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 cecro