564&rft.isbn=&rft.btitle=&rft.title=Cancer+Research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Fixed archival tissue purify DNA and primers for good PCR yield AN - 16317933; 4255056 AB - The analysis of archival formalin-fixed, paraffin-embedded tissue samples becomes increasingly important for molecular biology studies. As fixation and paraffin-embedding cause alterations of proteins and nucleic acids, archival sources of DNA must be handled with care. To address the need for specificity and reproducibility, we developed an improved protocol for semi-automated DNA extraction adapted to fixed, embedded tissue samples, and a PCR approach using HPLC-purified primers. JF - Molecular Biotechnology AU - Weirich, G AU - Hornauer, MA AU - Bruening, T AU - Hoefler, H AU - Brauch, H AD - National Cancer Institute, Laboratory of Immunobiology, Bldg. 560, Rm. 12-71, Frederick, MD 21702, USA Y1 - 1997/12// PY - 1997 DA - Dec 1997 SP - 299 EP - 301 VL - 8 IS - 3 SN - 1073-6085, 1073-6085 KW - polymerase chain reaction KW - tissue fixation KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Agricultural and Environmental Biotechnology Abstracts KW - W3 33243:Molecular methods KW - W 30965:Miscellaneous, Reviews KW - W2 32243:Molecular methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16317933?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+Biotechnology&rft.atitle=Fixed+archival+tissue+purify+DNA+and+primers+for+good+PCR+yield&rft.au=Weirich%2C+G%3BHornauer%2C+MA%3BBruening%2C+T%3BHoefler%2C+H%3BBrauch%2C+H&rft.aulast=Weirich&rft.aufirst=G&rft.date=1997-12-01&rft.volume=8&rft.issue=3&rft.spage=299&rft.isbn=&rft.btitle=&rft.title=Molecular+Biotechnology&rft.issn=10736085&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Regulated human erythropoietin receptor expression in mouse brain AN - 16310034; 4248592 AB - Erythropoietin (Epo) is known for its role in erythropoiesis and acts by binding to its receptor (EpoR) on the surface of erythroid progenitors. EpoR activity follows the site of hematopoiesis from the embryonic yolk sac to the fetal liver and then the adult spleen and bone marrow. Expression of EpoR has also been observed in selected cells of non-hematopoietic origin, such as the embryonic mouse brain during mid-gestation, at levels comparable to adult bone marrow. EpoR transcripts in brain decrease during development falling by birth to less than 1-3% of the level in hematopoietic tissue. We have now recapitulated this pattern of expression using a human EpoR transgene consisting of an 80-kb human EpoR genomic fragment. The highest level of expression was observed in the embryonic yolk sac and fetal liver, analogous to the endogenous gene, in addition to expression in adult spleen and bone marrow. Although activity of this transgene in brain is initially lower than the endogenous gene, it does exhibit the down-regulation observed for the endogenous gene in adult brain. The expression pattern of hybrid transgenes of an hEpoR promoter fused to beta -galactosidase in 9.5-day embryos suggested that the hEpoR promoter region between -1778 and -150 bp 5' of the transcription start site is necessary to direct EpoR expression in the neural tube. EpoR expression in the neural tube may be the origin of the EpoR transcripts detected in brain during development. These data demonstrate that both the mouse and human EpoR genes contain regulatory elements to direct significant levels of expression in a developmentally controlled manner in brain and suggest that in addition to its function during erythropoiesis, EpoR may play a role in the development of selected non-hematopoietic tissue. JF - Journal of Biological Chemistry AU - Liu, Chun AU - Shen, Kun AU - Liu, Ziyao AU - Noguchi, C T AD - Lab. Chem. Biol., NIDDK, Natl. Institutes Health, Bethesda, MD 20892-1822, USA Y1 - 1997/12// PY - 1997 DA - Dec 1997 SP - 32395 EP - 32400 VL - 272 IS - 51 SN - 0021-9258, 0021-9258 KW - brain KW - erythropoietin KW - erythropoietin receptors KW - man KW - transgenic mice KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - W 30965:Miscellaneous, Reviews KW - W3 33055:Genetic engineering (general) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16310034?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Biological+Chemistry&rft.atitle=Regulated+human+erythropoietin+receptor+expression+in+mouse+brain&rft.au=Liu%2C+Chun%3BShen%2C+Kun%3BLiu%2C+Ziyao%3BNoguchi%2C+C+T&rft.aulast=Liu&rft.aufirst=Chun&rft.date=1997-12-01&rft.volume=272&rft.issue=51&rft.spage=32395&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Therapy of malignant brain tumors by intratumoral implantation of retroviral vector-producing cells AN - 16275070; 4288808 AB - Intratumoral implantation of murine cells modified to produce retroviral vectors containing the herpes simplex virus-thymidine kinase (HSV-TK) gene induces regression of experimental brain tumors in rodents after ganciclovir (GCV) administration. We evaluated this approach in 15 patients with progressive growth of recurrent malignant brain tumors. Antitumor activity was detected in five of the smaller tumors (1.4 plus or minus 0.5 ml). In situ hybridization for HSV-TK demonstrated survival of vector-producing cells (VPCs) at 7 days but indicated limited gene transfer to tumors, suggesting that indirect, "bystander," mechanisms provide local antitumor activity in human tumors. However, the response of only very small tumors in which a high density of vector-producing cells had been placed suggests that techniques to improve delivery and distribution of the therapeutic gene will need to be developed if clinical utility is to be achieved with this approach. JF - Nature Medicine AU - Ram, Z AU - Culver, K W AU - Oshiro, E M AU - Viola, J J AU - DeVroom, H L AU - Otto, E AU - Long, Zhifeng AU - Chiang, Yawen AU - McGarrity, G J AU - Muul, L M AU - Katz, D AU - Blaese, R M AU - Oldfield, E H AD - Surg. Neurol. Branch, Natl. Inst. Neurol. Disorders and Stroke (NINDS), 10/5D37, 10 Center Dr., Bethesda, MD 20892, USA Y1 - 1997/12// PY - 1997 DA - Dec 1997 SP - 1354 EP - 1361 VL - 3 IS - 12 SN - 1078-8956, 1078-8956 KW - HSV KW - brain KW - ganciclovir KW - gene therapy KW - herpes simplex virus KW - man KW - retrovirus KW - thymidine kinase KW - tumors KW - Biotechnology and Bioengineering Abstracts; CSA Neurosciences Abstracts; Genetics Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - N3 11129:Neural and glial oncology KW - G 07443:Gene therapy KW - W 30965:Miscellaneous, Reviews KW - W3 33180:Gene based (protocols, clinical trials, and animal models) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16275070?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+Medicine&rft.atitle=Therapy+of+malignant+brain+tumors+by+intratumoral+implantation+of+retroviral+vector-producing+cells&rft.au=Ram%2C+Z%3BCulver%2C+K+W%3BOshiro%2C+E+M%3BViola%2C+J+J%3BDeVroom%2C+H+L%3BOtto%2C+E%3BLong%2C+Zhifeng%3BChiang%2C+Yawen%3BMcGarrity%2C+G+J%3BMuul%2C+L+M%3BKatz%2C+D%3BBlaese%2C+R+M%3BOldfield%2C+E+H&rft.aulast=Ram&rft.aufirst=Z&rft.date=1997-12-01&rft.volume=3&rft.issue=12&rft.spage=1354&rft.isbn=&rft.btitle=&rft.title=Nature+Medicine&rft.issn=10788956&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Natural proteoglycan receptor analogs determine the dynamics of Opa adhesin-mediated gonococcal infection of Chang epithelial cells AN - 16250096; 4233742 AB - Many bacterial pathogens possess a complex machinery for the induction and/or secretion of factors that promote their uptake by mammalian cells. We searched for the molecular basis of the 60- to 90-min lag time in the interaction of Neisseria gonorrhoeae carrying the heparin-binding Opa adhesin with Chang epithelial cells. Infection assays in the presence of chloramphenicol demonstrated that the Opa-mediated gonococcal infection of Chang cells required bacterial protein synthesis when the microorganisms were derived from GC agar but not when grown in liquid media. Further analysis indicated that contact with agar ingredients rather than the growth state of the microorganisms determined the infection dynamics. DEAE chromatography of GC agar extracts and sodium dodecyl sulfate-polyacrylamide gel electrophoresis analyses and testing of collected fractions in infection assays identified negatively charged high-molecular-weight polysaccharides in the agar as inhibitors of the cellular infection. Electron microscopy showed that agar-grown gonococci were surrounded by a coat of alcian blue-positive material, probably representing accreted polysaccharides. Similar antiphagocytic material was isolated from bovine serum, indicating that in biological fluids gonococci producing the heparin-binding Opa adhesin may become covered with externally derived polysaccharides as well. Binding assays with gonococci and epithelial proteoglycan receptors revealed that polysaccharides derived from agar or serum compete with the proteoglycans for binding of the heparin-binding Opa adhesin and thus act as receptor analogs. Growth of gonococci in a polysaccharide-free environment resulted in optimal proteoglycan receptor binding and rapid bacterial entry into Chang cells. The recognition that gonococci with certain phenotypes can recruit surface polysaccharides that determine in vitro infection dynamics adds a different dimension to the well-recognized biological significance of genetic variation for this pathogen. JF - Infection and Immunity AU - van Putten, JPM AU - Hayes, S F AU - Duensing, T D AD - Rocky Mountain Laboratories, NIAID, NIH, 903 South 4th St., Hamilton, MT 59840-2999, USA Y1 - 1997/12// PY - 1997 DA - Dec 1997 SP - 5028 EP - 5034 VL - 65 IS - 12 SN - 0019-9567, 0019-9567 KW - adherence KW - epithelium KW - genetic variance KW - gonorrhea KW - mucosa KW - proteoglycans KW - Microbiology Abstracts B: Bacteriology KW - J 02721:Cell cycle, morphology and motility UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16250096?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Infection+and+Immunity&rft.atitle=Natural+proteoglycan+receptor+analogs+determine+the+dynamics+of+Opa+adhesin-mediated+gonococcal+infection+of+Chang+epithelial+cells&rft.au=van+Putten%2C+JPM%3BHayes%2C+S+F%3BDuensing%2C+T+D&rft.aulast=van+Putten&rft.aufirst=JPM&rft.date=1997-12-01&rft.volume=65&rft.issue=12&rft.spage=5028&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Correlations among human blood levels of specific PCB congeners and implications for epidemiologic studies AN - 16246794; 4232358 AB - Specific congeners of PCBs may differ with respect to their human health risks. For epidemiologic studies, measuring levels of specific congeners--as compared with estimating the concentration of total PCBs present, may be of limited value if levels of specific congeners are highly correlated. We examined the correlations among levels of specific congeners in three groups: controls from a case-control study of breast cancer in North Carolina and two groups from Wisconsin with exposure to fish from contaminated waters. Levels of specific congeners were, in general, highly correlated (Pearson r > 0.80). However, the level of congener 180, a heptachlorobiphenyl, tended to be less correlated with levels of lower-chlorinated biphenyls. Among the implications of these findings are that measurement of a select group of congeners may yield essentially the same information as measurement of a large panel, and may be more cost efficient. JF - American Journal of Industrial Medicine AU - DeVoto, E AU - Fiore, B J AU - Millikan, R AU - Anderson, HA AU - Sheldon, L AU - Sonzogni, W C AU - Longnecker, M P AD - NIEHS Epidemiol. Branch, P.O. Box 12233, MD A3-05, Research Triange Park, NC 27709, USA Y1 - 1997/12// PY - 1997 DA - Dec 1997 SP - 606 EP - 613 PB - JOHN WILEY & SONS, INC. VL - 32 IS - 6 SN - 0271-3586, 0271-3586 KW - PCB KW - USA, North Carolina KW - USA, Wisconsin KW - blood levels KW - environmental quality KW - epidemiology KW - man KW - Toxicology Abstracts; Health & Safety Science Abstracts KW - X 24153:Metabolism KW - H 12000:Epidemiology and Public Health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16246794?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Journal+of+Industrial+Medicine&rft.atitle=Correlations+among+human+blood+levels+of+specific+PCB+congeners+and+implications+for+epidemiologic+studies&rft.au=DeVoto%2C+E%3BFiore%2C+B+J%3BMillikan%2C+R%3BAnderson%2C+HA%3BSheldon%2C+L%3BSonzogni%2C+W+C%3BLongnecker%2C+M+P&rft.aulast=DeVoto&rft.aufirst=E&rft.date=1997-12-01&rft.volume=32&rft.issue=6&rft.spage=606&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Industrial+Medicine&rft.issn=02713586&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Shock toxicology with transgenics AN - 16238598; 4230034 AB - Transgenic models for the short-term assessment of chemical and drug safety have provided alternative systems to traditional animal toxicology studies and ultimately may facilitate the adoption of in vitro assays. Several in vivo models are available for assessing the carcinogenic potential of genotoxic chemicals, but few are applicable to the toxicity testing of chemicals that do not interact with DNA. In this issue, Maria Sacco and colleagues the Institute of Advanced Biomedical Technologies, National Research Council (Milan, Italy) have developed an in vivo bioassay that shows significant promise for the identification and evaluation of harmful nongenotoxic chemicals. JF - Nature Biotechnology AU - Cannon, R E AU - Tennant, R W AD - laboratory of environmental carcinogenesis and mutagenesis, National Institute of Environmental Health Sciences, PO Box 12233, Research Triangle Park, NC 27709, USA Y1 - 1997/12// PY - 1997 DA - Dec 1997 SP - 1349 EP - 1350 VL - 15 IS - 13 SN - 1087-0156, 1087-0156 KW - animal models KW - genotoxicity KW - reviews KW - toxicity testing KW - transgenic mice KW - Biotechnology and Bioengineering Abstracts; Toxicology Abstracts; Genetics Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - G 07220:General theory/testing systems KW - X 24221:Toxicity testing KW - W 30965:Miscellaneous, Reviews KW - W3 33055:Genetic engineering (general) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16238598?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+Biotechnology&rft.atitle=Shock+toxicology+with+transgenics&rft.au=Cannon%2C+R+E%3BTennant%2C+R+W&rft.aulast=Cannon&rft.aufirst=R&rft.date=1997-12-01&rft.volume=15&rft.issue=13&rft.spage=1349&rft.isbn=&rft.btitle=&rft.title=Nature+Biotechnology&rft.issn=10870156&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Interaction of NF-kappaB and NFAT with the interferon-gamma promoter. AN - 79430492; 9374532 AB - Interferon-gamma (IFN-gamma) is a pleiotropic lymphokine whose production is restricted to activated T cells and NK cells. Along with other cytokines, IFN-gamma gene expression is inhibited by the immunosuppressant cyclosporin A. We have previously identified an intronic enhancer region (C3) of the IFN-gamma gene that binds the NF-kappaB protein c-Rel and that shows partial DNA sequence homology with the cyclosporin A-sensitive NFAT binding site and the 3'-half of the NF-kappaB consensus site. Sequence analysis of the IFN-gamma promoter revealed the presence of two additional C3-related elements (C3-1P and C3-3P). In addition, an NF-kappaB site (IFN-gamma kappaB) was identified within the promoter region. Based on this observation, we have analyzed the potential role of NF-kappaB and NFAT family members in regulating IFN-gamma transcription. Electrophoretic mobility shift assay analysis demonstrated that after T cell activation, the p50 and p65 NF-kappaB subunits bind specifically to the newly identified IFN-gamma kappaB and C3-related sites. In addition, we identified the NFAT proteins as a component of the inducible complexes that bind to the C3-3P site. Site-directed mutagenesis and transfection studies demonstrate that calcineurin-inducible transcriptional factors enhance the transcriptional activity of the IFN-gamma promoter through the cyclosporin-sensitive C3-3P site, whereas NF-kappaB proteins functionally interact with the C3-related sites. In addition, when located downstream to the beta-galactosidase gene driven by the IFN-gamma promoter, the intronic C3 site worked in concert with both the IFN-gamma kappaB and the C3-3P site to enhance gene transcription. These results demonstrate that the coordinate activities of NFAT and NF-kappaB proteins are involved in the molecular mechanisms controlling IFN-gamma gene transcription. JF - The Journal of biological chemistry AU - Sica, A AU - Dorman, L AU - Viggiano, V AU - Cippitelli, M AU - Ghosh, P AU - Rice, N AU - Young, H A AD - Laboratory of Experimental Immunology, Division of Basic Sciences, National Cancer Institute, Frederick, Maryland 21702-1201, USA. Y1 - 1997/11/28/ PY - 1997 DA - 1997 Nov 28 SP - 30412 EP - 30420 VL - 272 IS - 48 SN - 0021-9258, 0021-9258 KW - DNA-Binding Proteins KW - 0 KW - NF-kappa B KW - NFATC Transcription Factors KW - Nuclear Proteins KW - Proto-Oncogene Proteins KW - Proto-Oncogene Proteins c-rel KW - Transcription Factors KW - Interferon-gamma KW - 82115-62-6 KW - Calcineurin KW - EC 3.1.3.16 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Calcineurin -- physiology KW - T-Lymphocytes -- metabolism KW - Base Sequence KW - Tumor Cells, Cultured KW - Humans KW - Enhancer Elements, Genetic KW - Proto-Oncogene Proteins -- metabolism KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Transcription, Genetic KW - Protein Binding KW - Structure-Activity Relationship KW - Binding Sites KW - Promoter Regions, Genetic KW - Interferon-gamma -- genetics KW - Transcription Factors -- metabolism KW - NF-kappa B -- metabolism KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79430492?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Interaction+of+NF-kappaB+and+NFAT+with+the+interferon-gamma+promoter.&rft.au=Sica%2C+A%3BDorman%2C+L%3BViggiano%2C+V%3BCippitelli%2C+M%3BGhosh%2C+P%3BRice%2C+N%3BYoung%2C+H+A&rft.aulast=Sica&rft.aufirst=A&rft.date=1997-11-28&rft.volume=272&rft.issue=48&rft.spage=30412&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 - 1997-12-22 N1 - Date created - 1997-12-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The rat S-adenosylhomocysteine hydrolase promoter. AN - 79461683; 9398607 AB - The 1.2-kb DNA sequence flanking the transcription start of the AdoHcy hydrolase gene was cloned into the luciferase reporter plasmid pGL3-basic, and promoter activity was measured in transiently transfected CHO cells. Deletion analysis showed that most promoter activity was located within a 153 bp fragment immediately upstream from the predominant transcription start. The 153 bp fragment includes sites for AP-2, glucocorticoid-responsive element, SP-1, and a TATA-like sequence TATTTAAA. Mutational analysis demonstrated that the SP-1 site nearest the start of transcription contributed significantly to promoter activity, whereas, the other elements, including the appropriately positioned TATTTAAA sequence, had little affect on promoter activity. JF - Biochemical and biophysical research communications AU - Merta, A AU - Aksamit, R R AU - Cantoni, G L AD - Laboratory of General and Comparative Biochemistry, National Institute of Mental Health, Bethesda, Maryland 20892, USA. Y1 - 1997/11/26/ PY - 1997 DA - 1997 Nov 26 SP - 580 EP - 585 VL - 240 IS - 3 SN - 0006-291X, 0006-291X KW - DNA Primers KW - 0 KW - RNA, Messenger KW - Hydrolases KW - EC 3.- KW - Adenosylhomocysteinase KW - EC 3.3.1.1 KW - Index Medicus KW - Animals KW - Blotting, Northern KW - DNA Mutational Analysis KW - RNA, Messenger -- analysis KW - Mutagenesis -- genetics KW - RNA, Messenger -- genetics KW - Cloning, Molecular KW - Rats KW - Base Sequence KW - Transfection -- genetics KW - Genes, Reporter KW - Molecular Sequence Data KW - CHO Cells KW - Sequence Deletion KW - Cricetinae KW - Hydrolases -- metabolism KW - Hydrolases -- genetics KW - Promoter Regions, Genetic -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79461683?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+rat+S-adenosylhomocysteine+hydrolase+promoter.&rft.au=Merta%2C+A%3BAksamit%2C+R+R%3BCantoni%2C+G+L&rft.aulast=Merta&rft.aufirst=A&rft.date=1997-11-26&rft.volume=240&rft.issue=3&rft.spage=580&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 - 1998-01-13 N1 - Date created - 1998-01-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - KSR stimulates Raf-1 activity in a kinase-independent manner. AN - 79459738; 9371754 AB - Kinase suppressor of Ras (KSR) is an evolutionarily conserved component of Ras-dependent signaling pathways. Here, we find that murine KSR (mKSR1) translocates from the cytoplasm to the plasma membrane in the presence of activated Ras. At the membrane, mKSR1 modulates Ras signaling by enhancing Raf-1 activity in a kinase-independent manner. The activation of Raf-1 is mediated by the mKSR1 cysteine-rich CA3 domain and involves a detergent labile cofactor that is not ceramide. These findings reveal another point of regulation for Ras-mediated signal transduction and further define a noncatalytic role for mKSR1 in the multistep process of Raf-1 activation. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Michaud, N R AU - Therrien, M AU - Cacace, A AU - Edsall, L C AU - Spiegel, S AU - Rubin, G M AU - Morrison, D K AD - Molecular Basis of Carcinogenesis Laboratory, National Cancer Institute, Frederick Cancer Research and Development Center, MD 21702, USA. Y1 - 1997/11/25/ PY - 1997 DA - 1997 Nov 25 SP - 12792 EP - 12796 VL - 94 IS - 24 SN - 0027-8424, 0027-8424 KW - Ceramides KW - 0 KW - Protein Kinases KW - EC 2.7.- KW - KSR-1 protein kinase KW - EC 2.7.1.- KW - Proto-Oncogene Proteins c-raf KW - EC 2.7.11.1 KW - Index Medicus KW - Animals KW - COS Cells KW - Enzyme Activation KW - Cell Membrane -- metabolism KW - Ceramides -- pharmacology KW - Protein Kinases -- metabolism KW - Proto-Oncogene Proteins c-raf -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79459738?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=KSR+stimulates+Raf-1+activity+in+a+kinase-independent+manner.&rft.au=Michaud%2C+N+R%3BTherrien%2C+M%3BCacace%2C+A%3BEdsall%2C+L+C%3BSpiegel%2C+S%3BRubin%2C+G+M%3BMorrison%2C+D+K&rft.aulast=Michaud&rft.aufirst=N&rft.date=1997-11-25&rft.volume=94&rft.issue=24&rft.spage=12792&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 - 1998-01-08 N1 - Date created - 1998-01-08 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cell. 1995 Dec 15;83(6):903-13 [8521514] EMBO J. 1997 May 1;16(9):2384-96 [9171352] J Biol Chem. 1996 Apr 5;271(14):8472-80 [8626548] Nature. 1996 Jun 27;381(6585):800-3 [8657285] Proc Natl Acad Sci U S A. 1996 Jul 9;93(14):6959-63 [8692926] Proc Natl Acad Sci U S A. 1996 Aug 6;93(16):8312-7 [8710867] J Biol Chem. 1996 Aug 2;271(31):18299-301 [8702464] Cell. 1996 Sep 6;86(5):777-86 [8797824] Genes Dev. 1996 Nov 1;10(21):2684-95 [8946910] Mol Cell Biol. 1997 Jan;17(1):46-53 [8972184] Protein Sci. 1997 Feb;6(2):477-80 [9041654] Curr Opin Cell Biol. 1997 Apr;9(2):161-7 [9069266] Curr Opin Cell Biol. 1997 Apr;9(2):174-9 [9069260] Cell. 1997 Apr 4;89(1):63-72 [9094715] Nature. 1996 Mar 7;380(6569):75-9 [8598911] Nature. 1987 Jan 22-28;325(6102):359-61 [3027568] Proc Natl Acad Sci U S A. 1989 Jul;86(13):4868-71 [2500657] Genes Dev. 1992 Apr;6(4):545-56 [1313769] J Biol Chem. 1992 Aug 15;267(23):16347-54 [1322899] J Biol Chem. 1993 Jan 5;268(1):13-6 [8380153] Nature. 1993 Jul 22;364(6435):308-13 [8332187] Proc Natl Acad Sci U S A. 1993 Sep 15;90(18):8310-3 [8104334] J Biol Chem. 1994 Feb 4;269(5):3125-8 [8106344] J Biol Chem. 1994 Apr 1;269(13):10000-7 [8144497] Nature. 1994 May 12;369(6476):156-60 [8177321] Trends Genet. 1994 Feb;10(2):44-8 [8191584] Nature. 1994 Jun 2;369(6479):411-4 [8196769] Science. 1994 Jun 3;264(5164):1463-7 [7811320] J Biol Chem. 1994 Jul 29;269(30):19200-2 [8034680] Nature. 1994 Aug 18;370(6490):527-32 [8052307] Proc Natl Acad Sci U S A. 1994 Sep 27;91(20):9544-8 [7937802] Mol Carcinog. 1995 Mar;12(3):166-76 [7893369] EMBO J. 1995 May 1;14(9):1961-9 [7744003] Mol Cell Biol. 1995 Jun;15(6):3390-7 [7760835] J Biol Chem. 1995 Jun 2;270(22):13541-7 [7768956] Cell. 1995 Jun 16;81(6):917-24 [7781068] Mol Cell Biol. 1995 Aug;15(8):4125-35 [7623807] J Biol Chem. 1995 Nov 10;270(45):26802-6 [7592920] Mol Cell Biol. 1996 Jan;16(1):105-14 [8524286] J Biol Chem. 1995 Dec 22;270(51):30274-7 [8530446] Cell. 1995 Dec 15;83(6):879-88 [8521512] Cell. 1995 Dec 15;83(6):889-901 [8521513] Oncogene. 1997 Apr 3;14(13):1571-80 [9129148] Curr Biol. 1997 May 1;7(5):294-300 [9115393] Erratum In: Proc Natl Acad Sci U S A 1998 mAR 3;95(5):2714-5 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inhibition of regulator of G protein signaling function by two mutant RGS4 proteins. AN - 79454534; 9371764 AB - Regulators of G protein signaling (RGS) proteins limit the lifetime of activated (GTP-bound) heterotrimeric G protein a subunits by acting as GTPase-activating proteins (GAPs). Mutation of two residues in RGS4, which, based on the crystal structure of RGS4 complexed with G(i alpha1)-GDP-AIF4-, directly contact G(i alpha1) (N88 and L159), essentially abolished RGS4 binding and GAP activity. Mutation of another contact residue (S164) partially inhibited both binding and GAP activity. Two other mutations, one of a contact residue (R167M/A) and the other an adjacent residue (F168A), also significantly reduced RGS4 binding to G(i alpha1)-GDP-AIF4-, but in addition redirected RGS4 binding toward the GTPgammaS-bound form. These two mutant proteins had severely impaired GAP activity, but in contrast to the others behaved as RGS antagonists in GAP and in vivo signaling assays. Overall, these results are consistent with the hypothesis that the predominant role of RGS proteins is to stabilize the transition state for GTP hydrolysis. In addition, mutant RGS proteins can be created with an altered binding preference for the G(i alpha)-GTP conformation, suggesting that efficient RGS antagonists can be developed. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Druey, K M AU - Kehrl, J H AD - Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1997/11/25/ PY - 1997 DA - 1997 Nov 25 SP - 12851 EP - 12856 VL - 94 IS - 24 SN - 0027-8424, 0027-8424 KW - GTPase-Activating Proteins KW - 0 KW - Proteins KW - RGS Proteins KW - RGS4 protein KW - 175335-35-0 KW - Calcium-Calmodulin-Dependent Protein Kinases KW - EC 2.7.11.17 KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - Index Medicus KW - Phenotype KW - Calcium-Calmodulin-Dependent Protein Kinases -- metabolism KW - Animals KW - Enzyme Activation KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Sequence Homology, Amino Acid KW - Protein Binding KW - Mutagenesis KW - Binding Sites KW - Proteins -- antagonists & inhibitors KW - GTP-Binding Proteins -- metabolism KW - Proteins -- metabolism KW - Proteins -- genetics KW - Signal Transduction UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79454534?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Inhibition+of+regulator+of+G+protein+signaling+function+by+two+mutant+RGS4+proteins.&rft.au=Druey%2C+K+M%3BKehrl%2C+J+H&rft.aulast=Druey&rft.aufirst=K&rft.date=1997-11-25&rft.volume=94&rft.issue=24&rft.spage=12851&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 - 1998-01-08 N1 - Date created - 1998-01-08 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cell. 1992 Aug 7;70(3):411-8 [1322796] Science. 1991 Sep 13;253(5025):1280-3 [1891716] Mol Cell Biochem. 1993 Nov;127-128:171-7 [7523847] Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):9828-31 [7937899] Nature. 1994 Nov 17;372(6503):276-9 [7969474] Cell. 1995 Jan 27;80(2):249-57 [7834744] Proc Natl Acad Sci U S A. 1995 Dec 5;92(25):11916-20 [8524874] Nature. 1996 Feb 22;379(6567):742-6 [8602223] Cell. 1996 Aug 9;86(3):445-52 [8756726] Nature. 1996 Sep 12;383(6596):172-5 [8774882] Nature. 1996 Sep 12;383(6596):175-7 [8774883] J Biol Chem. 1996 Nov 1;271(44):27209-12 [8910288] Proc Natl Acad Sci U S A. 1997 Jan 21;94(2):428-32 [9012799] J Biol Chem. 1997 Feb 14;272(7):3871-4 [9064301] Cell. 1997 Apr 18;89(2):251-61 [9108480] Proc Natl Acad Sci U S A. 1997 Jul 8;94(14):7216-20 [9207071] Science. 1997 Jul 18;277(5324):333-8 [9219684] Science. 1997 Jul 18;277(5324):329-30 [9518363] Nature. 1991 Jan 10;349(6305):117-27 [1898771] Science. 1994 Sep 2;265(5177):1405-12 [8073283] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inhibition of NF-kappaB DNA binding and nitric oxide induction in human T cells and lung adenocarcinoma cells by selenite treatment. AN - 79454051; 9371773 AB - NF-kappaB is a major transcription factor consisting of 50(p50)- and 65(p65)-kDa proteins that controls the expression of various genes, among which are those encoding cytokines, cell adhesion molecules, and inducible NO synthase (iNOS). After initial activation of NF-kappaB, which involves release and proteolysis of a bound inhibitor, essential cysteine residues are maintained in the active reduced state through the action of thioredoxin and thioredoxin reductase. In the present study, activation of NF-kappaB in human T cells and lung adenocarcinoma cells was induced by recombinant human tumor necrosis factor alpha or bacterial lipopolysaccharide. After lipopolysaccharide activation, nuclear extracts were treated with increasing concentrations of selenite, and the effects on DNA-binding activity of NF-kappaB were examined. Binding of NF-kappaB to nuclear responsive elements was decreased progressively by increasing selenite levels and, at 7 microM selenite, DNA-binding activity was completely inhibited. Selenite inhibition was reversed by addition of a dithiol, DTT. Proportional inhibition of iNOS activity as measured by decreased NO products in the medium (NO2- and NO3-) resulted from selenite addition to cell suspensions. This loss of iNOS activity was due to decreased synthesis of NO synthase protein. Selenium at low essential levels (nM) is required for synthesis of redox active selenoenzymes such as glutathione peroxidases and thioredoxin reductase, but in higher toxic levels (>5-10 microM) selenite can react with essential thiol groups on enzymes to form RS-Se-SR adducts with resultant inhibition of enzyme activity. Inhibition of NF-kappaB activity by selenite is presumed to be the result of adduct formation with the essential thiols of this transcription factor. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Kim, I Y AU - Stadtman, T C AD - Laboratory of Biochemistry, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1997/11/25/ PY - 1997 DA - 1997 Nov 25 SP - 12904 EP - 12907 VL - 94 IS - 24 SN - 0027-8424, 0027-8424 KW - NF-kappa B KW - 0 KW - Nitric Oxide KW - 31C4KY9ESH KW - DNA KW - 9007-49-2 KW - Nitric Oxide Synthase KW - EC 1.14.13.39 KW - Sodium Selenite KW - HIW548RQ3W KW - Index Medicus KW - Tumor Cells, Cultured KW - Nitric Oxide Synthase -- genetics KW - Humans KW - Jurkat Cells KW - Enzyme Induction KW - Protein Binding KW - Nitric Oxide Synthase -- biosynthesis KW - Adenocarcinoma -- metabolism KW - T-Lymphocytes -- metabolism KW - Nitric Oxide -- antagonists & inhibitors KW - Sodium Selenite -- pharmacology KW - DNA -- metabolism KW - T-Lymphocytes -- drug effects KW - Nitric Oxide -- biosynthesis KW - NF-kappa B -- metabolism KW - NF-kappa B -- antagonists & inhibitors KW - Lung Neoplasms -- pathology KW - Lung Neoplasms -- metabolism KW - Adenocarcinoma -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79454051?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Inhibition+of+NF-kappaB+DNA+binding+and+nitric+oxide+induction+in+human+T+cells+and+lung+adenocarcinoma+cells+by+selenite+treatment.&rft.au=Kim%2C+I+Y%3BStadtman%2C+T+C&rft.aulast=Kim&rft.aufirst=I&rft.date=1997-11-25&rft.volume=94&rft.issue=24&rft.spage=12904&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 - 1998-01-08 N1 - Date created - 1998-01-08 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1990 Oct;87(20):7861-5 [2146676] J Biol Chem. 1990 Sep 25;265(27):16039-42 [2168876] Biochim Biophys Acta. 1991 Apr 16;1072(1):63-80 [2018779] EMBO J. 1991 Aug;10(8):2247-58 [2065663] Arch Biochem Biophys. 1991 Aug 15;289(1):161-6 [1910313] J Exp Med. 1992 May 1;175(5):1181-94 [1314883] Int Rev Cytol. 1993;143:1-62 [8449662] J Biol Chem. 1993 May 25;268(15):11380-8 [8496188] J Exp Med. 1993 Jun 1;177(6):1779-84 [7684434] Anal Biochem. 1993 Aug 15;213(1):162-7 [8238869] J Biol Chem. 1994 Feb 18;269(7):4705-8 [7508926] J Biol Chem. 1994 May 13;269(19):13725-8 [7514592] J Leukoc Biol. 1994 Nov;56(5):576-82 [7525816] Proc Natl Acad Sci U S A. 1995 May 9;92(10):4497-501 [7753832] FEBS Lett. 1995 Jul 10;368(1):59-63 [7615089] Biochem Pharmacol. 1995 Sep 7;50(6):735-41 [7575632] J Biol Chem. 1995 Oct 20;270(42):24995-5000 [7559628] FEBS Lett. 1995 Dec 11;377(1):21-5 [8543010] Proc Natl Acad Sci U S A. 1996 Apr 16;93(8):3308-12 [8622934] Arch Toxicol. 1996;70(5):277-83 [8852698] Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):3633-8 [9108029] Annu Rev Immunol. 1997;15:351-69 [9143692] Biochemistry. 1969 Jun;8(6):2557-63 [5816383] Proc Natl Acad Sci U S A. 1976 Jun;73(6):2023-7 [1064872] Anal Biochem. 1976 May 7;72:248-54 [942051] Biochem J. 1979 Apr 15;180(1):213-8 [384997] Anal Biochem. 1982 Oct;126(1):131-8 [7181105] Mol Pharmacol. 1987 Jan;31(1):112-6 [3807888] J Virol. 1989 Aug;63(8):3220-6 [2501514] Mol Cell Biol. 1990 Apr;10(4):1498-506 [2181276] Science. 1990 Sep 7;249(4973):1157-61 [2118682] Proc Natl Acad Sci U S A. 1990 Dec;87(24):9943-7 [2263644] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The constitutively active mutant Galpha13 transforms mouse fibroblast cells deficient in insulin-like growth factor-I receptor. AN - 79429052; 9368001 AB - Insulin-like growth factor-I (IGF-I) receptor plays an important role in normal cell cycle progression and tumor growth, and it is thought to be essential for cellular transformation. To test this hypothesis, we stably transfected a GTPase-deficient mutant human Galpha13, which is highly oncogenic when overexpressed in vitro, into R- fibroblasts derived from IGF-I receptor-deficient mice. Northern blots of multiple clones revealed the expression of a 1.8-kilobase pair mutant Galpha13 transcript in transfected cells, in addition to the 6-kilobase pair endogenous mRNA. The transfection resulted in a doubling of the expression of Galpha13 protein in these cells as assessed by Western blot analysis. The transforming ability of the mutant Galpha13 was tested using the soft agar assay. Nontransfected R- cells cultured with 10% fetal bovine serum failed to form colonies after 3 weeks. Most of the mutant Galpha13-expressing clones formed significant numbers of colonies (11-50 colonies/1000 cells plated). Overexpression of the IGF-I receptor enabled R- cells to form colonies (27 colonies), and co-transfection of the mutant Galpha13 caused a further increase in colony formation (117-153 colonies) in three of five clones analyzed. Apparently Galpha13 works through pathways other than mitogen-activated protein kinase and c-Jun N-terminal kinase in transforming R- cells, because their activities were not significantly altered by the mutant Galpha13 expression. These results demonstrate that Galpha13 can induce cellular transformation through pathways apparently independent of the IGF-I receptor and that activation of the IGF-I receptor signaling pathways, although not essential for the transforming phenotype, enhances the effect of other pathways. JF - The Journal of biological chemistry AU - Liu, J L AU - Blakesley, V A AU - Gutkind, J S AU - LeRoith, D AD - Section on Cellular and Molecular Physiology, Diabetes Branch, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1997/11/21/ PY - 1997 DA - 1997 Nov 21 SP - 29438 EP - 29441 VL - 272 IS - 47 SN - 0021-9258, 0021-9258 KW - RNA, Messenger KW - 0 KW - Receptor, IGF Type 1 KW - EC 2.7.10.1 KW - Calcium-Calmodulin-Dependent Protein Kinases KW - EC 2.7.11.17 KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - Index Medicus KW - Calcium-Calmodulin-Dependent Protein Kinases -- metabolism KW - Animals KW - Cattle KW - RNA, Messenger -- metabolism KW - Transfection KW - Humans KW - Mice KW - Cell Line KW - Mutagenesis KW - Receptor, IGF Type 1 -- physiology KW - GTP-Binding Proteins -- physiology KW - Fibroblasts -- cytology KW - GTP-Binding Proteins -- genetics KW - Fibroblasts -- metabolism KW - Receptor, IGF Type 1 -- deficiency KW - Cell Transformation, Neoplastic UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79429052?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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+constitutively+active+mutant+Galpha13+transforms+mouse+fibroblast+cells+deficient+in+insulin-like+growth+factor-I+receptor.&rft.au=Liu%2C+J+L%3BBlakesley%2C+V+A%3BGutkind%2C+J+S%3BLeRoith%2C+D&rft.aulast=Liu&rft.aufirst=J&rft.date=1997-11-21&rft.volume=272&rft.issue=47&rft.spage=29438&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 - 1997-12-23 N1 - Date created - 1997-12-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Alcohol dehydrogenase 3 genotype and risk of oral cavity and pharyngeal cancers. AN - 79439690; 9390539 AB - The consumption of alcoholic beverages is a strong risk factor for cancers of the oral cavity and pharynx (oral cancers). Alcohol dehydrogenase type 3 (ADH3) metabolizes ethanol to acetaldehyde, a carcinogen. We evaluated whether individuals homozygous for the fast-metabolizing ADH3(1) allele (ADH3[1-1]) have a greater risk of developing oral cancer in the presence of alcoholic beverage consumption than those with the slow-metabolizing ADH3(2) allele (ADH3[1-2] and ADH3[2-2]). As part of a population-based study of oral cancer conducted in Puerto Rico, the ADH3 genotypes of 137 patients with histologically confirmed oral cancer and of 146 control subjects (i.e., individuals with no history of oral cancer) were determined by molecular genetic analysis of oral epithelial cell samples. Risks were estimated by use of multiple logistic regression analyses. Compared with nondrinkers with the ADH3(1-1) genotype, consumers of at least 57 alcoholic drinks per week with the ADH3(1-1), ADH3(1-2), and ADH3(2-2) genotypes had 40.1-fold (95% confidence interval [CI] = 5.4-296.0), 7.0-fold (95% CI = 1.4-35.0), and 4.4-fold (95% CI = 0.6-33.0) increased risks of oral cancer, respectively; the risk associated with the ADH3(1-1) genotype, compared with the ADH3(1-2) and ADH3(2-2) genotypes combined, was 5.3 (95% CI = 1.0-28.8) among such drinkers. Considering all levels of alcohol consumption, the risk of oral cancer per additional alcoholic drink per week increased 3.6% (95% CI = 1.9%-5.4%) for subjects with the ADH3(1-1) genotype and 2.0% (95% CI = 0.9%-3.0%) for subjects with the ADH3(1-2) or ADH3(2-2) genotype (two-sided P = .04). The ADH3(1-1) genotype appears to substantially increase the risk of ethanol-related oral cancer, thus providing further evidence for the carcinogenicity of acetaldehyde. JF - Journal of the National Cancer Institute AU - Harty, L C AU - Caporaso, N E AU - Hayes, R B AU - Winn, D M AU - Bravo-Otero, E AU - Blot, W J AU - Kleinman, D V AU - Brown, L M AU - Armenian, H K AU - Fraumeni, J F AU - Shields, P G AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892-7372, USA. hartyl@epndce.nci.nih.gov Y1 - 1997/11/19/ PY - 1997 DA - 1997 Nov 19 SP - 1698 EP - 1705 VL - 89 IS - 22 SN - 0027-8874, 0027-8874 KW - DNA Primers KW - 0 KW - Alcohol Dehydrogenase KW - EC 1.1.1.1 KW - Index Medicus KW - Genotype KW - Risk KW - Logistic Models KW - Humans KW - Case-Control Studies KW - Aged KW - Middle Aged KW - Male KW - Female KW - Pharyngeal Neoplasms -- etiology KW - Pharyngeal Neoplasms -- enzymology KW - Alcohol Dehydrogenase -- genetics KW - Mouth Neoplasms -- etiology KW - Mouth Neoplasms -- enzymology KW - Alcohol Drinking -- adverse effects KW - Pharyngeal Neoplasms -- genetics KW - Mouth Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79439690?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Alcohol+dehydrogenase+3+genotype+and+risk+of+oral+cavity+and+pharyngeal+cancers.&rft.au=Harty%2C+L+C%3BCaporaso%2C+N+E%3BHayes%2C+R+B%3BWinn%2C+D+M%3BBravo-Otero%2C+E%3BBlot%2C+W+J%3BKleinman%2C+D+V%3BBrown%2C+L+M%3BArmenian%2C+H+K%3BFraumeni%2C+J+F%3BShields%2C+P+G&rft.aulast=Harty&rft.aufirst=L&rft.date=1997-11-19&rft.volume=89&rft.issue=22&rft.spage=1698&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 - 1997-12-12 N1 - Date created - 1997-12-12 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Natl Cancer Inst. 1997 Nov 19;89(22):1656-7 [9390529] J Natl Cancer Inst. 1998 Jun 17;90(12):937-9 [9637146] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular characterization of fetal alcohol syndrome using mRNA differential display. AN - 79435603; 9388474 AB - The molecular pathogenesis of fetal alcohol syndrome (FAS) has not been well elucidated. The technique of mRNA differential display was used to characterize the etiology and to identify potential markers for FAS. Out of approximately 1,080 mRNA transcripts in mouse embryos that were analyzed, the levels of three mRNAs were altered by ethanol. Two of these mRNAs (one novel and one encoding heat shock protein 47) were also modulated by another teratogen, 3-methylcholanthrene. The third mRNA, encoding alpha-tropomyosin, was specifically up-regulated by ethanol. Consistent with the Northern blot data, immunoblot analysis demonstrated that the level of alpha-tropomyosin protein (31 kDa, most likely a brain specific isoform) was elevated in the embryos exposed to ethanol. JF - Biochemical and biophysical research communications AU - Lee, I J AU - Soh, Y AU - Song, B J AD - Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, Rockville, Maryland 20852, USA. Y1 - 1997/11/17/ PY - 1997 DA - 1997 Nov 17 SP - 309 EP - 313 VL - 240 IS - 2 SN - 0006-291X, 0006-291X KW - Biomarkers KW - 0 KW - RNA, Messenger KW - Tropomyosin KW - Ethanol KW - 3K9958V90M KW - Index Medicus KW - Animals, Newborn KW - Animals KW - Ethanol -- pharmacology KW - Gestational Age KW - Mice, Inbred C57BL KW - Liver -- metabolism KW - Disease Models, Animal KW - Mice KW - Brain -- metabolism KW - Placenta -- metabolism KW - Muscle, Skeletal -- metabolism KW - Female KW - Pregnancy KW - Fetal Alcohol Spectrum Disorders -- metabolism KW - Fetal Alcohol Spectrum Disorders -- genetics KW - Transcription, Genetic KW - Tropomyosin -- biosynthesis KW - RNA, Messenger -- biosynthesis KW - Gene Expression Regulation, Developmental -- drug effects KW - Fetal Alcohol Spectrum Disorders -- embryology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79435603?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Molecular+characterization+of+fetal+alcohol+syndrome+using+mRNA+differential+display.&rft.au=Lee%2C+I+J%3BSoh%2C+Y%3BSong%2C+B+J&rft.aulast=Lee&rft.aufirst=I&rft.date=1997-11-17&rft.volume=240&rft.issue=2&rft.spage=309&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 - 1997-12-23 N1 - Date created - 1997-12-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Critical contacts between HIV-1 integrase and viral DNA identified by structure-based analysis and photo-crosslinking. AN - 79410652; 9362498 AB - Analysis of the crystal structure of HIV-1 integrase reveals a cluster of lysine residues near the active site. Using site-directed mutagenesis and photo-crosslinking we find that Lys156 and Lys159 are critical for the functional interaction of integrase with viral DNA. Mutation of Lys156 or Lys159 to glutamate led to a loss of both 3' processing and strand transfer activities in vitro while maintaining the ability to interact with nonspecific DNA and support disintegration. However, mutation of both residues to glutamate produced a synergistic effect eliminating nearly all nonspecific DNA interaction and disintegration activity. In addition, virus containing either of these changes was replication-defective at the step of integration. Photo-crosslinking, using 5-iododeoxyuracil-substituted oligonucleotides, suggests that Lys159 interacts at the N7 position of the conserved deoxyadenosine adjacent to the scissile phosphodiester bond of viral DNA. Sequence conservation throughout retroviral integrases and certain bacterial transposases (e.g. Tn10/IS10) supports the premise that within those families of polynucleotidyl transferases, these residues are strategic for DNA interaction. JF - The EMBO journal AU - Jenkins, T M AU - Esposito, D AU - Engelman, A AU - Craigie, R AD - Laboratory of Molecular Biology, NIDDK, NIH, Bethesda, MD 20892-0560, USA. Y1 - 1997/11/17/ PY - 1997 DA - 1997 Nov 17 SP - 6849 EP - 6859 VL - 16 IS - 22 SN - 0261-4189, 0261-4189 KW - DNA, Viral KW - 0 KW - DNA-Binding Proteins KW - HIV Integrase KW - EC 2.7.7.- KW - Integrases KW - Lysine KW - K3Z4F929H6 KW - Index Medicus KW - AIDS/HIV KW - Models, Molecular KW - DNA Mutational Analysis KW - Integrases -- genetics KW - Amino Acid Sequence KW - Lysine -- genetics KW - Protein Binding KW - Binding Sites KW - Retroviridae -- enzymology KW - Virus Replication -- genetics KW - Conserved Sequence KW - Molecular Sequence Data KW - Substrate Specificity KW - Sequence Homology, Amino Acid KW - Species Specificity KW - Protein Conformation KW - DNA, Viral -- chemistry KW - DNA-Binding Proteins -- chemistry KW - HIV-1 -- enzymology KW - HIV Integrase -- chemistry KW - HIV Integrase -- metabolism KW - DNA-Binding Proteins -- metabolism KW - DNA, Viral -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79410652?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Critical+contacts+between+HIV-1+integrase+and+viral+DNA+identified+by+structure-based+analysis+and+photo-crosslinking.&rft.au=Jenkins%2C+T+M%3BEsposito%2C+D%3BEngelman%2C+A%3BCraigie%2C+R&rft.aulast=Jenkins&rft.aufirst=T&rft.date=1997-11-17&rft.volume=16&rft.issue=22&rft.spage=6849&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 - 1998-01-05 N1 - Date created - 1998-01-05 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Mol Microbiol. 1990 Jun;4(6):961-75 [2170815] Proc Natl Acad Sci U S A. 1991 Feb 15;88(4):1339-43 [1847518] J Virol. 1997 May;71(5):3507-14 [9094622] Nat Struct Biol. 1997 Jul;4(7):567-77 [9228950] J Virol. 1993 Jan;67(1):425-37 [8416376] Nucleic Acids Res. 1993 Mar 25;21(6):1419-25 [8464733] Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3428-32 [8386373] EMBO J. 1993 Aug;12(8):3261-7 [8344263] EMBO J. 1993 Aug;12(8):3269-75 [8344264] Nucleic Acids Res. 1993 Jul 25;21(15):3507-11 [8346030] Science. 1993 Nov 19;262(5137):1255-7 [7694369] J Virol. 1994 Mar;68(3):1633-42 [8107224] Trends Genet. 1993 Dec;9(12):433-8 [8122311] J Virol. 1994 Aug;68(8):4768-75 [8035478] Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):7316-20 [8041787] J Virol. 1994 Sep;68(9):5911-7 [8057470] Nucleic Acids Res. 1994 Oct 11;22(20):4103-10 [7937134] Nucleic Acids Res. 1994 Oct 11;22(20):4125-31 [7937137] J Virol. 1991 Aug;65(8):4350-8 [2072454] Nucleic Acids Res. 1991 Jul 25;19(14):3821-7 [1861975] J Virol. 1991 Oct;65(10):5624-30 [1895409] J Mol Graph. 1991 Dec;9(4):230-6, 242 [1772848] Science. 1992 Feb 7;255(5045):723-6 [1738845] AIDS Res Hum Retroviruses. 1992 Feb;8(2):297-304 [1540416] Mol Cell Biol. 1992 May;12(5):2331-8 [1314954] J Biol Chem. 1992 May 15;267(14):9639-44 [1577801] Virology. 1992 Jun;188(2):459-68 [1585629] Biochem Biophys Res Commun. 1992 Jun 30;185(3):874-80 [1627142] J Biol Chem. 1992 Aug 15;267(23):16037-40 [1322888] J Virol. 1992 Nov;66(11):6361-9 [1404595] Proc Natl Acad Sci U S A. 1992 Oct 15;89(20):9598-602 [1409671] J Virol. 1996 Oct;70(10):6820-5 [8794322] Proc Natl Acad Sci U S A. 1996 Nov 26;93(24):13659-64 [8942990] Genes Dev. 1997 Feb 1;11(3):371-82 [9030689] J Virol. 1994 Dec;68(12):8401-5 [7966634] Annu Rev Biochem. 1994;63:133-73 [7526778] J Virol. 1995 Jan;69(1):376-86 [7983732] Science. 1994 Dec 23;266(5193):1981-6 [7801124] Virology. 1995 Jan 10;206(1):448-56 [7831800] J Biol Chem. 1995 Feb 17;270(7):3320-6 [7852418] J Virol. 1995 May;69(5):2729-36 [7535863] Structure. 1995 Feb 15;3(2):131-4 [7735828] Mol Microbiol. 1995 Jan;15(1):13-23 [7752887] Proc Natl Acad Sci U S A. 1995 Jun 20;92(13):6057-61 [7597080] Biochemistry. 1995 Aug 8;34(31):9826-33 [7632683] J Virol. 1995 Sep;69(9):5908-11 [7637039] Virology. 1995 Aug 1;211(1):332-5 [7544046] J Virol. 1995 Nov;69(11):6687-96 [7474078] Nat Struct Biol. 1995 Sep;2(9):807-10 [7552753] J Mol Biol. 1995 Oct 20;253(2):333-46 [7563093] J Biol Chem. 1995 Dec 8;270(49):29299-306 [7493962] Biochem Biophys Res Commun. 1995 Dec 26;217(3):802-10 [8554601] J Virol. 1996 Feb;70(2):721-8 [8551608] Cell. 1996 Jan 26;84(2):223-33 [8565068] J Mol Biol. 1996 Mar 1;256(3):533-47 [8604136] Biochemistry. 1996 Mar 26;35(12):3837-44 [8620007] J Biol Chem. 1996 Mar 29;271(13):7712-8 [8631811] Curr Opin Struct Biol. 1996 Feb;6(1):76-83 [8696976] Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7 [271968] Virology. 1978 Aug;89(1):119-32 [210568] J Immunol. 1984 Jul;133(1):123-8 [6327821] J Virol. 1986 Aug;59(2):284-91 [3016298] Proc Natl Acad Sci U S A. 1986 Oct;83(20):7648-52 [2429313] Nucleic Acids Res. 1988 Aug 11;16(15):7351-67 [3045756] J Mol Biol. 1988 Sep 5;203(1):131-9 [3054118] Proc Natl Acad Sci U S A. 1990 Jul;87(13):5119-23 [2164223] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cellular adaptation to drug exposure: evolution of the drug-resistant phenotype. AN - 79415225; 9371507 AB - The efficacy of all chemotherapeutic agents is limited by the occurrence of drug resistance. For etoposide (VP-16), increased expression of MDR-1 or MRP and alterations in topoisomerase IIalpha have been shown to confer tolerance. To further understand resistance to VP-16, three sublines, designated MCF-7-VP17, ZR-75B-VP13, and MDA-MB-231-VP7, were initially isolated as single clones from parental cells by exposure to VP-16. Subsequently, a population of cells from each subline was exposed to 3-fold higher drug concentrations, allowing stable sublines to be established at higher extracellular drug concentrations. Characterization of the resistant sublines demonstrates the adaptation that occurs with advancing drug concentrations during in vitro selections. Reduced topoisomerase II mRNA and protein levels were observed in the initial isolates. This reduction was accompanied by a decrease in topoisomerase II activity and cellular growth rate and was associated with 6-314-fold resistance to topoisomerase II poisons. With advancing resistance, MRP expression increased and VP-16 accumulation decreased. This adaptation allowed for partial restoration of topoisomerase II activity as a result of increased expression (MCF-7-VP17 and ZR-75B-VP13) or hyperphosphorylation (MDA-MB-231-VP7), with a resultant increase in growth rate. In MDA-MB-231-VP7 cells, hyperphosphorylation coincided with increased casein kinase II mRNA and protein levels, suggesting a role for this kinase in the acquired hyperphosphorylation. In this cell line, hyperphosphorylation mediated the increased activity despite a fall in topoisomerase IIalpha protein levels secondary to an acquired 600-bp deletion in one topoisomerase IIalpha allele, which resulted in reduced protein levels. In all three sublines, high levels of resistance were attained as a result of synergism between the reduced topoisomerase IIalpha levels and MRP overexpression. These studies demonstrate how cellular adaptation to increasing drug pressure occurs and how more than one mechanism can contribute to the resistant phenotype when increasing selecting pressure is applied. Reduced expression of topoisomerase II is sufficient to confer substantial resistance early in the selection process, with synergy from MRP overexpression helping to confer high levels of resistance. JF - Cancer research AU - Matsumoto, Y AU - Takano, H AU - Fojo, T AD - Division of Clinical Sciences, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. Y1 - 1997/11/15/ PY - 1997 DA - 1997 Nov 15 SP - 5086 EP - 5092 VL - 57 IS - 22 SN - 0008-5472, 0008-5472 KW - Antineoplastic Agents, Phytogenic KW - 0 KW - RNA, Messenger KW - Etoposide KW - 6PLQ3CP4P3 KW - DNA Topoisomerases, Type II KW - EC 5.99.1.3 KW - Index Medicus KW - Phenotype KW - RNA, Messenger -- metabolism KW - Phosphorylation KW - Breast Neoplasms -- pathology KW - Tumor Cells, Cultured -- drug effects KW - Humans KW - Tumor Cells, Cultured -- pathology KW - Breast Neoplasms -- metabolism KW - Drug Resistance, Neoplasm KW - Sequence Deletion KW - Etoposide -- pharmacology KW - Drug Resistance, Multiple -- physiology KW - DNA Topoisomerases, Type II -- genetics KW - DNA Topoisomerases, Type II -- metabolism KW - Antineoplastic Agents, Phytogenic -- pharmacology KW - Tumor Stem Cell Assay KW - Etoposide -- metabolism KW - Antineoplastic Agents, Phytogenic -- metabolism KW - Drug Resistance, Multiple -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79415225?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cellular+adaptation+to+drug+exposure%3A+evolution+of+the+drug-resistant+phenotype.&rft.au=Matsumoto%2C+Y%3BTakano%2C+H%3BFojo%2C+T&rft.aulast=Matsumoto&rft.aufirst=Y&rft.date=1997-11-15&rft.volume=57&rft.issue=22&rft.spage=5086&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 - 1997-12-01 N1 - Date created - 1997-12-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Myeloperoxidase genetic polymorphism and lung cancer risk. AN - 79412916; 9371491 AB - Myeloperoxidase is a lysosomal enzyme found in high concentrations in human lung due to recruitment of neutrophils. Myeloperoxidase activates benzo[a]pyrene as well as aromatic amines in tobacco smoke and generates carcinogen-free radicals. A single base substitution (G to A) in the promoter region of the myeloperoxidase gene has recently been demonstrated to markedly reduce transcription. We developed an RFLP/PCR assay to test the hypothesis that the allele favoring lower transcription (A allele) reduces the risk of lung cancer. Among population controls, 7.8% of 459 Caucasians and 9.4% of 244 African-Americans inherited two copies of the A allele. Caucasians with the A/A genotype were at 70% reduced risk of lung cancer (odds ratio, 0.30; 95% confidence interval, 0.10-0.93; P = 0.04; 182 cases). A lesser reduction in risk was observed for African-Americans with this genotype (odds ratio, 0.61; 95% confidence interval, 0.26-1.41; 157 cases). Individuals who inherit two copies of an allele that reduces transcription of the myeloperoxidase gene may be at decreased risk of lung cancer. JF - Cancer research AU - London, S J AU - Lehman, T A AU - Taylor, J A AD - Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1997/11/15/ PY - 1997 DA - 1997 Nov 15 SP - 5001 EP - 5003 VL - 57 IS - 22 SN - 0008-5472, 0008-5472 KW - Peroxidase KW - EC 1.11.1.7 KW - Index Medicus KW - African Continental Ancestry Group -- genetics KW - Humans KW - Adult KW - Case-Control Studies KW - Smoking -- adverse effects KW - Aged KW - Promoter Regions, Genetic -- genetics KW - Middle Aged KW - European Continental Ancestry Group -- genetics KW - Male KW - Female KW - Lung Neoplasms -- enzymology KW - Peroxidase -- genetics KW - Polymorphism, Genetic -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79412916?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Myeloperoxidase+genetic+polymorphism+and+lung+cancer+risk.&rft.au=London%2C+S+J%3BLehman%2C+T+A%3BTaylor%2C+J+A&rft.aulast=London&rft.aufirst=S&rft.date=1997-11-15&rft.volume=57&rft.issue=22&rft.spage=5001&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 - 1997-12-01 N1 - Date created - 1997-12-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Induction of novel Grp75 isoforms by 2-deoxyglucose in human and murine fibroblasts. AN - 79589663; 9570370 AB - Grp75 is a stress-inducible mitochondrial chaperone which has a high homology to senescence-related protein, p66mot mortalin. In human cells the mortalin gene assigns to the locus of a putative tumor suppressor gene for myeloid malignancies. In order to study expression and localization of Grp75 and p66mot in human and murine fibroblast lines, polyclonal antibodies were raised to conserved portions of each sequence. HT1080 and C3H10T1/2 cells were treated with various Grp-inducing agents. A single 75 kDa band was detected by Western blot of cytoplasmic proteins which was not greatly altered after thermal stress or treatment with L-azetidine-2-carboxylic acid or nonactin. However, glucose deprivation by 2-deoxyglucose treatment induced five novel isoforms at 74-75 kDa mass. Mortalin at 66 kDa could not be detected under these treatment conditions. JF - Cancer letters AU - Merrick, B A AU - Walker, V R AU - He, C AU - Patterson, R M AU - Selkirk, J K AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle, NC 27709, USA. merrick@niehs.nih.gov Y1 - 1997/11/11/ PY - 1997 DA - 1997 Nov 11 SP - 185 EP - 190 VL - 119 IS - 2 SN - 0304-3835, 0304-3835 KW - Antimetabolites KW - 0 KW - Carrier Proteins KW - HSP70 Heat-Shock Proteins KW - HSPA9 protein, human KW - Hspa9a protein, mouse KW - Membrane Proteins KW - Mitochondrial Proteins KW - glucose-regulated proteins KW - mortalin KW - Deoxyglucose KW - 9G2MP84A8W KW - Index Medicus KW - Animals KW - Tumor Cells, Cultured -- metabolism KW - Tumor Cells, Cultured -- drug effects KW - Humans KW - Mice KW - Antimetabolites -- pharmacology KW - HSP70 Heat-Shock Proteins -- metabolism KW - HSP70 Heat-Shock Proteins -- genetics KW - Fibroblasts -- drug effects KW - Membrane Proteins -- metabolism KW - Membrane Proteins -- genetics KW - Deoxyglucose -- pharmacology KW - Fibroblasts -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79589663?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+letters&rft.atitle=Induction+of+novel+Grp75+isoforms+by+2-deoxyglucose+in+human+and+murine+fibroblasts.&rft.au=Merrick%2C+B+A%3BWalker%2C+V+R%3BHe%2C+C%3BPatterson%2C+R+M%3BSelkirk%2C+J+K&rft.aulast=Merrick&rft.aufirst=B&rft.date=1997-11-11&rft.volume=119&rft.issue=2&rft.spage=185&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 - 1998-05-11 N1 - Date created - 1998-05-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Seasonality of births in schizophrenia and bipolar disorder: a review of the literature. AN - 79512613; 9428062 AB - More than 250 studies, covering 29 Northern and five Southern Hemisphere countries, have been published on the birth seasonality of individuals who develop schizophrenia and/or bipolar disorder. Despite methodological problems, the studies are remarkably consistent in showing a 5-8% winter-spring excess of births for both schizophrenia and mania/bipolar disorder. This seasonal birth excess is also found in schizoaffective disorder (December-March), major depression (March-May), and autism (March) but not in other psychiatric conditions with the possible exceptions of eating disorders and antisocial personality disorder. The seasonal birth pattern also may shift over time. Attempts to correlate the seasonal birth excess with specific features of schizophrenia suggest that winter-spring births are probably related to urban births and to a negative family history. Possible correlations include lesser severity of illness and neurophysiological measures. There appears to be no correlation with gender, social class, race, measurable pregnancy and birth complications, clinical subtypes, or neurological, neuropsychological, or neuroimaging measures. Virtually no correlation studies have been done for bipolar disorder. Regarding the cause of the birth seasonality, statistical artifact and parental procreational habits are unlikely explanations. Seasonal effects of genes, subtle pregnancy and birth complications, light and internal chemistry, toxins, nutrition, temperature/weather, and infectious agents or a combination of these are all viable possibilities. JF - Schizophrenia research AU - Torrey, E F AU - Miller, J AU - Rawlings, R AU - Yolken, R H AD - Stanley Foundation Research Programs, NIMH Neuroscience Center, St. Elizabeths Hospital, Washington, DC 20032, USA. Y1 - 1997/11/07/ PY - 1997 DA - 1997 Nov 07 SP - 1 EP - 38 VL - 28 IS - 1 SN - 0920-9964, 0920-9964 KW - Index Medicus KW - Global Health KW - Epidemiologic Methods KW - Humans KW - Family Health KW - Maternal Exposure KW - Female KW - Pregnancy KW - Cohort Effect KW - Schizophrenia -- etiology KW - Bipolar Disorder -- epidemiology KW - Seasons KW - Periodicity KW - Schizophrenia -- epidemiology KW - Bipolar Disorder -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79512613?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Schizophrenia+research&rft.atitle=Seasonality+of+births+in+schizophrenia+and+bipolar+disorder%3A+a+review+of+the+literature.&rft.au=Torrey%2C+E+F%3BMiller%2C+J%3BRawlings%2C+R%3BYolken%2C+R+H&rft.aulast=Torrey&rft.aufirst=E&rft.date=1997-11-07&rft.volume=28&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Schizophrenia+research&rft.issn=09209964&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-02-23 N1 - Date created - 1998-02-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Both the catalytic and regulatory domains of protein kinase C chimeras modulate the proliferative properties of NIH 3T3 cells. AN - 79385536; 9353351 AB - Protein kinase C (PKC) isozymes exhibit important differences in terms of their regulation and biological functions. Not only may some PKC isoforms be active and others not for a given response, but the actions of different isoforms may even be antagonistic. In NIH 3T3 cells, for example, PKCdelta arrests cell growth whereas PKCepsilon stimulates it. To probe the contribution of the regulatory and the catalytic domains of PKC isozymes to isozyme-specific responses, we prepared chimeras between the regulatory and the catalytic domains of PKCalpha, -delta, and -epsilon. These chimeras, which preserve the overall structure of the native PKC enzymes, were stably expressed in mouse fibroblasts. A major objective was to characterize the growth properties of the cells that overexpress the various PKC constructs. Our data demonstrate that both the regulatory and the catalytic domains play roles in cell proliferation. The regulatory domain of PKCepsilon enhanced cell growth in the absence or presence of phorbol 12-myristate 13-acetate (PMA), and, in the presence of PMA, all chimeras with the PKCepsilon regulatory domain also gave rise to colonies in soft agar; the role of the catalytic domain of PKCepsilon was evident in the PMA-treated cells that overexpressed the PKC chimera containing the delta regulatory and the epsilon catalytic domains (PKCdelta/epsilon). The important contribution of the PKCepsilon catalytic domain to the growth of PKCdelta/epsilon-expressing cells was also evident in terms of a significantly increased saturation density in the presence of PMA, their formation of foci upon PMA treatment, and the induction of anchorage-independent growth. Aside from the growth-promoting effect of PKCepsilon, we have shown that most chimeras with PKCalpha and -delta regulatory domains inhibit cell growth. These results underscore the complex contributions of the regulatory and catalytic domains to the overall behavior of PKC. JF - The Journal of biological chemistry AU - Acs, P AU - Wang, Q J AU - Bögi, K AU - Marquez, A M AU - Lorenzo, P S AU - Bíró, T AU - Szállási, Z AU - Mushinski, J F AU - Blumberg, P M AD - Molecular Mechanisms of Tumor Promotion Section, Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1997/11/07/ PY - 1997 DA - 1997 Nov 07 SP - 28793 EP - 28799 VL - 272 IS - 45 SN - 0021-9258, 0021-9258 KW - Enzyme Inhibitors KW - 0 KW - Indoles KW - Isoenzymes KW - Maleimides KW - Platelet-Derived Growth Factor KW - Recombinant Fusion Proteins KW - Prkcd protein, mouse KW - EC 2.7.1.- KW - Prkce protein, mouse KW - Prkca protein, mouse KW - EC 2.7.11.13 KW - Protein Kinase C KW - Protein Kinase C-alpha KW - Protein Kinase C-delta KW - Protein Kinase C-epsilon KW - bisindolylmaleimide I KW - L79H6N0V6C KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - 3T3 Cells KW - Animals KW - Platelet-Derived Growth Factor -- pharmacology KW - Mice KW - Isoenzymes -- genetics KW - Isoenzymes -- metabolism KW - Binding Sites KW - Recombinant Fusion Proteins -- metabolism KW - Isoenzymes -- antagonists & inhibitors KW - Transfection KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Enzyme Inhibitors -- pharmacology KW - Indoles -- pharmacology KW - Catalysis KW - Cell Division KW - Maleimides -- pharmacology KW - Protein Kinase C -- metabolism KW - Protein Kinase C -- antagonists & inhibitors KW - Protein Kinase C -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79385536?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Both+the+catalytic+and+regulatory+domains+of+protein+kinase+C+chimeras+modulate+the+proliferative+properties+of+NIH+3T3+cells.&rft.au=Acs%2C+P%3BWang%2C+Q+J%3BB%C3%B6gi%2C+K%3BMarquez%2C+A+M%3BLorenzo%2C+P+S%3BB%C3%ADr%C3%B3%2C+T%3BSz%C3%A1ll%C3%A1si%2C+Z%3BMushinski%2C+J+F%3BBlumberg%2C+P+M&rft.aulast=Acs&rft.aufirst=P&rft.date=1997-11-07&rft.volume=272&rft.issue=45&rft.spage=28793&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 - 1997-12-12 N1 - Date created - 1997-12-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transplacental effects of 3'-azido-2',3'-dideoxythymidine (AZT): tumorigenicity in mice and genotoxicity in mice and monkeys. AN - 79408114; 9362158 AB - When given during pregnancy, the drug 3'-azido-2',3'-dideoxythymidine (AZT) substantially reduces maternal-fetal transmission of human immunodeficiency virus type 1 (HIV-1). However, AZT has been shown to be carcinogenic in adult mice after lifetime oral administration. In this study, we assessed the transplacental tumorigenic and genotoxic effects of AZT in the offspring of CD-1 mice and Erythrocebus patas monkeys given AZT orally during pregnancy. Pregnant mice were given daily doses of either 12.5 or 25.0 mg AZT on days 12 through 18 of gestation (last 37% of gestation period). Pregnant monkeys were given a daily dose of 10.0 mg AZT 5 days a week for the last 9.5-10 weeks of gestation (final 41%-43% of gestation period). AZT incorporation into nuclear and mitochondrial DNA and the length of chromosomal end (telomere) DNA were examined in multiple tissues of newborn mice and fetal monkeys. Additional mice were followed from birth and received no further treatment until subjected to necropsy and complete pathologic examination at 1 year of age. An anti-AZT radioimmunoassay was used to monitor AZT incorporation into DNA. At 1 year of age, the offspring of AZT-treated mice exhibited statistically significant, dose-dependent increases in tumor incidence and tumor multiplicity in the lungs, liver, and female reproductive organs. AZT incorporation into nuclear and mitochondrial DNA was detected in multiple organs of transplacentally exposed mice and monkeys. Shorter chromosomal telomeres were detected in liver and brain tissues from most AZT-exposed newborn mice but not in tissues from fetal monkeys. AZT is genotoxic in fetal mice and monkeys and is a moderately strong transplacental carcinogen in mice examined at 1 year of age. Careful long-term follow-up of AZT-exposed children would seem to be appropriate. JF - Journal of the National Cancer Institute AU - Olivero, O A AU - Anderson, L M AU - Diwan, B A AU - Haines, D C AU - Harbaugh, S W AU - Moskal, T J AU - Jones, A B AU - Rice, J M AU - Riggs, C W AU - Logsdon, D AU - Yuspa, S H AU - Poirier, M C AD - Division of Basic Sciences, National Cancer Institute, Bethesda, MD 20892-4255, USA. olivero@pop.nci.nih.gov Y1 - 1997/11/05/ PY - 1997 DA - 1997 Nov 05 SP - 1602 EP - 1608 VL - 89 IS - 21 SN - 0027-8874, 0027-8874 KW - Carcinogens KW - 0 KW - DNA, Mitochondrial KW - DNA, Neoplasm KW - Zidovudine KW - 4B9XT59T7S KW - Index Medicus KW - AIDS/HIV KW - Animals KW - Fetus -- drug effects KW - Dose-Response Relationship, Drug KW - Mice KW - Radioimmunoassay KW - Pregnancy KW - Animals, Newborn KW - Mice, Inbred Strains KW - DNA, Mitochondrial -- drug effects KW - Telomere -- drug effects KW - Placenta KW - Erythrocebus patas KW - Female KW - DNA, Neoplasm -- drug effects KW - Zidovudine -- adverse effects KW - Carcinogens -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79408114?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Transplacental+effects+of+3%27-azido-2%27%2C3%27-dideoxythymidine+%28AZT%29%3A+tumorigenicity+in+mice+and+genotoxicity+in+mice+and+monkeys.&rft.au=Olivero%2C+O+A%3BAnderson%2C+L+M%3BDiwan%2C+B+A%3BHaines%2C+D+C%3BHarbaugh%2C+S+W%3BMoskal%2C+T+J%3BJones%2C+A+B%3BRice%2C+J+M%3BRiggs%2C+C+W%3BLogsdon%2C+D%3BYuspa%2C+S+H%3BPoirier%2C+M+C&rft.aulast=Olivero&rft.aufirst=O&rft.date=1997-11-05&rft.volume=89&rft.issue=21&rft.spage=1602&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 - 1997-11-25 N1 - Date created - 1997-11-25 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Natl Cancer Inst. 1998 Aug 5;90(15):1171 [9701368] J Natl Cancer Inst. 1997 Nov 5;89(21):1566-7 [9362149] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Scaling effects in the perception of higher-order spatial correlations. AN - 85255094; pmid-9463692 AB - Human texture discrimination depends both on spatial-frequency content and on higher-order or multi-point correlations. Spatial-frequency discrimination exhibits a high degree of scale invariance over a range of several octaves, but the scaling behavior of sensitivity to higher-order correlation structure is unknown. We explored the scale dependence of texture discrimination for image ensembles which shared the same power spectrum, but differed in their higher-order correlations. Literally scaling the ensembles so that they occupy larger retinal regions results in discrimination performance that is largely independent of scale over a 3 octave range. Holding the display size constant and scaling the texture being sampled within the display over the same range produces performance that varies with scale appreciably. The ideal observer performance is computed, and the absolute efficiency is seen to be quite small, on the order of 10(-2)-10(-1). As the texture is scaled down, increasing the number of checks within the fixed display size, performance increases while the efficiency decreases. These dependencies remain when the stimulus onset asynchrony is increased from 50 to 500 msec. We created sets of textures which varied both in check number and correlation strength, for which ideal observer performance was equated. For the human observers, efficiency was significantly higher for textures with higher correlation strength, but fewer checks. These results are consistent with a model in which a fixed number of checks is processed in a scale-invariant manner, while the remainder of the display is processed much less efficiently. JF - Vision Research AU - Joseph, J S AU - Victor, J D AU - Optican, L M AD - Laboratory of Sensorimotor Research, National Eye Institute, NIH, Bethesda, MD 20892, USA. PY - 1997 SP - 3097 EP - 3107 VL - 37 IS - 22 SN - 0042-6989, 0042-6989 KW - Models, Psychological KW - Photic Stimulation KW - Support, U.S. Gov't, P.H.S. KW - Human KW - Psychophysics KW - Male KW - Pattern Recognition, Visual UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85255094?accountid=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=Vision+Research&rft.atitle=Scaling+effects+in+the+perception+of+higher-order+spatial+correlations.&rft.au=Joseph%2C+J+S%3BVictor%2C+J+D%3BOptican%2C+L+M&rft.aulast=Joseph&rft.aufirst=J&rft.date=1997-11-01&rft.volume=37&rft.issue=22&rft.spage=3097&rft.isbn=&rft.btitle=&rft.title=Vision+Research&rft.issn=00426989&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Signal transduction across alamethicin ion channels in the presence of noise. AN - 85252799; pmid-9370439 AB - We have studied voltage-dependent ion channels of alamethicin reconstituted into an artificial planar lipid bilayer membrane from the point of view of electric signal transduction. Signal transduction properties of these channels are highly sensitive to the external electric noise. Specifically, addition of bandwidth-restricted "white" noise of 10-20 mV (r.m.s.) to a small sine wave input signal increases the output signal by approximately 20-40 dB conserving, and even slightly increasing, the signal-to-noise ratio at the system output. We have developed a small-signal adiabatic theory of stochastic resonance for a threshold-free system of voltage-dependent ion channels. This theory describes our main experimental findings giving good qualitative understanding of the underlying mechanism. It predicts the right value of the output signal-to-noise ratio and provides a reliable estimate for the noise intensity corresponding to its maximum. Our results suggest that the alamethicin channel in a lipid bilayer is a good model system for studies of mechanisms of primary electrical signal processing in biology showing an important feature of signal transduction improvement by a fluctuating environment. JF - Biophysical Journal AU - Bezrukov, S M AU - Vodyanoy, I AD - National Institutes of Health, Bethesda, Maryland 20892-0580, USA. PY - 1997 SP - 2456 EP - 2464 VL - 73 IS - 5 SN - 0006-3495, 0006-3495 KW - Electric Conductivity KW - Models, Molecular KW - Alamethicin KW - Stochastic Processes KW - Ion Channels KW - Support, U.S. Gov't, Non-P.H.S. KW - Electrophysiology KW - Ionophores KW - Models, Biological KW - Liposomes KW - Mathematics KW - Ion Transport KW - Signal Transduction UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85252799?accountid=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=Signal+transduction+across+alamethicin+ion+channels+in+the+presence+of+noise.&rft.au=Bezrukov%2C+S+M%3BVodyanoy%2C+I&rft.aulast=Bezrukov&rft.aufirst=S&rft.date=1997-11-01&rft.volume=73&rft.issue=5&rft.spage=2456&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 - Effect of diamide on force generation and axial stiffness of the cochlear outer hair cell. AN - 85245744; pmid-9370475 AB - We found that diamide, which affects spectrin, reduces the axial stiffness of the cochlear outer hair cell, the cylindrically shaped mechanoreceptor cell with a unique voltage-sensitive motility. This effect thus provides a means of examining the relationship between the stiffness and the motility of the cell. For measuring axial stiffness and force production, we used an experimental configuration in which an elastic probe was attached to the cell near the cuticular plate and the other end of the cell was held with a patch pipette in the whole-cell recording mode. Diamide at concentrations of up to 5 mM reduced the axial stiffness in a dose-dependent manner to 165 nN per unit strain from 502 nN for untreated cells. The isometric force elicited by voltage pulses under whole-cell voltage clamp was also reduced to 35 pN/mV from 105 pN/mV for untreated cells. Thus the isometric force was approximately proportional to the axial stiffness. Our observations suggest a series connection between the motor and cytoskeletal elements and can be explained by the area motor model previously proposed for the outer hair cell. JF - Biophysical Journal AU - Adachi, M AU - Iwasa, Kuni H AD - Laboratory of Cellular Biology, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland 20892-0922, USA.; National Institute on Deafness and Other Communication Disorders PY - 1997 SP - 2809 EP - 2818 VL - 73 IS - 5 SN - 0006-3495, 0006-3495 KW - Cell Movement KW - Cytoskeleton KW - Diamide KW - Patch-Clamp Techniques KW - Guinea Pigs KW - Hair Cells, Outer KW - Animal KW - Membrane Potentials KW - Electrophysiology KW - Electric Stimulation KW - Models, Biological UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85245744?accountid=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+diamide+on+force+generation+and+axial+stiffness+of+the+cochlear+outer+hair+cell.&rft.au=Adachi%2C+M%3BIwasa%2C+Kuni+H&rft.aulast=Adachi&rft.aufirst=M&rft.date=1997-11-01&rft.volume=73&rft.issue=5&rft.spage=2809&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 - Serum hepatitis G virus RNA in patients with chronic viral hepatitis. AN - 85211697; pmid-9362178 AB - OBJECTIVES: The hepatitis G virus (HGV) is a newly described flavivirus that affects a high proportion of patients with chronic viral hepatitis: our objective was to determine what role HGV might play in the course of disease. METHODS: We evaluated stored serum samples from 108 patients with chronic hepatitis B and 99 patients with chronic hepatitis C who participated in trials of alpha-interferon or ribavirin for the presence of hepatitis B virus (HBV) DNA and hepatitis C virus (HCV) RNA by branched DNA and for the presence of HGV RNA by polymerase chain reaction (PCR), using primers from the NS5 region of the genome. RESULTS: Initially, 20 (19%) patients with hepatitis B and 11 (11%) with hepatitis C had HGV RNA in their serum. Patients with and without HGV infection were similar with regard to clinical features, laboratory tests, and hepatic histology. HGV RNA levels fell during interferon therapy and became undetectable in those receiving the highest doses; however, HGV RNA levels returned to pretreatment values when therapy was stopped. With ribavirin therapy, HGV RNA levels did not change. Two- to 12-yr follow-up serum samples were available from 17 initially HGV RNA-positive patients, of whom only 10 (59%) were still positive. CONCLUSIONS: HGV infection is common among patients with chronic hepatitis B and C but has little effect on the short-term course of disease or response to therapy. HGV RNA levels are suppressed but not eradicated by alpha-interferon and are unaffected by ribavirin treatment. Spontaneous loss of HGV RNA occurs over time in a proportion of patients. JF - The American Journal of Gastroenterology AU - Marrone, A AU - Shih, J W AU - Nakatsuji, Y AU - Alter, H J AU - Lau, D AU - Vergalla, J AU - Hoofnagle, J H AD - Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. PY - 1997 SP - 1992 EP - 1996 VL - 92 IS - 11 SN - 0002-9270, 0002-9270 KW - Regression Analysis KW - Chi-Square Distribution KW - Human KW - Hepatitis, Viral, Human KW - RNA, Viral KW - Flaviviridae KW - Polymerase Chain Reaction KW - Base Sequence KW - Hepatitis B, Chronic KW - Adult KW - Cohort Studies KW - Molecular Sequence Data KW - Middle Age KW - Hepatitis C, Chronic KW - Male KW - Female UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85211697?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+Journal+of+Gastroenterology&rft.atitle=Serum+hepatitis+G+virus+RNA+in+patients+with+chronic+viral+hepatitis.&rft.au=Marrone%2C+A%3BShih%2C+J+W%3BNakatsuji%2C+Y%3BAlter%2C+H+J%3BLau%2C+D%3BVergalla%2C+J%3BHoofnagle%2C+J+H&rft.aulast=Marrone&rft.aufirst=A&rft.date=1997-11-01&rft.volume=92&rft.issue=11&rft.spage=1992&rft.isbn=&rft.btitle=&rft.title=The+American+Journal+of+Gastroenterology&rft.issn=00029270&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Effects of stimulus intensity on laryngeal long latency responses in awake humans. AN - 85202524; pmid-9374178 AB - Percutaneous electrical stimulation applied to the internal branch of the superior laryngeal nerve (ISLN) results in two long latency laryngeal adductor responses in awake humans: an ipsilateral thyroarytenoid (TA) R1 muscle response at 16 ms, and later bilateral TA R2 muscle responses at 60 ms. The purpose of this study was to determine whether a functional relationship existed between the R1 and R2 responses by gradually increasing the level of electrical stimulation from threshold to supramaximal levels. R1 amplitude increased linearly with stimulation intensity in 9 of the 11 subjects, whereas R2 only had a positive linear relationship in 3 subjects and a negative relationship with stimulation intensity in 1 subject. Significant negative relationships were found between response latency and stimulation intensity in 3 subjects for the R1 responses and 3 other subjects for the R2 responses. Overall, R1 amplitudes increased systematically, whereas R2 responses varied in latency and amplitude with increasing stimulus intensity. Neither the latencies nor the amplitudes of the two responses were related after adjusting for stimulation intensity within subjects by using partial correlation coefficients. The R1 and R2 responses were functionally unrelated and most likely have different neural components. JF - Otolaryngology--Head and Neck Surgery AU - Yamashita, T AU - Nash, E A AU - Tanaka, Y AU - Ludlow, C L AD - Voice and Speech Section, Division of Intramural Research, National Institute on Deafness and Other Communication Disorders, Bethesda, Maryland 20892-1416, USA. PY - 1997 SP - 521 EP - 529 VL - 117 IS - 5 SN - 0194-5998, 0194-5998 KW - Laryngeal Nerves KW - Signal Processing, Computer-Assisted KW - Laryngeal Muscles KW - Area Under Curve KW - Differential Threshold KW - Electrodes, Implanted KW - Human KW - Electromyography KW - Electric Stimulation KW - Adult KW - Middle Age KW - Muscle Contraction KW - Reflex KW - Time Factors KW - Male KW - Female KW - Wakefulness KW - Reaction Time UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85202524?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Otolaryngology--Head+and+Neck+Surgery&rft.atitle=Effects+of+stimulus+intensity+on+laryngeal+long+latency+responses+in+awake+humans.&rft.au=Yamashita%2C+T%3BNash%2C+E+A%3BTanaka%2C+Y%3BLudlow%2C+C+L&rft.aulast=Yamashita&rft.aufirst=T&rft.date=1997-11-01&rft.volume=117&rft.issue=5&rft.spage=521&rft.isbn=&rft.btitle=&rft.title=Otolaryngology--Head+and+Neck+Surgery&rft.issn=01945998&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Phosphorothioated antisense c-myc oligonucleotide inhibits the growth of human colon carcinoma cells. AN - 79569099; 9494542 AB - The functional significance of c-myc overexpression in human colon carcinoma is unclear. Three human colon carcinoma cell lines, LS174T, SW1116 and SW48, were treated in vitro with phosphorothioate modified antisense oligonucleotides (ASO), complementary to the c-myc translation initiation site, or two control oligonucleotides. Growth was assayed by the methyl tetrazolium (MTT) assay and colony formation. C-myc, retinoblastoma (Rb), carcinoembryonic antigen (CEA), and alkaline phosphatase (AP) expression was assessed by immunoblotting. The ASO specifically inhibited growth of all three human colon carcinoma cell lines. Further studies were conducted on LS174T because growth inhibition was associated with a more differentiated morphology. In LS174T cells, ASO caused a dose dependent decrease in c-myc and Rb protein expression, but an increase in CEA and AP expression. The growth of human colon carcinoma cells is dependent on c-myc expression, and the inhibition of c-myc expression in LS174T is associated with a more differentiated phenotype. JF - Anticancer research AU - Yu, B W AU - Nguyen, D AU - Anderson, S AU - Allegra, C A AD - NCI-NMOB, National Naval Medical Center, Bethesda, MD 20889, USA. PY - 1997 SP - 4407 EP - 4413 VL - 17 IS - 6D SN - 0250-7005, 0250-7005 KW - Carcinoembryonic Antigen KW - 0 KW - Oligonucleotides, Antisense KW - Proto-Oncogene Proteins c-myc KW - Retinoblastoma Protein KW - Thionucleotides KW - Alkaline Phosphatase KW - EC 3.1.3.1 KW - Index Medicus KW - Proto-Oncogene Proteins c-myc -- biosynthesis KW - Protein Biosynthesis -- drug effects KW - Base Sequence KW - Carcinoembryonic Antigen -- biosynthesis KW - Tumor Cells, Cultured KW - Humans KW - Cell Division -- drug effects KW - Alkaline Phosphatase -- biosynthesis KW - Retinoblastoma Protein -- biosynthesis KW - Tumor Stem Cell Assay KW - Colonic Neoplasms KW - Oligonucleotides, Antisense -- toxicity KW - Genes, myc KW - Gene Expression Regulation, Neoplastic -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79569099?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Anticancer+research&rft.atitle=Phosphorothioated+antisense+c-myc+oligonucleotide+inhibits+the+growth+of+human+colon+carcinoma+cells.&rft.au=Yu%2C+B+W%3BNguyen%2C+D%3BAnderson%2C+S%3BAllegra%2C+C+A&rft.aulast=Yu&rft.aufirst=B&rft.date=1997-11-01&rft.volume=17&rft.issue=6D&rft.spage=4407&rft.isbn=&rft.btitle=&rft.title=Anticancer+research&rft.issn=02507005&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-26 N1 - Date created - 1998-03-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Predicting the in vitro toxicity of synthetic beta-amyloid (1-40). AN - 79546194; 9461056 AB - The in vitro toxicity of synthetic beta-amyloid (betaA4) is variable and unpredictable, limiting its use as a research tool. This study describes a method using Congo red (CR) to predict the in vitro toxicity of betaA4 solutions. Histopathologically, CR is used to stain the neuritic, betaA4-containing plaques, one of the hallmarks of Alzheimer's disease. In this study, synthetic betaA4 solutions were incubated with CR at a molar ratio of 1.0:2.5. The solutions were centrifuged and the absorbance of the supernatants were measured. Predictions of nontoxicity correlated with absorbance readings near zero. Toxicity was evaluated relative to control cells (vehicle only), using a hemocytometer to count PC-12 cells that excluded trypan blue. The positive predictive value of the test was 78% and the negative predictive value was 100%. To use this test, the toxic concentration(s) of betaA4 must first be established empirically. Then, the CR test can be used to evaluate the potential toxicity of betaA4 solutions at similar concentrations. Thus, this test can be used under a variety of laboratory circumstances. JF - Neurobiology of aging AU - Brining, S K AD - The National Institutes of Health, The National Institute on Aging, Bethesda, MD 20892-1582, USA. skb@helix.nih.gov PY - 1997 SP - 581 EP - 589 VL - 18 IS - 6 SN - 0197-4580, 0197-4580 KW - Amyloid beta-Peptides KW - 0 KW - Coloring Agents KW - Neuropeptides KW - Peptide Fragments KW - amyloid beta-protein (1-40) KW - Congo Red KW - 3U05FHG59S KW - Index Medicus KW - Rats KW - Animals KW - Electrophoresis, Polyacrylamide Gel KW - Humans KW - Neuropeptides -- toxicity KW - Coloring Agents -- chemistry KW - Predictive Value of Tests KW - Neuropeptides -- chemistry KW - Congo Red -- chemistry KW - Cell Death -- drug effects KW - Protein Conformation KW - PC12 Cells KW - Peptide Fragments -- toxicity KW - Peptide Fragments -- chemistry KW - Amyloid beta-Peptides -- toxicity KW - Amyloid beta-Peptides -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79546194?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurobiology+of+aging&rft.atitle=Predicting+the+in+vitro+toxicity+of+synthetic+beta-amyloid+%281-40%29.&rft.au=Brining%2C+S+K&rft.aulast=Brining&rft.aufirst=S&rft.date=1997-11-01&rft.volume=18&rft.issue=6&rft.spage=581&rft.isbn=&rft.btitle=&rft.title=Neurobiology+of+aging&rft.issn=01974580&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-05 N1 - Date created - 1998-03-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The carboxyl-terminal zinc-binding domain of the human papillomavirus E7 protein can be functionally replaced by the homologous sequences of the E6 protein. AN - 79544227; 9453149 AB - The carboxyl-terminus is necessary for the functional and structural integrity of the human papillomavirus (HPV) E7 oncoprotein. Since many mutations in this domain of E7 result in the formation of unstable proteins, we have evaluated the importance of this region by replacing it with structurally related domains derived from HPV E6 proteins. Biological analysis of these mutant chimeric E7/E6 proteins showed that they retained E7-specific biological activities including cooperation with the ras oncogene to transform primary baby rat kidney cells and transcriptional activation of an E2F responsive reporter plasmid. One of the chimeric proteins was impaired in its ability to physically disrupt pRB/E2F complexes in vitro suggesting that there are defined molecular determinants in the carboxyl-terminus of E7 for this activity. In contrast, none of these proteins exhibited E6-like properties including binding to p53 and/or degradation of associated proteins. JF - Virus research AU - Mavromatis, K O AU - Jones, D L AU - Mukherjee, R AU - Yee, C AU - Grace, M AU - Münger, K AD - Laboratory of Tumor Virus Biology, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1997/11// PY - 1997 DA - November 1997 SP - 109 EP - 118 VL - 52 IS - 1 SN - 0168-1702, 0168-1702 KW - E6 protein, Human papillomavirus type 16 KW - 0 KW - Oncogene Proteins, Viral KW - Papillomavirus E7 Proteins KW - Repressor Proteins KW - oncogene protein E7, Human papillomavirus type 16 KW - Zinc KW - J41CSQ7QDS KW - Index Medicus KW - Rats KW - Mutagenesis, Site-Directed KW - Animals KW - Humans KW - Molecular Sequence Data KW - Kidney -- cytology KW - Amino Acid Sequence KW - Cell Line KW - Zinc -- metabolism KW - Papillomaviridae KW - Oncogene Proteins, Viral -- genetics KW - Oncogene Proteins, Viral -- physiology KW - Sequence Homology, Amino Acid KW - Protein Structure, Tertiary KW - Oncogene Proteins, Viral -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79544227?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Virus+research&rft.atitle=The+carboxyl-terminal+zinc-binding+domain+of+the+human+papillomavirus+E7+protein+can+be+functionally+replaced+by+the+homologous+sequences+of+the+E6+protein.&rft.au=Mavromatis%2C+K+O%3BJones%2C+D+L%3BMukherjee%2C+R%3BYee%2C+C%3BGrace%2C+M%3BM%C3%BCnger%2C+K&rft.aulast=Mavromatis&rft.aufirst=K&rft.date=1997-11-01&rft.volume=52&rft.issue=1&rft.spage=109&rft.isbn=&rft.btitle=&rft.title=Virus+research&rft.issn=01681702&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-05 N1 - Date created - 1998-03-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Di(2-ethylhexyl) phthalate induces a functional zinc deficiency during pregnancy and teratogenesis that is independent of peroxisome proliferator-activated receptor-alpha. AN - 79542283; 9451755 AB - Di(2-ethylhexyl) phthalate (DEHP) is a peroxisome proliferator whose administration to rodents induces a pleiotropic response mediated by the peroxisome proliferator-activated receptor-alpha (PPAR alpha). The mechanisms underlying DEHP-induced reproductive toxicity and teratogenicity are not well understood but could be the result of an alteration in gene expression by PPAR alpha. Additionally, phthalate exposure is known to impair fetal zinc (Zn) levels during pregnancy. In this work, we investigated whether the reproductive toxicity and teratogenicity of DEHP are mediated by PPAR alpha and whether the receptor influences maternal and/or embryonic Zn metabolism. Pregnant female mice, homozygous wild-type (+/+) or PPAR alpha -null (-/-), were intubated with either vehicle alone or 1,000 mg DEHP/kg body weight on gestation day (GD) 8 and 9. Pregnancy outcome was evaluated on GD10 and GD18 in two cohorts of animals. Compared to controls, DEHP administration resulted in maternal toxicity, embryo/ fetal toxicity, and teratogenicity in both (+/+) and (-/-) mice. Maternal liver mRNA for cytochrome P-450 4A1 (CYP4A1) was higher in DEHP-treated (+/+) mice but not in DEHP-treated (-/-) mice on GD10, consistent with their respective phenotype. Maternal liver MT and Zn levels were significantly higher than in controls on GD10. In addition, embryonic Zn content was significantly lower in both genotypes treated with DEHP compared to controls. Results from this work show that DEHP-induced reproductive toxicity, teratogenicity, and altered Zn metabolism are not mediated through PPAR alpha-dependent mechanisms. In addition, this work suggests that DEHP-induced alterations in Zn metabolism contribute to the mechanisms underlying DEHP-induced reproductive toxicity and teratogenicity. JF - Teratology AU - Peters, J M AU - Taubeneck, M W AU - Keen, C L AU - Gonzalez, F J AD - Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. jpeters@helix.nih.gov Y1 - 1997/11// PY - 1997 DA - November 1997 SP - 311 EP - 316 VL - 56 IS - 5 SN - 0040-3709, 0040-3709 KW - Nuclear Proteins KW - 0 KW - Receptors, Cytoplasmic and Nuclear KW - Transcription Factors KW - Diethylhexyl Phthalate KW - C42K0PH13C KW - Zinc KW - J41CSQ7QDS KW - Index Medicus KW - Animals KW - Mice, Inbred C57BL KW - Mice KW - Fetus -- metabolism KW - Female KW - Pregnancy Outcome KW - Pregnancy KW - Receptors, Cytoplasmic and Nuclear -- physiology KW - Transcription Factors -- physiology KW - Pregnancy, Animal -- metabolism KW - Diethylhexyl Phthalate -- toxicity KW - Abnormalities, Drug-Induced -- etiology KW - Nuclear Proteins -- physiology KW - Zinc -- deficiency UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79542283?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Teratology&rft.atitle=Di%282-ethylhexyl%29+phthalate+induces+a+functional+zinc+deficiency+during+pregnancy+and+teratogenesis+that+is+independent+of+peroxisome+proliferator-activated+receptor-alpha.&rft.au=Peters%2C+J+M%3BTaubeneck%2C+M+W%3BKeen%2C+C+L%3BGonzalez%2C+F+J&rft.aulast=Peters&rft.aufirst=J&rft.date=1997-11-01&rft.volume=56&rft.issue=5&rft.spage=311&rft.isbn=&rft.btitle=&rft.title=Teratology&rft.issn=00403709&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-12 N1 - Date created - 1998-03-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Carcinogenic activity of the flame retardant, 2,2-bis(bromomethyl)-1,3-propanediol in rodents, and comparison with the carcinogenicity of other NTP brominated chemicals. AN - 79518770; 9437797 AB - Several brominated chemicals have been shown to be multisite-multispecies carcinogens in laboratory animals, and in this paper we report that the flame retardant, 2,2-bis(bromomethyl)-1,3-propanediol (BMP) is also a multisite carcinogen in both sexes of Fischer 344 rats and B6C3F1 mice. BMP was administered continuously in the diet for up to 2 yr to rats at doses of 0, 2,500, 5,000, or 10,000 ppm and to mice at doses of 0, 312, 625, or 1,250 ppm. Interim groups of rats were examined at 15 mo. An additional recovery group of male rats received the chemical for 3 mo at 20,000 ppm in the feed, and then the control diet for the remainder of the study. Chemical exposure caused neoplasms of the skin, subcutaneous tissue, mammary gland, Zymbal's gland, oral cavity, esophagus, forestomach, small intestine, large intestine, mesothelium, kidney, urinary bladder, lung, thyroid gland, seminal vesicle, hematopoietic system, and pancreas in the male rat; mammary gland, oral cavity, esophagus, and thyroid gland in the female rat; lung, kidney, and Harderian gland in male mice; and subcutaneous tissue, lung, and Harderian gland in the female mouse. The recovery group of male rats presented with the same spectrum of treatment-related neoplasms as in the core study. In this recovery group, BMP (at 20,000 ppm) caused irreversible effects at numerous sites after 90 days of exposure that was not detectable by histologic examination, but without further exposure resulted in carcinogenic responses at 2 yr. BMP is mutagenic in the salmonella test, but it was not determined if the BMP-induced effects that eventually lead to development of neoplasms at multiple sites are the same in both species and in all organ systems affected. JF - Toxicologic pathology AU - Dunnick, J K AU - Heath, J E AU - Farnell, D R AU - Prejean, J D AU - Haseman, J K AU - Elwell, M R AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. PY - 1997 SP - 541 EP - 548 VL - 25 IS - 6 SN - 0192-6233, 0192-6233 KW - Carcinogens KW - 0 KW - Flame Retardants KW - Hydrocarbons, Brominated KW - Propylene Glycols KW - 2,2-bis(bromomethyl)-1,3-propanediol KW - 3296-90-0 KW - Index Medicus KW - Rats KW - Mice, Inbred Strains KW - Animals KW - Rats, Inbred F344 KW - Neoplasms, Experimental -- chemically induced KW - Mice KW - Time Factors KW - Male KW - Female KW - Propylene Glycols -- toxicity KW - Carcinogens -- toxicity KW - Hydrocarbons, Brominated -- toxicity KW - Flame Retardants -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79518770?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Laryngoscope&rft.atitle=Evolution+of+research+otolaryngology--head+and+neck+surgery+over+the+past+century.&rft.au=Snow%2C+J+B&rft.aulast=Snow&rft.aufirst=J&rft.date=1996-05-01&rft.volume=106&rft.issue=5+Pt+1&rft.spage=529&rft.isbn=&rft.btitle=&rft.title=The+Laryngoscope&rft.issn=0023852X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-04 N1 - Date created - 1998-03-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A recombinant adenovirus expressing wild type p53 induces apoptosis in drug-resistant human breast cancer cells: a gene therapy approach for drug-resistant cancers. AN - 79480115; 9408609 AB - The cytotoxicity of a recombinant adenovirus expressing the wild type tumor suppressor gene p53 (AdWTp53) was studied in two human breast cancer MCF-7 sublines selected for resistance to adriamycin (MCF-Adr) and mitoxantrone (MCF-Mito). Although the levels of wild type p53 protein following infection with AdWTp53 are comparable in all cell lines, the two drug-resistant MCF-7 sublines were 300- and 18-fold more sensitive to killing by AdWTp53 compared with the drug-sensitive parental MCF-7 cell lines. In each cell line, AdWTp53 infection led to cell cycle arrest, and reduction of Cdk2 and cyclin B1-Cdc2 activity. Nucleosomal DNA fragmentation analysis (as a function of apoptosis) following AdWTp53 infection revealed that, while the parental MCF-7 cells failed to undergo apoptosis, both drug-resistant cell lines showed distinct DNA laddering. In MCF-Adr cells, a combination treatment of AdWTp53 and adriamycin was much more toxic than either of the reagents used individually. Finally, exposure of a mixed population of MCF-Adr and CD34+ cells to AdWTp53 selectively prevented MCF-Adr cell colony formation, while there was no inhibition of CFU-GM colony formation from CD34+ cells. These findings suggest that some drug-resistant human breast cancers may be effectively treated with adenovirus expressing wild type p53. JF - Cancer gene therapy AU - Seth, P AU - Katayose, D AU - Li, Z AU - Kim, M AU - Wersto, R AU - Craig, C AU - Shanmugam, N AU - Ohri, E AU - Mudahar, B AU - Rakkar, A N AU - Kodali, P AU - Cowan, K AD - Medical Breast Cancer Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. pseth@boxp.nih.gov PY - 1997 SP - 383 EP - 390 VL - 4 IS - 6 SN - 0929-1903, 0929-1903 KW - Tumor Suppressor Protein p53 KW - 0 KW - Doxorubicin KW - 80168379AG KW - Mitoxantrone KW - BZ114NVM5P KW - Index Medicus KW - Tumor Suppressor Protein p53 -- biosynthesis KW - Adenoviridae KW - Bone Marrow Purging KW - Humans KW - Cell Cycle -- physiology KW - Hematopoietic Stem Cells -- cytology KW - Doxorubicin -- toxicity KW - Drug Resistance, Neoplasm KW - Drug Resistance, Multiple KW - Cell Survival -- drug effects KW - Transfection KW - Mitoxantrone -- toxicity KW - Colony-Forming Units Assay KW - DNA Fragmentation KW - Cell Cycle -- drug effects KW - Female KW - Apoptosis KW - Genes, p53 KW - Breast Neoplasms -- pathology KW - Genetic Therapy -- methods KW - Breast Neoplasms -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79480115?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+gene+therapy&rft.atitle=A+recombinant+adenovirus+expressing+wild+type+p53+induces+apoptosis+in+drug-resistant+human+breast+cancer+cells%3A+a+gene+therapy+approach+for+drug-resistant+cancers.&rft.au=Seth%2C+P%3BKatayose%2C+D%3BLi%2C+Z%3BKim%2C+M%3BWersto%2C+R%3BCraig%2C+C%3BShanmugam%2C+N%3BOhri%2C+E%3BMudahar%2C+B%3BRakkar%2C+A+N%3BKodali%2C+P%3BCowan%2C+K&rft.aulast=Seth&rft.aufirst=P&rft.date=1997-11-01&rft.volume=4&rft.issue=6&rft.spage=383&rft.isbn=&rft.btitle=&rft.title=Cancer+gene+therapy&rft.issn=09291903&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-02-04 N1 - Date created - 1998-02-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Risk factors and early detection of lung cancer in a cohort of Chinese tin miners. AN - 79479735; 9408549 AB - To examine risk factors and establish a biologic specimen and data bank for the study of early markers of lung cancer. We designed a dynamic cohort using an ongoing lung cancer screening program among radon- and arsenic-exposed tin miners in Yunnan China. Through the first four years of the study, 8,346 miners aged 40 years and older with over 10 years of occupational exposure have been enrolled, risk factors have been assessed, annual sputum and chest radiographs have been obtained, and numerous biologic specimens have been collected. A total of 243 new lung cancer cases have been identified through 1995. Radon and arsenic exposures are the predominant risk factors, but lung cancer risk is also associated with chronic bronchitis and silicosis, as well as a number of exposure to tobacco smoke, including early age of first use, duration, and cumulative exposure. Tumor and sputum samples are being examined for early markers of lung cancer. A cohort of occupationally-exposed tin miners with an extensive biologic specimen repository has been successfully established to simultaneously study the etiology and early detection of lung cancer. JF - Annals of epidemiology AU - Qiao, Y L AU - Taylor, P R AU - Yao, S X AU - Erozan, Y S AU - Luo, X C AU - Barrett, M J AU - Yan, Q Y AU - Giffen, C A AU - Huang, S Q AU - Maher, M M AU - Forman, M R AU - Tockman, M S AD - Cancer Prevention Studies Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-7326, USA. Y1 - 1997/11// PY - 1997 DA - November 1997 SP - 533 EP - 541 VL - 7 IS - 8 SN - 1047-2797, 1047-2797 KW - Tin KW - 7440-31-5 KW - Arsenic KW - N712M78A8G KW - Radon KW - Q74S4N8N1G KW - Index Medicus KW - Arsenic -- adverse effects KW - Humans KW - Smoking -- adverse effects KW - Aged KW - Radon -- adverse effects KW - China -- epidemiology KW - Risk Factors KW - Adult KW - Cohort Studies KW - Surveys and Questionnaires KW - Incidence KW - Middle Aged KW - Female KW - Male KW - Occupational Diseases -- diagnosis KW - Lung Neoplasms -- etiology KW - Lung Neoplasms -- diagnosis KW - Lung Neoplasms -- epidemiology KW - Occupational Diseases -- etiology KW - Occupational Diseases -- epidemiology KW - Mining UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79479735?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+epidemiology&rft.atitle=Risk+factors+and+early+detection+of+lung+cancer+in+a+cohort+of+Chinese+tin+miners.&rft.au=Qiao%2C+Y+L%3BTaylor%2C+P+R%3BYao%2C+S+X%3BErozan%2C+Y+S%3BLuo%2C+X+C%3BBarrett%2C+M+J%3BYan%2C+Q+Y%3BGiffen%2C+C+A%3BHuang%2C+S+Q%3BMaher%2C+M+M%3BForman%2C+M+R%3BTockman%2C+M+S&rft.aulast=Qiao&rft.aufirst=Y&rft.date=1997-11-01&rft.volume=7&rft.issue=8&rft.spage=533&rft.isbn=&rft.btitle=&rft.title=Annals+of+epidemiology&rft.issn=10472797&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-01-22 N1 - Date created - 1998-01-22 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Ann Epidemiol. 1997 Nov;7(8):530-2 [9408548] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Investigation of hydrolytic deamination of 1-(2-hydroxy-1-phenylethyl)adenosine. AN - 79476389; 9403177 AB - The ring nitrogen of adenosine reacts at both the alpha- (benzylic) and beta-carbons of styrene oxide to form 1-substituted products. The 1-(2-hydroxy-1-phenylethyl)adenosines formed by oxirane ring opening at the alpha-position are prone to an unusually facile hydrolytic deamination. By conducting hydrolysis reactions in [18O]water and analyzing the reaction products by electrospray mass spectrometry, we find that deamination occurs by direct attack of water at the 6-position of the adenine ring system with displacement of the exocyclic amino group. JF - Chemical research in toxicology AU - Barlow, T AU - Ding, J AU - Vouros, P AU - Dipple, A AD - Chemistry of Carcinogenesis Laboratory, NCI-Frederick Cancer Research and Development Center, Maryland 21702, USA. barlowt@ncifcrf.gov Y1 - 1997/11// PY - 1997 DA - November 1997 SP - 1247 EP - 1249 VL - 10 IS - 11 SN - 0893-228X, 0893-228X KW - 1-(2-hydroxy-1-phenylethyl)adenosine KW - 0 KW - Epoxy Compounds KW - styrene oxide KW - 9QH06NGT6O KW - Adenosine KW - K72T3FS567 KW - Index Medicus KW - Mass Spectrometry KW - Stereoisomerism KW - Deamination KW - Spectrophotometry, Ultraviolet KW - Cyclization KW - Hydrolysis KW - Magnetic Resonance Spectroscopy KW - Adenosine -- chemistry KW - Adenosine -- analogs & derivatives KW - Epoxy Compounds -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79476389?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Investigation+of+hydrolytic+deamination+of+1-%282-hydroxy-1-phenylethyl%29adenosine.&rft.au=Barlow%2C+T%3BDing%2C+J%3BVouros%2C+P%3BDipple%2C+A&rft.aulast=Barlow&rft.aufirst=T&rft.date=1997-11-01&rft.volume=10&rft.issue=11&rft.spage=1247&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 - 1998-02-10 N1 - Date created - 1998-02-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dopaminergic mediation of the discriminative stimulus effects of bupropion in rats. AN - 79462579; 9399385 AB - Bupropion is a novel, non-tricyclic antidepressant with a primary pharmacological action of monoamine uptake inhibition. The drug resembles a psychostimulant in terms of its neurochemical and behavioural profiles in vivo, but it does not reliably produce stimulant-like effects in humans at clinically prescribed doses. Bupropion binds with modest selectivity to the dopamine transporter, but its behavioural effects have often been attributed to its inhibition of norepinephrine uptake. This experiment examines monoaminergic involvement in the discriminative stimulus effects of bupropion. Rats were trained to press one lever when injected i.p. with bupropion (17.0 mg/kg), and another lever when injected with saline. In substitution tests, dose-response curves were obtained for several monoamine uptake inhibitors. Nine of ten dopamine uptake blockers fully substituted for bupropion; the exception, indatraline (LU 19-005), partially substituted (71% bupropion-appropriate responding). Serotonin and norepinephrine uptake blockers (zimelidine and nisoxetine, respectively) produced negligible or limited substitution, and the anti-muscarinic dopamine uptake blocker benztropine produced limited partial substitution. A series of dopamine D1-like and D2-like receptor agonists were also tested: only the D2-like agonist RU 24213 fully substituted; three other D2-like agonists and four D1-like agonists partially substituted (50% < drug responding < 80%). Antagonism of the discriminative effects of bupropion was obtained with a D1- and a D2-like dopamine antagonist. The results demonstrate strong similarities with those obtained using other dopamine uptake inhibitors as training drugs, and support the view that the behavioural effects of bupropion are primarily mediated by dopaminergic mechanisms. JF - Psychopharmacology AU - Terry, P AU - Katz, J L AD - Psychobiology Section, NIDA Intramural Research Program, National Institutes of Health, Baltimore, MD 21224, USA. Y1 - 1997/11// PY - 1997 DA - November 1997 SP - 201 EP - 212 VL - 134 IS - 2 SN - 0033-3158, 0033-3158 KW - Dopamine D2 Receptor Antagonists KW - 0 KW - Dopamine Uptake Inhibitors KW - Receptors, Dopamine D1 KW - Receptors, Dopamine D2 KW - Bupropion KW - 01ZG3TPX31 KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Rats KW - Discrimination Learning -- drug effects KW - Animals KW - Rats, Sprague-Dawley KW - Drug Interactions KW - Reinforcement Schedule KW - Receptors, Dopamine D1 -- agonists KW - Dose-Response Relationship, Drug KW - Receptors, Dopamine D1 -- antagonists & inhibitors KW - Receptors, Dopamine D2 -- agonists KW - Male KW - Discrimination (Psychology) -- drug effects KW - Dopamine -- physiology KW - Dopamine Uptake Inhibitors -- pharmacology KW - Bupropion -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79462579?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psychopharmacology&rft.atitle=Dopaminergic+mediation+of+the+discriminative+stimulus+effects+of+bupropion+in+rats.&rft.au=Terry%2C+P%3BKatz%2C+J+L&rft.aulast=Terry&rft.aufirst=P&rft.date=1997-11-01&rft.volume=134&rft.issue=2&rft.spage=201&rft.isbn=&rft.btitle=&rft.title=Psychopharmacology&rft.issn=00333158&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-01-09 N1 - Date created - 1998-01-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of chronic ethanol on the mobilization of arachidonate and docosahexaenoate stimulated by the type 2A serotonin receptor agonist (+/-)-2,5-dimethoxy-4-iodoamphetamine hydrochloride in C6 glioma cells. AN - 79452007; 9394119 AB - We studied the effects of chronic ethanol exposure on the mobilization of polyunsaturated fatty acids stimulated by activation of the type 2A serotonin receptor in C6 glioma cells. In our in vitro model, we prelabeled cells with [3H]arachidonate and [14C]docosahexaenonate and subsequently stimulated with the type 2A serotonin receptor agonist (+/-)-2,5-dimethoxy-4-iodoamphetamine hydrochloride. In as early as 10 days of exposure to 20 or 50 mM ethanol, the (+/-)-2,5-dimethoxy-4-iodoamphetamine hydrochloride-simulated mobilization of [3H]arachidonic acid [[3H]AA) and [14C]docosahexaenoic acid ([14C]DHA) was significantly inhibited, and this inhibition was accompanied by decreased mobilization of intracellular [Ca2+]i. Exposure to ethanol did not alter significantly the release of [3H]AA and [14C]DHA stimulated by the calcium ionophore A23187 nor the incorporation of [3H]AA and [14C]DHA into cellular lipids. Decreased mobilization of polyunsaturated fatty acids and calcium in astroglia may contribute to neurotoxicity caused by chronic ethanol exposure. JF - Alcoholism, clinical and experimental research AU - Garcia, M C AU - Kim, K Y AU - Hough, C AU - Kim, H Y AD - Section of Mass Spectrometry, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD 20852. USA. Y1 - 1997/11// PY - 1997 DA - November 1997 SP - 1465 EP - 1470 VL - 21 IS - 8 SN - 0145-6008, 0145-6008 KW - Amphetamines KW - 0 KW - Receptor, Serotonin, 5-HT2A KW - Receptors, Serotonin KW - Serotonin Receptor Agonists KW - Docosahexaenoic Acids KW - 25167-62-8 KW - Arachidonic Acid KW - 27YG812J1I KW - Ethanol KW - 3K9958V90M KW - 4-iodo-2,5-dimethoxyphenylisopropylamine KW - OOM10GW9UE KW - Index Medicus KW - Rats KW - Brain Neoplasms KW - Animals KW - Tumor Cells, Cultured -- physiology KW - Cell Survival -- drug effects KW - Tumor Cells, Cultured -- drug effects KW - Glioma KW - Serotonin Receptor Agonists -- pharmacology KW - Receptors, Serotonin -- physiology KW - Receptors, Serotonin -- drug effects KW - Docosahexaenoic Acids -- pharmacology KW - Amphetamines -- pharmacology KW - Astrocytes -- drug effects KW - Ethanol -- toxicity KW - Arachidonic Acid -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79452007?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Alcoholism%2C+clinical+and+experimental+research&rft.atitle=Effects+of+chronic+ethanol+on+the+mobilization+of+arachidonate+and+docosahexaenoate+stimulated+by+the+type+2A+serotonin+receptor+agonist+%28%2B%2F-%29-2%2C5-dimethoxy-4-iodoamphetamine+hydrochloride+in+C6+glioma+cells.&rft.au=Garcia%2C+M+C%3BKim%2C+K+Y%3BHough%2C+C%3BKim%2C+H+Y&rft.aulast=Garcia&rft.aufirst=M&rft.date=1997-11-01&rft.volume=21&rft.issue=8&rft.spage=1465&rft.isbn=&rft.btitle=&rft.title=Alcoholism%2C+clinical+and+experimental+research&rft.issn=01456008&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-01-16 N1 - Date created - 1998-01-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Induction of replicative DNA synthesis and PPAR alpha-dependent gene transcription by Wy-14 643 in primary rat hepatocyte and non-parenchymal cell co-cultures. AN - 79446789; 9395205 AB - Peroxisome proliferators (PP) are known hepatocarcinogens in rats and mice. We have investigated the ability of Wyeth-14 643 (Wy), a PP and potent rodent carcinogen, to induce replicative DNA synthesis and to modulate the levels of peroxisome proliferator activated receptor-alpha (PPAR alpha) transcriptionally-dependent genes in primary rat hepatocyte (HPC) cultures and hepatocyte/nonparenchymal cell (HPC/NPC) co-cultures maintained on Matrigel. Four days after plating, cells were treated with Wy and replicative DNA synthesis was quantitated using [3H]thymidine incorporation and specific mRNA transcript levels were determined by reverse-transcriptase polymerase chain reaction (RT-PCR). An increase in HPC replicative DNA synthesis was detected at 48 h in both Wy-treated HPC and HPC/NPC co-cultures relative to controls. This increase was approximately 3- and 6-fold in HPC and HPC/NPC cultures respectively, and was Wy concentration-dependent. The levels of PPAR alpha-transcriptionally dependent genes [cytochrome P4504A1, acyl-CoA oxidase (AOxase), and liver-fatty acid binding protein (L-FABP)] transcripts were determined as indicators of PPAR alpha activation. These transcripts increased dose-dependently at 48 h in HPC/NPC cultures up to 10 microM Wy. Similarly, RT-PCR product levels were also increased in HPC cultures with 10 microM Wy at 48 h. In conclusion, we have investigated the transcription of PPAR alpha-dependent genes and HPC replicative DNA synthesis by Wy in HPC/NPC co-cultures. Results of this work are clearly more reflective of the known in vivo effects of PP and suggest that HPC/NPC co-cultures are more appropriate than HPC cultures for such studies. The effect of PP on human HPC/NPC co-cultures is currently being investigated in our laboratory in an attempt to assess human risks to these chemicals more directly. JF - Carcinogenesis AU - Karam, W G AU - Ghanayem, B I AD - Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institutes of Health, RTP, NC 27709, USA. Y1 - 1997/11// PY - 1997 DA - November 1997 SP - 2077 EP - 2083 VL - 18 IS - 11 SN - 0143-3334, 0143-3334 KW - Carcinogens KW - 0 KW - Pyrimidines KW - Receptors, Cytoplasmic and Nuclear KW - Transcription Factors KW - pirinixic acid KW - 86C4MRT55A KW - DNA KW - 9007-49-2 KW - Thymidine KW - VC2W18DGKR KW - Index Medicus KW - Thymidine -- metabolism KW - Rats KW - Coculture Techniques KW - Animals KW - Rats, Inbred F344 KW - Cells, Cultured KW - DNA -- biosynthesis KW - Male KW - Receptors, Cytoplasmic and Nuclear -- physiology KW - Transcription Factors -- physiology KW - Transcription, Genetic -- drug effects KW - Liver -- drug effects KW - Pyrimidines -- toxicity KW - Carcinogens -- toxicity KW - Liver -- metabolism KW - DNA Replication -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79446789?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Induction+of+replicative+DNA+synthesis+and+PPAR+alpha-dependent+gene+transcription+by+Wy-14+643+in+primary+rat+hepatocyte+and+non-parenchymal+cell+co-cultures.&rft.au=Karam%2C+W+G%3BGhanayem%2C+B+I&rft.aulast=Karam&rft.aufirst=W&rft.date=1997-11-01&rft.volume=18&rft.issue=11&rft.spage=2077&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-12-30 N1 - Date created - 1997-12-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Energy-dependent expression of platelet-von Willebrand factor on the surface of unstimulated and stimulated platelets. AN - 79442711; 9390640 AB - We have studied the energy requirements (adenosine triphosphate) for the expression of platelet-von Willbrand factor on platelets under conditions in which glycolysis and/or oxidative phosphorylation were inhibited. We found that platelet-vWf expression on the surfaces of both unstimulated and stimulated platelets required energy and was maximally decreased when metabolic ATP was maximally depleted. Platelet-vWf expression correlated directly with estimates of adenylate energy charge in both unstimulated and stimulated platelets. In addition, platelet shape change and agonist-induced intracellular Ca2+ flux were maintained at lower AECs than were either platelet aggregation or alpha-granule secretion. Our results indicate that the surface expression of platelet-vWf on unstimulated platelets is a dynamic process, and that energy is required to maintain basal amounts of platelet-vWf on the platelet surface. Our data also suggest that the metabolic ATP required to effect changes in platelet shape is less than that necessary to maintain basal platelet-vWf surface expression or to produce full alpha-granule secretion. We show that platelet-shape change in the absence of alpha-granule secretion can result in an increase in platelet-vWf surface expression. JF - The Journal of laboratory and clinical medicine AU - Parker, R I AU - Gralnick, H R AD - Clinical Pathology Department, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1997/11// PY - 1997 DA - November 1997 SP - 520 EP - 529 VL - 130 IS - 5 SN - 0022-2143, 0022-2143 KW - beta-Thromboglobulin KW - 0 KW - von Willebrand Factor KW - Rotenone KW - 03L9OT429T KW - antimycin KW - 11118-72-2 KW - Antimycin A KW - 642-15-9 KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - Deoxyglucose KW - 9G2MP84A8W KW - Thrombin KW - EC 3.4.21.5 KW - Potassium Cyanide KW - MQD255M2ZO KW - 2,4-Dinitrophenol KW - Q13SKS21MN KW - Calcium KW - SY7Q814VUP KW - Abridged Index Medicus KW - Index Medicus KW - Cell Size KW - Calcium -- blood KW - beta-Thromboglobulin -- secretion KW - Humans KW - Energy Metabolism KW - Rotenone -- pharmacology KW - Protein Binding KW - Potassium Cyanide -- pharmacology KW - Antimycin A -- pharmacology KW - Platelet Aggregation KW - Glycolysis -- drug effects KW - Antimycin A -- analogs & derivatives KW - Oxidative Phosphorylation -- drug effects KW - Thrombin -- pharmacology KW - 2,4-Dinitrophenol -- pharmacology KW - Cell Membrane -- metabolism KW - Deoxyglucose -- pharmacology KW - Thrombin -- metabolism KW - von Willebrand Factor -- metabolism KW - Blood Platelets -- drug effects KW - Adenosine Triphosphate -- metabolism KW - Platelet Activation KW - Blood Platelets -- cytology KW - Blood Platelets -- metabolism KW - von Willebrand Factor -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79442711?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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+laboratory+and+clinical+medicine&rft.atitle=Energy-dependent+expression+of+platelet-von+Willebrand+factor+on+the+surface+of+unstimulated+and+stimulated+platelets.&rft.au=Parker%2C+R+I%3BGralnick%2C+H+R&rft.aulast=Parker&rft.aufirst=R&rft.date=1997-11-01&rft.volume=130&rft.issue=5&rft.spage=520&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+laboratory+and+clinical+medicine&rft.issn=00222143&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-12-18 N1 - Date created - 1997-12-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of PPAR alpha in the mechanism of action of the nongenotoxic carcinogen and peroxisome proliferator Wy-14,643. AN - 79441454; 9395198 AB - Chronic administration of peroxisome proliferators to mice and rats results in hepatomegaly and ultimately carcinogenesis. The mechanism underlying the carcinogenic effect of nongenotoxic peroxisome proliferators is not well understood. To determine whether nongenotoxic carcinogenesis is receptor mediated, we evaluated the effect of the prototypical peroxisome proliferator Wy-14,643 on replicative DNA synthesis and carcinogenesis in the PPAR alpha-null mouse line. Male mice (F4, Sv/129 ter) of both genotypes (+/+) and (-/-) were fed either a control diet or one containing 0.1% Wy-14,643 for either 1 week, 5 weeks, or 11 months. Wild-type mice fed the Wy-14,643 diet for 1 or 5 weeks showed increased hepatic labeling by bromodeoxyuridine (BrDU) compared to untreated controls. In contrast, there was no increase in hepatic BrDU labeling index in (-/-) mice fed the Wy-14,643 diet for the same time periods compared to controls. After 11 months, 100% of the (+/+) mice fed the Wy-14,643 diet had multiple hepatocellular neoplasms, including adenomas and carcinomas, while the (-/-) mice fed the Wy-14,643 diet were unaffected. This work demonstrates that the effects of Wy-14,643 on replicative DNA synthesis and hepatocarcinogenesis are mediated by PPAR alpha. JF - Carcinogenesis AU - Peters, J M AU - Cattley, R C AU - Gonzalez, F J AD - Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1997/11// PY - 1997 DA - November 1997 SP - 2029 EP - 2033 VL - 18 IS - 11 SN - 0143-3334, 0143-3334 KW - Carcinogens KW - 0 KW - Pyrimidines KW - Receptors, Cytoplasmic and Nuclear KW - Transcription Factors KW - pirinixic acid KW - 86C4MRT55A KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Animals KW - Liver -- pathology KW - Liver -- drug effects KW - Mice KW - DNA -- biosynthesis KW - Male KW - Receptors, Cytoplasmic and Nuclear -- physiology KW - Transcription Factors -- physiology KW - Pyrimidines -- toxicity KW - Carcinogens -- toxicity KW - Liver Neoplasms, Experimental -- chemically induced KW - Microbodies -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79441454?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Role+of+PPAR+alpha+in+the+mechanism+of+action+of+the+nongenotoxic+carcinogen+and+peroxisome+proliferator+Wy-14%2C643.&rft.au=Peters%2C+J+M%3BCattley%2C+R+C%3BGonzalez%2C+F+J&rft.aulast=Peters&rft.aufirst=J&rft.date=1997-11-01&rft.volume=18&rft.issue=11&rft.spage=2029&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-12-30 N1 - Date created - 1997-12-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Functional characterization of the rat mdr1b encoded P-glycoprotein: not all inducing agents are substrates. AN - 79440063; 9395229 AB - The multidrug resistance (mdr) genes encode P-glycoproteins, integral membrane proteins which function as drug efflux transporters. Exposure of animals in vivo and cells in vitro to a variety of xenobiotics leads to increased mdr1 gene expression and higher levels of P-glycoprotein. This response may protect cells from the cytotoxic effects of these compounds. In this investigation we functionally expressed the rat mdr1b gene in NIH 3T3 cells and assessed the ability of the encoded P-glycoprotein to protect these cells from the cytotoxicity of xenobiotics known to induce mdr1b expression. In long-term colony survival assays, stably expressed mdr1b conferred resistance to cytotoxic drugs such as colchicine, vinblastine and doxorubicin, but not to 5-fluorouracil nor to the carcinogens aflatoxin B1 and N-hydroxy-acetylaminofluorene. The mdr reversal agent verapamil restored cytotoxicity of colchicine, doxorubicin, actinomycin D, vinblastine and taxol, but had no effect on the sensitivity of these cells to 5-fluorouracil, aflatoxin B1 or N-hydroxy-acetylaminofluorene. In a competitive transport assay, verapamil and, to a lesser extent, colchicine blocked the increased efflux of the fluorescent dye rhodamine 123 from mdr1b-transfected cells, whereas aflatoxin B1 did not compete for this export. These data demonstrate that expression of the rat mdr1b encoded P-glycoprotein can protect cells from a diverse group of compounds previously identified to be mdr substrates, however, other effective inducers of mdr expression, such as aflatoxin B1 and N-hydroxy-acetylaminofluorene, remain potent cytotoxins despite high levels of P-glycoprotein. The fact that compounds which are not themselves substrates can induce P-glycoprotein expression may have implications for pharmacokinetic interactions and chemotherapy. JF - Carcinogenesis AU - Santoni-Rugiu, E AU - Silverman, J A AD - Division of Basic Sciences, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1997/11// PY - 1997 DA - November 1997 SP - 2255 EP - 2263 VL - 18 IS - 11 SN - 0143-3334, 0143-3334 KW - P-Glycoprotein KW - 0 KW - RNA, Messenger KW - Rhodamines KW - Rhodamine 123 KW - 1N3CZ14C5O KW - Hydroxyacetylaminofluorene KW - 53-95-2 KW - Aflatoxin B1 KW - 9N2N2Y55MH KW - Index Medicus KW - 3T3 Cells KW - Animals KW - Rhodamines -- metabolism KW - RNA, Messenger -- analysis KW - Liver -- metabolism KW - Mice KW - Rats KW - Rats, Inbred F344 KW - Liver -- drug effects KW - Aflatoxin B1 -- toxicity KW - Male KW - Hydroxyacetylaminofluorene -- toxicity KW - P-Glycoprotein -- physiology KW - P-Glycoprotein -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79440063?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Functional+characterization+of+the+rat+mdr1b+encoded+P-glycoprotein%3A+not+all+inducing+agents+are+substrates.&rft.au=Santoni-Rugiu%2C+E%3BSilverman%2C+J+A&rft.aulast=Santoni-Rugiu&rft.aufirst=E&rft.date=1997-11-01&rft.volume=18&rft.issue=11&rft.spage=2255&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-12-30 N1 - Date created - 1997-12-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A role for REV3 in mutagenesis during double-strand break repair in Saccharomyces cerevisiae. AN - 79434127; 9383049 AB - Recombinational repair of double-strand breaks (DSBs), traditionally believed to be an error-free DNA repair pathway, was recently shown to increase the frequency of mutations in a nearby interval. The reversion rate of trp1 alleles (either nonsense or frameshift mutations) near an HO-endonuclease cleavage site is increased at least 100-fold among cells that have experienced an HO-mediated DSB. We report here that in strains deleted for rev3 this DSB-associated reversion of a nonsense mutation was greatly decreased. Thus REV3, which encodes a subunit of the translesion DNA polymerase zeta, was responsible for the majority of these base substitution errors near a DSB. However, rev3 strains showed no decrease in HO-stimulated recombination, implying that another DNA polymerase also functioned in recombinational repair of a DSB. Reversion of trp1 frameshift alleles near a DSB was not reduced in rev3 strains, indicating that another polymerase could act during DSB repair to make these frameshift errors. Analysis of spontaneous reversion in haploid strains suggested that Rev3p had a greater role in making point mutations than in frameshift mutations. JF - Genetics AU - Holbeck, S L AU - Strathern, J N AD - National Cancer Institute-Frederick Cancer Research and Development Center, ABL-Basic Research Program, Maryland 21702-1201, USA. Y1 - 1997/11// PY - 1997 DA - November 1997 SP - 1017 EP - 1024 VL - 147 IS - 3 SN - 0016-6731, 0016-6731 KW - Fungal Proteins KW - 0 KW - Saccharomyces cerevisiae Proteins KW - DNA-Directed DNA Polymerase KW - EC 2.7.7.7 KW - REV3 protein, S cerevisiae KW - HO protein, S cerevisiae KW - EC 3.1.21.- KW - SCEI protein, S cerevisiae KW - Deoxyribonucleases, Type II Site-Specific KW - EC 3.1.21.4 KW - Aldose-Ketose Isomerases KW - EC 5.3.1.- KW - TRP1 protein, S cerevisiae KW - EC 5.3.1.24 KW - Index Medicus KW - Frameshift Mutation KW - Point Mutation KW - Mutagenesis KW - Deoxyribonucleases, Type II Site-Specific -- metabolism KW - Saccharomyces cerevisiae -- genetics KW - Fungal Proteins -- physiology KW - DNA-Directed DNA Polymerase -- physiology KW - DNA Repair KW - Saccharomyces cerevisiae -- enzymology KW - Fungal Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79434127?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+role+for+REV3+in+mutagenesis+during+double-strand+break+repair+in+Saccharomyces+cerevisiae.&rft.au=Holbeck%2C+S+L%3BStrathern%2C+J+N&rft.aulast=Holbeck&rft.aufirst=S&rft.date=1997-11-01&rft.volume=168&rft.issue=5&rft.spage=571&rft.isbn=&rft.btitle=&rft.title=The+British+journal+of+psychiatry+%3A+the+journal+of+mental+science&rft.issn=00071250&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-02-05 N1 - Date created - 1998-02-05 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Mol Gen Genet. 1983;189(1):113-7 [6574304] Cell. 1983 May;33(1):25-35 [6380756] Mol Gen Genet. 1984;195(3):487-90 [6381967] Mol Gen Genet. 1984;197(2):345-6 [6394957] Cold Spring Harb Symp Quant Biol. 1984;49:97-104 [6397325] Cell. 1985 Nov;43(1):369-77 [3907855] Genetics. 1987 Aug;116(4):541-5 [3305158] Microbiol Rev. 1988 Mar;52(1):70-102 [3280967] J Bacteriol. 1989 Jan;171(1):230-7 [2492497] J Bacteriol. 1989 Oct;171(10):5659-67 [2676986] Cell. 1990 Jun 15;61(6):1089-101 [2190690] Curr Genet. 1990 Jul;18(1):29-39 [2173978] Nucleic Acids Res. 1992 Mar 25;20(6):1425 [1561104] Genetics. 1992 Aug;131(4):783-9 [1516815] Genetics. 1992 Sep;132(1):9-21 [1398066] Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10777-81 [1438275] Mol Cell Biol. 1993 Feb;13(2):1051-8 [8423775] Cell. 1993 Feb 12;72(3):397-406 [8381717] Proc Natl Acad Sci U S A. 1993 Sep 1;90(17):8169-73 [8367479] Cell. 1993 Dec 17;75(6):1215-25 [8261515] Cell. 1993 Dec 17;75(6):1227-36 [8261516] Science. 1994 Apr 8;264(5156):258-60 [8146657] Mol Cell Biol. 1994 Jun;14(6):3971-80 [8196636] Curr Opin Genet Dev. 1994 Apr;4(2):212-20 [8032198] Genetics. 1994 Jul;137(3):637-46 [8088509] J Biol Chem. 1995 Aug 18;270(33):19516-23 [7543900] Curr Opin Immunol. 1995 Apr;7(2):248-54 [7546385] Cell. 1997 Jan 24;88(2):155-8 [9008154] Cell. 1997 Feb 7;88(3):375-84 [9039264] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mortality study of pesticide applicators and other employees of a lawn care service company. AN - 79432861; 9383716 AB - In response to reports linking non-Hodgkin's lymphoma (NHL) and the herbicide 2,4-dichlorophenoxyacetic acid, a retrospective cohort mortality study of 32,600 employees of a lawn care company was conducted. The cohort was generally young with short-duration employment and follow-up. In comparison to the US population, the cohort had significantly decreased mortality from all causes of death combined (307 deaths), arteriosclerotic heart disease, and accidents. There were 45 cancer deaths (59.6 expected, standardized mortality ratio [SMR] = 0.76, 95% confidence interval [CI] = 0.55, 1.01). Bladder cancer mortality was significantly increased, but two of the three observed deaths had no direct occupational contact with pesticides. There were four deaths due to NHL (SMR = 1.14, CI = 0.31, 2.91); three were male lawn applicators (SMR = 1.63, CI = 0.33, 4.77), with two of the applicators employed for three or more years (SMR = 7.11, CI = 1.78, 28.42). No other cause of death was significantly elevated among lawn applicators as a group or among those employed for three or more years. Although based on very small numbers and perhaps due to chance, the NHL excess is consistent with several earlier studies. JF - Journal of occupational and environmental medicine AU - Zahm, S H AD - Occupational Epidemiology Branch, National Cancer Institute, Rockville, Md. 20892-7364, USA. Y1 - 1997/11// PY - 1997 DA - November 1997 SP - 1055 EP - 1067 VL - 39 IS - 11 SN - 1076-2752, 1076-2752 KW - Pesticides KW - 0 KW - Index Medicus KW - Humans KW - Retrospective Studies KW - Ohio -- epidemiology KW - Predictive Value of Tests KW - Age Distribution KW - Lymphoma, Non-Hodgkin -- mortality KW - Survival Rate KW - Risk Factors KW - Adult KW - Cohort Studies KW - Confidence Intervals KW - Middle Aged KW - Occupations -- classification KW - United States -- epidemiology KW - Sex Distribution KW - Female KW - Male KW - Agricultural Workers' Diseases -- mortality KW - Neoplasms -- mortality KW - Neoplasms -- chemically induced KW - Agricultural Workers' Diseases -- chemically induced KW - Occupational Exposure -- adverse effects KW - Pesticides -- adverse effects KW - Cause of Death UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79432861?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+occupational+and+environmental+medicine&rft.atitle=Mortality+study+of+pesticide+applicators+and+other+employees+of+a+lawn+care+service+company.&rft.au=Zahm%2C+S+H&rft.aulast=Zahm&rft.aufirst=S&rft.date=1997-11-01&rft.volume=39&rft.issue=11&rft.spage=1055&rft.isbn=&rft.btitle=&rft.title=Journal+of+occupational+and+environmental+medicine&rft.issn=10762752&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-01-02 N1 - Date created - 1998-01-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phenolphthalein-containing laxative use in relation to adenomatous colorectal polyps in three studies. AN - 79428876; 9370521 AB - Phenolphthalein, the active ingredient in many laxatives, was recently found to be a carcinogen in animal models. Human data suggest a laxative-colon cancer association, but few data specifically address the effects of phenolthalein-containing laxatives. We examined use of phenolphtalein-containing laxatives in relation to occurrence of adenomatous colorectal polyps in data from three case-control studies. The study conducted in Los Angeles, California (1991-1993), and the two studies conducted in North Carolina (1988-1990 and 1992-1995) altogether included 866 cases and 1,066 controls. The prevalence of using phenolphthalein-containing laxatives at least once a week in the recent past, however, was less than 5% among these subjects. The multivariate-adjusted odds ratios associated with recent use of phenolphthalein-containing laxatives once a week or more were 1.8 -95% confidence interval (CI), 0.5-6.2] in Los Angeles, 1.0 (CI, 0.4-2.2) in North Carolina (1988-1990), and 1.1 (CI, 0.2-5.7) in North Carolina (1992-1995). For use of other types of laxatives, the corresponding odds ratios were 1.3 (CI, 0.9-1.9) in Los Angeles, 1.0 (CI, 0.5-1.7) in North Carolina (1988-1990), and 0.9 (CI, 0.4-1.8) in North Carolina (1992-1995). Although the low prevalence of frequent use made for relatively wide confidence intervals, overall these data suggest that use of phenolphthalein-containing laxatives does not increase risk of adenomatous colorectal polyps. JF - Environmental health perspectives AU - Longnecker, M P AU - Sandler, D P AU - Haile, R W AU - Sandler, R S AD - Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709 USA. Y1 - 1997/11// PY - 1997 DA - November 1997 SP - 1210 EP - 1212 VL - 105 IS - 11 SN - 0091-6765, 0091-6765 KW - Cathartics KW - 0 KW - Phenolphthaleins KW - Phenolphthalein KW - 6QK969R2IF KW - Index Medicus KW - Odds Ratio KW - Risk Factors KW - Humans KW - Adult KW - Case-Control Studies KW - Aged KW - Middle Aged KW - Male KW - Female KW - Prevalence KW - Phenolphthaleins -- adverse effects KW - Cathartics -- adverse effects KW - Intestinal Polyps -- etiology KW - Colorectal Neoplasms -- etiology KW - Colorectal Neoplasms -- chemically induced KW - Adenomatous Polyps -- chemically induced KW - Adenomatous Polyps -- etiology KW - Intestinal Polyps -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79428876?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Phenolphthalein-containing+laxative+use+in+relation+to+adenomatous+colorectal+polyps+in+three+studies.&rft.au=Longnecker%2C+M+P%3BSandler%2C+D+P%3BHaile%2C+R+W%3BSandler%2C+R+S&rft.aulast=Longnecker&rft.aufirst=M&rft.date=1997-11-01&rft.volume=105&rft.issue=11&rft.spage=1210&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 - 1998-01-15 N1 - Date created - 1998-01-15 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Br J Cancer. 1996 Jun;73(11):1431-5 [8645593] Epidemiology. 1996 May;7(3):275-80 [8728441] Cancer Res. 1996 Nov 1;56(21):4922-6 [8895745] J Natl Cancer Inst. 1996 Dec 4;88(23):1717-30 [8944002] Am J Epidemiol. 1986 Sep;124(3):453-69 [3740045] Am J Epidemiol. 1992 May 15;135(10):1114-26; discussion 1127-36 [1632423] Z Gastroenterol. 1993 Feb;31(2):140-3 [8465555] Cancer Epidemiol Biomarkers Prev. 1993 Mar-Apr;2(2):159-76 [8467251] Gastroenterology. 1993 May;104(5):1445-51 [8482454] J Natl Cancer Inst. 1993 Jun 2;85(11):884-91 [8388061] Pharmacology. 1993 Oct;47 Suppl 1:224-33 [8234434] N Engl J Med. 1993 Dec 30;329(27):1977-81 [8247072] Epidemiol Rev. 1993;15(2):499-545 [8174669] Epidemiol Rev. 1994;16(2):273-97 [7713180] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - rG-CSF reduces endotoxemia and improves survival during E. coli pneumonia. AN - 79427757; 9375307 AB - We investigated the effects of recombinant granulocyte colony-stimulating factor (rG-CSF) during canine bacterial pneumonia. Beagles with chronic tracheostomies received daily subcutaneous rG-CSF (5 micrograms/kg body wt) or placebo for 14 days, beginning 9 days before intrabronchial inoculation with E. coli. Animals received antibiotics and fluid support; a subset received humidified oxygen (fractional inspired O2 0.40). Compared with controls, rG-CSF increased circulating neutrophil counts (57.4 vs. 11.0 x 10(3)/mm3, day 1 after infection; P = 0.0001), decreased plasma endotoxin (7.5 vs. 1.1 EU/ml at 8 h; P < 0.01) and serum tumor necrosis factor-alpha (3,402 vs. 729 pg/ml at 2 h; P = 0.01) levels, and prolonged survival (relative risk of death = 0.45, 95% confidence interval 0.21-0.97; P = 0.038). Also, rG-CSF attenuated sepsis-associated myocardial dysfunction (P < 0.001). rG-CSF had no effect on pulmonary function or on blood and lung bacteria counts (all P = not significant). Other animals challenged with endotoxin (4 mg/kg i.v.) after similar treatment with rG-CSF had lower serum endotoxin levels (7.62 vs. 5.81 log EU/ml at 6 h; P < 0.01) and less cardiovascular dysfunction (P < 0.05 to < 0.002) but similar tumor necrosis factor-alpha levels (P = not significant) compared with controls. Thus prophylactic rG-CSF sufficient to increase circulating neutrophils during bacterial pneumonia may improve cardiovascular function and survival by mechanisms that in part enhance the clearance of bacterial toxins but do not improve lung function. JF - Journal of applied physiology (Bethesda, Md. : 1985) AU - Freeman, B D AU - Quezado, Z AU - Zeni, F AU - Natanson, C AU - Danner, R L AU - Banks, S AU - Quezado, M AU - Fitz, Y AU - Bacher, J AU - Eichacker, P Q AD - Critical Care Medicine Department, National Institutes of Health, Bethesda, Maryland 20892-1662, USA. Y1 - 1997/11// PY - 1997 DA - November 1997 SP - 1467 EP - 1475 VL - 83 IS - 5 SN - 8750-7587, 8750-7587 KW - Endotoxins KW - 0 KW - Indicators and Reagents KW - Granulocyte Colony-Stimulating Factor KW - 143011-72-7 KW - endotoxin, Escherichia coli KW - 67924-63-4 KW - Index Medicus KW - Respiratory Function Tests KW - Hemodynamics -- physiology KW - Animals KW - Injections, Intravenous KW - Dogs KW - Survival KW - Endotoxins -- administration & dosage KW - Endotoxins -- toxicity KW - Leukocyte Count KW - Lung -- microbiology KW - Escherichia coli Infections -- microbiology KW - Granulocyte Colony-Stimulating Factor -- therapeutic use KW - Pneumonia, Bacterial -- drug therapy KW - Escherichia coli Infections -- drug therapy KW - Endotoxemia -- prevention & control KW - Pneumonia, Bacterial -- microbiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79427757?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+applied+physiology+%28Bethesda%2C+Md.+%3A+1985%29&rft.atitle=rG-CSF+reduces+endotoxemia+and+improves+survival+during+E.+coli+pneumonia.&rft.au=Freeman%2C+B+D%3BQuezado%2C+Z%3BZeni%2C+F%3BNatanson%2C+C%3BDanner%2C+R+L%3BBanks%2C+S%3BQuezado%2C+M%3BFitz%2C+Y%3BBacher%2C+J%3BEichacker%2C+P+Q&rft.aulast=Freeman&rft.aufirst=B&rft.date=1997-11-01&rft.volume=83&rft.issue=5&rft.spage=1467&rft.isbn=&rft.btitle=&rft.title=Journal+of+applied+physiology+%28Bethesda%2C+Md.+%3A+1985%29&rft.issn=87507587&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-12-30 N1 - Date created - 1997-12-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Expression and regulation of gamma-glutamyl transpeptidase-related enzyme in tracheal cells. AN - 79427563; 9374738 AB - Glutathione plays an essential role in protecting the pulmonary system from toxic insults. gamma-Glutamyl transpeptidase-related enzyme (GGT-rel) is a novel protein capable of cleaving the gamma-glutamyl peptide bond of glutathione and of converting leukotriene C4 to leukotriene D4. A rat homologue of GGT-rel was identified and was found to be highly expressed in cultures of differentiating rat tracheal epithelial (RTE) cells. The 2.6-kb cDNA predicts a 572-amino acid protein with 79% identity to human GGT-rel. GGT-rel was weakly expressed in normal trachea but was strongly induced by epidermal growth factor in cultures of RTE cells. GGT-rel was also highly expressed in lung tumors induced by inhalation of isobutyl nitrite. These results demonstrate that GGT-rel 1) is expressed in normal tracheal cells, 2) can be induced by epidermal growth factor, and 3) is elevated after chemical exposure. The induction of high levels of GGT-rel may play an important role in protecting the lung from oxidative stress or other toxic insults. JF - The American journal of physiology AU - Potdar, P D AU - Andrews, K L AU - Nettesheim, P AU - Ostrowski, L E AD - Laboratory of Pulmonary Pathobiology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1997/11// PY - 1997 DA - November 1997 SP - L1082 EP - L1089 VL - 273 IS - 5 Pt 1 SN - 0002-9513, 0002-9513 KW - Carcinogens KW - 0 KW - DNA Primers KW - Nitrites KW - Epidermal Growth Factor KW - 62229-50-9 KW - gamma-glutamyltransferase related enzyme KW - EC 2.3.2.- KW - gamma-Glutamyltransferase KW - EC 2.3.2.2 KW - isobutyl nitrite KW - GW9WAB6QOM KW - Index Medicus KW - Animals KW - Humans KW - Organ Specificity KW - Amino Acid Sequence KW - Epidermal Growth Factor -- pharmacology KW - Rats KW - Polymerase Chain Reaction KW - Base Sequence KW - Epithelial Cells -- cytology KW - Epithelial Cells -- enzymology KW - Sequence Alignment KW - Cells, Cultured KW - Molecular Sequence Data KW - Sequence Homology, Amino Acid KW - Cell Differentiation -- drug effects KW - Lung Neoplasms -- enzymology KW - gamma-Glutamyltransferase -- chemistry KW - Gene Expression Regulation, Enzymologic -- drug effects KW - gamma-Glutamyltransferase -- biosynthesis KW - Trachea -- cytology KW - Lung Neoplasms -- chemically induced KW - Trachea -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79427563?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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+physiology&rft.atitle=Expression+and+regulation+of+gamma-glutamyl+transpeptidase-related+enzyme+in+tracheal+cells.&rft.au=Potdar%2C+P+D%3BAndrews%2C+K+L%3BNettesheim%2C+P%3BOstrowski%2C+L+E&rft.aulast=Potdar&rft.aufirst=P&rft.date=1997-11-01&rft.volume=273&rft.issue=5+Pt+1&rft.spage=L1082&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+physiology&rft.issn=00029513&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-12-17 N1 - Date created - 1997-12-17 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - U76252; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Age-related negative associations between parameters of cytogenetic damage and ex vivo (+/-)-anti-benzo(a)pyrene diolepoxide-induced unscheduled DNA synthesis in smoking humans. AN - 79419344; 9367068 AB - Chemical or physical modification of DNA may cause an increase in genomic mutations or other genetic alterations, which may ultimately result in the onset of cancer. To avoid these deleterious effects of DNA damage, humans possess DNA repair mechanisms. Decreased DNA repair, induced ex vivo by UV light or ionizing radiation in human peripheral blood lymphocytes (PBLs), has been associated with aging. The aim of this study was to investigate whether repair of DNA damage, after ex vivo exposure of PBLs obtained from smokers (n = 20) to (+/-)-anti-benzo(a)pyrene diolepoxide [(+/-)-anti-BPDE], which is a mixture of reactive metabolites from the environmental carcinogen benzo(a)pyrene, is also associated with age. Furthermore, age-related associations between ex vivo (+/-)-anti-BPDE-induced DNA repair and the frequency of endogenous cytogenetic damage (sister chromatid exchange frequencies and micronuclei frequencies) in PBLs were evaluated. A statistically significant negative association was observed between ex vivo (+/-)-anti-BPDE-induced unscheduled DNA synthesis and age of the donors. Also, parameters of endogenous lymphocytic cytogenetic damage were negatively associated with ex vivo (+/-)-anti-BPDE-induced unscheduled DNA synthesis and positively associated with age in this population. It is concluded that, with increasing age, a decrease in lymphocytic excision repair capacity may be responsible for increased lymphocytic DNA damage in smokers. JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology AU - Stierum, R H AU - Hageman, G J AU - van Herwijnen, M H AU - van der Veer, M S AU - Kleinjans, J C AD - Department of Health Risk Analysis and Toxicology, University of Limburg, Maastricht, The Netherlands. stierumr@grc.nia.nih.gov Y1 - 1997/11// PY - 1997 DA - November 1997 SP - 943 EP - 948 VL - 6 IS - 11 SN - 1055-9965, 1055-9965 KW - Benzopyrenes KW - 0 KW - Carcinogens, Environmental KW - Tobacco Smoke Pollution KW - benzo(a)pyrene diolepoxide I KW - 60268-85-1 KW - Index Medicus KW - Micronuclei, Chromosome-Defective -- genetics KW - Micronuclei, Chromosome-Defective -- drug effects KW - Humans KW - Adult KW - Middle Aged KW - Sister Chromatid Exchange -- genetics KW - Lymphocytes -- ultrastructure KW - Lymphocytes -- drug effects KW - Male KW - Benzopyrenes -- adverse effects KW - Carcinogens, Environmental -- adverse effects KW - Tobacco Smoke Pollution -- adverse effects KW - Smoking -- adverse effects KW - Benzopyrenes -- pharmacology KW - DNA Damage -- genetics KW - DNA Repair -- drug effects KW - Aging -- genetics KW - Carcinogens, Environmental -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79419344?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Age-related+negative+associations+between+parameters+of+cytogenetic+damage+and+ex+vivo+%28%2B%2F-%29-anti-benzo%28a%29pyrene+diolepoxide-induced+unscheduled+DNA+synthesis+in+smoking+humans.&rft.au=Stierum%2C+R+H%3BHageman%2C+G+J%3Bvan+Herwijnen%2C+M+H%3Bvan+der+Veer%2C+M+S%3BKleinjans%2C+J+C&rft.aulast=Stierum&rft.aufirst=R&rft.date=1997-11-01&rft.volume=6&rft.issue=11&rft.spage=943&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 - 1997-12-30 N1 - Date created - 1997-12-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of early growth response gene-1 (Egr-1) as a phorbol myristate acetate-induced gene in lung cancer cells by differential mRNA display. AN - 79418400; 9374113 AB - Cellular regulatory genes including transcription factors may play an important role in the induction, maintenance, and progression of lung cancer. These regulatory genes are inducible by various mitogenic stimuli including phorbol myristate acetate (PMA). The differential mRNA display method was used to identify potential early response genes regulated by PMA in non-small cell lung cancer (NSCLC) cell lines. Using this technique, several cDNA fragments were found to be potentially differentially regulated by PMA in the squamous NSCLC cell line NCI-H157. One of these cDNA fragments of approximately 100 bp was determined to be differentially induced by at least 30-fold by PMA by northern blot analysis and to hybridize to a single 3.4 kb mRNA species. This cDNA fragment was cloned, sequenced, and identified to be identical to a portion of the 3'-untranslated region of the human early growth response gene-1 (Egr-1). Using Egr-1 cDNA as a probe, it was demonstrated that PMA induces Egr-1 mRNA expression in at least three other NSCLC cells as well. In addition, PMA caused a transient increase in expression of the Egr-1 transcript reaching a maximum level by 1 h before decreasing in NCI-H157 and three other types of NSCLC cells. Treatment of these NSCLC cells with TGF-beta1 showed a transient increase in Egr-1 mRNA similar to PMA which also reached a maximum level after 1 h. Normal human bronchial epithelial (NHBE) cells also showed a rapid, transient increase in expression of Egr-1 mRNA after treatment with PMA. In contrast, treatment of NHBE cells with TGF-beta1 showed that expression of Egr-1 mRNA increased by 1 h but reached a maximum level only after 6 h. These results indicate that both PMA and TGF-beta1 can induce Egr- mRNA expression in NSCLC cells and NHBE cells; however, while PMA induces Egr-1 mRNA similarly in both cell types, TGF-beta1 induces Egr-1 mRNA expression more rapidly and more transiently in NSCLC cells than in NHBE cells. Our results suggest that Egr-1 may play different roles in response to mitogens in normal and malignant lung cells. JF - American journal of respiratory cell and molecular biology AU - You, L AU - Jakowlew, S B AD - National Cancer Institute, Medicine Branch, Rockville, Maryland 20850, USA. Y1 - 1997/11// PY - 1997 DA - November 1997 SP - 617 EP - 624 VL - 17 IS - 5 SN - 1044-1549, 1044-1549 KW - Carcinogens KW - 0 KW - DNA-Binding Proteins KW - EGR1 protein, human KW - Early Growth Response Protein 1 KW - Immediate-Early Proteins KW - RNA, Messenger KW - Transcription Factors KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Base Sequence KW - Tumor Cells, Cultured KW - Humans KW - RNA, Messenger -- analysis KW - Molecular Sequence Data KW - Cell Differentiation -- drug effects KW - Carcinogens -- pharmacology KW - Carcinoma, Non-Small-Cell Lung -- genetics KW - DNA-Binding Proteins -- genetics KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Lung Neoplasms -- genetics KW - Transcription Factors -- genetics KW - Gene Expression Regulation, Neoplastic -- drug effects KW - Lung Neoplasms -- pathology KW - Carcinoma, Non-Small-Cell Lung -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79418400?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+respiratory+cell+and+molecular+biology&rft.atitle=Identification+of+early+growth+response+gene-1+%28Egr-1%29+as+a+phorbol+myristate+acetate-induced+gene+in+lung+cancer+cells+by+differential+mRNA+display.&rft.au=You%2C+L%3BJakowlew%2C+S+B&rft.aulast=You&rft.aufirst=L&rft.date=1997-11-01&rft.volume=17&rft.issue=5&rft.spage=617&rft.isbn=&rft.btitle=&rft.title=American+journal+of+respiratory+cell+and+molecular+biology&rft.issn=10441549&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-12-09 N1 - Date created - 1997-12-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - p53 mutations in esophageal tumors from a high incidence area of China in relation to patient diet and smoking history. AN - 79417004; 9367071 AB - Esophageal tumors from 29 patients residing in Guangzhou, China were examined for mutations in exons 5-8 of the p53 tumor suppressor gene and for p53 protein accumulation in tumor cell nuclei. Anamnestic data for each patient, which included information on family history of cancer, tobacco smoking, drinking of alcoholic beverages, and dietary habits such as consumption of pickled vegetables, were recorded. Screening of DNA from tumor cells microdissected from biopsies was performed by PCR amplification of p53 gene exons 5-8, denaturing gradient gel electrophoresis analysis, and DNA sequencing. Mutations were identified in 20 of 29 tumors (69%). All tumors harboring a missense mutation in the p53 gene also showed nuclear accumulation of the tumor suppressor protein by immunohistochemistry. The most common p53 mutations in these tumors were guanine to adenine (G-->A) transitions (10 of 20 tumors; 50%). We did not find multiple mutations at codon 176, in contrast to Lung et al. in their recent study of esophageal cancer patients from Guangzhou (M. L. Lung et al., Cancer Epidemiol. Biomark. Prev., 5: 277-284, 1996). The mutation prevalence was high both in smokers (13 mutations in 20 smokers; 65%) and in nonsmokers (7 of 9 tumors with mutations; 78%), an observation that differs from that of studies in European and North American patients, which demonstrate a much higher prevalence of p53 mutations in smokers than in nonsmokers (reviewed in R. Montesano et al., Int. J. Cancer Predict. Oncol., 69: 225-235, 1996.). Our findings in this pilot study of tumor suppressor gene mutations in patients from Guangzhou support a large body of epidemiological observations pointing to dietary mutagenic carcinogens peculiar to populations in China at high risk of esophageal cancer. JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology AU - Bennett, W P AU - von Brevern, M C AU - Zhu, S M AU - Bartsch, H AU - Muehlbauer, K R AU - Hollstein, M C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1997/11// PY - 1997 DA - November 1997 SP - 963 EP - 966 VL - 6 IS - 11 SN - 1055-9965, 1055-9965 KW - Index Medicus KW - Carcinoma, Squamous Cell -- epidemiology KW - Exons KW - DNA Mutational Analysis KW - Humans KW - Smoking -- adverse effects KW - Aged KW - Pilot Projects KW - Adenocarcinoma -- genetics KW - Diet -- adverse effects KW - Polymerase Chain Reaction KW - Adenocarcinoma -- epidemiology KW - Risk Factors KW - China -- epidemiology KW - Adult KW - Carcinoma, Squamous Cell -- genetics KW - Incidence KW - Middle Aged KW - Immunohistochemistry KW - Male KW - Female KW - Genes, p53 -- genetics KW - Esophageal Neoplasms -- genetics KW - Mutation KW - Esophageal Neoplasms -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79417004?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=p53+mutations+in+esophageal+tumors+from+a+high+incidence+area+of+China+in+relation+to+patient+diet+and+smoking+history.&rft.au=Bennett%2C+W+P%3Bvon+Brevern%2C+M+C%3BZhu%2C+S+M%3BBartsch%2C+H%3BMuehlbauer%2C+K+R%3BHollstein%2C+M+C&rft.aulast=Bennett&rft.aufirst=W&rft.date=1997-11-01&rft.volume=6&rft.issue=11&rft.spage=963&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 - 1997-12-30 N1 - Date created - 1997-12-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A case-cohort study of an early biomarker of lung cancer in a screening cohort of Yunnan tin miners in China. AN - 79416271; 9367062 AB - We initiated the present study to evaluate the accuracy of a new epithelial biomarker of early lung cancer. We tested the hypothesis that expression of a tumor-associated antigen by exfoliated sputum epithelial cells has greater accuracy (sensitivity and specificity) for the detection of preclinical, localized lung cancer than do routine clinical detection methods. Monoclonal antibody (MAb) 703D4 recognizes heterogeneous nuclear ribonuclear protein (hnRNP) A2/B1. We compared the accuracy of hnRNP up-regulation with cytology and radiographic screening for lung cancer detection in miners who were highly exposed to tobacco smoke, radon, and arsenic in southwestern China. The results showed that MAb 703D4 detection of hnRNP expression by sputum epithelial cells had greater accuracy for the detection of lung cancer than did routine screening methods, particularly for early (localized) disease. Among 57 cases and 76 noncases at the first screening, overall MAb detection of hnRNP was more sensitive (74 versus 21% for cytology and 42% for chest x-ray) but had lower specificity (70 versus 100% for cytology and 90% for chest x-ray) than standard methods. Recognizing hnRNP up-regulation resulted in detection of approximately one-third more early cases than did the combination of X-ray and cytology. Detection of hnRNP A2/B1 expression appears to be a good initial screening test for lung carcinogenesis, as it identified 74% of those who developed subsequent clinical lung cancer. Future studies might separate individuals with high lung cancer risk by MAb detection, confirming the positives with markers having greater specificity (e.g., clinical studies that become positive later in the morphological progression). JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology AU - Qiao, Y L AU - Tockman, M S AU - Li, L AU - Erozan, Y S AU - Yao, S X AU - Barrett, M J AU - Zhou, W H AU - Giffen, C A AU - Luo, X C AU - Taylor, P R AD - Cancer Prevention Studies Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1997/11// PY - 1997 DA - November 1997 SP - 893 EP - 900 VL - 6 IS - 11 SN - 1055-9965, 1055-9965 KW - Antibodies, Monoclonal KW - 0 KW - Biomarkers, Tumor KW - Heterogeneous-Nuclear Ribonucleoprotein Group A-B KW - Heterogeneous-Nuclear Ribonucleoproteins KW - Neoplasm Proteins KW - Ribonucleoproteins KW - Tobacco Smoke Pollution KW - hnRNP A2 KW - Tin KW - 7440-31-5 KW - Arsenic KW - N712M78A8G KW - Radon KW - Q74S4N8N1G KW - Index Medicus KW - Sensitivity and Specificity KW - Occupational Exposure KW - Humans KW - Aged KW - Epithelial Cells -- metabolism KW - Mass Screening KW - Adult KW - Case-Control Studies KW - Middle Aged KW - Mining KW - China KW - Immunoenzyme Techniques KW - Occupational Diseases -- diagnosis KW - Biomarkers, Tumor -- metabolism KW - Sputum -- cytology KW - Occupational Diseases -- metabolism KW - Lung Neoplasms -- prevention & control KW - Lung Neoplasms -- diagnosis KW - Occupational Diseases -- prevention & control KW - Ribonucleoproteins -- metabolism KW - Sputum -- metabolism KW - Neoplasm Proteins -- metabolism KW - Lung Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79416271?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+case-cohort+study+of+an+early+biomarker+of+lung+cancer+in+a+screening+cohort+of+Yunnan+tin+miners+in+China.&rft.au=Qiao%2C+Y+L%3BTockman%2C+M+S%3BLi%2C+L%3BErozan%2C+Y+S%3BYao%2C+S+X%3BBarrett%2C+M+J%3BZhou%2C+W+H%3BGiffen%2C+C+A%3BLuo%2C+X+C%3BTaylor%2C+P+R&rft.aulast=Qiao&rft.aufirst=Y&rft.date=1997-11-01&rft.volume=6&rft.issue=11&rft.spage=893&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 - 1997-12-30 N1 - Date created - 1997-12-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hepatocyte nuclear factor 1 and the glucocorticoid receptor synergistically activate transcription of the rat insulin-like growth factor binding protein-1 gene. AN - 79413987; 9369450 AB - The insulin-like growth factor (IGF) binding proteins (IGFBPs) are a family of proteins that bind IGF-I and IGF-II and modulate their biological activities. IGFBP-1 is distinctive among the IGFBPs in its rapid regulation in response to metabolic and hormonal changes. The synthetic glucocorticoid, dexamethasone, increases IGFBP-1 mRNA abundance and gene transcription in rat liver and in H4-II-E rat hepatoma cells. A glucocorticoid response element (GRE) located at nucleotide (nt) -91/-77 is required for dexamethasone to stimulate rat IGFBP-1 promoter activity in transient transfection assays in H4-II-E cells. In addition to the GRE, three accessory regulatory sites [a putative hepatocyte nuclear factor-1 (HNF-1) site (nt -62/-50), an insulin-response element (nt -108/-99), and an upstream site (nt -252/-236)] are involved in dexamethasone stimulation under some, but not all, circumstances. The present study begins to address the mechanism by which transcription factors bound to the putative HNF-1 site act synergistically with the glucocorticoid receptor (GR) bound to the GRE. In gel shift assays, HNF-1alpha and HNF-1beta in H4-II-E extracts bind to the palindromic HNF-1 site. Both half-sites are required. Overexpression of HNF-1beta enhances dexamethasone-stimulated promoter activity. Both the HNF-1 site and the GRE must be intact for stimulation to occur. By contrast, overexpression of HNF-1alpha does not enhance dexamethasone-stimulated promoter activity, although, as also observed with overexpression of HNF-1beta, it inhibits basal promoter activity. Thus, the synergistic effects of HNF-1beta and the GR on dexamethasone-stimulated promoter activity require that they are bound to the HNF-1 site and the GRE, respectively, and may involve protein-protein interactions between the transcription factors, or between them and the basal transcription machinery or a steroid receptor coactivator. Synergy between the ubiquitously expressed GR and HNF-1, which is developmentally regulated and expressed in a limited number of tissues, provides a possible mechanism for tissue- and development-specific regulation of glucocorticoid action. JF - Molecular endocrinology (Baltimore, Md.) AU - Suh, D S AU - Rechler, M M AD - Molecular and Cellular Endocrinology Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892, USA. Y1 - 1997/11// PY - 1997 DA - November 1997 SP - 1822 EP - 1831 VL - 11 IS - 12 SN - 0888-8809, 0888-8809 KW - Carrier Proteins KW - 0 KW - DNA-Binding Proteins KW - Hepatocyte Nuclear Factor 1-alpha KW - Hnf1a protein, rat KW - Nuclear Proteins KW - Pregnancy Proteins KW - Receptors, Glucocorticoid KW - Transcription Factors KW - pregnancy-associated alpha 1-glycoprotein, rat KW - Hepatocyte Nuclear Factor 1 KW - 126548-29-6 KW - Hepatocyte Nuclear Factor 1-beta KW - 138674-15-4 KW - Dexamethasone KW - 7S5I7G3JQL KW - Index Medicus KW - Animals KW - Cell Nucleus -- metabolism KW - Electrophoresis, Polyacrylamide Gel KW - Dexamethasone -- pharmacology KW - Rats KW - Tumor Cells, Cultured KW - Promoter Regions, Genetic -- drug effects KW - Protein Binding -- genetics KW - Drug Synergism KW - Cell Nucleus -- genetics KW - Transcription Factors -- physiology KW - Pregnancy Proteins -- drug effects KW - Carrier Proteins -- drug effects KW - Carrier Proteins -- genetics KW - Pregnancy Proteins -- genetics KW - Transcriptional Activation -- drug effects KW - Transcription Factors -- genetics KW - Transcription Factors -- biosynthesis KW - Receptors, Glucocorticoid -- physiology KW - Receptors, Glucocorticoid -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79413987?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Hepatocyte+nuclear+factor+1+and+the+glucocorticoid+receptor+synergistically+activate+transcription+of+the+rat+insulin-like+growth+factor+binding+protein-1+gene.&rft.au=Suh%2C+D+S%3BRechler%2C+M+M&rft.aulast=Suh&rft.aufirst=D&rft.date=1997-11-01&rft.volume=11&rft.issue=12&rft.spage=1822&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 - 1997-12-04 N1 - Date created - 1997-12-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Loss of heterozygosity at chromosome segment Xq25-26.1 in advanced human ovarian carcinomas. AN - 79412576; 9365830 AB - To determine whether a tumor suppressor gene of importance to epithelial ovarian cancer resides on the X chromosome, we examined loss of heterozygosity (LOH) in 123 epithelial ovarian cancer cases. In 54 such cases, we examined LOH at 26 loci on the human X chromosome. In eight cases, we examined LOH in 14 loci and in 61 cases we examined LOH in 13 loci. Matched DNA samples from tumors and corresponding normal tissues were analyzed by polymerase chain reaction (PCR) amplification of microsatellite markers. Frequent losses were found in epithelial carcinomas at the Xq25-26.l region, including DXS1206 (34.5% loss in informative cases), DXS1047 (27.7%), HPRT (24.1%), and DXS1062 (33.3%). The minimum overlapping region of LOH was approximately 5 megabases (Mb), flanked by DXS1206 (Xq25) and HPRT (Xq26.1). The methylation status of the remaining allele of the androgen receptor gene in the tumors exhibiting LOH at the Xq25-26.1 region suggested that the loss was exclusively in the inactive X chromosome. We next determined whether a significant relationship exists between Xq LOH and other parameters, including histologic grade and/or clinical stage of the tumors and LOH at TP53. The Xq LOH had a significant association with grade 2 to 3 tumors at stages II to IV. Sixteen of 18 cases that showed Xq LOH revealed LOH at the TP53 locus, and 45% of tumors exhibiting LOH at TP53 showed Xq LOH. These results suggest that there may be a tumor suppressor gene or genes which escape inactivation of the X chromosome at Xq25-26.1, and that the loss of the gene(s) at Xq25-26.1 is frequently accompanied by loss of the TP53 or loss of another gene on chromosome 17. These losses may contribute to the progression from a well-differentiated to a more poorly differentiated state or to metastatic aggressiveness. JF - Genes, chromosomes & cancer AU - Choi, C AU - Cho, S AU - Horikawa, I AU - Berchuck, A AU - Wang, N AU - Cedrone, E AU - Jhung, S W AU - Lee, J B AU - Kerr, J AU - Chenevix-Trench, G AU - Kim, S AU - Barrett, J C AU - Koi, M AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1997/11// PY - 1997 DA - November 1997 SP - 234 EP - 242 VL - 20 IS - 3 SN - 1045-2257, 1045-2257 KW - DNA, Neoplasm KW - 0 KW - Index Medicus KW - Polymerase Chain Reaction KW - Microsatellite Repeats KW - Neoplasm Staging KW - Genes, Tumor Suppressor -- genetics KW - Humans KW - Genes, p53 -- genetics KW - DNA, Neoplasm -- isolation & purification KW - Chromosome Mapping KW - Female KW - Carcinoma -- pathology KW - Ovarian Neoplasms -- genetics KW - Ovarian Neoplasms -- pathology KW - X Chromosome -- genetics KW - Loss of Heterozygosity -- genetics KW - Carcinoma -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79412576?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genes%2C+chromosomes+%26+cancer&rft.atitle=Loss+of+heterozygosity+at+chromosome+segment+Xq25-26.1+in+advanced+human+ovarian+carcinomas.&rft.au=Choi%2C+C%3BCho%2C+S%3BHorikawa%2C+I%3BBerchuck%2C+A%3BWang%2C+N%3BCedrone%2C+E%3BJhung%2C+S+W%3BLee%2C+J+B%3BKerr%2C+J%3BChenevix-Trench%2C+G%3BKim%2C+S%3BBarrett%2C+J+C%3BKoi%2C+M&rft.aulast=Choi&rft.aufirst=C&rft.date=1997-11-01&rft.volume=20&rft.issue=3&rft.spage=234&rft.isbn=&rft.btitle=&rft.title=Genes%2C+chromosomes+%26+cancer&rft.issn=10452257&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-01-08 N1 - Date created - 1998-01-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cytokines, macrophages, and leukocytes in brain ischemia. AN - 79412303; 9371141 JF - Neurology AU - Hallenbeck, J M AD - Stroke Branch, National Institute for Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20897-4128, USA. Y1 - 1997/11// PY - 1997 DA - November 1997 SP - S5 EP - S9 VL - 49 IS - 5 Suppl 4 SN - 0028-3878, 0028-3878 KW - Antibodies, Monoclonal KW - 0 KW - Epitopes KW - Interleukin-1 KW - Lipopolysaccharides KW - Tumor Necrosis Factor-alpha KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Gerbillinae KW - Rats, Inbred SHR KW - Leukocytes -- immunology KW - Hypertension -- immunology KW - Endothelium, Vascular -- immunology KW - Ischemic Preconditioning KW - Rats KW - Carotid Arteries KW - Hypertension -- chemically induced KW - Monocytes -- cytology KW - Cell Adhesion -- immunology KW - Epitopes -- immunology KW - Organ Culture Techniques KW - Male KW - Macrophages -- cytology KW - Macrophages -- immunology KW - Ischemic Attack, Transient -- immunology KW - Interleukin-1 -- immunology KW - Reperfusion Injury -- immunology KW - Tumor Necrosis Factor-alpha -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79412303?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurology&rft.atitle=Cytokines%2C+macrophages%2C+and+leukocytes+in+brain+ischemia.&rft.au=Hallenbeck%2C+J+M&rft.aulast=Hallenbeck&rft.aufirst=J&rft.date=1997-11-01&rft.volume=49&rft.issue=5+Suppl+4&rft.spage=S5&rft.isbn=&rft.btitle=&rft.title=Neurology&rft.issn=00283878&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-12-15 N1 - Date created - 1997-12-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Retinoic acid downregulates growth, fibronectin and RAR alpha in 3T3 cells: Ha-ras blocks this response and RA metabolism. AN - 79405159; 9365540 AB - Retinoic acid (RA) reduced growth, fibronectin, and retinoic acid receptor (RAR alpha) in NIH 3T3 cells but not in cells transformed by the Ha-ras oncogene. RA lowered RAR alpha transcript and protein, increased RAR beta transcripts, and had no effect on RAR gamma. H-ras transformation downregulated RAR expression and abolished responsiveness to RA. Ha-ras-transformed cells were as active as normal NIH-3T3 cells in RA uptake but were unable to degrade it to medium oxidation product, so that, paradoxically, the resistant cells accumulated 20-30-fold as much RA as the sensitive cells. RA sensitivity/insensitivity correlated with RA metabolism/lack thereof in 15 cell lines in serum-free medium. These data suggest a relationship between RA inhibition of cell growth and intracellular RA metabolism. JF - Journal of cellular physiology AU - De Luca, L M AU - Scita, G AU - Takatsuka, J AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1997/11// PY - 1997 DA - November 1997 SP - 297 EP - 300 VL - 173 IS - 2 SN - 0021-9541, 0021-9541 KW - Fibronectins KW - 0 KW - Receptors, Retinoic Acid KW - Tretinoin KW - 5688UTC01R KW - Index Medicus KW - Animals KW - Genes, ras -- physiology KW - Cell Division -- drug effects KW - Mice KW - Receptors, Retinoic Acid -- metabolism KW - Tretinoin -- pharmacology KW - 3T3 Cells -- drug effects KW - Tretinoin -- metabolism KW - 3T3 Cells -- metabolism KW - Fibronectins -- metabolism KW - 3T3 Cells -- cytology KW - Receptors, Retinoic Acid -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79405159?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Retinoic+acid+downregulates+growth%2C+fibronectin+and+RAR+alpha+in+3T3+cells%3A+Ha-ras+blocks+this+response+and+RA+metabolism.&rft.au=De+Luca%2C+L+M%3BScita%2C+G%3BTakatsuka%2C+J&rft.aulast=De+Luca&rft.aufirst=L&rft.date=1997-11-01&rft.volume=173&rft.issue=2&rft.spage=297&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 - 1997-12-11 N1 - Date created - 1997-12-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - p53 tumor-suppressor gene: clues to molecular carcinogenesis. AN - 79405100; 9365531 AB - The tumor-suppressor gene product p53 is clearly a component in several biochemical pathways, including transcription, DNA repair, genomic stability, cell-cycle control and apoptosis, that are central to human carcinogenesis. The p53 is functionally inactivated by mutational, viral, and cellular mechanisms in the majority of human cancers. Analysis of the spectrum of p53 mutations provides clues to the etiology and molecular pathogenesis of cancer. Recent insight into the p53-mediated biochemical pathways of cell-cycle arrest and apoptosis has provided further understanding of the mechanisms related to p53-mediated tumor suppression. This insight in turn may provide the potential molecular targets for the development of rational multimodality cancer therapy, including chemo-, immuno-, and gene-therapeutic strategies. The convergence of previously parallel lines of basic, clinical, and epidemiologic investigation may provide an opportunity to transfer research findings rapidly from the laboratory to the clinic. JF - Journal of cellular physiology AU - Wang, X W AU - Harris, C C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4255, USA. Y1 - 1997/11// PY - 1997 DA - November 1997 SP - 247 EP - 255 VL - 173 IS - 2 SN - 0021-9541, 0021-9541 KW - Tumor Suppressor Protein p53 KW - 0 KW - Index Medicus KW - DNA Repair -- physiology KW - Animals KW - Tumor Suppressor Protein p53 -- physiology KW - Humans KW - Tumor Suppressor Protein p53 -- genetics KW - Models, Biological KW - Transcription, Genetic -- physiology KW - G1 Phase -- physiology KW - Genes, p53 -- physiology KW - Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79405100?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=p53+tumor-suppressor+gene%3A+clues+to+molecular+carcinogenesis.&rft.au=Wang%2C+X+W%3BHarris%2C+C+C&rft.aulast=Wang&rft.aufirst=X&rft.date=1997-11-01&rft.volume=173&rft.issue=2&rft.spage=247&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 - 1997-12-11 N1 - Date created - 1997-12-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cloning and analysis of the promoter region of CXCR4, a coreceptor for HIV-1 entry. AN - 79402951; 9379028 AB - The chemokine receptor CXCR4 (also designated fusin and LESTR) is a cofactor for fusion and entry of T cell-tropic strains of HIV-1. CXCR4 is expressed in various cell types; however, the mechanisms involved in the regulation of its expression remain unknown. To delineate these mechanisms, approximately 1.2 kb of DNA from the immediate 5' upstream region of CXCR4 gene was cloned, sequenced, and characterized. Transient expression assays using CXCR4 promoter/luciferase gene reporter constructs revealed that stimulation with PMA plus ionomycin up-regulates the CXCR4 promoter activity in the A3.01 CD4+ T cell line and PBL and that a DNA fragment from -93 to +59 relative to the transcription start site contributes markedly to the basal and induced activity. This fragment contains a consensus TATA box, two potential GC boxes, and a potential nuclear respiratory factor (NRF)-1 binding site, which were confirmed by gel mobility shift assays and footprinting analysis. Mutagenesis studies revealed that a NRF-1 site is especially important for the basal and induced activity of the CXCR4 promoter. Transient expression assays further revealed that stimulation of PBL with either IL-2 or Abs to CD3 and CD28 enhances the CXCR4 promoter activity. Inducibility of the CXCR4 promoter activity by T cell stimulation suggests that overexpression of CXCR4 may be one of the mechanisms whereby immune activation and/or perturbation of the cytokine network up-regulate HIV expression and replication and thus contribute to the progression of HIV disease. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Moriuchi, M AU - Moriuchi, H AU - Turner, W AU - Fauci, A S AD - Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-1576, USA. Y1 - 1997/11/01/ PY - 1997 DA - 1997 Nov 01 SP - 4322 EP - 4329 VL - 159 IS - 9 SN - 0022-1767, 0022-1767 KW - Receptors, CXCR4 KW - 0 KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Humans KW - Molecular Sequence Data KW - Sequence Analysis, DNA KW - T-Lymphocytes -- virology KW - Cell Line KW - Cloning, Molecular KW - Promoter Regions, Genetic -- genetics KW - Virus Replication -- physiology KW - Receptors, CXCR4 -- genetics KW - HIV-1 -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79402951?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cloning+and+analysis+of+the+promoter+region+of+CXCR4%2C+a+coreceptor+for+HIV-1+entry.&rft.au=Moriuchi%2C+M%3BMoriuchi%2C+H%3BTurner%2C+W%3BFauci%2C+A+S&rft.aulast=Moriuchi&rft.aufirst=M&rft.date=1997-11-01&rft.volume=159&rft.issue=9&rft.spage=4322&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 - 1997-11-12 N1 - Date created - 1997-11-12 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - U81003; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Methotrexate use in systemic vasculitis. AN - 79401315; 9361158 AB - Although GS and CYC have been important agents in improving the outcome and survival of patients with systemic vasculitis, they carry their own risk of drug-induced morbidity and mortality. It has also become apparent that these medications are not the final answer in disease management because some forms of vasculitis have the potential to relapse or be treatment resistant. For these reasons, the pursuit of effective, less toxic therapeutic alternatives is critical. Initial results from the use of MTX in systemic vasculitis have been encouraging. Although drug-related toxicity and disease relapse have still been found to occur, MTX appears to be a valuable addition in the treatment of vasculitis. Further studies will be necessary to determine the optimal way that this agent may be used to safely and effectively manage vasculitic disease. JF - Rheumatic diseases clinics of North America AU - Langford, C A AU - Sneller, M C AU - Hoffman, G S AD - Immunologic Diseases Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland. Y1 - 1997/11// PY - 1997 DA - November 1997 SP - 841 EP - 853 VL - 23 IS - 4 SN - 0889-857X, 0889-857X KW - Antirheumatic Agents KW - 0 KW - Methotrexate KW - YL5FZ2Y5U1 KW - Index Medicus KW - Prospective Studies KW - Humans KW - Treatment Outcome KW - Clinical Trials as Topic KW - Male KW - Female KW - Takayasu Arteritis -- drug therapy KW - Methotrexate -- therapeutic use KW - Giant Cell Arteritis -- drug therapy KW - Granulomatosis with Polyangiitis -- drug therapy KW - Antirheumatic Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79401315?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Rheumatic+diseases+clinics+of+North+America&rft.atitle=Methotrexate+use+in+systemic+vasculitis.&rft.au=Langford%2C+C+A%3BSneller%2C+M+C%3BHoffman%2C+G+S&rft.aulast=Langford&rft.aufirst=C&rft.date=1997-11-01&rft.volume=23&rft.issue=4&rft.spage=841&rft.isbn=&rft.btitle=&rft.title=Rheumatic+diseases+clinics+of+North+America&rft.issn=0889857X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-12-10 N1 - Date created - 1997-12-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Alternating MOPP and ABVD chemotherapy plus mantle-field radiation therapy in patients with massive mediastinal Hodgkin's disease. AN - 79398545; 9363863 AB - To evaluate the efficacy and toxicity of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP)/doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy plus mantle-field radiation therapy in the treatment of patients with massive mediastinal Hodgkin's disease of any stage. Eighty patients presented with Hodgkin's disease and a mediastinal mass greater than one third the greatest chest diameter on chest radiograph. Patients were staged and treated with MOPP alternated with ABVD chemotherapy for a total of six cycles. Patients then received 10 Gy mantle-field radiation therapy delivered to the original extent of disease followed by 25 to 35 Gy to the residual abnormalities. The complete response (CR) rate was 89%. With a median follow-up duration of 10 years, disease-free survival of the complete responders is 78% at 15 years and overall survival is 75% at 15 years. For patients with stage I or II disease, disease-free survival was 76% at 15 years and overall survival was 79%; for those with stage III or IV disease, disease-free survival was 82% at 15 years and overall survival was 64%. Age, stage, sex, B symptoms, number of extranodal sites, lactate dehydrogenase (LDH) levels, erythrocyte sedimentation rate, and platelet count did not influence treatment outcome. Treatment-related pneumonitis was noted in 16% of patients (fatal in one), mainly in those older than age 35 years who received total doses of radiation therapy greater than 42 Gy. Fertility is more often preserved with MOPP/ABVD therapy than with MOPP chemotherapy and there appears to be less pulmonary and cardiac disease than with ABVD chemotherapy. Two patients have developed second solid tumors within radiation ports and one relapsed patient developed acute leukemia after MOPP salvage therapy. MOPP/ABVD followed by mantle-field radiation therapy is an effective treatment for all stages of Hodgkin's disease that present with a large mediastinal mass. Our data suggest that the large mediastinal mass is a more dominant determinant of prognosis than Ann Arbor stage or other clinical prognostic factors. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Longo, D L AU - Glatstein, E AU - Duffey, P L AU - Young, R C AU - Ihde, D C AU - Bastian, A W AU - Wilson, W H AU - Wittes, R E AU - Jaffe, E S AU - Hubbard, S M AU - DeVita, V T AD - Medicine Branch, Laboratory of Pathology, National Cancer Institute, Bethesda, MD, USA. Y1 - 1997/11// PY - 1997 DA - November 1997 SP - 3338 EP - 3346 VL - 15 IS - 11 SN - 0732-183X, 0732-183X KW - Bleomycin KW - 11056-06-7 KW - Procarbazine KW - 35S93Y190K KW - Mechlorethamine KW - 50D9XSG0VR KW - Vincristine KW - 5J49Q6B70F KW - Vinblastine KW - 5V9KLZ54CY KW - Dacarbazine KW - 7GR28W0FJI KW - Doxorubicin KW - 80168379AG KW - Prednisone KW - VB0R961HZT KW - Index Medicus KW - Disease-Free Survival KW - Mechlorethamine -- administration & dosage KW - Bleomycin -- administration & dosage KW - Combined Modality Therapy KW - Humans KW - Vincristine -- administration & dosage KW - Child KW - Doxorubicin -- administration & dosage KW - Procarbazine -- administration & dosage KW - Prospective Studies KW - Adult KW - Vinblastine -- administration & dosage KW - Treatment Outcome KW - Middle Aged KW - Dacarbazine -- administration & dosage KW - Adolescent KW - Prednisone -- administration & dosage KW - Female KW - Male KW - Hodgkin Disease -- radiotherapy KW - Mediastinal Neoplasms -- drug therapy KW - Hodgkin Disease -- drug therapy KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Mediastinal Neoplasms -- radiotherapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79398545?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Alternating+MOPP+and+ABVD+chemotherapy+plus+mantle-field+radiation+therapy+in+patients+with+massive+mediastinal+Hodgkin%27s+disease.&rft.au=Collier%2C+C+D%3BOshima%2C+H%3BSimons%2C+S+S&rft.aulast=Collier&rft.aufirst=C&rft.date=1996-05-01&rft.volume=10&rft.issue=5&rft.spage=463&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 - 1997-12-02 N1 - Date created - 1997-12-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Intraventricular immunotoxin therapy for leptomeningeal neoplasia. AN - 79398211; 9361057 AB - The goals of this clinical trial of intraventricular 454A12-rRA therapy were to identify dose-limiting toxicities, to evaluate the pharmacokinetics of single-dose intraventricular 454A12-rRA, and to detect antitumor activity. We performed a pilot study of intraventricular therapy with the immunotoxin 454A12-rRA in eight patients with leptomeningeal spread of systemic neoplasia. The immunotoxin 454A12-rRA is a conjugate of a monoclonal antibody against the human transferrin receptor and recombinant ricin A chain, the enzymatically active subunit of the protein toxin ricin. Patients were treated with single doses of 454A12-rRA ranging from 1.2 to 1200 micrograms. The early phase half-life of 454A12-rRA in ventricular cerebrospinal fluid (CSF) averaged 44 +/- 21 minutes, and the late phase half-life averaged 237 +/- 86 minutes. The clearance of the immunotoxin was faster than the clearance of coinjected technetium-99m-diethylenetriamine penta-acetic acid, averaging approximately 2.4-fold greater. No 454A12-rRA degradation was detected by Western blot analysis of ventricular CSF for a period of 24 hours, and bioactivity was retained in CSF paralleling the concentration of immunotoxin. No acute or chronic drug toxicity was identified in patients who received less than or equal to 38 micrograms of 454A12-rRA by intraventricular injection. Doses more than or equal to 120 micrograms caused a CSF inflammatory response that was associated with transient headache, vomiting, and altered mental status. This acute syndrome was responsive to steroids and CSF drainage. No systemic toxicity was detected. In four of the eight patients, a greater than 50% reduction of tumor cell counts in the lumbar CSF occurred within 5 to 7 days after the intraventricular dose of 454A12-rRA; however, no patient had their CSF cleared of tumor, and clinical or magnetic resonance imaging evidence of tumor progression was demonstrated in seven of the eight patients after treatment. Tumoricidal concentrations of the immunotoxin 454A12-rRA can be attained safely in the CSF of patients with leptomeningeal tumor spread. JF - Neurosurgery AU - Laske, D W AU - Muraszko, K M AU - Oldfield, E H AU - DeVroom, H L AU - Sung, C AU - Dedrick, R L AU - Simon, T R AU - Colandrea, J AU - Copeland, C AU - Katz, D AU - Greenfield, L AU - Groves, E S AU - Houston, L L AU - Youle, R J AD - Surgical Neurology Branch, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1997/11// PY - 1997 DA - November 1997 SP - 1039 EP - 49; discussion 1049-51 VL - 41 IS - 5 SN - 0148-396X, 0148-396X KW - Antibodies, Monoclonal KW - 0 KW - Immunotoxins KW - Receptors, Transferrin KW - Recombinant Proteins KW - Ricin KW - 9009-86-3 KW - Technetium Tc 99m Pentetate KW - VW78417PU1 KW - Index Medicus KW - Breast Neoplasms -- drug therapy KW - Animals KW - Humans KW - Recombinant Proteins -- pharmacokinetics KW - Metabolic Clearance Rate KW - Aged KW - Pilot Projects KW - Mice KW - Cerebral Ventricles KW - Infusions, Parenteral KW - Melanoma -- pathology KW - Breast Neoplasms -- pathology KW - Half-Life KW - Adult KW - Melanoma -- drug therapy KW - Receptors, Transferrin -- immunology KW - Middle Aged KW - Recombinant Proteins -- therapeutic use KW - Recombinant Proteins -- administration & dosage KW - Female KW - Spinal Cord Neoplasms -- secondary KW - Immunotoxins -- pharmacokinetics KW - Spinal Cord Neoplasms -- drug therapy KW - Spinal Cord Neoplasms -- pathology KW - Meningeal Neoplasms -- secondary KW - Ricin -- administration & dosage KW - Meningeal Neoplasms -- drug therapy KW - Ricin -- therapeutic use KW - Ricin -- pharmacokinetics KW - Immunotoxins -- therapeutic use KW - Immunotoxins -- administration & dosage KW - Meningeal Neoplasms -- radiotherapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79398211?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurosurgery&rft.atitle=Intraventricular+immunotoxin+therapy+for+leptomeningeal+neoplasia.&rft.au=Laske%2C+D+W%3BMuraszko%2C+K+M%3BOldfield%2C+E+H%3BDeVroom%2C+H+L%3BSung%2C+C%3BDedrick%2C+R+L%3BSimon%2C+T+R%3BColandrea%2C+J%3BCopeland%2C+C%3BKatz%2C+D%3BGreenfield%2C+L%3BGroves%2C+E+S%3BHouston%2C+L+L%3BYoule%2C+R+J&rft.aulast=Laske&rft.aufirst=D&rft.date=1997-11-01&rft.volume=41&rft.issue=5&rft.spage=1039&rft.isbn=&rft.btitle=&rft.title=Neurosurgery&rft.issn=0148396X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-12-22 N1 - Date created - 1997-12-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phase I trial and pharmacokinetic study of all-trans-retinoic acid administered on an intermittent schedule in combination with interferon-alpha2a in pediatric patients with refractory cancer. AN - 79397293; 9363862 AB - To determine the maximum-tolerated dose (MTD) of all-trans-retinoic acid (ATRA) administered on an intermittent oral schedule with interferon-alpha2a (IFN-alpha2a) in children with refractory cancer, and whether the marked reduction in plasma ATRA concentrations observed with chronic daily oral dosing could be circumvented with an intermittent dosing schedule. Thirty-three children with refractory cancer (stratified by age, 12 years) were treated with ATRA 3 consecutive days per week and IFN-alpha2a 3 x 10(6) U/m2 5 consecutive days per week, both repeated weekly. The starting dose of ATRA was 60 mg/m2/d divided into three doses, with planned escalations to 90 and 120 mg/m2/d. Because severe headaches have been noted to occur on the initial day of ATRA administration, only two of three doses of ATRA were administered on day 1 of each week. Pseudotumor cerebri or dose-limiting headache was observed in two of five patients older than 12 years treated at the 120-mg/m2/d dose level and in one of six < or = 12 years at the 90-mg/m2/d level. Other non-dose-limiting toxicities of ATRA included reversible elevations in hepatic transaminases and triglycerides, dry skin, cheilitis, and nausea/vomiting. One child with recurrent neuroblastoma had an objective response of 6 months' duration, and one with recurrent Wilms' tumor had histologic maturation of multiple tumors. This intermittent schedule allowed for exposure to relatively high plasma concentrations of ATRA on a repetitive basis. Following 30-mg/m2 doses, the ATRA area under the concentration-time curve (AUC) decreased from 96 +/- 14 micromol/L/min on day 1 to 26 +/- 24 micromol/L/min by day 3 of drug administration, but on day 1 of the fourth consecutive week of therapy, the AUC averaged 110 +/- 16 micromol/L/min. The recommended pediatric phase II dose of ATRA administered on this schedule is 90 mg/m2/d. An intermittent schedule of ATRA administration appears to circumvent the low plasma drug exposure that is a result of the sustained upregulation of metabolism when this drug is administered on a chronic daily schedule. Based on the results of this trial, a phase II trial of ATRA/IFN-alpha2a in neuroblastoma and Wilms' tumor using this schedule is in progress. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Adamson, P C AU - Reaman, G AU - Finklestein, J Z AU - Feusner, J AU - Berg, S L AU - Blaney, S M AU - O'Brien, M AU - Murphy, R F AU - Balis, F M AD - Pediatric Branch, National Cancer Institute, Bethesda, MD 20892, USA. adamsonp@pbmac.nci.nih.gov Y1 - 1997/11// PY - 1997 DA - November 1997 SP - 3330 EP - 3337 VL - 15 IS - 11 SN - 0732-183X, 0732-183X KW - Interferon-alpha KW - 0 KW - Recombinant Proteins KW - interferon alfa-2a KW - 47RRR83SK7 KW - Tretinoin KW - 5688UTC01R KW - Index Medicus KW - Drug Administration Schedule KW - Area Under Curve KW - Humans KW - Adult KW - Child KW - Wilms Tumor -- therapy KW - Wilms Tumor -- pathology KW - Adolescent KW - Male KW - Female KW - Chromatography, High Pressure Liquid KW - Interferon-alpha -- administration & dosage KW - Tretinoin -- blood KW - Tretinoin -- administration & dosage KW - Neoplasms -- therapy KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Tretinoin -- pharmacokinetics KW - Tretinoin -- adverse effects KW - Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79397293?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.atitle=Phase+I+trial+and+pharmacokinetic+study+of+all-trans-retinoic+acid+administered+on+an+intermittent+schedule+in+combination+with+interferon-alpha2a+in+pediatric+patients+with+refractory+cancer.&rft.au=Adamson%2C+P+C%3BReaman%2C+G%3BFinklestein%2C+J+Z%3BFeusner%2C+J%3BBerg%2C+S+L%3BBlaney%2C+S+M%3BO%27Brien%2C+M%3BMurphy%2C+R+F%3BBalis%2C+F+M&rft.aulast=Adamson&rft.aufirst=P&rft.date=1997-11-01&rft.volume=15&rft.issue=11&rft.spage=3330&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 - 1997-12-02 N1 - Date created - 1997-12-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nutritional issues and HIV/AIDS: assessment and treatment strategies. AN - 79387974; 9356968 AB - Ongoing nutritional assessment is vital in the care of adults and children with HIV infection. Nutritional deficiency is a common manifestation of HIV disease and results from a variety of factors. Nurses caring for individuals with HIV infection in a variety of settings can be instrumental in identifying nutritional deficits, linking patients with appropriate medical/nutritional support services, and assuring that appropriate nutritional interventions are implemented. This article summarizes etiologies of HIV-associated nutritional deficiencies, reviews important components of nutrition assessment (including nutrition-related side effects of approved medications commonly used in HIV disease), provides an overview of common nutritional problems and interventions, and lists some available nutritional resources. JF - The Journal of the Association of Nurses in AIDS Care : JANAC AU - Walsek, C AU - Zafonte, M AU - Bowers, J M AD - NIH National Cancer Institute, USA. PY - 1997 SP - 71 EP - 80 VL - 8 IS - 6 SN - 1055-3290, 1055-3290 KW - Antiviral Agents KW - 0 KW - Index Medicus KW - Nursing KW - AIDS/HIV KW - Humans KW - Adult KW - Child KW - Diet KW - Nutrition Disorders -- diagnosis KW - HIV Infections -- complications KW - Nutrition Disorders -- etiology KW - Nutrition Assessment KW - HIV Infections -- drug therapy KW - Antiviral Agents -- adverse effects KW - Nutrition Disorders -- therapy KW - HIV Infections -- nursing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79387974?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+the+Association+of+Nurses+in+AIDS+Care+%3A+JANAC&rft.atitle=Nutritional+issues+and+HIV%2FAIDS%3A+assessment+and+treatment+strategies.&rft.au=Walsek%2C+C%3BZafonte%2C+M%3BBowers%2C+J+M&rft.aulast=Walsek&rft.aufirst=C&rft.date=1997-11-01&rft.volume=8&rft.issue=6&rft.spage=71&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+the+Association+of+Nurses+in+AIDS+Care+%3A+JANAC&rft.issn=10553290&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-12-05 N1 - Date created - 1997-12-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - l-alpha-Acetylmethadol, l-alpha-acetyl-N-normethadol and l-alpha-acetyl-N,N-dinormethadol: comparisons with morphine and methadone in suppression of the opioid withdrawal syndrome in the dog. AN - 79386113; 9353405 AB - l-alpha-Acetyl-N-normethadol (nor-LAAM) and l-alpha-acetyl-N, N-dinormethadol (dinor-LAAM) are active metabolites of the opiate l-alpha-acetylmethadol (LAAM), and they contribute to the prolonged actions of the parent compound. Single doses of nor-LAAM, dinor-LAAM, LAAM, methadone and morphine were given intravenously to the chronic spinal dog to determine acute, single-dose effects and their ability to suppress withdrawal in morphine-dependent dogs. These opioids produced dose-dependent antinociception, decreases in body temperature and pupillary constriction. For these measures, dinor-LAAM was 1.5 to 3 times and nor-LAAM 6 to 12 times as potent as LAAM. Five hours after the acute administration of LAAM or either of the metabolites, a 1-mg/kg dose of naltrexone given intravenously produced withdrawal, indicating the presence of acute physical dependence. In dogs physically dependent on a daily dose of 125 mg of morphine, nor-LAAM was 9 times as potent as either LAAM or dinor-LAAM in suppressing spontaneous withdrawal 40 hr after the last dose of morphine. The efficacies of LAAM and its demethylated metabolites in the dog for producing acute opiate effects were comparable with those of morphine and methadone. There was a trend, however, for LAAM to suppress the expression of abstinence more fully than either metabolite. The usefulness of LAAM as a treatment for opiate addiction is likely due in part to the equivalent efficacies and higher potencies of its nor and dinor metabolites. JF - The Journal of pharmacology and experimental therapeutics AU - Vaupel, D B AU - Jasinski, D R AD - Brain Imaging Section, Intramural Research Program, National Institute on Drug Abuse, Baltimore, Maryland 21224, USA. bvaupel@nida.gov Y1 - 1997/11// PY - 1997 DA - November 1997 SP - 833 EP - 842 VL - 283 IS - 2 SN - 0022-3565, 0022-3565 KW - Analgesics, Opioid KW - 0 KW - paracymethadol KW - 1477-39-0 KW - 1 alpha-acetyldinormethadol KW - 40488-01-5 KW - Morphine KW - 76I7G6D29C KW - Methadyl Acetate KW - L59OC40KWJ KW - Methadone KW - UC6VBE7V1Z KW - Index Medicus KW - Animals KW - Dose-Response Relationship, Drug KW - Dogs KW - Methadyl Acetate -- pharmacology KW - Analgesics, Opioid -- pharmacology KW - Methadyl Acetate -- analogs & derivatives KW - Substance Withdrawal Syndrome -- drug therapy KW - Opioid-Related Disorders -- drug therapy KW - Morphine -- pharmacology KW - Methadone -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79386113?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=l-alpha-Acetylmethadol%2C+l-alpha-acetyl-N-normethadol+and+l-alpha-acetyl-N%2CN-dinormethadol%3A+comparisons+with+morphine+and+methadone+in+suppression+of+the+opioid+withdrawal+syndrome+in+the+dog.&rft.au=Vaupel%2C+D+B%3BJasinski%2C+D+R&rft.aulast=Vaupel&rft.aufirst=D&rft.date=1997-11-01&rft.volume=283&rft.issue=2&rft.spage=833&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 - 1997-12-08 N1 - Date created - 1997-12-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Motor response to a dopamine D3 receptor preferring agonist compared to apomorphine in levodopa-primed 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine monkeys. AN - 79384541; 9353400 AB - The profile of dopamine receptor subtype activation contributing to the therapeutic efficacy and motor response complications of levodopa (nonselective pro-agonist) in Parkinson's disease remains unclear. Potent, selective, short-acting dopamine D2 receptor subfamily agonists show good antiparkinsonian efficacy but produce dyskinesias comparable to levodopa. Nonetheless, agonists displaying higher affinity for dopamine receptors other than the D2 subtype may have a better therapeutic index. To clarify this issue, we compared the nonselective dopamine D1/D2 receptor subfamilies agonist apomorphine to the dopamine D3 receptor preferring agonist [R-(+)-trans-3,4,4a,10b-tetrahydro-4-propyl-2H,5H-[1]benzopyrano[4 , 3-b]-1,4-oxazin-9-ol] (PD 128,907) in 6 levodopa-primed , 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned parkinsonian monkeys with reproducible dyskinesias. Single s.c. dosing with the lowest fully effective dose of apomorphine (averaging 27.9 +/- 4.5 microg/kg) and PD 128,907 (averaging 41.7 +/- 4.4 microg/kg) yielded equivalent antiparkinsonian efficacy on the behavioral scale and portable activity monitoring used. A comparable significant dose-dependent increase in the response magnitude and duration was seen with two higher doses. The severity of dyskinesia was also similar between the two drugs. When the lower dose for each drug was administered six times at a fixed 90-min interval, both drugs remained efficacious with no significant tolerance observed. The D3 receptor preferring antagonist U-99194A significantly reduced the motor effects of both apomorphine and PD 128,907. Thus, increased D3 receptor tone does not acutely ameliorate dyskinesias in levodopa-primed parkinsonian monkeys. Given the reported lack of affinity of PD 128,907 for central D1 receptors, our data support the concept that the pharmacological activation of D1 receptors is not mandatory for relief of parkinsonism and production of dyskinesia. JF - The Journal of pharmacology and experimental therapeutics AU - Blanchet, P J AU - Konitsiotis, S AU - Chase, T N AD - Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-1406, USA. Y1 - 1997/11// PY - 1997 DA - November 1997 SP - 794 EP - 799 VL - 283 IS - 2 SN - 0022-3565, 0022-3565 KW - Antiparkinson Agents KW - 0 KW - Dopamine Agonists KW - Receptors, Dopamine D1 KW - Receptors, Dopamine D2 KW - Receptors, Dopamine D3 KW - Levodopa KW - 46627O600J KW - Apomorphine KW - N21FAR7B4S KW - Index Medicus KW - Animals KW - Macaca fascicularis KW - Receptors, Dopamine D1 -- drug effects KW - Antiparkinson Agents -- pharmacology KW - Male KW - Female KW - Levodopa -- pharmacology KW - Dopamine Agonists -- pharmacology KW - MPTP Poisoning KW - Apomorphine -- pharmacology KW - Receptors, Dopamine D2 -- agonists KW - Dopamine Agonists -- toxicity KW - Receptors, Dopamine D2 -- drug effects KW - Motor Activity -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79384541?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Motor+response+to+a+dopamine+D3+receptor+preferring+agonist+compared+to+apomorphine+in+levodopa-primed+1-methyl-4-phenyl-1%2C2%2C3%2C6-tetrahydropyridine+monkeys.&rft.au=Blanchet%2C+P+J%3BKonitsiotis%2C+S%3BChase%2C+T+N&rft.aulast=Blanchet&rft.aufirst=P&rft.date=1997-11-01&rft.volume=283&rft.issue=2&rft.spage=794&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 - 1997-12-08 N1 - Date created - 1997-12-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - PTEN/MMAC1 mutations in endometrial cancers. AN - 79378452; 9354433 AB - Endometrial carcinomas represent the most common gynecological cancer in the United States, yet the molecular genetic events that underlie the development of these tumors remain obscure. Chromosome 10 is implicated in the pathogenesis of endometrial carcinoma based on loss of heterozygosity (LOH), comparative genomic hybridization, and cytogenetics. Recently, a potential tumor suppressor gene, PTEN/MMAC1, with homology to dual-specificity phosphatases and to the cytoskeletal proteins tensin and auxillin was identified on chromosome 10. This gene is mutated in several types of advanced tumors that display frequent LOH on chromosome 10, most notably glioblastomas. Additionally, germ-line mutations of PTEN/MMAC1 are responsible for several familial neoplastic disorders, including Cowden disease and Bannayan-Zonana syndrome. Because this locus is included in the region of LOH in many endometrial carcinomas, we examined 70 endometrial carcinomas for alterations in PTEN/MMAC1. Somatic mutations were detected in 24 cases (34%) including 21 cases that resulted in premature truncation of the protein, 2 tumors with missense alterations in the conserved phosphatase domain, and 1 tumor with a large insertion. These data indicate that PTEN/MMAC1 is more commonly mutated than any other known gene in endometrial cancers. JF - Cancer research AU - Risinger, J I AU - Hayes, A K AU - Berchuck, A AU - Barrett, J C AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1997/11/01/ PY - 1997 DA - 1997 Nov 01 SP - 4736 EP - 4738 VL - 57 IS - 21 SN - 0008-5472, 0008-5472 KW - Index Medicus KW - Microsatellite Repeats -- genetics KW - Humans KW - Female KW - Gene Deletion KW - Genes, Tumor Suppressor -- genetics KW - Chromosomes, Human, Pair 10 -- genetics KW - Mutation -- genetics KW - Adenocarcinoma -- genetics KW - Endometrial Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79378452?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Common+core+sequences+are+found+in+skeletal+muscle+slow-+and+fast-fiber-type-specific+regulatory+elements.&rft.au=Nakayama%2C+M%3BStauffer%2C+J%3BCheng%2C+J%3BBanerjee-Basu%2C+S%3BWawrousek%2C+E%3BBuonanno%2C+A&rft.aulast=Nakayama&rft.aufirst=M&rft.date=1996-05-01&rft.volume=16&rft.issue=5&rft.spage=2408&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 - 1997-11-20 N1 - Date created - 1997-11-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dietary restriction reduces insulin-like growth factor I levels, which modulates apoptosis, cell proliferation, and tumor progression in p53-deficient mice. AN - 79373544; 9354418 AB - Diet contributes to over one-third of cancer deaths in the Western world, yet the factors in the diet that influence cancer are not elucidated. A reduction in caloric intake dramatically slows cancer progression in rodents, and this may be a major contribution to dietary effects on cancer. Insulin-like growth factor I (IGF-I) is lowered during dietary restriction (DR) in both humans and rats. Because IGF-I modulates cell proliferation, apoptosis, and tumorigenesis, the mechanisms behind the protective effects of DR may depend on the reduction of this multifaceted growth factor. To test this hypothesis, IGF-I was restored during DR to ascertain if lowering of IGF-I was central to slowing bladder cancer progression during DR. Heterozygous p53-deficient mice received a bladder carcinogen, p-cresidine, to induce preneoplasia. After confirmation of bladder urothelial preneoplasia, the mice were divided into three groups: (a) ad libitum; (b) 20% DR; and (c) 20% DR plus IGF-I (IGF-I/DR). Serum IGF-I was lowered 24% by DR but was completely restored in the IGF-I/DR-treated mice using recombinant IGF-I administered via osmotic minipumps. Although tumor progression was decreased by DR, restoration of IGF-I serum levels in DR-treated mice increased the stage of the cancers. Furthermore, IGF-I modulated tumor progression independent of changes in body weight. Rates of apoptosis in the preneoplastic lesions were 10 times higher in DR-treated mice compared to those in IGF/DR- and ad libitum-treated mice. Administration of IGF-I to DR-treated mice also stimulated cell proliferation 6-fold in hyperplastic foci. In conclusion, DR lowered IGF-I levels, thereby favoring apoptosis over cell proliferation and ultimately slowing tumor progression. This is the first mechanistic study demonstrating that IGF-I supplementation abrogates the protective effect of DR on neoplastic progression. JF - Cancer research AU - Dunn, S E AU - Kari, F W AU - French, J AU - Leininger, J R AU - Travlos, G AU - Wilson, R AU - Barrett, J C AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina 27709, USA. Y1 - 1997/11/01/ PY - 1997 DA - 1997 Nov 01 SP - 4667 EP - 4672 VL - 57 IS - 21 SN - 0008-5472, 0008-5472 KW - Aniline Compounds KW - 0 KW - Carcinogens KW - cresidine KW - 4C11L78UR3 KW - Insulin-Like Growth Factor I KW - 67763-96-6 KW - Index Medicus KW - Urinary Bladder -- pathology KW - Animals KW - Urothelium -- drug effects KW - Neoplasm Staging KW - Cell Division -- drug effects KW - Disease Progression KW - Mice KW - Urinary Bladder -- drug effects KW - Hyperplasia -- chemically induced KW - Urothelium -- pathology KW - Incidence KW - Male KW - Mice, Transgenic -- genetics KW - Carcinoma, Transitional Cell -- pathology KW - Precancerous Conditions -- diet therapy KW - Urinary Bladder Neoplasms -- pathology KW - Carcinoma, Transitional Cell -- blood KW - Insulin-Like Growth Factor I -- metabolism KW - Carcinoma, Transitional Cell -- chemically induced KW - Precancerous Conditions -- blood KW - Insulin-Like Growth Factor I -- pharmacology KW - Precancerous Conditions -- pathology KW - Precancerous Conditions -- chemically induced KW - Apoptosis -- drug effects KW - Urinary Bladder Neoplasms -- diet therapy KW - Carcinoma, Transitional Cell -- diet therapy KW - Urinary Bladder Neoplasms -- blood KW - Urinary Bladder Neoplasms -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79373544?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Dietary+restriction+reduces+insulin-like+growth+factor+I+levels%2C+which+modulates+apoptosis%2C+cell+proliferation%2C+and+tumor+progression+in+p53-deficient+mice.&rft.au=Dunn%2C+S+E%3BKari%2C+F+W%3BFrench%2C+J%3BLeininger%2C+J+R%3BTravlos%2C+G%3BWilson%2C+R%3BBarrett%2C+J+C&rft.aulast=Dunn&rft.aufirst=S&rft.date=1997-11-01&rft.volume=57&rft.issue=21&rft.spage=4667&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 - 1997-11-20 N1 - Date created - 1997-11-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular epidemiology: carcinogen-DNA adducts and genetic susceptibility. AN - 79366205; 9349686 AB - Molecular epidemiological studies assess individual chemical exposures and genetic susceptibility in order to identify cancer risk. Such studies incorporate the development, application, and validation of biomarkers of cancer risk in order to enhance cancer risk assessments, focus cancer prevention strategies, and elucidate mechanisms of carcinogenesis. Current studies of molecular epidemiology are based upon an understanding of the complex, multistage process of carcinogenesis and interindividual variations in response to carcinogenic exposures. Quantitative methods to measure human exposures to carcinogens continue to improve and have been successfully applied to a number of epidemiological studies. Genetic predispositions to cancer, both inherited and acquired, have been and continue to be identified. The combined approach of associating genetic polymorphisms with carcinogen-DNA adduct measurements, in order to assess cancer risk, is showing considerable promise. It is hoped that, in the future, molecular epidemiologists will be able to develop a risk profile for an individual that includes assessment of multiple biomarkers. The field has the near-term potential to have a significant impact on regulatory quantitative risk assessments, which may aid in the determination of allowable exposures. Molecular epidemiological data may also aid in the identification of individuals who will most benefit by cancer prevention strategies. JF - Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.) AU - Warren, A J AU - Shields, P G AD - Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4255, USA. Y1 - 1997/11// PY - 1997 DA - November 1997 SP - 172 EP - 180 VL - 216 IS - 2 SN - 0037-9727, 0037-9727 KW - Biomarkers, Tumor KW - 0 KW - Carcinogens KW - DNA Adducts KW - Index Medicus KW - Carcinogens -- metabolism KW - DNA Damage KW - Risk Factors KW - Humans KW - Biomarkers, Tumor -- analysis KW - DNA Adducts -- analysis KW - Neoplasms -- epidemiology KW - Molecular Epidemiology -- methods KW - Genetic Predisposition to Disease KW - Neoplasms -- genetics KW - Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79366205?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+Society+for+Experimental+Biology+and+Medicine.+Society+for+Experimental+Biology+and+Medicine+%28New+York%2C+N.Y.%29&rft.atitle=Molecular+epidemiology%3A+carcinogen-DNA+adducts+and+genetic+susceptibility.&rft.au=Warren%2C+A+J%3BShields%2C+P+G&rft.aulast=Warren&rft.aufirst=A&rft.date=1997-11-01&rft.volume=216&rft.issue=2&rft.spage=172&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+Society+for+Experimental+Biology+and+Medicine.+Society+for+Experimental+Biology+and+Medicine+%28New+York%2C+N.Y.%29&rft.issn=00379727&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-11-19 N1 - Date created - 1997-11-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Constraints on CD4 recovery postchemotherapy in adults: thymic insufficiency and apoptotic decline of expanded peripheral CD4 cells. AN - 79361208; 9345067 AB - To examine the mechanisms of CD4 reconstitution in an adult population, lymphocyte repopulation was assessed following dose-intense chemotherapy in 25 breast cancer patients, ages 33 to 69 years. Chemotherapy resulted in a greater than 60% reduction in total CD4 T cells and, in particular, a greater than 90% loss of the CD45RA+ CD4 cells. CD4 recovery was protracted, achieving less than 50% of pretreatment levels after 12 to 14 months. Two facets of the CD4 recovery were notable. First, generation of CD45RA+ CD4 cells played only a minor role in the first year, suggesting that thymic production was not the main route of CD4 regeneration. Indeed, recovery of CD45RA+ CD4 cell levels remained limited in half of the patients even after 2 years. Second, expansion of the mature peripheral CD4 cells (CD45RO+) remaining after chemotherapy was the main source of early CD4 repopulation, peaking at 3 to 6 months postchemotherapy. This expansion was limited in duration, however, and was followed by a secondary decline, such that the total CD45RO+ CD4 levels at 9 to 12 months were lower than at 6 months. When stimulated by mitogens, an increased susceptibility to apoptosis was observed in postchemotherapy CD4 cells as compared with those from normal donors. The elevated expression of markers such as HLA-DR during chemotherapy and for several months postchemotherapy is consistent with the presence of an activated T-cell population. CD4 apoptotic frequency correlated with the frequency of HLA-DR expression on T cells. Thus, CD4 recovery is constrained in adults by a limited thymic regenerative capacity and by an increased susceptibility to apoptosis within the expanding peripheral CD4 population. JF - Blood AU - Hakim, F T AU - Cepeda, R AU - Kaimei, S AU - Mackall, C L AU - McAtee, N AU - Zujewski, J AU - Cowan, K AU - Gress, R E AD - Medicine Branch and Pediatric Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1997/11/01/ PY - 1997 DA - 1997 Nov 01 SP - 3789 EP - 3798 VL - 90 IS - 9 SN - 0006-4971, 0006-4971 KW - Antigens, CD4 KW - 0 KW - Abridged Index Medicus KW - Index Medicus KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Female KW - Breast Neoplasms -- immunology KW - Breast Neoplasms -- drug therapy KW - Thymus Gland -- immunology KW - Breast Neoplasms -- pathology KW - CD4-Positive T-Lymphocytes -- pathology KW - Apoptosis -- immunology KW - Thymus Gland -- pathology KW - CD4-Positive T-Lymphocytes -- immunology 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/79361208?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Constraints+on+CD4+recovery+postchemotherapy+in+adults%3A+thymic+insufficiency+and+apoptotic+decline+of+expanded+peripheral+CD4+cells.&rft.au=Hakim%2C+F+T%3BCepeda%2C+R%3BKaimei%2C+S%3BMackall%2C+C+L%3BMcAtee%2C+N%3BZujewski%2C+J%3BCowan%2C+K%3BGress%2C+R+E&rft.aulast=Hakim&rft.aufirst=F&rft.date=1997-11-01&rft.volume=90&rft.issue=9&rft.spage=3789&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-11-18 N1 - Date created - 1997-11-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of salicylate on 3,4-methylenedioxymethamphetamine (MDMA)-induced neurotoxicity in rats. AN - 79314836; 9329062 AB - The drug 3,4-methylenedioxymethamphetamine (MDMA) is a serotonergic neurotoxicant that causes hyperthermia and depletion of serotonin (5-HT) and 5-hydroxy-indole-3-acetic acid (5-HIAA) in the central nervous system. Formation of neurotoxic metabolites of MDMA, e.g., 2,4,5-trihydroxy-methamphetamine and 2,4,5-trihydroxyamphetamine, involves hydroxyl and/or superoxide free radicals. The present study was designed to determine whether the hydroxyl free-radical-trapping agent salicylate could provide protection against MDMA neurotoxicity in rats. In the acute studies, sodium salicylate (12.5-400 mg/kg, calculated as free acid) was injected interperitoneally (i.p.) 1 h before subcutaneous (s.c.) injections of MDMA (20 mg/kg as base). In the chronic studies, sodium salicylate (3.1-100 mg/kg) was injected i.p. 1 h before repeated s.c. injections of MDMA (10 mg/kg as base, twice daily, at 0830 and 1730 h for 4 consecutive days). Repeated MDMA administration depleted contents of 5-HT and 5-HIAA in the frontal cortex, hippocampus and striatum. Coadministration of salicylate plus MDMA did not significantly alter MDMA-induced depletion of 5-HT and 5-HIAA in these tissues. Thus, salicylate, a hydroxyl free-radical-trapping agent, does not protect against MDMA-induced hyperthermia and depletion of 5-HT and 5-HIAA. These observations suggest that MDMA-induced neurotoxicity may occur mainly through the production of superoxide or other radicals rather than hydroxyl free radicals. Salicylate actually potentiated MDMA-induced hyperthermia and lethality, findings that might be of clinical relevance. JF - Pharmacology, biochemistry, and behavior AU - Yeh, S Y AD - Molecular Neuropsychiatry Section, National Institute on Drug Abuse, National Institute of Health, Baltimore, MD 21224, USA. Y1 - 1997/11// PY - 1997 DA - November 1997 SP - 701 EP - 708 VL - 58 IS - 3 SN - 0091-3057, 0091-3057 KW - Adrenergic Uptake Inhibitors KW - 0 KW - Biogenic Monoamines KW - Free Radical Scavengers KW - Salicylates KW - Superoxides KW - 11062-77-4 KW - Hydroxyl Radical KW - 3352-57-6 KW - N-Methyl-3,4-methylenedioxyamphetamine KW - KE1SEN21RM KW - Salicylic Acid KW - O414PZ4LPZ KW - Index Medicus KW - Rats KW - Injections, Intraperitoneal KW - Animals KW - Superoxides -- metabolism KW - Rats, Sprague-Dawley KW - Body Temperature -- drug effects KW - Hydroxyl Radical -- metabolism KW - Brain Chemistry -- drug effects KW - Biogenic Monoamines -- metabolism KW - Male KW - Salicylates -- toxicity KW - Salicylates -- administration & dosage KW - Free Radical Scavengers -- toxicity KW - Nervous System Diseases -- metabolism KW - N-Methyl-3,4-methylenedioxyamphetamine -- toxicity KW - Free Radical Scavengers -- administration & dosage KW - Adrenergic Uptake Inhibitors -- toxicity KW - Nervous System Diseases -- chemically induced KW - Free Radical Scavengers -- pharmacology KW - Salicylates -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79314836?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pharmacology%2C+biochemistry%2C+and+behavior&rft.atitle=Effects+of+salicylate+on+3%2C4-methylenedioxymethamphetamine+%28MDMA%29-induced+neurotoxicity+in+rats.&rft.au=Yeh%2C+S+Y&rft.aulast=Yeh&rft.aufirst=S&rft.date=1997-11-01&rft.volume=58&rft.issue=3&rft.spage=701&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 - 1998-02-06 N1 - Date created - 1998-02-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Helicobacter Infections of Rodents and Carcinogenesis Bioassays AN - 755139657; 13645887 JF - Toxicologic Pathology AU - Ward, Jerrold M AD - NCI Veterinary Pathology National Cancer Institute NCI-FCRDC, Fairview 201 Frederick, Maryland 21702-1201 Y1 - 1997/11// PY - 1997 DA - Nov 1997 SP - 590 PB - Sage Publications Ltd., 6 Bonhill St. London EC2A 4PU UK VL - 25 IS - 6 SN - 0192-6233, 0192-6233 KW - Toxicology Abstracts UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/755139657?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicologic+Pathology&rft.atitle=Helicobacter+Infections+of+Rodents+and+Carcinogenesis+Bioassays&rft.au=Ward%2C+Jerrold+M&rft.aulast=Ward&rft.aufirst=Jerrold&rft.date=1997-11-01&rft.volume=25&rft.issue=6&rft.spage=590&rft.isbn=&rft.btitle=&rft.title=Toxicologic+Pathology&rft.issn=01926233&rft_id=info:doi/10.1177%2F019262339702500608 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-09-01 N1 - Last updated - 2012-03-29 DO - http://dx.doi.org/10.1177/019262339702500608 ER - TY - JOUR T1 - A PCR-RFLP Method for the Detection of Helicobacter hepaticus in Frozen or Fixed Liver from B6C3F1 Mice AN - 755138169; 13645890 AB - Establishing the diagnosis of Helicobacter hepaticus infection in mouse liver has recently become important for the interpretation of rodent carcinogenicity bioassays. A seminested primer polymerase chain reaction (PCR) amplification of the bacterial 16S ribosomal RNA gene in combination with a restriction fragment length polymorphism (RFLP) assay was designed to identify and distinguish H. hepaticus from H. muridarum and H. bilis in mouse liver. The PCR-RFLP assay was applied to formalin-fixed, paraffin-embedded and, when available, corresponding frozen liver tissues from male and female B6C3F, mice with or without histologic evidence of infection from various National Toxicology Program 2-yr bioassay studies. PCR products consistent with H. hepaticus were detected in 10-80% of livers from mice in studies with other evidence of infection that were frozen or fixed for less than 24 hr but not in liver fixed for several weeks. The sensitivity of the PCR-RFLP assay for H. hepaticus on formalin-fixed, paraffin-embedded mouse liver varied between studies from markedly decreased when compared to the results from frozen liver or histologic evaluation to nearly equivalent or more sensitive than histologic evaluation. The PCR-RFLP results appeared dependent on the duration of fixation and bacterial load but not on the presence of hepatitis, sampling from neoplastic or nonneoplastic liver, or sex of the mouse. JF - Toxicologic Pathology AU - Malarkey, David E AU - Ton, Thai-Vu AU - Hailey, James R AU - Devereux, Theodora R AD - Department of Microbiology, Pathology, and Parasitology, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina 27606,, Environmental Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, David_Malarkey@ncsu.edu Y1 - 1997/11// PY - 1997 DA - Nov 1997 SP - 606 EP - 612 PB - Sage Publications Ltd., 6 Bonhill St. London EC2A 4PU UK VL - 25 IS - 6 SN - 0192-6233, 0192-6233 KW - Microbiology Abstracts B: Bacteriology; Toxicology Abstracts KW - Hepatitis KW - Carcinogenicity KW - Helicobacter hepaticus KW - Liver KW - Restriction fragment length polymorphism KW - Polymerase chain reaction KW - Primers KW - Sampling KW - Infection KW - rRNA 16S KW - Sex KW - J 02310:Genetics & Taxonomy KW - X 24300:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/755138169?accountid=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=Toxicologic+Pathology&rft.atitle=A+PCR-RFLP+Method+for+the+Detection+of+Helicobacter+hepaticus+in+Frozen+or+Fixed+Liver+from+B6C3F1+Mice&rft.au=Malarkey%2C+David+E%3BTon%2C+Thai-Vu%3BHailey%2C+James+R%3BDevereux%2C+Theodora+R&rft.aulast=Malarkey&rft.aufirst=David&rft.date=1997-11-01&rft.volume=25&rft.issue=6&rft.spage=606&rft.isbn=&rft.btitle=&rft.title=Toxicologic+Pathology&rft.issn=01926233&rft_id=info:doi/10.1177%2F019262339702500611 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-09-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - Hepatitis; Carcinogenicity; Restriction fragment length polymorphism; Liver; Polymerase chain reaction; Primers; Sampling; Infection; rRNA 16S; Sex; Helicobacter hepaticus DO - http://dx.doi.org/10.1177/019262339702500611 ER - TY - JOUR T1 - Alteration in Cell Kinetics in Control B6C3F1 Mice Infected with Helicobacter hepaticus AN - 755136318; 13645888 AB - The discovery of Helicobacter hepaticus infection, H. hepaticus hepatitis, and increased incidence of liver tumors in control males from several recent National Toxicology Program B6C3F, mouse carcinogenicity bioassays raised questions regarding the suitability of these bioassays for hazard identification. The purpose of this study was to determine if changes in cell proliferation and death at terminal sacrifice might be linked to the increased liver tumor incidences among control males. In control males, enhanced rates of hepatocyte proliferation, as assessed by immunostaining for proliferating cell nuclear antigen (PCNA), and apoptosis, as assessed from hematoxylin and eosin- and TUNEL-stained preparations, were seen in 3 bioassays with H. hepaticus hepatitis. One bioassay with H. hepaticus infection without attendant hepatitis and one bioassay without H. hepaticus or hepatitis did not have elevated rates of hepatocyte proliferation or apoptosis. There was no significant effect on PCNA cell proliferation indices or apoptosis in females. The present findings are indicative of a clear association between the presence of H. hepaticus infection with attendant hepatitis, increased cell proliferation and apoptosis, and increased incidences of hepatocellular neoplasia in males but not in females. Thus, the interpretation of liver tumor responses in H. hepaticus-infected studies is considered to be confounded in male mice. The lack of enhanced cell proliferation or hepatocellular neoplasia in control females suggests that bioassay results from females are valid for hazard identification. Furthermore, the absence of enhanced cell proliferation in lungs and kidneys of male and females suggests that neoplastic effects at these sites are not exacerbated by H. hepaticus infection. JF - Toxicologic Pathology AU - Nyska, Abraham AU - Maronpot, Robert R AU - Eldridge, Sandra R AU - Haseman, Joseph K AU - Hailey, James R AD - National Toxicology Program, National Institute of Environmental Health Sciences, P.O. Box 12233, Research Triangle Park, North Carolina 27709, maronpot@niehs.nih.gov Y1 - 1997/11// PY - 1997 DA - Nov 1997 SP - 591 EP - 596 PB - Sage Publications Ltd., 6 Bonhill St. London EC2A 4PU UK VL - 25 IS - 6 SN - 0192-6233, 0192-6233 KW - Microbiology Abstracts B: Bacteriology; Toxicology Abstracts KW - Apoptosis KW - Hepatocytes KW - Tumors KW - Proliferating cell nuclear antigen KW - Infection KW - Neoplasia KW - Hepatitis KW - Lung KW - Carcinogenicity KW - Kinetics KW - Helicobacter hepaticus KW - Kidney KW - Liver KW - Cell proliferation KW - J 02410:Animal Diseases KW - X 24300:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/755136318?accountid=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=Toxicologic+Pathology&rft.atitle=Alteration+in+Cell+Kinetics+in+Control+B6C3F1+Mice+Infected+with+Helicobacter+hepaticus&rft.au=Nyska%2C+Abraham%3BMaronpot%2C+Robert+R%3BEldridge%2C+Sandra+R%3BHaseman%2C+Joseph+K%3BHailey%2C+James+R&rft.aulast=Nyska&rft.aufirst=Abraham&rft.date=1997-11-01&rft.volume=66&rft.issue=5&rft.spage=1868&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 revised - 2010-09-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - Apoptosis; Hepatocytes; Tumors; Infection; Proliferating cell nuclear antigen; Neoplasia; Hepatitis; Carcinogenicity; Lung; Kinetics; Liver; Kidney; Cell proliferation; Helicobacter hepaticus DO - http://dx.doi.org/10.1177/019262339702500609 ER - TY - JOUR T1 - Phenolphthalein Induces Thymic Lymphomas Accompanied by Loss of the p53 Wild Type Allele in Heterozygous p53-Deficient (c) Mice AN - 755136199; 13645880 AB - Epidemiology studies have indicated that many human cancers are influenced by environmental factors. Genetically altered mouse model systems offer us the opportunity to study the interaction of chemicals with genetic predisposition to cancer. Using the heterozygous p53-deficient (c) mouse, an animal model carrying one wild type p53 gene and one p53 null allele, we studied the effects of phenolphthalein on tumor induction and p53 gene alterations. Earlier studies showed that phenolphthalein caused carcinogenic effects in Fisher 344 rats and B6C3F, mice after a 2-yr dosing period (Dunnick and Hailey, Cancer Res. 56: 4922-4926, 1996). The p53 (c) mice received phenolphthalein in the feed at concentrations of 200, 375, 750, 3,000, or 12,000 ppm (approximately 43, 84, 174, 689, or 2,375 mg/kg body weight/day or 129, 252, 522, 2,867, or 7,128 mg/m super(2) body surface area/day) for up to 6 mo. A target organ cancer site that accumulated p53 protein in the B6C3F, mouse (i.e., thymic lymphoma) was also a target site for cancer in the p53 (c) mouse. In the p53 (c) mouse, treatment-related atypical hyperplasia and malignant lymphoma of thymic origin were seen in the control and dosed groups at a combined incidence of 0, 5, 5, 25, 100, and 95%, respectively. Twenty-one of the thymic lymphomas were examined for p53 gene changes, and all showed loss of the p53 wild type allele. Chemical-induced ovarian tumors in the B6C3F, mouse showed no evidence for p53 protein accumulation and did not occur in the p53 (c) mouse. The p53-deficient (c) mouse model responded to phenolphthalein treatment with a carcinogenic response in the thymus after only 4 mo of dosing. This carcinogenic response took 2 yr to develop in the conventional B6C3F, mouse bioassay. The p53-deficient (c) mouse is an important model for identifying a carcinogenic response after short-term (<6 mo) exposures. Our studies show that exposure to phenolphthalein combined with a genetic predisposition to cancer can potentiate the carcinogenic process and cause p53 gene alterations, a gene alteration found in many human cancers. JF - Toxicologic Pathology AU - Dunnick, June K AU - Hardisty, Jerry F AU - Herbert, Ronald A AU - Seely, John C AU - Furedi-Machacek, EMarianna AU - Foley, Julie F AU - Lacks, Gregory D AU - Stasiewicz, Stanley AU - French, John E AD - National Institute of Environmental Health Sciences Y1 - 1997/11// PY - 1997 DA - Nov 1997 SP - 533 EP - 540 PB - Sage Publications Ltd., 6 Bonhill St. London EC2A 4PU UK VL - 25 IS - 6 SN - 0192-6233, 0192-6233 KW - Toxicology Abstracts; Oncogenes & Growth Factors Abstracts; Immunology Abstracts KW - phenolphthalein KW - Surface area KW - Thymus KW - Animal models KW - Tumors KW - Environmental factors KW - Cancer KW - p53 protein KW - Hyperplasia KW - Epidemiology KW - Body weight KW - Lymphoma KW - F 06955:Immunomodulation & Immunopharmacology KW - B 26670:Tumor Suppressors KW - X 24300:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/755136199?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicologic+Pathology&rft.atitle=Phenolphthalein+Induces+Thymic+Lymphomas+Accompanied+by+Loss+of+the+p53+Wild+Type+Allele+in+Heterozygous+p53-Deficient+%28c%29+Mice&rft.au=Dunnick%2C+June+K%3BHardisty%2C+Jerry+F%3BHerbert%2C+Ronald+A%3BSeely%2C+John+C%3BFuredi-Machacek%2C+EMarianna%3BFoley%2C+Julie+F%3BLacks%2C+Gregory+D%3BStasiewicz%2C+Stanley%3BFrench%2C+John+E&rft.aulast=Dunnick&rft.aufirst=June&rft.date=1997-11-01&rft.volume=25&rft.issue=6&rft.spage=533&rft.isbn=&rft.btitle=&rft.title=Toxicologic+Pathology&rft.issn=01926233&rft_id=info:doi/10.1177%2F019262339702500601 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-09-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - Hyperplasia; Body weight; Epidemiology; Surface area; phenolphthalein; Thymus; Animal models; Tumors; Environmental factors; Lymphoma; Cancer; p53 protein DO - http://dx.doi.org/10.1177/019262339702500601 ER - TY - JOUR T1 - Prevalence and Characteristics of Trauma and Posttraumatic Stress Disorder in a Southwestern American Indian Community AN - 61559924; 9815883 AB - Uses psychiatric interview data from 247 tribal members, ages 21+, of a southwestern American Indian community to examine the relationship between trauma frequency & type & posttraumatic stress disorder (PTSD) prevalence. Results showed PTSD prevalence to be 21%, significantly higher than the US average. The most predictive factor for women was the experience of physical assault, while for men it was a history of combat or having experienced 10+ traumatic events. Comparisons between these findings & national studies indicate that the American Indian sample had PTSD rates comparable to those of severely traumatized groups, eg, survivors of mass combat or shootings. 2 Tables, 37 References. Adapted from the source document. JF - The American Journal of Psychiatry AU - Robin, Robert W AU - Chester, Barbara AU - Rasmussen, Jolene K AU - Jaranson, James M AU - Goldman, David AD - LNG/NIAAA/NIH, PO Box 617 Sitka AK 99835 rwrobin@ptialaska.net Y1 - 1997/11// PY - 1997 DA - November 1997 SP - 1582 EP - 1588 VL - 154 IS - 11 SN - 0002-953X, 0002-953X KW - Western States KW - Sex Differences KW - Community Mental Health KW - Posttraumatic Stress Disorder KW - American Indians KW - article KW - 0410: group interactions; social group identity & intergroup relations (groups based on race & ethnicity, age, & sexual orientation) KW - 2046: sociology of health and medicine; social psychiatry (mental health) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/61559924?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Asocabs&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+Journal+of+Psychiatry&rft.atitle=Prevalence+and+Characteristics+of+Trauma+and+Posttraumatic+Stress+Disorder+in+a+Southwestern+American+Indian+Community&rft.au=Robin%2C+Robert+W%3BChester%2C+Barbara%3BRasmussen%2C+Jolene+K%3BJaranson%2C+James+M%3BGoldman%2C+David&rft.aulast=Robin&rft.aufirst=Robert&rft.date=1997-11-01&rft.volume=154&rft.issue=11&rft.spage=1582&rft.isbn=&rft.btitle=&rft.title=The+American+Journal+of+Psychiatry&rft.issn=0002953X&rft_id=info:doi/ LA - English DB - Sociological Abstracts N1 - Date revised - 2007-04-01 N1 - Last updated - 2016-09-28 N1 - CODEN - AJPSAO N1 - SubjectsTermNotLitGenreText - American Indians; Posttraumatic Stress Disorder; Community Mental Health; Western States; Sex Differences ER - TY - MGZN T1 - The flu story AN - 215886644; 03562181 AB - Influenza is an acute respiratory infection caused by a variety of viruses. It is important because of the seriousness of complications that can develop. The symptoms, strains and prevention of flu are discussed. JF - Healthline AU - National Institute of Allergy and Infectious Diseases Y1 - 1997/11// PY - 1997 DA - Nov 1997 SP - 10 EP - 11 CY - Menlo Park PB - Healthline Publishers, Inc. VL - 16 IS - 11 KW - Public Health And Safety KW - Influenza KW - Infections KW - Respiratory system KW - Preventive medicine UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/215886644?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthcompleteshell&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Healthline&rft.atitle=The+flu+story&rft.au=National+Institute+of+Allergy+and+Infectious+Diseases&rft.aulast=National+Institute+of+Allergy+and+Infectious+Diseases&rft.aufirst=&rft.date=1997-11-01&rft.volume=16&rft.issue=11&rft.spage=10&rft.isbn=&rft.btitle=&rft.title=Healthline&rft.issn=07367929&rft_id=info:doi/ LA - English DB - ProQuest Central; ProQuest Environmental Science Collection N1 - Copyright - Copyright Healthline Publishers, Inc. Nov 1997 N1 - Last updated - 2014-05-19 ER - TY - JOUR T1 - Intracerebral hemorrhage after intravenous t-PA therapy for ischemic stroke AN - 197807341 JF - Stroke AU - NINDS t-PA Stroke Study Group AD - NINDS t-PA Stroke Study Group Y1 - 1997/11// PY - 1997 DA - Nov 1997 SP - 2109 CY - Hagerstown PB - American Heart Association, Inc. VL - 28 IS - 11 SN - 00392499 KW - Medical Sciences--Cardiovascular Diseases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/197807341?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthcompleteshell&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Stroke&rft.atitle=Intracerebral+hemorrhage+after+intravenous+t-PA+therapy+for+ischemic+stroke&rft.au=NINDS+t-PA+Stroke+Study+Group&rft.aulast=NINDS+t-PA+Stroke+Study+Group&rft.aufirst=&rft.date=1997-11-01&rft.volume=28&rft.issue=11&rft.spage=2109&rft.isbn=&rft.btitle=&rft.title=Stroke&rft.issn=00392499&rft_id=info:doi/ LA - English DB - ProQuest Central N1 - Copyright - Copyright American Heart Association, Inc. Nov 1997 N1 - Last updated - 2014-05-26 N1 - CODEN - SJCCA7 ER - TY - JOUR T1 - Generalized efficacy of t-PA for acute stroke: Subgroup analysis of the NINDS t-PA Stroke Trial AN - 197807186 JF - Stroke AU - NINDS t-PA Stroke Study Group AD - NINDS t-PA Stroke Study Group Y1 - 1997/11// PY - 1997 DA - Nov 1997 SP - 2119 CY - Hagerstown PB - American Heart Association, Inc. VL - 28 IS - 11 SN - 00392499 KW - Medical Sciences--Cardiovascular Diseases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/197807186?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthcompleteshell&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Stroke&rft.atitle=Generalized+efficacy+of+t-PA+for+acute+stroke%3A+Subgroup+analysis+of+the+NINDS+t-PA+Stroke+Trial&rft.au=NINDS+t-PA+Stroke+Study+Group&rft.aulast=NINDS+t-PA+Stroke+Study+Group&rft.aufirst=&rft.date=1997-11-01&rft.volume=28&rft.issue=11&rft.spage=2119&rft.isbn=&rft.btitle=&rft.title=Stroke&rft.issn=00392499&rft_id=info:doi/ LA - English DB - ProQuest Central N1 - Copyright - Copyright American Heart Association, Inc. Nov 1997 N1 - Last updated - 2014-05-26 N1 - CODEN - SJCCA7 ER - TY - JOUR T1 - The structure, function, and regulation of cytochrome P450 2A enzymes AN - 17151259; 4446848 AB - Are there any common structural, functional, or regulatory properties that are characteristic of the cytochrome P450 2A enzymes besides the high identity of the overall amino acid sequences (> 55%)? Can the information accumulated for the CYP2A enzymes be applied to understand the general nature of P450s beyond this subfamily? This review describes recent studies to elucidate what the CYP2A enzymes are, rather than to cover every published study on the CYP2A subfamily. Two recent review articles are available for additional information. JF - Drug Metabolism Reviews AU - Honkakoski, P AU - Negishi, M AD - Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institutes of Health, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA, negishi@niehs.nih.gov Y1 - 1997/11// PY - 1997 DA - Nov 1997 SP - 977 EP - 996 VL - 29 IS - 4 SN - 0360-2532, 0360-2532 KW - cytochrome P4502A KW - Toxicology Abstracts KW - Drug metabolism KW - Gene regulation KW - Reviews KW - Enzymes KW - X 24250:Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17151259?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Drug+Metabolism+Reviews&rft.atitle=The+structure%2C+function%2C+and+regulation+of+cytochrome+P450+2A+enzymes&rft.au=Honkakoski%2C+P%3BNegishi%2C+M&rft.aulast=Honkakoski&rft.aufirst=P&rft.date=1997-11-01&rft.volume=29&rft.issue=4&rft.spage=977&rft.isbn=&rft.btitle=&rft.title=Drug+Metabolism+Reviews&rft.issn=03602532&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - SuppNotes - Issue includes special section on the North Jersey ACS Drug Metabolism Discussion Group Symposium. N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Reviews; Enzymes; Gene regulation; Drug metabolism ER - TY - JOUR T1 - Specificity of an Escherichia coli RNA polymerase-associated NTPase AN - 16384564; 4270765 AB - Standard preparations of Escherichia coli RNA polymerase harbor a 70 kDa protein with NTPase ( beta - gamma cleavage) activity that is not a recognized polymerase subunit. The NTPase activity of this component, before and after separation from the polymerase, is strongly dependent on the presence of DNA; single-stranded polydeoxynucleotides are more effective than double-stranded. ATP and GTP are cleaved, the latter much less readily. The NTPase as it occurs with the polymerase displays cleavage preference for NTPs that are not complementary to the DNA, a fact that has led to proposals for involvement of the NTPase in transcriptional error prevention [Volloch, V. Z., Rits, L. & Tumerman, L. (1979) Nucleic Acids Res. 6, 1535-1546; Libby, R. T., Nelson, J. L., Calvo, J. M., & Gallant, J. A. (1989) EMBO J. 8, 3253-3158]. We find, however, that the lesser cleavage in the presence of complementary DNA results from competition for the NTP between the processes of incorporation by the polymerase and of cleavage by the NTPase, operating on the same substrate pool. The greater cleavage with noncomplementary DNA occurs because of the lack of incorporation by the polymerase, which then does not compete with the NTpase for the substrate pool. Thus, these findings indicate that the cleavage preference of the NTPase for noncomplementary NTPs is not part of a mechanism for error prevention during transcription. JF - Biochemistry (Washington) AU - Butzow, J J AU - Garland, C AU - Van Lee, L AU - Eichhorn, G L AD - National Institutes of Health, National Institute on Aging, Gerontology Research Center, Bayview Campus, Baltimore, MD 21224, USA Y1 - 1997/11// PY - 1997 DA - Nov 1997 SP - 14794 EP - 14798 VL - 36 IS - 47 SN - 0006-2960, 0006-2960 KW - NTPase KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - N 14721:RNA polymerases KW - J 02728:Enzymes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16384564?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemistry+%28Washington%29&rft.atitle=Specificity+of+an+Escherichia+coli+RNA+polymerase-associated+NTPase&rft.au=Butzow%2C+J+J%3BGarland%2C+C%3BVan+Lee%2C+L%3BEichhorn%2C+G+L&rft.aulast=Butzow&rft.aufirst=J&rft.date=1997-11-01&rft.volume=36&rft.issue=47&rft.spage=14794&rft.isbn=&rft.btitle=&rft.title=Biochemistry+%28Washington%29&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - An early step in Pseudomonas exotoxin action is removal of the terminal lysine residue, which allows binding to the KDEL receptor AN - 16337170; 4270754 AB - During the intoxication process, Pseudomonas exotoxin (PE) and immunotoxins containing PE internalize into the target cell and become processed into two fragments, and the carboxyl fragment translocates into the cytosol where it inactivates elongation factor 2. We have proposed that after internalization into cells the carboxyl-terminal fragment of PE (amino acids 280-613), which ends in REDLK, binds to the KDEL receptor (ERD2) which carries it to the endoplasmic reticulum, from which the PE fragment translocates to the cytosol. Earlier experiments showing that REDL but not REDLK binds to the KDEL receptor suggested that the terminal lysine is removed sometime during the intoxication process. To determine if and where this occurs, we exposed a peptide ending in REDLK to malignant cells in culture and found that binding to the KDEL receptor was restored. Restoration of receptor binding also occurred if a peptide or toxin ending in REDLK at its carboxyl terminus was incubated with plasma, indicating that the terminal lysine is removed prior to entry of the toxin into the cell. We conclude that plasma carboxypeptidase(s) cleave(s) the lysine residue from the carboxyl terminus of PE and PE-containing immunotoxins as an early and essential step in their cellular intoxication pathway. JF - Biochemistry (Washington) AU - Hessler, J L AU - Kreitman, R J AD - Laboratory of Molecular Biology, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, 37/4E16, 37 Convent Drive, MSC 4255, Bethesda, MD 20892, USA Y1 - 1997/11// PY - 1997 DA - Nov 1997 SP - 14577 EP - 14582 VL - 36 IS - 47 SN - 0006-2960, 0006-2960 KW - Toxicology Abstracts; Microbiology Abstracts B: Bacteriology KW - X 24171:Microbial KW - J 02823:In vitro and in vivo effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16337170?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemistry+%28Washington%29&rft.atitle=An+early+step+in+Pseudomonas+exotoxin+action+is+removal+of+the+terminal+lysine+residue%2C+which+allows+binding+to+the+KDEL+receptor&rft.au=Hessler%2C+J+L%3BKreitman%2C+R+J&rft.aulast=Hessler&rft.aufirst=J&rft.date=1997-11-01&rft.volume=36&rft.issue=47&rft.spage=14577&rft.isbn=&rft.btitle=&rft.title=Biochemistry+%28Washington%29&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Intermediate-size trials for the evaluation of HIV vaccine candidates: A workshop summary. AN - 16333035; 4264877 AB - There has been considerable debate over what evidence from preclinical and clinical studies is required to advance an HIV vaccine candidate to phase III efficacy testing. Given this situation, conduct of intermediate-size trials is proposed as a method for assessing the plausibility that a vaccine candidate would prevent chronic HIV infection. Designed to observe 45 incident infections in the control group, these preliminary efficacy trials could rule out candidates with low or no efficacy while advancing those candidates with some evidence of protection to definitive trials. In addition, these trials could provide clues about correlates of immunity. A threefold or greater difference in the postvaccination geometric mean titer of neutralizing antibody can be readily detected between infected and uninfected vaccinees. Differences in CD8 super(+) cytotoxic T lymphocytes, however, are more difficult to detect. Intermediate-size trials could also discern a 0.5 log10 or greater difference in plasma HIV-1 RNA levels between infected vaccinees and infected controls. Such differences in viral load might suggest disease amelioration or reduction in infectiousness. Given the large variability in CD4 count and its relatively modest average decline in the year after infection, a slower decline in CD4 count among infected vaccinees would not be detectable. With limited resources, intermediate-size trials could contribute significantly to HIV vaccine development. JF - Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology AU - Rida, W AU - Fast, P AU - Hoff, R AU - Fleming, T AD - Biostatistics Research Branch, Division of AIDS, NIAID, Solar Building, 2A02, Bethesda, MD 20892-7620, USA Y1 - 1997/11// PY - 1997 DA - Nov 1997 SP - 195 EP - 203 VL - 16 IS - 3 SN - 1077-9450, 1077-9450 KW - CD4 antigen KW - CD8 antigen KW - HIV KW - disease control KW - human immunodeficiency virus KW - infection KW - vaccines KW - Immunology Abstracts; Microbiology Abstracts A: Industrial & Applied Microbiology; Virology & AIDS Abstracts KW - F 06807:Active immunization KW - A 01097:Viruses KW - V 22003:AIDS: Immunological aspects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16333035?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologya&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Acquired+Immune+Deficiency+Syndromes+and+Human+Retrovirology&rft.atitle=Intermediate-size+trials+for+the+evaluation+of+HIV+vaccine+candidates%3A+A+workshop+summary.&rft.au=Rida%2C+W%3BFast%2C+P%3BHoff%2C+R%3BFleming%2C+T&rft.aulast=Rida&rft.aufirst=W&rft.date=1997-11-01&rft.volume=16&rft.issue=3&rft.spage=195&rft.isbn=&rft.btitle=&rft.title=Journal+of+Acquired+Immune+Deficiency+Syndromes+and+Human+Retrovirology&rft.issn=10779450&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Retrovirus-mediated gene transfer of ornithine- delta -aminotransferase into keratinocytes from gyrate atrophy patients AN - 16314515; 4252591 AB - Gyrate atrophy is a progressive blindness associated with deficiency of ornithine aminotransferase (OAT). The strategy of using an autologous keratinocyte graft, modified to express high levels of OAT as an ornithine-catabolizing skin-based enzyme sink, is investigated. Two OAT-containing retroviral vectors were constructed with or without a resistance gene. When packaged in a retroviral vector particle generated with the gibbon ape leukemia (GALV) virus envelope (PG13), these vectors could readily transduce >50% of target kerantinocytes. The transduced keratinocytes in culture expressed up to 75-fold more OAT than normal control keratinocytes and these gene-modified cells extracted [ super(14)C]ornithine more efficiently than controls. The vector prepared without neo transduced cells more efficiently and led to higher levels of OAT expression than the neo-containing vector. Ornithine catabolism was maintained at high levels when the transduced patient keratinocytes were differentiated in vitro as a multilayered cutaneous organoid. JF - Human Gene Therapy AU - Jensen, T G AU - Sullivan, D M AU - Morgan, R A AU - Taichman, L B AU - Nussenblatt, R B AU - Blaese, R M AU - Csaky, K G AD - National Institutes of Health, Bldg. 10, Rm. 10N119, 9000 Rockville Pk., Bethesda, MD 20892-1858, USA Y1 - 1997/11// PY - 1997 DA - Nov 1997 SP - 2125 EP - 2132 VL - 8 IS - 17 SN - 1043-0342, 1043-0342 KW - blindness KW - gene transfer KW - gyrate atrophy KW - keratinocytes KW - man KW - ornithine transaminase KW - ornithine- delta -aminotransferase KW - retrovirus KW - Biotechnology and Bioengineering Abstracts; Genetics Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - G 07443:Gene therapy KW - W 30965:Miscellaneous, Reviews KW - W3 33180:Gene based (protocols, clinical trials, and animal models) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16314515?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+Gene+Therapy&rft.atitle=Retrovirus-mediated+gene+transfer+of+ornithine-+delta+-aminotransferase+into+keratinocytes+from+gyrate+atrophy+patients&rft.au=Jensen%2C+T+G%3BSullivan%2C+D+M%3BMorgan%2C+R+A%3BTaichman%2C+L+B%3BNussenblatt%2C+R+B%3BBlaese%2C+R+M%3BCsaky%2C+K+G&rft.aulast=Jensen&rft.aufirst=T&rft.date=1997-11-01&rft.volume=8&rft.issue=17&rft.spage=2125&rft.isbn=&rft.btitle=&rft.title=Human+Gene+Therapy&rft.issn=10430342&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Natural killer cell lines kill autologous beta sub(2)-microglobulin-deficient melanoma cells: Implications for cancer immunotherapy AN - 16314203; 4252610 AB - Cancer vaccines used to generate specific cytotoxic T lymphocytes are not effective against tumor cells that have lost or suppressed expression of their class I major histocompatibility complex proteins. This loss is common in some cancers and particularly in metastatic lesions. We show that beta sub(2)-microglobulin-deficient class I-negative melanoma variants derived from patients undergoing specific T cell therapy are lysed by heterologous as well as autologous natural killer (NK) lines and clones, but not by specific T cells. Moreover, the minor NK cell fraction but not the major T cell fraction derived from heterologous lymphokine activated killer cells kills those tumor cell lines. ICAM-1 expression by the different class I protein deficient tumors was correlated with their sensitivity to lysis by NK cells. Adoptive autologous NK therapy may be an important supplement to consider in the design of new cancer immunotherapies. JF - Proceedings of the National Academy of Sciences, USA AU - Porgador, A AU - Mandelboim, O AU - Restifo, N P AU - Strominger, J L AD - Lymphocyte Biology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, Division of Cancer Treatment, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA Y1 - 1997/11// PY - 1997 DA - Nov 1997 SP - 13140 EP - 13145 VL - 94 IS - 24 SN - 0027-8424, 0027-8424 KW - beta 2-microglobulin KW - adoptive transfer KW - class I molecules KW - immunotherapy KW - major histocompatibility complex KW - melanoma KW - natural killer cells KW - Biotechnology and Bioengineering Abstracts; Immunology Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - F 06818:Cancer immunotherapy KW - W3 33170:Cellular based KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16314203?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.atitle=Natural+killer+cell+lines+kill+autologous+beta+sub%282%29-microglobulin-deficient+melanoma+cells%3A+Implications+for+cancer+immunotherapy&rft.au=Porgador%2C+A%3BMandelboim%2C+O%3BRestifo%2C+N+P%3BStrominger%2C+J+L&rft.aulast=Porgador&rft.aufirst=A&rft.date=1997-11-01&rft.volume=94&rft.issue=24&rft.spage=13140&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Semliki Forest virus-mediated production of retroviral vector RNA in retroviral packaging cells AN - 16311525; 4252583 AB - Retroviral vectors are efficient tools for gene transfer studies. Their major advantage is that they can permanently integrate the transgene into the target cell's genome. However, because of the compulsory nuclear expression phase of their life cycle, it can be difficult for retroviruses to carry complex expression cassettes. In a attempt to mimic the structural features of most eukaryotic genes and obtain a potentially self-amplifying system for retrovirus production, we tested the feasibility of Semliki Forest virus (SFV) expression to mediate cytoplasmic synthesis of retrovirus vector RNA. An equivalent of a retrovirus virion RNA (retrovirus vector cassette, RVC) was cloned under the SFV 26S promoter, and full-length chimeric SFV-RVC RNA was produced in vitro. This RNA was introduced into retrovirus packaging cells, either via electroporation or transduction in SFV virions, and supernatants were analyzed for the presence of biologically active retroviruses. We demonstrate that this strategy can be used for cytoplasmic retrovirus production. The resulting viral particles are fully functional; they can transduce target cells, undergo reverse transcription, and integrate into genomic DNA. We also demonstrate that the SFV virion-based RVC delivery into packaging cells can yield high transient titers, in this case more than 10 super(5) G418 super(R) cfu/ml. This study shows that a simple, oneplasmid, heterologous viral RNA production system can be used to create functional retroviral RNA outside the cell nucleus. JF - Human Gene Therapy AU - Wahlfors, J J AU - Xanthopoulos, K G AU - Morgan, R A AD - Clinical Gene Therapy Branch, National Human Genome Research Institute, National Institutes of Health, Building 10, Room 10C103, Bethesda, MD 20892-1851, USA Y1 - 1997/11// PY - 1997 DA - Nov 1997 SP - 2031 EP - 2041 VL - 8 IS - 17 SN - 1043-0342, 1043-0342 KW - Semliki Forest virus KW - expression vectors KW - packaging cells KW - retrovirus KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - W 30965:Miscellaneous, Reviews KW - W3 33182:Packaging cell lines for gene therapy vectors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16311525?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+Gene+Therapy&rft.atitle=Semliki+Forest+virus-mediated+production+of+retroviral+vector+RNA+in+retroviral+packaging+cells&rft.au=Wahlfors%2C+J+J%3BXanthopoulos%2C+K+G%3BMorgan%2C+R+A&rft.aulast=Wahlfors&rft.aufirst=J&rft.date=1997-11-01&rft.volume=8&rft.issue=17&rft.spage=2031&rft.isbn=&rft.btitle=&rft.title=Human+Gene+Therapy&rft.issn=10430342&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - The effects of perinatal/juvenile methoxychlor exposure on adult rat nervous, immune, and reproductive system function AN - 16307699; 4243910 AB - In order to address data gaps identified by the NAS report Pesticides in the Diets of Infants and Children, a study was performed using methoxychlor (MXC). Female rats were gavaged with MXC at 0, 5, 50, or 150 mg/kg/day for the week before and the week after birth, whereupon the pups were directly dosed with MXC from postnatal day (pnd) 7. Some dams were killed pnd7 and milk and plasma were assayed for MXC and metabolites. For one cohort of juveniles, treatment stopped at pnd21; a modified functional observational battery was used to assess neurobehavioral changes. Other cohorts of juveniles were dosed until pnd42 and evaluated for changes to the immune system and for reproductive toxicity. Dose-dependent amounts of MXC and metabolites were present in milk and plasma of dams and pups. The high dose of MXC reduced litter size by approximately 17%. Ano-genital distance was unchanged, although vaginal opening was accelerated in all treated groups, and male prepuce separation was delayed at the middle and high doses by 8 and 34 days, respectively. In the neurobehavioral evaluation, high-dose males were more excitable, but other changes were inconsistent and insubstantial. A decrease in the antibody plaque-forming cell response was seen in males only. Adult estrous cyclicity was disrupted at 50 and 150 MXC, doses which also showed reduced rates of pregnancy and delivery. Uterine weights (corrected for pregnancy) were reduced in all treated pregnant females. High-dose males impregnated fewer untreated females; epididymal sperm count and testis weight were reduced at the high, or top two, doses, respectively. All groups of treated females showed uterine dysplasias and less mammary alveolar development; estrous levels of follicle stimulating hormone were lower in all treated groups, and estrus progesterone levels were lower at 50 and 150 MXC, attributed to fewer corpora lutea secondary to ovulation defects. These data collectively show that the primary adult effects of early exposure to MXC are reproductive, show that 5 mg/kg/day is not a NO(A)EL in rats with this exposure paradigm (based on changes in day of vaginal opening, pubertal ovary weights, adult uterine and seminal vesicle weights, and female hormone data) and imply that the sites of action are both central and peripheral. JF - Fundamental and Applied Toxicology AU - Chapin, R E AU - Harris, M W AU - Davis, B J AU - Ward, S M AU - Wilson, R E AU - Mauney, MA AU - Lockhart, A C AU - Smialowicz, R J AU - Moser, V C AU - Burka, L T AU - Collins, B J AD - Reprod. Toxicol. Group, Natl. Toxicol. Prog., NIEHS, MD B3-05, P.O. Box 12233, RTP, NC 27709, USA Y1 - 1997/11// PY - 1997 DA - Nov 1997 SP - 138 EP - 157 VL - 40 IS - 1 SN - 0272-0590, 0272-0590 KW - immune system KW - methoxychlor KW - nervous system KW - pesticides KW - rats KW - reproduction KW - Toxicology Abstracts KW - X 24134:Pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16307699?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Fundamental+and+Applied+Toxicology&rft.atitle=The+effects+of+perinatal%2Fjuvenile+methoxychlor+exposure+on+adult+rat+nervous%2C+immune%2C+and+reproductive+system+function&rft.au=Chapin%2C+R+E%3BHarris%2C+M+W%3BDavis%2C+B+J%3BWard%2C+S+M%3BWilson%2C+R+E%3BMauney%2C+MA%3BLockhart%2C+A+C%3BSmialowicz%2C+R+J%3BMoser%2C+V+C%3BBurka%2C+L+T%3BCollins%2C+B+J&rft.aulast=Chapin&rft.aufirst=R&rft.date=1997-11-01&rft.volume=40&rft.issue=1&rft.spage=138&rft.isbn=&rft.btitle=&rft.title=Fundamental+and+Applied+Toxicology&rft.issn=02720590&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Design and discovery of HIV-1 integrase inhibitors AN - 16291014; 4289793 AB - The rapid emergence of human immunodeficiency virus (HIV) strains resistant to available drugs implies that effective treatment modalities will require the use of a combination of drugs targeting different sites of the HIV life cycle. Integrase is emerging as a novel target for intervention by chemotherapeutics. As part of a program to develop novel antiviral agents, we have studied a large number of compounds with activity against HIV-1 replication in the National Cancer Institute (NCI) Antiviral Drug Program. In this review, we present a comprehensive review of all such inhibitors reported to date. JF - Drug Discovery Today AU - Neamati, N AU - Sunder, S AU - Pommier, Y AD - Laboratory of Molecular Pharmacology, Division of Basic Sciences, National Cancer Institute, Building 37, Room 5C25, Bethesda, MD 20892-4255, USA Y1 - 1997/11// PY - 1997 DA - Nov 1997 SP - 487 EP - 498 VL - 2 IS - 11 SN - 1359-6446, 1359-6446 KW - HIV-1 KW - human immunodeficiency virus 1 KW - integrase inhibitors KW - reviews KW - Biotechnology and Bioengineering Abstracts; Virology & AIDS Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - V 22100:Antiviral agents KW - W3 33372:Antiviral agents KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16291014?accountid=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=Drug+Discovery+Today&rft.atitle=Design+and+discovery+of+HIV-1+integrase+inhibitors&rft.au=Neamati%2C+N%3BSunder%2C+S%3BPommier%2C+Y&rft.aulast=Neamati&rft.aufirst=N&rft.date=1997-11-01&rft.volume=2&rft.issue=11&rft.spage=487&rft.isbn=&rft.btitle=&rft.title=Drug+Discovery+Today&rft.issn=13596446&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Immunization with a Syngeneic Tumor Infected with Recombinant Vaccinia Virus Expressing Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) Induces Tumor Regression and Long-Lasting Systemic Immunity AN - 16274927; 4261567 AB - A recombinant vaccinia virus encoding the gene for granulocyte-macrophage colony-stimulating factor (rV-GM-CSF) was used to infect the poorly immunogenic murine colon adenocarcinoma cell line, MC-38. Infection of MC-38 tumor cells with rV-GM-CSF completely suppressed the growth of the MC-38 primary tumors, whereas progressively growing tumors were formed in mice injected with MC-38 cells infected with wild type V-Wyeth. Irradiation of the recipient B6 mice before implantation of rV-GM-CSF-infected tumor cells resulted in the development of progressively growing tumors. Moreover, in vivo T-cell depletion studies revealed that growth suppression of the rV-GM-CSF-infected tumor cells was dependent on the presence of both CD4 super(+) and CD8 super(+) T-cell subsets. Subsequent studies established that this immunity was long-lasting and antigen specific, as demonstrated by the protection of rV-GM-CSF-immunized mice from MC-38 tumor challenge but not from challenge with another syngeneic tumor cell type. No such effects were observed when MC-38 tumor cells were infected with recombinant vaccinia viruses expressing interleukin (IL)-2 or IL-6. The results demonstrate that paracrine release of biologically active murine GM-CSF by tumor cells infected with rV-GM-CSF enhances the intrinsic immunogenicity of a poorly immunogenic murine tumor. Presumably the augmentation of tumor immunogenicity induces an antigen-specific T-cell-dependent antitumor response that prevents the formation of primary tumors and protects mice from tumor challenge. Thus in this experimental model, GM-CSF functions as a highly effective vaccine adjuvant. JF - Journal of Immunotherapy with Emphasis on Tumor Biology AU - McLaughlin, J P AU - Abrams, S AU - Kantor, J AU - Dobrzanski, MJ AU - Greenbaum, J AU - Schlom, J AU - Greiner, J W AD - Laboratory of Tumor Immunology and Biology, National Cancer Institute, National Institutes of Health, Room 8B07, Building 10, Bethesda, MD 20892, USA Y1 - 1997/11// PY - 1997 DA - Nov 1997 SP - 449 EP - 459 VL - 20 IS - 6 SN - 1053-8550, 1053-8550 KW - cancer vaccines KW - granulocyte-macrophage colony-stimulating factor KW - mice KW - vaccinia virus KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - F 06818:Cancer immunotherapy KW - W3 33350:Cancer vaccines KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16274927?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Immunotherapy+with+Emphasis+on+Tumor+Biology&rft.atitle=Immunization+with+a+Syngeneic+Tumor+Infected+with+Recombinant+Vaccinia+Virus+Expressing+Granulocyte-Macrophage+Colony-Stimulating+Factor+%28GM-CSF%29+Induces+Tumor+Regression+and+Long-Lasting+Systemic+Immunity&rft.au=McLaughlin%2C+J+P%3BAbrams%2C+S%3BKantor%2C+J%3BDobrzanski%2C+MJ%3BGreenbaum%2C+J%3BSchlom%2C+J%3BGreiner%2C+J+W&rft.aulast=McLaughlin&rft.aufirst=J&rft.date=1997-11-01&rft.volume=20&rft.issue=6&rft.spage=449&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immunotherapy+with+Emphasis+on+Tumor+Biology&rft.issn=10538550&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Lack of correlation between hepatic prostaglandin concentrations and DNA synthesis after the administration of phenobarbital and the peroxisome proliferator ciprofibrate in rats AN - 16239669; 4225489 AB - Peroxisome proliferators are a class of chemicals that induce and promote hepatic tumors in rodents. These compounds are not genotoxic, and the mechanism by which they induce and promote tumors is poorly understood. Phenobarbital (PB) also is a hepatic tumor promoter that produces a different natural history than peroxisome proliferators during the promotion of hepatocarcinogenesis. In addition, opposite effects on hepatic eicosanoid concentrations have been demonstrated previously. In this experiment, we examined whether higher hepatic eicosanoid concentrations correlated with the induction of DNA synthesis after the administration of PB or the peroxisome proliferator ciprofibrate (CIP). PB (0.05% in diet) or CIP (0.01% in diet) was fed to rats from 1-10 days. For the rats treated with CIP, the peroxisomal enzyme fatty acyl-CoA oxidase increased gradually from day 1 to day 10. PB treated rats had a higher cytochrome P450 2B1/2 activity over the entire course of feeding. Hepatic prostaglandins E sub(2) and F sub(2 alpha ) concentrations were significantly reduced in the rats treated with CIP, while no significant differences were seen between the control and PB-treated rats. DNA synthesis was increased in both PB-treated and CIP-treated rats. These results show that higher eicosanoid concentrations do not correlate with the induction of hepatic DNA synthesis by CIP or PB. JF - Toxicology AU - Leung, L K AU - Glauert, H P AD - National Cancer Institute, Laboratory of Nutritional and Molecular Regulation, Frederick, MD 21702, USA Y1 - 1997/11// PY - 1997 DA - Nov 1997 SP - 101 EP - 109 VL - 123 IS - 1-2 SN - 0300-483X, 0300-483X KW - Ciprofibrate KW - DNA biosynthesis KW - Liver KW - Phenobarbital KW - Prostaglandins KW - eicosanoids KW - peroxisome proliferators KW - rats KW - Toxicology Abstracts KW - X 24240:Miscellaneous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16239669?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology&rft.atitle=Lack+of+correlation+between+hepatic+prostaglandin+concentrations+and+DNA+synthesis+after+the+administration+of+phenobarbital+and+the+peroxisome+proliferator+ciprofibrate+in+rats&rft.au=Leung%2C+L+K%3BGlauert%2C+H+P&rft.aulast=Leung&rft.aufirst=L&rft.date=1997-11-01&rft.volume=123&rft.issue=1-2&rft.spage=101&rft.isbn=&rft.btitle=&rft.title=Toxicology&rft.issn=0300483X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Transient gene expression from yeast artificial chromosome DNA in mammalian cells is enhanced by adenovirus AN - 16238945; 4230038 AB - The introduction of high molecular weight DNA into mammalian cells is useful for gene expression studies. However, current transfection strategies are inefficient, necessitating propagation of stable DNA transformants prior to analysis of gene expression. Here we demonstrate that transient lipid-mediated DNA transfection can be used to assess gene expression from yeast artificial chromosomes (YACs) containing the 230 kb cystic fibrosis transmembrane conductance regulator gene (CFTR) and Escherichia coli lacZ. We also show that psoralen-UV inactivated adenovirus significantly enhances transfection efficiency. The ability to deliver high molecular weight DNA using lipid-mediated transfection should expedite the analysis of large human genes contained within artificial chromosome vectors. JF - Nucleic Acids Research AU - Chen, Min AU - Compton, ST AU - Coviello, V F AU - Green, ED AU - Ashlock, MA AD - National Human Genome Research Institute, Genetics and Molecular Biology Branch, Building 49, Room 3A76, 49 Convent Drive, MSC 4442, Bethesda, MD 20892, USA Y1 - 1997/11// PY - 1997 DA - Nov 1997 SP - 4416 EP - 4418 VL - 25 IS - 21 SN - 0305-1048, 0305-1048 KW - CFTR gene KW - adenovirus KW - lipids KW - transfection KW - yeast artificial chromosomes KW - Biotechnology and Bioengineering Abstracts; Genetics Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - W3 33243:Molecular methods KW - W 30965:Miscellaneous, Reviews KW - G 07191:Analysis techniques UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16238945?accountid=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=Transient+gene+expression+from+yeast+artificial+chromosome+DNA+in+mammalian+cells+is+enhanced+by+adenovirus&rft.au=Chen%2C+Min%3BCompton%2C+ST%3BCoviello%2C+V+F%3BGreen%2C+ED%3BAshlock%2C+MA&rft.aulast=Chen&rft.aufirst=Min&rft.date=1997-11-01&rft.volume=25&rft.issue=21&rft.spage=4416&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 - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Second cancers after medulloblastoma: Population-based results from the United States and Sweden AN - 16237532; 4225448 AB - Medulloblastoma, one of the most common central nervous system (CNS) tumors in children, requires aggressive multimodality therapy including surgery, radiation therapy, and occasionally chemotherapy. Given its intensive treatment regimen and improved survival during the past 20 years, it is likely that a cohort of survivors will result who may incur consequences of therapy, including a second cancer. We used population-based data from the United States and Sweden to estimate risks of second neoplasms in patients with histologically confirmed medulloblastoma (n = 1,262). Overall, there was a 5.4-fold excess of second neoplasms (95 percent confidence interval = 3.3-8.4) based on 20 observed and 3.7 expected cancers. The second cancers occurred eight to 432 months after initial diagnosis (median, 73 months) with significantly elevated ratios for all intervals examined except for less than one year after initial diagnosis. Significantly elevated risks were seen for cancers of the salivary glands, cervix uteri, brain and CNS, thyroid gland, and acute lymphoblastic leukemia. Of the 15 second cancers with treatment data, seven occurred in the radiation field or within areas of scatter while two others may have been radiation-related. Although based on small numbers of second cancers, the results suggest that as survival increases, some patients with medulloblastoma will have an increased risk of a second cancer, particularly a radiation-related cancer. Thus, as survival improves, late-occurring consequences of diagnosis and treatment will need to be carefully assessed. Identification of patients hypersensitive to radiation therapy, such as those with Gorlin Syndrome, should also be attempted in order to reduce the sequelae from intensive radiation exposure. JF - Cancer Causes & Control AU - Goldstein, A M AU - Yuen, J AU - Tucker, MA AD - Genetic Epidemiology Branch, National Cancer Institute, Executive Plaza North, Room 439, 6130 Executive Blvd. MSC 7372, Bethesda, MD 20892-7372, USA Y1 - 1997/11// PY - 1997 DA - Nov 1997 SP - 865 EP - 871 VL - 8 IS - 6 SN - 0957-5243, 0957-5243 KW - Cancer KW - Children KW - Radiotherapy KW - Risk assessment KW - Sweden KW - USA KW - man KW - medulloblastoma KW - relapses KW - survival KW - Toxicology Abstracts KW - X 24221:Toxicity testing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16237532?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Causes+%26+Control&rft.atitle=Second+cancers+after+medulloblastoma%3A+Population-based+results+from+the+United+States+and+Sweden&rft.au=Goldstein%2C+A+M%3BYuen%2C+J%3BTucker%2C+MA&rft.aulast=Goldstein&rft.aufirst=A&rft.date=1997-11-01&rft.volume=8&rft.issue=6&rft.spage=865&rft.isbn=&rft.btitle=&rft.title=Cancer+Causes+%26+Control&rft.issn=09575243&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Detoxified lipooligosaccharide from nontypeable Haemophilus influenzae conjugated to proteins confers protection against otitis media in chinchillas AN - 16226988; 4225051 AB - Detoxified-lipooligosaccharide (dLOS)-protein conjugates from nontypeable Haemophilus influenzae (NTHi) elicited a significant rise of anti-LOS antibodies with bactericidal activity in rabbits. In this study, we evaluated whether vaccination with the conjugates would protect against NTHi otitis media in chinchillas. Fifty-eight chinchillas received three subcutaneous or intramuscular injections of dLOS-conjugated tetanus toxoid, dLOS-conjugated high-molecular-weight proteins from NTHi, or saline (control) in Freund's adjuvant and then were challenged by intrabullar inoculation with 140 CFU of NTHi. All vaccinated animals responded with elevated serum titers of anti-LOS antibody, and 49% (19 of 39) demonstrated bactericidal activity against the homologous strain. Otitis media with culture-positive NTHi effusions developed in all 19 controls and 56% (22 of 39) of the vaccinated animals during a period of 21 days. Bacterial counts of the middle ear effusions were lower in the vaccine groups than in the controls. The incidences of infection in the unchallenged ear or inner ear were 26 or 28% in the vaccine groups and 53 or 58% in the controls. The signs of infection observed by otoscopy were less severe in the vaccine groups than in the controls. There was no significant difference between the two vaccine groups. These data indicate that active immunization with LOS-based conjugates reduces the incidence of NTHi-induced otitis media. JF - Infection and Immunity AU - Gu, Xin-Xing AU - Sun, Jianzhong AU - Jin, Sunji AU - Barenkamp, S J AU - Lim, D J AU - Robbins, J B AU - Battey, J AD - NIDCD, NIH, 5 Research Court, Rockville, MD 20850, USA Y1 - 1997/11// PY - 1997 DA - Nov 1997 SP - 4488 EP - 4493 VL - 65 IS - 11 SN - 0019-9567, 0019-9567 KW - Animal models KW - Detoxification KW - Haemophilus influenzae KW - Otitis media KW - Proteins KW - Vaccination KW - chinchillas KW - lipooligosaccharides KW - proteins KW - Immunology Abstracts; Microbiology Abstracts B: Bacteriology KW - J 02834:Vaccination and immunization KW - F 06807:Active immunization UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16226988?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Infection+and+Immunity&rft.atitle=Detoxified+lipooligosaccharide+from+nontypeable+Haemophilus+influenzae+conjugated+to+proteins+confers+protection+against+otitis+media+in+chinchillas&rft.au=Gu%2C+Xin-Xing%3BSun%2C+Jianzhong%3BJin%2C+Sunji%3BBarenkamp%2C+S+J%3BLim%2C+D+J%3BRobbins%2C+J+B%3BBattey%2C+J&rft.aulast=Gu&rft.aufirst=Xin-Xing&rft.date=1997-11-01&rft.volume=65&rft.issue=11&rft.spage=4488&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Construction and enhanced cytotoxicity of a [cyanovirin-N]-[Pseudomonas exotoxin] conjugate against human immunodeficiency virus-infected cells. AN - 79426491; 9367864 AB - Cyanovirin-N (CV-N) is a novel 11-kDa anti-HIV(human immunodeficiency virus) protein that binds with high affinity to the viral envelope glycoprotein gp120. In contrast to soluble CD4 and most known neutralizing antibodies that bind gp120, CV-N exerts potent anti-viral activity against primary clinical HIV isolates as well as laboratory-adapted strains of HIV. Here we describe the recombinant production, purification, and characterization of a chimeric toxin molecule, FLAG-CV-N-PE38, that contains CV-N as a gp120-targeting moiety linked to the translocation and cytotoxic domains of Pseudomonas exotoxin A. FLAG-CV-N-PE38 showed enhanced cytotoxicity to HIV-infected, gp120-expressing H9 cells compared to uninfected H9 cells. Competition experiments with free CV-N provided further support that the enhanced FLAG-CV-N-PE38-induced cytotoxicity was due to interactions of the CV-N moiety with cell surface gp120. This study establishes the feasibility of use of CV-N as a gp120-targeting sequence for construction and experimental therapeutic investigations of unique new chimeric toxins designed to selectively destroy HIV-infected host cells. JF - Biochemical and biophysical research communications AU - Mori, T AU - Shoemaker, R H AU - McMahon, J B AU - Gulakowski, R J AU - Gustafson, K R AU - Boyd, M R AD - Laboratory of Drug Discovery Research and Development, National Cancer Institute, Frederick, Maryland 21702-1201, USA. Y1 - 1997/10/29/ PY - 1997 DA - 1997 Oct 29 SP - 884 EP - 888 VL - 239 IS - 3 SN - 0006-291X, 0006-291X KW - Anti-HIV Agents KW - 0 KW - Bacterial Proteins KW - Bacterial Toxins KW - Carrier Proteins KW - Exotoxins KW - HIV Envelope Protein gp120 KW - Recombinant Fusion Proteins KW - Virulence Factors KW - cyanovirin N KW - 184539-38-6 KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - toxA protein, Pseudomonas aeruginosa KW - EC 2.4.2.31 KW - Index Medicus KW - AIDS/HIV KW - Leukemia KW - Tumor Cells, Cultured KW - Humans KW - Enzyme-Linked Immunosorbent Assay KW - Plasmids KW - HIV Envelope Protein gp120 -- biosynthesis KW - Anti-HIV Agents -- chemistry KW - Anti-HIV Agents -- toxicity KW - Exotoxins -- genetics KW - Pseudomonas aeruginosa -- genetics KW - Carrier Proteins -- chemistry KW - Carrier Proteins -- genetics KW - Carrier Proteins -- toxicity KW - Exotoxins -- chemistry KW - Recombinant Fusion Proteins -- toxicity KW - Recombinant Fusion Proteins -- chemistry KW - Anti-HIV Agents -- chemical synthesis KW - Exotoxins -- toxicity KW - HIV-1 -- drug effects KW - Recombinant Fusion Proteins -- chemical synthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79426491?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Construction+and+enhanced+cytotoxicity+of+a+%5Bcyanovirin-N%5D-%5BPseudomonas+exotoxin%5D+conjugate+against+human+immunodeficiency+virus-infected+cells.&rft.au=Mori%2C+T%3BShoemaker%2C+R+H%3BMcMahon%2C+J+B%3BGulakowski%2C+R+J%3BGustafson%2C+K+R%3BBoyd%2C+M+R&rft.aulast=Mori&rft.aufirst=T&rft.date=1997-10-29&rft.volume=239&rft.issue=3&rft.spage=884&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 - 1997-12-12 N1 - Date created - 1997-12-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evaluation of beta-tethymustine, a new anticancer compound, in murine tumour models. AN - 79652496; 18372515 AB - beta-Tethymustine, 1-[2- {bis(2'-chloroethyl)amino}ethyl]spiro[imidazolidine-4,2'-(1'H),3',4'-dihydronaphthalene]-2,5-dione, has been synthesised and LD50 value determined in Swiss male mice, which was found to be 100.00 mg/kg by single i.p. injection. The following three criteria, namely ascites cell count, ascites fluid measurement and increase in median survival times (MST) of drug-treated (T) over untreated control (C) mice, were studied for evaluation of its antitumour efficacy in vivo in three murine ascites tumours, namely Ehrlich ascites carcinoma (EAC), sarcoma-180 (S-180) and Dalton's lymphoma (DL). At the optimum dose range of 8.0 mg/kg (higher) to 4.0 mg/kg (lower) for 1-7 days treatment following tumour transplantation on day 0, it exhibited a very high percentage of inhibition of both the ascites cell and fluid in these models and displayed excellent ILS(max) value of 80 in EAC, 224 in S-180 and 240 in DL, respectively, showing 'curative' effect (2-3/6 mice having 90 days survival rate). It also demonstrated a high ILS value of 150 with one cure/six mice bearing S-180 for 6 days prior to drug therapy. Screening results were compared with two clinical drugs, cyclophosphamide and 5-fluorouracil, serving as positive controls. Its chemical alkylating activity was compared with nor-HN2 (NSC 10873) and spiromustine (NSC 172112). The results indicate that it possesses greater alkylating activity than nor-HN2 and comparable activity with spiromustine. JF - Cancer letters AU - Ghosh, M AU - Bhattacharya, S AU - Sadhu, U AU - Dutta, S AU - Sanyal, U AD - Department of Chemotherapy, Chittaranjan National Cancer Institute, Calcutta 700 026, India. Y1 - 1997/10/28/ PY - 1997 DA - 1997 Oct 28 SP - 7 EP - 12 VL - 119 IS - 1 SN - 0304-3835, 0304-3835 KW - Antineoplastic Agents, Alkylating KW - 0 KW - Imidazolidines KW - Naphthalenes KW - beta-tethymustine KW - Index Medicus KW - Drug Screening Assays, Antitumor KW - Animals KW - Dose-Response Relationship, Drug KW - Lethal Dose 50 KW - Mice KW - Alkylation -- drug effects KW - Male KW - Imidazolidines -- administration & dosage KW - Naphthalenes -- chemistry KW - Naphthalenes -- administration & dosage KW - Imidazolidines -- chemistry KW - Antineoplastic Agents, Alkylating -- administration & dosage KW - Neoplasms, Experimental -- drug therapy KW - Antineoplastic Agents, Alkylating -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79652496?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+beta-tethymustine%2C+a+new+anticancer+compound%2C+in+murine+tumour+models.&rft.au=Ghosh%2C+M%3BBhattacharya%2C+S%3BSadhu%2C+U%3BDutta%2C+S%3BSanyal%2C+U&rft.aulast=Ghosh&rft.aufirst=M&rft.date=1997-10-28&rft.volume=119&rft.issue=1&rft.spage=7&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 - 2008-05-20 N1 - Date created - 2008-03-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Glutamate metabotropic receptor agonist 1S,3R-ACPD induces internucleosomal DNA fragmentation and cell death in rat striatum. AN - 79476106; 9406954 AB - Glutamate metabotropic receptor mediated mechanisms have been implicated in both neuroprotection and neurotoxicity. To characterize these mechanisms further in vivo, the effects of an intrastriatally injected metabotropic receptor agonist, trans-(1S,3R)-1-amino-1,3-cyclopentanedicarboxylic acid (1S,3R-ACPD), were studied alone and together with N-methyl-D-aspartate (NMDA) or kainic acid (KA) receptor agonists on DNA fragmentation and nerve cell death. 1S,3R-ACPD induced internucleosomal DNA fragmentation of striatal cells in a dose-dependent manner. TUNEL and propidium iodide staining showed DNA fragmentation and profound nuclear condensation around the injection site. Fragmented nuclei were occasionally seen under light microscopy. Internucleosomal DNA fragmentation induced by 1S,3R-ACPD was attenuated by the protein synthesis inhibitor cycloheximide as well as by the non-selective and selective metabotropic receptor antagonists L-(+)-2-amino-3-phosphonopionic acid (L-AP3), (RS)-aminoindan-1,5-dicarboxylic acid and (RS)-alpha-methylserine-o-phosphate monophenyl ester, respectively. The 1S,3R-ACPD (100-900 nmol) induced death of striatal neurons was suggested by the reduction in NMDA and D1 dopamine receptors by up to 13% (P < 0.05) and 20% (P < 0.05) as well as by the decline in GAD67 mRNA (25%, P < 0.01) and proenkephalin mRNA levels (35%, P < 0.01). Interestingly, 1S,3R-ACPD attenuated internucleosomal DNA fragmentation induced by NMDA, but potentiated that induced by KA. These results suggest that metabotropic receptor stimulation leads to the death of striatal neurons by a mechanism having the biochemical stigmata of apoptosis. Moreover, metabotropic receptor stimulation evidently exerts opposite effects on pre- or postsynaptic mechanisms contributing to the NMDA and KA-induced apoptotic-like death of these neurons. JF - Brain research AU - Wang, Y AU - Qin, Z H AU - Nakai, M AU - Chase, T N AD - Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892-1406, USA. Y1 - 1997/10/24/ PY - 1997 DA - 1997 Oct 24 SP - 45 EP - 56 VL - 772 IS - 1-2 SN - 0006-8993, 0006-8993 KW - Excitatory Amino Acid Antagonists KW - 0 KW - Neurotoxins KW - Nucleosomes KW - Protein Synthesis Inhibitors KW - Receptors, Metabotropic Glutamate KW - Cycloleucine KW - 0TQU7668EI KW - 1-amino-1,3-dicarboxycyclopentane KW - 111900-32-4 KW - 2-amino-3-phosphonopropionic acid KW - 5652-28-8 KW - Alanine KW - OF5P57N2ZX KW - Index Medicus KW - Rats KW - Histocytochemistry -- methods KW - Animals KW - Alanine -- analogs & derivatives KW - Rats, Sprague-Dawley KW - In Situ Hybridization KW - Protein Synthesis Inhibitors -- pharmacology KW - Electrophoresis, Agar Gel KW - Cell Death -- drug effects KW - Autoradiography KW - Alanine -- pharmacology KW - Excitatory Amino Acid Antagonists -- pharmacology KW - Nucleosomes -- drug effects KW - Cycloleucine -- toxicity KW - Cycloleucine -- analogs & derivatives KW - Receptors, Metabotropic Glutamate -- agonists KW - Neurotoxins -- toxicity KW - DNA Fragmentation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79476106?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Glutamate+metabotropic+receptor+agonist+1S%2C3R-ACPD+induces+internucleosomal+DNA+fragmentation+and+cell+death+in+rat+striatum.&rft.au=Wang%2C+Y%3BQin%2C+Z+H%3BNakai%2C+M%3BChase%2C+T+N&rft.aulast=Wang&rft.aufirst=Y&rft.date=1997-10-24&rft.volume=772&rft.issue=1-2&rft.spage=45&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 - 1998-02-19 N1 - Date created - 1998-02-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetic toxicity studies of 1,2,3,4-tetrahydro-9-acridinamine (tacrine). AN - 79458064; 9393611 AB - The mutagenicity and clastogenicity of 1,2,3,4-tetrahydro-9-acridinamine (tacrine) were studied in vitro using the Salmonella mutagenicity test and the induction of chromosome aberrations in Chinese hamster ovary (CHO) cells, and in the mouse bone marrow micronucleus test in vivo. This chemical is currently being used to treat dementia arising from Alzheimer's Disease. Tacrine was mutagenic in Salmonella but did not produce chromosome damage in CHO cells or in mouse bone marrow cells. A clear mutagenic response was seen in strain TA97 with rat and hamster liver S9; inconsistent results were obtained without S9. No mutagenicity was seen in strains TA98 and TA100 without S9, and inconsistent results were seen with S9. There was no induction of chromosome aberrations in cultured CHO cells with or without S9. Oral administration to mice of tacrine daily for three days did not result in the induction of micronuclei in their bone marrow cells. The mutagenic response in Salmonella, and the structure of the molecule, suggests that tacrine may be carcinogenic when tested in rodents. This information must be considered when preparing benefit-risk determinations for medical uses of this substance. JF - Mutation research AU - Zeiger, E AU - Erexson, G AU - Mortelmans, K AU - Thilagar, A AD - Environmental Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. zeiger@niehs.nih.gov Y1 - 1997/10/24/ PY - 1997 DA - 1997 Oct 24 SP - 189 EP - 197 VL - 393 IS - 3 SN - 0027-5107, 0027-5107 KW - Cholinesterase Inhibitors KW - 0 KW - Tacrine KW - 4VX7YNB537 KW - Index Medicus KW - Rats KW - Bone Marrow Cells -- drug effects KW - Animals KW - Rats, Inbred F344 KW - Mutagenicity Tests KW - CHO Cells -- drug effects KW - Mice KW - Female KW - Cricetinae KW - Tacrine -- toxicity KW - Micronuclei, Chromosome-Defective -- drug effects KW - Cholinesterase Inhibitors -- toxicity KW - Tacrine -- chemistry KW - Cholinesterase Inhibitors -- chemistry KW - Chromosome Aberrations KW - Salmonella typhimurium -- drug effects KW - Salmonella typhimurium -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79458064?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Genetic+toxicity+studies+of+1%2C2%2C3%2C4-tetrahydro-9-acridinamine+%28tacrine%29.&rft.au=Zeiger%2C+E%3BErexson%2C+G%3BMortelmans%2C+K%3BThilagar%2C+A&rft.aulast=Zeiger&rft.aufirst=E&rft.date=1997-10-24&rft.volume=393&rft.issue=3&rft.spage=189&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 - 1997-12-23 N1 - Date created - 1997-12-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Targeted therapy of cancer with recombinant immunotoxins. AN - 79447127; 9395287 JF - Biochimica et biophysica acta AU - Pastan, I AD - Laboratory of Molecular Biology, DBS, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA. pasta@helix.nih.gov Y1 - 1997/10/24/ PY - 1997 DA - 1997 Oct 24 SP - C1 EP - C6 VL - 1333 IS - 2 SN - 0006-3002, 0006-3002 KW - Antibodies, Monoclonal KW - 0 KW - Bacterial Toxins 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 - Humans KW - Escherichia coli -- genetics KW - Recombinant Fusion Proteins -- therapeutic use KW - Antibodies, Monoclonal -- therapeutic use KW - Exotoxins -- genetics KW - Immunotoxins -- therapeutic use KW - Neoplasms -- therapy KW - Exotoxins -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79447127?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Targeted+therapy+of+cancer+with+recombinant+immunotoxins.&rft.au=Pastan%2C+I&rft.aulast=Pastan&rft.aufirst=I&rft.date=1997-10-24&rft.volume=1333&rft.issue=2&rft.spage=C1&rft.isbn=&rft.btitle=&rft.title=Biochimica+et+biophysica+acta&rft.issn=00063002&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-12-15 N1 - Date created - 1997-12-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - An oxidative damage-specific endonuclease from rat liver mitochondria. AN - 79354878; 9341184 AB - Reactive oxygen species have been shown to generate mutagenic lesions in DNA. One of the most abundant lesions in both nuclear and mitochondrial DNA is 7,8-dihydro-8-oxoguanine (8-oxoG). We report here the partial purification and characterization of a mitochondrial oxidative damage endonuclease (mtODE) from rat liver that recognizes and incises at 8-oxoG and abasic sites in duplex DNA. Rat liver mitochondria were purified by differential and Percoll gradient centrifugation, and mtODE was extracted from Triton X-100-solubilized mitochondria. Incision activity was measured using a radiolabeled double-stranded DNA oligonucleotide containing a unique 8-oxoG, and reaction products were separated by polyacrylamide gel electrophoresis. Gel filtration chromatography predicts mtODE's molecular mass to be between 25 and 30 kDa. mtODE has a monovalent cation optimum between 50 and 100 mM KCl and a pH optimum between 7.5 and 8. mtODE does not require any co-factors and is active in the presence of 5 mM EDTA. It is specific for 8-oxoG and preferentially incises at 8-oxoG:C base pairs. mtODE is a putative 8-oxoG glycosylase/lyase enzyme, because it can be covalently linked to the 8-oxoG oligonucleotide by sodium borohydride reduction. Comparison of mtODE's activity with other known 8-oxoG glycosylases/lyases and mitochondrial enzymes reveals that this may be a novel protein. JF - The Journal of biological chemistry AU - Croteau, D L AU - ap Rhys, C M AU - Hudson, E K AU - Dianov, G L AU - Hansford, R G AU - Bohr, V A AD - Laboratory of Molecular Genetics, NIA, National Institutes of Health, Baltimore, Maryland 21224, USA. Y1 - 1997/10/24/ PY - 1997 DA - 1997 Oct 24 SP - 27338 EP - 27344 VL - 272 IS - 43 SN - 0021-9258, 0021-9258 KW - Oligodeoxyribonucleotides KW - 0 KW - 8-hydroxyguanine KW - 5614-64-2 KW - Guanine KW - 5Z93L87A1R KW - Endodeoxyribonucleases KW - EC 3.1.- KW - 3'-phosphoglycoaldehyde diesterase KW - EC 3.1.25.- KW - mitochondrial oxidative damage endonuclease KW - Index Medicus KW - Rats KW - Cell Fractionation KW - Animals KW - Base Sequence KW - Chromatography, Gel KW - Oligodeoxyribonucleotides -- chemistry KW - Rats, Wistar KW - Guanine -- analogs & derivatives KW - Substrate Specificity KW - Oligodeoxyribonucleotides -- metabolism KW - Molecular Weight KW - Male KW - Mitochondria, Liver -- enzymology KW - DNA Repair KW - Endodeoxyribonucleases -- isolation & purification KW - Oxidative Stress KW - Mitochondria, Liver -- ultrastructure KW - Endodeoxyribonucleases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79354878?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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+oxidative+damage-specific+endonuclease+from+rat+liver+mitochondria.&rft.au=Croteau%2C+D+L%3Bap+Rhys%2C+C+M%3BHudson%2C+E+K%3BDianov%2C+G+L%3BHansford%2C+R+G%3BBohr%2C+V+A&rft.aulast=Croteau&rft.aufirst=D&rft.date=1997-10-24&rft.volume=272&rft.issue=43&rft.spage=27338&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 - 1997-11-28 N1 - Date created - 1997-11-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Lyn associates with the juxtamembrane region of c-Kit and is activated by stem cell factor in hematopoietic cell lines and normal progenitor cells. AN - 79354265; 9341198 AB - Stem cell factor (SCF) is a cytokine critical for normal hematopoiesis. The receptor for SCF is c-Kit, a receptor tyrosine kinase. Our laboratory is interested in delineating critical components of the SCF signal transduction pathway in hematopoietic tissue. The present study examines activation of Src family members in response to SCF. Stimulation of cell lines as well as normal progenitor cells with SCF rapidly increased tyrosine phosphorylation of the Src family member Lyn. Peak responses were noted 10-20 min after SCF treatment, and phosphorylation of Lyn returned to basal levels 60-90 min after stimulation. SCF also induced increases in Lyn kinase activity in vitro. Lyn coimmunoprecipitated with c-Kit, and studies with GST fusion proteins demonstrated that Lyn readily associated with the juxtamembrane region of c-Kit. Treatment of cells with either Lyn antisense oligonucleotides or PP1, a Src family inhibitor, resulted in dramatic inhibition of SCF-induced proliferation. These data demonstrate that SCF rapidly activates Lyn and suggest that Lyn is critical in SCF-induced proliferation in hematopoietic cells. JF - The Journal of biological chemistry AU - Linnekin, D AU - DeBerry, C S AU - Mou, S AD - Laboratory of Leukocyte Biology, Division of Basic Sciences, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, Maryland 21702-1201, USA. linnekin@ncifcrf.gov Y1 - 1997/10/24/ PY - 1997 DA - 1997 Oct 24 SP - 27450 EP - 27455 VL - 272 IS - 43 SN - 0021-9258, 0021-9258 KW - Recombinant Fusion Proteins KW - 0 KW - Recombinant Proteins KW - Stem Cell Factor KW - Granulocyte-Macrophage Colony-Stimulating Factor KW - 83869-56-1 KW - Proto-Oncogene Proteins c-kit KW - EC 2.7.10.1 KW - lyn protein-tyrosine kinase KW - EC 2.7.10.2 KW - src-Family Kinases KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Recombinant Fusion Proteins -- biosynthesis KW - Recombinant Proteins -- pharmacology KW - Enzyme Activation KW - Humans KW - Cell Division -- drug effects KW - Recombinant Fusion Proteins -- isolation & purification KW - Granulocyte-Macrophage Colony-Stimulating Factor -- pharmacology KW - Binding Sites KW - Recombinant Fusion Proteins -- metabolism KW - Phosphorylation KW - Cells, Cultured KW - Kinetics KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Cell Membrane -- metabolism KW - Cell Line KW - Proto-Oncogene Proteins c-kit -- metabolism KW - Proto-Oncogene Proteins c-kit -- isolation & purification KW - Liver -- cytology KW - Proto-Oncogene Proteins c-kit -- chemistry KW - src-Family Kinases -- metabolism KW - Stem Cell Factor -- pharmacology KW - Hematopoietic Stem Cells -- cytology KW - Hematopoietic Stem Cells -- metabolism KW - Liver -- embryology KW - src-Family Kinases -- isolation & purification KW - src-Family Kinases -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79354265?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Lyn+associates+with+the+juxtamembrane+region+of+c-Kit+and+is+activated+by+stem+cell+factor+in+hematopoietic+cell+lines+and+normal+progenitor+cells.&rft.au=Linnekin%2C+D%3BDeBerry%2C+C+S%3BMou%2C+S&rft.aulast=Linnekin&rft.aufirst=D&rft.date=1997-10-24&rft.volume=272&rft.issue=43&rft.spage=27450&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 - 1997-11-28 N1 - Date created - 1997-11-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Functional domain mapping of the clathrin-associated adaptor medium chains mu1 and mu2. AN - 79354104; 9341158 AB - The clathrin-associated adaptors AP-1 and AP-2 are heterotetrameric complexes involved in the recognition of sorting signals present within the cytosolic domain of integral membrane proteins. The medium chains of these complexes, mu1 and mu2, have been implicated in two types of interaction: assembly with the beta1 and beta2 chains of the corresponding complexes and recognition of tyrosine-based sorting signals. In this study, we report the results of a structure-function analysis of the mu1 and mu2 chains aimed at identifying regions of the molecules that are responsible for each of the two interactions. Analyses using the yeast two-hybrid system and proteolytic digestion experiments suggest that mu1 and mu2 have a bipartite structure, with the amino-terminal one-third (residues 1-145 of mu1 and mu2) being involved in assembly with the beta chains and the carboxyl-terminal two-thirds (residues 147-423 of mu1 and 164-435 of mu2) binding tyrosine-based sorting signals. These observations support a model in which the amino-terminal one-third of mu2 is embedded within the core of the AP-2 complex, while the carboxyl-terminal two-thirds of the protein are exposed to the medium, placing this region in a position to interact with tyrosine-based sorting signals. JF - The Journal of biological chemistry AU - Aguilar, R C AU - Ohno, H AU - Roche, K W AU - Bonifacino, J S AD - Cell Biology and Metabolism Branch, NICHD, National Institutes of Health, Bethesda, Maryland 20892-5430, USA. Y1 - 1997/10/24/ PY - 1997 DA - 1997 Oct 24 SP - 27160 EP - 27166 VL - 272 IS - 43 SN - 0021-9258, 0021-9258 KW - APM1 protein, S cerevisiae KW - 0 KW - Adaptor Protein Complex 1 KW - Adaptor Protein Complex 2 KW - Adaptor Protein Complex 3 KW - Adaptor Protein Complex mu Subunits KW - Adaptor Proteins, Vesicular Transport KW - Antibodies KW - Clathrin KW - DNA-Binding Proteins KW - Fungal Proteins KW - GAL4 protein, S cerevisiae KW - Macromolecular Substances KW - Nerve Tissue Proteins KW - Phosphoproteins KW - Recombinant Fusion Proteins KW - Saccharomyces cerevisiae Proteins KW - Transcription Factors KW - adaptor protein complex 1, mu 1 subunit KW - adaptor protein complex 1, mu 2 subunit KW - adaptor protein complex 2, mu 1 subunit KW - adaptor protein complex 2, mu 2 subunit KW - Tyrosine KW - 42HK56048U KW - beta-Galactosidase KW - EC 3.2.1.23 KW - Index Medicus KW - Recombinant Fusion Proteins -- biosynthesis KW - Two-Hybrid System Techniques KW - Fungal Proteins -- biosynthesis KW - Transcription, Genetic KW - Amino Acid Sequence KW - Cloning, Organism KW - Protein Multimerization KW - Saccharomyces cerevisiae KW - Recombinant Fusion Proteins -- chemistry KW - Recombinant Fusion Proteins -- metabolism KW - Mutagenesis, Site-Directed KW - Kinetics KW - Molecular Sequence Data KW - beta-Galactosidase -- biosynthesis KW - Amino Acid Substitution KW - Sequence Deletion KW - Clathrin -- metabolism KW - Phosphoproteins -- chemistry KW - Nerve Tissue Proteins -- metabolism KW - Nerve Tissue Proteins -- chemistry KW - Phosphoproteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79354104?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Functional+domain+mapping+of+the+clathrin-associated+adaptor+medium+chains+mu1+and+mu2.&rft.au=Aguilar%2C+R+C%3BOhno%2C+H%3BRoche%2C+K+W%3BBonifacino%2C+J+S&rft.aulast=Aguilar&rft.aufirst=R&rft.date=1997-10-24&rft.volume=272&rft.issue=43&rft.spage=27160&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 - 1997-11-28 N1 - Date created - 1997-11-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The histone acetyltransferase activity of human GCN5 and PCAF is stabilized by coenzymes. AN - 79353472; 9341171 AB - Here we report that PCAF and human GCN5, two related type A histone acetyltransferases, are unstable enzymes that under the commonly used assay conditions are rapidly and irreversibly inactivated. In addition, we report that free histone H1, although not acetylated in vivo, is a preferred and convenient in vitro substrate for the study of PCAF, human GCN5, and possibly other type A histone acetyltransferases. Using either histone H1 or histone H3 as substrates, we find that preincubation with either acetyl-CoA or CoA stabilizes the acetyltransferase activities of PCAF, human GCN5 and an enzymatically active PCAF deletion mutant containing the C-terminal half of the protein. The stabilization requires the continuous presence of coenzyme, suggesting that the acetyltransferase-coenzyme complexes are stable, while the isolated apoenzymes are not. Human GCN5 and the N-terminal deletion mutant of PCAF are stabilized equally well by preincubation with either CoA or acetyl-CoA, while intact PCAF is better stabilized by acetyl-CoA than by CoA. Intact PCAF, but not the N-terminal truncation mutant or human GCN5, is autoacetylated. These findings raise the possibility that the intracellular concentrations of the coenzymes affect the stability and therefore the nuclear activity of these acetyltransferases. JF - The Journal of biological chemistry AU - Herrera, J E AU - Bergel, M AU - Yang, X J AU - Nakatani, Y AU - Bustin, M AD - Laboratory of Molecular Carcinogenesis, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. herr@helix.nih.gov Y1 - 1997/10/24/ PY - 1997 DA - 1997 Oct 24 SP - 27253 EP - 27258 VL - 272 IS - 43 SN - 0021-9258, 0021-9258 KW - Cell Cycle Proteins KW - 0 KW - Coenzymes KW - Histones KW - Saccharomyces cerevisiae Proteins KW - Trans-Activators KW - Transcription Factors KW - Acetyl Coenzyme A KW - 72-89-9 KW - Acetyltransferases KW - EC 2.3.1.- KW - Acetyl-CoA C-Acyltransferase KW - EC 2.3.1.16 KW - Histone Acetyltransferases KW - EC 2.3.1.48 KW - KAT2A protein, human KW - p300-CBP Transcription Factors KW - p300-CBP-associated factor KW - Index Medicus KW - Acetylation KW - Kinetics KW - Humans KW - Enzyme Stability KW - Substrate Specificity KW - Trans-Activators -- metabolism KW - Acetyltransferases -- metabolism KW - Histones -- metabolism KW - Coenzymes -- metabolism KW - Acetyl-CoA C-Acyltransferase -- metabolism KW - Acetyl Coenzyme A -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79353472?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=In+vivo+%28Athens%2C+Greece%29&rft.atitle=Nitrosamines%2C+alcohol%2C+and+gastrointestinal+tract+cancer%3A+recent+epidemiology+and+experimentation.&rft.au=Chhabra%2C+S+K%3BSouliotis%2C+V+L%3BKyrtopoulos%2C+S+A%3BAnderson%2C+L+M&rft.aulast=Chhabra&rft.aufirst=S&rft.date=1996-05-01&rft.volume=10&rft.issue=3&rft.spage=265&rft.isbn=&rft.btitle=&rft.title=In+vivo+%28Athens%2C+Greece%29&rft.issn=0258851X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-11-28 N1 - Date created - 1997-11-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Alterations in lipoprotein metabolism in peroxisome proliferator-activated receptor alpha-deficient mice. AN - 79351655; 9341179 AB - The peroxisome proliferator-activated receptor-alpha (PPARalpha) controls gene expression in response to a diverse class of compounds collectively referred to as peroxisome proliferators. Whereas most known peroxisome proliferators are of exogenous origin and include hypolipidemic drugs and other industrial chemicals, several endogenous PPARalpha activators have been identified such as fatty acids and steroids. The latter finding and the fact that PPARalpha modulates target genes encoding enzymes involved in lipid metabolism suggest a role for PPARalpha in lipid metabolism. This was investigated in the PPARalpha-deficient mouse model. Basal levels of total serum cholesterol, high density lipoprotein cholesterol, hepatic apolipoprotein A-I mRNA, and serum apolipoprotein A-I in PPARalpha-deficient mice are significantly higher compared with wild-type controls. Treatment with the fibrate Wy 14,643 decreased apoA-I serum levels and hepatic mRNA levels in wild-type mice, whereas no effect was detected in the PPARalpha-deficient mice. Administration of the fibrate Wy 14,643 to wild-type mice results in marked depression of hepatic apolipoprotein C-III mRNA and serum triglycerides compared with untreated controls. In contrast, PPARalpha-deficient mice were unaffected by Wy 14,643 treatment. These studies demonstrate that PPARalpha modulates basal levels of serum cholesterol, in particular high density lipoprotein cholesterol, and establish that fibrate-induced modulation in hepatic apolipoprotein A-I, C-III mRNA, and serum triglycerides observed in wild-type mice is mediated by PPARalpha. JF - The Journal of biological chemistry AU - Peters, J M AU - Hennuyer, N AU - Staels, B AU - Fruchart, J C AU - Fievet, C AU - Gonzalez, F J AU - Auwerx, J AD - Laboratory of Metabolism, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1997/10/24/ PY - 1997 DA - 1997 Oct 24 SP - 27307 EP - 27312 VL - 272 IS - 43 SN - 0021-9258, 0021-9258 KW - Anticholesteremic Agents KW - 0 KW - Apolipoprotein A-I KW - Apolipoprotein C-III KW - Apolipoproteins C KW - Cholesterol, HDL KW - Lipoproteins KW - Nuclear Proteins KW - Phospholipids KW - Pyrimidines KW - RNA, Messenger KW - Receptors, Cytoplasmic and Nuclear KW - Transcription Factors KW - Triglycerides KW - pirinixic acid KW - 86C4MRT55A KW - Cholesterol KW - 97C5T2UQ7J KW - Index Medicus KW - Triglycerides -- blood KW - Animals KW - Apolipoproteins C -- biosynthesis KW - Pyrimidines -- pharmacology KW - Anticholesteremic Agents -- pharmacology KW - Mice KW - Mice, Knockout KW - Phospholipids -- blood KW - Apolipoprotein A-I -- biosynthesis KW - Cholesterol -- blood KW - Mice, Inbred Strains KW - Nuclear Proteins -- deficiency KW - Apolipoprotein A-I -- blood KW - RNA, Messenger -- metabolism KW - Cholesterol, HDL -- blood KW - Mice, Inbred C57BL KW - Microbodies -- metabolism KW - Lipoproteins -- metabolism KW - Liver -- drug effects KW - Liver -- metabolism KW - Transcription Factors -- deficiency KW - Receptors, Cytoplasmic and Nuclear -- genetics KW - Receptors, Cytoplasmic and Nuclear -- deficiency KW - Transcription Factors -- genetics KW - Lipoproteins -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79351655?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Alterations+in+lipoprotein+metabolism+in+peroxisome+proliferator-activated+receptor+alpha-deficient+mice.&rft.au=Peters%2C+J+M%3BHennuyer%2C+N%3BStaels%2C+B%3BFruchart%2C+J+C%3BFievet%2C+C%3BGonzalez%2C+F+J%3BAuwerx%2C+J&rft.aulast=Peters&rft.aufirst=J&rft.date=1997-10-24&rft.volume=272&rft.issue=43&rft.spage=27307&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 - 1997-11-28 N1 - Date created - 1997-11-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Defining the minimal domain of Ku80 for interaction with Ku70. AN - 79351615; 9341172 AB - The Ku protein has a critical function in the repair of double-strand DNA breaks induced for example by ionizing radiation or during VDJ recombination. Ku serves as the DNA-binding subunit of the DNA-dependent kinase and is a heterodimeric protein composed of 80- and 70-kDa subunits. We used the two-hybrid system to analyze the interaction domains of the Ku subunits and to identify possible additional partners for Ku. Screening a human cDNA library with the Ku heterodimer did not reveal any novel partners. Screening with the individual subunits, we detected only Ku70 clones interacting with Ku80 and only Ku80 clones interacting with Ku70, indicating that these are the primary partners for one another. Ku80 and Ku70 formed only heterodimers and did not homodimerize. Ku80 was restricted to interacting with just one Ku70 molecule at a time. The minimal functional interaction domain of Ku80 that interacted with Ku70 was defined. It consisted of a 28-amino acid region extending from amino acid 449 to 477. This region was crucial for interaction with Ku70, since mutation within this critical site at amino acids 453 and 454 abrogated the ability to interact with Ku70. We furthermore verified that the same region is crucial for interaction with Ku70 using in vitro co-translation of both subunits followed by an immunoprecipitation with anti-Ku70 antibodies. This interaction domain of Ku80 does not contain any motif previously recognized in protein-protein interactions. JF - The Journal of biological chemistry AU - Osipovich, O AU - Durum, S K AU - Muegge, K AD - Laboratory of Molecular Immunoregulation, NCI, National Institutes of Health, Frederick, Maryland 21702-1201, USA. Y1 - 1997/10/24/ PY - 1997 DA - 1997 Oct 24 SP - 27259 EP - 27265 VL - 272 IS - 43 SN - 0021-9258, 0021-9258 KW - Antigens, Nuclear KW - 0 KW - DNA-Binding Proteins KW - Macromolecular Substances KW - Nuclear Proteins KW - Recombinant Fusion Proteins KW - Saccharomyces cerevisiae Proteins KW - high affinity DNA-binding factor, S cerevisiae KW - beta-Galactosidase KW - EC 3.2.1.23 KW - DNA Helicases KW - EC 3.6.4.- KW - XRCC5 protein, human KW - EC 3.6.4.12 KW - Xrcc6 protein, human KW - Ku Autoantigen KW - EC 4.2.99.- KW - Index Medicus KW - DNA Repair KW - Humans KW - Cloning, Organism KW - Binding Sites KW - Recombinant Fusion Proteins -- chemistry KW - Saccharomyces cerevisiae KW - Mutagenesis, Site-Directed KW - Recombinant Fusion Proteins -- metabolism KW - beta-Galactosidase -- metabolism KW - Transfection KW - Point Mutation KW - Sequence Deletion KW - DNA-Binding Proteins -- chemistry KW - Nuclear Proteins -- chemistry KW - Nuclear Proteins -- metabolism KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79351615?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Hypertension+%28Dallas%2C+Tex.+%3A+1979%29&rft.atitle=Effects+of+cyclosporin+A+on+the+synthesis%2C+excretion%2C+and+metabolism+of+endothelin+in+the+rat.&rft.au=Abassi%2C+Z+A%3BPieruzzi%2C+F%3BNakhoul%2C+F%3BKeiser%2C+H+R&rft.aulast=Abassi&rft.aufirst=Z&rft.date=1996-05-01&rft.volume=27&rft.issue=5&rft.spage=1140&rft.isbn=&rft.btitle=&rft.title=Hypertension+%28Dallas%2C+Tex.+%3A+1979%29&rft.issn=0194911X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-11-28 N1 - Date created - 1997-11-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - An update of the National Toxicology Program database on nasal carcinogens AN - 16222672; 4211844 AB - Nearly 500 long-term rodent carcinogenicity studies carried out by the National Cancer Institute and the National Toxicology Program were examined, and 12 chemicals were identified that produced nasal tumors: allyl glycidol ether, p-cresidine, 1,2-dibromo-3-chloropropane, 1,2-dibromoethane, 2,3-dibromo-1-propanol, dimethylvinyl chloride, 1,4-dioxane, 1,2-epoxybutane, iodinated glycerol, procarbazine, propylene oxide, and 2,6-xylidine. All 12 of these chemicals produced nasal tumors in rats, and 5 also produced nasal tumors in mice. Most of the nasal carcinogens (1) produced tumor increases in both sexes, (2) produced tumors at other sites as well, (3) had significantly reduced survival at doses that were carcinogenic, and (4) were genotoxic. Only 5 of the 12 nasal carcinogens were administered by inhalation. A variety of different types of nasal cavity tumors were produced, and specific tumor rates are given for those chemicals causing multiple tumor types. Increased incidences of nasal neoplasms were often accompanied by suppurative/acute inflammation, epithelial/focal hyperplasia and squamous metaplasia. However, high incidences of these nonneoplastic nasal lesions were also frequently seen in inhalation studies showing no evidence of nasal carcinogenicity, suggesting that in general nasal carcinogenesis is not associated with the magnitude of chronic toxicity observed at this site. JF - Mutation Research AU - Haseman, J K AU - Hailey, J R AD - Statistics and Biomathematics Branch, National Institute of Environmental Health Sciences, P.O. Box 12233, Research Triangle Park, NC 27709, USA, haseman@fred.niehs.nih.g00 Y1 - 1997/10/20/ PY - 1997 DA - 1997 Oct 20 SP - 3 EP - 11 PB - Elsevier Science B.V. VL - 380 IS - 1-2 SN - 0027-5107, 0027-5107 KW - National Toxicology Program KW - chronic toxicity KW - Toxicology Abstracts KW - X 24240:Miscellaneous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16222672?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+Research&rft.atitle=An+update+of+the+National+Toxicology+Program+database+on+nasal+carcinogens&rft.au=Haseman%2C+J+K%3BHailey%2C+J+R&rft.aulast=Haseman&rft.aufirst=J&rft.date=1997-10-20&rft.volume=380&rft.issue=1-2&rft.spage=3&rft.isbn=&rft.btitle=&rft.title=Mutation+Research&rft.issn=00275107&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Solution structure of the I gamma subdomain of the Mu end DNA-binding domain of phage Mu transposase. AN - 79419723; 9367742 AB - The MuA transposase of phase Mu is a large modular protein that plays a central role in transposition. We show that the Mu end DNA-binding domain, I beta gamma, which is responsible for binding the DNA attachment sites at each end of the Mu genome, comprises two subdomains, I beta and I gamma, that are structurally autonomous and do not interact with each other in the absence of DNA. The solution structure of the I gamma subdomain has been determined by multidimensional NMR spectroscopy. The structure of I gamma comprises a four helix bundle and, despite the absence of any significant sequence identity, the topology of the first three helices is very similar to that of the homeodomain family of helix-turn-helix DNA-binding proteins. The helix-turn-helix motif of I gamma, however, differs from that of the homeodomains in so far as the loop is longer and the second helix is shorter, reminiscent of that in the POU-specific domain. JF - Journal of molecular biology AU - Clubb, R T AU - Schumacher, S AU - Mizuuchi, K AU - Gronenborn, A M AU - Clore, G M AD - Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0520, USA. Y1 - 1997/10/17/ PY - 1997 DA - 1997 Oct 17 SP - 19 EP - 25 VL - 273 IS - 1 SN - 0022-2836, 0022-2836 KW - DNA, Viral KW - 0 KW - Homeodomain Proteins KW - Recombinant Proteins KW - Transposases KW - EC 2.7.7.- KW - Index Medicus KW - Protein Structure, Secondary KW - Models, Molecular KW - Mutagenesis, Site-Directed -- genetics KW - Escherichia coli -- genetics KW - Amino Acid Sequence KW - Homeodomain Proteins -- chemistry KW - Magnetic Resonance Spectroscopy KW - Gene Expression -- genetics KW - Homeodomain Proteins -- genetics KW - Sequence Deletion -- genetics KW - Molecular Sequence Data KW - Helix-Turn-Helix Motifs KW - Recombinant Proteins -- chemistry KW - Transposases -- chemistry KW - Transposases -- metabolism KW - Transposases -- genetics KW - Bacteriophage mu -- enzymology KW - DNA, Viral -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79419723?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+molecular+biology&rft.atitle=Solution+structure+of+the+I+gamma+subdomain+of+the+Mu+end+DNA-binding+domain+of+phage+Mu+transposase.&rft.au=Clubb%2C+R+T%3BSchumacher%2C+S%3BMizuuchi%2C+K%3BGronenborn%2C+A+M%3BClore%2C+G+M&rft.aulast=Clubb&rft.aufirst=R&rft.date=1997-10-17&rft.volume=273&rft.issue=1&rft.spage=19&rft.isbn=&rft.btitle=&rft.title=Journal+of+molecular+biology&rft.issn=00222836&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-12-05 N1 - Date created - 1997-12-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Trapping of mammalian topoisomerase I and recombinations induced by damaged DNA containing nicks or gaps. Importance of DNA end phosphorylation and camptothecin effects. AN - 79335510; 9334220 AB - We used purified mammalian topoisomerases I (top1) and oligonucleotides containing a unique top1 cleavage site to study top1-mediated cleavage and recombination in the presence of nicks and short gaps mimicking DNA damage. In general, top1 cleavage was not induced opposite to the nicks, and nicks upstream from the top1 cleavage site suppressed top1 activity. Irreversible top1 cleavage complexes ("suicide products" or "aborted complexes") were produced in DNA containing nicks or short gaps just opposite to the normal top1 cleavage site. Camptothecin enhanced the formation of the aborted top1 complexes only for nicks downstream from the cleavage site. These aborted (suicide) complexes can mediate DNA recombination and promote illegitimate recombination by catalyzing the ligation of nonhomologous DNA fragments (acceptors). We report for the first time that top1-mediated recombination is greatly enhanced by the presence of a phosphate at the 5' terminus of the top1 aborted complex (donor DNA). By contrast, phosphorylation of the 3' terminus of the gap did not affect recombination. At concentrations that strongly enhanced inhibition of intramolecular religation, resulting in an increase of top1 cleavable complexes, camptothecin did not reduce recombination (intermolecular religation). Nicks or gaps with 5'-phosphate termini would be expected to be produced directly by ionizing radiations or by processing of abasic sites and DNA lesions induced by carcinogens or drugs used in cancer chemotherapy. Thus, these results further demonstrate that DNA damage can efficiently trap top1-cleavable complexes and enhance top1-mediated DNA recombination. JF - The Journal of biological chemistry AU - Pourquier, P AU - Pilon, A A AU - Kohlhagen, G AU - Mazumder, A AU - Sharma, A AU - Pommier, Y AD - Laboratory of Molecular Pharmacology, Division of Basic Sciences, NCI, National Institutes of Health, Bethesda, Maryland 20892-4255, USA. Y1 - 1997/10/17/ PY - 1997 DA - 1997 Oct 17 SP - 26441 EP - 26447 VL - 272 IS - 42 SN - 0021-9258, 0021-9258 KW - Enzyme Inhibitors KW - 0 KW - Topoisomerase I Inhibitors KW - DNA KW - 9007-49-2 KW - DNA Topoisomerases, Type I KW - EC 5.99.1.2 KW - Camptothecin KW - XT3Z54Z28A KW - Index Medicus KW - Phosphorylation KW - Humans KW - Camptothecin -- pharmacology KW - DNA Damage KW - DNA -- metabolism KW - Recombination, Genetic KW - Enzyme Inhibitors -- pharmacology KW - DNA Topoisomerases, Type I -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79335510?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Isolation+of+genes+amplified+in+human+cancers+by+microdissection+mediated+cDNA+capture.&rft.au=Gracia%2C+E%3BFischer%2C+U%3BelKahloun%2C+A%3BTrent%2C+J+M%3BMeese%2C+E%3BMeltzer%2C+P+S&rft.aulast=Gracia&rft.aufirst=E&rft.date=1996-05-01&rft.volume=5&rft.issue=5&rft.spage=595&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 - 1997-11-17 N1 - Date created - 1997-11-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Subclinical neurological and neurovascular deficits in cocaine dependence. Gender and psychosocial considerations. AN - 79415886; 9369998 AB - Neurological and neurovascular deficits were reported in cocaine abusers. In order to examine the contribution of cocaine use severity as well as other psychosocial factors to these deficits, we examined the following measures in a sample of cocaine abusers (n = 70): blood flow (transcranial Doppler sonography), and psychosocial measures (the Norbeck Social Support Questionnaire, the Symptom Check List 90R, the Beck Hopelessness Scale, and the Ellison Wellness Scale). Blood flow in the anterior and medial cerebral arteries was lower in the cocaine abusers than in the control subjects. Both cocaine use and psychosocial measures significantly predicted decreases in blood flow. JF - Annals of the New York Academy of Sciences AU - King, D E AU - Herning, R I AU - Cadet, J L AD - Molecular Neuropsychiatry Section, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 21224, USA. Y1 - 1997/10/15/ PY - 1997 DA - 1997 Oct 15 SP - 328 EP - 331 VL - 825 SN - 0077-8923, 0077-8923 KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Regression Analysis KW - Reference Values KW - Blood Pressure KW - Attitude to Health KW - Anxiety KW - Sex Characteristics KW - Humans KW - Adult KW - Ultrasonography, Doppler, Transcranial KW - Social Support KW - Pulse KW - Male KW - Female KW - Substance-Related Disorders -- physiopathology KW - Cerebrovascular Circulation KW - Cerebral Arteries -- physiopathology KW - Substance-Related Disorders -- psychology KW - Cerebral Arteries -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79415886?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Subclinical+neurological+and+neurovascular+deficits+in+cocaine+dependence.+Gender+and+psychosocial+considerations.&rft.au=King%2C+D+E%3BHerning%2C+R+I%3BCadet%2C+J+L&rft.aulast=King&rft.aufirst=D&rft.date=1997-10-15&rft.volume=825&rft.issue=&rft.spage=328&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 - 1997-12-09 N1 - Date created - 1997-12-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cocaine dependence. A clinical syndrome requiring neuroprotection. AN - 79415823; 9369997 AB - Cocaine use has increased the frequency of medical complications among younger individuals. Neurological and neurovascular complications include strokes, seizures, transient ischemic attacks, and headaches. Subclinical deficits in cerebral perfusion and EEG have been noted in this population. Although these subclinical deficits may be an indication of increased risk of medical complications, the prophalactic treatment of cocaine abusers with neuroprotective agents has not yet been advocated. Blood flow of the anterior and medial cerebral arteries was measured by transcranial Doppler sonography in cocaine abusers (n = 70) and control subjects (n = 20) to determine whether cocaine abusers might have reduced cerebral blood flow in large cerebral arteries. Blood flow was measured within three days of and again about 28 days after admission of subjects to an inpatient research ward to determine whether blood flow improved with monitored abstinence. The mean, systolic, and diastolic velocities as well as the Pulsatility Index (PI) in both arteries differed between the control and cocaine abusers (p < 0.05). After about a month of abstinence, blood flow for the cocaine-dependent subjects increased. These preliminary findings suggest that blood flow is reduced in cocaine abusers and that there is a slight improvement with abstinence. Further research is needed to determine whether blood flow in abstinent cocaine abusers can be increased by pharmacological manipulations. JF - Annals of the New York Academy of Sciences AU - Herning, R I AU - King, D E AU - Better, W AU - Cadet, J L AD - Molecular Neuropsychiatry Section, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 21224, USA. Y1 - 1997/10/15/ PY - 1997 DA - 1997 Oct 15 SP - 323 EP - 327 VL - 825 SN - 0077-8923, 0077-8923 KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Severity of Illness Index KW - Demography KW - Intelligence KW - Reference Values KW - Syndrome KW - Humans KW - Electroencephalography KW - Adult KW - Ultrasonography, Doppler, Transcranial KW - Pulse KW - Systole KW - Regional Blood Flow KW - Male KW - Female KW - Substance-Related Disorders -- physiopathology KW - Substance-Related Disorders -- diagnostic imaging KW - Cerebrovascular Circulation KW - Cerebral Arteries -- physiopathology KW - Cerebral Arteries -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79415823?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cocaine+dependence.+A+clinical+syndrome+requiring+neuroprotection.&rft.au=Herning%2C+R+I%3BKing%2C+D+E%3BBetter%2C+W%3BCadet%2C+J+L&rft.aulast=Herning&rft.aufirst=R&rft.date=1997-10-15&rft.volume=825&rft.issue=&rft.spage=323&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 - 1997-12-09 N1 - Date created - 1997-12-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Expression of a dominant-negative retinoic acid receptor construct reduces retinoic acid metabolism and retinoic acid-induced inhibition of NIH-3T3 cell growth. AN - 79391956; 9377552 AB - We have previously reported an unexpected relationship between retinoic acid-induced inhibition of cell growth and the ability of various cell lines to metabolize the retinoid. Here, we report that stable expression of the truncated retinoic acid receptor RAR alpha403, transduced in NIH-3T3 cells by a retroviral vector, rendered the cells resistant to retinoic acid for growth inhibition and reduced their ability to metabolize the retinoid at the same time as it blunted the induction of the target gene transglutaminase II. The data suggest that retinoic acid receptors mediate the growth-inhibitory action of retinoic acid as well as its metabolism and the induction of transglutaminase II. JF - Cancer research AU - Isogai, M AU - Chiantore, M V AU - Haque, M AU - Scita, G AU - De Luca, L M AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, Maryland 20892-4255, USA. Y1 - 1997/10/15/ PY - 1997 DA - 1997 Oct 15 SP - 4460 EP - 4464 VL - 57 IS - 20 SN - 0008-5472, 0008-5472 KW - Rara protein, mouse KW - 0 KW - Receptors, Retinoic Acid KW - Recombinant Proteins KW - Retinoic Acid Receptor alpha KW - Tretinoin KW - 5688UTC01R KW - Transglutaminases KW - EC 2.3.2.13 KW - Index Medicus KW - 3T3 Cells KW - Animals KW - Recombinant Proteins -- biosynthesis KW - Retroviridae KW - Cell Division -- drug effects KW - Transglutaminases -- biosynthesis KW - Mice KW - Transfection KW - Genetic Vectors KW - Kinetics KW - Enzyme Induction KW - Sequence Deletion KW - Tretinoin -- pharmacology KW - Receptors, Retinoic Acid -- physiology KW - Receptors, Retinoic Acid -- biosynthesis KW - Tretinoin -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79391956?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Expression+of+a+dominant-negative+retinoic+acid+receptor+construct+reduces+retinoic+acid+metabolism+and+retinoic+acid-induced+inhibition+of+NIH-3T3+cell+growth.&rft.au=Isogai%2C+M%3BChiantore%2C+M+V%3BHaque%2C+M%3BScita%2C+G%3BDe+Luca%2C+L+M&rft.aulast=Isogai&rft.aufirst=M&rft.date=1997-10-15&rft.volume=57&rft.issue=20&rft.spage=4460&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 - 1997-11-10 N1 - Date created - 1997-11-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hypermutability of UV-treated plasmids in dysplastic nevus/familial melanoma cell lines. AN - 79391201; 9377580 AB - Members of cutaneous melanoma (CM) families with dysplastic nevi (DN) are at high risk of developing CM. Using a shuttle vector plasmid, pSP189, cell lines from three patients with CM plus DN were previously found to have elevated post-UV plasmid mutability. To investigate familial occurrence of this cellular phenotype, we examined post-UV plasmid mutability in 31 lymphoblastoid cell lines from 6 familial CM kindreds. In comparison to 16 normal control lines, we found an abnormally elevated post-UV plasmid mutability in cell lines from 13 of 13 patients with CM plus DN (P = 1.5 x 10(-8)) and from 5 of 8 patients with DN only (P = 0.001). Elevated spontaneous plasmid mutation frequency (MF) was also present in cell lines from six of the CM plus DN patients (P = 0.002) and three of the DN-only patients (P = 0.028). However, cell lines from two patients with CM without DN had normal post-UV plasmid MF. Although not specific for CM patients, of 27 cell lines with elevated post-UV plasmid MF, only 8 were from donors who did not have CM + DN or DN (19 of 24 versus 8 of 28; P = 0.0003). This study indicates that post-UV plasmid hypermutability is a laboratory marker for members of melanoma-prone families and suggests that patients with familial CM have a defective mechanism for handling UV-induced DNA damage. JF - Cancer research AU - Moriwaki, S I AU - Tarone, R E AU - Tucker, M A AU - Goldstein, A M AU - Kraemer, K H AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1997/10/15/ PY - 1997 DA - 1997 Oct 15 SP - 4637 EP - 4641 VL - 57 IS - 20 SN - 0008-5472, 0008-5472 KW - Index Medicus KW - Mutagenicity Tests KW - Age Factors KW - DNA Repair KW - Tumor Cells, Cultured KW - Humans KW - Genetic Vectors KW - Xeroderma Pigmentosum -- genetics KW - Family KW - Lymphocytes KW - Cell Line, Transformed KW - Herpesvirus 4, Human KW - Skin Neoplasms -- genetics KW - Ultraviolet Rays KW - Melanoma -- genetics KW - Dysplastic Nevus Syndrome -- genetics KW - Plasmids -- radiation effects KW - Mutagenesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79391201?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Hypermutability+of+UV-treated+plasmids+in+dysplastic+nevus%2Ffamilial+melanoma+cell+lines.&rft.au=Moriwaki%2C+S+I%3BTarone%2C+R+E%3BTucker%2C+M+A%3BGoldstein%2C+A+M%3BKraemer%2C+K+H&rft.aulast=Moriwaki&rft.aufirst=S&rft.date=1997-10-15&rft.volume=57&rft.issue=20&rft.spage=4637&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 - 1997-11-10 N1 - Date created - 1997-11-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of epidermal growth factor receptor and c-erbB2 pathway inhibitors by correlation with gene expression patterns. AN - 79348054; 9337347 AB - Growth factor receptor-signaling pathways are potentially important targets for anticancer therapy. The interaction of anticancer agents with specific molecular targets can be identified by correlating target expression patterns with cytotoxicity patterns. We sought to identify new agents that target and inhibit the activity of the epidermal growth factor (EGF) receptor and of c-erbB2 (also called HER2 or neu), by correlating EGF receptor, transforming growth factor (TGF)-alpha (a ligand for EGF receptor), and c-erbB2 messenger RNA (mRNA) expression levels with the results of cytotoxicity assays of the 49000 compounds in the National Cancer Institute (NCI) drug screen database. The levels of mRNAs were measured and used to generate a molecular target database for the 60 cell lines of the NCI anticancer drug screen. The computer analysis program, COMPARE, was used to search for cytotoxicity patterns in the NCI drug screen database that were highly correlated with EGF receptor, TGF-alpha, or c-erbB2 mRNA expression patterns. The putative EGF receptor-inhibiting compounds were tested for effects on basal tyrosine phosphorylation, in vitro EGF receptor tyrosine kinase activity, and EGF-dependent growth. Putative ErbB2-inhibiting compounds were tested for effects on antibody-induced ErbB2 tyrosine kinase activity. EGF receptor mRNA and TGF-alpha mRNA levels were highest in cell lines derived from renal cancers, and c-erbB2 mRNA levels were highest in cells derived from breast, ovarian, and colon cancers. Twenty-five compounds with high correlation coefficients (for cytotoxicity and levels of the measured mRNAs) were tested as inhibitors of the EGF receptor or c-erbB2 signaling pathways; 14 compounds were identified as inhibitors of these pathways. The most potent compound, B4, inhibited autophosphorylation (which occurs following activation) of ErbB2 by 50% in whole cells at 7.7 microM. Novel EGF receptor or c-erbB2 pathway inhibitors can be identified in the NCI drug screen by correlation of cytotoxicity patterns with EGF receptor or c-erbB2 mRNA expression levels. JF - Journal of the National Cancer Institute AU - Wosikowski, K AU - Schuurhuis, D AU - Johnson, K AU - Paull, K D AU - Myers, T G AU - Weinstein, J N AU - Bates, S E AD - Division of Clinical Sciences, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1997/10/15/ PY - 1997 DA - 1997 Oct 15 SP - 1505 EP - 1515 VL - 89 IS - 20 SN - 0027-8874, 0027-8874 KW - Antineoplastic Agents KW - 0 KW - RNA, Messenger KW - Transforming Growth Factor alpha KW - Epidermal Growth Factor KW - 62229-50-9 KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - Receptor, ErbB-2 KW - Index Medicus KW - Drug Screening Assays, Antitumor KW - Ovarian Neoplasms KW - Humans KW - Cell Division -- drug effects KW - Breast Neoplasms KW - Epidermal Growth Factor -- pharmacology KW - Gene Expression Regulation, Neoplastic -- drug effects KW - RNA, Messenger -- biosynthesis KW - Structure-Activity Relationship KW - Tumor Cells, Cultured KW - Kidney Neoplasms KW - Cluster Analysis KW - Colonic Neoplasms KW - Cell Line KW - Female KW - Transcription, Genetic -- drug effects KW - Receptor, Epidermal Growth Factor -- metabolism KW - Transforming Growth Factor alpha -- biosynthesis KW - Antineoplastic Agents -- toxicity KW - Receptor, ErbB-2 -- biosynthesis KW - Receptor, Epidermal Growth Factor -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79348054?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Identification+of+epidermal+growth+factor+receptor+and+c-erbB2+pathway+inhibitors+by+correlation+with+gene+expression+patterns.&rft.au=Wosikowski%2C+K%3BSchuurhuis%2C+D%3BJohnson%2C+K%3BPaull%2C+K+D%3BMyers%2C+T+G%3BWeinstein%2C+J+N%3BBates%2C+S+E&rft.aulast=Wosikowski&rft.aufirst=K&rft.date=1997-10-15&rft.volume=89&rft.issue=20&rft.spage=1505&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 - 1997-10-31 N1 - Date created - 1997-10-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cancer incidence after retinoblastoma. Radiation dose and sarcoma risk. AN - 79327405; 9333268 AB - There is a substantial risk of a second cancer for persons with hereditary retinoblastoma, which is enhanced by radiotherapy. To examine long-term risk of new primary cancers in survivors of childhood retinoblastoma and quantify the role of radiotherapy in sarcoma development. Cohort incidence study of patients with retinoblastoma followed for a median of 20 years, and nested case-control study of a radiation dose-response relationship for bone and soft tissue sarcomas. A total of 1604 patients with retinoblastoma who survived at least 1 year after diagnosis, identified from hospital records in Massachusetts and New York during 1914 to 1984. Incidence of subsequent cancers was statistically significantly elevated only in the 961 patients with hereditary retinoblastoma, in whom 190 cancers were diagnosed, vs 6.3 expected in the general population (relative risk [RR], 30 [95% confidence interval, 26-47]). Cumulative incidence (+/-SE) of a second cancer at 50 years after diagnosis was 51.0% (+/-6.2%) for hereditary retinoblastoma, and 5.0% (+/-3.0%) for nonhereditary retinoblastoma. All 114 sarcomas of diverse histologic types occurred in patients with hereditary retinoblastoma. For soft tissue sarcomas, the RRs showed a stepwise increase at all dose categories, and were statistically significant at 10 to 29.9 Gy and 30 to 59.9 Gy. A radiation risk for all sarcomas combined was evident at doses above 5 Gy, rising to 10.7-fold at doses of 60 Gy or greater (P<.05). Genetic predisposition has a substantial impact on risk of subsequent cancers in retinoblastoma patients, which is further increased by radiation treatment. A radiation dose-response relationship is demonstrated for all sarcomas and, for the first time in humans, for soft tissue sarcomas. Retinoblastoma patients should be examined for new cancers and followed into later life to determine whether their extraordinary cancer risk extends to common cancers of adulthood. JF - JAMA AU - Wong, F L AU - Boice, J D AU - Abramson, D H AU - Tarone, R E AU - Kleinerman, R A AU - Stovall, M AU - Goldman, M B AU - Seddon, J M AU - Tarbell, N AU - Fraumeni, J F AU - Li, F P AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Md 20892, USA. Y1 - 1997/10/15/ PY - 1997 DA - 1997 Oct 15 SP - 1262 EP - 1267 VL - 278 IS - 15 SN - 0098-7484, 0098-7484 KW - Abridged Index Medicus KW - Index Medicus KW - Humans KW - Child KW - Dose-Response Relationship, Radiation KW - Child, Preschool KW - Infant KW - Risk KW - Radiotherapy Dosage KW - Adult KW - Cohort Studies KW - Case-Control Studies KW - Incidence KW - Middle Aged KW - Statistics as Topic KW - Adolescent KW - Time Factors KW - Survivors KW - Female KW - Male KW - Survival Analysis KW - Eye Neoplasms -- genetics KW - Neoplasms, Second Primary -- epidemiology KW - Neoplasms, Radiation-Induced -- etiology KW - Neoplasms, Second Primary -- etiology KW - Neoplasms, Radiation-Induced -- epidemiology KW - Eye Neoplasms -- radiotherapy KW - Retinoblastoma -- genetics KW - Retinoblastoma -- radiotherapy KW - Sarcoma -- etiology KW - Sarcoma -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79327405?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cancer+incidence+after+retinoblastoma.+Radiation+dose+and+sarcoma+risk.&rft.au=Wong%2C+F+L%3BBoice%2C+J+D%3BAbramson%2C+D+H%3BTarone%2C+R+E%3BKleinerman%2C+R+A%3BStovall%2C+M%3BGoldman%2C+M+B%3BSeddon%2C+J+M%3BTarbell%2C+N%3BFraumeni%2C+J+F%3BLi%2C+F+P&rft.aulast=Wong&rft.aufirst=F&rft.date=1997-10-15&rft.volume=278&rft.issue=15&rft.spage=1262&rft.isbn=&rft.btitle=&rft.title=JAMA&rft.issn=00987484&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-10-22 N1 - Date created - 1997-10-22 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: JAMA. 1997 Oct 15;278(15):1284-5 [9333273] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In vivo sequencing of camptothecin-induced topoisomerase I cleavage sites in human colon carcinoma cells. AN - 79315024; 9321666 AB - Camptothecin (CPT) is a specific topoisomerase I (top1) poison which traps top1 cleavable complexes; e.g. top1-linked DNA single-strand breaks with 5'-hydroxyl and 3'-top1 linked termini. CPT is also a potent anticancer agent and several of its derivatives have recently shown activity in the chemotherapy of solid tumors. Our aim was to apply the ligation-mediated polymerase chain reaction (LM-PCR) method to DNA extracted from CPT-treated cells in order to: (i) evaluate LM-PCR as a sensitive technique to detect in vivo CPT-induced cleavable complexes; (ii) investigate the frequency and distribution of CPT-induced DNA damage in vivo ; and (iii) compare the distribution and intensity of cleavage sites in vivo and in vitro. This report describes a protocol allowing the sequencing of top1-mediated DNA strand breaks induced by CPT in the coding strand of the 18S rRNA gene of human colon carcinoma cells. CPT or its clinical derivatives, topotecan, CPT-11, SN-38, and 9-aminocamptothecin differed in their potency and exhibited differences in their DNA cleavage pattern, which is consistent with our previous in vitro studies [Tanizawa et al . (1995) Biochemistry , 43, 7200-7206]. CPT-induced DNA cleavages induced in the presence of purified top1 were induced at the same sites in the human 18S rDNA. However, the relative intensity of the cleavages were different in vivo and in vitro. Because mammalian cells contain approximately 300 copies of the rDNA gene per genome, rDNA could be used to monitor CPT-induced DNA cleavage in different cell lines and possibly in tumor samples. JF - Nucleic acids research AU - Pondarré, C AU - Strumberg, D AU - Fujimori, A AU - Torres-León, R AU - Pommier, Y AD - Laboratory of Molecular Pharmacology, Division of Basic Sciences, Bldg 37, Rm 5C25, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA. Y1 - 1997/10/15/ PY - 1997 DA - 1997 Oct 15 SP - 4111 EP - 4116 VL - 25 IS - 20 SN - 0305-1048, 0305-1048 KW - Antineoplastic Agents, Phytogenic KW - 0 KW - DNA, Neoplasm KW - DNA, Ribosomal KW - Enzyme Inhibitors KW - RNA, Ribosomal, 18S KW - Topoisomerase I Inhibitors KW - DNA Topoisomerases, Type I KW - EC 5.99.1.2 KW - Camptothecin KW - XT3Z54Z28A KW - Index Medicus KW - Polymerase Chain Reaction KW - Base Sequence KW - Tumor Cells, Cultured KW - DNA Damage KW - Humans KW - Molecular Sequence Data KW - Enzyme Inhibitors -- pharmacology KW - DNA, Ribosomal -- metabolism KW - RNA, Ribosomal, 18S -- chemistry KW - Binding Sites KW - DNA, Neoplasm -- chemistry KW - Colonic Neoplasms -- genetics KW - Camptothecin -- pharmacology KW - Antineoplastic Agents, Phytogenic -- pharmacology KW - Sequence Analysis, DNA KW - DNA, Neoplasm -- metabolism KW - DNA Topoisomerases, Type I -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79315024?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=In+vivo+sequencing+of+camptothecin-induced+topoisomerase+I+cleavage+sites+in+human+colon+carcinoma+cells.&rft.au=Pondarr%C3%A9%2C+C%3BStrumberg%2C+D%3BFujimori%2C+A%3BTorres-Le%C3%B3n%2C+R%3BPommier%2C+Y&rft.aulast=Pondarr%C3%A9&rft.aufirst=C&rft.date=1997-10-15&rft.volume=25&rft.issue=20&rft.spage=4111&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 - 1997-12-02 N1 - Date created - 1997-12-02 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: EMBO J. 1984 Mar;3(3):671-6 [6325181] Annu Rev Biochem. 1996;65:635-92 [8811192] Hum Genet. 1986 Jul;73(3):193-8 [3015766] Mol Cell Biol. 1987 Jan;7(1):141-8 [3031452] Proc Natl Acad Sci U S A. 1987 May;84(10):3185-8 [3033639] Cell. 1987 Sep 25;50(7):1109-17 [2887294] Proc Natl Acad Sci U S A. 1988 Feb;85(4):1060-4 [2829214] Cell. 1988 Feb 26;52(4):585-97 [2830030] Cancer Res. 1988 Apr 1;48(7):1722-6 [2832051] J Mol Biol. 1988 Jul 20;202(2):333-42 [2845097] Cancer Res. 1989 Sep 15;49(18):5016-22 [2548707] Science. 1989 Nov 10;246(4931):810-3 [2814502] Nucleic Acids Res. 1989 Nov 11;17(21):8521-32 [2555774] Cell. 1990 Jan 12;60(1):141-9 [2153054] Pharmacol Ther. 1991;49(1-2):55-77 [1852788] Mol Cell Biochem. 1991 Mar 13;101(2):115-24 [1650425] J Biol Chem. 1991 Oct 25;266(30):20418-23 [1657924] J Mol Biol. 1991 Dec 5;222(3):669-78 [1660929] Biochemistry. 1992 Mar 10;31(9):2492-501 [1312349] Nucleic Acids Res. 1993 Nov 11;21(22):5157-66 [8255771] J Biol Chem. 1994 Mar 18;269(11):7893-900 [8132507] Cancer Invest. 1994;12(5):530-42 [7922710] Protein Expr Purif. 1994 Aug;5(4):364-70 [7950383] J Biol Chem. 1994 Nov 18;269(46):28702-7 [7961822] Biochem Biophys Res Commun. 1994 Dec 30;205(3):1601-9 [7811242] Cancer Res. 1995 May 15;55(10):2116-21 [7743511] Biochemistry. 1995 May 30;34(21):7200-6 [7766631] Biochim Biophys Acta. 1995 May 17;1262(1):1-14 [7772596] J Biol Chem. 1985 Nov 25;260(27):14873-8 [2997227] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Functional cleavage of the common cytokine receptor gamma chain (gammac) by calpain. AN - 79326860; 9326644 AB - The small subunit of calpain, a calcium-dependent cysteine protease, was found to interact with the cytoplasmic domain of the common cytokine receptor gamma chain (gammac) in a yeast two-hybrid interaction trap assay. This interaction was functional as demonstrated by the ability of calpain to cleave in vitro-translated wild-type gammac, but not gammac containing a mutation in the PEST (proline, glutamate, serine, and threonine) sequence in its cytoplasmic domain, as well as by the ability of endogenous calpain to mediate cleavage of gammac in a calcium-dependent fashion. In T cell receptor-stimulated murine thymocytes, calpain inhibitors decreased cleavage of gammac. Moreover, in single positive CD4(+) thymocytes, not only did a calpain inhibitor augment CD3-induced proliferation, but antibodies to gammac blocked this effect. Finally, treatment of cells with ionomycin could inhibit interleukin 2-induced STAT protein activation, but this inhibition could be reversed by calpain inhibitors. Together, these data suggest that calpain-mediated cleavage of gammac represents a mechanism by which gammac-dependent signaling can be controlled. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Noguchi, M AU - Sarin, A AU - Aman, M J AU - Nakajima, H AU - Shores, E W AU - Henkart, P A AU - Leonard, W J AD - Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1997/10/14/ PY - 1997 DA - 1997 Oct 14 SP - 11534 EP - 11539 VL - 94 IS - 21 SN - 0027-8424, 0027-8424 KW - DNA Primers KW - 0 KW - Interleukin-2 KW - Macromolecular Substances KW - Receptor-CD3 Complex, Antigen, T-Cell KW - Receptors, Cytokine KW - Recombinant Proteins KW - Threonine KW - 2ZD004190S KW - Glutamic Acid KW - 3KX376GY7L KW - Serine KW - 452VLY9402 KW - Ionomycin KW - 56092-81-0 KW - Proline KW - 9DLQ4CIU6V KW - Calpain KW - EC 3.4.22.- KW - Index Medicus KW - CD4-Positive T-Lymphocytes -- cytology KW - Animals KW - Recombinant Proteins -- biosynthesis KW - Humans KW - CD4-Positive T-Lymphocytes -- immunology KW - Ionomycin -- pharmacology KW - Lymphocyte Activation KW - Mutagenesis, Site-Directed KW - Sequence Alignment KW - Recombinant Proteins -- metabolism KW - Molecular Sequence Data KW - Receptor-CD3 Complex, Antigen, T-Cell -- physiology KW - Recombinant Proteins -- chemistry KW - Signal Transduction KW - Amino Acid Substitution KW - Interleukin-2 -- pharmacology KW - Protein Biosynthesis KW - Amino Acid Sequence KW - Mice KW - CD4-Positive T-Lymphocytes -- drug effects KW - Polymerase Chain Reaction KW - Base Sequence KW - Cells, Cultured KW - Mice, Inbred C57BL KW - Substrate Specificity KW - T-Lymphocytes -- cytology KW - Receptors, Cytokine -- biosynthesis KW - T-Lymphocytes -- drug effects KW - Receptors, Cytokine -- metabolism KW - Receptors, Cytokine -- chemistry KW - T-Lymphocytes -- immunology KW - Calpain -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79326860?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Functional+cleavage+of+the+common+cytokine+receptor+gamma+chain+%28gammac%29+by+calpain.&rft.au=Noguchi%2C+M%3BSarin%2C+A%3BAman%2C+M+J%3BNakajima%2C+H%3BShores%2C+E+W%3BHenkart%2C+P+A%3BLeonard%2C+W+J&rft.aulast=Noguchi&rft.aufirst=M&rft.date=1997-10-14&rft.volume=94&rft.issue=21&rft.spage=11534&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 - 1997-11-24 N1 - Date created - 1997-11-24 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cell. 1995 Aug 11;82(3):349-52 [7634323] Immunology. 1995 Jun;85(2):331-7 [7642225] Annu Rev Med. 1996;47:229-39 [8712778] J Immunol. 1989 Sep 15;143(6):1801-6 [2528581] J Biochem. 1989 Aug;106(2):274-81 [2553682] Nature. 1989 Nov 30;342(6249):505-11 [2555717] J Immunol. 1990 Sep 1;145(5):1364-8 [1974564] Cell. 1990 Dec 21;63(6):1249-56 [2148123] Int Immunol. 1990;2(1):83-9 [2150922] Science. 1991 Jun 14;252(5012):1523-8 [2047859] Physiol Rev. 1991 Jul;71(3):813-47 [2057527] FEBS Lett. 1991 Aug 5;287(1-2):57-61 [1908791] Semin Cell Biol. 1990 Dec;1(6):433-40 [2103894] Science. 1992 Jul 3;257(5066):96-9 [1621102] Science. 1992 Jul 17;257(5068):379-82 [1631559] Cytometry. 1992;13(8):809-21 [1458998] Genes Dev. 1993 Apr;7(4):555-69 [8384581] Proc Natl Acad Sci U S A. 1993 Mar 15;90(6):2189-93 [8460122] Cell. 1993 Apr 9;73(1):147-57 [8462096] Eur J Immunol. 1993 Jul;23(7):1623-9 [8325338] Immunol Today. 1993 Jul;14(7):338-9 [8363721] J Biol Chem. 1993 Oct 25;268(30):22733-6 [8226783] Science. 1993 Dec 17;262(5141):1874-7 [8266076] Science. 1993 Dec 17;262(5141):1877-80 [8266077] Science. 1993 Dec 17;262(5141):1880-3 [8266078] Cell. 1994 Jan 14;76(1):17-27 [8287475] J Biol Chem. 1994 Jan 21;269(3):1599-602 [8294403] J Exp Med. 1994 Feb 1;179(2):709-13 [8294878] Science. 1994 Feb 25;263(5150):1139-43 [7509084] J Biol Chem. 1994 Feb 25;269(8):5937-43 [7509794] Cell. 1994 Feb 25;76(4):651-63 [8124708] Science. 1994 Mar 11;263(5152):1453-4 [8128231] J Immunol. 1994 May 1;152(9):4270-81 [7908916] FEBS Lett. 1994 Apr 18;343(1):1-5 [8163008] J Cell Physiol. 1994 May;159(2):229-37 [8163563] Nature. 1994 May 26;369(6478):330-3 [8183373] Nature. 1994 May 26;369(6478):333-6 [7514277] Blood. 1994 Jun 15;83(12):3462-7 [8204874] Annu Rev Immunol. 1994;12:675-705 [8011294] EMBO J. 1994 Jun 15;13(12):2822-30 [8026467] Science. 1994 Nov 11;266(5187):1039-42 [7973657] Science. 1994 Nov 11;266(5187):1042-5 [7973658] Science. 1994 Nov 11;266(5187):1045-7 [7973659] Proc Natl Acad Sci U S A. 1995 Jan 17;92(2):377-81 [7831294] Proc Natl Acad Sci U S A. 1996 Mar 5;93(5):2077-82 [8700888] Immunol Rev. 1995 Dec;148:97-114 [8825284] Proc Natl Acad Sci U S A. 1993 Sep 15;90(18):8464-8 [8378320] J Immunol. 1985 Apr;134(4):2431-5 [3919094] Science. 1986 Oct 17;234(4774):364-8 [2876518] Immunol Rev. 1988 Jan;101:173-90 [3280468] Nature. 1989 Jan 12;337(6203):181-4 [2521375] Immunol Rev. 1989 Feb;107:141-58 [2465990] J Immunol. 1989 May 1;142(9):3006-12 [2523422] Adv Enzyme Regul. 1988;27:135-51 [2907964] Nature. 1989 Jul 20;340(6230):245-6 [2547163] Biochem Int. 1989 Feb;18(2):263-94 [2548504] J Biol Chem. 1995 Feb 3;270(5):2032-5 [7836429] J Immunol. 1995 Feb 15;154(4):1596-605 [7530740] Eur J Immunol. 1995 Jan;25(1):291-4 [7843245] J Biol Chem. 1995 Feb 10;270(6):2497-505 [7852311] Immunity. 1994 Apr;1(1):45-56 [7889398] Immunity. 1995 Mar;2(3):223-38 [7697543] Immunol Rev. 1994 Dec;142:343-63 [7698800] Immunity. 1995 Apr;2(4):331-9 [7719938] J Immunol. 1995 Jun 1;154(11):5806-12 [7751630] Proc Natl Acad Sci U S A. 1995 Jun 6;92(12):5491-5 [7777536] Immunity. 1995 Jan;2(1):89-100 [7600304] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Fluorescence in situ hybridization analysis of keratinocyte growth factor gene amplification and dispersion in evolution of great apes and humans. AN - 79326827; 9326632 AB - Keratinocyte growth factor (KGF) is a member of the fibroblast growth factor family. Portions of the gene encoding KGF were amplified during primate evolution and are present in multiple nonprocessed copies in the human genome. Nucleotide analysis of a representative sampling of these KGF-like sequences indicated that they were at least 95% identical to corresponding regions of the KGF gene. To localize these sequences to specific chromosomal sites in human and higher primates, we used fluorescence in situ hybridization. In human, using a cosmid probe encoding KGF exon 1, we assigned the location of the KGF gene to chromosome 15q15-21.1. In addition, copies of KGF-like sequences hybridizing only with a cosmid probe encoding exons 2 and 3 were localized to dispersed sites on chromosome 2q21, 9p11, 9q12-13, 18p11, 18q11, 21q11, and 21q21.1. The distribution of KGF-like sequences suggests a role for alphoid DNA in their amplification and dispersion. In chimpanzee, KGF-like sequences were observed at five chromosomal sites, which were each homologous to sites in human, while in gorilla, a subset of four of these homologous sites was identified; in orangutan two sites were identified, while gibbon exhibited only a single site. The chromosomal localization of KGF sequences in human and great ape genomes indicates that amplification and dispersion occurred in multiple discrete steps, with initial KGF gene duplication and dispersion taking place in gibbon and involving loci corresponding to human chromosomes 15 and 21. These findings support the concept of a closer evolutionary relationship of human and chimpanzee and a possible selective pressure for such dispersion during the evolution of higher primates. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Zimonjic, D B AU - Kelley, M J AU - Rubin, J S AU - Aaronson, S A AU - Popescu, N C AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1997/10/14/ PY - 1997 DA - 1997 Oct 14 SP - 11461 EP - 11465 VL - 94 IS - 21 SN - 0027-8424, 0027-8424 KW - FGF7 protein, human KW - 0 KW - Fibroblast Growth Factor 10 KW - Growth Substances KW - Fibroblast Growth Factor 7 KW - 126469-10-1 KW - Fibroblast Growth Factors KW - 62031-54-3 KW - Index Medicus KW - Karyotyping KW - Animals KW - Exons KW - Humans KW - Hylobates -- genetics KW - Pongo pygmaeus -- genetics KW - In Situ Hybridization, Fluorescence KW - Cosmids KW - Gorilla gorilla -- genetics KW - Pregnancy KW - Gene Amplification KW - Chromosomes, Human KW - Pan troglodytes -- genetics KW - Placenta -- metabolism KW - Female KW - Growth Substances -- genetics KW - Hominidae -- genetics KW - Growth Substances -- biosynthesis KW - Chromosome Mapping KW - Evolution, Molecular UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79326827?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Fluorescence+in+situ+hybridization+analysis+of+keratinocyte+growth+factor+gene+amplification+and+dispersion+in+evolution+of+great+apes+and+humans.&rft.au=Zimonjic%2C+D+B%3BKelley%2C+M+J%3BRubin%2C+J+S%3BAaronson%2C+S+A%3BPopescu%2C+N+C&rft.aulast=Zimonjic&rft.aufirst=D&rft.date=1997-10-14&rft.volume=94&rft.issue=21&rft.spage=11461&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 - 1997-11-24 N1 - Date created - 1997-11-24 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Mol Evol. 1995 Oct;41(4):487-91 [7563136] Cancer Genet Cytogenet. 1995 Apr;80(2):100-2 [7736422] Hereditas. 1968;59(1):169-87 [5662632] Nature. 1987 Apr 2-8;326(6112):501-5 [3453121] Chromosoma. 1988;96(6):443-53 [3219915] Proc Natl Acad Sci U S A. 1989 Feb;86(3):802-6 [2915979] Science. 1989 Aug 18;245(4919):752-5 [2475908] Hum Genet. 1989 Dec;84(1):27-34 [2606474] Proc Natl Acad Sci U S A. 1991 Oct 15;88(20):9051-5 [1924367] Genomics. 1991 Sep;11(1):15-23 [1765373] Proc Natl Acad Sci U S A. 1992 Sep 15;89(18):8611-5 [1528869] Proc Natl Acad Sci U S A. 1992 Oct 1;89(19):9287-91 [1409637] Hum Genet. 1993 Feb;90(6):577-83 [8444464] Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):1872-6 [8446601] Nat Genet. 1992 Sep;2(1):11-2 [1303243] Cytogenet Cell Genet. 1994;65(3):184-5 [8222757] Genomics. 1994 Mar 15;20(2):333-5 [8020992] J Biol Chem. 1995 May 12;270(19):11230-7 [7744756] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Good pain, bad pain. AN - 79349214; 9340772 JF - Science (New York, N.Y.) AU - Iadarola, J M AU - Caudle, R M AD - Pain and Neurosensory Mechanisms Branch, National Institute of Dental Research, NIH, Bethesda, MD 20892-4410, USA. iadarola@yoda.nidr.nih.gov Y1 - 1997/10/10/ PY - 1997 DA - 1997 Oct 10 SP - 239 EP - 240 VL - 278 IS - 5336 SN - 0036-8075, 0036-8075 KW - Immunotoxins KW - 0 KW - Isoenzymes KW - Plant Proteins KW - Receptors, Neurokinin-1 KW - Ribosome Inactivating Proteins, Type 1 KW - Substance P KW - 33507-63-0 KW - protein kinase C gamma KW - EC 2.7.1.- KW - Protein Kinase C KW - EC 2.7.11.13 KW - N-Glycosyl Hydrolases KW - EC 3.2.2.- KW - saporin KW - EC 3.2.2.22 KW - Index Medicus KW - Animals KW - Pain -- physiopathology KW - Spinal Cord KW - Receptors, Neurokinin-1 -- biosynthesis KW - Humans KW - Mice KW - Rats KW - Gene Expression Regulation KW - Neuronal Plasticity KW - Substance P -- administration & dosage KW - Mutation KW - Signal Transduction KW - Protein Kinase C -- metabolism KW - Pain Management KW - Neurons -- metabolism KW - Hyperalgesia -- physiopathology KW - Hyperalgesia -- therapy KW - Protein Kinase C -- genetics KW - Isoenzymes -- genetics KW - Plant Proteins -- administration & dosage KW - Isoenzymes -- metabolism KW - Neurons -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79349214?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Good+pain%2C+bad+pain.&rft.au=Iadarola%2C+J+M%3BCaudle%2C+R+M&rft.aulast=Iadarola&rft.aufirst=J&rft.date=1997-10-10&rft.volume=278&rft.issue=5336&rft.spage=239&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 - 1997-10-23 N1 - Date created - 1997-10-23 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment On: Science. 1997 Oct 10;278(5336):275-9 [9323204] Science. 1997 Oct 10;278(5336):279-83 [9323205] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - ADP-ribosylation factor 6 regulates a novel plasma membrane recycling pathway. AN - 79317418; 9314528 AB - ADP-ribosylation factor (ARF) 6 localizes to the plasma membrane (PM) in its GTP state and to a tubulovesicular compartment in its GDP state in HeLa cells that express wild-type or mutant forms of this GTPase. Aluminum fluoride (AlF) treatment of ARF6-transfected cells redistributes ARF6 to the PM and stimulates the formation of actin-rich surface protrusions. Here we show that cytochalasin D (CD) treatment inhibited formation of the AlF-induced protrusions and shifted the distribution of ARF6 to a tubular membrane compartment emanating from the juxtanuclear region of cells, which resembled the compartment where the GTP-binding defective mutant of ARF6 localized. This membrane compartment was distinct from transferrin-positive endosomes, could be detected in the absence of ARF6 overexpression or CD treatment, and was accessible to loading by PM proteins lacking clathrin/AP-2 cytoplasmic targeting sequences, such as the IL-2 receptor alpha subunit Tac. ARF6 and surface Tac moved into this compartment and back out to the PM in the absence of pharmacologic treatment. Whereas AlF treatment blocked internalization, CD treatment blocked the recycling of wild-type ARF6 and Tac back to the PM; these blocks were mimicked by expression of ARF6 mutants Q67L and T27N, which were predicted to be in either the GTP- or GDP-bound state, respectively. Thus, the ARF6 GTP cycle regulates this membrane traffic pathway. The delivery of ARF6 and membrane to defined sites along the PM may provide components necessary for remodeling the cell surface and the underlying actin cytoskeleton. JF - The Journal of cell biology AU - Radhakrishna, H AU - Donaldson, J G AD - Laboratory of Cell Biology, National Heart, Lung, and Blood Institute, Bethesda, Maryland 20892, USA. Y1 - 1997/10/06/ PY - 1997 DA - 1997 Oct 06 SP - 49 EP - 61 VL - 139 IS - 1 SN - 0021-9525, 0021-9525 KW - Biomarkers KW - 0 KW - Receptors, Interleukin-2 KW - Cytochalasin D KW - 22144-77-0 KW - GTP Phosphohydrolases KW - EC 3.6.1.- KW - GTP-Binding Proteins KW - ADP-Ribosylation Factors KW - EC 3.6.5.2 KW - Adenylyl Cyclases KW - EC 4.6.1.1 KW - Index Medicus KW - Microtubules -- enzymology KW - Cell Membrane -- enzymology KW - Cell Membrane -- drug effects KW - HeLa Cells KW - Humans KW - Receptors, Interleukin-2 -- antagonists & inhibitors KW - Microtubules -- physiology KW - Cell Membrane -- physiology KW - Microtubules -- drug effects KW - Adenylyl Cyclases -- physiology KW - Receptors, Interleukin-2 -- metabolism KW - Receptors, Interleukin-2 -- physiology KW - Cell Compartmentation -- drug effects KW - Cytochalasin D -- pharmacology KW - Mutagenesis, Insertional KW - GTP Phosphohydrolases -- physiology KW - GTP-Binding Proteins -- metabolism KW - Endocytosis -- drug effects KW - GTP-Binding Proteins -- physiology KW - GTP-Binding Proteins -- genetics KW - Endocytosis -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79317418?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=p53+tumor+suppressor+gene%3A+at+the+crossroads+of+molecular+carcinogenesis%2C+molecular+epidemiology%2C+and+cancer+risk+assessment.&rft.au=Harris%2C+C+C&rft.aulast=Harris&rft.aufirst=C&rft.date=1996-05-01&rft.volume=104+Suppl+3&rft.issue=&rft.spage=435&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 - 1998-02-18 N1 - Date created - 1998-02-18 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1982 Aug;79(16):4888-91 [6289322] J Cell Biol. 1996 Aug;134(4):935-47 [8769418] J Biol Chem. 1983 Apr 25;258(8):4715-24 [6300098] J Cell Biol. 1983 Aug;97(2):508-21 [6309862] Cell. 1984 Jul;37(3):789-800 [6204769] Nature. 1984 Oct 18-24;311(5987):626-31 [6090948] Hybridoma. 1985 Summer;4(2):91-102 [2408992] J Biol Chem. 1996 Sep 6;271(36):21767-74 [8702973] J Cell Sci. 1996 Jul;109 ( Pt 7):1655-65 [8832388] J Cell Biol. 1996 Nov;135(4):913-24 [8922376] Annu Rev Cell Dev Biol. 1996;12:575-625 [8970738] J Biol Chem. 1997 Jan 31;272(5):2788-93 [9006918] J Cell Biol. 1997 Jan 27;136(2):319-30 [9015303] J Cell Biol. 1997 Feb 10;136(3):583-95 [9024689] J Biol Chem. 1994 May 6;269(18):13325-30 [8175763] J Cell Biol. 1994 Jun;125(6):1265-74 [7515888] Proc Natl Acad Sci U S A. 1994 Nov 22;91(24):11718-22 [7972129] Curr Opin Cell Biol. 1994 Aug;6(4):527-32 [7986529] Science. 1995 Feb 24;267(5201):1175-8 [7855600] J Cell Biol. 1995 Mar;128(6):1003-17 [7896867] Proc Natl Acad Sci U S A. 1986 Mar;83(5):1463-6 [3081898] J Biol Chem. 1986 Jun 15;261(17):7906-11 [3086320] Cell. 1987 Dec 24;51(6):1053-62 [2826014] Mol Cell Biol. 1988 Jan;8(1):466-72 [2827008] J Cell Biol. 1989 Jun;108(6):2169-81 [2738091] J Cell Biol. 1989 Jul;109(1):73-83 [2663883] Cell Motil Cytoskeleton. 1989;13(3):127-44 [2776221] Cell. 1990 Apr 6;61(1):171-83 [2156628] Cell. 1990 Nov 2;63(3):503-13 [2225064] J Biol Chem. 1991 Feb 5;266(4):2606-14 [1899243] J Biol Chem. 1991 Feb 15;266(5):2772-7 [1993656] J Cell Biol. 1991 Feb;112(4):579-88 [1993732] J Cell Biol. 1991 Nov;115(3):635-53 [1918157] Cell. 1991 Nov 1;67(3):591-600 [1657400] Cell. 1991 Nov 1;67(3):601-16 [1682055] Cell. 1991 Nov 1;67(3):617-27 [1934063] Cell. 1992 Apr 3;69(1):129-38 [1555237] Proc Natl Acad Sci U S A. 1992 Jul 15;89(14):6408-12 [1631136] Cell. 1992 Sep 4;70(5):729-40 [1516131] Nature. 1992 Nov 26;360(6402):350-2 [1448151] Nature. 1992 Nov 26;360(6402):352-4 [1448152] J Biol Chem. 1993 May 5;268(13):9555-63 [8486645] J Biol Chem. 1993 Jun 5;268(16):12083-9 [8505331] J Cell Biol. 1993 Jun;121(6):1257-69 [8509447] J Cell Biol. 1993 Nov;123(3):561-73 [8227126] J Cell Biol. 1993 Dec;123(6 Pt 1):1365-71 [8253837] Cell. 1993 Dec 17;75(6):1137-44 [8261513] J Biol Chem. 1994 Jan 14;269(2):1437-48 [8288610] Science. 1994 Jan 28;263(5146):523-6 [8290961] J Cell Biol. 1994 Feb;124(3):289-300 [8294513] J Biol Chem. 1994 Feb 4;269(5):3135-8 [8106346] J Cell Biol. 1995 Apr;129(2):459-71 [7721946] J Biol Chem. 1995 May 26;270(21):12327-30 [7759471] Curr Opin Cell Biol. 1995 Aug;7(4):552-63 [7495576] Curr Opin Cell Biol. 1995 Aug;7(4):573-80 [7495578] J Cell Biol. 1995 Oct;131(2):351-69 [7593164] J Biol Chem. 1995 Dec 15;270(50):29640-3 [8530346] J Cell Biol. 1996 Jul;134(2):295-306 [8707816] J Cell Biol. 1983 Jan;96(1):1-27 [6298247] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Murine vesicular monoamine transporter 2: molecular cloning and genomic structure. AN - 79438435; 9387858 AB - The principal brain vesicular monoamine transporter (VMAT2) pumps monoamines including dopamine, norepinephrine, serotonin and histamine from neuronal cytoplasm into synaptic vesicles and is implicated in actions of certain psychostimulants and selective neurotoxins. To improve understanding of this gene and its regulation, and to facilitate study of the roles played by this important molecule in mouse genetic models, we have cloned murine VMAT2 cDNA and genomic sequences. A 4.2-kb mouse VMAT2 cDNA hybridized to a 4.3-kb mRNA expressed chiefly in brainstem. Murine cDNA and genomic DNA analyses reveal an open reading frame of 1551 bp encoding 517 amino acids that display 92, 96 and 60% amino-acid identity with human and rat VMAT2, and rat vesicular acetylcholine transporter sequences, respectively. This open reading frame is distributed over 15 of 16 identified exons, and spans > 35 kb of genomic DNA. A major transcriptional initiation site is identified 107 bp 5' to the translational initiation ATG codon using primer extension/5' rapid amplification of cDNA ends. Sequences immediately 5' of this putative transcription start site lack 'TATA' or 'CATT' boxes, but contain consensus sequences that may bind cAMP response element, Sp1, AP2 and other transcription factors. Identification of these genomic sequences facilitates construction of homologous recombinant mice, provides a template for gene structures in the vesicular transporter family, and identifies sequences elements that could contribute to the specific patterns of regulated VMAT2 expression in monoaminergic neurons. JF - Brain research. Molecular brain research AU - Takahashi, N AU - Uhl, G AD - Molecular Neurobiology Branch, Intramural Research Program, National Institute on Drug Abuse, NIH, Baltimore, MD 21224, USA. Y1 - 1997/10/03/ PY - 1997 DA - 1997 Oct 03 SP - 7 EP - 14 VL - 49 IS - 1-2 SN - 0169-328X, 0169-328X KW - DNA, Complementary KW - 0 KW - Membrane Glycoproteins KW - Membrane Transport Proteins KW - Neuropeptides KW - Neurotransmitter Agents KW - RNA, Messenger KW - Recombinant Proteins KW - SLC18A2 protein, human KW - Slc18a2 protein, mouse KW - Slc18a2 protein, rat KW - Vesicular Biogenic Amine Transport Proteins KW - Vesicular Monoamine Transport Proteins KW - Index Medicus KW - Animals KW - Brain Stem -- metabolism KW - Recombinant Proteins -- biosynthesis KW - Exons KW - Open Reading Frames KW - Humans KW - Transcription, Genetic KW - Amino Acid Sequence KW - Mice KW - RNA, Messenger -- biosynthesis KW - Cloning, Molecular KW - Rats KW - Regulatory Sequences, Nucleic Acid KW - Base Sequence KW - Sequence Alignment KW - Conserved Sequence KW - Introns KW - Molecular Sequence Data KW - Recombinant Proteins -- chemistry KW - Sequence Homology, Amino Acid KW - Membrane Glycoproteins -- chemistry KW - Membrane Glycoproteins -- biosynthesis KW - Brain -- metabolism KW - Membrane Glycoproteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79438435?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain+research.+Molecular+brain+research&rft.atitle=Murine+vesicular+monoamine+transporter+2%3A+molecular+cloning+and+genomic+structure.&rft.au=Takahashi%2C+N%3BUhl%2C+G&rft.aulast=Takahashi&rft.aufirst=N&rft.date=1997-10-03&rft.volume=49&rft.issue=1-2&rft.spage=7&rft.isbn=&rft.btitle=&rft.title=Brain+research.+Molecular+brain+research&rft.issn=0169328X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-02-11 N1 - Date created - 1998-02-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characterization of the long-lasting activator protein-1 complex induced by kainic acid treatment. AN - 79422525; 9372202 AB - Kainic acid is known to induce seizures, neuronal damage and cell loss in the rat hippocampus. Our laboratory has shown that a single kainic acid injection elicits acute increases of activator protein-1 DNA-binding activity and this activity stays at an elevated level for 2 weeks after kainic acid injection. However, some pathological changes such as mossy fiber sprouting do not occur until 2-3 weeks after the kainic acid injection and the specific transcription factors regulating the long-term events after kainic acid treatment are not clear. To determine the involvement of activator protein-1 transcription factors in the long-term events after kainic acid treatment, gel mobility-shift and Western blot analyses were used. The results showed that two activator protein-1 complexes with different mobilities occur during the acute stage. However, only the faster-migrating complex as well as the 35-37-kDa fos-related antigen and Jun-D proteins were seen during the late stage. These results suggest that different activator protein-1 complexes exist at different stages after convulsions and that they regulate ensembles of different genes. JF - Brain research AU - Feng, Z AU - Zhang, W AU - Hudson, P AU - Bing, G AU - Feng, W AU - Hong, J S AD - Neuropharmacology Section, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. feng@niehs.nih.gov Y1 - 1997/10/03/ PY - 1997 DA - 1997 Oct 03 SP - 53 EP - 59 VL - 770 IS - 1-2 SN - 0006-8993, 0006-8993 KW - Excitatory Amino Acid Agonists KW - 0 KW - Peptide Fragments KW - Proto-Oncogene Proteins c-fos KW - Proto-Oncogene Proteins c-jun KW - Transcription Factor AP-1 KW - Kainic Acid KW - SIV03811UC KW - Index Medicus KW - Peptide Fragments -- metabolism KW - Animals KW - Proto-Oncogene Proteins c-jun -- immunology KW - Proto-Oncogene Proteins c-fos -- metabolism KW - Hippocampus -- metabolism KW - Peptide Fragments -- analysis KW - Proto-Oncogene Proteins c-jun -- metabolism KW - Peptide Fragments -- immunology KW - Proto-Oncogene Proteins c-jun -- analysis KW - Rats KW - Antibody Specificity KW - Rats, Inbred F344 KW - Blotting, Western KW - Proto-Oncogene Proteins c-fos -- analysis KW - Time Factors KW - Hippocampus -- chemistry KW - Male KW - Seizures -- chemically induced KW - Transcription Factor AP-1 -- metabolism KW - Transcription Factor AP-1 -- analysis KW - Transcription Factor AP-1 -- chemistry KW - Seizures -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79422525?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Characterization+of+the+long-lasting+activator+protein-1+complex+induced+by+kainic+acid+treatment.&rft.au=Feng%2C+Z%3BZhang%2C+W%3BHudson%2C+P%3BBing%2C+G%3BFeng%2C+W%3BHong%2C+J+S&rft.aulast=Feng&rft.aufirst=Z&rft.date=1997-10-03&rft.volume=770&rft.issue=1-2&rft.spage=53&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 - 1998-01-21 N1 - Date created - 1998-01-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The coiled-coil region of the G protein beta subunit. Mutational analysis of Ggamma and effector interactions. AN - 79317360; 9312156 AB - The beta and gamma subunits of the heterotrimeric G proteins remain tightly associated throughout the signaling cycle as the betagamma dimer interacts with Galpha, receptors, and effectors. A coiled-coil structure involving alpha-helical segments at the N termini of the beta and gamma subunits contributes to the dimerization interface and has been implicated in effector signaling in yeast. Scanning mutagenesis of the coiled-coil region of the mammalian beta1 subunit was performed to examine the effect of point mutations on betagamma assembly and effector signaling in COS cell cotransfection assays. In addition to the E10K mutation described previously, mutations A11E, L14E, and I18E in beta1 were found to block betagamma association, as evidenced by the failure of the Gbeta mutants to undergo cytosolic translocation with cotransfected nonisoprenylated Ggamma. Although none of 14 beta1 point mutations prevented the betagamma-dependent activation of the c-Jun N-terminal kinase (JNK) effector pathway, the D20K point mutation enhanced JNK but not phospholipase C-beta2 activation. These findings implicate the coiled-coil region of Gbeta in JNK signaling, provide further evidence that the structural features of the betagamma complex mediating effector regulation may differ among effectors, and identify single codons in the mammalian beta subunit where mutation might yield a phenotype of defective signal transduction. JF - The Journal of biological chemistry AU - Pellegrino, S AU - Zhang, S AU - Garritsen, A AU - Simonds, W F AD - Metabolic Diseases Branch, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1997/10/03/ PY - 1997 DA - 1997 Oct 03 SP - 25360 EP - 25366 VL - 272 IS - 40 SN - 0021-9258, 0021-9258 KW - DNA, Complementary KW - 0 KW - Isoenzymes KW - Macromolecular Substances KW - Recombinant Proteins KW - Calcium-Calmodulin-Dependent Protein Kinases KW - EC 2.7.11.17 KW - JNK Mitogen-Activated Protein Kinases KW - EC 2.7.11.24 KW - Mitogen-Activated Protein Kinases KW - Type C Phospholipases KW - EC 3.1.4.- KW - Phospholipase C beta KW - EC 3.1.4.11 KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - Index Medicus KW - Animals KW - Models, Structural KW - COS Cells KW - Recombinant Proteins -- biosynthesis KW - Isoenzymes -- metabolism KW - Type C Phospholipases -- metabolism KW - Mutagenesis, Site-Directed KW - Sequence Alignment KW - Recombinant Proteins -- metabolism KW - Molecular Sequence Data KW - Point Mutation KW - Recombinant Proteins -- chemistry KW - Signal Transduction KW - Calcium-Calmodulin-Dependent Protein Kinases -- metabolism KW - Amino Acid Sequence KW - Schizosaccharomyces KW - Cloning, Molecular KW - Saccharomyces cerevisiae KW - Conserved Sequence KW - Transfection KW - Kinetics KW - Restriction Mapping KW - Plants KW - Protein Structure, Secondary KW - GTP-Binding Proteins -- biosynthesis KW - GTP-Binding Proteins -- metabolism KW - GTP-Binding Proteins -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79317360?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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+coiled-coil+region+of+the+G+protein+beta+subunit.+Mutational+analysis+of+Ggamma+and+effector+interactions.&rft.au=Pellegrino%2C+S%3BZhang%2C+S%3BGarritsen%2C+A%3BSimonds%2C+W+F&rft.aulast=Pellegrino&rft.aufirst=S&rft.date=1997-10-03&rft.volume=272&rft.issue=40&rft.spage=25360&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 - 1997-10-22 N1 - Date created - 1997-10-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Sites of interaction between kinase-related protein and smooth muscle myosin. AN - 79317314; 9312155 AB - Kinase-related protein, also known as KRP or telokin, is an independently expressed protein product derived from a gene within the gene for myosin light chain kinase (MLCK). KRP binds to unphosphorylated smooth muscle myosin filaments and stabilizes them against ATP-induced depolymerization in vitro. KRP competes with MLCK for binding to myosin, suggesting that both proteins bind to myosin by the KRP domain (Shirinsky, V. P., Vorotnikov, A. V., Birukov, K. G., Nanaev, A. K., Collinge, M., Lukas, T. J., Sellers, J. R., and Watterson, D. M. (1993) J. Biol. Chem. 268, 16578-16583). In this study, we investigated which regions of myosin and KRP interact in vitro. Using cosedimentation assays, we determined that KRP binds to unphosphorylated myosin with a stoichiometry of 1 mol of KRP/1 mol of myosin and an affinity of 5.5 microM. KRP slows the rate of proteolytic cleavage of the head-tail junction of heavy meromyosin by papain and chymotrypsin, suggesting it is binding to this region of myosin. In addition, competition experiments, using soluble headless fragments of nonmuscle myosin, confirmed that KRP interacts with the regulatory light chain binding region of myosin. The regions important for KRP's binding to myosin were investigated using bacterially expressed KRP truncation mutants. We determined that the acid-rich sequence between Gly138 and Asp151 of KRP is required for high affinity myosin binding, and that the amino terminus and beta-barrel regions weakly interact with myosin. All KRP truncations, at concentrations comparable to their KD values, exhibited some stabilization of myosin filaments against ATP depolymerization in vitro, suggesting that KRP's ability to stabilize myosin filaments is commensurate with its myosin binding affinity. KRP weakened the Km but not the Vmax of phosphorylation of myosin by MLCK, demonstrating that bound KRP does not prevent MLCK from activating myosin. JF - The Journal of biological chemistry AU - Silver, D L AU - Vorotnikov, A V AU - Watterson, D M AU - Shirinsky, V P AU - Sellers, J R AD - Laboratory of Molecular Cardiology, NHLBI, Bethesda, Maryland 20892, USA. Y1 - 1997/10/03/ PY - 1997 DA - 1997 Oct 03 SP - 25353 EP - 25359 VL - 272 IS - 40 SN - 0021-9258, 0021-9258 KW - Calcium-Binding Proteins KW - 0 KW - DNA Primers KW - Muscle Proteins KW - Recombinant Proteins KW - kinesin-II KW - 147096-75-1 KW - Myosins KW - EC 3.6.4.1 KW - Kinesin KW - EC 3.6.4.4 KW - Index Medicus KW - Animals KW - Models, Structural KW - Turkeys KW - Amino Acid Sequence KW - Binding Sites KW - Mutagenesis, Site-Directed KW - Recombinant Proteins -- isolation & purification KW - Polymerase Chain Reaction KW - Base Sequence KW - Chickens KW - Recombinant Proteins -- metabolism KW - Molecular Sequence Data KW - Crystallography, X-Ray KW - Recombinant Proteins -- chemistry KW - Sequence Deletion KW - Gizzard, Avian KW - Muscle Proteins -- metabolism KW - Myosins -- metabolism KW - Protein Structure, Secondary KW - Muscle Proteins -- chemistry KW - Calcium-Binding Proteins -- isolation & purification KW - Myosins -- chemistry KW - Muscle Proteins -- isolation & purification KW - Calcium-Binding Proteins -- metabolism KW - Calcium-Binding Proteins -- chemistry KW - Muscle, Smooth -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79317314?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Sites+of+interaction+between+kinase-related+protein+and+smooth+muscle+myosin.&rft.au=Silver%2C+D+L%3BVorotnikov%2C+A+V%3BWatterson%2C+D+M%3BShirinsky%2C+V+P%3BSellers%2C+J+R&rft.aulast=Silver&rft.aufirst=D&rft.date=1997-10-03&rft.volume=272&rft.issue=40&rft.spage=25353&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 - 1997-10-22 N1 - Date created - 1997-10-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characterization of a GDP dissociation inhibitory region of ADP-ribosylation factor domain protein ARD1. AN - 79314989; 9312116 AB - ADP-ribosylation factors (ARFs) are approximately 20-kDa guanine nucleotide-binding proteins initially identified by their ability to stimulate cholera toxin ADP-ribosyltransferase activity and later recognized as critical components in intracellular vesicular transport and phospholipase D activation. ARF domain protein 1 (ARD1) is a member of the ARF family that differs from other ARFs by the presence of a 46-kDa amino-terminal extension. We previously reported that this extension acts as a GTPase-activating protein for the ARF domain of ARD1 (Vitale, N., Moss, J., and Vaughan, M. (1996) Proc. Natl. Acad. Sci. U. S. A. 93, 1941-1944). Both GTP binding and GTP hydrolysis are necessary for physiological function of guanine nucleotide-binding proteins, and the rates of GDP/GTP exchange and GTPase activity are critical in the activation/deactivation cycle. Dissociation of GDP from the ARF domain of ARD1 was faster than from ARD1 itself (both proteins synthesized in Escherichia coli). Using deletion mutations, it was demonstrated that the 15 amino acids directly preceding the ARF domain were responsible for decreasing the rate of GDP dissociation but not guanosine 5-[gamma-thio]triphosphate dissociation. By site-specific mutagenesis it was shown that hydrophobic amino acids in this region were particularly important in stabilizing the GDP-bound form of ARD1. It is suggested that, like the amino-terminal segment of ARF, the equivalent region in ARD1, located between the GTPase-activating protein and ARF domains, may act as a GDP dissociation inhibitor. JF - The Journal of biological chemistry AU - Vitale, N AU - Moss, J AU - Vaughan, M AD - Pulmonary-Critical Care Medicine Branch, NHLBI, National Institutes of Health, Bethesda, Maryland 20892, USA. vitalen@fido.nhlbi.nih.gov Y1 - 1997/10/03/ PY - 1997 DA - 1997 Oct 03 SP - 25077 EP - 25082 VL - 272 IS - 40 SN - 0021-9258, 0021-9258 KW - DNA Primers KW - 0 KW - Recombinant Proteins KW - Thionucleotides KW - Guanosine Diphosphate KW - 146-91-8 KW - Guanosine 5'-O-(3-Thiotriphosphate) KW - 37589-80-3 KW - guanosine 5'-O-(2-thiodiphosphate) KW - 71376-97-1 KW - Guanosine Triphosphate KW - 86-01-1 KW - Thrombin KW - EC 3.4.21.5 KW - GTP Phosphohydrolases KW - EC 3.6.1.- KW - GTP-Binding Proteins KW - ADP-Ribosylation Factors KW - EC 3.6.5.2 KW - Index Medicus KW - Animals KW - Recombinant Proteins -- biosynthesis KW - Thionucleotides -- metabolism KW - Amino Acid Sequence KW - Cloning, Molecular KW - Guanosine Triphosphate -- metabolism KW - Mutagenesis, Site-Directed KW - Polymerase Chain Reaction KW - Base Sequence KW - Cattle KW - Recombinant Proteins -- metabolism KW - GTP Phosphohydrolases -- metabolism KW - Kinetics KW - Molecular Sequence Data KW - Escherichia coli KW - Guanosine 5'-O-(3-Thiotriphosphate) -- metabolism KW - Recombinant Proteins -- chemistry KW - Sequence Deletion KW - GTP-Binding Proteins -- biosynthesis KW - Guanosine Diphosphate -- metabolism KW - GTP-Binding Proteins -- metabolism KW - Guanosine Diphosphate -- analogs & derivatives KW - GTP-Binding Proteins -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79314989?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Characterization+of+a+GDP+dissociation+inhibitory+region+of+ADP-ribosylation+factor+domain+protein+ARD1.&rft.au=Vitale%2C+N%3BMoss%2C+J%3BVaughan%2C+M&rft.aulast=Vitale&rft.aufirst=N&rft.date=1997-10-03&rft.volume=272&rft.issue=40&rft.spage=25077&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 - 1997-10-22 N1 - Date created - 1997-10-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Addiction is a brain disease, and it matters. AN - 79306795; 9311924 AB - Scientific advances over the past 20 years have shown that drug addiction is a chronic, relapsing disease that results from the prolonged effects of drugs on the brain. As with many other brain diseases, addiction has embedded behavioral and social-context aspects that are important parts of the disorder itself. Therefore, the most effective treatment approaches will include biological, behavioral, and social-context components. Recognizing addiction as a chronic, relapsing brain disorder characterized by compulsive drug seeking and use can impact society's overall health and social policy strategies and help diminish the health and social costs associated with drug abuse and addiction. JF - Science (New York, N.Y.) AU - Leshner, A I AD - National Institute on Drug Abuse, National Institutes of Health, 5600 Fishers Lane, Room 10-05, Rockville, MD 20857, USA. leshner@nih.gov Y1 - 1997/10/03/ PY - 1997 DA - 1997 Oct 03 SP - 45 EP - 47 VL - 278 IS - 5335 SN - 0036-8075, 0036-8075 KW - Index Medicus KW - Behavior, Addictive KW - Public Health KW - Humans KW - Brain -- drug effects KW - Chronic Disease KW - Social Problems KW - Health Policy KW - Brain -- physiology KW - Recurrence KW - Substance-Related Disorders -- therapy KW - Substance-Related Disorders -- etiology KW - Brain Diseases -- chemically induced KW - Brain Diseases -- physiopathology KW - Substance-Related Disorders -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79306795?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Addiction+is+a+brain+disease%2C+and+it+matters.&rft.au=Leshner%2C+A+I&rft.aulast=Leshner&rft.aufirst=A&rft.date=1997-10-03&rft.volume=278&rft.issue=5335&rft.spage=45&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 - 1997-10-23 N1 - Date created - 1997-10-23 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Comment In: Science. 1998 May 8;280(5365):807-8 [9599150] J Addict Dis. 2016 Oct-Dec;35(4):213-217 [27192094] N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Clinical profile of mania in children and adolescents from the Indian subcontinent. AN - 85272519; pmid-9356772 AB - OBJECTIVES: To see whether classic DSM-III-R criteria for mania are applicable to Indian youngsters and to examine the clinical presentation of mania in an Indian child and adolescent psychiatric sample. METHOD: Fifty subjects with a diagnosis of functional psychosis as per the definition in ICD-9 were recruited from the population referred during the study period of approximately one year (n = 840) to the Child and Adolescent Psychiatry (CAP) clinic of the National Institute of Mental Health and Neuro Sciences (NIMHANS), Bangalore, South India. The subjects were systematically evaluated using a standardized clinical interview and demographic questionnaire and were classified according to DSM-III-R. The subjects who satisfied DSM-III-R criteria for mania formed the sample for this study. RESULTS: Twenty-one subjects received a diagnosis of mania according to DSM-III-R. The most common symptoms of mania included pressure of speech, irritability, elation, distractibility, increased self-esteem, expansive mood, flight of ideas, and grandiose delusions. No subject had comorbid attention-deficit hyperactivity disorder (ADHD). Additionally, 13 (61%) of the 21 manic subjects had delusions and/or hallucinations. The other common symptoms included psychomotor agitation, reduced sleep, anger, temper tantrums, decreased concentration, disobedience, aggression, and hyperactivity. CONCLUSIONS: Mania was diagnosable in Indian children and adolescents using classic DSM-III-R criteria. The clinical profile appears to be generally similar to that seen in adults. ADHD is not a comorbid condition. The presence of aggressive or disruptive behaviours and hyperactivity in childhood- and adolescent-onset mania, however, could lead to a misdiagnosis of attention-deficit hyperactivity disorder/conduct disorder (ADHD/CD). Similarly, the presence of psychotic features could lead to a misdiagnosis of schizophrenia. JF - Canadian Journal of Psychiatry. Revue Canadienne de Psychiatrie AU - Reddy, Y C AU - Girimaji, S AU - Srinath, S AD - Department of Psychiatry, National Institute of Mental Health and Neuro Sciences, Bangalore, India. PY - 1997 SP - 841 EP - 846 VL - 42 IS - 8 SN - 0706-7437, 0706-7437 KW - Diagnosis, Differential KW - Psychiatric Status Rating Scales KW - Bipolar Disorder KW - Human KW - Adult KW - Child KW - Adolescent KW - Psychometrics KW - Female KW - Male KW - India KW - Developing Countries UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85272519?accountid=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=Canadian+Journal+of+Psychiatry.+Revue+Canadienne+de+Psychiatrie&rft.atitle=Clinical+profile+of+mania+in+children+and+adolescents+from+the+Indian+subcontinent.&rft.au=Reddy%2C+Y+C%3BGirimaji%2C+S%3BSrinath%2C+S&rft.aulast=Reddy&rft.aufirst=Y&rft.date=1997-10-01&rft.volume=42&rft.issue=8&rft.spage=841&rft.isbn=&rft.btitle=&rft.title=Canadian+Journal+of+Psychiatry.+Revue+Canadienne+de+Psychiatrie&rft.issn=07067437&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Improved sensitivity of detection with the commercial automated gel electrophoresis (HPGE-1000) apparatus through modification of its optical system. AN - 85269108; pmid-9420151 AB - In a representative application to a fluorescently detectable protein of commercial automated gel electrophoresis apparatus (HPGE-1000, LabIntelligence, Belmont, CA) the sensitivity of detection by fluorescence was significantly increased by elimination of the mirror below the gel tray. That increase in detection sensitivity is due to a decrease of fluorescent background noise by nearly one order of magnitude, overcompensating a decrease in signal by a factor of two. The resulting increase in signal/noise ratio, i.e., detection sensitivity, should allow for lowered sample loads by which the band width is reduced with benefits to resolution. JF - Electrophoresis AU - Yarmola, E AU - Chrambach, A AD - Laboratory of Cellular and Molecular Biophysics, NICHD, National Institutes of Health, Bethesda, MD 20892-1580, USA. PY - 1997 SP - 1951 EP - 1954 VL - 18 IS - 11 SN - 0173-0835, 0173-0835 KW - Sensitivity and Specificity KW - Fluorescence KW - Electrophoresis, Agar Gel KW - Autoanalysis KW - Phycoerythrin KW - Optics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85269108?accountid=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=Electrophoresis&rft.atitle=Improved+sensitivity+of+detection+with+the+commercial+automated+gel+electrophoresis+%28HPGE-1000%29+apparatus+through+modification+of+its+optical+system.&rft.au=Yarmola%2C+E%3BChrambach%2C+A&rft.aulast=Yarmola&rft.aufirst=E&rft.date=1997-10-01&rft.volume=18&rft.issue=11&rft.spage=1951&rft.isbn=&rft.btitle=&rft.title=Electrophoresis&rft.issn=01730835&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Ethical complexities of conducting research in developing countries. AN - 85244173; pmid-9309109 AB - Ethical challenges are posed by attempts to conduct clinical trials in developing countries. Such trials must seek interventions that could realistically benefit the population involved. An inadequate understanding of the complexity of such trials has led to unfair charges that developing country trials of interventions to prevent maternal-infant transmission of HIV are comparable with the infamous Tuskegee study where subjects were deprived of available treatment for syphilis. The system of ethical protection developed after the Tuskegee scandal called for respect for persons, beneficence, and justice in research trials. To apply these principles to research in developing countries requires the support and involvement of the host country as well as an understanding of how conditions in the host country may differ from conditions in the partner country and, thus, may require different types of clinical trials. The current debate hinges on the morality of using a placebo control when the AIDS Clinical Trials Group protocol 076 is being effectively used in other parts of the world. The 076 protocol, however, has not been proved effective in developing country settings, and its per person treatment cost exceeds that which can be assumed by developing countries. The most compelling response to criticisms of the placebo-control test designs is that it provides definitive answers to safety and effectiveness questions in the study setting. Debate on this issue is healthy but should be informed by adequate knowledge of local factors that influence research. JF - The New England Journal of Medicine AU - Varmus, H AU - Satcher, D AD - National Institutes of Health, Bethesda, MD 20892-0148, USA. PY - 1997 SP - 1003 EP - 1005 VL - 337 IS - 14 SN - 0028-4793, 0028-4793 KW - HIV Infections KW - Beneficence KW - Human KW - Disease Transmission, Vertical KW - Pregnancy Complications, Infectious KW - Ethical Review KW - Zidovudine KW - Placebos KW - Federal Government KW - Personal Autonomy KW - Internationality KW - Female KW - Pregnancy KW - Risk Assessment KW - Control Groups KW - Pregnant Women KW - Ethics, Medical KW - Developing Countries KW - Clinical Trials KW - Therapeutic Human Experimentation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85244173?accountid=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+New+England+Journal+of+Medicine&rft.atitle=Ethical+complexities+of+conducting+research+in+developing+countries.&rft.au=Varmus%2C+H%3BSatcher%2C+D&rft.aulast=Varmus&rft.aufirst=H&rft.date=1997-10-01&rft.volume=337&rft.issue=14&rft.spage=1003&rft.isbn=&rft.btitle=&rft.title=The+New+England+Journal+of+Medicine&rft.issn=00284793&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Expression of the nicotinic acetylcholine receptor subunit, alpha9, in the guinea pig cochlea. AN - 85241565; pmid-9367232 AB - Acetylcholine is a major neurotransmitter of the cochlear efferent system. Based on its high level of expression in hair cells, the recently cloned nicotinic receptor subunit, alpha9 [Elgoyhen et al., Cell 79 (1994) 705-715], is likely to be the postsynaptic receptor for acetylcholine in hair cells either as a homomeric complex or with other subunits yet to be identified. To further study this receptor, we cloned and sequenced alpha9 cDNA from the guinea pig organ of Corti library [Wilcox and Fex, Hear. Res. 62 (1992) 124-126]. The sequence of the guinea pig alpha9 cDNA is similar to that of the rat, with identities of 85% and 89% at the nucleotide and amino acid levels, respectively. Most differences are in the cytoplasmic loop domain between the transmembrane segments 3 and 4. We also observed minor differences in the putative ligand binding regions. Pharmacological differences between acetylcholine receptors on outer hair cells of rat and guinea pig have been reported, and the minor structural changes we observe could account for these differences. Reverse transcription-polymerase chain reaction analysis showed a high expression of alpha9 in the organ of Corti while expression was low or not detected in the spiral ganglion. In situ hybridization histochemistry showed expression of alpha9 mRNA in both inner and outer hair cells, with much higher expression in outer hair cells than in inner hair cells. In the inner hair cell, silver grains were more abundant over the basal part of the cell than over the apical part. Immunocytochemistry showed a pattern of distribution of the alpha9 protein similar to that seen for mRNA with in situ hybridization. Immunolabeling was most intense at the bases of both inner and outer hair cells. To determine the effect of hair cell loss on alpha9 expression, hair cells were destroyed by either systemic or local application of kanamycin. This treatment led to a down regulation of alpha9 in hair cells; this down regulation appeared to precede hair cell degeneration. In the spiral ganglion, a transient up regulation of alpha9, as determined by RT-PCR, was seen 4-6 weeks after kanamycin treatment. JF - Hearing Research AU - Park, H J AU - Niedzielski, A S AU - Wenthold, R J AD - Laboratory of Neurochemistry, NIDCD, NIH, Bethesda, MD 20892, USA. PY - 1997 SP - 95 EP - 105 VL - 112 IS - 1-2 SN - 0378-5955, 0378-5955 KW - Cochlea KW - Sequence Homology, Nucleic Acid KW - Guinea Pigs KW - Animal KW - Gene Expression KW - Amino Acid Sequence KW - Kanamycin KW - Cloning, Molecular KW - Rats KW - Polymerase Chain Reaction KW - DNA, Complementary KW - In Situ Hybridization KW - Base Sequence KW - Receptors, Nicotinic KW - DNA Primers KW - Molecular Sequence Data KW - Sequence Homology, Amino Acid KW - Immunohistochemistry KW - Male KW - Protein Conformation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85241565?accountid=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=Hearing+Research&rft.atitle=Expression+of+the+nicotinic+acetylcholine+receptor+subunit%2C+alpha9%2C+in+the+guinea+pig+cochlea.&rft.au=Park%2C+H+J%3BNiedzielski%2C+A+S%3BWenthold%2C+R+J&rft.aulast=Park&rft.aufirst=H&rft.date=1997-10-01&rft.volume=112&rft.issue=1-2&rft.spage=95&rft.isbn=&rft.btitle=&rft.title=Hearing+Research&rft.issn=03785955&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - The glutamate receptor subunit delta1 is highly expressed in hair cells of the auditory and vestibular systems. AN - 85219083; pmid-9295397 AB - In the inner ear, fast excitatory synaptic transmission is mediated by ionotropic glutamate receptors, including AMPA, kainate, and NMDA receptors. The recently identified delta1 and delta2 glutamate receptors share low homology with the other three types, and no clear response or ligand binding has been obtained from cells transfected with delta alone or in combination with other ionotropic receptors. Studies of mice lacking expression of delta2 show that this subunit plays a crucial role in plasticity of cerebellar glutamatergic synapses. In addition, these mice show a deficit in vestibular compensation. These findings and the nature of glutamatergic synapses between vestibulocochlear hair cells and primary afferent dendrites suggest that delta receptors may be functionally important in the inner ear and prompted us to investigate the expression of delta receptors in the cochlea and peripheral vestibular system. Reverse transcription and DNA amplification by PCR combined with immunocytochemistry and in situ hybridization were used. Our results show that the expression of delta1 in the organ of Corti is intense and restricted to the inner hair cells, whereas delta1 is expressed in all spiral ganglion neurons as well as in their satellite glial cells. In the vestibular end organ, delta1 was highly expressed in both hair cell types and also was expressed in the vestibular ganglion neurons. The prominent expression of delta1 in inner hair cells and in type I and type II vestibular hair cells suggests a functional role in hair cell neurotransmission. JF - The Journal of Neuroscience AU - Safieddine, S AU - Wenthold, R J AD - Laboratory of Neurochemistry, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland 20892, USA. PY - 1997 SP - 7523 EP - 7531 VL - 17 IS - 19 SN - 0270-6474, 0270-6474 KW - Rats KW - Polymerase Chain Reaction KW - Blotting, Western KW - In Situ Hybridization KW - Hair Cells KW - Auditory Pathways KW - Guinea Pigs KW - Animal KW - Receptors, Glutamate KW - Transcription, Genetic KW - Vestibule KW - Immunohistochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85219083?accountid=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=Carcinogenesis&rft.atitle=Expression+of+transforming+growth+factor+alpha%2Fepidermal+growth+factor+receptor%2C+hepatocyte+growth+factor%2Fc-met+and+acidic+fibroblast+growth+factor%2Ffibroblast+growth+factor+receptors+during+hepatocarcinogenesis.&rft.au=Hu%2C+Z%3BEvarts%2C+R+P%3BFujio%2C+K%3BOmori%2C+N%3BOmori%2C+M%3BMarsden%2C+E+R%3BThorgeirsson%2C+S+S&rft.aulast=Hu&rft.aufirst=Z&rft.date=1996-05-01&rft.volume=17&rft.issue=5&rft.spage=931&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Antifolates in clinical development. AN - 79507203; 9420020 AB - Many novel antifolate compounds with unique pharmacologic properties are currently in clinical development. These newer antifolates differ from methotrexate, the most widely used and studied drug in this class, in terms of their lipid solubility and cellular transport affinity, their level of polyglutamation, and their specificity for inhibiting folate-dependent enzymes, such as dihydrofolate reductase, thymidylate synthase, or glycinamide ribonucleotide formyltransferase. The current status (ie, mechanism of action, clinical response rates, and toxicity) of some of the newer antifolate compounds presently in clinical testing, including edatrexate, piritrexim, raltritrexed, LY 231514, AG337, AG331, 1843U89, ZD 9331, and lometrexol, is reviewed. JF - Seminars in oncology AU - Takimoto, C H AD - Developmental Therapeutics Department, National Cancer Institute, Bethesda Naval Hospital, MD 20889-5105, USA. Y1 - 1997/10// PY - 1997 DA - October 1997 SP - S18 EP - 40-S18-51 VL - 24 IS - 5 Suppl 18 SN - 0093-7754, 0093-7754 KW - Antimetabolites, Antineoplastic KW - 0 KW - Enzyme Inhibitors KW - Folic Acid Antagonists KW - Glutamates KW - Indoles KW - Isoindoles KW - Pyrimidines KW - Quinazolines KW - Tetrahydrofolates KW - Thiophenes KW - ZD 9331 KW - Pemetrexed KW - 04Q9AIZ7NO KW - 1843U89 KW - 139987-54-5 KW - Guanine KW - 5Z93L87A1R KW - lometrexol KW - 6P3AVY8A7Q KW - Thymidylate Synthase KW - EC 2.1.1.45 KW - raltitrexed KW - FCB9EGG971 KW - edatrexate KW - JT4X6Z1HRR KW - Aminopterin KW - JYB41CTM2Q KW - nolatrexed KW - K75ZUN743Q KW - piritrexim KW - MK2A783ZUT KW - Index Medicus KW - Animals KW - Pyrimidines -- therapeutic use KW - Humans KW - Aminopterin -- pharmacology KW - Guanine -- therapeutic use KW - Thiophenes -- therapeutic use KW - Thiophenes -- pharmacology KW - Tetrahydrofolates -- pharmacology KW - Tetrahydrofolates -- therapeutic use KW - Enzyme Inhibitors -- therapeutic use KW - Clinical Trials as Topic KW - Pyrimidines -- pharmacology KW - Glutamates -- therapeutic use KW - Thymidylate Synthase -- antagonists & inhibitors KW - Glutamates -- pharmacology KW - Aminopterin -- therapeutic use KW - Quinazolines -- therapeutic use KW - Enzyme Inhibitors -- pharmacology KW - Aminopterin -- analogs & derivatives KW - Indoles -- therapeutic use KW - Guanine -- analogs & derivatives KW - Indoles -- pharmacology KW - Guanine -- pharmacology KW - Quinazolines -- pharmacology KW - Folic Acid Antagonists -- therapeutic use KW - Folic Acid Antagonists -- pharmacology KW - Drug Design KW - Antimetabolites, Antineoplastic -- therapeutic use KW - Antimetabolites, Antineoplastic -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79507203?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Antifolates+in+clinical+development.&rft.au=Takimoto%2C+C+H&rft.aulast=Takimoto&rft.aufirst=C&rft.date=1997-10-01&rft.volume=24&rft.issue=5+Suppl+18&rft.spage=S18&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 - 1998-01-14 N1 - Date created - 1998-01-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Systemic treatment options in advanced colorectal cancer: perspectives on combination 5-fluorouracil plus leucovorin. AN - 79492318; 9420016 AB - A variety of 5-fluorouracil (5-FU)- based chemotherapy regimens have been investigated in colorectal cancer patients in randomized trials over the past decade. The standard regimen for treatment of colorectal cancer is combination 5-FU plus leucovorin (LV). The results from 12 randomized trials indicate that 5-FU/LV is more active than single-agent 5-FU (25% v 14% of evaluable patients); however, median survival was unchanged (12.2 months v 11.4 months, respectively). Furthermore, the weekly and monthly schedules of 5-FU/LV are therapeutically equivalent, although the spectrum of toxicity differs. On the monthly schedule, a LV dose of 200 mg/m2 appears to have no advantage over 20 mg/m2; however, on the weekly schedule, high-dose LV appeared to be slightly more effective than low-dose LV (2-hour infusion) (25% v 18%) at the cost of a higher incidence of severe diarrhea (26% v 14%). Furthermore, similar response rates are observed with the racemic commercial formulation of LV and the pure (I-LV) active stereoisomer. Other modulatory strategies that appear to produce higher response rates than single-agent intravenous push 5-FU include sequential methotrexate/5-FU (19% v 10%) and continuous infusion schedules (22% v 14%). Although 5-FU-modulated strategies improve response rates over those observed with single-agent 5-FU, median survival in multi-institutional trials unfortunately has not generally exceeded 12 months. The mechanism of action, clinical activity, and toxicity of single-agent 5-FU and 5-FU-modulated regimens are reviewed. JF - Seminars in oncology AU - Grem, J L AD - Developmental Therapeutics Department, Medicine Branch, National Cancer Institute, National Naval Medical Center, Bethesda, MD 20889-5105, USA. Y1 - 1997/10// PY - 1997 DA - October 1997 SP - S18 EP - 8-S18-18 VL - 24 IS - 5 Suppl 18 SN - 0093-7754, 0093-7754 KW - Antidotes KW - 0 KW - Antimetabolites, Antineoplastic KW - Immunologic Factors KW - Leucovorin KW - Q573I9DVLP KW - Fluorouracil KW - U3P01618RT KW - Index Medicus KW - Drug Therapy, Combination KW - Randomized Controlled Trials as Topic KW - Drug Administration Schedule KW - Humans KW - Antimetabolites, Antineoplastic -- administration & dosage KW - Immunologic Factors -- administration & dosage KW - Antidotes -- administration & dosage KW - Leucovorin -- administration & dosage KW - Antidotes -- therapeutic use KW - Colorectal Neoplasms -- drug therapy KW - Antimetabolites, Antineoplastic -- pharmacology KW - Fluorouracil -- administration & dosage KW - Fluorouracil -- therapeutic use KW - Immunologic Factors -- therapeutic use KW - Fluorouracil -- pharmacology KW - Antimetabolites, Antineoplastic -- therapeutic use KW - Leucovorin -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79492318?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Systemic+treatment+options+in+advanced+colorectal+cancer%3A+perspectives+on+combination+5-fluorouracil+plus+leucovorin.&rft.au=Grem%2C+J+L&rft.aulast=Grem&rft.aufirst=J&rft.date=1997-10-01&rft.volume=24&rft.issue=5+Suppl+18&rft.spage=S18&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 - 1998-01-14 N1 - Date created - 1998-01-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mu opioid receptor gene variants: lack of association with alcohol dependence. AN - 79469176; 9399694 AB - The mu opioid receptor is implicated in the reward, tolerance and withdrawal effects of alcohol and other drugs of abuse. This hypothesis is supported by the effects of alcohol on beta-endorphin release, of mu opioid receptor agonists and antagonists on alcohol consumption, and by the activation of the dopaminergic reward system by both alcohol and opiates. In addition, the murine mu opioid receptor locus, Oprm, is implicated as the major quantitative trait locus (QTL) affecting the different levels of morphine consumption between two inbred mouse strains that also exhibit differences in alcohol and cocaine consumption. Detection of genetic variation affecting OPRM1 expression or mu opioid receptor function would be an important step towards understanding the origins of inter-individual variation in response to mu opioid receptor ligands and in diseases of substance dependence. We directly sequenced the human mu opioid receptor locus, OPRM1, to detect natural variation that might affect function and/or be associated with psychiatric phenotypes related to opioid function. Four DNA sequence variants were found: three non-synonymous substitutions (Ala6Val [rare], Asn40Asp, [0.10-0.16], Ser147Cys [rare]) and one intronic variant (IVS2+691G/C [0.55-0.63]). OPRM1 alleles, genotypes and haplotypes from three psychiatrically characterized population samples (US Caucasian [USC, n=100], Finnish Caucasian [FC, n=324] and Southwestern American Indian [SAI, n=367]), were used to perform association and sib-pair linkage analyses with alcohol and drug dependence diagnoses. No significant association of OPRM1 genetic variation to phenotype was observed. This analysis has 80% power to detect a small to moderate effect of OPRM1 variation on alcohol dependence and 100% power to detect effects of the magnitude of the ALDH2*2 variant. While these data do not support a role of the mu opioid receptor in susceptibility to alcohol dependence, the potential relationship between OPRM1 genetic variation and response to endogenous opioids and exogenous opiates can now be investigated. JF - Molecular psychiatry AU - Bergen, A W AU - Kokoszka, J AU - Peterson, R AU - Long, J C AU - Virkkunen, M AU - Linnoila, M AU - Goldman, D AD - Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, Rockville, Maryland 20852, USA. awb@dicbr.niaaa.nih.gov PY - 1997 SP - 490 EP - 494 VL - 2 IS - 6 SN - 1359-4184, 1359-4184 KW - Receptors, Opioid, mu KW - 0 KW - Index Medicus KW - United States KW - Genetic Linkage KW - Regression Analysis KW - Animals KW - Exons KW - Finland KW - Humans KW - Nuclear Family KW - Mice KW - Asian Continental Ancestry Group -- genetics KW - Chromosome Mapping KW - Quantitative Trait, Heritable KW - Genotype KW - Polymerase Chain Reaction KW - Mice, Inbred Strains KW - Haplotypes KW - Adult KW - Point Mutation KW - Substance-Related Disorders -- genetics KW - Southwestern United States KW - Female KW - Male KW - Genetic Variation KW - Alcoholism -- genetics KW - European Continental Ancestry Group -- genetics KW - Indians, North American -- genetics KW - Receptors, Opioid, mu -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79469176?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+psychiatry&rft.atitle=Mu+opioid+receptor+gene+variants%3A+lack+of+association+with+alcohol+dependence.&rft.au=Bergen%2C+A+W%3BKokoszka%2C+J%3BPeterson%2C+R%3BLong%2C+J+C%3BVirkkunen%2C+M%3BLinnoila%2C+M%3BGoldman%2C+D&rft.aulast=Bergen&rft.aufirst=A&rft.date=1997-10-01&rft.volume=2&rft.issue=6&rft.spage=490&rft.isbn=&rft.btitle=&rft.title=Molecular+psychiatry&rft.issn=13594184&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-01-15 N1 - Date created - 1998-01-15 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF024517; GENBANK; AF024515; AF024516 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Menarche in a cohort of 188 long-term survivors of acute lymphoblastic leukemia. AN - 79443415; 9386666 AB - As more children survive acute lymphoblastic leukemia (ALL), questions are raised regarding how the disease and its therapy affect their pubertal development. The National Institute of Child Health and Human Development-National Cancer Institute-Children's Cancer Group Leukemia Follow-Up Study used a historical cohort design to investigate menarche in 188 ALL survivors who were premanarchal at diagnosis, aged at least 18 years, at least 2 years after diagnosis, alive, and in remission. Female siblings of ALL survivors (n = 218) served as control subjects. Menarche occurred within the normal age range in 92% of survivors and 96% of the control subjects (p = 0.09). Early menarche occurred in four survivors (2%) and three control subjects (1%). Delayed, absent, or medically induced menarche was reported by 12 survivors (6%) and six control subjects (3%). Compared with the control subjects, survivors of ALL who received 1800 cGy cranial radiation before the age of 8 years had significantly earlier menarche, relative hazard (RH) of 2.2 (95% confidence interval: 1.4, 3.4 [p = 0.0003]). Survivors receiving 2400 cGy of craniospinal radiation with or without abdominal radiation had significantly later menarche than the control subjects, RH 0.4 (95% confidence interval: 0.3, 0.7 [p = 0.0002]). In this large cohort of ALL survivors, the risk of disordered menarche was low. However, younger subjects receiving 1800 cGy cranial radiation and those receiving 2400 cGy below the diaphragm required careful monitoring. JF - The Journal of pediatrics AU - Mills, J L AU - Fears, T R AU - Robison, L L AU - Nicholson, H S AU - Sklar, C A AU - Byrne, J AD - Pediatric Epidemiology Section, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1997/10// PY - 1997 DA - October 1997 SP - 598 EP - 602 VL - 131 IS - 4 SN - 0022-3476, 0022-3476 KW - Abridged Index Medicus KW - Index Medicus KW - Humans KW - Cohort Studies KW - Child KW - Dose-Response Relationship, Radiation KW - Adolescent KW - Female KW - Menarche -- radiation effects KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma -- radiotherapy KW - Survivors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79443415?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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+pediatrics&rft.atitle=Menarche+in+a+cohort+of+188+long-term+survivors+of+acute+lymphoblastic+leukemia.&rft.au=Mills%2C+J+L%3BFears%2C+T+R%3BRobison%2C+L+L%3BNicholson%2C+H+S%3BSklar%2C+C+A%3BByrne%2C+J&rft.aulast=Mills&rft.aufirst=J&rft.date=1997-10-01&rft.volume=131&rft.issue=4&rft.spage=598&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+pediatrics&rft.issn=00223476&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-01-06 N1 - Date created - 1998-01-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pimozide-induced depression in men who stutter. AN - 79430166; 9375593 AB - Neuroleptic-related dysphoric reactions are well recognized in the context of psychiatric disorders, especially in association with extrapyramidal side effects. Very few controlled data exist regarding the effects of neuroleptics on the mood of psychiatrically "normal" subjects. In this study, the depressogenic effect of the neuroleptic drug pimozide was assessed in men without psychiatric disorders. Eight men with developmental stuttering but no past or present psychiatric illness participated in a double-blind, placebo-controlled study assessing the effect of 6 weeks of pimozide treatment on speech fluency and mood. Four of the seven subjects who were compliant with the treatment developed marked depressive symptoms. No clear association was found between these reactions and pimozide dose, blood level, or degree of neurologic side effects. Symptoms abated soon after drug discontinuation. Pimozide induced significant depressive symptoms in this group of psychiatrically normal men who stutter. Neuroleptic drugs may have a causal effect in the induction of depression in psychiatrically normal subjects, ostensibly independent of dose or severity of neurologic side effects. JF - The Journal of clinical psychiatry AU - Bloch, M AU - Stager, S AU - Braun, A AU - Calis, K A AU - Turcasso, N M AU - Grothe, D R AU - Rubinow, D R AD - Department of Health and Human Services, National Institute of Mental Health, Bethesda, Md. 20892-1276, USA. Y1 - 1997/10// PY - 1997 DA - October 1997 SP - 433 EP - 436 VL - 58 IS - 10 SN - 0160-6689, 0160-6689 KW - Antipsychotic Agents KW - 0 KW - Placebos KW - Pimozide KW - 1HIZ4DL86F KW - Index Medicus KW - Severity of Illness Index KW - Affect -- drug effects KW - Sex Factors KW - Double-Blind Method KW - Humans KW - Personality Inventory KW - Psychiatric Status Rating Scales KW - Adult KW - Cross-Over Studies KW - Middle Aged KW - Adolescent KW - Speech -- drug effects KW - Male KW - Basal Ganglia Diseases -- chemically induced KW - Pimozide -- therapeutic use KW - Pimozide -- adverse effects KW - Stuttering -- psychology KW - Stuttering -- drug therapy KW - Depressive Disorder -- chemically induced KW - Antipsychotic Agents -- therapeutic use KW - Depressive Disorder -- diagnosis KW - Antipsychotic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79430166?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=The+bryostatins+inhibit+growth+of+B16%2FF10+melanoma+cells+in+vitro+through+a+protein+kinase+C-independent+mechanism%3A+dissociation+of+activities+using+26-epi-bryostatin+1.&rft.au=Szallasi%2C+Z%3BDu%2C+L%3BLevine%2C+R%3BLewin%2C+N+E%3BNguyen%2C+P+N%3BWilliams%2C+M+D%3BPettit%2C+G+R%3BBlumberg%2C+P+M&rft.aulast=Szallasi&rft.aufirst=Z&rft.date=1996-05-01&rft.volume=56&rft.issue=9&rft.spage=2105&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 - 1997-12-08 N1 - Date created - 1997-12-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A novel role for the peritrophic matrix in protecting Leishmania from the hydrolytic activities of the sand fly midgut. AN - 79411401; 9364562 AB - The role of the peritrophic matrix (PM) in the development of Leishmania major infections in a natural vector, Phlebotomus papatasi, was investigated by addition of exogenous chitinase to the bloodmeal, which completely blocked PM formation. Surprisingly, the absence of the PM was associated with the loss of midgut infections. The chitinase was not directly toxic to the parasite, nor were midgut infections lost due to premature expulsion of the bloodmeal. Most parasites were killed in chitinase-treated flies within the first 4 h after feeding. Substantial early killing was also observed in control flies, suggesting that the lack of PM exacerbates lethal conditions which normally exist in the blood-fed midgut. Early parasite mortality was reversed by soybean trypsin inhibitor. Allosamadin, a specific inhibitor of chitinase, led to a thickening of the PM, and also prevented the early parasite mortality seen in infected flies. Susceptibility to gut proteases was extremely high in transitional-stage parasites, while amastigotes and fully transformed promastigotes were relatively resistant. A novel role for the PM in promoting parasite survival is suggested, in which the PM creates a barrier to the rapid diffusion of digestive enzymes, and limits the exposure of parasites to these enzymes during the time when they are especially vulnerable to proteolytic damage. JF - Parasitology AU - Pimenta, P F AU - Modi, G B AU - Pereira, S T AU - Shahabuddin, M AU - Sacks, D L AD - Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1997/10// PY - 1997 DA - October 1997 SP - 359 EP - 369 VL - 115 ( Pt 4) SN - 0031-1820, 0031-1820 KW - Trisaccharides KW - 0 KW - allosamidin KW - 103782-08-7 KW - Chitinases KW - EC 3.2.1.14 KW - Trypsin KW - EC 3.4.21.4 KW - Acetylglucosamine KW - V956696549 KW - Index Medicus KW - Eating KW - Animals KW - Acetylglucosamine -- pharmacology KW - Chitinases -- pharmacology KW - Hydrolysis KW - Chitinases -- antagonists & inhibitors KW - Acetylglucosamine -- analogs & derivatives KW - Trisaccharides -- pharmacology KW - Insect Vectors -- parasitology KW - Digestive System -- anatomy & histology KW - Phlebotomus -- parasitology KW - Leishmania major -- drug effects KW - Insect Vectors -- anatomy & histology KW - Phlebotomus -- anatomy & histology KW - Digestive System -- metabolism KW - Digestive System -- parasitology KW - Trypsin -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79411401?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Parasitology&rft.atitle=A+novel+role+for+the+peritrophic+matrix+in+protecting+Leishmania+from+the+hydrolytic+activities+of+the+sand+fly+midgut.&rft.au=Pimenta%2C+P+F%3BModi%2C+G+B%3BPereira%2C+S+T%3BShahabuddin%2C+M%3BSacks%2C+D+L&rft.aulast=Pimenta&rft.aufirst=P&rft.date=1997-10-01&rft.volume=115+%28+Pt+4%29&rft.issue=&rft.spage=359&rft.isbn=&rft.btitle=&rft.title=Parasitology&rft.issn=00311820&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-12-18 N1 - Date created - 1997-12-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Enhancement of the transcription potential of nascent chromatin by chromosomal proteins HMG-14/-17 is coupled to nucleosome assembly and not DNA synthesis. AN - 79410403; 9364931 AB - We have previously demonstrated that in Xenopus egg extracts, which support DNA strand synthesis and chromatin assembly, incorporation of chromosomal proteins HMG-14/-17 into nascent nucleosomes increases the transcriptional potential of a chromatin template carrying the Xenopus 5S RNA gene. Here we use the single-stranded and double-stranded forms of a plasmid carrying a 5S RNA maxigene, to test whether the effect of HMG-14/-17 on transcription requires DNA synthesis and whether these proteins will affect transcription through a region containing nucleosomes. We find that most of the transcripts were about 350 nucleotides long, suggesting that HMG-14/-17 enhance transcription through a region that could contain nucleosomes. HMG-14/-17 enhance transcription of chromatin templates assembled onto double-stranded DNA, in the absence of DNA synthesis. Single-round transcription assays suggest that HMG-14/-17 increase transcription from templates assembled onto both single- and double-stranded DNA by increasing the specific activity, and not the number, of transcriptionally active templates. We conclude that the effect of HMG-14/-17 on the transcriptional potential of chromatin is linked to nucleosome assembly and is not linked to DNA synthesis. JF - DNA and cell biology AU - Weigmann, N AU - Trieschmann, L AU - Bustin, M AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1997/10// PY - 1997 DA - October 1997 SP - 1207 EP - 1216 VL - 16 IS - 10 SN - 1044-5498, 1044-5498 KW - Chromatin KW - 0 KW - DNA, Single-Stranded KW - High Mobility Group Proteins KW - Nucleosomes KW - RNA, Messenger KW - RNA, Ribosomal, 5S KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Xenopus laevis KW - Xenopus -- genetics KW - Animals KW - Plasmids -- metabolism KW - RNA, Ribosomal, 5S -- genetics KW - Templates, Genetic KW - RNA, Messenger -- biosynthesis KW - DNA, Single-Stranded -- biosynthesis KW - Chromatin -- genetics KW - Ovum KW - High Mobility Group Proteins -- physiology KW - Nucleosomes -- metabolism KW - DNA -- biosynthesis KW - Transcription, Genetic -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79410403?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=DNA+and+cell+biology&rft.atitle=Enhancement+of+the+transcription+potential+of+nascent+chromatin+by+chromosomal+proteins+HMG-14%2F-17+is+coupled+to+nucleosome+assembly+and+not+DNA+synthesis.&rft.au=Weigmann%2C+N%3BTrieschmann%2C+L%3BBustin%2C+M&rft.aulast=Weigmann&rft.aufirst=N&rft.date=1997-10-01&rft.volume=16&rft.issue=10&rft.spage=1207&rft.isbn=&rft.btitle=&rft.title=DNA+and+cell+biology&rft.issn=10445498&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-12-08 N1 - Date created - 1997-12-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Proliferative lesions of oviduct and uterus in CD-1 mice exposed prenatally to tamoxifen. AN - 79403510; 9364013 AB - Tamoxifen (TAM) is widely used as adjuvant breast cancer therapy after surgery and as a chemopreventive agent in women of child-bearing age. However, TAM therapy has been shown to result in an increased incidence of endometrial carcinoma in women. The present study was designed to investigate the effects of TAM (5 mg/kg and 7.5 mg/kg body wt) given i.g. to pregnant CD-1 mice (1x/day, days 12 through 18 of gestation) on their female offspring. Progressive proliferative hyperplasia of the oviduct was frequently seen in TAM-exposed offspring, reaching 100% incidence by 52 weeks in both treatment groups. These females also developed progressive proliferative uterine lesions, including moderate/severe cystic endometrial hyperplasia (34-50%) and polypoid adenomas (27-30%) between 53 and 78 weeks. Deciduomas (15%) occurred at young ages (12 and 24 weeks) while leiomyomas (14%), a malignant leiomyosarcoma, and ovarian granulosa cell tumors (14%), were found between 72 and 78 weeks. Our findings thus suggest a strong association between transplacental TAM and reproductive tract abnormalities in female CD-1 mice. JF - Carcinogenesis AU - Diwan, B A AU - Anderson, L M AU - Ward, J M AD - Intramural Research Support Program, SAIC Frederick, National Cancer Institute, Frederick Cancer Research and Development Center, MD 21702-1201, USA. Y1 - 1997/10// PY - 1997 DA - October 1997 SP - 2009 EP - 2014 VL - 18 IS - 10 SN - 0143-3334, 0143-3334 KW - Anticarcinogenic Agents KW - 0 KW - Estrogen Antagonists KW - Tamoxifen KW - 094ZI81Y45 KW - Index Medicus KW - Endometrial Hyperplasia -- chemically induced KW - Animals KW - Hyperplasia -- chemically induced KW - Uterine Neoplasms -- chemically induced KW - Precancerous Conditions -- chemically induced KW - Mice KW - Polyps -- chemically induced KW - Male KW - Female KW - Pregnancy KW - Fallopian Tubes -- pathology KW - Fallopian Tubes -- drug effects KW - Estrogen Antagonists -- adverse effects KW - Tamoxifen -- adverse effects KW - Anticarcinogenic Agents -- adverse effects KW - Uterus -- drug effects KW - Prenatal Exposure Delayed Effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79403510?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Proliferative+lesions+of+oviduct+and+uterus+in+CD-1+mice+exposed+prenatally+to+tamoxifen.&rft.au=Diwan%2C+B+A%3BAnderson%2C+L+M%3BWard%2C+J+M&rft.aulast=Diwan&rft.aufirst=B&rft.date=1997-10-01&rft.volume=18&rft.issue=10&rft.spage=2009&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-11-24 N1 - Date created - 1997-11-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A Ca(2+)-sensing receptor mutation causes hypoparathyroidism by increasing receptor sensitivity to Ca2+ and maximal signal transduction. AN - 79398705; 9380434 AB - Activating mutations of the Ca(2+)-sensing receptor (CaR) gene cause autosomal dominant hypoparathyroidism. Functional expression studies have been reported for several mutations, but have produced conflicting results. Thus, the mechanism by which these mutations activate the receptor is unclear. We describe here a new family with autosomal dominant hypoparathyroidism. The mother and three daughters experienced muscle spasms and/or seizures from early childhood. They were treated with oral calcium and vitamin D analogs, and all four patients developed hypercalciuria, nephrocalcinosis, and renal insufficiency. In this family, we identified a heterozygous missense mutation (F612S) involving the extracellular region of the CaR. The mutation cosegregated with disease. It was not present in 50 normal control individuals. We used site-directed mutagenesis to introduce this mutation into the CaR cDNA, and then expressed the mutant receptor in human embryonic kidney (HEK)-293 cells. In these cells, the accumulation of inositol phosphates was measured as a function of extracellular Ca2+ concentration. Compared with the wild-type receptor, the mutant receptor showed a left-shift in the concentration-response curve and an increase in the maximal response to high Ca2+ concentration. These effects did not appear to be mediated by changes in levels of receptor expression, as judged by ELISA, or by changes in receptor glycosylation, as judged by Western analysis. We conclude that this CaR mutation causes hypoparathyroidism by a dual increase in receptor sensitivity to extracellular Ca2+ and maximal signal transduction capacity. JF - Pediatric research AU - Mancilla, E E AU - De Luca, F AU - Ray, K AU - Winer, K K AU - Fan, G F AU - Baron, J AD - Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1997/10// PY - 1997 DA - October 1997 SP - 443 EP - 447 VL - 42 IS - 4 SN - 0031-3998, 0031-3998 KW - Membrane Proteins KW - 0 KW - Receptors, Cell Surface KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Sensitivity and Specificity KW - Blotting, Western KW - Sequence Analysis KW - Humans KW - Cell Line -- drug effects KW - Membrane Proteins -- biosynthesis KW - Adult KW - Child KW - Female KW - Calcium -- metabolism KW - Signal Transduction -- physiology KW - Hyperparathyroidism -- etiology KW - Calcium -- pharmacology KW - Receptors, Cell Surface -- genetics KW - Receptors, Cell Surface -- physiology KW - Receptors, Cell Surface -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79398705?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pediatric+research&rft.atitle=A+Ca%282%2B%29-sensing+receptor+mutation+causes+hypoparathyroidism+by+increasing+receptor+sensitivity+to+Ca2%2B+and+maximal+signal+transduction.&rft.au=Mancilla%2C+E+E%3BDe+Luca%2C+F%3BRay%2C+K%3BWiner%2C+K+K%3BFan%2C+G+F%3BBaron%2C+J&rft.aulast=Mancilla&rft.aufirst=E&rft.date=1997-10-01&rft.volume=42&rft.issue=4&rft.spage=443&rft.isbn=&rft.btitle=&rft.title=Pediatric+research&rft.issn=00313998&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-11-12 N1 - Date created - 1997-11-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Comparison of inflammatory lung responses in Wistar rats and C57 and DBA mice following acute exposure to cadmium oxide fumes. AN - 79369482; 9344887 AB - Inhalation of cadmium oxide (CdO) is a significant form of human exposure to cadmium (Cd). Furthermore, there is epidemiological and experimental data relating Cd inhalation with lung cancer. Animal studies indicate that rats are more susceptible to Cd-induced lung cancer than mice, but interstrain sensitivity differences to Cd-induced pulmonary inflammation or carcinogenesis have not been addressed in either species. We compared pulmonary inflammatory processes in Wistar Furth (WF) rats with those in C57 and DBA mice exposed to freshly generated CdO fumes in nose-only inhalation chambers. Animals were exposed to 1 mg Cd/m3 for 3 hr and terminated immediately or 1, 3, and 5 days after exposure. Control animals were exposed to air/argon furnace gases. Cd-induced lung injury was assessed by bronchoalveolar lavage fluid (BALF) analyses, histopathology, and immunohistochemical detection of cell proliferation. Inhalation of CdO resulted in pulmonary inflammatory processes that varied widely across species and strains. C57 mice responded with faster and greater influx of neutrophils and proliferation of alveolar macrophages, type II epithelial cells, and bronchiolar epithelial cells compared to DBA mice or WF rats. DBA mice retained a greater percentage of inhaled Cd in the lungs and presented higher levels of BALF protein than C57 mice or rats. In comparison to mice, WF rats responded with a more transient inflammatory response in BALF parameters and higher degree of acute inflammation in lung tissue. The more pronounced proliferation of alveolar and bronchiolar epithelial cells observed in C57 mice might indicate higher susceptibility of this mice strain to Cd-induced lung carcinogenesis compared to DBA mice or WF rats. Furthermore, the present results of fewer inflammatory cells and lower proliferation of epithelial cells in DBA mice in association with our previous observation of higher Cd-induced metallothionein protein in this strain suggest that DBA might be less susceptible to the pulmonary carcinogenic effects of inhaled Cd than C57 mice or WF rats. We conclude that mice might not necessarily be more resistant than rats to the carcinogenic effects of inhaled Cd, since intraspecies susceptibility differences are strongly suggested by the present data. An extrapolation of this conclusion is that genetic variations in the human population may determine individual sensitivity differences to inhaled Cd. Copyright 1997 Academic Press. JF - Toxicology and applied pharmacology AU - McKenna, I M AU - Waalkes, M P AU - Chen, L C AU - Gordon, T AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, Frederick, Maryland 21702, USA. mckennai@bprb.nci.nih.gov Y1 - 1997/10// PY - 1997 DA - October 1997 SP - 196 EP - 206 VL - 146 IS - 2 SN - 0041-008X, 0041-008X KW - Cadmium Compounds KW - 0 KW - Oxides KW - Proliferating Cell Nuclear Antigen KW - Cadmium KW - 00BH33GNGH KW - cadmium oxide KW - 0H3KWS8KJ3 KW - Index Medicus KW - Animals KW - Cell Division -- drug effects KW - Mice KW - Proliferating Cell Nuclear Antigen -- analysis KW - Macrophages, Alveolar -- drug effects KW - Mice, Inbred DBA KW - Rats KW - Neutrophils -- drug effects KW - Epithelial Cells -- drug effects KW - Rats, Wistar KW - Mice, Inbred C57BL KW - Administration, Inhalation KW - Species Specificity KW - Immunohistochemistry KW - Male KW - Oxides -- administration & dosage KW - Cadmium Compounds -- administration & dosage KW - Bronchoalveolar Lavage Fluid -- chemistry KW - Cadmium -- analysis KW - Lung -- drug effects KW - Cadmium Compounds -- toxicity KW - Oxides -- toxicity KW - Lung -- pathology KW - Lung -- metabolism KW - Bronchi -- drug effects KW - Bronchi -- pathology KW - Bronchoalveolar Lavage Fluid -- cytology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79369482?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Bone+marrow+transplantation&rft.atitle=Specific+depletion+of+alloreactivity+against+haplotype+mismatched+related+individuals+by+a+recombinant+immunotoxin%3A+a+new+approach+to+graft-versus-host+disease+prophylaxis+in+haploidentical+bone+marrow+transplantation.&rft.au=Mavroudis%2C+D+A%3BJiang%2C+Y+Z%3BHensel%2C+N%3BLewalle%2C+P%3BCouriel%2C+D%3BKreitman%2C+R+J%3BPastan%2C+I%3BBarrett%2C+A+J&rft.aulast=Mavroudis&rft.aufirst=D&rft.date=1996-05-01&rft.volume=17&rft.issue=5&rft.spage=793&rft.isbn=&rft.btitle=&rft.title=Bone+marrow+transplantation&rft.issn=02683369&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-11-24 N1 - Date created - 1997-11-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Do endogenous volatile organic chemicals measured in breath reflect and maintain CYP2E1 levels in vivo? AN - 79364521; 9344893 AB - The effect of trans-1,2-dichloroethylene (DCE), an inhibitor of cytochrome P450 (P450) 2E1 (CYP2E1), on the composition and quantity of volatile organic chemicals (VOCs) expired in the breath of male F-344 rats was determined in parallel with hepatic P450 activity and content. Hepatic microsomes were prepared from groups of rats prior to dosing and at 2, 5, 12, and 24 hr postdosing with DCE (100 mg/kg ip), and total P450 content and the activity of CYP2E1 was determined. Breath was collected from parallel groups of rats predose and at several intervals that encompassed the time points for rats euthanized for microsome preparation. Over 100 breath components were identified by GC/MS and quantitated by GC/FID. The overall change in the profile of breath VOCs resulting from administration of DCE was striking. An increase of approximately 1000% was measured in the mass of non-DCE-derived VOCs exhaled 4-6 hr after dosing, but there was no increase in hepatic lipid peroxidation. In addition to hexane, short-chain methyl ketones were particularly affected, and percentage increases in response to inhibition were inversely related to chain length, with acetone and 2-butanone > 2-pentanone >> 2-hexanone > 2-heptanone. There were no statistically significant decreases in total content of P450, but the activity of CYP2E1 was diminished about 65% at 2 and 5 hr after DCE treatment. However, 24 hr after inhibitor administration the total mass of VOCs expired was only marginally elevated above baseline and CYP2E1 activity was not significantly different from that of untreated rats. The compounds most markedly increased upon inhibition of CYP2E1 are also excellent inducers of that isozyme, and this finding is consistent with the hypothesis that these chemicals are important to the normal homeostasis of CYP2E1. The increase in breath components observed following inhibition of CYP2E1 suggests that VOCs in breath can reflect the activity of that isozyme in vivo. Copyright 1997 Academic Press. JF - Toxicology and applied pharmacology AU - Mathews, J M AU - Raymer, J H AU - Etheridge, A S AU - Velez, G R AU - Bucher, J R AD - Research Triangle Institute, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. mathews@rti.org Y1 - 1997/10// PY - 1997 DA - October 1997 SP - 255 EP - 260 VL - 146 IS - 2 SN - 0041-008X, 0041-008X KW - Butanones KW - 0 KW - Cytochrome P-450 CYP2E1 Inhibitors KW - Dichloroethylenes KW - Hexanes KW - Hydrocarbons KW - Ketones KW - Pentanones KW - Acetone KW - 1364PS73AF KW - n-hexane KW - 2DDG612ED8 KW - methylethyl ketone KW - 6PT9KLV9IO KW - 2-heptanone KW - 89VVP1B008 KW - Cytochrome P-450 CYP2E1 KW - EC 1.14.13.- KW - 2-pentanone KW - I97392I10V KW - 1,2-dichloroethylene KW - XU9RUA6YUT KW - Index Medicus KW - Rats KW - Injections, Intraperitoneal KW - Hexanes -- analysis KW - Animals KW - Rats, Inbred F344 KW - Pentanones -- analysis KW - Butanones -- analysis KW - Lipid Peroxidation -- drug effects KW - Gas Chromatography-Mass Spectrometry KW - Acetone -- analysis KW - Volatilization KW - Substrate Specificity KW - Methylation KW - Male KW - Dichloroethylenes -- toxicity KW - Hydrocarbons -- analysis KW - Cytochrome P-450 CYP2E1 -- analysis KW - Microsomes, Liver -- enzymology KW - Microsomes, Liver -- drug effects KW - Ketones -- analysis KW - Cytochrome P-450 CYP2E1 -- metabolism KW - Dichloroethylenes -- administration & dosage KW - Breath Tests UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79364521?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Do+endogenous+volatile+organic+chemicals+measured+in+breath+reflect+and+maintain+CYP2E1+levels+in+vivo%3F&rft.au=Mathews%2C+J+M%3BRaymer%2C+J+H%3BEtheridge%2C+A+S%3BVelez%2C+G+R%3BBucher%2C+J+R&rft.aulast=Mathews&rft.aufirst=J&rft.date=1997-10-01&rft.volume=146&rft.issue=2&rft.spage=255&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 - 1997-11-24 N1 - Date created - 1997-11-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In vivo evidence of free radical formation in the rat lung after exposure to an emission source air pollution particle. AN - 79361550; 9348432 AB - Exposure to air pollution particles can be associated with increased human morbidity and mortality. The mechanism(s) of lung injury remains unknown. We tested the hypothesis that lung exposure to oil fly ash (an emission source air pollution particle) causes in vivo free radical production. Electron spin resonance (ESR) in conjunction with the spin trap alpha-(4-pyridyl 1-oxide)-N-tert-butylnitrone (4-POBN) was used to detect radical adducts. Rats were instilled with 500 micrograms of either oil fly ash or saline. Twenty-four hours later, ESR spectroscopy of the chloroform extract from lungs of animals exposed to the oil fly ash gave a spectrum consistent with a carbon-centered radical adduct (hyperfine coupling constants alpha N = 15.0 G and alpha H beta = 2.5 G), while those spectra from lungs instilled with saline revealed a much weaker signal. This signal was reproduced by instilling animals with the soluble fraction of the oil fly ash, which contains soluble metal compounds. The same signal was observed after instillation of either a mixture of vanadium, nickel, and iron sulfates or VOSO4 alone. We conclude that, after instillation of an air pollution particle in the rat, ESR analysis of lung tissue demonstrates in vivo free radical production. This generation of free radicals appears to be associated with soluble metals in the oil fly ash. JF - Chemical research in toxicology AU - Kadiiska, M B AU - Mason, R P AU - Dreher, K L AU - Costa, D L AU - Ghio, A J AD - Laboratory of Pharmacology and Chemistry, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 1997/10// PY - 1997 DA - October 1997 SP - 1104 EP - 1108 VL - 10 IS - 10 SN - 0893-228X, 0893-228X KW - Coal Ash KW - 0 KW - Free Radicals KW - Metals KW - Particulate Matter KW - Carbon KW - 7440-44-0 KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Electron Spin Resonance Spectroscopy KW - Male KW - Air Pollution KW - Lung -- drug effects KW - Lung -- metabolism KW - Carbon -- toxicity KW - Metals -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79361550?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=In+vivo+evidence+of+free+radical+formation+in+the+rat+lung+after+exposure+to+an+emission+source+air+pollution+particle.&rft.au=Kadiiska%2C+M+B%3BMason%2C+R+P%3BDreher%2C+K+L%3BCosta%2C+D+L%3BGhio%2C+A+J&rft.aulast=Kadiiska&rft.aufirst=M&rft.date=1997-10-01&rft.volume=10&rft.issue=10&rft.spage=1104&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 - 1997-11-20 N1 - Date created - 1997-11-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Toxicity of divinylbenzene-55 for B6C3F1 mice in a two-week inhalation study. AN - 79360767; 9344621 AB - Divinylbenzene (DVB) is a crosslinking monomer used primarily for copolymerization with styrene to produce ion-exchange resins. The toxicity of inhaled DVB was investigated because of the potential for worker exposure and the structural similarity of DVB to styrene, a potential carcinogen. Male and female B6C3F1 mice were exposed to 0, 25, 50, or 75 ppm DVB for 6 hr/day, 5 days/week for up to 2 weeks. Six mice/sex/dose group were killed after 3, 5, and 10 exposures and six mice/sex in the 75 ppm group were killed 7 days after 10 exposures. The most severe effects occurred in the nasal cavity and liver, with less severe effects occurring in the kidneys. In the nasal cavity olfactory epithelium acute necrosis and inflammation were present at early time points followed by regeneration, architectural reorganization, and focal respiratory metaplasia by 7 days after the last exposure. Olfactory epithelial changes were concentration-dependent with extensive involvement at 75 ppm and peripheral sparing at 25 ppm. There was also necrosis and regeneration of olfactory-associated Bowman's glands as well as the lateral nasal (Steno's) glands. Hepatocellular centrilobular (CL) necrosis was observed only in the 75 ppm dose group and was similar to that caused by styrene. A time-dependent progression was observed, characterized by CL degeneration after 1 exposure, necrosis after 3 and 5 exposures, and chronic inflammation with CL karyomegaly after 10 exposures and 7 days after the 10th exposure. Hepatic GSH levels were decreased in a dose-dependent manner. In the kidneys, transient tubular damage was observed in some male mice exposed to 75 ppm, and appeared to be a response to DVB-induced tubular epithelial injury. Copyright 1997 Society of Toxicology. JF - Fundamental and applied toxicology : official journal of the Society of Toxicology AU - Morgan, D L AU - Mahler, J F AU - Wilson, R E AU - Moorman, M P AU - Price, H C AU - O'connor, R W AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1997/10// PY - 1997 DA - October 1997 SP - 89 EP - 100 VL - 39 IS - 2 SN - 0272-0590, 0272-0590 KW - Carcinogens KW - 0 KW - Vinyl Compounds KW - Superoxide Dismutase KW - EC 1.15.1.1 KW - Alanine Transaminase KW - EC 2.6.1.2 KW - Glutathione KW - GAN16C9B8O KW - divinyl benzene KW - IZ715T4SBU KW - Index Medicus KW - Animals KW - Dose-Response Relationship, Drug KW - Superoxide Dismutase -- blood KW - Olfactory Mucosa -- pathology KW - Mice KW - Inflammation KW - Alanine Transaminase -- blood KW - Necrosis KW - Glutathione -- analysis KW - Administration, Inhalation KW - Female KW - Male KW - Olfactory Mucosa -- drug effects KW - Vinyl Compounds -- toxicity KW - Nasal Cavity -- pathology KW - Liver -- pathology KW - Kidney Tubules -- pathology KW - Liver -- drug effects KW - Kidney Tubules -- drug effects KW - Carcinogens -- toxicity KW - Nasal Cavity -- drug effects KW - Vinyl Compounds -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79360767?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Toxicity+of+divinylbenzene-55+for+B6C3F1+mice+in+a+two-week+inhalation+study.&rft.au=Morgan%2C+D+L%3BMahler%2C+J+F%3BWilson%2C+R+E%3BMoorman%2C+M+P%3BPrice%2C+H+C%3BO%27connor%2C+R+W&rft.aulast=Morgan&rft.aufirst=D&rft.date=1997-10-01&rft.volume=39&rft.issue=2&rft.spage=89&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 - 1997-12-16 N1 - Date created - 1997-12-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of small GTP-binding proteins in lovastatin-induced cataracts. AN - 79355164; 9344354 AB - To investigate the biochemical mechanisms involved in the cataract induced by lovastatin, a commonly used cholesterol-lowering agent. The effects of lovastatin on lens transparency and on lens epithelial cell proliferation and structure have been investigated using organ-cultured rat lenses and cultured epithelial cells from human and rabbit lenses, respectively. Lens histologic and morphologic changes were recorded microscopically. Small GTP-binding protein profiles were determined by [alpha-32P] GTP overlay assays. Rat lenses organ cultured for 7 days with lovastatin, a 3-hydroxy-3-methylglutaryl CoA reductase inhibitor, developed frank subcapsular opacity. Lens epithelial cells (both human and rabbit) demonstrated extensive morphologic changes and inhibition of proliferation when treated with lovastatin. Histologic sections of lovastatin-treated lenses showed partial to complete degeneration of the central epithelium, distortion of elongating epithelial cells, and extensive vacuole formation in the equatorial regions of the cortex. Supplementation of the medium with DL-mevalonic acid (a precursor of isoprenoids whose synthesis is inhibited by lovastatin) prevented the lovastatin-induced changes in whole lenses or in lens epithelial cell cultures, whereas supplementation with cholesterol had no such effect. GTP-binding proteins accumulated in the soluble fractions of lovastatin-treated lens epithelial cells. This was consistent with a blockade in isoprenylation preventing normal association with membranes. The findings suggest that impairment of the function of small GTP-binding proteins, due to a lovastatin-induced blockade in their isoprenylation, affects lens cell structure and proliferation in tissue culture and induces lens opacity in organ culture. These findings are consistent with the proposed roles of small GTP-binding proteins as molecular switches that regulate fundamental cellular processes, including growth, differentiation, and maintenance of cell structure. JF - Investigative ophthalmology & visual science AU - Rao, P V AU - Robison, W G AU - Bettelheim, F AU - Lin, L R AU - Reddy, V N AU - Zigler, J S AD - Laboratory of Mechanisms of Ocular Diseases, National Eye Institute, NIH, Bethesda, Maryland 20892-2735, USA. Y1 - 1997/10// PY - 1997 DA - October 1997 SP - 2313 EP - 2321 VL - 38 IS - 11 SN - 0146-0404, 0146-0404 KW - Hydroxymethylglutaryl-CoA Reductase Inhibitors KW - 0 KW - Lovastatin KW - 9LHU78OQFD KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - Mevalonic Acid KW - S5UOB36OCZ KW - Index Medicus KW - Animals KW - Humans KW - Cell Division -- drug effects KW - Rabbits KW - Epithelium -- drug effects KW - Protein Prenylation KW - Rats KW - Epithelium -- physiopathology KW - Infant KW - Rats, Sprague-Dawley KW - Cells, Cultured KW - Macaca mulatta KW - Cell Differentiation -- drug effects KW - Epithelium -- pathology KW - Organ Culture Techniques KW - Mevalonic Acid -- pharmacology KW - Microscopy, Electron, Scanning KW - Lens, Crystalline -- ultrastructure KW - Cataract -- pathology KW - Lens, Crystalline -- drug effects KW - Cataract -- chemically induced KW - Lens, Crystalline -- physiopathology KW - Cataract -- physiopathology KW - GTP-Binding Proteins -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79355164?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Role+of+small+GTP-binding+proteins+in+lovastatin-induced+cataracts.&rft.au=Rao%2C+P+V%3BRobison%2C+W+G%3BBettelheim%2C+F%3BLin%2C+L+R%3BReddy%2C+V+N%3BZigler%2C+J+S&rft.aulast=Rao&rft.aufirst=P&rft.date=1997-10-01&rft.volume=38&rft.issue=11&rft.spage=2313&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 - 1997-10-30 N1 - Date created - 1997-10-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The epidemiology of soft tissue sarcoma. AN - 79355064; 9344316 AB - Soft tissue sarcoma (STS) accounts for approximately 1% of all cancers diagnosed annually in the United States. Population-based data from Connecticut covering the years 1935-1989 have shown an increasing incidence of STS in both genders, with a greater increase among men than women. The recent increase in acquired immune deficiency syndrome-related Kaposi's sarcoma does not explain the upward trend in STS, dating back decades. Etiologic heterogeneity is suggested by epidemiologic variations that have been observed by subsite and cell type. Among the environmental factors associated with STS are external radiation therapy, Thorotrast, arsenical pesticides and medications, phenoxyherbicides, dioxin, vinyl chloride, immunosuppressive drugs, alkylating agents, androgen-anabolic steroids, human immunodeficiency virus, and human herpes virus type 8. In addition, STS occurs excessively among persons with certain heritable states including retinoblastoma, Li-Fraumeni syndrome, Gardner's syndrome, Werner's syndrome, nevoid basal cell carcinoma syndrome, neurofibromatosis type 1, and some immunodeficiency syndromes. These risk factors account for a minority of STS cases but provide leads for further epidemiologic and interdisciplinary studies into the genetic and environmental determinants of various forms of STS. JF - Seminars in oncology AU - Zahm, S H AU - Fraumeni, J F AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD 20892-7364, USA. Y1 - 1997/10// PY - 1997 DA - October 1997 SP - 504 EP - 514 VL - 24 IS - 5 SN - 0093-7754, 0093-7754 KW - Index Medicus KW - AIDS/HIV KW - Risk Factors KW - Humans KW - SEER Program KW - Environmental Exposure KW - Incidence KW - United States -- epidemiology KW - Male KW - Female KW - Sarcoma -- etiology KW - Sarcoma -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79355064?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+epidemiology+of+soft+tissue+sarcoma.&rft.au=Zahm%2C+S+H%3BFraumeni%2C+J+F&rft.aulast=Zahm&rft.aufirst=S&rft.date=1997-10-01&rft.volume=24&rft.issue=5&rft.spage=504&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 - 1997-11-04 N1 - Date created - 1997-11-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Modification of a PCR-based site-directed mutagenesis method. AN - 79352292; 9343663 JF - BioTechniques AU - Fisher, C L AU - Pei, G K AD - NCI-FCRDC, Frederick, MD 21702, USA. fisherc@ncifcrf.gov Y1 - 1997/10// PY - 1997 DA - October 1997 SP - 570 EP - 1, 574 VL - 23 IS - 4 SN - 0736-6205, 0736-6205 KW - DNA, Complementary KW - 0 KW - Proto-Oncogene Proteins KW - Proto-Oncogene Proteins c-ets KW - Transcription Factors KW - endodeoxyribonuclease DpnI KW - EC 3.1.21.- KW - Deoxyribonucleases, Type II Site-Specific KW - EC 3.1.21.4 KW - Index Medicus KW - Saccharomyces cerevisiae -- genetics KW - Humans KW - Genetic Vectors KW - Deoxyribonucleases, Type II Site-Specific -- metabolism KW - Mutagenesis, Site-Directed KW - Polymerase Chain Reaction -- methods KW - Proto-Oncogene Proteins -- genetics KW - Transcription Factors -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79352292?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Modification+of+a+PCR-based+site-directed+mutagenesis+method.&rft.au=Fisher%2C+C+L%3BPei%2C+G+K&rft.aulast=Fisher&rft.aufirst=C&rft.date=1997-10-01&rft.volume=23&rft.issue=4&rft.spage=570&rft.isbn=&rft.btitle=&rft.title=BioTechniques&rft.issn=07366205&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-02-04 N1 - Date created - 1998-02-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Developmental exposure to diethylstilbestrol elicits demethylation of estrogen-responsive lactoferrin gene in mouse uterus. AN - 79326494; 9331098 AB - Alteration of DNA demethylation in five CpG sites (-547, -533, -475, -464, and -454) immediately upstream from the estrogen response element of lactoferrin promoter was determined in the uteri of immature (17-day-old) and mature (21- and 30-day-old) mice treated neonatally with DES. Only the CpG/-464 was found to be abnormally demethylated by diethylstilbestrol (DES) treatment in the mature uteri. This abnormal demethylation occurred in specific response to DES in neonatal mice, because DES injected into the 30-day-old mature mice did not demethylate CpG/-464. This site, however, remained methylated in the neonatally DES-treated/ovariectomized mice, indicating that this DES-elicited demethylation is under hormonal control. Thus, neonatal DES treatment appeared to imprint an abnormal, site-specific demethylation of CpG/-464, which requires ovarian hormones to occur in adult mice. Moreover, the demethylation was maintained in uterine tumors of the neonatally DES-treated mice. This mode of demethylation is reminiscent of uterine tumor formation, which also depends on both neonatal DES exposure and ovarian hormone stimulation in adulthood. Thus, neonatal DES treatment may induce tumor formation as well as demethylation through a common cellular process. JF - Cancer research AU - Li, S AU - Washburn, K A AU - Moore, R AU - Uno, T AU - Teng, C AU - Newbold, R R AU - McLachlan, J A AU - Negishi, M AD - Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina 27709, USA. Y1 - 1997/10/01/ PY - 1997 DA - 1997 Oct 01 SP - 4356 EP - 4359 VL - 57 IS - 19 SN - 0008-5472, 0008-5472 KW - Carcinogens KW - 0 KW - Estrogens KW - Diethylstilbestrol KW - 731DCA35BT KW - Lactoferrin KW - EC 3.4.21.- KW - Index Medicus KW - Animals, Newborn KW - Animals KW - Uterine Neoplasms -- genetics KW - Promoter Regions, Genetic KW - Age Factors KW - Genes KW - Uterine Neoplasms -- chemically induced KW - DNA Methylation -- drug effects KW - Ovariectomy KW - Mice KW - Uterine Neoplasms -- metabolism KW - Female KW - Uterine Neoplasms -- pathology KW - Uterus -- metabolism KW - Uterus -- growth & development KW - Lactoferrin -- genetics KW - Lactoferrin -- biosynthesis KW - Diethylstilbestrol -- toxicity KW - CpG Islands KW - Carcinogens -- toxicity KW - Estrogens -- physiology KW - Uterus -- drug effects KW - Gene Expression Regulation, Developmental -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79326494?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Developmental+exposure+to+diethylstilbestrol+elicits+demethylation+of+estrogen-responsive+lactoferrin+gene+in+mouse+uterus.&rft.au=Li%2C+S%3BWashburn%2C+K+A%3BMoore%2C+R%3BUno%2C+T%3BTeng%2C+C%3BNewbold%2C+R+R%3BMcLachlan%2C+J+A%3BNegishi%2C+M&rft.aulast=Li&rft.aufirst=S&rft.date=1997-10-01&rft.volume=57&rft.issue=19&rft.spage=4356&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 - 1997-10-28 N1 - Date created - 1997-10-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characterization of the p53 tumor suppressor pathway in cell lines of the National Cancer Institute anticancer drug screen and correlations with the growth-inhibitory potency of 123 anticancer agents. AN - 79326000; 9331090 AB - In the present study, we report the characterization of the p53 tumor suppressor pathway in the 60 cell lines of the National Cancer Institute (NCI) anticancer drug screen, as well as correlations between the integrity of this pathway and the growth-inhibitory potency of 123 anticancer agents in this screen. Assessment of p53 status in these lines was achieved through complete p53 cDNA sequencing, measurement of basal p53 protein levels and functional assessment of (a) transcriptional activity of p53 cDNA from each line in a yeast assay, (b) gamma-ray-induced G1 phase cell cycle arrest, and (c) gamma-ray-induced expression of CIP1/WAF1, GADD45, and MDM2 mRNA. Our investigations revealed that p53 gene mutations were common in the NCI cell screen lines: 39 of 58 cell lines analyzed contained a mutant p53 sequence. cDNA derived from almost all of the mutant p53 cell lines failed to transcriptionally activate a reporter gene in yeast, and the majority of mutant p53 lines studied expressed elevated basal levels of the mutant p53 protein. In contrast to most of the wild-type p53-containing lines, cells containing mutant p53 sequence were also deficient in gamma-ray induction of CIP1/WAF1, GADD45, and MDM2 mRNA and the ability to arrest in G1 following gamma-irradiation. Taken together, these assessments provided indications of the integrity of the p53 pathway in the 60 cell lines of the NCI cell screen. These individual p53 assessments were subsequently used to probe a database of growth-inhibitory potency for 123 "standard agents," which included the majority of clinically approved anticancer drugs. These 123 agents have been tested against these lines on multiple occasions, and a proposed mechanism of drug action had previously been assigned to each agent. Our analysis revealed that cells with mutant p53 sequence tended to exhibit less growth inhibition in this screen than the wild-type p53 cell lines when treated with the majority of clinically used anticancer agents: including DNA cross-linking agents, antimetabolites, and topoisomerase I and II inhibitors. Similar correlations were uncovered when we probed this database using most of the other indices of p53 status we assessed in the lines. Interestingly, a class of agents that differed in this respect was the antimitotic agents. Growth-inhibitory activity of these agents tended, in this assay, to be independent of p53 status. Our characterization of the p53 pathway in the NCI cell screen lines should prove useful to researchers investigating fundamental aspects of p53 biology and pharmacology. This information also allows for the large-scale analysis of the more than 60,000 compounds tested against these lines for novel agents that might exploit defective p53 function as a means of preferential toxicity. JF - Cancer research AU - O'Connor, P M AU - Jackman, J AU - Bae, I AU - Myers, T G AU - Fan, S AU - Mutoh, M AU - Scudiero, D A AU - Monks, A AU - Sausville, E A AU - Weinstein, J N AU - Friend, S AU - Fornace, A J AU - Kohn, K W AD - Division of Basic Sciences, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. oconnorp@dc37a.nci.nih.gov Y1 - 1997/10/01/ PY - 1997 DA - 1997 Oct 01 SP - 4285 EP - 4300 VL - 57 IS - 19 SN - 0008-5472, 0008-5472 KW - Antineoplastic Agents KW - 0 KW - CDKN1A protein, human KW - Cyclin-Dependent Kinase Inhibitor p21 KW - Cyclins KW - DNA, Complementary KW - GADD45 protein KW - Intracellular Signaling Peptides and Proteins KW - Neoplasm Proteins KW - Nuclear Proteins KW - Proteins KW - Proto-Oncogene Proteins KW - RNA, Messenger KW - RNA, Neoplasm KW - Tumor Suppressor Protein p53 KW - MDM2 protein, human KW - EC 2.3.2.27 KW - Proto-Oncogene Proteins c-mdm2 KW - Index Medicus KW - United States KW - RNA, Neoplasm -- biosynthesis KW - Tumor Suppressor Protein p53 -- physiology KW - Cyclins -- biosynthesis KW - Humans KW - RNA, Messenger -- genetics KW - Neoplasms -- genetics KW - RNA, Messenger -- biosynthesis KW - Proto-Oncogene Proteins -- biosynthesis KW - Saccharomyces cerevisiae -- metabolism KW - Neoplasm Proteins -- genetics KW - Transcriptional Activation -- genetics KW - Cell Cycle -- radiation effects KW - Proto-Oncogene Proteins -- genetics KW - Cyclins -- genetics KW - Neoplasm Proteins -- biosynthesis KW - Protein Biosynthesis KW - DNA, Complementary -- genetics KW - Gamma Rays KW - Reference Standards KW - RNA, Neoplasm -- genetics KW - Proteins -- genetics KW - Loss of Heterozygosity KW - Neoplasms -- pathology KW - National Institutes of Health (U.S.) KW - Genes, p53 KW - Tumor Cells, Cultured -- drug effects KW - Gene Expression Regulation, Neoplastic -- radiation effects KW - Gene Expression Regulation, Neoplastic -- drug effects KW - Antineoplastic Agents -- pharmacology KW - Tumor Cells, Cultured -- radiation effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79326000?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Characterization+of+the+p53+tumor+suppressor+pathway+in+cell+lines+of+the+National+Cancer+Institute+anticancer+drug+screen+and+correlations+with+the+growth-inhibitory+potency+of+123+anticancer+agents.&rft.au=O%27Connor%2C+P+M%3BJackman%2C+J%3BBae%2C+I%3BMyers%2C+T+G%3BFan%2C+S%3BMutoh%2C+M%3BScudiero%2C+D+A%3BMonks%2C+A%3BSausville%2C+E+A%3BWeinstein%2C+J+N%3BFriend%2C+S%3BFornace%2C+A+J%3BKohn%2C+K+W&rft.aulast=O%27Connor&rft.aufirst=P&rft.date=1997-10-01&rft.volume=57&rft.issue=19&rft.spage=4285&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 - 1997-10-28 N1 - Date created - 1997-10-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Free amino acids reflect impact of selenite-dependent stress on primary metabolism in rat lens. AN - 79325345; 9330851 AB - A decrease in phase separation temperature, prior to nuclear cataract, has been correlated with elevated free amino acid content. Hence, we determined how selenite-induced stress alters free amino acid pools in the rat lens, following a single subcutaneous dose of sodium selenite (30 nmol g-1 body weight) in 10- to 14-day-old Sprague Dawley rats. Oxidative stress was evident in lenses 24 h after rats were treated with selenite. Glutathione content was decreased by 60% in the lens cortex and nucleus; the flux of glucose through the pentose phosphate pathway was increased; and glycerol-3-phosphate content was elevated. Amino acid transport, evaluated as 14C-cycloleucine uptake, was not altered, although 14C-glutamine was oxidized at a slower rate. Lenses from treated animals displayed, among the free amino acids, increased glutamine, proline, serine, glycine and the branched chain amino acids, while aspartate, glutamate, and taurine were less. A systemic delivery of sodium selenite caused oxidative stress in the rat lens. Direct effects on primary metabolism altered free amino acid pools that may contribute to transient and permanent changes in lens transparency. JF - Current eye research AU - Mitton, K P AU - Hess, J L AU - Bunce, G E AD - Laboratory of Mechanisms of Ocular Diseases, National Eye Institute, National Institutes of Health, Bethesda, MD, USA. Y1 - 1997/10// PY - 1997 DA - October 1997 SP - 997 EP - 1005 VL - 16 IS - 10 SN - 0271-3683, 0271-3683 KW - Amino Acids KW - 0 KW - Glycerophosphates KW - Glutamine KW - 0RH81L854J KW - Cycloleucine KW - 0TQU7668EI KW - alpha-glycerophosphoric acid KW - 9NTI6P3O4X KW - Glutathione KW - GAN16C9B8O KW - Sodium Selenite KW - HIW548RQ3W KW - Glucose KW - IY9XDZ35W2 KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Glutamine -- metabolism KW - Pentose Phosphate Pathway KW - Glutathione -- metabolism KW - Glucose -- metabolism KW - Biological Transport KW - Glycerophosphates -- metabolism KW - Cycloleucine -- metabolism KW - Cataract -- metabolism KW - Sodium Selenite -- toxicity KW - Lens, Crystalline -- metabolism KW - Lens, Crystalline -- drug effects KW - Cataract -- chemically induced KW - Oxidative Stress -- drug effects KW - Amino Acids -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79325345?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+eye+research&rft.atitle=Free+amino+acids+reflect+impact+of+selenite-dependent+stress+on+primary+metabolism+in+rat+lens.&rft.au=Mitton%2C+K+P%3BHess%2C+J+L%3BBunce%2C+G+E&rft.aulast=Mitton&rft.aufirst=K&rft.date=1997-10-01&rft.volume=16&rft.issue=10&rft.spage=997&rft.isbn=&rft.btitle=&rft.title=Current+eye+research&rft.issn=02713683&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-11-03 N1 - Date created - 1997-11-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The absolute number of trans-rearrangements between the TCRG and TCRB loci is predictive of lymphoma risk: a severe combined immune deficiency (SCID) murine model. AN - 79323004; 9331104 AB - Pilot studies in human populations have demonstrated a correlation between the level of antigen receptor trans-rearrangements and risk (at the population level) of lymphoid malignancy. Irradiation of newborn severe combined immune deficiency mice results in an increased risk of subsequent development of thymic lymphoma (100% of mice so irradiated are dead of thymic lymphoma by 20 weeks of age). We, therefore, assayed the occurrence of trans-rearrangements in this well-controlled mouse mutant system and found a 50-100-fold increase in the absolute number of TCRGV-TCRBJ trans-rearrangements compared to unirradiated littermates (and a comparable fold increase over age-matched BALB/c mice) at 2 weeks following irradiation. We also found a marked disproportion in generating trans-rearrangements versus intralocus rearrangements in the severe combined immune deficiency system compared to BALB/c, independent of irradiation. The trans-rearrangements noted were polyclonal in nature. These data, again, suggest that the absolute level of antigen receptor trans-rearrangements may serve as a biomarker of lymphoma risk. JF - Cancer research AU - Lista, F AU - Bertness, V AU - Guidos, C J AU - Danska, J S AU - Kirsch, I R AD - Genetics Department, Medicine Branch, National Cancer Institute, Bethesda, Maryland 20889, USA. Y1 - 1997/10/01/ PY - 1997 DA - 1997 Oct 01 SP - 4408 EP - 4413 VL - 57 IS - 19 SN - 0008-5472, 0008-5472 KW - Biomarkers KW - 0 KW - Receptors, Antigen, T-Cell KW - DNA Nucleotidyltransferases KW - EC 2.7.7.- KW - VDJ Recombinases KW - Index Medicus KW - Animals KW - Severe Combined Immunodeficiency -- complications KW - Mice KW - Mice, Inbred BALB C KW - Severe Combined Immunodeficiency -- genetics KW - DNA Repair -- genetics KW - Animals, Newborn KW - Risk KW - Mice, SCID KW - Female KW - Male KW - DNA Nucleotidyltransferases -- metabolism KW - Lymphoma -- etiology KW - Neoplasms, Radiation-Induced -- etiology KW - Lymphoma -- genetics KW - Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor KW - Gene Rearrangement, beta-Chain T-Cell Antigen Receptor KW - Neoplasms, Radiation-Induced -- genetics KW - Receptors, Antigen, T-Cell -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79323004?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=The+absolute+number+of+trans-rearrangements+between+the+TCRG+and+TCRB+loci+is+predictive+of+lymphoma+risk%3A+a+severe+combined+immune+deficiency+%28SCID%29+murine+model.&rft.au=Lista%2C+F%3BBertness%2C+V%3BGuidos%2C+C+J%3BDanska%2C+J+S%3BKirsch%2C+I+R&rft.aulast=Lista&rft.aufirst=F&rft.date=1997-10-01&rft.volume=57&rft.issue=19&rft.spage=4408&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 - 1997-10-28 N1 - Date created - 1997-10-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Sequence-specific single-strand RNA binding protein encoded by the human LINE-1 retrotransposon. AN - 79321760; 9312060 AB - Previous experiments using human teratocarcinoma cells indicated that p40, the protein encoded by the first open reading frame (ORF) of the human LINE-1 (L1Hs) retrotransposon, occurs in a large cytoplasmic ribonucleoprotein complex in direct association with L1Hs RNA(s), the p40 RNP complex. We have now investigated the interaction between partially purified p40 and L1Hs RNA in vitro using an RNA binding assay dependent on co-immunoprecipitation of p40 and bound RNA. These experiments identified two p40 binding sites on the full-length sense strand L1Hs RNA. Both sites are in the second ORF of the 6000 nt RNA: site A between residues 1999 and 2039 and site B between residues 4839 and 4875. The two RNA segments share homologous regions. Experiments involving UV cross-linking followed by immunoprecipitation indicate that p40 in the in vitro complex is directly associated with L1Hs RNA, as it is in the p40 RNP complex found in teratocarcinoma cells. Binding and competition experiments demonstrate that p40 binds to single-stranded RNA containing a p40 binding site, but not to single-stranded or double-stranded DNA, double-stranded RNA or a DNA-RNA hybrid containing a binding site sequence. Thus, p40 appears to be a sequence-specific, single-strand RNA binding protein. JF - The EMBO journal AU - Hohjoh, H AU - Singer, M F AD - Laboratory of Biochemistry, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1997/10/01/ PY - 1997 DA - 1997 Oct 01 SP - 6034 EP - 6043 VL - 16 IS - 19 SN - 0261-4189, 0261-4189 KW - DNA-Binding Proteins KW - 0 KW - RNA-Binding Proteins KW - Retroelements KW - L1Hs-encoded protein p40, human KW - 148349-28-4 KW - RNA KW - 63231-63-0 KW - Index Medicus KW - Base Sequence KW - Tumor Cells, Cultured KW - HeLa Cells KW - Open Reading Frames KW - Humans KW - Binding, Competitive KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Retroelements -- genetics KW - Leucine Zippers -- genetics KW - RNA-Binding Proteins -- metabolism KW - RNA-Binding Proteins -- genetics KW - RNA -- metabolism KW - DNA-Binding Proteins -- genetics KW - RNA-Binding Proteins -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79321760?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Sequence-specific+single-strand+RNA+binding+protein+encoded+by+the+human+LINE-1+retrotransposon.&rft.au=Hohjoh%2C+H%3BSinger%2C+M+F&rft.aulast=Hohjoh&rft.aufirst=H&rft.date=1997-10-01&rft.volume=16&rft.issue=19&rft.spage=6034&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 - 1997-12-10 N1 - Date created - 1997-12-10 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Mol Cell Biol. 1983 May;3(5):787-95 [6865942] J Mol Biol. 1997 Aug 8;271(1):7-12 [9300051] Mol Cell Biol. 1986 Jan;6(1):168-82 [3023821] Biochim Biophys Acta. 1987 Dec 8;910(3):203-12 [2445384] Proc Natl Acad Sci U S A. 1990 Sep;87(18):6990-4 [1698287] Mol Cell Biol. 1990 Dec;10(12):6718-29 [1701022] Mol Cell Biol. 1991 Sep;11(9):4804-7 [1715025] Trends Biochem Sci. 1991 Jun;16(6):214-20 [1716386] Science. 1991 Dec 20;254(5039):1805-8 [1662412] Science. 1991 Dec 20;254(5039):1808-10 [1722352] Trends Biochem Sci. 1991 Nov;16(11):417-22 [1776171] J Biol Chem. 1992 Oct 5;267(28):19765-8 [1328181] Mol Cell Biol. 1993 Sep;13(9):5383-92 [8395003] Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11533-7 [8265584] Gene. 1993 Dec 15;135(1-2):183-8 [8276257] Science. 1994 Jul 29;265(5172):615-21 [8036511] Trends Biochem Sci. 1995 May;20(5):191-7 [7610483] Trends Biochem Sci. 1995 Jun;20(6):235-40 [7543225] EMBO J. 1996 Feb 1;15(3):630-9 [8599946] Cell. 1996 Nov 29;87(5):905-16 [8945517] Cell. 1996 Nov 29;87(5):917-27 [8945518] Nat Genet. 1997 May;16(1):37-43 [9140393] Proc Natl Acad Sci U S A. 1986 Jun;83(11):3875-9 [3012536] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Gallium nitrate optic neuropathy. AN - 79318208; 9323956 AB - To report a patient with visual loss after systemic administration of gallium nitrate. Case report. After receiving intravenous gallium nitrate, a 77-year-old man developed bilateral visual loss and optic neuropathy with central scotomas on visual field testing and diminished P2-wave amplitude on visual evoked potential examination. The condition worsened after oral corticosteroid therapy. Partial recovery of optic nerve function in both eyes was present after 12 months of oral ferrous sulfate administration. Partially reversible bilateral optic neuropathy may occur after administration of gallium nitrate in the absence of other chemotherapeutic agents. Ophthalmic examinations are indicated in patients who receive gallium nitrate. JF - American journal of ophthalmology AU - Csaky, K G AU - Caruso, R C AD - Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA. kcsaky@helix.nih.gov Y1 - 1997/10// PY - 1997 DA - October 1997 SP - 567 EP - 568 VL - 124 IS - 4 SN - 0002-9394, 0002-9394 KW - Antineoplastic Agents KW - 0 KW - Antineoplastic Agents, Hormonal KW - Gallium KW - CH46OC8YV4 KW - Prednisone KW - VB0R961HZT KW - gallium nitrate KW - VRA0C6810N KW - Abridged Index Medicus KW - Index Medicus KW - Vision Disorders -- chemically induced KW - Prednisone -- adverse effects KW - Prednisone -- therapeutic use KW - Humans KW - Aged KW - Prostatic Neoplasms -- drug therapy KW - Adenocarcinoma -- drug therapy KW - Scotoma -- chemically induced KW - Antineoplastic Agents, Hormonal -- therapeutic use KW - Antineoplastic Agents, Hormonal -- adverse effects KW - Male KW - Gallium -- adverse effects KW - Gallium -- therapeutic use KW - Antineoplastic Agents -- therapeutic use KW - Optic Nerve Diseases -- chemically induced KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79318208?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Gallium+nitrate+optic+neuropathy.&rft.au=Csaky%2C+K+G%3BCaruso%2C+R+C&rft.aulast=Csaky&rft.aufirst=K&rft.date=1997-10-01&rft.volume=124&rft.issue=4&rft.spage=567&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 - 1997-11-05 N1 - Date created - 1997-11-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Clostridium septicum alpha-toxin is proteolytically activated by furin. AN - 79316085; 9317018 AB - Clostridium septicum alpha-toxin is secreted as an inactive 46,450-Da protoxin. The protoxin is activated by proteolytic cleavage near the C terminus, which eventually causes the release of a 45-amino-acid fragment. Proteoytic activation and loss of the propeptide allow alpha-toxin to oligomerize and form pores on the plasma membrane, which results in colloidal-osmotic lysis. Activation may be accomplished in vitro by cleavage with trypsin at Arg367 (J. Ballard, Y. Sokolov, W. L. Yuan, B. L. Kagan, and R. K. Tweten, Mol. Microbiol. 10:627-634, 1993), which is located within the sequence KKRRGKR367S. A conspicuous feature of this site is a recognition site (RGKR) for the eukaryotic protease furin. Pro-alpha-toxin (AT[pro]) that was digested with trypsin or recombinant soluble furin yielded the 41,327-Da active form (AT[act]). A mutated alpha-toxin in which the furin consensus site was altered to KKRSGSRS at the cleavage site (AT[SGSR]) was cleaved and activated by trypsin but not by furin. In cytotoxicity assays, wild-type Chinese hamster ovary (CHO) and furin-deficient CHO (FD11) cells were killed by AT(pro) but not by AT(SGSR). Both cell types were killed by AT(SGSR) that was preactivated with trypsin. Propidium iodide uptake assays revealed that FD11 cells were approximately 22% less sensitive to AT(pro) than were CHO cells. AT(pro)-induced cell lysis of FD11 cells, assessed by propidium iodide uptake, was partially prevented by leupeptin (5 mM) and completely prevented by antipain (2.5 mM). The inhibition by antipain suggested the presence of cysteine or serine proteases that could also activate AT(pro). These findings demonstrate that furin is involved in the activation of C. septicum alpha-toxin on the cell surface but that alternate eukaryotic proteases can also activate the toxin. Regardless of the activating protease, the furin consensus site appears to be essential for the activation of alpha-toxin on the cell surface. JF - Infection and immunity AU - Gordon, V M AU - Benz, R AU - Fujii, K AU - Leppla, S H AU - Tweten, R K AD - National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892-4350, USA. Y1 - 1997/10// PY - 1997 DA - October 1997 SP - 4130 EP - 4134 VL - 65 IS - 10 SN - 0019-9567, 0019-9567 KW - Bacterial Toxins KW - 0 KW - Cysteine Proteinase Inhibitors KW - Recombinant Proteins KW - hemolytic toxin, Clostridium septicum KW - Propidium KW - 36015-30-2 KW - Antipain KW - 37691-11-5 KW - Subtilisins KW - EC 3.4.21.- KW - Trypsin KW - EC 3.4.21.4 KW - Furin KW - EC 3.4.21.75 KW - Index Medicus KW - Animals KW - Dose-Response Relationship, Drug KW - CHO Cells -- enzymology KW - Antipain -- pharmacology KW - Cysteine Proteinase Inhibitors -- pharmacology KW - Recombinant Proteins -- metabolism KW - Hemolysis KW - Toxicity Tests KW - Trypsin -- metabolism KW - Propidium -- metabolism KW - Mutation KW - Cricetinae KW - Bacterial Toxins -- genetics KW - Clostridium KW - Bacterial Toxins -- metabolism KW - Subtilisins -- genetics KW - Protein Processing, Post-Translational KW - Bacterial Toxins -- toxicity KW - Subtilisins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79316085?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Infection+and+immunity&rft.atitle=Clostridium+septicum+alpha-toxin+is+proteolytically+activated+by+furin.&rft.au=Gordon%2C+V+M%3BBenz%2C+R%3BFujii%2C+K%3BLeppla%2C+S+H%3BTweten%2C+R+K&rft.aulast=Gordon&rft.aufirst=V&rft.date=1997-10-01&rft.volume=65&rft.issue=10&rft.spage=4130&rft.isbn=&rft.btitle=&rft.title=Infection+and+immunity&rft.issn=00199567&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-10-30 N1 - Date created - 1997-10-30 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Can J Surg. 1994 Jun;37(3):245-9 [8199947] Nature. 1994 Jan 20;367(6460):292-5 [7510043] J Cell Biol. 1994 Sep;126(5):1157-72 [7914893] Mol Microbiol. 1993 Nov;10(3):627-34 [7968539] J Biol Chem. 1994 Dec 16;269(50):31831-5 [7989356] Infect Immun. 1995 Jan;63(1):340-4 [7806374] Infect Immun. 1995 Jan;63(1):82-7 [7806387] Clin Infect Dis. 1995 Jan;20(1):202-3 [7727661] J Biol Chem. 1995 May 5;270(18):10817-21 [7738018] Mol Microbiol. 1997 Feb;23(3):551-8 [9044288] Mol Microbiol. 1997 Aug;25(3):429-40 [9302006] Proc Natl Acad Sci U S A. 1986 Mar;83(5):1320-4 [3006045] Proc Natl Acad Sci U S A. 1986 May;83(10):3136-40 [3486414] J Biol Chem. 1989 Jun 25;264(18):10402-4 [2732229] Gene. 1989 Apr 15;77(1):51-9 [2744487] Rev Infect Dis. 1990 Mar-Apr;12(2):286-96 [2330482] Cell. 1991 Jul 12;66(1):1-3 [2070411] Infect Immun. 1992 Mar;60(3):784-90 [1541552] EMBO J. 1992 Jul;11(7):2407-14 [1628614] Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10277-81 [1438214] J Biol Chem. 1993 Dec 15;268(35):26461-5 [8253774] Infect Immun. 1994 Feb;62(2):333-40 [8300195] EMBO J. 1994 Jan 1;13(1):18-33 [7508380] Aust N Z J Surg. 1994 Aug;64(8):574-5 [8048901] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Species heterogeneity between gerbils and rats: quinolinate production by microglia and astrocytes and accumulations in response to ischemic brain injury and systemic immune activation. AN - 79315524; 9326281 AB - Quinolinic acid is an excitotoxic kynurenine pathway metabolite, the concentration of which increases in human brain during immune activation. The present study compared quinolinate responses to systemic and brain immune activation in gerbils and rats. Global cerebral ischemia in gerbils, but not rats, increased hippocampus indoleamine-2,3-dioxygenase activity and quinolinate levels 4 days postinjury. In a rat focal ischemia model, small increases in quinolinate concentrations occurred in infarcted regions on days 1, 3, and 7, although concentrations remained below serum values. In gerbils, systemic immune activation by an intraperitoneal injection of endotoxin (1 mg/kg of body weight) increased quinolinate levels in brain, blood, lung, liver, and spleen, with proportional increases in lung indoleamine-2,3-dioxygenase activity at 24 h postinjection. In rats, however, no significant quinolinate content changes occurred, whereas lung indoleamine-2,3-dioxygenase activity increased slightly. Gerbil, but not rat, brain microglia and peritoneal monocytes produced large quantities of [13C(6)]-quinolinate from L-[13C(6)]tryptophan. Gerbil astrocytes produced relatively small quantities of quinolinate, whereas rat astrocytes produced no detectable amounts. These results demonstrate that the limited capacity of rats to replicate elevations in brain and blood quinolinic acid levels in response to immune activation is attributable to blunted increases in local indoleamine-2,3-dioxygenase activity and a low capacity of microglia, astrocytes, and macrophages to convert L-tryptophan to quinolinate. JF - Journal of neurochemistry AU - Heyes, M P AU - Saito, K AU - Chen, C Y AU - Proescholdt, M G AU - Nowak, T S AU - Li, J AU - Beagles, K E AU - Proescholdt, M A AU - Zito, M A AU - Kawai, K AU - Markey, S P AD - Laboratory of Neurotoxicology, National Institute of Mental Health, Bethesda, Maryland 20892, U.S.A. Y1 - 1997/10// PY - 1997 DA - October 1997 SP - 1519 EP - 1529 VL - 69 IS - 4 SN - 0022-3042, 0022-3042 KW - Lipopolysaccharides KW - 0 KW - Kynurenine KW - 343-65-7 KW - Quinolinic Acid KW - F6F0HK1URN KW - Index Medicus KW - Injections, Intraperitoneal KW - Animals KW - Rats, Sprague-Dawley KW - Lipopolysaccharides -- pharmacology KW - Encephalitis -- etiology KW - Monocytes -- metabolism KW - Rats, Wistar KW - Kynurenine -- metabolism KW - Encephalitis -- metabolism KW - Species Specificity KW - Quinolinic Acid -- metabolism KW - Brain Ischemia -- complications KW - Rats -- physiology KW - Brain Ischemia -- metabolism KW - Gerbillinae -- physiology KW - Immune System -- physiology KW - Microglia -- metabolism KW - Astrocytes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79315524?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Species+heterogeneity+between+gerbils+and+rats%3A+quinolinate+production+by+microglia+and+astrocytes+and+accumulations+in+response+to+ischemic+brain+injury+and+systemic+immune+activation.&rft.au=Heyes%2C+M+P%3BSaito%2C+K%3BChen%2C+C+Y%3BProescholdt%2C+M+G%3BNowak%2C+T+S%3BLi%2C+J%3BBeagles%2C+K+E%3BProescholdt%2C+M+A%3BZito%2C+M+A%3BKawai%2C+K%3BMarkey%2C+S+P&rft.aulast=Heyes&rft.aufirst=M&rft.date=1997-10-01&rft.volume=69&rft.issue=4&rft.spage=1519&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 - 1997-10-27 N1 - Date created - 1997-10-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutational analysis of the proposed gibbon ape leukemia virus binding site in Pit1 suggests that other regions are important for infection. AN - 79310749; 9311908 AB - Region A of Pit1 (residues 550 to 558 in domain IV) and related receptors has remained the only sequence implicated in gibbon ape leukemia virus (GALV) infection, and an acidic residue at the first position appeared indispensable. The region has also been proposed to be the GALV binding site, but this lacks empirical support. Whether an acidic residue at the first position in this sequence is a definitive requirement for GALV infection has also remained unclear; certain receptors retain function even in the absence of this acidic residue. We report here that in Pit1 an acidic residue is dispensable not only at position 550 but also at 553 alone and at both positions. Further, the virus requires no specific residue at either position. Mutations generated a collection of region A sequences, often with fundamentally different physicochemical properties (overall hydrophobicity or hydrophilicity and net charge of -1, or 0, or +1), and yet Pit1 remained an efficient GALV receptor. A comparison of these sequences and a few previously published ones from highly efficient GALV receptors revealed that every position in region A can vary without affecting GALV entry. Even Pit2 is nonfunctional for GALV only because it has lysine at the first position in its region A, which is otherwise highly diverse from region A of Pit1. We propose that region A itself is not the GALV binding motif and that other sequences are required for virus entry. Indeed, certain Pit1/Pit2 chimeras revealed that sequences outside domain IV are specifically important for GALV infection. JF - Journal of virology AU - Chaudry, G J AU - Eiden, M V AD - Laboratory of Cellular and Molecular Regulation, National Institute of Mental Health, Bethesda, Maryland 20892-4068, USA. Y1 - 1997/10// PY - 1997 DA - October 1997 SP - 8078 EP - 8081 VL - 71 IS - 10 SN - 0022-538X, 0022-538X KW - Carrier Proteins KW - 0 KW - Membrane Glycoproteins KW - Membrane Proteins KW - Receptors, Virus KW - Recombinant Fusion Proteins KW - ecotropic murine leukemia virus receptor KW - leukemia virus receptor, gibbon ape KW - Index Medicus KW - AIDS/HIV KW - Mutagenesis, Site-Directed KW - Animals KW - Carrier Proteins -- metabolism KW - Carrier Proteins -- chemistry KW - Membrane Proteins -- chemistry KW - Hylobates KW - Membrane Proteins -- metabolism KW - Point Mutation KW - CHO Cells KW - Amino Acid Sequence KW - Cricetinae KW - Retroviridae Infections -- virology KW - Leukemia Virus, Gibbon Ape -- pathogenicity KW - Tumor Virus Infections -- virology KW - Leukemia Virus, Gibbon Ape -- metabolism KW - Receptors, Virus -- metabolism KW - Receptors, Virus -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79310749?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mutational+analysis+of+the+proposed+gibbon+ape+leukemia+virus+binding+site+in+Pit1+suggests+that+other+regions+are+important+for+infection.&rft.au=Chaudry%2C+G+J%3BEiden%2C+M+V&rft.aulast=Chaudry&rft.aufirst=G&rft.date=1997-10-01&rft.volume=71&rft.issue=10&rft.spage=8078&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 - 1997-10-20 N1 - Date created - 1997-10-20 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Virol. 1991 May;65(5):2220-4 [1850008] Cell Growth Differ. 1990 Mar;1(3):119-27 [2078500] J Virol. 1992 Feb;66(2):1219-22 [1309898] J Virol. 1992 Mar;66(3):1635-40 [1531369] Virology. 1993 Jul;195(1):1-5 [8391178] J Virol. 1993 Sep;67(9):5472-7 [8394458] J Virol. 1993 Nov;67(11):6733-6 [8411375] J Virol. 1993 Nov;67(11):6737-41 [8411376] Proc Natl Acad Sci U S A. 1994 Jan 4;91(1):78-82 [8278411] Proc Natl Acad Sci U S A. 1994 Feb 1;91(3):1168-72 [8302848] Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):7071-5 [8041748] J Gen Virol. 1994 Aug;75 ( Pt 8):1901-8 [8046392] J Biol Chem. 1994 Oct 14;269(41):25426-31 [7929240] J Virol. 1994 Dec;68(12):7697-703 [7966559] J Virol. 1994 Dec;68(12):8270-6 [7966619] J Virol. 1995 Apr;69(4):2401-5 [7884886] J Virol. 1996 Feb;70(2):1080-5 [8551566] Science. 1996 May 10;272(5263):872-7 [8629022] Nature. 1996 Jun 20;381(6584):661-6 [8649511] Nature. 1996 Jun 20;381(6584):667-73 [8649512] Cell. 1996 Jun 28;85(7):1135-48 [8674119] Cell. 1996 Jun 28;85(7):1149-58 [8674120] Science. 1996 Jun 28;272(5270):1955-8 [8658171] J Virol. 1996 Oct;70(10):6982-6 [8794342] Cell. 1996 Nov 15;87(4):745-56 [8929542] Nature. 1984 Dec 20-1985 Jan 2;312(5996):763-7 [6096719] Cell. 1986 Nov 7;47(3):333-48 [3094962] Mol Cell Biol. 1986 Aug;6(8):2895-902 [3785217] Adv Virus Res. 1989;36:107-51 [2500008] Biotechniques. 1989 Oct;7(9):980-2, 984-6, 989-90 [2631796] J Virol. 1991 Apr;65(4):1743-7 [1672162] J Virol. 1991 Nov;65(11):6316-9 [1656098] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of leuprolide-induced hypogonadism and testosterone replacement on sleep, melatonin, and prolactin secretion in men. AN - 79310372; 9329339 AB - The possible role of gonadal steroids in regulating sleep and circadian rhythms in humans has received relatively little attention despite the importance of the topic to several clinical syndromes. Pharmacologically induced hypogonadism, with and without gonadal steroid replacement, provides an opportunity to examine these questions within a controlled experimental design. We used leuprolide acetate, with and without testosterone replacement, to study the role of testosterone in the regulation of sleep and of melatonin, PRL, and TSH secretion in men. Results from 10 men revealed significant decreases in 24-h PRL levels and in the percentage and time of stage 4 sleep in the hypogonadal state compared with testosterone replacement. There were no differences in melatonin or TSH secretion or in the timing or duration of sleep between the two hormonal conditions. These results indicate that testosterone has relatively specific and discrete effects on sleep and hormonal rhythms in men. JF - The Journal of clinical endocrinology and metabolism AU - Leibenluft, E AU - Schmidt, P J AU - Turner, E H AU - Danaceau, M A AU - Ashman, S B AU - Wehr, T A AU - Rubinow, D R AD - Clinical Psychobiology Branch, National Institute of Mental Health, Bethesda, Maryland 20892, USA. Y1 - 1997/10// PY - 1997 DA - October 1997 SP - 3203 EP - 3207 VL - 82 IS - 10 SN - 0021-972X, 0021-972X KW - Hormones KW - 0 KW - Testosterone KW - 3XMK78S47O KW - Prolactin KW - 9002-62-4 KW - Thyrotropin KW - 9002-71-5 KW - Leuprolide KW - EFY6W0M8TG KW - Melatonin KW - JL5DK93RCL KW - Abridged Index Medicus KW - Index Medicus KW - Thyrotropin -- secretion KW - Melatonin -- secretion KW - Circadian Rhythm KW - Prolactin -- secretion KW - Humans KW - Adult KW - Body Temperature -- physiology KW - Middle Aged KW - Adolescent KW - Male KW - Hormones -- secretion KW - Testosterone -- pharmacology KW - Sleep -- drug effects KW - Sex Characteristics KW - Hypogonadism -- physiopathology KW - Hypogonadism -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79310372?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+clinical+endocrinology+and+metabolism&rft.atitle=Effects+of+leuprolide-induced+hypogonadism+and+testosterone+replacement+on+sleep%2C+melatonin%2C+and+prolactin+secretion+in+men.&rft.au=Leibenluft%2C+E%3BSchmidt%2C+P+J%3BTurner%2C+E+H%3BDanaceau%2C+M+A%3BAshman%2C+S+B%3BWehr%2C+T+A%3BRubinow%2C+D+R&rft.aulast=Leibenluft&rft.aufirst=E&rft.date=1997-10-01&rft.volume=82&rft.issue=10&rft.spage=3203&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+clinical+endocrinology+and+metabolism&rft.issn=0021972X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-11-17 N1 - Date created - 1997-11-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Risk of second malignant neoplasms among long-term survivors of testicular cancer. AN - 79309873; 9326912 AB - We have quantified the site-specific risk of second malignant neoplasms among nearly 29,000 survivors (> or = 1 year) of testicular cancer, taking into account the histologic type of initial cancer and the primary therapy used to treat it. The study cohort consisted of 28,843 men identified within 16 population-based tumor registries in North America and Europe; over 3300 men had survived more than 20 years. New invasive cancers were identified through a search of registry files. Second cancers were reported in 1406 men (observed-to-expected ratio [O/E] = 1.43; 95% confidence interval = 1.36-1.51), with statistically significant excesses noted for acute lymphoblastic leukemia (O/E = 5.20), acute nonlymphocytic leukemia (O/E = 3.07), melanoma (O/E = 1.69), non-Hodgkin's lymphoma (O/E = 1.88), and cancers of the stomach (O/E = 1.95), colon (O/E = 1.27), rectum (O/E = 1.41), pancreas (O/E = 2.21), prostate (O/E = 1.26), kidney (O/E = 1.50), bladder (O/E = 2.02), thyroid (O/E = 2.92), and connective tissue (O/E = 3.16). Overall risk was similar after seminomas (O/E = 1.42) or nonseminomatous tumors (O/E = 1.50). Risk of solid tumors increased with time since the diagnosis of testicular cancer, yielding an O/E = 1.54 (O = 369) among 20-year survivors (two-sided P for trend = .00002). Secondary leukemia was associated with both radiotherapy and chemotherapy, whereas excess cancers of the stomach, bladder, and, possibly, pancreas were associated mainly with radiotherapy. Men with testicular cancer continue to be at significantly elevated risk of second malignant neoplasms for more than two decades following initial diagnosis. Patterns of excess second cancers suggest that many factors may be involved, although the precise roles of treatment, natural history, diagnostic surveillance, and other influences are yet to be clarified. JF - Journal of the National Cancer Institute AU - Travis, L B AU - Curtis, R E AU - Storm, H AU - Hall, P AU - Holowaty, E AU - Van Leeuwen, F E AU - Kohler, B A AU - Pukkala, E AU - Lynch, C F AU - Andersson, M AU - Bergfeldt, K AU - Clarke, E A AU - Wiklund, T AU - Stoter, G AU - Gospodarowicz, M AU - Sturgeon, J AU - Fraumeni, J F AU - Boice, J D AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1997/10/01/ PY - 1997 DA - 1997 Oct 01 SP - 1429 EP - 1439 VL - 89 IS - 19 SN - 0027-8874, 0027-8874 KW - Antineoplastic Agents KW - 0 KW - Index Medicus KW - United States KW - Stomach Neoplasms -- pathology KW - Prostatic Neoplasms -- epidemiology KW - Neoplasms, Connective Tissue -- epidemiology KW - Urinary Bladder Neoplasms -- epidemiology KW - Humans KW - SEER Program KW - Rectal Neoplasms -- epidemiology KW - Kidney Neoplasms -- epidemiology KW - Radiotherapy -- adverse effects KW - Antineoplastic Agents -- adverse effects KW - Melanoma -- epidemiology KW - Registries KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma -- epidemiology KW - Colonic Neoplasms -- epidemiology KW - Lymphoma, Non-Hodgkin -- epidemiology KW - Survival Rate KW - Risk Factors KW - Leukemia, Myeloid, Acute -- epidemiology KW - Seminoma -- therapy KW - Confidence Intervals KW - Pancreatic Neoplasms -- epidemiology KW - Male KW - Testicular Neoplasms -- therapy KW - Neoplasms, Second Primary -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79309873?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Risk+of+second+malignant+neoplasms+among+long-term+survivors+of+testicular+cancer.&rft.au=Travis%2C+L+B%3BCurtis%2C+R+E%3BStorm%2C+H%3BHall%2C+P%3BHolowaty%2C+E%3BVan+Leeuwen%2C+F+E%3BKohler%2C+B+A%3BPukkala%2C+E%3BLynch%2C+C+F%3BAndersson%2C+M%3BBergfeldt%2C+K%3BClarke%2C+E+A%3BWiklund%2C+T%3BStoter%2C+G%3BGospodarowicz%2C+M%3BSturgeon%2C+J%3BFraumeni%2C+J+F%3BBoice%2C+J+D&rft.aulast=Travis&rft.aufirst=L&rft.date=1997-10-01&rft.volume=89&rft.issue=19&rft.spage=1429&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 - 1997-10-31 N1 - Date created - 1997-10-31 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Natl Cancer Inst. 1997 Oct 1;89(19):1394-5 [9326905] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutations in the 5' end of the herpes simplex virus type 2 latency-associated transcript (LAT) promoter affect LAT expression in vivo but not the rate of spontaneous reactivation of genital herpes. AN - 79308757; 9311880 AB - The primary herpes simplex virus type 2 (HSV-2) latency-associated transcript (LAT) promoter influences LAT expression and rates of virus reactivation. We explored the biological importance of particular neuronally responsive regions within the promoter by creating new recombinant viruses bearing a targeted deletion (246 bp [strain 524]) or a point mutation (2 bp [strain 167]) in this region. These recombinant viruses grew efficiently in vitro and in vivo, caused acute genital disease in guinea pigs, and, as measured by quantitative-competitive (QC) DNA PCR, established latency, all as well as did the wild-type parental HSV-2 strain 333, the rescuant strain 524R, and the previously described 624-bp LAT- promoter deletion mutant. By QC-reverse transcriptase PCR of RNA from latently infected ganglia, mutant 167 expressed wild-type levels of LAT and the deletion mutant 524 expressed 9- to 15-fold less LAT than normal, while the LAT expression of the LAT- mutant was undetectable or at least 5 log units less than that of the wild type. The rates of recurrence of genital lesions were normal for recombinant viruses 524 and 167 but reduced (as expected) for the LAT- mutant. Alteration of a subset of LAT promoter elements reduced LAT expression by 1 log unit but did not influence the rate of spontaneous disease reactivation in vivo. Far greater reductions in LAT expression are necessary before reactivation rates are noticeably changed. JF - Journal of virology AU - Wang, K AU - Pesnicak, L AU - Straus, S E AD - Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892, USA. knwang@nih.gov Y1 - 1997/10// PY - 1997 DA - October 1997 SP - 7903 EP - 7910 VL - 71 IS - 10 SN - 0022-538X, 0022-538X KW - DNA Primers KW - 0 KW - DNA, Viral KW - RNA-Directed DNA Polymerase KW - EC 2.7.7.49 KW - Index Medicus KW - Virus Replication KW - Animals KW - Viral Plaque Assay KW - Gene Expression Regulation, Viral KW - Guinea Pigs KW - Transcription, Genetic KW - Recurrence KW - Mutagenesis, Site-Directed KW - Polymerase Chain Reaction KW - Skin -- virology KW - Epithelium -- virology KW - DNA, Viral -- analysis KW - Ganglia, Spinal -- virology KW - Cercopithecus aethiops KW - Vagina -- virology KW - Point Mutation KW - Vero Cells KW - Time Factors KW - Female KW - Sequence Deletion KW - Virus Latency -- genetics KW - Promoter Regions, Genetic KW - Herpesvirus 2, Human -- genetics KW - Herpes Genitalis -- physiopathology KW - Herpesvirus 2, Human -- isolation & purification KW - Herpesvirus 2, Human -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79308757?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mutations+in+the+5%27+end+of+the+herpes+simplex+virus+type+2+latency-associated+transcript+%28LAT%29+promoter+affect+LAT+expression+in+vivo+but+not+the+rate+of+spontaneous+reactivation+of+genital+herpes.&rft.au=Wang%2C+K%3BPesnicak%2C+L%3BStraus%2C+S+E&rft.aulast=Wang&rft.aufirst=K&rft.date=1997-10-01&rft.volume=71&rft.issue=10&rft.spage=7903&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 - 1997-10-20 N1 - Date created - 1997-10-20 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Virol. 1989 Oct;63(10):4455-8 [2550678] J Virol. 1989 Sep;63(9):3844-51 [2474674] Proc Natl Acad Sci U S A. 1991 Jan 1;88(1):48-52 [1846042] J Virol. 1991 Oct;65(10):5619-23 [1654458] J Virol. 1992 Apr;66(4):2157-69 [1312626] Virology. 1993 Oct;196(2):868-72 [8396815] J Virol. 1994 Apr;68(4):2239-52 [8139009] J Infect Dis. 1994 May;169(5):1084-7 [8169396] J Virol. 1994 Dec;68(12):8045-55 [7966594] J Virol. 1994 Dec;68(12):8071-81 [7966597] J Exp Med. 1995 Jan 1;181(1):297-306 [7807009] J Virol. 1995 May;69(5):2873-80 [7707511] J Virol. 1995 Dec;69(12):7899-908 [7494302] J Virol. 1996 Feb;70(2):976-84 [8551638] J Virol. 1996 Apr;70(4):2449-59 [8642650] J Virol. 1996 Mar;70(3):1535-41 [8627672] J Virol. 1996 Mar;70(3):2014-8 [8627728] J Virol. 1996 Oct;70(10):7270-4 [8794381] Virology. 1996 Nov 1;225(1):72-81 [8918535] J Virol. 1997 Jul;71(7):5432-40 [9188615] J Virol. 1997 Aug;71(8):5885-93 [9223478] Virology. 1973 Apr;52(2):456-67 [4705382] J Infect Dis. 1982 Sep;146(3):397-404 [6286797] Science. 1987 Feb 27;235(4792):1056-9 [2434993] Proc Natl Acad Sci U S A. 1987 May;84(10):3204-8 [3033640] J Virol. 1988 Sep;62(9):3493-6 [2841498] EMBO J. 1989 Feb;8(2):505-11 [2542019] J Virol. 1989 Jul;63(7):2893-900 [2542601] J Infect Dis. 1991 Jan;163(1):23-8 [1845807] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Increased oxidative DNA damage and hepatocyte overexpression of specific cytochrome P450 isoforms in hepatitis of mice infected with Helicobacter hepaticus. AN - 79307999; 9327726 AB - A recently discovered bacterium, Helicobacter hepaticus, infects the intrahepatic bile canaliculi of mice, causing a severe chronic hepatitis culminating in liver cancer. Thus, it affords an animal model for study of bacteria-associated tumorigenesis including H. pylori-related gastric cancer. Reactive oxygen species are often postulated to contribute to this process. We now report that hepatitis of male mice infected with H. hepaticus show significant increases in the oxidatively damaged DNA deoxynucleoside 8-hydroxydeoxyguanosine, with the degree of damage increasing with progression of the disease. Perfusion of infected livers with nitro blue tetrazolium revealed that superoxide was produced in the cytoplasm of hepatocytes, especially in association with plasmacytic infiltrates near portal triads. Contrary to expectations, Kupffer cells, macrophages, and neutrophils were rarely involved. However, levels of cytochrome P450 (CYP) isoforms 1A2 and 2A5 in hepatocytes appeared to be greatly increased, as indicated by the number of cells positive in immunohistochemistry and the intensity of staining in many cells, concomitant with severe hepatitis. The CYP2A5 immunohistochemical staining co-localized with formazan deposits resulting from nitro blue tetrazolium reduction and occurred in nuclei as well as cytoplasm. These findings suggest that CYP2A5 contributes to the superoxide production and 8-hydroxydeoxyguanosine formation, although reactive oxygen species from an unknown source in the hepatocytes leading to CYP2A5 induction or coincidental occurrence of these events are also possibilities. Three glutathione S-transferase isoforms, mGSTP1-1 (pi), mGSTA1-1 (YaYa), and mGSTA4-4, also showed striking increases evidencing major oxidative stress in these livers. JF - The American journal of pathology AU - Sipowicz, M A AU - Chomarat, P AU - Diwan, B A AU - Anver, M A AU - Awasthi, Y C AU - Ward, J M AU - Rice, J M AU - Kasprzak, K S AU - Wild, C P AU - Anderson, L M AD - Laboratory of Comparative Carcinogenesis, Frederick Cancer Research and Development Center, National Cancer Institute, Maryland 21702, USA. Y1 - 1997/10// PY - 1997 DA - October 1997 SP - 933 EP - 941 VL - 151 IS - 4 SN - 0002-9440, 0002-9440 KW - Reactive Oxygen Species KW - 0 KW - Superoxides KW - 11062-77-4 KW - 8-oxo-7-hydrodeoxyguanosine KW - 88847-89-6 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 - Cyp2a5 protein, mouse KW - Cytochrome P-450 CYP1A2 KW - Cytochrome P-450 CYP2A6 KW - Cytochrome P450 Family 2 KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Deoxyguanosine KW - G9481N71RO KW - Abridged Index Medicus KW - Index Medicus KW - Immunoblotting KW - Animals KW - Superoxides -- metabolism KW - Deoxyguanosine -- metabolism KW - Helicobacter -- isolation & purification KW - Glutathione Transferase -- metabolism KW - Mice KW - Immunohistochemistry KW - Male KW - Deoxyguanosine -- analogs & derivatives KW - Reactive Oxygen Species -- metabolism KW - Liver -- pathology KW - Liver -- enzymology KW - Hepatitis, Animal -- pathology KW - Mixed Function Oxygenases -- metabolism KW - Helicobacter Infections -- enzymology KW - DNA Damage KW - Hepatitis, Animal -- genetics KW - Cytochrome P-450 CYP1A2 -- metabolism KW - Cytochrome P-450 Enzyme System -- metabolism KW - Helicobacter Infections -- pathology KW - Hepatitis, Animal -- enzymology KW - Helicobacter Infections -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79307999?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Increased+oxidative+DNA+damage+and+hepatocyte+overexpression+of+specific+cytochrome+P450+isoforms+in+hepatitis+of+mice+infected+with+Helicobacter+hepaticus.&rft.au=Sipowicz%2C+M+A%3BChomarat%2C+P%3BDiwan%2C+B+A%3BAnver%2C+M+A%3BAwasthi%2C+Y+C%3BWard%2C+J+M%3BRice%2C+J+M%3BKasprzak%2C+K+S%3BWild%2C+C+P%3BAnderson%2C+L+M&rft.aulast=Sipowicz&rft.aufirst=M&rft.date=1997-10-01&rft.volume=151&rft.issue=4&rft.spage=933&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 - 1997-10-30 N1 - Date created - 1997-10-30 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Drug Metab Rev. 1979;10(2):209-23 [399458] In Vivo. 1996 May-Jun;10(3):285-92 [8797029] Biochem Pharmacol. 1989 Apr 15;38(8):1313-9 [2495801] Arch Biochem Biophys. 1989 May 15;271(1):139-48 [2712571] Basic Life Sci. 1988;49:517-21 [2854996] Arch Biochem Biophys. 1989 Aug 15;273(1):42-57 [2502947] Proc Natl Acad Sci U S A. 1990 Jun;87(12):4533-7 [2352934] Toxicol Appl Pharmacol. 1990 Sep 15;105(3):351-63 [2173169] Biochem Pharmacol. 1991 May 1;41(9):1331-4 [2018565] Biochim Biophys Acta. 1992 Mar 5;1116(1):17-23 [1311603] J Pathol. 1992 May;167(1):83-9 [1625063] Hepatology. 1992 Sep;16(3):682-7 [1505911] Biochem Pharmacol. 1993 Feb 9;45(3):585-92 [8442758] Biochemistry. 1993 Jul 13;32(27):6928-37 [7687464] Mol Carcinog. 1993;7(4):276-80 [8352886] Emerg Infect Dis. 1995 Oct-Dec;1(4):129-31 [8903182] Mol Pharmacol. 1993 Oct;44(4):707-15 [8232220] J Biol Chem. 1994 Jan 14;269(2):992-1000 [7904605] Cancer Res. 1994 Jun 15;54(12):3171-2 [8205535] J Natl Cancer Inst. 1994 Aug 17;86(16):1222-7 [8040890] Biochem Pharmacol. 1994 Jul 5;48(1):155-9 [8043018] J Clin Microbiol. 1994 May;32(5):1238-45 [8051250] Mol Carcinog. 1994 Oct;11(2):74-80 [7916995] Mol Carcinog. 1994 Oct;11(2):81-9 [7916996] Am J Pathol. 1994 Oct;145(4):959-68 [7943185] Proc Natl Acad Sci U S A. 1994 Dec 20;91(26):12808-12 [7809125] Carcinogenesis. 1995 Feb;16(2):253-8 [7859356] Toxicol Appl Pharmacol. 1995 Mar;131(1):63-72 [7878679] Res Commun Mol Pathol Pharmacol. 1995 Feb;87(2):221-36 [7749659] Am J Surg Pathol. 1995;19 Suppl 1:S37-43 [7762738] Biochem Soc Trans. 1995 May;23(2):423-5 [7672434] Gastroenterology. 1995 Nov;109(5):1589-99 [7557143] Biochem Biophys Res Commun. 1995 Nov 22;216(3):793-800 [7488195] Toxicol Appl Pharmacol. 1996 Jan;136(1):79-86 [8560483] Biochim Biophys Acta. 1996 Mar 15;1289(2):238-46 [8600980] Cancer Res. 1996 Mar 15;56(6):1279-82 [8640814] Infect Immun. 1996 May;64(5):1548-58 [8613359] Toxicol Appl Pharmacol. 1996 May;138(1):140-8 [8658503] Crit Rev Biochem Mol Biol. 1995;30(6):445-600 [8770536] Hepatology. 1996 Sep;24(3):649-56 [8781338] Carcinogenesis. 1987 Oct;8(10):1365-73 [3477337] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Health communication in the prevention of alcohol, tobacco, and drug use. AN - 79300949; 9307892 AB - Research on substance abuse prevention programs indicates that effectiveness is greater when multiple intervention approaches that address the specific vocabulary, perceptions, and values of the target population are employed. The field of health communication provides unique perspectives on media that can be applied to increase the salience and effectiveness of substance abuse prevention programs. Well-designed and well-delivered health communications have the capacity for reaching remote audiences, changing health attitudes and behavior, shaping social norms, changing the way health issues are portrayed by the popular media, and influencing decisions about legislation and policies. Health communication approaches are generally employed within the broad context of health promotion programs, along with education, community development, empowerment, and social change approaches. This article describes the role of health communication in substance abuse prevention, reviews major conceptualizations of health communication, and introduces the unique features of the four articles included in this special section of Health Education & Behavior. JF - Health education & behavior : the official publication of the Society for Public Health Education AU - Simons-Morton, B G AU - Donohew, L AU - Crump, A D AD - Prevention Research Branch/DESPR, National Institute of Child Health and Human Development, Bethesda, Maryland 20852, USA. MortonB@HD01.NICHD.NIH.GOV Y1 - 1997/10// PY - 1997 DA - October 1997 SP - 544 EP - 554 VL - 24 IS - 5 SN - 1090-1981, 1090-1981 KW - Index Medicus KW - Culture KW - Minority Groups KW - Humans KW - Diffusion of Innovation KW - Adult KW - Persuasive Communication KW - Consumer Advocacy KW - Adolescent KW - Mass Media KW - Male KW - Female KW - Health Promotion -- methods KW - Communications Media KW - Alcohol-Related Disorders -- prevention & control KW - Tobacco Use Disorder -- prevention & control KW - Substance-Related Disorders -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79300949?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Health+education+%26+behavior+%3A+the+official+publication+of+the+Society+for+Public+Health+Education&rft.atitle=Health+communication+in+the+prevention+of+alcohol%2C+tobacco%2C+and+drug+use.&rft.au=Simons-Morton%2C+B+G%3BDonohew%2C+L%3BCrump%2C+A+D&rft.aulast=Simons-Morton&rft.aufirst=B&rft.date=1997-10-01&rft.volume=24&rft.issue=5&rft.spage=544&rft.isbn=&rft.btitle=&rft.title=Health+education+%26+behavior+%3A+the+official+publication+of+the+Society+for+Public+Health+Education&rft.issn=10901981&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-11-18 N1 - Date created - 1997-11-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A CDR-grafted (humanized) domain-deleted antitumor antibody. AN - 78719772; 10851481 AB - While several murine monoclonal antibodies (MAbs) directed against carcinoma associated antigens have shown excellent tumor targeting properties in clinical trials, the use of radiolabeled MAbs for both diagnostic and therapeutic applications has been hindered by two factors: (a) the induction of host anti-immunoglobulin (Ig) responses and (b) slow plasma clearance of unbound radiolabeled MAb, resulting in bone marrow toxicity for therapeutic application, and long intervals between MAb administration and tumor detection for diagnostic applications. This report describes the development of the first recombinant Ig with properties designed to reduce or eliminate both of the above problems: a complementarity determining region (CDR)-grafted humanized (Hu) MAb with a CH2 domain deletion (delta CH2). The MAb chosen for engineering was CC49, which is directed against a pancarcinoma antigen designated TAG-72 that is expressed on the majority of colorectal, gastric, breast, ovarian, prostate, pancreatic and lung carcinomas. When characterized for antigen binding in solid phase competition radioimmunoassays, the HuCC49 delta CH2 MAb completely inhibited the binding of murine (mu) CC49 and HuCC49 for TAG-72. The relative affinity constants (Ka) of MAbs HuCC49 delta CH2, HuCC49 and muCC49 were 5.1 x 10(-9), 2.1 x 10(-9) and 2.3 x 10(-9), respectively. The plasma clearance of 131I-HuCC49 delta CH2 was significantly faster than that of intact 125I-HuCC49 after either i.v. or i.p. administration in athymic mice (p(2)0.05). Biodistribution studies in athymic mice bearing human colon carcinoma xenografts after i.v. or i.p. administration of 131I-HuCC49 delta CH2 and 125I-HuCC49 demonstrated the efficient tumor localization and substantially lower percent of the injected dose (%ID/g) of the HuCC49 delta CH2 in normal tissues. This is reflected in the significantly higher radiolocalization indices (%ID/g in tumor divided by %ID/g in normal tissue) observed with the HuCC49 delta CH2 for most normal tissues tested (p(2)0.05). The differential between the rate of plasma clearance of HuCC49 delta CH2 and HuCC49 was even more pronounced in SCID mice, which have been shown to be an appropriate model to study the metabolism of human IgG. These studies thus describe the development of a recombinant Ig molecule which, for the first time, combines 1) the properties of more rapid blood clearance than an intact humanized Ig molecule--without loss of antigen binding affinity--and 2) reduced potential for eliciting a human anti-murine antibody (HAMA) response in patients. These studies also demonstrate the potential utility of HuCC49 delta CH2 for i.p. as well as i.v. radioimmunodiagnosis and radioimmunotherapy in patients with TAG-72 positive tumors. JF - Cancer biotherapy & radiopharmaceuticals AU - Slavin-Chiorini, D C AU - Kashmiri, S V AU - Lee, H S AU - Milenic, D E AU - Poole, D J AU - Bernon, E AU - Schlom, J AU - Hand, P H AD - Laboratory of Tumor Immunology and Biology, National Cancer Institute, National Institutes of Health Bethesda, Maryland 20892, USA. Y1 - 1997/10// PY - 1997 DA - October 1997 SP - 305 EP - 316 VL - 12 IS - 5 SN - 1084-9785, 1084-9785 KW - Antibodies, Monoclonal KW - 0 KW - Antigens, Neoplasm KW - Glycoproteins KW - Recombinant Proteins KW - tumor-associated antigen 72 KW - Index Medicus KW - Animals KW - Tumor Cells, Cultured KW - Humans KW - Recombinant Proteins -- pharmacokinetics KW - Mice, Nude KW - Mice KW - Tissue Distribution KW - Mice, SCID KW - Radioimmunoassay KW - Glycoproteins -- immunology KW - Radioimmunotherapy KW - Antibodies, Monoclonal -- pharmacokinetics KW - Antigens, Neoplasm -- immunology KW - Antibodies, Monoclonal -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78719772?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+biotherapy+%26+radiopharmaceuticals&rft.atitle=A+CDR-grafted+%28humanized%29+domain-deleted+antitumor+antibody.&rft.au=Slavin-Chiorini%2C+D+C%3BKashmiri%2C+S+V%3BLee%2C+H+S%3BMilenic%2C+D+E%3BPoole%2C+D+J%3BBernon%2C+E%3BSchlom%2C+J%3BHand%2C+P+H&rft.aulast=Slavin-Chiorini&rft.aufirst=D&rft.date=1997-10-01&rft.volume=12&rft.issue=5&rft.spage=305&rft.isbn=&rft.btitle=&rft.title=Cancer+biotherapy+%26+radiopharmaceuticals&rft.issn=10849785&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-07-19 N1 - Date created - 2000-07-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mammary gland development and tumorigenesis in estrogen receptor knockout mice. AN - 78711610; 10935020 AB - Estrogens are important for the development of the mammary gland and strongly associated with oncogenesis in this tissue. The biological effects of estrogens are mediated through the estrogen receptor (ER), a member of the nuclear receptor superfamily. The estrogen/ER signaling pathway plays a central role in mammary gland development, regulating the expression and activity of other growth factors and their receptors. The generation of the ER knockout (ERKO) mouse has made it possible to directly understand the contribution of ER in mammary development and has provided an unique opportunity to study estrogen action in carcinogenesis. A mammary oncogene (Wnt-1) was introduced into the ERKO background to determine if the absence of the ER would affect the development of tumors induced by oncogenic stimulation. The development, hyperplasia, and tumorigenesis in mammary glands from the ERKO/Wnt-1 mouse line are described. These studies provide the impetus to evaluate the effect of other oncogenes in mammary tumorigenesis in the absence of estrogen/ER signaling. JF - Journal of mammary gland biology and neoplasia AU - Bocchinfuso, W P AU - Korach, K S AD - Receptor Biology Section, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 1997/10// PY - 1997 DA - October 1997 SP - 323 EP - 334 VL - 2 IS - 4 SN - 1083-3021, 1083-3021 KW - Receptors, Estrogen KW - 0 KW - Index Medicus KW - Animals KW - Disease Models, Animal KW - Mice KW - Female KW - Receptors, Estrogen -- genetics KW - Mammary Glands, Animal -- physiology KW - Mammary Glands, Animal -- pathology KW - Receptors, Estrogen -- deficiency KW - Mammary Neoplasms, Experimental -- genetics KW - Mammary Neoplasms, Experimental -- etiology KW - Mammary Glands, Animal -- embryology KW - Mice, Knockout KW - Mammary Neoplasms, Experimental -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78711610?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+mammary+gland+biology+and+neoplasia&rft.atitle=Mammary+gland+development+and+tumorigenesis+in+estrogen+receptor+knockout+mice.&rft.au=Bocchinfuso%2C+W+P%3BKorach%2C+K+S&rft.aulast=Bocchinfuso&rft.aufirst=W&rft.date=1997-10-01&rft.volume=2&rft.issue=4&rft.spage=323&rft.isbn=&rft.btitle=&rft.title=Journal+of+mammary+gland+biology+and+neoplasia&rft.issn=10833021&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-08-22 N1 - Date created - 2000-08-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Post-exercise depression of motor evoked potentials as a function of exercise duration AN - 17360851; 4390068 AB - Post-exercise facilitation and post-exercise depression are phenomena described in motor evoked potentials (MEPs) elicited to transcranial magnetic stimulation. Brief, non-fatiguing muscle activation produces post-exercise facilitation, and prolonged fatiguing muscle activation produces post-exercise depression. We studied 12 normal subjects to determine whether post-exercise depression occurs before fatigue is reached. We recorded MEPs from the resting extensor carpi radialis muscle after increasing the duration of isometric wrist extension, at 50% of maximum voluntary contraction, until the muscle fatigued. Fatigue was defined as the inability to maintain that force. The mean exercise duration before the muscle fatigued was 130 s, and post-exercise depression occurred only beyond 90 s of exercise. We conclude that post-exercise depression is detectable only after prolonged muscle activation. JF - Electromyography and Motor Control AU - Samii, A AU - Wassermann, E M AU - Hallett, M AD - Human Motor Control Section, Medical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Building 10, Room SN226, 10 Center Drive, MSC- 1428, Bethesda, MD 20892-1428, USA, hallett@codon.nih.gov Y1 - 1997/10// PY - 1997 DA - Oct 1997 SP - 352 EP - 356 VL - 105 IS - 5 SN - 0924-980X, 0924-980X KW - extensor carpi radialis muscle KW - man KW - motor evoked potentials KW - normal subjects KW - transcranial magnetic stimulation KW - Physical Education Index; CSA Neurosciences Abstracts KW - Fatigue KW - Depression KW - Exercise (duration) KW - Motor skills KW - Electromyography KW - Muscles KW - Muscles (fatigue) KW - Physical training KW - N3 11067:Clinical neurophysiology (EEGs, EMGs, EPs) KW - PE 090:Sports Medicine & Exercise Sport Science UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17360851?accountid=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=Electromyography+and+Motor+Control&rft.atitle=Post-exercise+depression+of+motor+evoked+potentials+as+a+function+of+exercise+duration&rft.au=Samii%2C+A%3BWassermann%2C+E+M%3BHallett%2C+M&rft.aulast=Samii&rft.aufirst=A&rft.date=1997-10-01&rft.volume=105&rft.issue=5&rft.spage=352&rft.isbn=&rft.btitle=&rft.title=Electromyography+and+Motor+Control&rft.issn=0924980X&rft_id=info:doi/ LA - English DB - Physical Education Index N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Muscles (fatigue); Motor skills; Physical training; Muscles; Depression; Fatigue; Exercise (duration); Electromyography ER - TY - JOUR T1 - Characterization of an endosymbiont infecting wood ticks, Dermacentor andersoni, as a member of the genus Francisella AN - 17107885; 4422342 AB - A microorganism (Dermacantor andersoni symbiont [DAS]) infecting Rocky Mountain wood ticks (D. andersoni) collected in the Bitterroot Mountains of western Montana was characterized as an endosymbiont belonging to the genus Francisella. Previously described as Wolbachia like, the organism's DNA was amplified from both naturally infected tick ovarial tissues and Vero cell cultures by PCR assay with primer sets derived from eubacterial 16S ribosomal DNA (rDNA) and Francisella membrane protein genes. The 16S rDNA gene sequence of the DAS was most similar (95.4%) to that of Francisella tularensis subsp. tularensis. Through a combination of Gimenez staining, PCR assay, and restriction fragment length polymorphism analysis, 102 of 108 female ticks collected from 1992 to 1996 were infected. Transovarial transmission to female progeny was 95.6%, but we found no evidence of horizontal transmission. JF - Applied and Environmental Microbiology AU - Niebylski, M L AU - Peacock, M G AU - Fischer, E R AU - Porcella, S F AU - Schwan, T G AD - Rocky Mountain Labs., NIAID-NIH, 903 S. Fourth St., Hamilton, MT 59840, USA Y1 - 1997/10// PY - 1997 DA - Oct 1997 SP - 3933 EP - 3940 VL - 63 IS - 10 SN - 0099-2240, 0099-2240 KW - DNA KW - USA, Montana KW - polymerase chain reaction KW - restriction fragment length polymorphism KW - ribotyping KW - symbionts KW - Entomology Abstracts; Microbiology Abstracts B: Bacteriology KW - Wolbachia KW - Francisella KW - Dermacentor andersoni KW - J 02870:Invertebrate bacteriology KW - Z 05200:Symbiosis & commensalism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17107885?accountid=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=Applied+and+Environmental+Microbiology&rft.atitle=Characterization+of+an+endosymbiont+infecting+wood+ticks%2C+Dermacentor+andersoni%2C+as+a+member+of+the+genus+Francisella&rft.au=Niebylski%2C+M+L%3BPeacock%2C+M+G%3BFischer%2C+E+R%3BPorcella%2C+S+F%3BSchwan%2C+T+G&rft.aulast=Niebylski&rft.aufirst=M&rft.date=1997-10-01&rft.volume=63&rft.issue=10&rft.spage=3933&rft.isbn=&rft.btitle=&rft.title=Applied+and+Environmental+Microbiology&rft.issn=00992240&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Dermacentor andersoni; Francisella; Wolbachia ER - TY - JOUR T1 - Dietary vitamin C and bone mineral density in postmenopausal women in Washington state, USA AN - 16537013; 4322339 AB - Study objective - To examine the relationship between dietary vitamin C and hip bone mineral density (BMD) in postmenopausal women. Design - This was a cross sectional study using retrospective diet and vitamin supplement data. Setting - The Seattle area of Washington State. Participants - Screenees for a clinical trial of a drug to prevent osteoporotic fractures; 1892 women aged 55-80 years who had hip bone densitometry and osteoporosis risk factor information. Main results - Mean energy adjusted dietary intake of vitamin C was 113 mg/day; including supplement use, mean intake was 407 mg/day. There were no differences in BMD according to diet-only vitamin C intake or combined dietary and supplemental vitamin C intake. Longer duration of vitamin C supplement use was associated with higher BMD in women who had not used oestrogen replacement therapy (trend p=0.02) and among women aged 55-64 years (trend p=0.01). Women aged 55-64 years who used vitamin C supplements for greater than or equal to 10 years had a higher BMD than non-users aged 55-64 years (multivariate adjusted mean BMD 0.699 (0.017)g/cm super(2) versus 0.655 (0.007)g/cm super(2), p= 0.02). Benefits were not evident in older age groups or in women who had used oestrogen in the past. Frequent intake of foods rich in vitamin C was not associated with BMD. Conclusion - There was no evidence that vitamin C from the diet was associated with BMD, although long term use of vitamin C supplements was associated with a higher BMD in the early postmenopausal years and among never users of oestrogen. JF - Journal of Epidemiology and Community Health AU - Leveille, S G AU - LaCroix, A Z AU - Koepsell, T D AU - Beresford, SA AU - Van Belle, G AU - Buchner, D M AD - Epidemiology, Demography, and Biometry Program, National Institute on Aging, 7201 Wisconsin Avenue, Suite 3C-309, Bethesda, MD 20892, USA Y1 - 1997/10// PY - 1997 DA - Oct 1997 SP - 479 EP - 484 VL - 51 IS - 5 KW - USA, Washington, Seattle KW - fractures KW - osteoporosis KW - post-menopause KW - supplements KW - vitamins KW - Risk Abstracts KW - Bone KW - Diets KW - Nutrients KW - Public health KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16537013?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Epidemiology+and+Community+Health&rft.atitle=Dietary+vitamin+C+and+bone+mineral+density+in+postmenopausal+women+in+Washington+state%2C+USA&rft.au=Leveille%2C+S+G%3BLaCroix%2C+A+Z%3BKoepsell%2C+T+D%3BBeresford%2C+SA%3BVan+Belle%2C+G%3BBuchner%2C+D+M&rft.aulast=Leveille&rft.aufirst=S&rft.date=1997-10-01&rft.volume=51&rft.issue=5&rft.spage=479&rft.isbn=&rft.btitle=&rft.title=Journal+of+Epidemiology+and+Community+Health&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Diets; Bone; Public health; Nutrients ER - TY - JOUR T1 - Differential response of human monocytes to Neisseria gonorrhoeae variants expressing pili and opacity proteins AN - 16528194; 4422276 AB - Experiments in vitro suggest that Neisseria gonorrhoeae surface variation plays a key role in gonococcal pathogenesis by providing the appropriate bacterial phenotypes to go through different stages of the infection. Here we report on the effects of phase and antigen variation of two major gonococcal adhesins, pili and opacity (Opa) outer membrane proteins, on the interaction of the gonococci with human monocytes. Using a set of recombinants of gonococcus strain MS11 that each express 1 of 11 genetically defined Opa proteins or a defined type of pilus, we found that both Opa proteins and pili promote bacterial phagocytosis by monocytes in the absence of serum and that this feature largely depends on the type of protein that is expressed. One of the Opa proteins (Opa sub(50)) strongly promoted uptake by monocytes but had little effect on the interaction with polymorphonuclear leukocytes under the conditions employed. Similarly, the phagocytosis-promoting effect of the pill was much more pronounced in monocytes than in neutrophils (4-fold versus 22-fold stimulation of uptake, respectively). Only a subpopulation of both types of phagocytes actively ingested bacteria, as has been observed during natural infections. Measurements of luminol-enhanced chemiluminescence demonstrated that phagocytosis of opaque but not piliated gonococci was accompanied by an increase in oxygen-reactive metabolites. These findings demonstrate that the monocyte response towards gonococci is highly dependent on the bacterial phenotype and differs from the neutrophil response. This diversity in bacterial behavior towards various types of human phagocytic cells underlines the biological impact of gonococcal surface variation and may explain previous contradictory results on this subject. JF - Infection and Immunity AU - Knepper, B AU - Heuer, I AU - Meyer, T F AU - van Putten, JPM AD - Rocky Mountain Labs., NIAID, NIH, 903 South 4th St., Hamilton, MT 59840-2999, USA Y1 - 1997/10// PY - 1997 DA - Oct 1997 SP - 4122 EP - 4129 VL - 65 IS - 10 SN - 0019-9567, 0019-9567 KW - Neisseria gonorrhoeae KW - gonorrhea KW - immune response KW - membrane proteins KW - monocytes KW - outer membranes KW - pili KW - Immunology Abstracts; Microbiology Abstracts B: Bacteriology KW - J 02833:Immune response and immune mechanisms KW - F 06771:Function UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16528194?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Infection+and+Immunity&rft.atitle=Differential+response+of+human+monocytes+to+Neisseria+gonorrhoeae+variants+expressing+pili+and+opacity+proteins&rft.au=Knepper%2C+B%3BHeuer%2C+I%3BMeyer%2C+T+F%3Bvan+Putten%2C+JPM&rft.aulast=Knepper&rft.aufirst=B&rft.date=1997-10-01&rft.volume=65&rft.issue=10&rft.spage=4122&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Nebulized interleukin 2 liposomes: Aerosol characteristics and biodistribution AN - 16448146; 4343856 AB - Although interleukin 2 (IL-2) has been associated with modest anti-tumour responses in man, treatment-related toxicity has limited its widespread use. The local delivery of liposomal formulations of interleukin 2 to the lung as aerosols has been demonstrated to be non-toxic, biologically active, and associated with regression of spontaneous pulmonary metastases in dogs. This study was undertaken to evaluate the physical and biological characteristics of nebulized interleukin 2 liposomes. The aerosol droplet size distribution and the physical stability of interleukin 2 liposomes were examined in-vitro using an Andersen cascade impactor and studies of liposome entrapment of interleukin 2 before and after nebulization. The biological stability of interleukin 2 liposomes after nebulization was demonstrated using the CTLL-2 bioassay for interleukin 2. In-vivo studies of pulmonary biodistribution and clearance of inhaled technetium ( super(99m)Tc)-labelled interleukin 2 liposomes were undertaken in a normal dog. Aerosols of free interleukin 2 and of interleukin 2 liposomes were compared in both in-vitro and in-vivo experiments. The mass median aerodynamic diameter (MMAD) and geometric standard deviation (GSD) of interleukin 2 liposomes were 1.98 mu m and 2.02, respectively. Independent analysis of aerosol particle-size distribution using the constitutive components of the interleukin 2 liposomes (interleukin 2:lipid:HSA) demonstrated a close correlation of size distributions (r=0.9445; P <0.001). The entrapment of interleukin 2 in liposomes was 93 plus or minus 4.3% before nebulization and 90 plus or minus 8.9% after. After delivery to an anaesthetized dog, interleukin 2 liposome aerosols were deposited evenly throughout the lung (mean plus or minus s.d. central lung-to-peripheral lung deposition was 1.12 plus or minus 0.03). After approximately 24 h inhalation, interleukin 2 liposomes were retained within the lung and were taken up in part by the spleen. The results of this study are indicative of the stability of this interleukin 2 liposome formulation to nebulization. Such nebulization might be an attractive immunotherapeutic strategy for treatment of pulmonary metastases and primary lung cancers. JF - Journal of Pharmacy and Pharmacology AU - Khanna, C AU - Waldrep, J C AU - Anderson, P M AU - Weischelbaum, R W AU - Hasz, DE AU - Katsanis, E AU - Klausner, J S AD - Pediatric Branch, National Cancer Institute, National Institutes of Health, Building 10, Room 13N240, 10 Centre Dr. MSC 1928, Bethesda, MD 20892-1928, USA Y1 - 1997/10// PY - 1997 DA - Oct 1997 SP - 960 EP - 971 VL - 49 IS - 10 SN - 0022-3573, 0022-3573 KW - aerosols KW - carcinoma KW - interleukin 2 KW - liposomes KW - lung KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - W3 33150:Cytokine based KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16448146?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Pharmacy+and+Pharmacology&rft.atitle=Nebulized+interleukin+2+liposomes%3A+Aerosol+characteristics+and+biodistribution&rft.au=Khanna%2C+C%3BWaldrep%2C+J+C%3BAnderson%2C+P+M%3BWeischelbaum%2C+R+W%3BHasz%2C+DE%3BKatsanis%2C+E%3BKlausner%2C+J+S&rft.aulast=Khanna&rft.aufirst=C&rft.date=1997-10-01&rft.volume=49&rft.issue=10&rft.spage=960&rft.isbn=&rft.btitle=&rft.title=Journal+of+Pharmacy+and+Pharmacology&rft.issn=00223573&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Leptospirosis AN - 16347301; 4301555 AB - Leptospirosis has recently been recognized as another reemerging infectious disease, both as epidemic in developing countries (Nicaragua, India) and as endemic in industrialized countries (USA). Molecular techniques have been successfully used for speciation, but have not replaced the gold standard serological techniques for identifying leptospires to the serovar level. Polymerase chain reaction is becoming the ideal diagnostic test, because leptospiral DNA can be detected both on the initial presentation of clinical illness and even months later, and results are rapidly available. Modern techniques of cellular and molecular biology are beginning to unravel the pathogenesis and pathophysiology of leptospirosis. Treatment continues to rely on penicillins and tetracyclines, but morbidity and mortality should decline as improvements in rapid diagnostic techniques become widely adopted and the disease becomes more widely recognized. JF - Current Opinion in Infectious Diseases AU - Vinetz, J M AD - Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, 9000 Rockville Pike, Building 4, Room 126, Bethesda, MD 20892-0425, USA Y1 - 1997/10// PY - 1997 DA - Oct 1997 SP - 357 EP - 361 VL - 10 IS - 5 SN - 0951-7375, 0951-7375 KW - India KW - Nicaragua KW - USA KW - leptospirosis KW - reviews KW - Microbiology Abstracts B: Bacteriology KW - J 02855:Human Bacteriology: Others UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16347301?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+Opinion+in+Infectious+Diseases&rft.atitle=Leptospirosis&rft.au=Vinetz%2C+J+M&rft.aulast=Vinetz&rft.aufirst=J&rft.date=1997-10-01&rft.volume=10&rft.issue=5&rft.spage=357&rft.isbn=&rft.btitle=&rft.title=Current+Opinion+in+Infectious+Diseases&rft.issn=09517375&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Roles for lambda Orf and Escherichia coli RecO, RecR and RecF in lambda recombination AN - 16258820; 4240872 AB - Bacteriophage lambda lacking its Red recombination functions requires either its own gene product, Orf, or the product of Escherichia coli's recO, recR and recF genes (RecORF) for efficient recombination in recBC sbcB sbcC mutant cells (the RecF pathway). Phage crosses under conditions of a partial block to DNA replication have revealed the following: (1) In the presence of Orf, RecF pathway recombination is similar to lambda Red recombination; (2) Orf is necessary for focusing recombination toward the right end of the chromosome as lambda is conventionally drawn; (3) RecORF-mediated RecF pathway recombination is not focused toward the right end of the chromosome, which may indicate that RecORF travels along the DNA; (4) both Orf- and RecORF-mediated RecF pathway recombination are stimulated by DNA replication; and (5) low level recombination in the simultaneous absence of Orf and RecORF may occur by a break-copy mechanism that is not initiated by a double strand break. Models for the roles of Orf and RecO, RecR and RecF in recombination are presented. JF - Genetics AU - Sawitzke, JA AU - Stahl, F W AD - ABL-Basic Res. Prog., NCI-Frederick, P.O. Box B, Frederick, MD 21702-1201, USA Y1 - 1997/10// PY - 1997 DA - Oct 1997 SP - 357 EP - 369 VL - 147 IS - 2 SN - 0016-6731, 0016-6731 KW - DNA KW - RecF protein KW - RecO protein KW - RecR protein KW - recF gene KW - recO gene KW - recR gene KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - J 02727:Amino acids, peptides and proteins KW - N 14940:Nucleic acid-binding proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16258820?accountid=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=Genetics&rft.atitle=Roles+for+lambda+Orf+and+Escherichia+coli+RecO%2C+RecR+and+RecF+in+lambda+recombination&rft.au=Sawitzke%2C+JA%3BStahl%2C+F+W&rft.aulast=Sawitzke&rft.aufirst=JA&rft.date=1997-10-01&rft.volume=147&rft.issue=2&rft.spage=357&rft.isbn=&rft.btitle=&rft.title=Genetics&rft.issn=00166731&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Ornithine- delta -aminotransferase expression and ornithine metabolism in cultured epidermal keratinocytes: Toward metabolic sink therapy for gyrate atrophy AN - 16257605; 4229998 AB - There is now strong evidence that the chorioretinal degeneration associated with ornithine- delta -aminotransferase (OAT) deficiency is a consequence of hyperornithinemia. Therefore development of a metabolic system for clearing ornithine from the circulation is being pursued as a potential treatment. The skin is considered an attractive location for such a metabolic system because autologous cells can be safely and easily utilized. This study was undertaken to determine the ornithine metabolizing capacity of epidermal keratinocytes expressing normal and superphysiologic amounts of OAT. The data show that overexpression of OAT in keratinocytes cultured from a gyrate atrophy patient restores ornithine metabolism and results in a rate of ornithine disappearance from the medium that is significantly higher than the rate of disappearance from the medium bathing normal keratinocytes. In addition, OAT activity determined in soluble protein prepared from sonicates suggests that the capacity to maintain plasma ornithine within the normal range is contained within an accomplishable graft of keratinocytes overexpressing OAT. However, the actual rate of ornithine disappearance from the media was significantly less than predicted from enzyme activity assays. Following ornithine metabolite production by intact cells suggests that ornithine metabolism is limited primarily by clearance of downstream metabolites, as opposed to substrate delivery. JF - Gene Therapy AU - Sullivan, D M AU - Jensen, T G AU - Taichman, L B AU - Csaky, K G AD - National Institutes of Health, Building 10, Room 10N202, 10 Center Drive, MSC 1858, Bethesda, MD 20892-1858, USA Y1 - 1997/10// PY - 1997 DA - Oct 1997 SP - 1036 EP - 1044 VL - 4 IS - 10 SN - 0969-7128, 0969-7128 KW - epidermis KW - gene therapy KW - keratinocytes KW - metabolic disorders KW - ornithine KW - ornithine- delta -aminotransferase KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - W 30965:Miscellaneous, Reviews KW - W3 33055:Genetic engineering (general) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16257605?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Gene+Therapy&rft.atitle=Ornithine-+delta+-aminotransferase+expression+and+ornithine+metabolism+in+cultured+epidermal+keratinocytes%3A+Toward+metabolic+sink+therapy+for+gyrate+atrophy&rft.au=Sullivan%2C+D+M%3BJensen%2C+T+G%3BTaichman%2C+L+B%3BCsaky%2C+K+G&rft.aulast=Sullivan&rft.aufirst=D&rft.date=1997-10-01&rft.volume=4&rft.issue=10&rft.spage=1036&rft.isbn=&rft.btitle=&rft.title=Gene+Therapy&rft.issn=09697128&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Chaperone-mediated reduction of RepA dimerization is associated with RepA conformational change AN - 16255662; 4240666 AB - RepA, the initiator protein of plasmid P1, binds to multiple sites (iterons) in the origin. The binding normally requires participation of chaperones, DnaJ, DnaK and GrpE. When purified, RepA appears dimeric and is inactive in iteron binding. On reaction with chaperones, a species active in iteron binding is formed and found to be monomeric. To test whether the chaperones can reduce dimerization, RepA was used to replace the dimerization domain of the lambda repressor. The hybrid protein repressed the lambda operator efficiently, indicating that RepA can dimerize in vivo. A further increase in repressor activity was seen in dnaJ mutant cells. These results are consistent with a chaperone-mediated reduction of RepA dimerization. We also found that RepA mutants defective in dimerization still depend on DnaJ for iteron binding. Conversely, RepA mutants that no longer require chaperones for iteron binding remain dimerization proficient. These results indicate that the chaperone dependence of RepA activity is not solely owing to RepA dimerization. Our results are most simply explained by a chaperone-mediated conformational change in RepA protomer that activates iteron binding. This conformational change also results in reduced RepA dimerization. JF - Molecular Microbiology AU - Dibbens, JA AU - Muraiso, K AU - Chattoraj, D K AD - Lab. Biochem., NCI, NIH, Bethesda, MD 20892-4255, USA Y1 - 1997/10// PY - 1997 DA - Oct 1997 SP - 185 EP - 195 VL - 26 IS - 1 SN - 0950-382X, 0950-382X KW - RepA protein KW - bacteria KW - chaperones KW - conformational analysis KW - dimerization KW - plasmid P1 KW - Microbiology Abstracts B: Bacteriology KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16255662?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+Microbiology&rft.atitle=Chaperone-mediated+reduction+of+RepA+dimerization+is+associated+with+RepA+conformational+change&rft.au=Dibbens%2C+JA%3BMuraiso%2C+K%3BChattoraj%2C+D+K&rft.aulast=Dibbens&rft.aufirst=JA&rft.date=1997-10-01&rft.volume=26&rft.issue=1&rft.spage=185&rft.isbn=&rft.btitle=&rft.title=Molecular+Microbiology&rft.issn=0950382X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Plasma phospholipid transfer protein. Adenovirus-mediated overexpression in mice leads to decreased plasma high density lipoprotein (HDL) and enhanced hepatic uptake of phospholipids and cholesteryl esters from HDL AN - 16234630; 4216856 AB - In vitro studies have shown that plasma phospholipid transfer protein (PLTP) converts isolated human high density lipoprotein-3 (HDL sub(3)) into larger HDL particles and generates lipid-poor apoA-I containing nascent HDL. To evaluate the role of PLTP in vivo we generated recombinant adenovirus vectors containing either human PLTP cDNA (rPLTP.AdV) or the reporter luciferase cDNA as a control. After intravenous infusion of 4 x 10 super(7) plaque-forming units (low dose) and 4 x 10 super(8) plaqueforming units (high dose) of rPLTP.AdV into mice, PLTP activity in plasma increased from base-line levels of 8.4 plus or minus 0.2 to 108 plus or minus 17 and from 8.9 plus or minus 0.6 to 352 plus or minus 31 mu mol /ml/h, respectively, on day 4 (both p < 0.001). Thus, both low and high doses of rPLTP.AdV led to pronounced overexpression of human PLTP in mice. On day 4 after treatment, mice treated with low and high doses of rPLTP.AdV showed decreased HDL cholesterol (-54% and -91%) and apoA-I (-64% and -98%) (all p < 0.05). Kinetic studies revealed that the fractional catabolic rates of HDL labeled with [ super(3)H]phosphatidylcholine, [ super(14)C]phosphatidylcholine ether, [ super(3)H]cholesteryl ether, and super(125)I-labeled mouse apoA-I were increased by 8.5-, 8.7-, 3.8-, and 2.8-fold, respectively, in mice treated with low dose rPLTP.AdV (all p < 0.001). After injection of labeled HDL, mice treated with rPLTP.AdV showed an increased accumulation of labeled PC ether (+304%) and cholesteryl ether (+92%) in the liver (both p < 0.05). Two-dimensional gel electrophoresis of plasma 5 min after injection of HDL labeled with super(125)I-apoA-I demonstrated increased levels of newly generated pre- beta -HDL in mice overexpressing PLTP. In conclusion, HDL remodeling mediated by PLTP generates nascent, lipid-poor apoA-I in vivo and accelerates the hepatic uptake of HDL surface and core lipids in mice treated with rPLTP.AdV. Accelerated catabolism of HDL in mice overexpressing PLTP leads to low HDL levels. Our data indicate an important role for PLTP in modulating reverse cholesterol transport in vivo. JF - Journal of Biological Chemistry AU - Foeger, B AU - Santamarina-Fojo, S AU - Shamburek, R D AU - Parrot, CL AU - Talley, G D AU - Brewer, HB Jr AD - National Institutes of Health, Molecular Disease Branch, National Heart, Lung, and Blood Institute, Bldg. 10, Room 7N102, 10 Center Dr. MSC 1666, Bethesda, MD 20892, USA Y1 - 1997/10// PY - 1997 DA - Oct 1997 SP - 27393 EP - 27400 VL - 272 IS - 43 SN - 0021-9258, 0021-9258 KW - adenovirus KW - cholesterol KW - lipoprotein (high density) KW - liver KW - mice KW - phospholipids KW - plasma phospholipid transfer protein KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - W3 33056:Animal models of human disease KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16234630?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Biological+Chemistry&rft.atitle=Plasma+phospholipid+transfer+protein.+Adenovirus-mediated+overexpression+in+mice+leads+to+decreased+plasma+high+density+lipoprotein+%28HDL%29+and+enhanced+hepatic+uptake+of+phospholipids+and+cholesteryl+esters+from+HDL&rft.au=Foeger%2C+B%3BSantamarina-Fojo%2C+S%3BShamburek%2C+R+D%3BParrot%2C+CL%3BTalley%2C+G+D%3BBrewer%2C+HB+Jr&rft.aulast=Foeger&rft.aufirst=B&rft.date=1997-10-01&rft.volume=272&rft.issue=43&rft.spage=27393&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Rickettsia rickettsii growth and temperature-inducible protein expression in embryonic tick cell lines AN - 16223144; 4220991 AB - Rickettsia rickettsii has limited adverse effects on its arthropod vector, but causes severe disease in man. To model differences in host-parasite interaction, R. rickettsii growth and protein expression were examined at temperatures reflective of host environment in the tick cell lines DALBE3 and IDE2, the human endothelial cell line ECV304, and the African green monkey kidney cell line Vero76. At low multiplicities of infection, rickettsial titres increased 10 super(2)-10 super(3)-fold in all cell lines after incubation for 3 days at 34 degree C. At higher multiplicites and with extended incubation, R. rickettsii showed enhanced survival in tick versus mammalian cells. No difference in rickettsial ultrastructure or protein profiles was detected between different host cell types. Rickettsial proteins of 42, 43, 48, 75 and 100 kDa are induced in tick cells shifted from 28 degree to 34 degree C, but not in cells maintained at 28 degree C. This temperature response may be associated with expression of rickettsial determinants that are pathogenic to mammalian hosts. JF - Journal of Medical Microbiology AU - Policastro, P F AU - Munderloh, U G AU - Fischer, E R AU - Hackstadt, T AD - Lab. Intracellular Parasites, Rocky Mountain Labs., NIAID, NIH, Hamilton, MT 59840, USA Y1 - 1997/10// PY - 1997 DA - Oct 1997 SP - 839 EP - 845 VL - 46 IS - 10 SN - 0022-2615, 0022-2615 KW - cell lines KW - proteins KW - temperature KW - Entomology Abstracts; Microbiology Abstracts B: Bacteriology KW - J 02870:Invertebrate bacteriology KW - Z 05182:Pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16223144?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Medical+Microbiology&rft.atitle=Rickettsia+rickettsii+growth+and+temperature-inducible+protein+expression+in+embryonic+tick+cell+lines&rft.au=Policastro%2C+P+F%3BMunderloh%2C+U+G%3BFischer%2C+E+R%3BHackstadt%2C+T&rft.aulast=Policastro&rft.aufirst=P&rft.date=1997-10-01&rft.volume=46&rft.issue=10&rft.spage=839&rft.isbn=&rft.btitle=&rft.title=Journal+of+Medical+Microbiology&rft.issn=00222615&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Adenovirus-mediated gene transfer of fibroblast growth factor-1: Angiogenesis and tumorigenicity in nude mice AN - 16220209; 4216397 AB - Gene transfer of angiogenic growth factors with replication-deficient recombinant adenovirus (Ad) vectors may provide a new approach to the treatment of ischemic diseases. To determine if Ad-infected cells could stimulate angiogenesis in vivo and to assess the tumorigenicity of cells infected with these vectors, NIH3T3 fibroblasts infected with Ad vectors coding for human acidic fibroblast growth factor (aFGF-I) were used in angiogenic and tumorigenic assays. Infected cells induced a strong angiogenic response in vivo, while cells infected with control virus did not. Stable 3T3 transfectants expressing the FGF-I gene were also highly angiogenic and exhibited growth in soft agar, while Ad-infected cells did not. Ad-infected cells grew transiently in nude mice, whereas 3T3 transfectants formed large tumors which grew exponentially. Extrapolation of cell dose-response curves showed that a minimum of 1.5 x 10 super(4) infected cells were required for transient tumor cell growth in vivo. Ad-infected cells cultured in vitro for 30 days lost their invasive phenotype and the ability for transient cell growth in nude mice. Thus, phenotypic changes induced by Ad-mediated gene transfer of FGF-I are transient both in vitro and in vivo, suggesting that these Ad vectors do not have tumorigenic potential. Stimulation of angiogenesis by Ad-infected cells may be useful for the evaluation of anti-angiogenic and anti-tumor agents. JF - International Journal of Cancer AU - Pili, R AU - Chang, J AU - Muhlhauser, J AU - Crystal, R G AU - Capogrossi, M C AU - Passaniti, A AD - Gerontology Research Center, Box 12, National Institute on Aging (NIH), 4940 Eastern Avenue, Baltimore, MD 21224, USA Y1 - 1997/10// PY - 1997 DA - Oct 1997 SP - 258 EP - 263 PB - JOHN WILEY & SONS, INC. VL - 73 IS - 2 SN - 0020-7136, 0020-7136 KW - adenovirus KW - angiogenesis KW - fibroblast growth factor (acidic) KW - gene transfer KW - mice KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Oncogenes & Growth Factors Abstracts KW - B 26060:FGF & FGF receptor family/Hst-1/Int-2/KGF KW - W 30965:Miscellaneous, Reviews KW - W3 33180:Gene based (protocols, clinical trials, and animal models) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16220209?accountid=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=International+Journal+of+Cancer&rft.atitle=Adenovirus-mediated+gene+transfer+of+fibroblast+growth+factor-1%3A+Angiogenesis+and+tumorigenicity+in+nude+mice&rft.au=Pili%2C+R%3BChang%2C+J%3BMuhlhauser%2C+J%3BCrystal%2C+R+G%3BCapogrossi%2C+M+C%3BPassaniti%2C+A&rft.aulast=Pili&rft.aufirst=R&rft.date=1997-10-01&rft.volume=73&rft.issue=2&rft.spage=258&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Cancer&rft.issn=00207136&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Alu-mediated detection of DNA damage in the human genome AN - 16211909; 4209620 JF - Mutation Research AU - Englander, E W AU - Howard, B H AD - Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA Y1 - 1997/10// PY - 1997 DA - Oct 1997 SP - 31 EP - 39 PB - ELSEVIER SCIENCE B.V. VL - 385 IS - 1 SN - 0921-8777, 0921-8777 KW - man KW - Toxicology Abstracts; Genetics Abstracts KW - X 24210:Radiation & radioactive materials KW - G 07233:Radiation (U.V.) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16211909?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+Research&rft.atitle=Alu-mediated+detection+of+DNA+damage+in+the+human+genome&rft.au=Englander%2C+E+W%3BHoward%2C+B+H&rft.aulast=Englander&rft.aufirst=E&rft.date=1997-10-01&rft.volume=385&rft.issue=1&rft.spage=31&rft.isbn=&rft.btitle=&rft.title=Mutation+Research&rft.issn=09218777&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - SuppNotes - Shriners Burns Institute, Department of Surgery, University of Texas Medical Branch, 815 Market Street, Galveston, Texas 77550-2725. Tel.: +1 409-770-6990/6727; N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Transgenic factor VIII: The milky way and beyond AN - 16098699; 4203236 AB - More than 200 million years ago, nature developed the mammary gland and a novel way to provide nourishment to the newborn in the form of milk. The domestication of ruminants 6000 years ago allowed humankind to tap into a large reservoir of milk, and today its processed products fill the shelves of dairycases in supermarkets worldwide. Now, Paleyanda and colleagues have added yet another, and rather exotic, item to the long list of dairy products--human factor VIII. JF - Nature Biotechnology AU - Hennighausen, L AD - Laboratory of biochemistry and metabolism, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health, Bethesda, MD 20892-1812, USA Y1 - 1997/10// PY - 1997 DA - Oct 1997 SP - 945 EP - 946 VL - 15 IS - 10 SN - 1087-0156, 1087-0156 KW - coagulation factor VIII KW - pigs KW - transgenic pigs KW - Biotechnology and Bioengineering Abstracts; Genetics Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Transgenic animals KW - reviews KW - milk KW - mammary gland KW - W3 33340:Other proteins, peptides, amino acids KW - G 07418:GENERAL KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16098699?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+Biotechnology&rft.atitle=Transgenic+factor+VIII%3A+The+milky+way+and+beyond&rft.au=Hennighausen%2C+L&rft.aulast=Hennighausen&rft.aufirst=L&rft.date=1997-10-01&rft.volume=15&rft.issue=10&rft.spage=945&rft.isbn=&rft.btitle=&rft.title=Nature+Biotechnology&rft.issn=10870156&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - Transgenic animals; reviews; milk; mammary gland ER - TY - JOUR T1 - Association of arsenic-induced malignant transformation with DNA hypomethylation and aberrant gene expression. AN - 79383540; 9380733 AB - Inorganic arsenic, a human carcinogen, is enzymatically methylated for detoxication, consuming S-adenosyl-methionine (SAM) in the process. The fact that DNA methyltransferases (MeTases) require this same methyl donor suggests a role for methylation in arsenic carcinogenesis. Here we test the hypothesis that arsenic-induced initiation results from DNA hypomethylation caused by continuous methyl depletion. The hypothesis was tested by first inducing transformation in a rat liver epithelial cell line by chronic exposure to low levels of arsenic, as confirmed by the development of highly aggressive, malignant tumors after inoculation of cells into Nude mice. Global DNA hypomethylation occurred concurrently with malignant transformation and in the presence of depressed levels of S-adenosyl-methionine. Arsenic-induced DNA hypomethylation was a function of dose and exposure duration, and remained constant even after withdrawal of arsenic. Hyperexpressibility of the MT gene, a gene for which expression is clearly controlled by DNA methylation, was also detected in transformed cells. Acute arsenic or arsenic at nontransforming levels did not induce global hypomethylation of DNA. Whereas transcription of DNA MeTase was elevated, the MeTase enzymatic activity was reduced with arsenic transformation. Taken together, these results indicate arsenic can act as a carcinogen by inducing DNA hypomethylation, which in turn facilitates aberrant gene expression, and they constitute a tenable theory of mechanism in arsenic carcinogenesis. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Zhao, C Q AU - Young, M R AU - Diwan, B A AU - Coogan, T P AU - Waalkes, M P AD - Inorganic Carcinogenesis Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute/National Institute on Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. Y1 - 1997/09/30/ PY - 1997 DA - 1997 Sep 30 SP - 10907 EP - 10912 VL - 94 IS - 20 SN - 0027-8424, 0027-8424 KW - Arsenites KW - 0 KW - Carcinogens KW - Sodium Compounds KW - sodium arsenite KW - 48OVY2OC72 KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Mice, Nude KW - Mice KW - Cell Line KW - DNA Methylation KW - Arsenites -- toxicity KW - Sodium Compounds -- toxicity KW - Gene Expression KW - Carcinogens -- toxicity KW - Cell Transformation, Neoplastic -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79383540?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Association+of+arsenic-induced+malignant+transformation+with+DNA+hypomethylation+and+aberrant+gene+expression.&rft.au=Zhao%2C+C+Q%3BYoung%2C+M+R%3BDiwan%2C+B+A%3BCoogan%2C+T+P%3BWaalkes%2C+M+P&rft.aulast=Zhao&rft.aufirst=C&rft.date=1997-09-30&rft.volume=94&rft.issue=20&rft.spage=10907&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 - 1997-11-10 N1 - Date created - 1997-11-10 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1996 Apr 30;93(9):4045-50 [8633014] J Pharmacol Exp Ther. 1996 May;277(2):1026-33 [8627513] Proc Natl Acad Sci U S A. 1997 Mar 18;94(6):2545-50 [9122232] In Vitro. 1976 Aug;12(8):541-53 [11177] Cell. 1981 Jul;25(1):233-40 [6168387] Environ Res. 1981 Aug;25(2):286-93 [7274192] Environ Mutagen. 1980;2(3):371-9 [6459229] Toxicol Appl Pharmacol. 1982 Oct;66(1):134-42 [7157381] J Pharm Pharmacol. 1984 Feb;36(2):85-9 [6143811] Anal Biochem. 1984 Jul;140(1):108-16 [6486398] Carcinogenesis. 1985 Oct;6(10):1421-6 [3840060] Environ Mutagen. 1985;7(5):787-804 [3899634] Proc Natl Acad Sci U S A. 1986 Jan;83(1):33-7 [3510430] Cancer Res. 1987 Jan 1;47(1):80-8 [2431769] Environ Res. 1987 Feb;42(1):72-82 [3803345] Biochem J. 1986 Dec 1;240(2):313-24 [3545184] Jpn J Cancer Res. 1987 Jul;78(7):695-704 [3040653] Science. 1987 Oct 9;238(4824):163-70 [3310230] Carcinogenesis. 1987 Dec;8(12):1889-97 [2445499] Science. 1988 Jul 1;241(4861):79-81 [3388020] Chem Biol Interact. 1988;66(3-4):189-204 [2456160] N Engl J Med. 1988 Sep 1;319(9):525-32 [2841597] Oncogene. 1988 Aug;3(2):163-8 [3412774] Carcinogenesis. 1989 May;10(5):933-7 [2650909] J Nutr. 1989 Oct;119(10):1478-82 [2531221] J Biol Chem. 1990 Jan 5;265(1):221-6 [1967174] Biol Rev Camb Philos Soc. 1990 Nov;65(4):431-71 [2265224] J Biochem Biophys Methods. 1991 Jan;22(1):19-22 [2005357] Proc Natl Acad Sci U S A. 1991 Aug 1;88(15):6515-8 [1650472] Nucleic Acids Res. 1991 Aug 11;19(15):4293 [1870982] Microbiol Rev. 1991 Sep;55(3):451-8 [1943996] Chem Res Toxicol. 1990 Jul-Aug;3(4):281-8 [2133072] Biochem Pharmacol. 1992 Oct 6;44(7):1283-9 [1417952] J Pharmacol Exp Ther. 1993 Sep;266(3):1656-63 [8371163] Proc Natl Acad Sci U S A. 1993 Oct 1;90(19):8886-90 [8415626] Nucleic Acids Res. 1994 Jan 11;22(1):1-10 [8127644] Mol Carcinog. 1994 Mar;9(3):155-66 [7908202] Cancer Lett. 1994 Apr 29;79(1):9-16 [7910516] Cancer. 1994 Aug 1;74(3):893-9 [8039116] Drug Metab Rev. 1994;26(1-2):185-99 [8082564] Eur J Biochem. 1994 Sep 1;224(2):431-7 [7925357] Mol Carcinog. 1994 Dec;11(4):185-8 [7999259] Environ Health Perspect. 1994 Sep;102 Suppl 3:97-100 [7843143] Toxicol Appl Pharmacol. 1995 Feb;130(2):229-36 [7871536] Cell. 1995 Oct 6;83(1):13-5 [7553865] Toxicol Appl Pharmacol. 1996 Sep;140(1):77-84 [8806872] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Extrapyramidal side effects with risperidone and haloperidol at comparable D2 receptor occupancy levels. AN - 79375514; 9351491 AB - Risperidone is an antipsychotic drug with high affinity at dopamine D2 and serotonin 5-HT2 receptors. Previous clinical studies have proposed that risperidone's pharmacologic profile may produce improved efficacy for negative psychotic symptoms and decreased propensity for extrapyramidal side effects; features shared by so-called 'atypical' neuroleptics. To determine if routine risperidone treatment is associated with a unique degree of D2 receptor occupancy and pattern of clinical effects, we used [123I]IBZM SPECT to determine D2 occupancy in subjects treated with routine clinical doses of risperidone (n = 12) or haloperidol (n = 7). Both risperidone and haloperidol produced D2 occupancy levels between approximately 60 and 90% at standard clinical doses. There was no significant difference between occupancy levels obtained with haloperidol or risperidone. Drug-induced parkinsonism was observed in subjects treated with risperidone (42%) and haloperidol (29%) and was observed at occupancy levels above 60%. Based on these observations, it is concluded that 5-HT2 blockade obtained with risperidone at D2 occupancy rates of 60% and above does not appear to protect against the risk for extrapyramidal side effects. JF - Psychiatry research AU - Knable, M B AU - Heinz, A AU - Raedler, T AU - Weinberger, D R AD - National Institute of Mental Health, Intramural Research Program, Clinical Brain Disorders Branch, Washington, D.C. 20032, USA. knablem@dirpc.nimh.nih.gov Y1 - 1997/09/29/ PY - 1997 DA - 1997 Sep 29 SP - 91 EP - 101 VL - 75 IS - 2 SN - 0165-1781, 0165-1781 KW - Antipsychotic Agents KW - 0 KW - Benzamides KW - Dopamine Antagonists KW - Pyrrolidines KW - Receptors, Dopamine D2 KW - 3-iodo-2-hydroxy-6-methoxy-N-((1-ethyl-2-pyrrolidinyl)methyl)benzamide KW - 84226-06-2 KW - Haloperidol KW - J6292F8L3D KW - Risperidone KW - L6UH7ZF8HC KW - Index Medicus KW - Drug Therapy, Combination KW - Parkinson Disease, Secondary -- chemically induced KW - Brain Mapping KW - Tomography, Emission-Computed, Single-Photon KW - Humans KW - Brain -- drug effects KW - Adult KW - Neurologic Examination -- drug effects KW - Middle Aged KW - Male KW - Female KW - Haloperidol -- adverse effects KW - Haloperidol -- therapeutic use KW - Antipsychotic Agents -- therapeutic use KW - Receptors, Dopamine D2 -- drug effects KW - Risperidone -- adverse effects KW - Antipsychotic Agents -- adverse effects KW - Risperidone -- therapeutic use KW - Basal Ganglia Diseases -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79375514?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Extrapyramidal+side+effects+with+risperidone+and+haloperidol+at+comparable+D2+receptor+occupancy+levels.&rft.au=Knable%2C+M+B%3BHeinz%2C+A%3BRaedler%2C+T%3BWeinberger%2C+D+R&rft.aulast=Knable&rft.aufirst=M&rft.date=1997-09-29&rft.volume=75&rft.issue=2&rft.spage=91&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 - 1997-12-16 N1 - Date created - 1997-12-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of serine 643 of protein kinase C-delta as an important autophosphorylation site for its enzymatic activity. AN - 79298460; 9305920 AB - To investigate the role of serine/threonine autophosphorylation of protein kinase C-delta (PKC-delta), we mutated serine 643 of PKC-delta to an alanine residue (PKC-deltaS643A). Two different expression vectors containing PKC-deltaS643A mutant cDNAs were transfected and expressed in 32D myeloid progenitor cells. In vitro autophosphorylation assays demonstrated 65-83% reduction in autophosphorylation of PKC-deltaS643A in comparison to wild type PKC-delta (PKC-deltaWT). The enzymatic activity of PKC-deltaS643A mutant as measured by phosphorylating the PKC-delta pseudosubstrate region-derived substrate was also reduced more than 70% in comparison to that of PKC-deltaWT. In vivo labeling and subsequent two-dimensional phosphopeptide analysis demonstrated that at least one phosphopeptide was absent in PKC-deltaS643A when compared with PKC-deltaWT, further substantiating that serine 643 is phosphorylated in vivo. Localization and 12-O-tetradecanoylphorbol-13-acetate-dependent translocation and tyrosine phosphorylation of PKC-deltaS643A were not altered in comparison to PKC-deltaWT, indicating that mutagenesis did not affect the structural integrity of the mutant protein. 12-O-Tetradecanoylphorbol-13-acetate-mediated monocytic differentiation of 32D cells overexpressing PKC-deltaS643A mutant protein was impaired in comparison to that of PKC-deltaWT transfectant. Taken together, our results demonstrate that serine 643 of PKC-delta is a major autophosphorylation site, and phosphorylation of this site plays an important role in controlling its enzymatic activity and biological function. JF - The Journal of biological chemistry AU - Li, W AU - Zhang, J AU - Bottaro, D P AU - Pierce, J H AD - Laboratory of Cellular and Molecular Biology, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA. Liwe@dc37a.nci.nih.gov Y1 - 1997/09/26/ PY - 1997 DA - 1997 Sep 26 SP - 24550 EP - 24555 VL - 272 IS - 39 SN - 0021-9258, 0021-9258 KW - DNA, Complementary KW - 0 KW - Isoenzymes KW - Serine KW - 452VLY9402 KW - Prkcd protein, mouse KW - EC 2.7.1.- KW - Protein Kinase C KW - EC 2.7.11.13 KW - Protein Kinase C-delta KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - Biological Transport KW - Amino Acid Sequence KW - Mice KW - Mutagenesis, Site-Directed KW - Sequence Alignment KW - Phosphorylation KW - Monocytes -- cytology KW - Molecular Sequence Data KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Monocytes -- drug effects KW - Substrate Specificity KW - Cell Differentiation -- drug effects KW - Protein Kinase C -- metabolism KW - Isoenzymes -- chemistry KW - Protein Kinase C -- genetics KW - Protein Kinase C -- chemistry KW - Isoenzymes -- genetics KW - Serine -- metabolism KW - Isoenzymes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79298460?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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+serine+643+of+protein+kinase+C-delta+as+an+important+autophosphorylation+site+for+its+enzymatic+activity.&rft.au=Li%2C+W%3BZhang%2C+J%3BBottaro%2C+D+P%3BPierce%2C+J+H&rft.aulast=Li&rft.aufirst=W&rft.date=1997-09-26&rft.volume=272&rft.issue=39&rft.spage=24550&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 - 1997-10-23 N1 - Date created - 1997-10-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Reliability of the alcohol and drug modules of the Alcohol Use Disorder and Associated Disabilities Interview Schedule--Alcohol/Drug-Revised (AUDADIS-ADR): an international comparison. AN - 79306331; 9306043 AB - The purpose of the present study was to examine the test-retest reliability of the alcohol and drug modules of the AUDADIS-ADR in three sites: Bangalore, India, Jebel, Romania and Sydney, Australia. The overall reliability of ICD-10, DSM-IV and DSM-III-R dependence diagnoses was found to be good to excellent for each substance, including alcohol, for each time frame, regardless of whether the total sample or user subsample figured into the calculations. Reliability associated with corresponding harmful use and abuse diagnoses were mixed, but generally lower. Reliability statistics for Bangalore were generally lower than those of the Jebel and Sydney sites, particularly for alcohol diagnostic criteria. Implications of these results are discussed, in conjunction with results from the discrepancy interview protocol analyses within sites, in terms of future revisions to the AUDADIS-ADR and its training procedures tailored to developing countries. JF - Drug and alcohol dependence AU - Chatterji, S AU - Saunders, J B AU - Vrasti, R AU - Grant, B F AU - Hasin, D AU - Mager, D AD - National Institute of Mental Health and Neurosciences, Bangalore, India. Y1 - 1997/09/25/ PY - 1997 DA - 1997 Sep 25 SP - 171 EP - 185 VL - 47 IS - 3 SN - 0376-8716, 0376-8716 KW - Psychotropic Drugs KW - 0 KW - Street Drugs KW - Index Medicus KW - World Health Organization KW - Reproducibility of Results KW - Humans KW - Cross-Cultural Comparison KW - Adult KW - Middle Aged KW - Developing Countries KW - Psychometrics KW - Male KW - Female KW - Substance-Related Disorders -- diagnosis KW - Alcoholism -- epidemiology KW - Alcoholism -- diagnosis KW - Substance-Related Disorders -- psychology KW - Psychiatric Status Rating Scales -- statistics & numerical data KW - Alcoholism -- psychology KW - Substance-Related Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79306331?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Reliability+of+the+alcohol+and+drug+modules+of+the+Alcohol+Use+Disorder+and+Associated+Disabilities+Interview+Schedule--Alcohol%2FDrug-Revised+%28AUDADIS-ADR%29%3A+an+international+comparison.&rft.au=Chatterji%2C+S%3BSaunders%2C+J+B%3BVrasti%2C+R%3BGrant%2C+B+F%3BHasin%2C+D%3BMager%2C+D&rft.aulast=Chatterji&rft.aufirst=S&rft.date=1997-09-25&rft.volume=47&rft.issue=3&rft.spage=171&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 - 1997-10-24 N1 - Date created - 1997-10-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Retroviral Mediated Gene Transfer of the Fanconi Anemia Complementation Group C Gene to Hematopoietic Progenitors of Group C Patients AN - 17283972; 4510680 AB - Fanconi anemia (FA) is a rare genetic disorder characterized by progressive pancytopenia, congenital abnormalities, and a predisposition to malignancy. Therapy is currently limited to allogeneic marrow transplantation; patients lacking a suitable donor usually die from aplasia or acute leukemia. Recently, mutation in a novel gene named FACC (Fanconi anemia C-complementing) has been identified as causing one type of FA. FACC mutations, which introduce splicing errors or stop codons, have been identified in similar to 15% of FA patients. We have recently been successful in functional complementation of four FA cell lines using retroviral vectors to transfer a copy of the normal FACC gene. We also analyzed the ability of our viral vectors to functionally correct hematopoietic progenitor cells from a patient bearing a splice donor mutation. As for the lymphoid cell lines, these CD34-enriched cells were extremely sensitive to MMC. After infection of these progenitor cells with viral vectors beating normal FACC, the progenitors gave rise to increased numbers of colonies both in the absence and presence of up to 5 nM MMC, whereas control cells were completely destroyed by 1 nM MMC. In summary, we have demonstrated that: (1) retroviral vectors can be engineered to transfer a normal FACC gene to FA(C) lymphoid cell lines and primary hematopoietic cells; (2) introduction of a normal FACC gene into CD34 super(+) progenitors markedly enhances their growth in the absence and presence of MMC. This study is designed to determine whether hematopoietic progenitors transduced with the normal FACC gene can be reinfused safely into FA(C) patients. CD34 super(+) cells obtained from G-CSF mobilized peripheral blood will be transduced ex vivo over a 72-hour period in the presence of IL-3, IL-6, and Stem Cell Factor with the FACC retroviral vector. These transduced cells will be reinfused into FA(C) patients. Patients will be monitored for toxicities as well as evidence of successful gene transfer and expression. The procedure will be repeated up to a total of 4 times with each treatment 2-4 months apart. Theoretically, these rescued stem cells should have a selective growth advantage within the hypoplastic FA marrow environment in vivo. JF - Human Gene Therapy AU - Liu, J M AU - Young, N S AU - Walsh, CE AU - Cottler-Fox, M AU - Carter, C AU - Dunbar, C AU - Barrett, A J AU - Emmons, R AD - Hematology Branch, NHLBI, Bldg. 10, Rm. 7C103, Bethesda, MD 20892, USA Y1 - 1997/09/20/ PY - 1997 DA - 1997 Sep 20 SP - 1715 EP - 1730 VL - 8 IS - 14 SN - 1043-0342, 1043-0342 KW - FACC gene KW - retrovirus KW - Biotechnology and Bioengineering Abstracts; Genetics Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Stem cells KW - Retrovirus KW - Gene transfer KW - Fanconi syndrome KW - Hemopoiesis KW - G 07443:Gene therapy KW - W 30965:Miscellaneous, Reviews KW - W3 33180:Gene based (protocols, clinical trials, and animal models) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17283972?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+Gene+Therapy&rft.atitle=Retroviral+Mediated+Gene+Transfer+of+the+Fanconi+Anemia+Complementation+Group+C+Gene+to+Hematopoietic+Progenitors+of+Group+C+Patients&rft.au=Liu%2C+J+M%3BYoung%2C+N+S%3BWalsh%2C+CE%3BCottler-Fox%2C+M%3BCarter%2C+C%3BDunbar%2C+C%3BBarrett%2C+A+J%3BEmmons%2C+R&rft.aulast=Liu&rft.aufirst=J&rft.date=1997-09-20&rft.volume=8&rft.issue=14&rft.spage=1715&rft.isbn=&rft.btitle=&rft.title=Human+Gene+Therapy&rft.issn=10430342&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Retrovirus; Fanconi syndrome; Gene transfer; Hemopoiesis; Stem cells ER - TY - JOUR T1 - Uptake and tissue distribution of chromium(III) in mice after a single intraperitoneal or subcutaneous administration. AN - 79396197; 9381486 AB - The tissue levels of chromium were followed after single intraperitoneal or subcutaneous injection of 1 mmol CrCl3/kg body wt. in Swiss male mice. Blood levels were similar after both treatment modes, with half-lives of 31-41 h. Organs not directly exposed by i.p. treatment contained similar amounts in the two groups, with kidneys > lungs > heart > brain. However, after i.p. treatment peritoneal organs (liver, spleen, pancreas and testis) had 40- to 200-fold more chromium compared with s.c. Assay of subsurface liver tissue and of testes removed via the scrotum indicated infiltration of the organs, rather than surface adsorption, of peritoneal chromium. Relative chromium concentrations after i.p. treatment were liver > pancreas = spleen > testis and after s.c. liver > spleen > testis > pancreas. Thus, s.c. treatment with CrCl3 is as effective as i.p. in terms of absorption into the blood. Treatment i.p., leading to direct uptake into peritoneal organs, is an effective way to deliver high chromium doses to these organs, but does not model likely human exposure. JF - Toxicology letters AU - Sipowicz, M A AU - Anderson, L M AU - Utermahlen, W E AU - Issaq, H J AU - Kasprzak, K S AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute, SAIC-Frederick, Frederick Cancer Research and Development Center, MD 21702, USA. Y1 - 1997/09/19/ PY - 1997 DA - 1997 Sep 19 SP - 9 EP - 14 VL - 93 IS - 1 SN - 0378-4274, 0378-4274 KW - Chlorides KW - 0 KW - Chromium Compounds KW - Chromium KW - 0R0008Q3JB KW - chromic chloride KW - KB1PCR9DMW KW - Index Medicus KW - Injections, Intraperitoneal KW - Animals KW - Half-Life KW - Chromium -- blood KW - Injections, Subcutaneous KW - Mice KW - Tissue Distribution KW - Male KW - Chromium Compounds -- pharmacokinetics KW - Chlorides -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79396197?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+letters&rft.atitle=Uptake+and+tissue+distribution+of+chromium%28III%29+in+mice+after+a+single+intraperitoneal+or+subcutaneous+administration.&rft.au=Sipowicz%2C+M+A%3BAnderson%2C+L+M%3BUtermahlen%2C+W+E%3BIssaq%2C+H+J%3BKasprzak%2C+K+S&rft.aulast=Sipowicz&rft.aufirst=M&rft.date=1997-09-19&rft.volume=93&rft.issue=1&rft.spage=9&rft.isbn=&rft.btitle=&rft.title=Toxicology+letters&rft.issn=03784274&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-11-12 N1 - Date created - 1997-11-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Photocross-linking of the NH2-terminal region of Taq MutS protein to the major groove of a heteroduplex DNA. AN - 79286753; 9295328 AB - The MutS DNA mismatch repair protein recognizes heteroduplex DNAs containing mispaired or unpaired bases. To identify regions of MutS protein in close proximity to the heteroduplex DNA, we have utilized the photoactivated cross-linking moiety 5-iododeoxyuridine (5-IdUrd). Nucleoprotein complexes of Thermus aquaticus MutS protein bound to monosubstituted 5-IdUrd-containing heteroduplex DNAs were cross-linked with long-wavelength ultraviolet light. Positioning of the 5-IdUrd moiety at one of three positions within the DNA bulge, two nucleotides upstream or three nucleotides downstream of the unpaired base, resulted in an identical subset of cross-linked peptides as determined by proteolytic fingerprinting. The tryptic peptide cross-linked to an unpaired 5-IdUrd residue was determined by peptide sequencing to correspond to a highly conserved region spanning residues 25-49. Cross-linking to the bulge nucleotide occurred at Phe-39, indicating that this residue contacts, or is in close proximity to, the unpaired base of a heteroduplex DNA. Site-directed mutagenesis resulting in the substitution of Ala for Phe-39 reduced the affinity of the mutant protein for heteroduplex DNA by roughly 3 orders of magnitude, but had no apparent effect on its ability to dimerize, its thermostability, or its ATPase activity. These results implicate the region in the vicinity of Phe-39 as being crucial for heteroduplex DNA binding by Taq MutS protein. JF - The Journal of biological chemistry AU - Malkov, V A AU - Biswas, I AU - Camerini-Otero, R D AU - Hsieh, P AD - Genetics and Biochemistry Branch, NIDDK, National Institutes of Health, Bethesda, Maryland 20892-1810, USA. Y1 - 1997/09/19/ PY - 1997 DA - 1997 Sep 19 SP - 23811 EP - 23817 VL - 272 IS - 38 SN - 0021-9258, 0021-9258 KW - Bacterial Proteins KW - 0 KW - DNA-Binding Proteins KW - Escherichia coli Proteins KW - Nucleic Acid Heteroduplexes KW - DNA KW - 9007-49-2 KW - Adenosine Triphosphatases KW - EC 3.6.1.- KW - MutS DNA Mismatch-Binding Protein KW - EC 3.6.1.3 KW - MutS protein, E coli KW - Index Medicus KW - Photochemistry KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Sequence Homology, Amino Acid KW - Protein Binding KW - Bacterial Proteins -- genetics KW - Thermus -- chemistry KW - Bacterial Proteins -- chemistry KW - DNA -- metabolism KW - Bacterial Proteins -- metabolism KW - DNA -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79286753?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Photocross-linking+of+the+NH2-terminal+region+of+Taq+MutS+protein+to+the+major+groove+of+a+heteroduplex+DNA.&rft.au=Malkov%2C+V+A%3BBiswas%2C+I%3BCamerini-Otero%2C+R+D%3BHsieh%2C+P&rft.aulast=Malkov&rft.aufirst=V&rft.date=1997-09-19&rft.volume=272&rft.issue=38&rft.spage=23811&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 - 1997-10-23 N1 - Date created - 1997-10-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Steroid-induced conformational changes at ends of the hormone-binding domain in the rat glucocorticoid receptor are independent of agonist versus antagonist activity. AN - 79279771; 9295350 AB - The underlying molecular mechanism for the expression of agonist versus antagonist activity for a given receptor-steroid complex is still not known. One attractive hypothesis, based on data from progesterone receptors, is that agonist versus antagonist binding induces unique conformations at the C terminus of receptors, which can be detected by the different fragments produced by partial proteolysis. We now report that the determinants of glucocorticoid receptor (GR)-antagonist complex activity are more complex. Steroid binding did cause a conformational change in the GR that was detected by partial trypsin digestion, as described previously (Simons, S. S., Jr., Sistare, F. D., and Chakraborti, P. K. (1989) J. Biol. Chem. 264, 14493-14497). However, there was no uniformity in the digestion patterns of unactivated or activated receptors bound by a series of six structurally different antagonists including the affinity labeling antiglucocorticoid dexamethasone 21-mesylate. A total of four resistant bands were observed on SDS-polyacrylamide gels in the range of 30-27 kDa. Using a series of point mutations and epitope-specific antibodies, it was determined that the 30-kDa species represented the entire C-terminal sequence of amino acids 518-795, whereas the other bands arose from additional N-terminal and/or C-terminal cleavages. Bioassays with GRs containing various point and deletion mutations failed to reveal any C-terminal alterations that could convert antagonists into biologically active agonists. Thus, the presence or absence of C-terminal amino acids of the GR did not uniquely determine either the appearance of smaller trypsin-resistant fragments or the nature of the biological response of receptor-bound antisteroids. When compared with the current model of the ligand-binding domain, which is based on the x-ray structures of the comparable region of thyroid and retinoic acid receptors, the present results suggest that sequences outside of the model structure are relevant for the binding and biological activity of GRs. JF - The Journal of biological chemistry AU - Modarress, K J AU - Opoku, J AU - Xu, M AU - Sarlis, N J AU - Simons, S S AD - Steroid Hormones Section, NIDDK/Laboratory of Molecular and Cellular Biology, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1997/09/19/ PY - 1997 DA - 1997 Sep 19 SP - 23986 EP - 23994 VL - 272 IS - 38 SN - 0021-9258, 0021-9258 KW - Receptors, Glucocorticoid KW - 0 KW - Steroids KW - Endopeptidases KW - EC 3.4.- KW - Trypsin KW - EC 3.4.21.4 KW - Index Medicus KW - Trypsin -- chemistry KW - Rats KW - Animals KW - Peptide Mapping KW - COS Cells KW - Endopeptidases -- metabolism KW - Hydrolysis KW - Protein Conformation KW - Mutagenesis KW - Receptors, Glucocorticoid -- drug effects KW - Receptors, Glucocorticoid -- chemistry KW - Steroids -- pharmacology KW - Receptors, Glucocorticoid -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79279771?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Steroid-induced+conformational+changes+at+ends+of+the+hormone-binding+domain+in+the+rat+glucocorticoid+receptor+are+independent+of+agonist+versus+antagonist+activity.&rft.au=Modarress%2C+K+J%3BOpoku%2C+J%3BXu%2C+M%3BSarlis%2C+N+J%3BSimons%2C+S+S&rft.aulast=Modarress&rft.aufirst=K&rft.date=1997-09-19&rft.volume=272&rft.issue=38&rft.spage=23986&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 - 1997-10-23 N1 - Date created - 1997-10-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Increased LRP mRNA expression is associated with the MDR phenotype in intrinsically resistant human cancer cell lines. AN - 79385397; 9378536 AB - Multidrug resistance (MDR) in human cancer cells is multifactorial. Previously, we reported on the association between expression of P-glycoprotein (Pgp), the multidrug resistance-associated protein (MRP), and the lung resistance protein (LRP) with the MDR phenotype in the NCI panel of 60 human cancer cell lines used for in vitro anticancer drug screening. Eight cell lines from this panel, manifesting widely divergent levels of in vitro drug resistance were chosen to investigate the role of MRP and LRP expression at the molecular level. LRP mRNA levels, as determined by ribonuclease protection assay, varied significantly among the 8 cell lines, and correlated closely with in vitro drug resistance to both MDR and non-MDR related drugs. LRP mRNA expression was determined to be a stronger correlate of drug sensitivity than protein expression. In contrast, MRP mRNA levels were not significantly correlated with drug sensitivity. The rates of newly transcribed LRP or MRP mRNA did not correlate with mRNA levels, indicating that mRNA stability or other features of processing may be important in regulation of LRP and MRP mRNA levels. Using Southern blot analysis, LRP gene amplification was shown not to be associated with LRP overexpression. These data suggest that LRP expression may be an important determinant of the MDR phenotype in cell lines intrinsically resistant to cancer chemotherapeutic agents. JF - International journal of cancer AU - Laurençot, C M AU - Scheffer, G L AU - Scheper, R J AU - Shoemaker, R H AD - Division of Cancer Treatment, Diagnosis and Centers, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702, USA. Y1 - 1997/09/17/ PY - 1997 DA - 1997 Sep 17 SP - 1021 EP - 1026 VL - 72 IS - 6 SN - 0020-7136, 0020-7136 KW - Antineoplastic Agents KW - 0 KW - Glycoproteins KW - Multidrug Resistance-Associated Proteins KW - Neoplasm Proteins KW - RNA, Messenger KW - Vault Ribonucleoprotein Particles KW - major vault protein KW - Amsacrine KW - 00DPD30SOY KW - Doxorubicin KW - 80168379AG KW - Cisplatin KW - Q20Q21Q62J KW - Melphalan KW - Q41OR9510P KW - Index Medicus KW - Amsacrine -- toxicity KW - Ovarian Neoplasms KW - Humans KW - Doxorubicin -- toxicity KW - Cell Nucleus KW - Melphalan -- toxicity KW - RNA, Messenger -- biosynthesis KW - Phenotype KW - Leukemia KW - Tumor Cells, Cultured KW - Kidney Neoplasms KW - Lung Neoplasms KW - Cisplatin -- toxicity KW - ATP-Binding Cassette Transporters -- biosynthesis KW - Colonic Neoplasms KW - Female KW - Neoplasm Proteins -- biosynthesis KW - Glycoproteins -- biosynthesis KW - Antineoplastic Agents -- toxicity KW - Transcription, Genetic KW - Drug Resistance, Multiple -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79385397?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+journal+of+cancer&rft.atitle=Increased+LRP+mRNA+expression+is+associated+with+the+MDR+phenotype+in+intrinsically+resistant+human+cancer+cell+lines.&rft.au=Lauren%C3%A7ot%2C+C+M%3BScheffer%2C+G+L%3BScheper%2C+R+J%3BShoemaker%2C+R+H&rft.aulast=Lauren%C3%A7ot&rft.aufirst=C&rft.date=1997-09-17&rft.volume=72&rft.issue=6&rft.spage=1021&rft.isbn=&rft.btitle=&rft.title=International+journal+of+cancer&rft.issn=00207136&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-11-10 N1 - Date created - 1997-11-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Breast implants and cancer. AN - 79298436; 9308703 AB - Although silicone breast implants have been linked to various short-term complications, less is known about their long-range effects. Most attention has focused on connective tissue disorders, but the range of immunologic disturbances observed in women with implants suggests that consideration also be given to other chronic diseases, including cancer. The greatest attention has focused on breast cancer, given clinical reports suggesting an association and observations that mammographic visualization is deterred by implants. Findings from epidemiologic studies, however, actually suggest that breast cancer risk might be reduced among women with implants, although the biologic mechanism remains undefined. In addition, most studies do not suggest that women with breast implants have more advanced breast cancer at diagnosis or a worse prognosis than those without implants. The majority of studies have focused on women who received implants for cosmetic reasons, with little previous investigation of women who received implants for breast reconstruction following cancer surgery. In terms of other cancers, animal as well as clinical data suggest potential risks of sarcomas and hematologic cancers, including multiple myeloma. The risk of these cancers has not yet been adequately addressed by epidemiologic studies, although several ongoing studies should provide insights. It will be important for studies to consider effects of other lifestyle factors as well as to analyze relationships according to duration of implantation, a demonstrated determinant of implant deterioration. In addition, consideration should be given to type of implant, including implants with polyurethane foam covers, which can leak toluene diamine, a demonstrated carcinogen in animals. JF - Journal of the National Cancer Institute AU - Brinton, L A AU - Brown, S L AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892-7374, USA. Y1 - 1997/09/17/ PY - 1997 DA - 1997 Sep 17 SP - 1341 EP - 1349 VL - 89 IS - 18 SN - 0027-8874, 0027-8874 KW - Polyurethanes KW - 0 KW - Index Medicus KW - Risk KW - Mammography KW - Humans KW - Sarcoma KW - Case-Control Studies KW - Lymphoma KW - Polyurethanes -- adverse effects KW - Female KW - Multiple Myeloma KW - Breast Neoplasms -- diagnostic imaging KW - Breast Implants KW - Breast Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79298436?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Breast+implants+and+cancer.&rft.au=Brinton%2C+L+A%3BBrown%2C+S+L&rft.aulast=Brinton&rft.aufirst=L&rft.date=1997-09-17&rft.volume=89&rft.issue=18&rft.spage=1341&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 - 1997-10-02 N1 - Date created - 1997-10-02 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Natl Cancer Inst. 1998 Feb 4;90(3):248-9 [9462686] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Abrogation of an S-phase checkpoint and potentiation of camptothecin cytotoxicity by 7-hydroxystaurosporine (UCN-01) in human cancer cell lines, possibly influenced by p53 function. AN - 79306626; 9307289 AB - 7-Hydroxystaurosporine (UCN-01) is a selective protein kinase C inhibitor in clinical trial for cancer treatment. In this study, we found that nanomolar concentrations of camptothecin (CPT), a topoisomerase I inhibitor, arrest or delay cell cycle progression during the S and G2 phases in p53 mutant human colon carcinoma HT29 cells and that UCN-01 abrogates the S-phase arrest or delay induced by CPT. Under these conditions, CPT increased cyclin A levels and cyclin A/cyclin-dependent kinase 2 activity. UCN-01 prevented the increase of cyclin A/cyclin-dependent kinase 2 activity induced by CPT and enhanced Cdc2 kinase activity. Replication protein A (RPA2) was hyperphosphorylated after CPT treatment, and this effect was also abrogated by UCN-01. UCN-01 potentiated the cytotoxicity of CPT and reduced by 6-fold the concentration of CPT required to kill 50% of the HT-29 cells, as determined by clonogenic assays. This effect was observed at concentrations of UCN-01 that alone were not cytotoxic and had no detectable effect on cell cycle progression. UCN-01 markedly potentiated the cytotoxicity of CPT also in HCT116/E6 and MCF-7/ADR cells defective for p53 function, whereas significantly less potentiation was observed in p53-wild-type HCT116 and MCF-7 cells. These results suggest the existence of an S-phase checkpoint that delays replication and that may extend the time available for DNA repair. Thus, pharmacological abrogation of CPT-induced S- and G2-phase checkpoints by UCN-01 may provide an effective strategy for enhancing the chemotherapeutic activity of CPT, particularly against p53-defective tumors. JF - Cancer research AU - Shao, R G AU - Cao, C X AU - Shimizu, T AU - O'Connor, P M AU - Kohn, K W AU - Pommier, Y AD - Laboratory of Molecular Pharmacology, Division of Basic Sciences, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. Y1 - 1997/09/15/ PY - 1997 DA - 1997 Sep 15 SP - 4029 EP - 4035 VL - 57 IS - 18 SN - 0008-5472, 0008-5472 KW - Alkaloids KW - 0 KW - Cell Cycle Proteins KW - DNA, Neoplasm KW - Enzyme Inhibitors KW - Tumor Suppressor Protein p53 KW - 7-hydroxystaurosporine KW - 7BU5H4V94A KW - Protein Kinase C KW - EC 2.7.11.13 KW - Staurosporine KW - H88EPA0A3N KW - Camptothecin KW - XT3Z54Z28A KW - Index Medicus KW - Protein Kinase C -- antagonists & inhibitors KW - Blotting, Western KW - Enzyme Inhibitors -- administration & dosage KW - Tumor Cells, Cultured KW - Genes, p53 KW - Humans KW - Drug Synergism KW - Staurosporine -- analogs & derivatives KW - DNA, Neoplasm -- biosynthesis KW - Cell Cycle Proteins -- metabolism KW - Tumor Suppressor Protein p53 -- physiology KW - S Phase -- drug effects KW - Camptothecin -- administration & dosage KW - Alkaloids -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79306626?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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.+Symposium+proceedings&rft.atitle=Multistage+carcinogenesis+in+the+skin.&rft.au=Yuspa%2C+S+H%3BDlugosz%2C+A+A%3BDenning%2C+M+F%3BGlick%2C+A+B&rft.aulast=Yuspa&rft.aufirst=S&rft.date=1996-04-01&rft.volume=1&rft.issue=2&rft.spage=147&rft.isbn=&rft.btitle=&rft.title=The+journal+of+investigative+dermatology.+Symposium+proceedings&rft.issn=10870024&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-10-20 N1 - Date created - 1997-10-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Correction of hypermutability, N-methyl-N'-nitro-N-nitrosoguanidine resistance, and defective DNA mismatch repair by introducing chromosome 2 into human tumor cells with mutations in MSH2 and MSH6. AN - 79301924; 9307278 AB - The human DNA mismatch repair genes hMSH2 and hMSH6 encode the proteins that, together, bind to mismatches to initiate repair of replication errors. Human tumor cells containing mutations in these genes have strongly elevated mutation rates in selectable genes and at microsatellite loci, although mutations in these genes cause somewhat different mutator phenotypes. These cells are also resistant to killing by certain drugs and are defective in mismatch repair. Because the elevated mutation rates in these cells may lead to mutations in additional genes that are causally related to the other defects, here we attempt to establish a cause-effect relationship between the hMSH2 and hMSH6 gene mutations and the observed phenotypes. The endometrial tumor cell line HEC59 contains mutations in both alleles of hMSH2. The colon tumor cell line HCT15 contains mutations in hMSH6 and also has a sequence change in a conserved region of the coding sequence for DNA polymerase delta, a replicative DNA polymerase. We introduced human chromosome 2 containing the wild-type hMSH2 and hMSH6 genes into HEC59 and HCT15 cells. Introduction of chromosome 2 to HEC59 cells restored microsatellite stability, sensitivity to N-methyl-N'-nitro-N-nitrosoguanidine treatment, and mismatch repair activity. Transfer of chromosome 2 to HCT15 cells also reduced the mutation rate at the HPRT locus and restored sensitivity to N-methyl-N'-nitro-N-nitrosoguanidine treatment and mismatch repair activity. The results demonstrate that the observed defects are causally related to mutations in genes on chromosome 2, probably hMSH2 or hMSH6, but are not related to sequence changes in other genes, including the gene encoding DNA polymerase delta. JF - Cancer research AU - Umar, A AU - Koi, M AU - Risinger, J I AU - Glaab, W E AU - Tindall, K R AU - Kolodner, R D AU - Boland, C R AU - Barrett, J C AU - Kunkel, T A AD - Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1997/09/15/ PY - 1997 DA - 1997 Sep 15 SP - 3949 EP - 3955 VL - 57 IS - 18 SN - 0008-5472, 0008-5472 KW - DNA-Binding Proteins KW - 0 KW - G-T mismatch-binding protein KW - Proto-Oncogene Proteins KW - Methylnitronitrosoguanidine KW - 12H3O2UGSF KW - MSH2 protein, human KW - EC 3.6.1.3 KW - MutS Homolog 2 Protein KW - Index Medicus KW - Microsatellite Repeats KW - Tumor Cells, Cultured KW - Cell Fusion KW - Humans KW - Methylnitronitrosoguanidine -- pharmacology KW - Drug Resistance, Neoplasm KW - Sequence Deletion KW - DNA Repair KW - Chromosomes, Human, Pair 2 KW - DNA-Binding Proteins -- physiology KW - Proto-Oncogene Proteins -- physiology KW - Mutagenesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79301924?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Correction+of+hypermutability%2C+N-methyl-N%27-nitro-N-nitrosoguanidine+resistance%2C+and+defective+DNA+mismatch+repair+by+introducing+chromosome+2+into+human+tumor+cells+with+mutations+in+MSH2+and+MSH6.&rft.au=Umar%2C+A%3BKoi%2C+M%3BRisinger%2C+J+I%3BGlaab%2C+W+E%3BTindall%2C+K+R%3BKolodner%2C+R+D%3BBoland%2C+C+R%3BBarrett%2C+J+C%3BKunkel%2C+T+A&rft.aulast=Umar&rft.aufirst=A&rft.date=1997-09-15&rft.volume=57&rft.issue=18&rft.spage=3949&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 - 1997-10-20 N1 - Date created - 1997-10-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The Rep68 protein of adeno-associated virus type 2 increases RNA levels from the human cytomegalovirus major immediate early promoter. AN - 79288014; 9299629 AB - The Rep68 and Rep78 proteins of adeno-associated virus type-2 (AAV) are multifunctional DNA binding proteins which are involved in the positive and negative regulation of AAV genes, as well as various cellular and heterologous viral genes. In this study we report that Rep68 enhances expression from the major immediate early promoter (MIEP) of human cytomegalovirus (HCMV). This Rep-mediated enhancement of RNA levels is abrogated by the introduction of a Rep recognition sequence (RRS) at either position -18 or -244 in the HCMV-MIEP. However, a mutant RRS (mRRS), which is not bound by Rep68 is unable to negate the effect of Rep68. Sequence analysis and electrophoretic mobility shift assays showed no Rep68 binding sites within the wild-type HCMV-MIEP. Rep68 may therefore be enhancing expression from the HCMV-MIEP by interacting with other regulatory proteins that have an effect on the expression from this promoter or by altering the expression of a cellular gene whose product influences the HCMV-MIEP. Our results may also help to explain the previous observation that coinfection with AAV enhances the cytopathic effect of HCMV. Copyright 1997 Academic Press. JF - Virology AU - Wonderling, R S AU - Kyöstiö, S R AU - Walker, S L AU - Owens, R A AD - National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1997/09/15/ PY - 1997 DA - 1997 Sep 15 SP - 167 EP - 176 VL - 236 IS - 1 SN - 0042-6822, 0042-6822 KW - DNA Primers KW - 0 KW - DNA-Binding Proteins KW - Immediate-Early Proteins KW - RNA, Viral KW - Recombinant Fusion Proteins KW - Viral Proteins KW - rep proteins, Adeno-associated virus 2 KW - 137750-19-7 KW - Chloramphenicol O-Acetyltransferase KW - EC 2.3.1.28 KW - Index Medicus KW - Recombinant Fusion Proteins -- biosynthesis KW - Chloramphenicol O-Acetyltransferase -- biosynthesis KW - Sequence Homology, Nucleic Acid KW - Humans KW - Mutagenesis, Site-Directed KW - Polymerase Chain Reaction KW - Base Sequence KW - Sequence Alignment KW - Transfection KW - Kidney KW - Molecular Sequence Data KW - Cell Line KW - Sequence Deletion KW - Immediate-Early Proteins -- biosynthesis KW - Promoter Regions, Genetic KW - Dependovirus -- physiology KW - Cytomegalovirus -- metabolism KW - RNA, Viral -- biosynthesis KW - Cytomegalovirus -- genetics KW - Viral Proteins -- metabolism KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79288014?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+Rep68+protein+of+adeno-associated+virus+type+2+increases+RNA+levels+from+the+human+cytomegalovirus+major+immediate+early+promoter.&rft.au=Wonderling%2C+R+S%3BKy%C3%B6sti%C3%B6%2C+S+R%3BWalker%2C+S+L%3BOwens%2C+R+A&rft.aulast=Wonderling&rft.aufirst=R&rft.date=1997-09-15&rft.volume=236&rft.issue=1&rft.spage=167&rft.isbn=&rft.btitle=&rft.title=Virology&rft.issn=00426822&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-10-09 N1 - Date created - 1997-10-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Insulin and endometrial cancer. AN - 79279744; 9290508 AB - Elevated insulin levels may explain part of the increased risk of endometrial cancer observed in obese postmenopausal women. Circulating sex hormones and fasting C-peptide levels were measured in sera obtained from 165 postmenopausal endometrial cancer cases accrued between June 1, 1987, and May 15, 1990, from hospitals in Chicago, Illinois; Hershey, Pennsylvania; Irvine and Long Beach, California; Minneapolis, Minnesota; and Winston-Salem, North Carolina, and 180 community and hysterectomy controls. Women with a personal history of diabetes were excluded. Among controls, C-peptide was positively correlated with body mass index (BMI) ((r = 0.44), waist-to-thigh circumference ratio ((r = 0.24), estrone ((r = 0.18), and estradiol ((r = 0.28) (albumin-bound (r = 0.45), and free (r = 0.37)) and negatively correlated with sex hormone-binding globulin (r = -0.48). In age-adjusted analyses, the odds ratios and 95% confidence intervals for tertiles of C-peptide and endometrial cancer were, from lowest to highest: 1.0 (reference), 0.78 (95% confidence interval (CI) 0.43-1.4), and 2.2 (95% CI 1.3-3.7). Further adjustment for BMI substantially attenuated the odds ratios for the highest tertile of C-peptide (odds ratio = 1.2, 95% CI 0.63-2.1), and adjustment for body mass index and other risk factors for endometrial cancer eliminated the association (odds ratio = 1.0, 95% CI 0.55-2.0). In contrast, adjustment for C-peptide had little influence on the magnitude of the positive associations between body mass index (odds ratio for highest vs. lowest tertile, without and with adjustment for C-peptide = 4.1 (95% CI 2.3-7.5) and 3.7 (95% CI 1.9-7.1), respectively) or several steroid hormones and endometrial cancer. These data are not consistent with the hypothesis that the effect of obesity on endometrial cancer risk is mediated through high insulin levels. JF - American journal of epidemiology AU - Troisi, R AU - Potischman, N AU - Hoover, R N AU - Siiteri, P AU - Brinton, L A AD - Environmental Epidemiology Branch, National Cancer Institute, Bethesda, MD 20892-7374, USA. Y1 - 1997/09/15/ PY - 1997 DA - 1997 Sep 15 SP - 476 EP - 482 VL - 146 IS - 6 SN - 0002-9262, 0002-9262 KW - C-Peptide KW - 0 KW - Contraceptives, Oral, Hormonal KW - Gonadal Steroid Hormones KW - Cholesterol KW - 97C5T2UQ7J KW - Index Medicus KW - Parity KW - Odds Ratio KW - Age Factors KW - C-Peptide -- blood KW - Humans KW - Aged KW - Body Mass Index KW - Contraceptives, Oral, Hormonal -- adverse effects KW - Gonadal Steroid Hormones -- blood KW - Obesity -- complications KW - Obesity -- blood KW - Cholesterol -- blood KW - Estrogen Replacement Therapy -- adverse effects KW - Risk Factors KW - Adult KW - Menarche KW - Middle Aged KW - Body Constitution KW - Female KW - Endometrial Neoplasms -- physiopathology KW - Endometrial Neoplasms -- blood KW - Endometrial Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79279744?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+epidemiology&rft.atitle=Insulin+and+endometrial+cancer.&rft.au=Troisi%2C+R%3BPotischman%2C+N%3BHoover%2C+R+N%3BSiiteri%2C+P%3BBrinton%2C+L+A&rft.aulast=Troisi&rft.aufirst=R&rft.date=1997-09-15&rft.volume=146&rft.issue=6&rft.spage=476&rft.isbn=&rft.btitle=&rft.title=American+journal+of+epidemiology&rft.issn=00029262&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-09-18 N1 - Date created - 1997-09-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Multiple dimeric forms of human CD69 result from differential addition of N-glycans to typical (Asn-X-Ser/Thr) and atypical (Asn-X-cys) glycosylation motifs. AN - 79274783; 9287313 AB - CD69 is expressed on the surface of all hematopoietically derived leukocytes and is suggested to function as a multipurpose cell-surface trigger molecule important in the development and activation of many different cell types. Human CD69 contains only a single consensus sequence for N-linked oligosaccharide addition within its extracellular domain (Asn-Val-Thr), yet exists as two distinct glycoforms that are assembled together into disulfide-linked homodimers and heterodimers. The molecular basis for human CD69 heterogeneity has remained elusive. In the current report we show that human CD69 glycoforms are generated before the egress of CD69 proteins from the endoplasmic reticulum to the Golgi and are synthesized under conditions where Golgi processing is inhibited, effectively ruling out the possibility that CD69 heterogeneity results from the differential processing of a single glycosylation site in the Golgi complex. Importantly, these data demonstrate that contrary to current belief, not one but two sites for N-glycan addition exist within the human CD69 extracellular domain and identify the second, "cryptic" CD69 N-glycan attachment site as the atypical Cys-containing glycosylation motif, Asn-Ala-Cys. The results in this study provide a molecular basis for human CD69 heterogeneity and show that multiple dimeric forms of human CD69 result from the variable addition of N-glycans to atypical and typical glycosylation motifs within the CD69 extracellular domain. JF - The Journal of biological chemistry AU - Vance, B A AU - Wu, W AU - Ribaudo, R K AU - Segal, D M AU - Kearse, K P AD - Experimental Immunology Branch, NCI, National Institutes of Health, Bethesda, Maryland 20892-1360, USA. Y1 - 1997/09/12/ PY - 1997 DA - 1997 Sep 12 SP - 23117 EP - 23122 VL - 272 IS - 37 SN - 0021-9258, 0021-9258 KW - Antigens, CD KW - 0 KW - Antigens, Differentiation, T-Lymphocyte KW - CD69 antigen KW - Disulfides KW - Glycoproteins KW - Lectins, C-Type KW - Polysaccharides KW - Asparagine KW - 7006-34-0 KW - Index Medicus KW - Endoplasmic Reticulum -- metabolism KW - Protein Biosynthesis KW - Models, Molecular KW - DNA Mutational Analysis KW - Dimerization KW - Humans KW - Polysaccharides -- metabolism KW - Transcription, Genetic KW - Glycosylation KW - Disulfides -- metabolism KW - Mutagenesis, Site-Directed KW - T-Lymphocytes -- metabolism KW - Golgi Apparatus -- metabolism KW - Cell-Free System KW - Antigens, Differentiation, T-Lymphocyte -- genetics KW - Consensus Sequence -- genetics KW - Antigens, Differentiation, T-Lymphocyte -- metabolism KW - Glycoproteins -- metabolism KW - Glycoproteins -- chemistry KW - Antigens, CD -- chemistry KW - Protein Processing, Post-Translational KW - Asparagine -- metabolism KW - Antigens, CD -- metabolism KW - Antigens, Differentiation, T-Lymphocyte -- chemistry KW - Antigens, CD -- genetics KW - Glycoproteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79274783?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Multiple+dimeric+forms+of+human+CD69+result+from+differential+addition+of+N-glycans+to+typical+%28Asn-X-Ser%2FThr%29+and+atypical+%28Asn-X-cys%29+glycosylation+motifs.&rft.au=Vance%2C+B+A%3BWu%2C+W%3BRibaudo%2C+R+K%3BSegal%2C+D+M%3BKearse%2C+K+P&rft.aulast=Vance&rft.aufirst=B&rft.date=1997-09-12&rft.volume=272&rft.issue=37&rft.spage=23117&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 - 1997-10-01 N1 - Date created - 1997-10-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Temporary amelioration of symptoms with intravenous cyclophosphamide in amyotrophic lateral sclerosis. AN - 79239666; 9268246 AB - Based on the evidence that autoimmunity may play a role in the pathogenesis of amyotrophic lateral sclerosis (ALS), a variety of immunomodulating agents have been used in the treatment. In an uncontrolled trial we treated 44 patients of ALS with intravenous cyclophosphamide (IVCP) at a total dose of 1.5 g/m2 given over a period of 8 to 10 days. The patients were evaluated using neurological score which included bulbar, motor and daily activity scores before and following treatment. Twenty three patients showed a significant improvement (P=<0.001) in the composite and the individual scores. The improvement persisted only for 2 to 3 months. Amongst them the severely (7) and moderately (16) affected (score less than or more than 150) showed almost a similar response to treatment. A comparison of the improved group of 23 patients with the unimproved group of 21 patients did not reveal any significant factors which influenced the response to IVCP. However, there was a suggestion that patients below the age of 60 years and a duration of illness less than 12 months may respond to the drug. In conclusion, treatment with intravenous cyclophosphamide resulted in mild and temporary improvement in clinical status of the patients with amyotrophic lateral sclerosis. This may be considered as an alternative method of treatment in developing countries where newer drugs are not available and affordable. JF - Journal of the neurological sciences AU - Gourie-Devi, M AU - Nalini, A AU - Subbakrishna, D K AD - Department of Neurology, National Institute of Mental Health and Neuro Sciences, Bangalore, India. Y1 - 1997/09/10/ PY - 1997 DA - 1997 Sep 10 SP - 167 EP - 172 VL - 150 IS - 2 SN - 0022-510X, 0022-510X KW - Immunosuppressive Agents KW - 0 KW - Cyclophosphamide KW - 8N3DW7272P KW - Index Medicus KW - Injections, Intravenous KW - Dose-Response Relationship, Drug KW - Humans KW - Nervous System -- drug effects KW - Adult KW - Treatment Outcome KW - Nervous System -- physiopathology KW - Aged KW - Middle Aged KW - Time Factors KW - Male KW - Female KW - Cyclophosphamide -- therapeutic use KW - Immunosuppressive Agents -- therapeutic use KW - Amyotrophic Lateral Sclerosis -- drug therapy KW - Amyotrophic Lateral Sclerosis -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79239666?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+neurological+sciences&rft.atitle=Temporary+amelioration+of+symptoms+with+intravenous+cyclophosphamide+in+amyotrophic+lateral+sclerosis.&rft.au=Gourie-Devi%2C+M%3BNalini%2C+A%3BSubbakrishna%2C+D+K&rft.aulast=Gourie-Devi&rft.aufirst=M&rft.date=1997-09-10&rft.volume=150&rft.issue=2&rft.spage=167&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+neurological+sciences&rft.issn=0022510X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-10-06 N1 - Date created - 1997-10-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Analysis of sequence requirements for biological activity of cyanovirin-N, a potent HIV (human immunodeficiency virus)-inactivating protein. AN - 79291916; 9299482 AB - Site-directed mutagenesis of DNA constructs coding for the novel, HIV-inactivating proteins cyanovirin-N (CV-N) and FLAG-cyanovirin-N (F-CV-N) was performed using mutagenic oligonucleotide primers in the polymerase chain reaction or by a restriction site elimination maneuver. The mutant constructs were expressed in Escherichia coli and the recombinant protein products were tested for binding to the HIV surface envelope glycoprotein gp 120 and for antiviral activity against infectious HIV. Results showed an overall very high correlation (r2 > 0.9) between the relative gp120 binding affinities and the anti-HIV activities of CV-N, F-CV-N, and the various mutants. An outlier, however, was a mutant which lacked one of the internal disulfide linkages normally present in CV-N and which showed modest gp120 binding but no antiviral activity against HIV. These findings are consistent with the view that gp120 binding is a necessary but not sufficient requirement for the HIV-inactivating activity of CV-N and related proteins; the sequence specificities for gp120 binding and anti-HIV activity are not identical. JF - Biochemical and biophysical research communications AU - Mori, T AU - Shoemaker, R H AU - Gulakowski, R J AU - Krepps, B L AU - McMahon, J B AU - Gustafson, K R AU - Pannell, L K AU - Boyd, M R AD - Laboratory of Drug Discovery Research and Development, National Cancer Institute-FCRDC, Frederick, Maryland 21702-1201, USA. Y1 - 1997/09/08/ PY - 1997 DA - 1997 Sep 08 SP - 218 EP - 222 VL - 238 IS - 1 SN - 0006-291X, 0006-291X KW - Anti-HIV Agents KW - 0 KW - Bacterial Proteins KW - Carrier Proteins KW - Disulfides KW - HIV Envelope Protein gp120 KW - cyanovirin N KW - 184539-38-6 KW - Serine KW - 452VLY9402 KW - Cysteine KW - K848JZ4886 KW - Index Medicus KW - AIDS/HIV KW - Cysteine -- genetics KW - Humans KW - HIV Envelope Protein gp120 -- genetics KW - HIV Envelope Protein gp120 -- metabolism KW - Structure-Activity Relationship KW - Serine -- genetics KW - Mutagenesis, Site-Directed KW - Disulfides -- chemistry KW - Sequence Analysis KW - Molecular Sequence Data KW - Protein Binding -- genetics KW - Protein Structure, Tertiary KW - Sequence Homology, Amino Acid KW - Sequence Deletion KW - Anti-HIV Agents -- chemistry KW - Bacterial Proteins -- genetics KW - Carrier Proteins -- chemistry KW - Bacterial Proteins -- pharmacology KW - Bacterial Proteins -- chemistry KW - Carrier Proteins -- genetics KW - Anti-HIV Agents -- pharmacology KW - Amino Acid Sequence -- genetics KW - Carrier Proteins -- pharmacology KW - Amino Acid Sequence -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79291916?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Analysis+of+sequence+requirements+for+biological+activity+of+cyanovirin-N%2C+a+potent+HIV+%28human+immunodeficiency+virus%29-inactivating+protein.&rft.au=Mori%2C+T%3BShoemaker%2C+R+H%3BGulakowski%2C+R+J%3BKrepps%2C+B+L%3BMcMahon%2C+J+B%3BGustafson%2C+K+R%3BPannell%2C+L+K%3BBoyd%2C+M+R&rft.aulast=Mori&rft.aufirst=T&rft.date=1997-09-08&rft.volume=238&rft.issue=1&rft.spage=218&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 - 1997-10-09 N1 - Date created - 1997-10-09 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - L48551; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phosphorylation of T-lymphocyte plasma membrane-associated proteins by ectoprotein kinases: implications for a possible role for ectophosphorylation in T-cell effector functions. AN - 79319125; 9315612 AB - Extracellular adenosine triphosphate (ATPo) has been suggested to play a role in lymphocyte effector functions. Recently, it has been suggested that MgATP2- may be the molecular species which is involved in modulating the lytic interaction between cytotoxic T-lymphocytes (CTL) and their target cells. In this study, we provide evidence that ATPo mediates the phosphorylation of extracellular proteins on T-lymphocytes through the action of ectoprotein kinases. The ectophosphorylation is temperature-dependent, supported by Mg2+ and Mn2+, and both ATP and GTP, whereas kinase activity and/or substrates were removed by pretreatment of intact lymphocytes with trypsin. We show the presence of extracellular ATP/GTP-binding sites, indicating the presence of ectoenzymes on intact lymphocytes. The major ectoprotein kinase was identified as a casein kinase II-like protein kinase and could be inhibited by heparin, whereas its activity was enhanced by spermine. The ectoprotein kinase showed remarkable substrate specificity, phosphorylating the serum protein vitronectin, but not fibronectin. In experiments with the cell-impermeable protein kinase inhibitor K-252b, we demonstrate the possible functional importance of ectoprotein kinase in CTL-mediated cytotoxicity, i.e., target cell death was completely blocked by K-252b without affecting intracellular phosphorylation. These results suggest that ectoprotein phosphorylation may possibly be an important event in immunologically relevant cell-cell interactions. JF - Biochimica et biophysica acta AU - Redegeld, F A AU - Smith, P AU - Apasov, S AU - Sitkovsky, M V AD - Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1997/09/04/ PY - 1997 DA - 1997 Sep 04 SP - 151 EP - 165 VL - 1328 IS - 2 SN - 0006-3002, 0006-3002 KW - Carbazoles KW - 0 KW - Cations KW - Enzyme Inhibitors KW - Indole Alkaloids KW - Membrane Proteins KW - Protein Kinase Inhibitors KW - Guanosine Triphosphate KW - 86-01-1 KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - staurosporine aglycone KW - 97161-97-2 KW - Protein Kinases KW - EC 2.7.- KW - ectoprotein kinase KW - EC 2.7.1.- KW - Casein Kinase II KW - EC 2.7.11.1 KW - Protein-Serine-Threonine Kinases KW - Index Medicus KW - Animals KW - Mice KW - Guanosine Triphosphate -- metabolism KW - Phosphorylation KW - Adenosine Triphosphate -- metabolism KW - Carbazoles -- pharmacology KW - Cytotoxicity Tests, Immunologic KW - Enzyme Inhibitors -- pharmacology KW - Substrate Specificity KW - Cations -- pharmacology KW - Protein Kinases -- metabolism KW - Cell Membrane -- enzymology KW - Protein Kinases -- drug effects KW - Cytotoxicity, Immunologic -- physiology KW - Membrane Proteins -- metabolism KW - T-Lymphocytes, Cytotoxic -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79319125?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Phosphorylation+of+T-lymphocyte+plasma+membrane-associated+proteins+by+ectoprotein+kinases%3A+implications+for+a+possible+role+for+ectophosphorylation+in+T-cell+effector+functions.&rft.au=Redegeld%2C+F+A%3BSmith%2C+P%3BApasov%2C+S%3BSitkovsky%2C+M+V&rft.aulast=Redegeld&rft.aufirst=F&rft.date=1997-09-04&rft.volume=1328&rft.issue=2&rft.spage=151&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 - 1997-10-22 N1 - Date created - 1997-10-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Frequency of HLA allele-specific peptide motifs in HIV-1 proteins correlates with the allele's association with relative rates of disease progression after HIV-1 infection. AN - 79240837; 9275206 AB - An HLA allele-specific cytotoxic T lymphocyte response is thought to influence the rate of disease progression in HIV-1-infected individuals. In a prior study of 139 HIV-1-infected homosexual men, we identified HLA class I alleles and observed an association of specific alleles with different relative hazards for progression to AIDS. Seeking an explanation for this association, we searched HIV-1 protein sequences to determine the number of peptides matching motifs defined by combinations of specific amino acids reported to bind 16 class I alleles. Analyzing complete sequences of 12 clade B HIV isolates, we determined the number of allele motifs that were conserved (occurring in all 12 isolates) and nonconserved (occurring in only one isolate), as well as the average number of allele motifs per isolate. We found significant correlations with an allele's association with disease progression for counts of conserved motifs in gag (R = 0.73; P = 0.002), pol (R = 0.58, P = 0.024), gp120 (R = 0.78, P = 0.00056), and total viral protein sequences (R = 0.67, P = 0.0058) and also for counts of nonconserved motifs in gag (R = 0.62, P = 0.013), pol (R = 0.74, P = 0.0017), gp41 (R = 0.52, P = 0.046), and total viral protein (R = 0.71, P = 0.0033). We also found significant correlations for the average number of motifs per isolate for gag, pol, gp120, and total viral protein. This study provides a plausible functional explanation for the observed association of different HLA alleles with variable rates of disease progression. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Nelson, G W AU - Kaslow, R AU - Mann, D L AD - Laboratory of Viral Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, Frederick, MD 21702-1201, USA. Y1 - 1997/09/02/ PY - 1997 DA - 1997 Sep 02 SP - 9802 EP - 9807 VL - 94 IS - 18 SN - 0027-8424, 0027-8424 KW - Antigens, Viral KW - 0 KW - HLA Antigens KW - Viral Proteins KW - Index Medicus KW - AIDS/HIV KW - Alleles KW - Humans KW - Antigens, Viral -- immunology KW - Antigens, Viral -- genetics KW - Epitope Mapping KW - Viral Proteins -- immunology KW - Viral Proteins -- genetics KW - HLA Antigens -- genetics KW - HIV-1 -- genetics KW - HIV-1 -- immunology KW - HIV Infections -- virology KW - HIV Infections -- immunology KW - HLA Antigens -- immunology KW - HIV Infections -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79240837?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Frequency+of+HLA+allele-specific+peptide+motifs+in+HIV-1+proteins+correlates+with+the+allele%27s+association+with+relative+rates+of+disease+progression+after+HIV-1+infection.&rft.au=Nelson%2C+G+W%3BKaslow%2C+R%3BMann%2C+D+L&rft.aulast=Nelson&rft.aufirst=G&rft.date=1997-09-02&rft.volume=94&rft.issue=18&rft.spage=9802&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 - 1997-10-01 N1 - Date created - 1997-10-01 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Exp Med. 1994 Oct 1;180(4):1283-93 [7523570] J Clin Invest. 1994 Mar;93(3):1293-7 [8132769] J Immunol. 1995 Jan 1;154(1):247-59 [7527812] J Biol Chem. 1994 Dec 23;269(51):32426-34 [7528217] Immunogenetics. 1995;41(4):178-228 [7890324] J Exp Med. 1995 Apr 1;181(4):1365-72 [7699324] AIDS. 1995 Feb;9(2):121-7 [7536421] Int Immunol. 1995 Feb;7(2):223-8 [7734418] Nature. 1995 Jun 15;375(6532):606-11 [7791879] Immunity. 1995 Jul;3(1):65-77 [7542549] Cell. 1995 Jul 28;82(2):177-82 [7628008] J Immunol. 1994 Apr 15;152(8):3904-12 [7511661] J Immunol. 1994 Apr 15;152(8):3913-24 [8144960] J Exp Med. 1994 Apr 1;179(4):1261-71 [8145043] J Virol. 1994 May;68(5):3145-53 [7908700] Int Immunol. 1994 Feb;6(2):255-61 [8155602] Curr Opin Immunol. 1994 Feb;6(1):1-2 [8172671] Curr Opin Immunol. 1994 Feb;6(1):13-23 [7513522] Nature. 1994 Jun 2;369(6479):403-7 [7515165] J Virol. 1994 Jul;68(7):4650-5 [8207839] Nature. 1994 Aug 11;370(6489):463-7 [8047166] J Virol. 1994 Sep;68(9):6103-10 [8057491] J Exp Med. 1994 Sep 1;180(3):1129-34 [7520468] J Exp Med. 1994 Sep 1;180(3):779-82 [7520471] J Virol. 1994 Oct;68(10):6672-83 [8084001] Eur J Immunol. 1994 Sep;24(9):2196-202 [7522167] J Immunol. 1995 Aug 15;155(4):2232-9 [7543542] J Virol. 1995 Nov;69(11):6911-6 [7474108] Int Immunol. 1995 Apr;7(4):653-63 [7547693] Nat Med. 1995 Jan;1(1):59-64 [7584954] Int Immunol. 1995 Jun;7(6):905-9 [7577798] Immunogenetics. 1996;43(1-2):27-37 [8537119] Science. 1996 Jan 19;271(5247):324-8 [8553066] Eur J Immunol. 1996 Jan;26(1):224-30 [8566071] Immunogenetics. 1996;43(5):268-76 [9110930] Science. 1996 Apr 5;272(5258):67-74 [8600539] Nat Med. 1996 Apr;2(4):405-11 [8597949] Science. 1996 Apr 26;272(5261):537-42 [8614801] Int Immunol. 1996 May;8(5):651-9 [8671652] Curr Opin Immunol. 1996 Feb;8(1):59-67 [8729447] Proc Natl Acad Sci U S A. 1988 Nov;85(22):8638-42 [2460873] Annu Rev Immunol. 1989;7:601-24 [2469442] Blood. 1989 May 15;73(7):1909-14 [2785419] Nature. 1989 Dec 7;342(6250):692-6 [2594067] J Immunol. 1990 Jul 1;145(1):127-35 [1694201] Nature. 1990 Aug 16;346(6285):629-33 [1696684] Nature. 1990 Nov 15;348(6298):248-51 [2234092] J Immunol. 1991 Mar 1;146(5):1560-5 [1704397] J Immunol. 1991 Sep 1;147(5):1512-21 [1715361] Nature. 1991 Dec 12;354(6353):453-9 [1721107] J Exp Med. 1992 Apr 1;175(4):961-71 [1372650] Cell. 1992 Sep 18;70(6):1035-48 [1525820] Immunogenetics. 1993;38(2):161-2 [8482580] J Exp Med. 1994 Feb 1;179(2):463-72 [8294860] Eur J Immunol. 1994 Mar;24(3):777-80 [8125145] Curr Opin Immunol. 1996 Feb;8(1):68-74 [8729448] AIDS. 1996 Sep;10(10):1075-83 [8874623] J Immunol. 1994 Dec 15;153(12):5586-92 [7527444] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - VMAT2 knockout mice: heterozygotes display reduced amphetamine-conditioned reward, enhanced amphetamine locomotion, and enhanced MPTP toxicity. AN - 79238714; 9275230 AB - The brain vesicular monoamine transporter (VMAT2) pumps monoamine neurotransmitters and Parkinsonism-inducing dopamine neurotoxins such as 1-methyl-4-phenyl-phenypyridinium (MPP+) from neuronal cytoplasm into synaptic vesicles, from which amphetamines cause their release. Amphetamines and MPP+ each also act at nonvesicular sites, providing current uncertainties about the contributions of vesicular actions to their in vivo effects. To assess vesicular contributions to amphetamine-induced locomotion, amphetamine-induced reward, and sequestration and resistance to dopaminergic neurotoxins, we have constructed transgenic VMAT2 knockout mice. Heterozygous VMAT2 knockouts are viable into adult life and display VMAT2 levels one-half that of wild-type values, accompanied by smaller changes in monoaminergic markers, heart rate, and blood pressure. Weight gain, fertility, habituation, passive avoidance, and locomotor activities are similar to wild-type littermates. In these heterozygotes, amphetamine produces enhanced locomotion but diminished behavioral reward, as measured by conditioned place preference. Administration of the MPP+ precursor N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine to heterozygotes produces more than twice the dopamine cell losses found in wild-type mice. These mice provide novel information about the contributions of synaptic vesicular actions of monoaminergic drugs and neurotoxins and suggest that intact synaptic vesicle function may contribute more to amphetamine-conditioned reward than to amphetamine-induced locomotion. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Takahashi, N AU - Miner, L L AU - Sora, I AU - Ujike, H AU - Revay, R S AU - Kostic, V AU - Jackson-Lewis, V AU - Przedborski, S AU - Uhl, G R AD - Molecular Neurobiology Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1997/09/02/ PY - 1997 DA - 1997 Sep 02 SP - 9938 EP - 9943 VL - 94 IS - 18 SN - 0027-8424, 0027-8424 KW - Central Nervous System Stimulants KW - 0 KW - Dopamine Agents KW - Membrane Glycoproteins KW - Membrane Transport Proteins KW - Neuropeptides KW - Slc18a2 protein, mouse KW - Vesicular Biogenic Amine Transport Proteins KW - Vesicular Monoamine Transport Proteins KW - Amphetamine KW - CK833KGX7E KW - Index Medicus KW - Animals KW - Locomotion -- physiology KW - Heterozygote KW - Mice KW - Locomotion -- drug effects KW - Dopamine Agents -- toxicity KW - Behavior, Animal -- drug effects KW - Central Nervous System Stimulants -- pharmacology KW - Mice, Knockout -- physiology KW - MPTP Poisoning KW - Behavior, Animal -- physiology KW - Amphetamine -- pharmacology KW - Membrane Glycoproteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79238714?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=VMAT2+knockout+mice%3A+heterozygotes+display+reduced+amphetamine-conditioned+reward%2C+enhanced+amphetamine+locomotion%2C+and+enhanced+MPTP+toxicity.&rft.au=Takahashi%2C+N%3BMiner%2C+L+L%3BSora%2C+I%3BUjike%2C+H%3BRevay%2C+R+S%3BKostic%2C+V%3BJackson-Lewis%2C+V%3BPrzedborski%2C+S%3BUhl%2C+G+R&rft.aulast=Takahashi&rft.aufirst=N&rft.date=1997-09-02&rft.volume=94&rft.issue=18&rft.spage=9938&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 - 1997-10-01 N1 - Date created - 1997-10-01 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Neurology. 1985 Aug;35(8):1215-8 [4022359] J Exp Biol. 1994 Nov;196:251-62 [7823026] J Neurochem. 1986 Aug;47(2):331-9 [3734781] Physiol Rev. 1988 Jan;68(1):232-307 [2892215] J Neurochem. 1988 Jun;50(6):1783-90 [2967349] Ann Neurol. 1988 Oct;24(4):574-6 [3239957] Eur J Pharmacol. 1989 Dec 7;173(2-3):177-82 [2576228] Neuron. 1990 Dec;5(6):797-808 [2268433] Cell. 1991 Feb 22;64(4):693-702 [1997203] Eur J Pharmacol. 1990 Aug 10;184(2-3):329-32 [2079102] Nature. 1991 Mar 28;350(6316):350-4 [2008212] Mol Pharmacol. 1976 Jul;12(4):568-80 [8699] Eur J Pharmacol. 1990 Nov 27;191(2):239-43 [2086242] Biochem Biophys Res Commun. 1991 May 15;176(3):1610-6 [1674869] Brain Res. 1991 Feb 1;540(1-2):159-63 [1829015] Nature. 1991 Nov 7;354(6348):66-70 [1944572] Science. 1991 Oct 25;254(5031):576-8 [1948034] J Neurochem. 1992 Mar;58(3):1016-22 [1531355] Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1817-21 [1347426] Brain Res Mol Brain Res. 1992 May;13(4):359-62 [1352613] Ann Neurol. 1992 Jul;32(1):109-11 [1642464] Cell. 1992 Aug 21;70(4):539-51 [1505023] Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10993-7 [1438304] Clin Chem. 1993 Feb;39(2):247-50 [8432013] Annu Rev Neurosci. 1993;16:73-93 [8096377] Annu Rev Pharmacol Toxicol. 1993;33:639-77 [8494354] Science. 1995 Sep 8;269(5229):1432-5 [7660127] J Comp Neurol. 1995 Aug 21;359(2):340-9 [7499533] Neurodegeneration. 1995 Sep;4(3):257-69 [8581558] Proc Natl Acad Sci U S A. 1996 May 14;93(10):4565-71 [8643444] Nature. 1996 Feb 15;379(6566):606-12 [8628395] Neuroreport. 1995 Nov 27;6(17):2314-6 [8747144] Proc Natl Acad Sci U S A. 1997 Feb 18;94(4):1544-9 [9037090] Ann Neurol. 1994 Apr;35(4):494-8 [8154880] Brain Res Mol Brain Res. 1994 Aug;25(1-2):90-6 [7984057] J Mol Evol. 1986;23(1):11-22 [3084797] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Crystal structures of the inactive D30N mutant of feline immunodeficiency virus protease complexed with a substrate and an inhibitor. AN - 79238052; 9271500 AB - Crystal structures of complexes of a D30N mutant of feline immunodeficiency virus protease (FIV PR) complexed with a statine-based inhibitor (LP-149), as well as with a substrate based on a modification of this inhibitor (LP-149S), have been solved and refined at resolutions of 2.0 and 1.85 A, respectively. Both the inhibitor and the substrate are bound in the active site of the mutant protease in a similar mode, which also resembles the mode of binding of LP-149 to the native protease. The carbonyl oxygen of the scissile bond in the substrate is not hydrated and is located within the distance of a hydrogen bond to an amido nitrogen atom from one of the two asparagines in the active site of the enzyme. The nitrogen atom of the scissile bond is 3.25 A from the conserved water molecule (Wat301). A model of a tetrahedral intermediate bound to the active site of the native enzyme was built by considering the interactions observed in all three crystal structures of FIV PR. Molecular dynamics simulations of this model bound to native wild-type FIV PR were carried out, to investigate the final stages of the catalytic mechanism of aspartic proteases. JF - Biochemistry AU - Laco, G S AU - Schalk-Hihi, C AU - Lubkowski, J AU - Morris, G AU - Zdanov, A AU - Olson, A AU - Elder, J H AU - Wlodawer, A AU - Gustchina, A AD - Macromolecular Structure Laboratory, NCI-Frederick Cancer Research and Development Center, Frederick, Maryland 21702, USA. Y1 - 1997/09/02/ PY - 1997 DA - 1997 Sep 02 SP - 10696 EP - 10708 VL - 36 IS - 35 SN - 0006-2960, 0006-2960 KW - LP 149 KW - 0 KW - Macromolecular Substances KW - Oligopeptides KW - Peptides KW - Protease Inhibitors KW - Solutions KW - Aspartic Acid KW - 30KYC7MIAI KW - Asparagine KW - 7006-34-0 KW - Aspartic Acid Endopeptidases KW - EC 3.4.23.- KW - FIV protease KW - Index Medicus KW - AIDS/HIV KW - Mutagenesis, Site-Directed KW - Aspartic Acid -- genetics KW - Oligopeptides -- chemistry KW - Asparagine -- genetics KW - Peptides -- metabolism KW - Oligopeptides -- metabolism KW - Crystallography, X-Ray KW - Binding Sites -- genetics KW - Substrate Specificity -- genetics KW - Enzyme Activation -- genetics KW - Protease Inhibitors -- chemistry KW - Protease Inhibitors -- metabolism KW - Aspartic Acid Endopeptidases -- genetics KW - Aspartic Acid Endopeptidases -- chemistry KW - Immunodeficiency Virus, Feline -- genetics KW - Immunodeficiency Virus, Feline -- enzymology KW - Aspartic Acid Endopeptidases -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79238052?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Crystal+structures+of+the+inactive+D30N+mutant+of+feline+immunodeficiency+virus+protease+complexed+with+a+substrate+and+an+inhibitor.&rft.au=Laco%2C+G+S%3BSchalk-Hihi%2C+C%3BLubkowski%2C+J%3BMorris%2C+G%3BZdanov%2C+A%3BOlson%2C+A%3BElder%2C+J+H%3BWlodawer%2C+A%3BGustchina%2C+A&rft.aulast=Laco&rft.aufirst=G&rft.date=1997-09-02&rft.volume=36&rft.issue=35&rft.spage=10696&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-09-17 N1 - Date created - 1997-09-17 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - 2FIV; PDB; 3FIV N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of exogenous melatonin administration and withdrawal in five patients with rapid-cycling bipolar disorder. AN - 79382907; 9378688 AB - The ready availability of exogenous melatonin means that its use in patients with mood disorders is probably not uncommon. Nonetheless, few controlled trials of exogenous melatonin in these patients have been conducted. Five patients with rapid-cycling DSM-III-R bipolar disorder were treated with melatonin 10 mg q.d. at 10:00 p.m. for 12 weeks. Melatonin was added to a stable regimen of medication and administered in a double-blind, placebo-controlled fashion. Melantonin administration had no positive effects. One patient developed a free-running (unentrained) sleep-wake cycle after melatonin withdrawal. In addition, in both this and a second patient, there is evidence that the administration of exogenous melatonin may have suppressed the secretion of endogenous melatonin. The administration of melatonin had no significant effects on mood or sleep. However, melatonin withdrawal delayed sleep onset time and may have had some mild mood-elevating effects. JF - The Journal of clinical psychiatry AU - Leibenluft, E AU - Feldman-Naim, S AU - Turner, E H AU - Wehr, T A AU - Rosenthal, N E AD - Clinical Psychobiology Branch, National Institute of Mental Health, Bethesda, Md. 20892-1390, USA. Y1 - 1997/09// PY - 1997 DA - September 1997 SP - 383 EP - 388 VL - 58 IS - 9 SN - 0160-6689, 0160-6689 KW - Placebos KW - 0 KW - Melatonin KW - JL5DK93RCL KW - Index Medicus KW - Drug Therapy, Combination KW - Drug Administration Schedule KW - Affect -- drug effects KW - Sleep -- drug effects KW - Double-Blind Method KW - Humans KW - Circadian Rhythm -- drug effects KW - Middle Aged KW - Female KW - Melatonin -- pharmacology KW - Substance Withdrawal Syndrome -- etiology KW - Melatonin -- adverse effects KW - Sleep Wake Disorders -- chemically induced KW - Melatonin -- therapeutic use KW - Bipolar Disorder -- drug therapy KW - Bipolar Disorder -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79382907?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Effects+of+exogenous+melatonin+administration+and+withdrawal+in+five+patients+with+rapid-cycling+bipolar+disorder.&rft.au=Leibenluft%2C+E%3BFeldman-Naim%2C+S%3BTurner%2C+E+H%3BWehr%2C+T+A%3BRosenthal%2C+N+E&rft.aulast=Leibenluft&rft.aufirst=E&rft.date=1997-09-01&rft.volume=58&rft.issue=9&rft.spage=383&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 - 1997-11-07 N1 - Date created - 1997-11-07 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Clin Psychiatry. 2000 Mar;61(3):215 [10817108] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hybridization between tammar wallaby (Macropus eugenii) populations from Western and South Australia. AN - 79382201; 9378916 AB - Populations of tammar wallabies (Macropus eugenii) occur in southwest Western Australia and on five Australian offshore islands, four in Western Australia and one in South Australia. The South Australia and Western Australia populations have probably been isolated from each other for 50,000-100,000 years. Studies have shown that there are morphological and genetic differences between these populations. Attempts at mating individuals from Garden Island (Western Australia) with individuals from Kangaroo Island (South Australia) indicate that while the two populations can hybridize in captivity and F1 hybrids of both sexes are fertile, a barrier to successful reproduction between these two populations is in the initial stages of development. JF - The Journal of heredity AU - McKenzie, L M AU - Cooper, D W AD - Laboratory of Viral Carcinogenesis, National Cancer Institute, Frederick, Maryland, USA. PY - 1997 SP - 398 EP - 400 VL - 88 IS - 5 SN - 0022-1503, 0022-1503 KW - Index Medicus KW - Animals KW - Fertility KW - Estrus KW - Litter Size KW - Australia KW - Geography KW - Male KW - Female KW - Hybridization, Genetic KW - Macropodidae -- genetics KW - Reproduction -- genetics KW - Macropodidae -- physiology KW - Crosses, Genetic UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79382201?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Hybridization+between+tammar+wallaby+%28Macropus+eugenii%29+populations+from+Western+and+South+Australia.&rft.au=McKenzie%2C+L+M%3BCooper%2C+D+W&rft.aulast=McKenzie&rft.aufirst=L&rft.date=1997-09-01&rft.volume=88&rft.issue=5&rft.spage=398&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 - 1997-11-07 N1 - Date created - 1997-11-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Female protein, amyloidosis, and hormonal carcinogenesis in Turkish hamster: differences from Syrian hamster. AN - 79319728; 9321870 AB - The Syrian hamster (Mesocricetus auratus) has been widely used as an experimental animal and is a unique model for three sex hormone-regulated events: 1) estrogen-initiated renal carcinogenesis, 2) sex-limited expression of amyloidosis, a ubiquitous disease, and 3) sex hormone control of a serum amyloid P component (SAP) called female protein (FP). In this study, we evaluated the closely related Turkish hamster (Mesocricetus brandti) for these three events and found some very different responses: 1) estrogen-initiated renal carcinogenesis was not found in Turkish hamster, 2) amyloidosis was not sex limited and actually was a rare disease in the Turkish hamster, and 3) Turkish hamsters did express a sex-limited SAP-FP in serum that was antigenically identical and structurally very similar (97.5%) to Syrian hamster SAP-FP. However, acute phase regulation of SAP-FP synthesis was different, and serum levels of this pentraxin were much lower than those found in the Syrian hamster. On the other hand, in contrast to findings in the Syrian hamster, hepatic tumors were relatively common in normal and especially in estrogen-treated Turkish hamsters. Therefore, although they are closely related, these two Mesocricetus hamster species have markedly dissimilar responses to sex hormones. JF - The American journal of physiology AU - Coe, J E AU - Cieplak, W AU - Hadlow, W J AU - Ross, M J AD - Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, Montana 59840, USA. Y1 - 1997/09// PY - 1997 DA - September 1997 SP - R934 EP - R941 VL - 273 IS - 3 Pt 2 SN - 0002-9513, 0002-9513 KW - Alpha-Globulins KW - 0 KW - Amyloid KW - Serum Amyloid P-Component KW - female protein, hamster KW - Tamoxifen KW - 094ZI81Y45 KW - Testosterone KW - 3XMK78S47O KW - C-Reactive Protein KW - 9007-41-4 KW - Index Medicus KW - Tamoxifen -- pharmacology KW - Animals KW - Sex Characteristics KW - Humans KW - Amino Acid Sequence KW - Mice KW - Orchiectomy KW - Testosterone -- pharmacology KW - Sequence Alignment KW - Seasons KW - Molecular Sequence Data KW - Incidence KW - Mesocricetus KW - Light KW - Sequence Homology, Amino Acid KW - Species Specificity KW - Female KW - Male KW - Cricetinae KW - C-Reactive Protein -- ultrastructure KW - Amyloidosis -- epidemiology KW - Serum Amyloid P-Component -- analysis KW - C-Reactive Protein -- chemistry KW - Alpha-Globulins -- chemistry KW - Liver Neoplasms -- epidemiology KW - Kidney Neoplasms -- epidemiology KW - Alpha-Globulins -- ultrastructure KW - Alpha-Globulins -- metabolism KW - C-Reactive Protein -- metabolism KW - Amyloid -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79319728?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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+physiology&rft.atitle=Female+protein%2C+amyloidosis%2C+and+hormonal+carcinogenesis+in+Turkish+hamster%3A+differences+from+Syrian+hamster.&rft.au=Coe%2C+J+E%3BCieplak%2C+W%3BHadlow%2C+W+J%3BRoss%2C+M+J&rft.aulast=Coe&rft.aufirst=J&rft.date=1997-09-01&rft.volume=273&rft.issue=3+Pt+2&rft.spage=R934&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+physiology&rft.issn=00029513&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-10-23 N1 - Date created - 1997-10-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of suicide risk factors using epidemiologic studies. AN - 79319415; 9323310 AB - Suicide is a complex outcome of multiple, inter-related factors. This article presents the epidemiology of completed and attempted suicide and discusses the known risk factors for suicide within a framework designed to encourage a systematic approach to theory testing and prevention. Mental and addictive disorders, frequently in co-occurrence, are the most powerful risk factors for suicide in all age groups, accounting for over 90 percent of all completed suicides. In combination with proximal risk factors such as access to firearms or other lethal means, recent and severe stressful life events, and intoxication, they can form the necessary and sufficient conditions for suicide. JF - The Psychiatric clinics of North America AU - Mościcki, E K AD - Prevention and Behavioral Medicine Research Branch, National Institute of Mental Health, National Institutes of Health, Rockville, Maryland, USA. Y1 - 1997/09// PY - 1997 DA - September 1997 SP - 499 EP - 517 VL - 20 IS - 3 SN - 0193-953X, 0193-953X KW - Index Medicus KW - Suicide, Attempted -- psychology KW - Humans KW - Substance-Related Disorders -- mortality KW - Aged KW - Child KW - Mental Disorders -- psychology KW - Substance-Related Disorders -- psychology KW - Mental Disorders -- mortality KW - Cause of Death KW - Risk KW - Suicide, Attempted -- statistics & numerical data KW - Aged, 80 and over KW - Life Change Events KW - Adult KW - Middle Aged KW - Adolescent KW - United States -- epidemiology KW - Female KW - Male KW - Suicide -- statistics & numerical data KW - Suicide -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79319415?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Psychiatric+clinics+of+North+America&rft.atitle=Identification+of+suicide+risk+factors+using+epidemiologic+studies.&rft.au=Mo%C5%9Bcicki%2C+E+K&rft.aulast=Mo%C5%9Bcicki&rft.aufirst=E&rft.date=1997-09-01&rft.volume=20&rft.issue=3&rft.spage=499&rft.isbn=&rft.btitle=&rft.title=The+Psychiatric+clinics+of+North+America&rft.issn=0193953X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-11-04 N1 - Date created - 1997-11-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Glutamate receptor subunit 2-selective antibody shows a differential distribution of calcium-impermeable AMPA receptors among populations of neurons. AN - 79286220; 9300771 AB - Alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors are the major excitatory neurotransmitter receptors of the central nervous system. AMPA receptor complexes that contain the AMPA-type glutamate receptor subunit 2 (GluR2) are responsible for the low calcium permeability typical of most AMPA receptors, and the absence of GluR2 may be a key factor in neurotoxicity. A polyclonal antibody was produced to a 16 amino acid peptide near the C-terminus of GluR2 and was affinity-purified in a three-step procedure. The antibody did not recognize other AMPA subunits in transfected cells with the use of either Western blots or immunocytochemistry. This highly specific GluR2 antibody was used to provide a specific morphological study of GluR2 protein distribution in neurons and synapses of the rat. GluR2 is prevalent in most principal neurons throughout the telencephalon. Neurons with few or no GluR2 subunits include two major types: 1) some populations of interneurons of the telencephalon and of some other areas and 2) many populations of principal neurons in the brainstem and spinal cord. Immunofluorescence showed that GluR2 immunolabeling was widespread, including in dendrites and puncta, in the hippocampus and neocortex. Where they were present, GluR2 subunits colocalized with other AMPA receptor subunits in individual neurons. Electron microscopy of the hippocampus showed GluR2-bearing, calcium-impermeable AMPA receptors postsynaptic to dendrite synapses of forebrain principal neurons. In addition, electron microscopy of the neocortex showed significant staining in postsynaptic profiles. Electron microscopy of the cerebellum revealed the presence of GluR2 subunits in the postsynaptic profiles of many parallel fiber/Purkinje cell spine synapses, whereas electron microscopy of the spinal cord showed substantial staining in the postsynaptic profiles of dorsal horn synapses, but not in ventral horn synapses. Both ultrastructural and immunofluorescence data showed that calcium-impermeable AMPA receptors are widespread in dendrite arborizations. JF - The Journal of comparative neurology AU - Petralia, R S AU - Wang, Y X AU - Mayat, E AU - Wenthold, R J AD - Laboratory of Neurochemistry, NIDCD, NIH, Bethesda, Maryland 20892-4162, USA. petralia@pop.nidcd.nih.gov Y1 - 1997/09/01/ PY - 1997 DA - 1997 Sep 01 SP - 456 EP - 476 VL - 385 IS - 3 SN - 0021-9967, 0021-9967 KW - Antibodies KW - 0 KW - Receptors, AMPA KW - Receptors, Glutamate KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Permeability KW - Antibody Specificity KW - Animals KW - Rats, Sprague-Dawley KW - Microscopy, Electron KW - Tissue Distribution KW - Immunohistochemistry KW - Fluorescent Antibody Technique KW - Male KW - Calcium -- metabolism KW - Antibodies -- immunology KW - Neurons -- metabolism KW - Receptors, Glutamate -- immunology KW - Brain -- cytology KW - Brain -- metabolism KW - Receptors, AMPA -- metabolism KW - Rats -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79286220?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+comparative+neurology&rft.atitle=Glutamate+receptor+subunit+2-selective+antibody+shows+a+differential+distribution+of+calcium-impermeable+AMPA+receptors+among+populations+of+neurons.&rft.au=Petralia%2C+R+S%3BWang%2C+Y+X%3BMayat%2C+E%3BWenthold%2C+R+J&rft.aulast=Petralia&rft.aufirst=R&rft.date=1997-09-01&rft.volume=63&rft.issue=4&rft.spage=420&rft.isbn=&rft.btitle=&rft.title=Photochemistry+and+photobiology&rft.issn=00318655&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-10-28 N1 - Date created - 1997-10-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Different kynurenine pathway enzymes limit quinolinic acid formation by various human cell types. AN - 79237818; 9291104 AB - Substantial increases in the tryptophan-kynurenine pathway metabolites, l-kynurenine and the neurotoxin quinolinic acid, occur in human brain, blood and systemic tissues during immune activation. Studies in vitro have shown that not all human cells are capable of synthesizing quinolinate. To investigate further the mechanisms that limit l-kynurenine and quinolinate production, the activities of kynurenine pathway enzymes and the ability of different human cells to convert pathway intermediates into quinolinate were compared. Stimulation with interferon gamma substantially increased indoleamine 2,3-dioxygenase activity and L-kynurenine production in primary peripheral blood macrophages and fetal brains (astrocytes and neurons), as well as cell lines derived from macrophage/monocytes (THP-1), U373MG astrocytoma, SKHEP1 liver and lung (MRC-9). High activities of kynurenine 3-hydroxylase, kynureninase or 3-hydroxyanthranilate 3,4-dioxygenase were found in interferon-gamma-stimulated macrophages, THP-1 cells and SKHEP1 cells, and these cells made large amounts of quinolinate when supplied with L-tryptophan, L-kynurenine, 3-hydroxykynurenine or 3-hydroxyanthranilate. Quinolinate production by human fetal brain cultures and U373MG cells was restricted by the low activities of kynurenine 3-hydroxylase, kynureninase and 3-hydroxyanthranilate 3,4-dioxygenase, and only small amounts of quinolinate were synthesized when cultures were supplied with L-tryptophan or 3-hydroxyanthranilate. In MRC-9 cells, quinolinate was produced only from 3-hydroxykynurenine and 3-hydroxyanthranilate, consistent with their low kynurenine 3-hydroxylase activity. The results are consistent with the notion that indoleamine 2,3-dioxygenase is an important regulatory enzyme in the production of L-kynurenine and quinolinate. Kynurenine 3-hydroxylase and, in some cells, kynureninase and 3-hydroxyanthranilate 3,4-dioxygenase are important determinants of whether a cell can make quinolinate. JF - The Biochemical journal AU - Heyes, M P AU - Chen, C Y AU - Major, E O AU - Saito, K AD - Laboratory of Neurotoxicology, NIMH, Bethesda, MD 20892-1262, USA. Y1 - 1997/09/01/ PY - 1997 DA - 1997 Sep 01 SP - 351 EP - 356 VL - 326 ( Pt 2) SN - 0264-6021, 0264-6021 KW - Lipopolysaccharides KW - 0 KW - Tumor Necrosis Factor-alpha KW - Kynurenine KW - 343-65-7 KW - Interferon-gamma KW - 82115-62-6 KW - Tryptophan Oxygenase KW - EC 1.13.11.11 KW - Quinolinic Acid KW - F6F0HK1URN KW - Index Medicus KW - Fetus KW - Liver -- cytology KW - Liver -- enzymology KW - Astrocytoma KW - Humans KW - Lipopolysaccharides -- pharmacology KW - Monocytes -- enzymology KW - Tumor Necrosis Factor-alpha -- pharmacology KW - Interferon-gamma -- pharmacology KW - B-Lymphocytes KW - Tryptophan Oxygenase -- metabolism KW - Tumor Cells, Cultured KW - Cells, Cultured KW - Lung KW - Cell Line KW - Macrophages -- enzymology KW - Brain -- enzymology KW - Brain -- cytology KW - Quinolinic Acid -- metabolism KW - Quinolinic Acid -- blood KW - Kynurenine -- metabolism KW - Brain -- metabolism KW - Macrophages -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79237818?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Biochemical+journal&rft.atitle=Different+kynurenine+pathway+enzymes+limit+quinolinic+acid+formation+by+various+human+cell+types.&rft.au=Heyes%2C+M+P%3BChen%2C+C+Y%3BMajor%2C+E+O%3BSaito%2C+K&rft.aulast=Heyes&rft.aufirst=M&rft.date=1997-09-01&rft.volume=326+%28+Pt+2%29&rft.issue=&rft.spage=351&rft.isbn=&rft.btitle=&rft.title=The+Biochemical+journal&rft.issn=02646021&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-09-29 N1 - Date created - 1997-09-29 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Biochem J. 1993 Apr 1;291 ( Pt 1):11-4 [8471029] J Neurochem. 1993 Jan;60(1):180-92 [8417138] Arch Biochem Biophys. 1993 Nov 15;307(1):104-9 [8239646] J Neurochem. 1993 Dec;61(6):2061-70 [8245962] Brain. 1993 Dec;116 ( Pt 6):1425-50 [8293279] J Neurochem. 1995 Nov;65(5):2217-26 [7595510] Biochem J. 1996 Dec 1;320 ( Pt 2):595-7 [8973572] J Neurochem. 1997 Jan;68(1):280-8 [8978736] Experientia. 1989 Jun 15;45(6):535-41 [2472288] Biochim Biophys Acta. 1982 Jul 16;717(1):56-60 [7104391] Mol Aspects Med. 1983;6(2):101-97 [6371429] J Biol Chem. 1986 Mar 15;261(8):3648-53 [2419335] Brain Res. 1988 Jul 1;470(1):146-50 [3409045] Anal Biochem. 1988 Aug 1;172(2):518-25 [3189792] J Chromatogr. 1988 Jul 15;428(2):340-4 [3215936] Anal Biochem. 1988 Oct;174(1):349-59 [2975477] J Neuropathol Exp Neurol. 1989 Jul;48(4):425-36 [2543798] Ann Neurol. 1991 Feb;29(2):202-9 [1826418] Biochem J. 1992 May 1;283 ( Pt 3):633-5 [1534219] FASEB J. 1992 Aug;6(11):2977-89 [1322853] Brain. 1992 Oct;115 ( Pt 5):1249-73 [1422788] Neuroscience. 1992 Nov;51(1):25-39 [1465184] J Biol Chem. 1993 Jul 25;268(21):15496-503 [8340378] N1 - Last updated - 2017-01-18 ER -